@article{chou_chen_yuan_cheng_he_monteiro-riviere_riviere_lin_2023, title={An artificial intelligence-assisted physiologically-based pharmacokinetic model to predict nanoparticle delivery to tumors in mice}, volume={361}, ISSN={["1873-4995"]}, url={http://dx.doi.org/10.1016/j.jconrel.2023.07.040}, DOI={10.1016/j.jconrel.2023.07.040}, abstractNote={The critical barrier for clinical translation of cancer nanomedicine stems from the inefficient delivery of nanoparticles (NPs) to target solid tumors. Rapid growth of computational power, new machine learning and artificial intelligence (AI) approaches provide new tools to address this challenge. In this study, we established an AI-assisted physiologically based pharmacokinetic (PBPK) model by integrating an AI-based quantitative structure-activity relationship (QSAR) model with a PBPK model to simulate tumor-targeted delivery efficiency (DE) and biodistribution of various NPs. The AI-based QSAR model was developed using machine learning and deep neural network algorithms that were trained with datasets from a published “Nano-Tumor Database” to predict critical input parameters of the PBPK model. The PBPK model with optimized NP cellular uptake kinetic parameters was used to predict the maximum delivery efficiency (DEmax) and DE at 24 (DE24) and 168 h (DE168) of different NPs in the tumor after intravenous injection and achieved a determination coefficient of R2 = 0.83 [root mean squared error (RMSE) = 3.01] for DE24, R2 = 0.56 (RMSE = 2.27) for DE168, and R2 = 0.82 (RMSE = 3.51) for DEmax. The AI-PBPK model predictions correlated well with available experimentally-measured pharmacokinetic profiles of different NPs in tumors after intravenous injection (R2 ≥ 0.70 for 133 out of 288 datasets). This AI-based PBPK model provides an efficient screening tool to rapidly predict delivery efficiency of a NP based on its physicochemical properties without relying on an animal training dataset.}, journal={JOURNAL OF CONTROLLED RELEASE}, publisher={Elsevier BV}, author={Chou, Wei-Chun and Chen, Qiran and Yuan, Long and Cheng, Yi-Hsien and He, Chunla and Monteiro-Riviere, Nancy A. and Riviere, Jim E. and Lin, Zhoumeng}, year={2023}, month={Sep}, pages={53–63} }
 @article{li_li_zhang_zeng_monteiro-riviere_chang_li_2022, title={Biocorona modulates the inflammatory response induced by gold nanoparticles in human epidermal keratinocytes}, volume={369}, url={http://dx.doi.org/10.1016/j.toxlet.2022.08.009}, DOI={10.1016/j.toxlet.2022.08.009}, abstractNote={The functional activities of gold nanoparticles (AuNPs) on biological systems depend on their physical-chemical properties and their surface functionalizations. Within a biological environment and depending on their surface characteristics, NPs can adsorb biomolecules (mostly proteins) present in the microenvironment, thereby forming a dynamic biomolecular corona on the surface. The presence of this biocorona changes the physical-chemical and functional properties of the NPs and how it interacts with cells. Here, we show that primary human epidermal keratinocytes (HEK) exposed in culture to branched polyethyleneimine (BPEI)-AuNPs, but not to lipoic acid (LA)-AuNPs, show potent particle uptake, decreased cell viability and enhanced production of inflammatory factors, while the presence of a human plasma-derived biocorona decreased NPs uptake and rescued cells from BPEI-AuNP-induced cell death. The mechanistic study revealed that the intracellular oxidative level greatly increased after the BPEI-AuNPs treatment, and the transcriptomic analysis showed that the dominant modulated pathways were related to oxidative stress and an antioxidant response. The stress level measured by flow cytometry also showed a significant decrease in the presence of a biocorona. Further anaylsis discovered that nuclear factor erythroid-2 related factor (Nrf2), a major regulator of anti-oxidant and anti-inflammatory genes, as the key factor related to the AuNPs induced oxidative stress and inflammation. This study provides futher understanding into the mechanisms on how NPs-induced cellular stress and reveals the protective effects of a biocorona on inflammatory responses in HEK at the molecular level, which provides important insights into the biological responses of AuNPs and their biocorona.}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Li, Xuejin and Li, Dongjie and Zhang, Guofang and Zeng, Yanqiao and Monteiro-Riviere, Nancy A. and Chang, Yan-Zhong and Li, Yang}, year={2022}, month={Oct}, pages={34–42} }
 @article{chou_cheng_riviere_monteiro-riviere_kreyling_lin_2022, title={Development of a multi-route physiologically based pharmacokinetic (PBPK) model for nanomaterials: a comparison between a traditional versus a new route-specific approach using gold nanoparticles in rats}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85133663328&partnerID=MN8TOARS}, DOI={10.1186/s12989-022-00489-4}, abstractNote={Abstract Background Physiologically based pharmacokinetic (PBPK) modeling is an important tool in predicting target organ dosimetry and risk assessment of nanoparticles (NPs). The methodology of building a multi-route PBPK model for NPs has not been established, nor systematically evaluated. In this study, we hypothesized that the traditional route-to-route extrapolation approach of PBPK modeling that is typically used for small molecules may not be appropriate for NPs. To test this hypothesis, the objective of this study was to develop a multi-route PBPK model for different sizes (1.4–200 nm) of gold nanoparticles (AuNPs) in adult rats following different routes of administration (i.e., intravenous (IV), oral gavage, intratracheal instillation, and endotracheal inhalation) using two approaches: a traditional route-to-route extrapolation approach for small molecules and a new approach that is based on route-specific data that we propose to be applied generally to NPs. Results We found that the PBPK model using this new approach had superior performance than the traditional approach. The final PBPK model was optimized rigorously using a Bayesian hierarchical approach with Markov chain Monte Carlo simulations, and then converted to a web-based interface using R Shiny. In addition, quantitative structure–activity relationships (QSAR) based multivariate linear regressions were established to predict the route-specific key biodistribution parameters (e.g., maximum uptake rate) based on the physicochemical properties of AuNPs (e.g., size, surface area, dose, Zeta potential, and NP numbers). These results showed the size and surface area of AuNPs were the main determinants for endocytic/phagocytic uptake rates regardless of the route of administration, while Zeta potential was an important parameter for the estimation of the exocytic release rates following IV administration. Conclusions This study suggests that traditional route-to-route extrapolation approaches for PBPK modeling of small molecules are not applicable to NPs. Therefore, multi-route PBPK models for NPs should be developed using route-specific data. This novel PBPK-based web interface serves as a foundation for extrapolating to other NPs and to humans to facilitate biodistribution estimation, safety, and risk assessment of NPs.}, number={1}, journal={Particle and Fibre Toxicology}, author={Chou, W.-C. and Cheng, Y.-H. and Riviere, J.E. and Monteiro-Riviere, N.A. and Kreyling, W.G. and Lin, Z.}, year={2022} }
 @misc{monteiro-riviere_2022, title={Perspectives of nanotoxicology: Introduction}, volume={14}, ISSN={["1939-0041"]}, url={https://doi.org/10.1002/wnan.1843}, DOI={10.1002/wnan.1843}, number={6}, journal={WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY}, author={Monteiro-Riviere, Nancy A.}, year={2022}, month={Nov} }
 @article{lin_chou_cheng_he_monteiro-riviere_riviere_2022, title={Predicting Nanoparticle Delivery to Tumors Using Machine Learning and Artificial Intelligence Approaches}, volume={17}, ISSN={["1178-2013"]}, url={https://doi.org/10.2147/IJN.S344208}, DOI={10.2147/IJN.S344208}, abstractNote={Low delivery efficiency of nanoparticles (NPs) to the tumor is a critical barrier in the field of cancer nanomedicine. Strategies on how to improve NP tumor delivery efficiency remain to be determined.This study analyzed the roles of NP physicochemical properties, tumor models, and cancer types in NP tumor delivery efficiency using multiple machine learning and artificial intelligence methods, using data from a recently published Nano-Tumor Database that contains 376 datasets generated from a physiologically based pharmacokinetic (PBPK) model.The deep neural network model adequately predicted the delivery efficiency of different NPs to different tumors and it outperformed all other machine learning methods; including random forest, support vector machine, linear regression, and bagged model methods. The adjusted determination coefficients (R2) in the full training dataset were 0.92, 0.77, 0.77 and 0.76 for the maximum delivery efficiency (DEmax), delivery efficiency at 24 h (DE24), at 168 h (DE168), and at the last sampling time (DETlast). The corresponding R2 values in the test dataset were 0.70, 0.46, 0.33 and 0.63, respectively. Also, this study showed that cancer type was an important determinant for the deep neural network model in predicting the tumor delivery efficiency across all endpoints (19-29%). Among all physicochemical properties, the Zeta potential and core material played a greater role than other properties, such as the type, shape, and targeting strategy.This study provides a quantitative model to improve the design of cancer nanomedicine with greater tumor delivery efficiency. These results help to improve our understanding of the causes of low NP tumor delivery efficiency. This study demonstrates the feasibility of integrating artificial intelligence with PBPK modeling approaches to study cancer nanomedicine.}, journal={INTERNATIONAL JOURNAL OF NANOMEDICINE}, publisher={Informa UK Limited}, author={Lin, Zhoumeng and Chou, Wei-Chun and Cheng, Yi-Hsien and He, Chunla and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2022}, pages={1365–1379} }
 @article{zhang_zhang_wang_wu_monteiro‐riviere_li_2021, title={The synergistic strategies for the
            immuno‐oncotherapy
            with photothermal nanoagents}, volume={13}, ISSN={1939-5116 1939-0041}, url={http://dx.doi.org/10.1002/wnan.1717}, DOI={10.1002/wnan.1717}, abstractNote={Immuno-oncotherapy has shown great promise for the cure of late-stage and metastatic cancer. Great efforts have tried to improve the overall response rate (ORR) and to reduce the immune-related adverse events (irAEs). Antigen presentation, T cell activation and killing are interlocking and distinct steps to initiate effective anti-tumor immune responses. Aiming to overcome the tumor immune evasion whose mechanisms include limited release of neoantigen, suppressed infiltration of antigen-presenting cells (APCs) and T cells, and the expression of immune checkpoints (ICPs), combinational therapeutic strategies have shown great potential by activating the anti-tumor immune responses together with deactivating immunosuppressive conditions simultaneously. In this direction, photothermal therapy (PTT) has attracted attention due to the efficient ablation of tumor cells, of which the released immunogenic tumor debris can activate host immune responses. The combination of immunoadjuvants and/or ICP inhibitors can boost the anti-tumor immune responses, realizing PTT-synergized immuno-oncotherapy. In this regard, numerous multifunctional nanomaterials have been designed with integration of photothermal and immuno-oncotherapeutic agents into one package via well-designed surface modification and functionalization. This review summarizes the recent studies on the synergistic strategies for the immuno-oncotherapy based on photothermal nanoagents and the mechanisms that trigger the systemic anti-tumor immune responses and PTT-synergized immuno-oncotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.}, number={5}, journal={WIREs Nanomedicine and Nanobiotechnology}, publisher={Wiley}, author={Zhang, Yuqian and Zhang, Guofang and Wang, Guocheng and Wu, Lidong and Monteiro‐Riviere, Nancy A. and Li, Yang}, year={2021}, month={Apr} }
 @article{delong_dean_glaspell_jaberi-douraki_ghosh_davis_monteiro-riviere_chandran_nguyen_aryal_et al._2020, title={Amino/Amido Conjugates Form to Nanoscale Cobalt Physiometacomposite (PMC) Materials Functionally Delivering Nucleic Acid Therapeutic to Nucleus Enhancing Anticancer Activity via Ras-Targeted Protein Interference}, volume={3}, url={https://doi.org/10.1021/acsabm.9b00798}, DOI={10.1021/acsabm.9b00798}, abstractNote={Aberrant splicing and protein interaction of Ras binding domain (RBD) are associated with melanoma drug resistance. Here, cobalt or nickel doped zinc oxide (ZnO) physiometacomposite (PMC) materials bind to RNA and peptide shown by Ninhydrin staining, UV-vis, Fourier transform infrared, and circular dichroism spectroscopy. PMCs deliver splice switching oligomer (SSO) into melanoma cells or 3-D tumor spheroids shown by flow cytometry, fluorescence microscopy, and bioluminescence. Stability in serum, liver, or tumor homogenate up to 48 h and B16F10 melanoma inhibition ≥98-99% is shown. These data suggest preclinical potential of PMC for delivery of SSO, RBD, or other nucleic acid therapeutic and anticancer peptides.}, number={1}, journal={ACS Applied Bio Materials}, publisher={American Chemical Society (ACS)}, author={DeLong, Robert K. and Dean, John and Glaspell, Garry and Jaberi-Douraki, Majid and Ghosh, Kartik and Davis, Daniel and Monteiro-Riviere, Nancy and Chandran, Parwathy and Nguyen, Tuyen and Aryal, Santosh and et al.}, year={2020}, month={Jan}, pages={175–179} }
 @misc{zhang_song_zhang_liang_chen_monteiro-riviere_boraschi_chang_li_li_2020, title={Gold Nanoparticles Induce Cell Stress by Interfering with the Cellular Protein Quality Control System}, volume={10}, url={http://dx.doi.org/10.21203/rs.3.rs-84361/v1}, DOI={10.21203/rs.3.rs-84361/v1}, abstractNote={Abstract The cellular protein quality control (PQC) system ensures the intracellular misfolded/unfolded proteins to be detected and eliminated. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the key mechanisms of PQC, which maintain protein homeostasis and ensure cell survival. Here, we show that after internalization by human epithelial cells, gold (Au) nanoparticles (NPs) localized in endoplasmic reticulum (ER) and induced an accumulation of misfolded/unfolded proteins. Au NPs activated UPR, but suppressed ERAD shown by a reduced degradation rate of the ERAD marker CD3-δ-YFP, which triggered ER stress through IRE1-XBP1-Chaperones and PERK-eIF2α-ATF4-CHOP pathways. The Au NP-dependent ER stress consequently induced the intracellular accumulation of ROS, and caused cell apoptosis/death, concomitant to production/release of inflammatory cytokines and chemokines. This study for the first time shows that NPs can interfere with the cellular PQC system by impairing ERAD activity, which in turn initiates a cascade of events leading to cell death and inflammation.}, publisher={Research Square}, author={Zhang, Guofang and Song, Qingle and Zhang, Yuqian and Liang, Ruijing and Chen, Liang and Monteiro-Riviere, Nancy and Boraschi, Diana and Chang, Yan-Zhong and Li, Hongchang and Li, Yang}, year={2020}, month={Oct} }
 @article{zhang_song_zhang_liang_chen_monteiro-riviere_boraschi_chang_li_li_2020, title={Gold Nanoparticles Induce Cell Stress by Interfering with the Cellular Protein Quality Control System}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85133623033&partnerID=MN8TOARS}, DOI={10.21203/rs.3.rs-84361}, journal={ResearchSquare}, author={Zhang, G. and Song, Q. and Zhang, Y. and Liang, R. and Chen, L. and Monteiro-Riviere, N. and Boraschi, D. and Chang, Y.-Z. and Li, H. and Li, Y.}, year={2020} }
 @article{cheng_he_riviere_monteiro-riviere_lin_2020, title={Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach}, volume={14}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/acsnano.9b08142}, DOI={10.1021/acsnano.9b08142}, abstractNote={Numerous studies have engineered nanoparticles with different physicochemical properties to enhance the delivery efficiency to solid tumors, yet the mean and median delivery efficiencies are only 1.48% and 0.70% of the injected dose (%ID), respectively, according to a study using a nonphysiologically based modeling approach based on published data from 2005 to 2015. In this study, we used physiologically based pharmacokinetic (PBPK) models to analyze 376 data sets covering a wide range of nanomedicines published from 2005 to 2018 and found mean and median delivery efficiencies at the last sampling time point of 2.23% and 0.76%ID, respectively. Also, the mean and median delivery efficiencies were 2.24% and 0.76%ID at 24 h and were decreased to 1.23% and 0.35%ID at 168 h, respectively, after intravenous administration. While these delivery efficiencies appear to be higher than previous findings, they are still quite low and represent a critical barrier in the clinical translation of nanomedicines. We explored the potential causes of this poor delivery efficiency using the more mechanistic PBPK perspective applied to a subset of gold nanoparticles and found that low delivery efficiency was associated with low distribution and permeability coefficients at the tumor site (P < 0.01). We also demonstrate how PBPK modeling and simulation can be used as an effective tool to investigate tumor delivery efficiency of nanomedicines.}, number={3}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Cheng, Yi-Hsien and He, Chunla and Riviere, Jim E. and Monteiro-Riviere, Nancy A. and Lin, Zhoumeng}, year={2020}, month={Feb}, pages={3075–3095} }
 @article{zhang_monteiro-riviere_2019, title={Toxicity assessment of six titanium dioxide nanoparticles in human epidermal keratinocytes}, volume={38}, url={https://doi.org/10.1080/15569527.2018.1527848}, DOI={10.1080/15569527.2018.1527848}, abstractNote={The aim of this study was to evaluate and compare the toxicity of six different types of titanium dioxide (TiO2) nanoparticles (NP) on human epidermal keratinocytes (HEK).Six TiO2 NP (A (10 nm), A*(32 nm), B (27.5 nm), C (200 nm), C*(30-40 nm), and D*(200-400 nm)) were suspended in water or culture medium and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). In addition, these NP were assayed with cell viability, cytokine release and cellular uptake in HEK.TiO2NP did not change in shape in the culture medium when visualized by TEM. There was an increase in agglomeration with all TiO2NP in the medium when measured by DLS. Since TiO2NP interfered with the CellTiter 96®AQueous One and MTT assays but had a minimal effect on alamar Blue (aB). The aB viability assay was selected to assess all six types of TiO2NP and sample B had a statistically significant decrease in viability at 0.4 mg/ml. A slight increase in TNF-α was noted in sample A*, C, and D* at as low as 0.05 mg/ml. Sample A* and B at certain concentrations showed an increase in Interleukin (IL)-6. IL-10 and IL-1β release for all TiO2NP were noted around the detection limit with no significant changes compared to control. A statistically significant decrease in IL-8 was noted for all TiO2NP at the highest concentrations due to the adsorption of IL-8 by TiO2. All TiO2NP were localized within cytoplasmic vacuoles of HEK and the element Ti was detected by energy-dispersive x-ray spectroscopy analysis.Based on cell viability, only sample B was slightly cytotoxic to HEK and samples B and A* have the potential to cause inflammation indicated by an increase in IL-6.}, number={1}, journal={Cutaneous and Ocular Toxicology}, publisher={Informa UK Limited}, author={Zhang, Leshuai W. and Monteiro-Riviere, Nancy A.}, year={2019}, month={Jan}, pages={66–80} }
 @article{riviere_jaberi-douraki_lillich_azizi_joo_choi_thakkar_monteiro-riviere_2018, title={Modeling gold nanoparticle biodistribution after arterial infusion into perfused tissue: effects of surface coating, size and protein corona}, volume={12}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390.2018.1476986}, DOI={10.1080/17435390.2018.1476986}, abstractNote={A detailed understanding of the factors governing nanomaterial biodistribution is needed to rationally design safe nanomedicines. This research details the pharmacokinetics of gold nanoparticle (AuNP) biodistribution after arterial infusion of 40 or 80 nm AuNP (1 μg/ml) into the isolated perfused porcine skin flap (IPPSF). AuNP had surface coatings consisting of neutral polyethylene glycol (PEG), anionic lipoic acid (LA), or cationic branched polyethylenimine (BPEI). Effect of a porcine plasma corona (PPC) on 40 nm BPEI and PEG-AuNP were assessed in the IPPSF. Au concentrations were determined by ICP/MS and arterial to venous concentration-time profiles were analyzed over 8 hr (4 hr infusion, 4 hr washout) using a two-compartment pharmacokinetic model. IPPSF viability and vascular function were assessed by change in glucose utilization, vascular resistance, or weight gain after perfusion. All AuNP demonstrated some degree of AuNP arterial extraction and skin flap retention, as well as enhanced kinetic parameters of tissue uptake; with BPEI-AuNP consistently having the greatest biodistribution even with a PPC. Toxicological effects were not detected. Transmission electron microscopy confirmed intracellular uptake of AuNP. These studies paralleled previous in vitro cell culture studies using the same AuNP in human endothelial and renal proximal tubule cells, hepatocytes, keratinocytes, showing BPEI-AuNP having the greatest uptake, although the presence of a PPC did not reduce IPPSF biodistribution as in the cell culture studies. These findings clearly indicate arterial to the venous extraction of AuNP after infusion with the magnitude of extraction being greatest with the BPEI surface coating and provide data and model structure necessary to construct the whole body physiologically based pharmacokinetic models capable of utilizing available in vitro data.}, number={10}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Riviere, Jim E. and Jaberi-Douraki, Majid and Lillich, James and Azizi, Tahmineh and Joo, Hyun and Choi, Kyoungju and Thakkar, Ravi and Monteiro-Riviere, Nancy A.}, year={2018}, month={Jun}, pages={1093–1112} }
 @article{cheng_riviere_monteiro-riviere_lin_2018, title={Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling}, volume={12}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390.2018.1459922}, DOI={10.1080/17435390.2018.1459922}, abstractNote={This study aimed to conduct an integrated and probabilistic risk assessment of gold nanoparticles (AuNPs) based on recently published in vitro and in vivo toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model. Dose-response relationships were characterized based on cell viability assays in various human cell types. A previously well-validated human PBPK model for AuNPs was applied to quantify internal concentrations in liver, kidney, skin, and venous plasma. By applying a Bayesian-based probabilistic risk assessment approach incorporating Monte Carlo simulation, probable human cell death fractions were characterized. Additionally, we implemented in vitro to in vivo and animal-to-human extrapolation approaches to independently estimate external exposure levels of AuNPs that cause minimal toxicity. Our results suggest that under the highest dosing level employed in existing animal studies (worst-case scenario), AuNPs coated with branched polyethylenimine (BPEI) would likely induce ∼90-100% cellular death, implying high cytotoxicity compared to <10% cell death induced by low-to-medium animal dosing levels, which are commonly used in animal studies. The estimated human equivalent doses associated with 5% cell death in liver and kidney were around 1 and 3 mg/kg, respectively. Based on points of departure reported in animal studies, the human equivalent dose estimates associated with gene expression changes and tissue cell apoptosis in liver were 0.005 and 0.5 mg/kg, respectively. Our analyzes provide insights into safety evaluation, risk prediction, and point of departure estimation of AuNP exposure for humans and illustrate an approach that could be applied to other NPs when sufficient data are available.}, number={5}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Cheng, Yi-Hsien and Riviere, Jim E. and Monteiro-Riviere, Nancy A. and Lin, Zhoumeng}, year={2018}, month={Apr}, pages={453–469} }
 @article{li_shi_radauer-preiml_andosch_casals_luetz-meindl_cobaleda_lin_jaberi-douraki_italiani_et al._2017, title={Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation}, volume={11}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390.2017.1401142}, DOI={10.1080/17435390.2017.1401142}, abstractNote={Nanoparticles (NPs) are easily contaminated by bacterial endotoxin (lipopolysaccharide [LPS]). The presence of LPS can be responsible for many immune/inflammatory effects attributed to NPs. In this study, we examined the effects of LPS adsorption on the NP surface on the formation of a biocorona in biological fluids and on the subsequent inflammation-inducing activity of NPs. Different gold (Au) NPs with sizes ranging from 10 to 80 nm and with different surface functionalization (sodium citrate, lipoic acid, and branched polyethyleneimine (BPEI), or polyethylene glycol (PEG)) were exposed to E. coli LPS under different conditions. The binding capacity of LPS to the surface of AuNPs was dose- and time-dependent. LPS attached to sodium citrate and lipoic acid coatings, but did not adhere to BPEI- or PEG-coated NPs. By computational simulation, the binding of LPS to AuNPs seems to follow the Langmuir absorption isotherm. The presence of LPS on AuNP surface interfered and caused a decrease in the formation of the expected biomolecular corona upon incubation in human plasma. LPS-coated AuNPs, but not the LPS-free NPs, induced significant inflammatory responses in vitro. Notably, while free LPS did also induce an anti-inflammatory response, LPS bound to NPs appeared unable to do so. In conclusion, the unintentional adsorption of LPS onto the NP surface can affect the biocorona formation and the inflammatory properties of NPs. Thus, for an accurate interpretation of NP interactions with cells, it is extremely important to be able to distinguish the intrinsic NP biological effects from those caused by biologically active contaminants such as endotoxin.}, number={9-10}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Li, Yang and Shi, Zhenzhen and Radauer-Preiml, Isabella and Andosch, Ancuela and Casals, Eudald and Luetz-Meindl, Ursula and Cobaleda, Macarena and Lin, Zhoumeng and Jaberi-Douraki, Majid and Italiani, Paola and et al.}, year={2017}, month={Nov}, pages={1157–1175} }
 @article{ortega_riviere_choi_monteiro-riviere_2017, title={Biocorona formation on gold nanoparticles modulates human proximal tubule kidney cell uptake, cytotoxicity and gene expression}, volume={42}, ISSN={0887-2333}, url={http://dx.doi.org/10.1016/j.tiv.2017.04.020}, DOI={10.1016/j.tiv.2017.04.020}, abstractNote={Gold nanoparticles (AuNP) adsorb macromolecules to form a protein corona (PC) after systemic delivery, to which the kidney as the primary excretory organ is constantly exposed. The role of the PC on AuNP cell uptake and toxicity was investigated in vitro in human proximal tubule cells (HPTC) using 40 and 80nm branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coated AuNP with or without (bare) PCs composed of human plasma (HP) or human serum albumin (HSA) for 0.25 to 24h. Time-dependent intracellular uptake, assessed by ICP-MS showed PC modulated cell uptake and cytotoxicity; with bare 40nm BPEI-AuNP showing the greatest responses. All AuNP showed minimal to no cytokine release. At the nontoxic dose, 40nm bare BPEI-AuNP significantly modified gene expression related to immunotoxicity, steatosis, and mitochondrial metabolism; while at the high dose, pathways of DNA damage and repair, apoptosis, fatty acid metabolism and heat shock response were modulated. HP corona BPEI-AuNP response was comparable to control. These studies clearly showed reduced uptake and cytotoxicity, as well as differentiated gene expression of AuNP with PCs, questioning the utility of in vitro studies using bare NP to assess in vivo effects. Significantly, only cationic bare BPEI-AuNP had HPTC uptake or cytotoxicity suggesting the relative safety of PEG and LA-AuNP as nanomedicine constructs.}, journal={Toxicology in Vitro}, publisher={Elsevier BV}, author={Ortega, M.T. and Riviere, J.E. and Choi, K. and Monteiro-Riviere, N.A.}, year={2017}, month={Aug}, pages={150–160} }
 @inbook{witzmann_monteiro-riviere_2017, title={Multi-walled carbon nanotube exposure alters protein expression in human keratinocytes}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053961363&partnerID=MN8TOARS}, DOI={10.1201/9781315114361}, booktitle={Nanomedicine in Cancer}, author={Witzmann, F.A. and Monteiro-Riviere, N.A.}, year={2017}, pages={461–485} }
 @inbook{monteiro-riviere_filon_2017, title={Skin}, ISBN={9780128091999}, url={http://dx.doi.org/10.1016/b978-0-12-809199-9.00015-x}, DOI={10.1016/b978-0-12-809199-9.00015-x}, abstractNote={The role of the skin as a potential route of exposure to nanomaterials is described in the present chapter. We survey the existing literature on various types of nanomaterials with respect to their penetration through the skin and toxicological responses. Most studies suggest minimal skin penetration and little to no systemic exposure. However, studies have also shown that nanoparticle size, shape, charge, surface properties, and vehicle/solvent as well as the choice of animal species are important determinants as to whether or not nanoparticles traverse through the rate-limiting lipid barrier of the stratum corneum. Long-term in vivo studies in animals or humans are needed because in vitro systems and differences in animal species provide limitations for a complete understanding of nanoparticle penetration through the skin.}, booktitle={Adverse Effects of Engineered Nanomaterials}, publisher={Elsevier}, author={Monteiro-Riviere, Nancy A. and Filon, Francesca Larese}, year={2017}, pages={357–380} }
 @article{chandran_riviere_monteiro-riviere_2017, title={Surface chemistry of gold nanoparticles determines the biocorona composition impacting cellular uptake, toxicity and gene expression profiles in human endothelial cells}, volume={11}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390.2017.1314036}, DOI={10.1080/17435390.2017.1314036}, abstractNote={This study investigated the role of nanoparticle size and surface chemistry on biocorona composition and its effect on uptake, toxicity and cellular responses in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona proteins among the various AuNP, revealing largely surface chemistry-dependent signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size distribution analysis revealed the relative instability and aggregation inducing potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular dichroism analysis showed surface chemistry-dependent conformational changes of proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC formation. Cell viability studies demonstrated dose-dependent toxicity of BPEI-AuNP. Transcriptional profiling studies revealed 126 genes, from 13 biological pathways, to be differentially regulated by 40 nm bare and PC-bound BPEI-AuNP (PC-BPEI-AuNP). Furthermore, PC formation relieved the toxicity of cationic BPEI-AuNP by modulating expression of genes involved in DNA damage and repair, heat shock response, mitochondrial energy metabolism, oxidative stress and antioxidant response, and ER stress and unfolded protein response cascades, which were aberrantly expressed in bare BPEI-AuNP-treated cells. NP surface chemistry is shown to play the dominant role over size in determining the biocorona composition, which in turn modulates cell uptake, and biological responses, consequently defining the potential safety and efficacy of nanoformulations.}, number={4}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Chandran, Parwathy and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2017}, month={Apr}, pages={507–519} }
 @article{lin_monteiro-riviere_kannan_riviere_2016, title={A computational framework for interspecies pharmacokinetics, exposure and toxicity assessment of gold nanoparticles}, volume={11}, ISSN={1743-5889 1748-6963}, url={http://dx.doi.org/10.2217/nnm.15.177}, DOI={10.2217/nnm.15.177}, abstractNote={Aim: To develop a comprehensive computational framework to simulate tissue distribution of gold nanoparticles (AuNP) across several species. Materials & methods: This framework was built on physiologically based pharmacokinetic modeling, calibrated and evaluated with multiple independent datasets. Results: Rats and pigs seem to be more appropriate models than mice in animal-to-human extrapolation of AuNP pharmacokinetics and that the dose and age should be considered. Incorporation of in vitro and/or in vivo cellular uptake and toxicity data into the model improved toxicity assessment of AuNP. Conclusion: These results partially explain the current low translation rate of nanotechnology-based drug delivery systems from mice to humans. This simulation approach may be applied to other nanomaterials and provides guidance to design future translational studies.}, number={2}, journal={Nanomedicine}, publisher={Future Medicine Ltd}, author={Lin, Zhoumeng and Monteiro-Riviere, Nancy A and Kannan, Raghuraman and Riviere, Jim E}, year={2016}, month={Jan}, pages={107–119} }
 @article{lin_monteiro-riviere_riviere_2016, title={A physiologically based pharmacokinetic model for polyethylene glycol-coated gold nanoparticles of different sizes in adult mice}, volume={10}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.3109/17435390.2015.1027314}, DOI={10.3109/17435390.2015.1027314}, abstractNote={Nanoparticles (NPs) are widely used in various fields of nanomedicine. A systematic understanding of NP pharmacokinetics is crucial in their design, applications, and risk assessment. In order to integrate available experimental information and to gain insights into NP pharmacokinetics, a membrane-limited physiologically based pharmacokinetic (PBPK) model for polyethylene glycol-coated gold (Au) NPs (PEG-coated AuNPs) was developed in mice. The model described endocytosis of the NPs in the liver, spleen, kidneys, and lungs and was calibrated using data from mice that were intravenously injected with 0.85 mg/kg 13 nm and 100 nm PEG-coated AuNPs. The model adequately predicted multiple external datasets for PEG-coated AuNPs of similar sizes (13-20 nm; 80-100 nm), indicating reliable predictive capability in suitable size ranges. Simulation results suggest that endocytosis of NPs is time and size dependent, i.e. endocytosis of larger NPs occurs immediately and predominately from the blood, whereas smaller NPs can diffuse through the capillary wall and their endocytosis appears mainly from the tissue with a 10-h delay, which may be the primary mechanism responsible for the reported size-dependent pharmacokinetics of NPs. Several physiological parameters (e.g. liver weight fraction of body weight) were identified to have a high influence on selected key dose metrics, indicating the need for additional interspecies comparison and scaling studies and to conduct pharmacokinetic studies of NPs in species that are more closely related to humans in these parameters. This PBPK model provides useful insights into the size, time, and species dependence of NP pharmacokinetics.}, number={2}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Lin, Zhoumeng and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2016}, pages={162–172} }
 @article{williams_rothe_barrett_chiodini_whyte_cronin_monteiro-riviere_plautz_roper_westerhout_et al._2016, title={Assessing the safety of cosmetic chemicals: Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern)}, volume={76}, ISSN={0273-2300}, url={http://dx.doi.org/10.1016/j.yrtph.2016.01.005}, DOI={10.1016/j.yrtph.2016.01.005}, abstractNote={Threshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual ‘dose’ applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool.}, journal={Regulatory Toxicology and Pharmacology}, publisher={Elsevier BV}, author={Williams, Faith M. and Rothe, Helga and Barrett, Gordon and Chiodini, Alessandro and Whyte, Jacqueline and Cronin, Mark T.D. and Monteiro-Riviere, Nancy A. and Plautz, James and Roper, Clive and Westerhout, Joost and et al.}, year={2016}, month={Apr}, pages={174–186} }
 @article{sasidharan_chandran_monteiro-riviere_2016, title={Biocorona Bound Gold Nanoparticles Augment Their Hematocompatibility Irrespective of Size or Surface Charge}, volume={2}, ISSN={2373-9878 2373-9878}, url={http://dx.doi.org/10.1021/acsbiomaterials.6b00368}, DOI={10.1021/acsbiomaterials.6b00368}, abstractNote={Despite colloidal gold nanoparticles (AuNP) being proposed for a multitude of biomedical applications, there is a lack of understanding on how the protein corona (PC) formation over AuNP influences its interaction with blood components. Herein, 40 and 80 nm AuNP with branched polyethylenimine, lipoic acid, and polyethylene glycol surface coatings were exposed to human plasma, and time-dependent evolution of the PC was evaluated using differential centrifugation sedimentation. Further, the impact of PC-AuNP interaction with human blood components was studied by evaluating red blood cell (RBC) aggregation, hemolysis, platelet activation and aggregation, prothrombin time, activated partial thromboplastin time, complement activation and cytokine release. In contrast to bare AuNP, PC-coated AuNP exhibited enhanced compatibility with RBC, platelets, and lymphocytes. More importantly, PC-AuNP did not activate the platelet coagulation cascade or complement system or elicit an immune response up to a relatively higher dose of 100 μg/mL. This study suggests that, irrespective of the physicochemical properties, the adsorption of the PC over AuNP significantly influences its biological impact by alleviating adverse hematotoxicity of bare NP.}, number={9}, journal={ACS Biomaterials Science & Engineering}, publisher={American Chemical Society (ACS)}, author={Sasidharan, Abhilash and Chandran, Parwathy and Monteiro-Riviere, Nancy A.}, year={2016}, month={Aug}, pages={1608–1618} }
 @inbook{narayan_boehm_monteiro-riviere_2016, place={Boca Ration, FL}, series={Pan Stanford Series on Nanomedicine}, title={Cell and Protein Interactions with Diamond}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85015904952&partnerID=MN8TOARS}, DOI={10.4032/9789814669238}, booktitle={Handbook of Clinical Nanomedicine: Law, Business, Regulation, Safety and Risk}, publisher={Pan Stafford Publishing/CRC Press}, author={Narayan, R.J. and Boehm, R.D. and Monteiro-Riviere, N.A.}, editor={Bawa, R. and Audette, G.F. and Reese, B.Editors}, year={2016}, pages={809–822}, collection={Pan Stanford Series on Nanomedicine} }
 @article{chen_monteiro-riviere_zhang_2016, title={Intracellular imaging of quantum dots, gold, and iron oxide nanoparticles with associated endocytic pathways}, volume={9}, ISSN={1939-5116}, url={http://dx.doi.org/10.1002/wnan.1419}, DOI={10.1002/wnan.1419}, abstractNote={Metallic nanoparticles (NP) have been used for biomedical applications especially for imaging. Compared to nonmetallic NP, metallic NP provide high contrast images because of their optical light scattering, magnetic resonance, X-ray absorption, or other physicochemical properties. In this review, a series of in vitro imaging techniques for metallic NP will be introduced, meanwhile their strengths and weaknesses will be discussed. By utilizing these imaging methods, the cellular uptake of metallic NP can be easily visualized to better understand the endocytic mechanisms of NP intracellular delivery. Several types of metallic NP that are used for imaging or as contrast agents such as quantum dots, gold, iron oxide, and other metallic NP will be presented. Cellular uptake of metallic NP and associated endocytic mechanisms highly depends upon the NP size, charge, surface coating, shape, or other factors such as cell type, cell differentiation status, cell surface status, external forces, protein binding, temperature, and the biological milieu. Classical endocytic routes such as lipid raft-mediated pathways, clathrin or caveolae-mediated pathways, macropinocytosis, and phagocytosis have been investigated, yet there is still a demand to determine other endocytic pathways. Knowing the different methodologies used to determine the endocytic pathways will increase the understanding of NP toxicity, cancer cell targeting, and imaging, so that surface coatings can be created for efficient cell uptake of metallic NP with minimal cytotoxicity WIREs Nanomed Nanobiotechnol 2017, 9:e1419. doi: 10.1002/wnan.1419 For further resources related to this article, please visit the WIREs website.}, number={2}, journal={Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology}, publisher={Wiley}, author={Chen, Dandan and Monteiro-Riviere, Nancy A. and Zhang, Leshuai W.}, year={2016}, month={Jul}, pages={e1419} }
 @article{li_monteiro-riviere_2016, title={Mechanisms of cell uptake, inflammatory potential and protein corona effects with gold nanoparticles}, volume={11}, ISSN={1743-5889 1748-6963}, url={http://dx.doi.org/10.2217/nnm-2016-0303}, DOI={10.2217/nnm-2016-0303}, abstractNote={Aim: To assess inflammation, cellular uptake and endocytic mechanisms of gold nanoparticles (AuNP) in human epidermal keratinocytes with and without a protein corona. Materials & methods: Human epidermal keratinocytes were exposed to 40 and 80 nm AuNP with lipoic acid, polyethylene glycol (PEG) and branched polyethyleneimine (BPEI) coatings with and without a protein corona up to 48 h. Inhibitors were selected to characterize endocytosis. Results & conclusion: BPEI-AuNP showed the greatest uptake, while PEG-AuNP had the least. Protein coronas decreased uptake and affected their mechanism. AuNP uptake was energy-dependent, except for 40 nm lipoic-AuNP. Most AuNP were internalized by clathrin and lipid raft-mediated endocytosis, except for 40 nm PEG was by raft/noncaveolae mediated endocytosis. Coronas inhibited caveolae-mediated-endocytosis with lipoic acid and BPEI-AuNP and altered 40 nm PEG-AuNP from raft/noncaveolae to clathrin. Inflammatory responses decreased with a plasma corona. Results suggest protein coronas significantly affect cellular uptake and inflammatory responses of AuNP.}, number={24}, journal={Nanomedicine}, publisher={Future Medicine Ltd}, author={Li, Yang and Monteiro-Riviere, Nancy A}, year={2016}, month={Dec}, pages={3185–3203} }
 @article{choi_koci_ortega_jeffery_riviere_monteiro riviere_2016, title={Mechanistic Toxicity Assessment of Hexahydroisohumulone in Canine Hepatocytes, Renal Proximal Tubules, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells}, volume={4}, ISSN={2332-2748}, url={http://dx.doi.org/10.19070/2332-2748-1600022}, DOI={10.19070/2332-2748-1600022}, abstractNote={In vitro test methods are used primarily for rapid screening of chemicals based on mechanistic understanding of toxicity to predict hazards and potential risks. We investigated organ-specific oxidative stress and the molecular mechanism of toxicity using the pathway-focused DNA array of the hop ingredient hexahydroisohumulone (HEX) with canine hepatocytes, canine proximal tubule cells (CPTC), bone marrow-derived mesenchymal stem cells (BMSC) and enterocyte-like cells (ELC). Free radical species were produced in HEX-treated hepatocytes and to a lesser extent in CPTC, BMSC and ELC. Transcriptional profiles showed 30.5% (113 genes) out of 370 genes were differentially expressed in hepatocytes followed by CPTC (21.6%, 80 genes), ELC (4.8%, 18 genes) and BMSC (1.0%, 4 genes). HEX predominantly affected DNA damage/ repair pathways in hepatocytes and CPTC, while for ELC endoplasmic reticulum (ER) stress/unfolded protein response (UPR) dominated. Cyclooxygenase-2 (COX-2) and C/EBP homologous protein (CHOP) were most abundant genes in HEX-treated hepatocytes and CPTC; networked complementary between various pathways resulting in its adverse effect on oxidative stress, ER stress/UPR, mitochondrial metabolism and apoptosis. This work contributes to the understanding of the molecular effects of HEX, cellular response to oxidative stress and provides insight into genes altered with HEX exposure and the cell-type specific responses in dogs.}, number={2}, journal={International Journal of Veterinary Health Science & Research}, publisher={SciDoc Publishers LLC}, author={Choi, K and Koci, J and Ortega, M.T. and Jeffery, B and Riviere, J.E. and Monteiro Riviere, N.A.}, year={2016}, month={Feb}, pages={88–103} }
 @article{choi_ortega_jeffery_riviere_monteiro-riviere_2016, title={Oxidative stress response in canine in vitro liver, kidney and intestinal models with seven potential dietary ingredients}, volume={241}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/j.toxlet.2015.11.012}, DOI={10.1016/j.toxlet.2015.11.012}, abstractNote={In vitro cell culture systems are a useful tool to rapidly assess the potential safety or toxicity of chemical constituents of food. Here, we investigated oxidative stress and organ-specific antioxidant responses by 7 potential dietary ingredients using canine in vitro culture of hepatocytes, proximal tubule cells (CPTC), bone marrow-derived mesenchymal stem cells (BMSC) and enterocyte-like cells (ELC). Cellular production of free radical species by denatonium benzoate (DB), epigallocatechin gallate (EPI), eucalyptol (EUC), green tea catechin extract (GTE) and sodium copper chlorophyllin (SCC), tetrahydroisohumulone (TRA) as well as xylitol (XYL) were continuously measured for reactive oxygen/nitrogen species (ROS/RNS) and superoxide (SO) for up to 24h. DB and TRA showed strong prooxidant activities in hepatocytes and to a lesser degree in ELC. DB was a weak prooxidant in BMSC. In contrast DB and TRA were antioxidants in CPTC. EPI was prooxidant in hepatocytes and BMSC but showed prooxidant and antioxidant activity in CPTC. SCC in hepatocytes (12.5mg/mL) and CPTC (0.78mg/mL) showed strong prooxidant and antioxidant activity in a concentration-dependent manner. GTE was effective antioxidant only in ELC. EUC and XYL did not induce ROS/RNS in all 4 cell types. SO production by EPI and TRA increased in hepatocytes but decreased by SCC in hepatocytes and ELC. These results suggest that organ-specific responses to oxidative stress by these potential prooxidant compounds may implicate a mechanism of their toxicities.}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Choi, Kyoungju and Ortega, Maria T. and Jeffery, Brett and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2016}, month={Jan}, pages={49–59} }
 @article{choi_riviere_monteiro-riviere_2016, title={Protein corona modulation of hepatocyte uptake and molecular mechanisms of gold nanoparticle toxicity}, volume={11}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390.2016.1264638}, DOI={10.1080/17435390.2016.1264638}, abstractNote={Protein corona formation over gold nanoparticles (AuNP) can modulate cellular responses by altering AuNP physicochemical properties. The liver plays an essential role in metabolism, detoxification and elimination of xenobiotics and drugs as well as circulating NP clearance. We investigated human hepatic uptake of 40 and 80 nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human serum albumin (HSA) coronas. AuNP-mediated cytotoxicity, reactive oxygen/reactive nitrogen species (ROS/RNS), and CYP activity in human hepatocytes as well as molecular mechanisms with 40 nm bare and HP BPEI-AuNP were investigated. Time-dependent increase in uptake occurred for all bare AuNP but HP and HSA decreased uptake except for 40 nm HP PEG-AuNP. BPEI-AuNP showed time-and concentration-dependent increase in ROS/RNS which correlated with cytotoxicity at 24 h. HP corona substantially reduced ROS/RNS. The 40 and 80 nm bare, HP or HSA LA- and PEG-AuNP were not toxic but HP was as cytotoxic as bare BPEI-AuNP. All bare and HP BPEI-AuNP, except for HP 80 nm BPEI-AuNP toward CYP1A2, inhibited CYP1A2, CYP2C9 and CYP3A4 activity. Transcriptional profiling was dose-dependent with 40 nm bare BPEI-AuNP (1.9% genes at IC10 and 18.9% at LC50) and HP (23.5% at LC50). Differentially expressed genes at LC50 were mainly involved in phase I metabolism and phospholipidosis pathways. Cytotoxicity of bare BPEI-AuNP caused an upregulation of antioxidant and pro-apoptotic genes. These studies contribute to a better understanding of the dramatic effect of protein coronas (PC) on AuNP cellular uptake, cytotoxicity and their underlying molecular mechanisms of action.}, number={1}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Choi, Kyoungju and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2016}, month={Dec}, pages={64–75} }
 @article{chen_zhang_monteiro-riviere_riviere_2016, title={Quantification of nanoparticle pesticide adsorption: computational approaches based on experimental data}, volume={10}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390.2016.1177745}, DOI={10.1080/17435390.2016.1177745}, abstractNote={Quantitative analysis of the interactions between nanomaterials and environmental contamINANts, such as pesticides, in natural water systems and food residuals is crucial for the application of nanomaterials-based tools for the detection of the presence of toxic substances, monitoring pollution levels and environmental remediation. Previously, the Biological Surface Adsorption Index (BSAI) has demonstrated promising capabilities of interaction characterization and prediction based on experimental data from small organic molecules. In this article, the first attempt of the application of such quantitative measures toward environmental endpoints by analyzing the interactions of a selected group of nanomaterials with a variety of pesticides was made. Statistical modeling was conducted on the experimental obtained adsorption data based on polynomial BSAI models, as well as models with the incorporation of artificial neural network methodologies. Finally, clustering analyzes were performed for the categorization of nanomaterials based on surface physicochemical properties using both polynomial indices and physical adsorption modeling parameters. These quantitative computational approaches support the application of BSAI modeling in the area of environmental contamINANt detection and remediation.}, number={8}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Chen, Ran and Zhang, Yuntao and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2016}, month={May}, pages={1118–1128} }
 @inbook{monteiro-riviere_2016, title={Safety of Nanoparticle Skin Penetration}, ISBN={9783662478615 9783662478622}, url={http://dx.doi.org/10.1007/978-3-662-47862-2_24}, DOI={10.1007/978-3-662-47862-2_24}, booktitle={Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement}, publisher={Springer Berlin Heidelberg}, author={Monteiro-Riviere, Nancy A.}, year={2016}, pages={363–376} }
 @article{ortega_jeffery_riviere_monteiro-riviere_2016, title={Toxicological effects of pet food ingredients on canine bone marrow-derived mesenchymal stem cells and enterocyte-like cells}, volume={36}, ISSN={0260-437X}, url={http://dx.doi.org/10.1002/jat.3158}, DOI={10.1002/jat.3158}, abstractNote={We developed an in vitro method to assess pet food ingredients safety. Canine bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into enterocyte-like cells (ELC) to assess toxicity in cells representing similar patterns of exposure in vivo. The toxicological profile of clove leave oil, eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine monophosphate was 59.42 ± 0.90 and 56.7 ± 3.5 mg ml–1 for BMSC and ELC; 56.84 ± 0.95 and 53.66 ± 1.36 mg ml–1 for GMP; 0.02 ± 0.001 and 1.25 ± 0.47 mg ml–1 for citric acid; 0.077 ± 0.002 and 0.037 ± 0.01 mg ml–1 for cinnamaldehyde; 0.002 ± 0.0001 and 0.002 ± 0.0008 mg ml–1 for thymol; 0.080 ± 0.003 and 0.059 ± 0.001 mg ml–1 for thyme oil; 0.111 ± 0.002 and 0.054 ± 0.01 mg ml–1 for cinnamon bark oil; 0.119 ± 0.0004 and 0.099 ± 0.011 mg ml–1 for clove leave oil; 0.04 ± 0.001 and 0.028 ± 0.002 mg ml–1 for eugenol; 2.80 ± 0.11 and 1.75 ± 0.51 mg ml–1 for ginger root extract; > 200 and 116.78 ± 7.35 mg ml–1 for sorbose. Lemon grass oil was evaluated at 0.003–0.9 in BMSC and .03-0.9 mg ml–1 in ELC and its mechanistic effect was investigated. The gene toxicology studies showed regulation of 61% genes in CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC. For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for mitochondrial energy metabolism. In conclusion, these studies provide a baseline against which differential toxicity of dietary feed ingredients can be assessed in vitro for direct effects on canine cells and demonstrate differential toxicity in differentiated cells that represent gastrointestinal epithelial cells. Copyright © 2015 John Wiley & Sons, Ltd.}, number={2}, journal={Journal of Applied Toxicology}, publisher={Wiley}, author={Ortega, M. T. and Jeffery, B. and Riviere, J. E. and Monteiro-Riviere, N. A.}, year={2016}, month={Feb}, pages={189–198} }
 @article{sasidharan_monteiro-riviere_2015, title={Biomedical applications of gold nanomaterials: opportunities and challenges}, volume={7}, ISSN={1939-5116}, url={http://dx.doi.org/10.1002/wnan.1341}, DOI={10.1002/wnan.1341}, abstractNote={In the past few years, there has been an unprecedented development of gold nanomaterials (AuNMs) for potential clinical applications. Owing to their advantageous physical, chemical, and biological properties, AuNMs have attracted great attention in the nanomedicine arena for applications in biological sensing, biomedical imaging, drug delivery, and photothermal therapy. Their tunable size, shape, and surface characteristics coupled with excellent biocompatibility render them ideal candidates for translation from bench-top to bedside. This review summarizes the recent research on the applications of AuNM with a focus on biomedical diagnostics and therapeutics. The bio-interaction of these NM with cells and their in vivo responses are presented. After reviewing these potential applications, future challenges and prospects are discussed and the suitability of how AuNMs are used as effective tools in clinical medicine is assessed. WIREs Nanomed Nanobiotechnol 2015, 7:779–796. doi: 10.1002/wnan.1341 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials}, number={6}, journal={Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology}, publisher={Wiley}, author={Sasidharan, Abhilash and Monteiro-Riviere, Nancy A.}, year={2015}, month={Mar}, pages={779–796} }
 @article{monteiro-riviere_ortega_choi_koci_lin_jeffery_riviere_2015, title={Comparative In Vitro Cytotoxicity of 20 Potential Food Ingredients in Canine Liver, Kidney, Bone Marrow-Derived Mesenchymal Stem Cells, and Enterocyte-like Cells}, volume={1}, ISSN={2332-1512 2332-1539}, url={http://dx.doi.org/10.1089/aivt.2015.0020}, DOI={10.1089/aivt.2015.0020}, abstractNote={To begin development of a mechanistically relevant humane alternative platform for safety assessment of dog food ingredients, comparative in vitro cytotoxicity of 20 ingredients was assessed in four canine cell types relevant for toxicity assessments. Previously, we described the toxicity of 13 compounds (clove leaf oil, eugenol, guanosine monophosphate [GMP], GMP plus inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol, lemon grass oil, xylitol, and citric acid) using in vitro primary canine cell culture models for liver, kidney, bone marrow-derived mesenchymal stem cells (BMSC), and enterocyte-like cells (ELC). In this report, dose–response cytotoxicity studies and LC50 using alamar blue assays are reported for seven additional compounds: denatonium benzoate, eucalyptol, hexahydroisohumulone, tetrahydroisohumulone, green tea catechin extract, epigallocatechin gallate, and sodium copper chlorophyllin. Data across 20 compounds were compared between different cell types and responses were not parallel, precluding the use of a single cell line for in vitro ingredient hazard assessment. Hepatocytes were most resistant to all compounds, consistent with their xenobiotic detoxification functions. BMSC and ELC showed an increase in sensitivity to the essential oils eucalyptol, eugenol, and thymol compared to renal cells and hepatocytes. These studies provide a baseline of acute cytotoxicity of 4 canine cell types to 20 different food components that begin to illustrate how such an in vitro panel could be used for hazard assessment.}, number={4}, journal={Applied In Vitro Toxicology}, publisher={Mary Ann Liebert Inc}, author={Monteiro-Riviere, Nancy A. and Ortega, Maria T. and Choi, Kyoungju and Koci, Juraj and Lin, Zhoumeng and Jeffery, Brett and Riviere, Jim E.}, year={2015}, month={Dec}, pages={276–288} }
 @inbook{monteiro-riviere_riviere_2015, place={Boca Raton, FL}, series={Pan Stanford series on biomedical nanotechnology}, title={Dermatotoxicity of Nanomaterials}, ISBN={9780429090752 9789814463379}, booktitle={Handbook of Safety Assessment of Nanomaterials: From Toxicological Testing to Personalized Medicine}, publisher={Jenny Stanford Publishing}, author={Monteiro-Riviere, N.A. and Riviere, J.E.}, editor={Fadeel, B.Editor}, year={2015}, pages={439–459,}, collection={Pan Stanford series on biomedical nanotechnology} }
 @article{sasidharan_riviere_monteiro-riviere_2015, title={Gold and silver nanoparticle interactions with human proteins: impact and implications in biocorona formation}, volume={3}, ISSN={2050-750X 2050-7518}, url={http://dx.doi.org/10.1039/c4tb01926a}, DOI={10.1039/c4tb01926a}, abstractNote={Metallic NP interaction with human proteins, biocorona formation and their impact on cellular uptake.}, number={10}, journal={Journal of Materials Chemistry B}, publisher={Royal Society of Chemistry (RSC)}, author={Sasidharan, Abhilash and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2015}, pages={2075–2082} }
 @inbook{samberg_lin_monteiro-riviere_2015, title={In Vitro and In Vivo Toxicity and Pharmacokinetics of Silver Nanoparticles}, ISBN={9789400761780}, url={http://dx.doi.org/10.1007/978-94-007-6178-0_331-2}, DOI={10.1007/978-94-007-6178-0_331-2}, booktitle={Encyclopedia of Nanotechnology}, publisher={Springer Netherlands}, author={Samberg, Meghan E. and Lin, Zhoumeng and Monteiro-Riviere, Nancy A.}, year={2015}, pages={1–14} }
 @article{koči_jeffery_riviere_monteiro-riviere_2015, title={In vitro safety assessment of food ingredients in canine renal proximal tubule cells}, volume={29}, ISSN={0887-2333}, url={http://dx.doi.org/10.1016/j.tiv.2014.11.002}, DOI={10.1016/j.tiv.2014.11.002}, abstractNote={In vitro models are useful tools to initially assess the toxicological safety hazards of food ingredients. Toxicities of cinnamaldehyde (CINA), cinnamon bark oil, lemongrass oil (LGO), thymol, thyme oil (TO), clove leaf oil, eugenol, ginger root extract (GRE), citric acid, guanosine monophosphate, inosine monophosphate and sorbose (SORB) were assessed in canine renal proximal tubule cells (CPTC) using viability assay and renal injury markers. At LC50, CINA was the most toxic (0.012 mg/ml), while SORB the least toxic (>100 mg/ml). Toxicities (LC50) of positive controls were as follows: 4-aminophenol (0.15 mg/ml in CPTC and 0.083 mg/ml in human PTC), neomycin (28.6 mg/ml in CPTC and 27.1 mg/ml in human PTC). XYL displayed lowest cytotoxic potency (LC50 = 82.7 mg/ml in CPTC). In vivo renal injury markers in CPTC were not significantly different from controls. The LGO toxicity mechanism was analyzed using qPCR and electron microscopy. Out of 370 genes, 57 genes (15.4%) were significantly up (34, 9.1%) or down (23, 6.2%) regulated, with the most upregulated gene gsta3 (∼200-fold) and the most affected pathway being oxidative stress. LGO induced damage of mitochondria, phospholipid accumulation and lack of a brush border. Viability assays along with mechanistic studies in the CPTC model may serve as a valuable in vitro toxicity screening tool.}, number={2}, journal={Toxicology in Vitro}, publisher={Elsevier BV}, author={Koči, J. and Jeffery, B. and Riviere, J.E. and Monteiro-Riviere, N.A.}, year={2015}, month={Mar}, pages={289–298} }
 @article{sahneh_scoglio_monteiro-riviere_riviere_2015, title={Predicting the impact of biocorona formation kinetics on interspecies extrapolations of nanoparticle biodistribution modeling}, volume={10}, ISSN={1743-5889 1748-6963}, url={http://dx.doi.org/10.2217/nnm.14.60}, DOI={10.2217/nnm.14.60}, abstractNote={Aim: To assess the impact of biocorona kinetics on expected tissue distribution of nanoparticles (NPs) across species. Materials & methods: The potential fate of NPs in vivo is described through a simple and descriptive pharmacokinetic model using rate processes dependent upon basal metabolic rate coupled to dynamics of protein corona. Results: Mismatch of time scales between interspecies allometric scaling and the kinetics of corona formation is potentially a fundamental issue with interspecies extrapolations of NP biodistribution. The impact of corona evolution on NP biodistribution across two species is maximal when corona transition half-life is close to the geometric mean of NP half-lives of the two species. Conclusion: While engineered NPs can successfully reach target cells in rodent models, the results may be different in humans due to the fact that the longer circulation time allows for further biocorona evolution.}, number={1}, journal={Nanomedicine}, publisher={Future Medicine Ltd}, author={Sahneh, Faryad Darabi and Scoglio, Caterina M and Monteiro-Riviere, Nancy A and Riviere, Jim E}, year={2015}, month={Jan}, pages={25–33} }
 @article{zhang_koci_jeffery_riviere_monteiro-riviere_2015, title={Safety assessment of potential food ingredients in canine hepatocytes}, volume={78}, ISSN={0278-6915}, url={http://dx.doi.org/10.1016/j.fct.2015.02.003}, DOI={10.1016/j.fct.2015.02.003}, abstractNote={This research aimed to develop in vitro methods to assess hazard of canine food ingredients. Canine hepatocytes were harvested and cell viability of clove-leaf oil (CLO), eugenol (EUG), lemongrass oil (LGO), guanosine monophosphate (GMP), inosine monophosphate (IMP), sorbose, ginger-root extract (GRE), cinnamon-bark oil (CBO), cinnamaldehyde (CINA), thymol oil (TO), thymol (THYM), and citric acid were assessed with positive controls: acetaminophen (APAP), aflatoxin B1 and xylitol. Molecular Toxicology PathwayFinder array (MTPF) analyzed toxicity mechanisms for LGO. LC50 for APAP was similar among human (3.45), rat (2.35), dog (4.26 mg/ml). Aflatoxin B1 had an LC50 of 4.43 (human), 5.78 (rat) and 6.05 (dog) µg/ml; xylitol did not decrease viability. LC50 of CLO (0.185 ± 0.075(SD)), EUG (0.165 ± 0.112), LGO (0.220 ± 0.012), GRE (1.54 ± 0.31) mg/ml; GMP (166.03 ± 41.83), GMP + IMP (208.67 ± 15.27) mM; CBO (0.08 ± 0.03), CINA (0.11 ± 0.01), TO (0.21 ± 0.03), THYM (0.05 ± 0.01), citric acid (1.58 ± 0.08) mg/ml, while sorbose was non-toxic. LGO induced upregulation of 16 and down-regulation of 24 genes, which CYP and heat shock most affected. These results suggest that in vitro assays such as this may be useful for hazard assessment of food ingredients for altered hepatic function.}, journal={Food and Chemical Toxicology}, publisher={Elsevier BV}, author={Zhang, Leshuai W. and Koci, Juraj and Jeffery, Brett and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2015}, month={Apr}, pages={105–115} }
 @inbook{riviere_monteiro-riviere_2014, title={Dermal Exposure and Absorption of Chemicals and Nanomaterials}, ISBN={9780128012383}, url={http://dx.doi.org/10.1016/b978-0-12-801238-3.01886-9}, DOI={10.1016/b978-0-12-801238-3.01886-9}, abstractNote={Skin is an important route of exposure to chemicals after occupational, environmental, and consumer product usage. Knowledge of the rate and extent of skin absorption is required for risk assessments to be made. The primary barrier to chemical absorption is the stratum corneum. Transport across this barrier is assumed to occur primarily by diffusion. Techniques for quantitating skin permeability using this assumption are presented, as are basic approaches to linking permeability to molecular properties using quantitative structure permeability relationships (QSPeR). Consideration is then given to how nanomaterial dermal absorption fits into this paradigm developed for small organic chemicals.}, booktitle={Reference Module in Biomedical Sciences}, publisher={Elsevier}, author={Riviere, J.E. and Monteiro-Riviere, N.A.}, year={2014} }
 @article{hall_george_kim_hwang_samberg_monteiro-riviere_narayan_2014, title={Growth of Zircone on Nanoporous Alumina Using Molecular Layer Deposition}, volume={66}, ISSN={["1543-1851"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84898791280&partnerID=MN8TOARS}, DOI={10.1007/s11837-014-0933-z}, number={4}, journal={JOM}, author={Hall, Robert A. and George, Steven M. and Kim, Yeongae and Hwang, Woonbong and Samberg, Meghan E. and Monteiro-Riviere, Nancy A. and Narayan, Roger J.}, year={2014}, month={Apr}, pages={649–653} }
 @article{samberg_mente_he_king_monteiro-riviere_2014, title={In Vitro Biocompatibility and Antibacterial Efficacy of a Degradable Poly(L-lactide-co-epsilon-caprolactone) Copolymer Incorporated with Silver Nanoparticles}, volume={42}, ISSN={["1573-9686"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84904246786&partnerID=MN8TOARS}, DOI={10.1007/s10439-013-0929-9}, abstractNote={Silver nanoparticles (Ag-nps) are currently used as a natural biocide to prevent undesired bacterial growth in clothing, cosmetics and medical products. The objective of the study was to impart antibacterial properties through the incorporation of Ag-nps at increasing concentrations to electrospun degradable 50:50 poly(l-lactide-co-epsilon-caprolactone) scaffolds for skin tissue engineering applications. The biocompatibility of the scaffolds containing Ag-nps was evaluated with human epidermal keratinocytes (HEK); cell viability and proliferation were evaluated using Live/Dead and alamarBlue viability assays following 7 and 14 days of cell culture on the scaffolds. Significant decreases in cell viability and proliferation were noted for the 1.0 mg(Ag) g(scaffold)−1 after 7 and 14 days on Ag-nps scaffolds. After 14 days, scanning electron microscopy revealed a confluent layer of HEK on the surface of the 0.0 and 0.1 mg(Ag) g(scaffold)−1. Both 0.5 and 1.0 mg(Ag) g(scaffold)−1 were capable of inhibiting both Gram positive and negative bacterial strains. Uniaxial tensile tests revealed a significant (p < 0.001) decrease in the modulus of elasticity following Ag-nps incorporation compared to control. These findings suggest that a scaffold containing between 0.5 and 1.0 mg(Ag) g(scaffold)−1 is both biocompatible and antibacterial, and is suitable for skin tissue engineering graft scaffolds.}, number={7}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Samberg, Meghan E. and Mente, Peter and He, Ting and King, Martin W. and Monteiro-Riviere, Nancy A.}, year={2014}, month={Jul}, pages={1482–1493} }
 @article{chen_zhang_darabi sahneh_scoglio_wohlleben_haase_monteiro-riviere_riviere_2014, title={Nanoparticle Surface Characterization and Clustering through Concentration-Dependent Surface Adsorption Modeling}, volume={8}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/nn503573s}, DOI={10.1021/nn503573s}, abstractNote={Quantitative characterization of nanoparticle interactions with their surrounding environment is vital for safe nanotechnological development and standardization. A recent quantitative measure, the biological surface adsorption index (BSAI), has demonstrated promising applications in nanomaterial surface characterization and biological/environmental prediction. This paper further advances the approach beyond the application of five descriptors in the original BSAI to address the concentration dependence of the descriptors, enabling better prediction of the adsorption profile and more accurate categorization of nanomaterials based on their surface properties. Statistical analysis on the obtained adsorption data was performed based on three different models: the original BSAI, a concentration-dependent polynomial model, and an infinite dilution model. These advancements in BSAI modeling showed a promising development in the application of quantitative predictive modeling in biological applications, nanomedicine, and environmental safety assessment of nanomaterials.}, number={9}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Chen, Ran and Zhang, Yuntao and Darabi Sahneh, Faryad and Scoglio, Caterina M. and Wohlleben, Wendel and Haase, Andrea and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2014}, month={Aug}, pages={9446–9456} }
 @book{monteiro-riviere_tran_2014, place={Boca Raton, FL}, edition={2nd}, title={Nanotoxicology: Progress toward Nanomedicine}, ISBN={9780429171420}, url={http://dx.doi.org/10.1201/b16562}, DOI={10.1201/b16562}, publisher={CRC Press}, year={2014} }
 @article{lin_monteiro-riviere_riviere_2014, title={Pharmacokinetics of metallic nanoparticles}, volume={7}, ISSN={1939-5116}, url={http://dx.doi.org/10.1002/wnan.1304}, DOI={10.1002/wnan.1304}, abstractNote={Metallic nanoparticles (NPs) have been widely applied in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. This review focuses on gold and silver (Ag) NPs, and briefly discusses iron oxide, titanium dioxide (TiO2), and zinc oxide NPs. Pharmacokinetics of metallic NPs depends on the particle type, size, surface charge, surface coating, protein binding, exposure route, dose, and species. Generally, blood half-life is shorter in rodents than in larger laboratory animals (e.g., rabbits or monkeys) and differs between intravenous and oral exposures. Oral, dermal, or inhalational absorption is low (≤5%), but may increase with smaller sizes, negative charge, and appropriate coatings. Metallic NPs can be distributed throughout the body, primarily accumulating in the liver, spleen, and lymph node due to nonspecific uptake by reticuloendothelial cells, and could remain in the body for ≥6 months. Metallic NPs (≤100 nm) can cross the blood–brain barrier (BBB), favored by coating with BBB-permeable neuropeptides. Placental transfer depends on the stage of embryonic/placental maturation and surface composition, and may be enhanced by coating with biocompatible molecules (e.g., ferritin or polyethylene glycol). Renal and biliary excretion is generally low due to persistent accumulation in tissues, but renal elimination could be substantially increased with smaller sizes and specific coatings (e.g., glutathione). Physiologically based pharmacokinetic models for gold/dendrimer composite nanodevices, AgNPs, and TiO2NPs have been developed in rats and the AgNP and TiO2NP models have been extrapolated to humans to support risk assessment and nanomedicine applications. WIREs Nanomed Nanobiotechnol 2015, 7:189–217. doi: 10.1002/wnan.1304 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials}, number={2}, journal={Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology}, publisher={Wiley}, author={Lin, Zhoumeng and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2014}, month={Oct}, pages={189–217} }
 @inbook{monteiro-riviere_2014, place={Boca Raton, FL}, edition={2nd}, title={Safety Implications of Nanomaterial Exposure to Skin}, ISBN={9780429171420}, url={http://dx.doi.org/10.1201/b16562-21}, DOI={10.1201/b16562-21}, abstractNote={The eld of nanotechnology has drastically grown because of development of engineered nanomaterials (ENMs) that can exhibit a variety of unique and tunable chemical and physical properties. It is these unique physicochemical properties that have made ENMs key components in material science, engineering, and medicine. This has led to an array of emerging technologies and numerous commercial products. Although nanomaterials (NMs) have widespread potential applications, skin penetration and toxicity of these ENMs have not been thoroughly evaluated under likely environmental, occupational, and medicinal exposure scenarios. Many challenges must be overcome before NMs can be used in nanomedicine and consumer products.13.1 Introduction .................................................................................................. 247 13.2 Skin Anatomy and Physiology......................................................................248 13.3 Model Systems Used to Assess Nanoparticle Absorption and Penetration.....249}, booktitle={Nanotoxicology: Progress toward nanomedicine}, publisher={CRC Press}, author={Monteiro-Riviere, N.A.}, editor={Monteiro-Riviere, N.A. and Tran, C. LangEditors}, year={2014}, pages={267–292} }
 @inbook{samberg_monteiro-riviere_2014, place={Boca Raton, FL}, edition={2nd}, title={Silver Nanoparticles in Biomedical Applications}, ISBN={9780429171420}, url={http://dx.doi.org/10.1201/b16562-30}, DOI={10.1201/b16562-30}, booktitle={Nanotoxicology: Progress toward Nanomedicine}, publisher={CRC Press}, author={Samberg, M.E. and Monteiro-Riviere, N.A.}, editor={Monteiro-Riviere, N.A. and Lang Tran, C.Editors}, year={2014}, month={Mar}, pages={425–442} }
 @article{boehm_chen_gittard_chichkov_monteiro-riviere_nasir_narayan_2014, title={Two-photon polymerization/micromolding of microscale barbs for medical applications}, volume={28}, ISSN={0169-4243 1568-5616}, url={http://dx.doi.org/10.1080/01694243.2012.693828}, DOI={10.1080/01694243.2012.693828}, abstractNote={Tissue barbs are small-scale structures that may be used for sutureless joining of tissues. In this study, several types of tissue barbs were fabricated using two-photon polymerization/micromolding, including two-pronged tissue barbs, eight-pronged tissue barbs, 10-pronged tissue barbs, and 16-pronged tissue barbs. Tissue barb penetration in porcine tissue was observed using confocal laser scanning microscopy. Constructs containing medical tape and tissue barbs were created by applying tissue barbs in a parallel arrangement to Transpore™ medical tape. These results suggest that two-photon polymerization/micromolding is an indirect rapid prototyping approach that may be used for high-throughput replication of tissue barbs and other microstructured solid wound sealants.}, number={3-4}, journal={Journal of Adhesion Science and Technology}, publisher={Informa UK Limited}, author={Boehm, R.D. and Chen, B. and Gittard, S.D. and Chichkov, B.N. and Monteiro-Riviere, N.A. and Nasir, A. and Narayan, R.J.}, year={2014}, month={Feb}, pages={387–398} }
 @article{samberg_tan_monteiro-riviere_orndorff_shirwaiker_2013, title={Biocompatibility analysis of an electrically-activated silver-based antibacterial surface system for medical device applications}, volume={24}, ISSN={["1573-4838"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84876410058&partnerID=MN8TOARS}, DOI={10.1007/s10856-012-4838-5}, number={3}, journal={JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE}, author={Samberg, Meghan E. and Tan, Zhuo and Monteiro-Riviere, Nancy A. and Orndorff, Paul E. and Shirwaiker, Rohan A.}, year={2013}, month={Mar}, pages={755–760} }
 @article{riviere_scoglio_sahneh_monteiro-riviere_2013, title={Computational approaches and metrics required for formulating biologically realistic nanomaterial pharmacokinetic models}, volume={6}, ISSN={1749-4699}, url={http://dx.doi.org/10.1088/1749-4699/6/1/014005}, DOI={10.1088/1749-4699/6/1/014005}, abstractNote={The field of nanomaterial pharmacokinetics is in its infancy, with major advances largely restricted by a lack of biologically relevant metrics, fundamental differences between particles and small molecules of organic chemicals and drugs relative to biological processes involved in disposition, a scarcity of sufficiently rich and characterized in vivo data and a lack of computational approaches to integrating nanomaterial properties to biological endpoints. A central concept that links nanomaterial properties to biological disposition, in addition to their colloidal properties, is the tendency to form a biocorona which modulates biological interactions including cellular uptake and biodistribution. Pharmacokinetic models must take this crucial process into consideration to accurately predict in vivo disposition, especially when extrapolating from laboratory animals to humans since allometric principles may not be applicable. The dynamics of corona formation, which modulates biological interactions including cellular uptake and biodistribution, is thereby a crucial process involved in the rate and extent of biodisposition. The challenge will be to develop a quantitative metric that characterizes a nanoparticle's surface adsorption forces that are important for predicting biocorona dynamics. These types of integrative quantitative approaches discussed in this paper for the dynamics of corona formation must be developed before realistic engineered nanomaterial risk assessment can be accomplished.}, number={1}, journal={Computational Science & Discovery}, publisher={IOP Publishing}, author={Riviere, Jim E and Scoglio, Caterina and Sahneh, Faryad D and Monteiro-Riviere, Nancy A}, year={2013}, month={Oct}, pages={014005} }
 @misc{shirwaiker_samberg_cohen_wysk_monteiro-riviere_2013, title={Nanomaterials and synergistic low-intensity direct current (LIDC) stimulation technology for orthopedic implantable medical devices}, volume={5}, ISSN={["1939-0041"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84876463086&partnerID=MN8TOARS}, DOI={10.1002/wnan.1201}, abstractNote={Nanomaterials play a significant role in biomedical research and applications because of their unique biological, mechanical, and electrical properties. In recent years, they have been utilized to improve the functionality and reliability of a wide range of implantable medical devices ranging from well-established orthopedic residual hardware devices (e.g., hip implants) that can repair defects in skeletal systems to emerging tissue engineering scaffolds that can repair or replace organ functions. This review summarizes the applications and efficacies of these nanomaterials that include synthetic or naturally occurring metals, polymers, ceramics, and composites in orthopedic implants, the largest market segment of implantable medical devices. The importance of synergistic engineering techniques that can augment or enhance the performance of nanomaterial applications in orthopedic implants is also discussed, the focus being on a low-intensity direct electric current (LIDC) stimulation technology to promote the long-term antibacterial efficacy of oligodynamic metal-based surfaces by ionization, while potentially accelerating tissue growth and osseointegration. While many nanomaterials have clearly demonstrated their ability to provide more effective implantable medical surfaces, further decisive investigations are necessary before they can translate into medically safe and commercially viable clinical applications. The article concludes with a discussion about some of the critical impending issues with the application of nanomaterials-based technologies in implantable medical devices, and potential directions to address these. WIREs Nanomed Nanobiotechnol 2013, 5:191–204. doi: 10.1002/wnan.1201 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement}, number={3}, journal={WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY}, author={Shirwaiker, Rohan A. and Samberg, Meghan E. and Cohen, Paul H. and Wysk, Richard A. and Monteiro-Riviere, Nancy A.}, year={2013}, pages={191–204} }
 @article{murray_kisin_inman_young_muhammed_burks_uheida_tkach_waltz_castranova_et al._2013, title={Oxidative Stress and Dermal Toxicity of Iron Oxide Nanoparticles In Vitro}, volume={67}, ISSN={["1559-0283"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84886583005&partnerID=MN8TOARS}, DOI={10.1007/s12013-012-9367-9}, number={2}, journal={CELL BIOCHEMISTRY AND BIOPHYSICS}, author={Murray, Ashley R. and Kisin, Elena and Inman, Alfred and Young, Shih-Houng and Muhammed, Mamoun and Burks, Terrance and Uheida, Abdusalam and Tkach, Alexey and Waltz, Micah and Castranova, Vincent and et al.}, year={2013}, month={Nov}, pages={461–476} }
 @misc{karadzovska_brooks_monteiro-riviere_riviere_2013, title={Predicting skin permeability from complex vehicles}, volume={65}, ISSN={["1872-8294"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84873522106&partnerID=MN8TOARS}, DOI={10.1016/j.addr.2012.01.019}, abstractNote={It is now widely accepted that vehicle and formulation components influence the rate and extent of passive chemical absorption through skin. Significant progress, over the last decades, has been made in predicting dermal absorption from a single vehicle; however the effect of a complex, realistic mixture has not received its due attention. Recent studies have aimed to bridge this gap by extending the use of quantitative structure–permeation relationship (QSPR) models based on linear free energy relationships (LFER) to predict dermal absorption from complex mixtures with the inclusion of significant molecular descriptors such as a mixture factor that accounts for the physicochemical properties of the vehicle/mixture components. These models have been compiled and statistically validated using the data generated from in vitro or ex vivo experimental techniques. This review highlights the progress made in predicting skin permeability from complex vehicles.}, number={2}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Karadzovska, Daniela and Brooks, James D. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2013}, month={Feb}, pages={265–277} }
 @article{monteiro-riviere_samberg_oldenburg_riviere_2013, title={Protein binding modulates the cellular uptake of silver nanoparticles into human cells: Implications for in vitro to in vivo extrapolations?}, volume={220}, ISSN={["1879-3169"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879479222&partnerID=MN8TOARS}, DOI={10.1016/j.toxlet.2013.04.022}, abstractNote={Nanoparticles (NP) absorbed in the body will come in contact with blood proteins and form NP/protein complexes termed protein coronas, which may modulate NP cellular uptake. This study quantitated human epidermal keratinocyte (HEK) uptake of silver (Ag) NP complexed to different human serum proteins. Prior to HEK dosing, AgNP (20nm and 110nm citrate BioPure™; 40nm and 120nm silica-coated) were preincubated for 2h at 37°C without (control) or with physiological levels of albumin (44mg/ml), IgG (14.5mg/ml) or transferrin (3mg/ml) to form protein-complexed NP. HEK were exposed to the protein incubated AgNP for 3h, rinsed and incubated for 24h, rinsed in buffer and lysed. Ag was assayed by inductively-coupled plasma optical emission spectrometry. Uptake of Ag in HEK was <4.1% of applied dose with proteins suppressing citrate, but not silica coated Ag uptake. IgG exposure dramatically reduced 110nm citrate AgNP uptake. In contrast, greatest uptake of 20nm silica AgNP was seen with IgG, while 110nm silica AgNP showed minimal protein effects. Electron microscopy confirmed cellular uptake of all NP but showed differences in the appearance and agglomeration state of the NP within HEK vacuoles. This work suggests that NP association with different serum proteins, purportedly forming different protein coronas, significantly modulates Ag uptake into HEK compared to native NP uptake, suggesting caution in extrapolating in vitro uptake data to predict behavior in vivo where the nature of the protein corona may determine patterns of cellular uptake, and thus biodistribution, biological activity and toxicity.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Monteiro-Riviere, Nancy A. and Samberg, Meghan E. and Oldenburg, Steven J. and Riviere, Jim E.}, year={2013}, month={Jul}, pages={286–293} }
 @inbook{monteiro-riviere_2013, place={New York, NY}, title={Skin Penetration of Engineered Nanomaterials}, volume={9781461450344}, ISBN={9781461450344 9781461450337}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84949176380&partnerID=MN8TOARS}, DOI={10.1007/978-1-4614-5034-4_6}, booktitle={Nanotechnology in Dermatology}, publisher={Springer}, author={Monteiro-Riviere, N.A.}, editor={Nasir, Eds A. and Friedman, A. and Wang, S.Editors}, year={2013}, pages={51–61} }
 @article{gittard_chen_xu_ovsianikov_chichkov_monteiro-riviere_narayan_2013, title={The effects of geometry on skin penetration and failure of polymer microneedles}, volume={27}, ISSN={["1568-5616"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84874631649&partnerID=MN8TOARS}, DOI={10.1080/01694243.2012.705101}, abstractNote={Microneedles are small-scale devices that may be used for drug delivery and biosensing. In this study, the forces required for mechanical failure, the modes of mechanical failure, as well as the mechanisms for microneedle penetration into porcine skin were examined. Microneedles produced from the acrylate-based polymer e-Shell 200 using an indirect rapid prototyping approach involving two-photon polymerization and poly(dimethylsiloxane) micromolding were found to possess sufficient strength for penetration of porcine skin. The failure forces were an order of magnitude greater than the forces necessary for full insertion into the skin. Bending was the most common form of failure; an increasing aspect ratio and a decreasing tip diameter were associated with lower failure forces. Video captured during skin penetration revealed that microneedle penetration into the skin occurred by means of a series of insertions and not by means of a single insertion event. Images obtained during and after skin penetration confirmed microneedle penetration of skin as well as transdermal delivery of lucifer yellow dye. These findings shed insight into the mechanisms of microneedle penetration and failure, facilitating design improvements for polymer microneedles.}, number={3}, journal={JOURNAL OF ADHESION SCIENCE AND TECHNOLOGY}, author={Gittard, Shaun D. and Chen, Bo and Xu, Huadong and Ovsianikov, Aleksandr and Chichkov, Boris N. and Monteiro-Riviere, Nancy A. and Narayan, Roger J.}, year={2013}, month={Feb}, pages={227–243} }
 @article{riviere_leavens_brooks_monteiro-riviere_2012, title={Acute vascular effects of nanoparticle infusion in isolated perfused skin}, volume={8}, ISSN={1549-9634}, url={http://dx.doi.org/10.1016/j.nano.2012.02.016}, DOI={10.1016/j.nano.2012.02.016}, abstractNote={The majority of studies on the effect of nanomaterials on biological function involves either isolated in vitro cell systems or are concerned with in vivo effects after inhalational or dermal exposure. The current work reports on an intriguing observation of the vascular effects seen in an ex vivo perfused tissue preparation, the isolated perfused porcine skin flap (IPPSF), in studies conducted to assess nanomaterial biodistribution. Compared with a relatively large dataset involving organic chemical infusions (n = 53), infusion of six different nanoparticles of diverse sizes and composition (silica or dextran coated Fe(2)O(3), silica or citrate coated silver, PEG or carboxylated quantum dots [QD]) resulted in statistically significant post-infusion flap weight gain and an increase in arterial perfusion pressure (especially with QD-PEG). In contrast, infusion with nC(60) nanoparticles did not produce these effects. These observations suggest certain nanoparticle infusions may be associated with acute vascular physiologic effects that merit further attention.In this study utilizing a perfused porcine skin flap, specific nanoparticle infusions were demonstrated to be associated with significant acute vascular physiological effects.}, number={4}, journal={Nanomedicine: Nanotechnology, Biology and Medicine}, publisher={Elsevier BV}, author={Riviere, Jim E. and Leavens, Teresa L. and Brooks, James D. and Monteiro-Riviere, Nancy A.}, year={2012}, month={May}, pages={428–431} }
 @article{baynes_riviere_franz_monteiro riviere_lehman_peyrou_toutain_2012, title={Challenges obtaining a biowaiver for topical veterinary dosage forms}, volume={35}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2012.01381.x}, DOI={10.1111/j.1365-2885.2012.01381.x}, abstractNote={Baynes, R., Riviere, J., Franz, T., Monteiro-Riviere, N., Lehman, P., Peyrou, M., Toutain, P.-L. Challenges obtaining a biowaiver for topical veterinary dosage forms. J. vet. Pharmacol. Therap.35 (Suppl. 1), 103–114. Obtaining a biowaiver for topical drugs used in veterinary species faces many of the same challenges associated with human topicals. However, the skin of domestic animals varies anatomically and biochemically and experimental approaches to assess bioequivalence (BE) in veterinary species have challenges that are not often encountered with human skin. This is especially the situation with locally acting drugs. The focus of this paper is to address several of the challenges associated with (i) determining the BE of these locally acting drugs and (ii) critically examine the current technological advances that can act as a surrogate for clinical trials.}, number={SUPPL. 1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Baynes, R. and Riviere, J. and Franz, T. and Monteiro Riviere, N. and Lehman, P. and Peyrou, M. and Toutain, P. L.}, year={2012}, month={Mar}, pages={103–114} }
 @inbook{monteiro riviere_larese filon_2012, place={Burlington}, title={Effects of Engineered Nanomaterials on Skin}, ISBN={9780123869760}, booktitle={Adverse Effects of Engineered Nanomaterials : Exposure, Toxicology, and Impact on Human Health}, publisher={Elsevier Science}, author={Monteiro Riviere, Na and Larese Filon, F}, editor={Fadeel, B. and Pietroiusti, A. and Shvedova, A.Editors}, year={2012}, pages={185–207} }
 @article{monteiro-riviere_inman_mathur_muhammed_fadeel_riviere_2012, title={Effects of eight nanoparticles of different sizes and shapes on human epidermal keratinocytes}, volume={132}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000302866900308&KeyUID=WOS:000302866900308}, journal={Journal of Investigative Dermatology}, author={Monteiro-Riviere, N. A. and Inman, A. O. and Mathur, S. and Muhammed, M. and Fadeel, B. and Riviere, J. E.}, year={2012}, pages={S52} }
 @inbook{samberg_monteiro-riviere_2012, place={Heidelberg, Germany}, title={In Vitro and In Vivo Toxicity of Silver Nanoparticles}, ISBN={9789048197514 9048197511 9789048197521}, booktitle={Encyclopedia of Nanotechnology}, publisher={Springer Verlag}, author={Samberg, M.E. and Monteiro-Riviere, N.A.}, editor={Bhushan), Ed B.Editor}, year={2012}, pages={1069–1077,} }
 @article{leavens_monteiro-riviere_inman_brooks_oldenburg_riviere_2012, title={In vitro biodistribution of silver nanoparticles in isolated perfused porcine skin flaps}, volume={32}, ISSN={["0260-437X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84866866954&partnerID=MN8TOARS}, DOI={10.1002/jat.2750}, abstractNote={Nanomaterials increasingly are playing a role in society for uses ranging from biomedicine to microelectronics; however, pharmacokinetic studies, which will be necessary for human health risk assessments, are limited. Currently the most widely used nanoparticle in consumer products is silver (Ag). The objective of the present study was to quantify the local biodistribution of two types of Ag nanoparticles, Ag-citrate and Ag-silica, in the isolated perfused porcine skin flap (IPPSF). IPPSFs were perfused for 4 h with 0.84 µg ml–1 Ag-citrate or 0.48 µg ml–1 Ag-silica followed by a 4-h perfusion with media only during a washout phase. Arterial and venous concentrations of Ag were measured in the media by inductively coupled plasma optical emission spectrometry (ICP-OES). Venous concentrations of Ag for both types of nanoparticles were best fit with a two compartment model. The normalized volumes of distribution estimated from the noncompartmental analysis of the venous concentrations indicated distribution of Ag greater than the vascular space; however, because total Ag was measured, the extravascular distribution could be attributed to diffusion of Ag ions. The estimated clearance for both types of Ag nanoparticles was 1 ml min–1, which was equal to the flap perfusion rate, indicating no detectable elimination of Ag from the system. Four hours after infusion of the Ag nanoparticles, the recovery of Ag in the venous effluent was 90 ± 5.0% and 87 ± 22 % of the infused Ag for Ag-citrate and Ag-silica, respectively. Copyright © 2012 John Wiley & Sons, Ltd.}, number={11}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Leavens, Teresa L. and Monteiro-Riviere, Nancy A. and Inman, Alfred O. and Brooks, James D. and Oldenburg, Steven J. and Riviere, Jim E.}, year={2012}, month={Nov}, pages={913–919} }
 @article{monteiro-riviere_linder_inman_saathoff_xia_riviere_2012, title={LACK OF HYDROXYLATED FULLERENE TOXICITY AFTER INTRAVENOUS ADMINISTRATION TO FEMALE SPRAGUE-DAWLEY RATS}, volume={75}, ISSN={["1087-2620"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000303594100001&KeyUID=WOS:000303594100001}, DOI={10.1080/15287394.2012.670894}, abstractNote={Hydroxylated fullerenes (C60OHx) or fullerols are water-soluble carbon nanoparticles that have been explored for potential therapeutic applications. This study assesses acute in vivo tolerance in 8-wk-old female Sprague-Dawley rats to intravenous (iv) administration of 10 mg/kg of well-characterized C60(OH)30. Complete histopathology and clinical chemistries are assessed at 8, 24, and 48 h after dosing. Minor histopathology changes are seen, primarily in one animal. No clinically significant chemistry changes were observed after treatment. These experiments suggest that this fullerol was well tolerated after iv administration to rats.}, number={7}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Monteiro-Riviere, Nancy A. and Linder, Keith E. and Inman, Alfred O. and Saathoff, John G. and Xia, Xin-Rui and Riviere, Jim E.}, year={2012}, pages={367–373} }
 @article{prow_monteiro-riviere_inman_grice_chen_zhao_sanchez_gierden_kendall_zvyagin_et al._2012, title={Quantum dot penetration into viable human skin}, volume={6}, ISSN={["1743-5404"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000299784600006&KeyUID=WOS:000299784600006}, DOI={10.3109/17435390.2011.569092}, abstractNote={Systematic studies probing the effects of nanoparticle surface modification and formulation pH are important in nanotoxicology and nanomedicine. In this study, we use laser-scanning fluorescence confocal microscopy to evaluate nanoparticle penetration in viable excised human skin that was intact or tape-stripped. Quantum dot (QD) fluorescent nanoparticles with three surface modifications: Polyethylene glycol (PEG), PEG-amine (PEG-NH₂) and PEG-carboxyl (PEG-COOH) were evaluated for human skin penetration from aqueous solutions at pH 7.0 and at pHs of solutions provided by the QD manufacturer: 8.3 (PEG, PEG-NH₂) and 9.0 (PEG-COOH). There was some penetration into intact viable epidermis of skin for the PEG-QD at pH 8.3, but not at pH 7.0 nor for any other QD at the pHs used. Upon tape stripping 30 strips of stratum corneum, all QDs penetrated through the viable epidermis and into the upper dermis within 24 h.}, number={2}, journal={NANOTOXICOLOGY}, author={Prow, Tarl W. and Monteiro-Riviere, Nancy A. and Inman, Alfred O. and Grice, Jeffrey E. and Chen, Xianfeng and Zhao, Xin and Sanchez, Washington H. and Gierden, Audrey and Kendall, Mark A. F. and Zvyagin, Andrei V. and et al.}, year={2012}, month={Mar}, pages={173–185} }
 @article{samberg_loboa_oldenburg_monteiro-riviere_2012, title={Silver nanoparticles do not influence stem cell differentiation but cause minimal toxicity}, volume={7}, ISSN={["1748-6963"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84868143959&partnerID=MN8TOARS}, DOI={10.2217/nnm.12.18}, abstractNote={Aims: To evaluate the toxicity and cellular uptake of both undifferentiated and differentiated human adipose-derived stem cells (hASCs) exposed to silver nanoparticles (Ag-NPs), and to assess their effect on hASC differentiation. Materials & methods: hASC were exposed to 10- or 20-nm Ag-NPs at concentrations of 0.1, 1.0, 10.0, 50.0 and 100.0 µg/ml either before or after differentiation down the adipogenic or osteogenic pathways. Results: Exposure of hASC to either 10- or 20-nm Ag-NPs resulted in no significant cytotoxicity to hASC, and minimal dose-dependent toxicity to adipogenic and osteogenic cells at 10 µg/ml. Each of the hASC, adipogenic and osteogenic cells showed cellular uptake of both 10- and 20-nm Ag-NPs, without causing significant ultrastructural alterations. Exposure to 10- or 20-nm Ag-NPs did not influence the differentiation of the cells, and at antimicrobial concentrations of Ag-NPs resulted in a minimal decrease in viability. Conclusion: The biocompatibility of Ag-NPs with both undifferentiated and differentiated hASC establishes their suitability for incorporation into tissue-engineered graft scaffolds, for the prevention of bacterial contamination upon implantation. Original submitted 28 September 2011; Revised submitted 15 November 2011; Published online 14 May 2012}, number={8}, journal={NANOMEDICINE}, author={Samberg, Meghan E. and Loboa, Elizabeth G. and Oldenburg, Steven J. and Monteiro-Riviere, Nancy A.}, year={2012}, month={Aug}, pages={1197–1209} }
 @inbook{monteiro-riviere_filon_2012, title={Skin}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879233315&partnerID=MN8TOARS}, DOI={10.1016/B978-0-12-386940-1.00011-8}, booktitle={Adverse Effects of Engineered Nanomaterials}, author={Monteiro-Riviere, N.A. and Filon, F.L.}, year={2012}, pages={185–207} }
 @article{skoog_sumant_monteiro-riviere_narayan_2012, title={Ultrananocrystalline Diamond-Coated Microporous Silicon Nitride Membranes for Medical Implant Applications}, volume={64}, ISSN={1047-4838 1543-1851}, url={http://dx.doi.org/10.1007/S11837-012-0300-X}, DOI={10.1007/s11837-012-0300-x}, number={4}, journal={JOM}, publisher={Springer Science and Business Media LLC}, author={Skoog, Shelby A. and Sumant, Anirudha V. and Monteiro-Riviere, Nancy A. and Narayan, Roger J.}, year={2012}, month={Apr}, pages={520–525} }
 @article{zhang_monteiro-riviere_2012, title={Use of confocal microscopy for nanoparticle drug delivery through skin}, volume={18}, ISSN={1083-3668}, url={http://dx.doi.org/10.1117/1.jbo.18.6.061214}, DOI={10.1117/1.JBO.18.6.061214}, abstractNote={Confocal laser scanning microscopy (CLSM) is a well-used microscopic tool that provides valuable morphological and functional information within cells and tissues. The application of CLSM to skin and the topical penetration of nanoparticles (NP) will be addressed. First, we describe the advantages of confocal microscopy compared to other techniques and its use relative to skin research. Second, we discuss the ability of CLSM to detect single NP. Regarding their interaction with skin, the appropriate method to retain nanoparticle localization in the tissue with minimal fixation is critically important. Also, the interaction of several different types of NP (quantum dots, fullerene and dendrimers) and their interaction with skin detected by CLSM under various conditions (flexed, tape stripped and abraded skin) is reviewed. Finally, human epidermal keratinocytes and dendritic cells that serve as appropriate in vitro models for skin cell interactions and cellular uptake of NP are also discussed. In conclusion, the unique functions of CLSM such as the ability to detect fluorescence, optical sectioning, three dimensional remodeling, as well as its use in the reflection mode in tandem with other methods, provides great promise with broad applications regarding the interactions of nanomaterials with skin.}, number={6}, journal={Journal of Biomedical Optics}, publisher={SPIE-Intl Soc Optical Eng}, author={Zhang, Leshuai W. and Monteiro-Riviere, Nancy A.}, year={2012}, month={Dec}, pages={061214} }
 @article{wiench_schulte_schneider_lan_ravenzwaay_monteiro-riviere_creutzenberg_landsiedel_2012, title={Zinc oxide - nanosize does not change the toxicological profile}, volume={385}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000300779500460&KeyUID=WOS:000300779500460}, journal={Naunyn-Schmiedebergs Archives of Pharmacology}, author={Wiench, K. and Schulte, S. and Schneider, S. and Lan, M-H and Ravenzwaay, B. and Monteiro-Riviere, N. and Creutzenberg, O. and Landsiedel, R.}, year={2012}, pages={104} }
 @article{samberg_orndorff_monteiro-riviere_2011, title={Antibacterial efficacy of silver nanoparticles of different sizes, surface conditions and synthesis methods}, volume={5}, ISSN={["1743-5404"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000290936000012&KeyUID=WOS:000290936000012}, DOI={10.3109/17435390.2010.525669}, abstractNote={Silver nanoparticles (Ag-nps) are used as a natural biocide to prevent undesired bacterial growth in clothing and cosmetics. The objective of this study was to assess the antibacterial efficacy of Ag-nps of different sizes, surface conditions, and synthesis methods against Escherichia coli, Ag-resistant E. coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Salmonella sp. Ag-nps samples were synthesized by: Base reduction with unmodified surfaces and used as synthesized (‘unwashed’; 20, 50 and 80 nm) or after 20 phosphate buffer washes (‘washed’; 20, 50 and 80 nm), or synthesized by laser ablation with carbon-stabilized surfaces (‘carbon-coated’; 25 and 35 nm). Unwashed Ag-nps were toxic to all bacterial strains at concentrations between 3.0–8.0 μg/ml. The washed Ag-nps and carbon-coated Ag-nps were toxic to all bacterial strains except Ag-resistant E. coli at concentrations between 64.0–1024.0 μg/ml. Ag-resistant E. coli died only when treated with unwashed Ag-nps or its supernatant, both of which contained formaldehyde.}, number={2}, journal={NANOTOXICOLOGY}, author={Samberg, Meghan E. and Orndorff, Paul E. and Monteiro-Riviere, Nancy A.}, year={2011}, month={Jun}, pages={244–253} }
 @article{hyde_stewart_scarel_parsons_shih_shih_lin_su_monteiro-riviere_narayan_et al._2011, title={Atomic layer deposition of titanium dioxide on cellulose acetate for enhanced hemostasis}, volume={6}, ISSN={1860-6768}, url={http://dx.doi.org/10.1002/biot.201000342}, DOI={10.1002/biot.201000342}, abstractNote={TiO2 films may be used to alter the wettability and hemocompatibility of cellulose materials. In this study, pure and stoichiometric TiO2 films were grown using atomic layer deposition on both silicon and cellulose substrates. The films were grown with uniform thicknesses and with a growth rate in agreement with literature results. The TiO2 films were shown to profoundly alter the water contact angle values of cellulose in a manner dependent upon processing characteristics. Higher amounts of protein adsorption indicated by blurry areas on images generated by scanning electron microscopy were noted on TiO2-coated cellulose acetate than on uncoated cellulose acetate. These results suggest that atomic layer deposition is an appropriate method for improving the biological properties of hemostatic agents and other blood-contacting biomaterials.}, number={2}, journal={Biotechnology Journal}, publisher={Wiley}, author={Hyde, G. Kevin and Stewart, S. Michael and Scarel, Giovanna and Parsons, Gregory N. and Shih, Chun-Che and Shih, Chun-Ming and Lin, Shing-Jong and Su, Yea-Yang and Monteiro-Riviere, Nancy A. and Narayan, Roger J. and et al.}, year={2011}, month={Feb}, pages={213–223} }
 @article{zhang_baeumer_monteiro-riviere_2011, title={Cellular uptake mechanisms and toxicity of quantum dots in dendritic cells}, volume={6}, ISSN={["1748-6963"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000293335200007&KeyUID=WOS:000293335200007}, DOI={10.2217/nnm.11.73}, abstractNote={Quantum dots (QDs) are nanoparticles with strong fluorescent emission and are novel tools used in biomedical applications, but the toxicity and mechanism of cellular uptake are poorly understood. QD655-COOH (negative charge, 18 nm) consist of a cadmium/selenide core and a zinc sulfide shell with a carboxylic acid coating with an emission wavelength of 655 nm. Materials & Methods: Peripheral blood mononuclear cells were isolated from porcine blood by gradient centrifugation, and monocytes, which are CD14 positive, were purified. Monocytes were differentiated into dendritic cells (DCs) with GM-CSF and IL-4. Results: Monocytes showed cellular uptake of QD655-COOH, while lymphocytes did not. Monocyte differentiation into DCs increased the cellular uptake by sixfold when dosed with 2 nM of QD655-COOH. Transmission electron microscopy depicted QD655-COOH in the cytoplasmic vacuoles of DCs. Twelve endocytic inhibitors demonstrated QD655-COOH endocytosis in DCs, which was recognized by clathrin and scavenger receptors and regulated by F-actin and phospholipase C. In addition, DC maturation with lipopolysaccharide (LPS) caused an increase in QD655-COOH uptake compared with DCs without LPS stimulation. Viability assays, including 96AQ, CCK-8, alamar blue and ApoTox, exhibited minimal toxicity in DCs dosed with QD655-COOH at 24 h. However, glutathione levels showed a significant decrease with 10 nM of QD655-COOH. Finally, QD655-COOH exposure was associated with a decrease in CD80/CD86 expression after LPS stimulation, suggesting suppression with DC maturation. Conclusion: These findings shed light on the mechanism of QD655-COOH uptake in DCs and that cellular uptake pathways are dependent on cell type and cell differentiation.}, number={5}, journal={NANOMEDICINE}, author={Zhang, Leshuai W. and Baeumer, Wolfgang and Monteiro-Riviere, Nancy A.}, year={2011}, month={Jul}, pages={777–791} }
 @article{monteiro-riviere_2011, title={Commentary on transcutaneous delivery}, volume={3}, ISSN={["1939-0041"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000298258800001&KeyUID=WOS:000298258800001}, DOI={10.1002/wnan.160}, abstractNote={This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials}, number={5}, journal={WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY}, author={Monteiro-Riviere, Nancy}, year={2011}, pages={439–440} }
 @article{gittard_miller_jin_martin_boehm_chisholm_stafslien_daniels_cilz_monteiro-riviere_et al._2011, title={Deposition of antimicrobial coatings on microstereolithography-fabricated microneedles}, volume={63}, ISSN={["1543-1851"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000291610800011&KeyUID=WOS:000291610800011}, DOI={10.1007/s11837-011-0093-3}, number={6}, journal={JOM}, author={Gittard, Shaun D. and Miller, Philip R. and Jin, Chunming and Martin, Timothy N. and Boehm, Ryan D. and Chisholm, Bret J. and Stafslien, Shane J. and Daniels, Justin W. and Cilz, Nicholas and Monteiro-Riviere, Nancy A. and et al.}, year={2011}, month={Jun}, pages={59–68} }
 @article{monteiro-riviere_riviere_inman_wiench_schulte_landsiedel_2011, title={Dermal Penetration of UVB-Damaged Skin by Titanium- and Zincoxide Nanoparticles in Sunscreen Formulations}, volume={383}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000288573100511&KeyUID=WOS:000288573100511}, journal={Naunyn-Schmiedebergs Archives of Pharmacology}, author={Monteiro-Riviere, N. and Riviere, J. and Inman, A. and Wiench, K. and Schulte, S. and Landsiedel, R.}, year={2011}, pages={101} }
 @article{saathoff_inman_xia_riviere_monteiro-riviere_2011, title={In vitro toxicity assessment of three hydroxylated fullerenes in human skin cells}, volume={25}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000298362500075&KeyUID=WOS:000298362500075}, DOI={10.1016/j.tiv.2011.09.013}, abstractNote={Carbon fullerenes possess unique properties and their interactions with biomolecules have widespread applications. Functionalization of fullerenes with hydroxyl groups (fullerenols) can increase the solubility and potential for cellular interaction, but the health and safety effects of varying degrees of fullerene hydroxylation in biological systems is poorly understood. Existing reports regarding the toxicity and inflammatory potential of fullerenols give conflicting conclusions. To further elucidate the potential for toxicity of fullerenols, human epidermal keratinocytes (HEK) were exposed to fullerenols (low (C60(OH)20), medium (C60(OH)24), and high (C60(OH)32)) at concentrations ranging from 0.000544–42.5 μg/ml for 24 and 48 h. A statistically significant (p < 0.05) decrease in viability with alamar Blue (aB) was noted only with C60(OH)32 at 42.5 μg/ml after 24 h. Nanoparticle (NP) controls showed minimal NP/assay interference of the three fullerenols with the aB viability assay. Normalized IL-8 concentration for C60(OH)20 was not significantly different from control, while C60(OH)24 and C60(OH)32 showed a significant decrease at 24 and 48 h. These results suggest that different hydroxylation of fullerenes caused no cytotoxicity or inflammation up to 8.55 μg/ml. These findings suggest that extrapolation across similar NP will be dependent upon surface chemistry and concentration which may affect the degree of agglomeration and thus biological effects.}, number={8}, journal={TOXICOLOGY IN VITRO}, author={Saathoff, J. G. and Inman, A. O. and Xia, X. R. and Riviere, J. E. and Monteiro-Riviere, N. A.}, year={2011}, month={Dec}, pages={2105–2112} }
 @article{miller_gittard_edwards_lopez_xiao_wheeler_monteiro-riviere_brozik_polsky_narayan_2011, title={Integrated carbon fiber electrodes within hollow polymer microneedles for transdermal electrochemical sensing}, volume={5}, ISSN={1932-1058}, url={http://dx.doi.org/10.1063/1.3569945}, DOI={10.1063/1.3569945}, abstractNote={In this study, carbon fiber electrodes were incorporated within a hollow microneedle array, which was fabricated using a digital micromirror device-based stereolithography instrument. Cell proliferation on the acrylate-based polymer used in microneedle fabrication was examined with human dermal fibroblasts and neonatal human epidermal keratinocytes. Studies involving full-thickness cadaveric porcine skin and trypan blue dye demonstrated that the hollow microneedles remained intact after puncturing the outermost layer of cadaveric porcine skin. The carbon fibers underwent chemical modification in order to enable detection of hydrogen peroxide and ascorbic acid; electrochemical measurements were demonstrated using integrated electrode-hollow microneedle devices.}, number={1}, journal={Biomicrofluidics}, publisher={AIP Publishing}, author={Miller, Philip R. and Gittard, Shaun D. and Edwards, Thayne L. and Lopez, DeAnna M. and Xiao, Xiaoyin and Wheeler, David R. and Monteiro-Riviere, Nancy A. and Brozik, Susan M. and Polsky, Ronen and Narayan, Roger J.}, year={2011}, month={Mar}, pages={013415} }
 @article{xia_monteiro-riviere_mathur_song_xiao_oldenberg_fadeel_riviere_2011, title={Mapping the Surface Adsorption Forces of Nanomaterials in Biological Systems}, volume={5}, ISSN={["1936-086X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000297143300069&KeyUID=WOS:000297143300069}, DOI={10.1021/nn203303c}, abstractNote={The biological surface adsorption index (BSAI) is a novel approach to characterize surface adsorption energy of nanomaterials that is the primary force behind nanoparticle aggregation, protein corona formation, and other complex interactions of nanomaterials within biological systems. Five quantitative nanodescriptors were obtained to represent the surface adsorption forces (hydrophobicity, hydrogen bond, polarity/polarizability, and lone-pair electrons) of the nanomaterial interaction with biological components. We have mapped the surface adsorption forces over 16 different nanomaterials. When the five-dimensional information of the nanodescriptors was reduced to two dimensions, the 16 nanomaterials were classified into distinct clusters according their surface adsorption properties. BSAI nanodescriptors are intrinsic properties of nanomaterials useful for quantitative structure–activity relationship (QSAR) model development. This is the first success in quantitative characterization of the surface adsorption forces of nanomaterials in biological conditions, which could open a quantitative avenue in predictive nanomedicine development, risk assessment, and safety evaluation of nanomaterials.}, number={11}, journal={ACS NANO}, author={Xia, Xin R. and Monteiro-Riviere, Nancy A. and Mathur, Sanjay and Song, Xuefeng and Xiao, Lisong and Oldenberg, Steven J. and Fadeel, Bengt and Riviere, Jim E.}, year={2011}, month={Nov}, pages={9074–9081} }
 @article{boehm_miller_hayes_monteiro-riviere_narayan_2011, title={Modification of microneedles using inkjet printing}, volume={1}, ISSN={2158-3226}, url={http://dx.doi.org/10.1063/1.3602461}, DOI={10.1063/1.3602461}, abstractNote={In this study, biodegradable acid anhydride copolymer microneedles containing quantum dots were fabricated by means of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing. Nanoindentation was performed to obtain the hardness and the Young's modulus of the biodegradable acid anhydride copolymer. Imaging of quantum dots within porcine skin was accomplished by means of multiphoton microscopy. Our results suggest that the combination of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing enables fabrication of solid biodegradable microneedles with a wide range of geometries as well as a wide range of pharmacologic agent compositions.}, number={2}, journal={AIP Advances}, publisher={AIP Publishing}, author={Boehm, R D and Miller, P R and Hayes, S L and Monteiro-Riviere, N A and Narayan, R J}, year={2011}, pages={022139} }
 @article{gittard_miller_boehm_ovsianikov_chichkov_heiser_gordon_monteiro-riviere_narayan_2011, title={Multiphoton microscopy of transdermal quantum dot delivery using two photon polymerization-fabricated polymer microneedles}, volume={149}, ISSN={["1364-5498"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000285924900015&KeyUID=WOS:000285924900015}, DOI={10.1039/c005374k}, abstractNote={Due to their ability to serve as fluorophores and drug delivery vehicles, quantum dots are a powerful tool for theranostics-based clinical applications. In this study, microneedle devices for transdermal drug delivery were fabricated by means of two-photon polymerization of an acrylate-based polymer. We examined proliferation of cells on this polymer using neonatal human epidermal keratinocytes and human dermal fibroblasts. The microneedle device was used to inject quantum dots into porcine skin; imaging of the quantum dots was performed using multiphoton microscopy.}, journal={FARADAY DISCUSSIONS}, author={Gittard, Shaun D. and Miller, Philip R. and Boehm, Ryan D. and Ovsianikov, Aleksandr and Chichkov, Boris N. and Heiser, Jeremy and Gordon, John and Monteiro-Riviere, Nancy A. and Narayan, Roger J.}, year={2011}, pages={171–185} }
 @article{monteiro-riviere_wiench_landsiedel_schulte_inman_riviere_2011, title={Safety Evaluation of Sunscreen Formulations Containing Titanium Dioxide and Zinc Oxide Nanoparticles in UVB Sunburned Skin: An In Vitro and In Vivo Study}, volume={123}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000294557500024&KeyUID=WOS:000294557500024}, DOI={10.1093/toxsci/kfr148}, abstractNote={Sunscreens containing titanium dioxide (TiO(2)) and zinc oxide (ZnO) nanoparticles (NP) are effective barriers against ultraviolet B (UVB) damage to skin, although little is known about their disposition in UVB-damaged skin. Pigs were exposed to UVB that resulted in moderate sunburn. For in vitro studies, skin in flow-through diffusion cells were treated 24 h with four sunscreen formulations as follows: 10% coated TiO(2) in oil/water (o/w), 10% coated TiO(2) in water/oil (w/o), 5% coated ZnO in o/w, and 5% uncoated ZnO in o/w. TiO(2) (rutile, crystallite) primary particle size was 10 × 50 nm with mean agglomerates of 200 nm (range ca. 90 nm--460 nm); mean for ZnO was 140 nm (range ca. 60--200 nm). Skin was processed for light microscopy, scanning (SEM) and transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). UVB-exposed skin had typical sunburn histology. TEM showed TiO(2) NP 17 layers into stratum corneum (SC), whereas ZnO remained on the surface. TOF-SIMS showed TiO(2) and ZnO epidermal penetration in both treatments. Perfusate analyzed by TEM/energy dispersive x-ray spectroscopy or inductively coupled plasma mass spectrometry detected no Ti or Zn, indicating minimal transdermal absorption. In vivo, skin was dosed at 24 h occluded with formulations and at 48 h. TiO(2) NP in o/w formulation penetrated 13 layers into UVB-damaged SC, whereas only 7 layers in normal skin; TiO(2) in w/o penetrated deeper in UVB-damaged SC. Coated and uncoated Zn NP in o/w were localized to the upper one to two SC layers in all skin. By SEM, NP were localized as agglomerates in formulation on the skin surface and base of hair. TOF-SIMS showed Ti within epidermis and superficial dermis, whereas Zn was limited to SC and upper epidermis in both treatments. In summary, UVB-damaged skin slightly enhanced TiO(2) NP or ZnO NP penetration in sunscreen formulations but no transdermal absorption was detected.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Monteiro-Riviere, N. A. and Wiench, K. and Landsiedel, R. and Schulte, S. and Inman, A. O. and Riviere, J. E.}, year={2011}, month={Sep}, pages={264–280} }
 @inbook{riviere_inman_monteiro-riviere_2010, place={Boca Raton, FL}, title={Absorption, Penetration, and Cutaneous Toxicity of Jet Fuels and Hydrocarbon Components}, ISBN={9780429141713}, url={http://dx.doi.org/10.1201/9781420080216-7}, DOI={10.1201/9781420080216-7}, booktitle={Jet Fuel Toxicology}, publisher={CRC Press}, author={Riviere, James E. and Inman, Alfred O. and Monteiro-Riviere, Nancy}, year={2010}, pages={119–134} }
 @inbook{riviere_inman_monteiro-riviere_2010, title={Absorption, penetration, and cutaneous toxicity of jet fuels and hydrocarbon components}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85055150980&partnerID=MN8TOARS}, DOI={10.1201/9781420080216}, booktitle={Jet Fuel Toxicology}, author={Riviere, J.E. and Inman, A.O. and Monteiro-Riviere, N.}, year={2010}, pages={119–134} }
 @article{xia_monteiro-riviere_riviere_2010, title={An index for characterization of nanomaterials in biological systems}, volume={5}, ISSN={1748-3387 1748-3395}, url={http://dx.doi.org/10.1038/nnano.2010.164}, DOI={10.1038/nnano.2010.164}, number={9}, journal={Nature Nanotechnology}, publisher={Springer Science and Business Media LLC}, author={Xia, Xin-Rui and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2010}, month={Aug}, pages={671–675} }
 @article{narayan_adiga_pellin_curtiss_stafslien_chisholm_monteiro-riviere_brigmon_elam_2010, title={Atomic layer deposition of nanoporous biomaterials}, volume={13}, ISSN={["1873-4103"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77949425892&partnerID=MN8TOARS}, DOI={10.1016/s1369-7021(10)70035-3}, abstractNote={Due to its chemical stability, uniform pore size, and high pore density, nanoporous alumina is being investigated for use in biosensing, drug delivery, hemodialysis, and other medical applications. In recent work, we have examined the use of atomic layer deposition for coating the surfaces of nanoporous alumina membranes. Zinc oxide coatings were deposited on nanoporous alumina membranes using atomic layer deposition. The zinc oxide-coated nanoporous alumina membranes demonstrated antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria. These results suggest that atomic layer deposition is an attractive technique for modifying the surfaces of nanoporous alumina membranes and other nanostructured biomaterials.}, number={3}, journal={MATERIALS TODAY}, author={Narayan, Roger J. and Adiga, Shashishekar P. and Pellin, Michael J. and Curtiss, Larry A. and Stafslien, Shane and Chisholm, Bret and Monteiro-Riviere, Nancy A. and Brigmon, Robin L. and Elam, Jeffrey W.}, year={2010}, month={Mar}, pages={60–64} }
 @article{narayan_adiga_pellin_curtiss_hryn_stafslien_chisholm_shih_shih_lin_et al._2010, title={Atomic layer deposition-based functionalization of materials for medical and environmental health applications}, volume={368}, ISSN={["1471-2962"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000275810800010&KeyUID=WOS:000275810800010}, DOI={10.1098/rsta.2010.0011}, abstractNote={Nanoporous alumina membranes exhibit high pore densities, well-controlled and uniform pore sizes, as well as straight pores. Owing to these unusual properties, nanoporous alumina membranes are currently being considered for use in implantable sensor membranes and water purification membranes. Atomic layer deposition is a thin-film growth process that may be used to modify the pore size in a nanoporous alumina membrane while retaining a narrow pore distribution. In addition, films deposited by means of atomic layer deposition may impart improved biological functionality to nanoporous alumina membranes. In this study, zinc oxide coatings and platinum coatings were deposited on nanoporous alumina membranes by means of atomic layer deposition. PEGylated nanoporous alumina membranes were prepared by self-assembly of 1-mercaptoundec-11-yl hexa(ethylene glycol) on platinum-coated nanoporous alumina membranes. The pores of the PEGylated nanoporous alumina membranes remained free of fouling after exposure to human platelet-rich plasma; protein adsorption, fibrin networks and platelet aggregation were not observed on the coated membrane surface. Zinc oxide-coated nanoporous alumina membranes demonstrated activity against two waterborne pathogens, Escherichia coli and Staphylococcus aureus. The results of this work indicate that nanoporous alumina membranes may be modified using atomic layer deposition for use in a variety of medical and environmental health applications.}, number={1917}, journal={PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES}, author={Narayan, Roger J. and Adiga, Shashishekar P. and Pellin, Michael J. and Curtiss, Larry A. and Hryn, Alexander J. and Stafslien, Shane and Chisholm, Bret and Shih, Chun-Che and Shih, Chun-Ming and Lin, Shing-Jong and et al.}, year={2010}, month={Apr}, pages={2033–2064} }
 @article{mariani_boozer_cherubini_vernau_campbell_dillard_early_gallagher_mackillop_munana_et al._2010, title={CYTOKINE AND CHEMOKINE LEVELS IN SERUM AND CEREBROSPINAL FLUID OF DOGS WITH INFLAMMATORY CENTRAL NERVOUS SYSTEM DISEASE}, volume={24}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000277416600262&KeyUID=WOS:000277416600262}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Mariani, C. L. and Boozer, L. B. and Cherubini, G. B. and Vernau, K. M. and Campbell, J. and Dillard, S. and Early, P. J. and Gallagher, R. and MacKillop, E. and Munana, K. R. and et al.}, year={2010}, pages={741} }
 @inbook{basak_gute_monteiro-riviere_witzmann_2010, title={Characterization of Toxicoproteomics Maps for Chemical Mixtures Using Information Theoretic Approach}, ISBN={9783527630196 9783527319923}, url={http://dx.doi.org/10.1002/9783527630196.ch8}, DOI={10.1002/9783527630196.ch8}, abstractNote={This chapter contains sections titled: Introduction Current Proteomics Technologies Mathematical Proteomics Approaches Experimental Methods Theoretical Calculation of Information Theoretic Biodescriptors Results Discussion and Conclusion Acknowledgments References}, booktitle={Principles and Practice of Mixtures Toxicology}, publisher={Wiley-VCH Verlag GmbH & Co. KGaA}, author={Basak, Subhash C. and Gute, Brian D. and Monteiro-Riviere, Nancy A. and Witzmann, Frank A.}, year={2010}, month={Dec}, pages={215–234} }
 @inbook{riviere_monteiro-riviere_2010, title={Dermal Exposure and Absorption of Chemicals and Nanomaterials*}, volume={1-14}, ISBN={9780080468846}, url={http://dx.doi.org/10.1016/b978-0-08-046884-6.00105-6}, DOI={10.1016/b978-0-08-046884-6.00105-6}, abstractNote={Skin is an important route of exposure to chemicals after occupational, environmental, and consumer product usage. Knowledge of the rate and extent of skin absorption is required for risk assessments to be made. The primary barrier to chemical absorption is the stratum corneum. Transport across this barrier is assumed to occur primarily by diffusion. Techniques for quantitating skin permeability using this assumption are presented, as are basic approaches to linking permeability to molecular properties using quantitative structure permeability relationships (QSPeR). Consideration is then given to how nanomaterial dermal absorption fits into this paradigm developed for small organic chemicals.}, booktitle={Comprehensive Toxicology}, publisher={Elsevier}, author={Riviere, J.E. and Monteiro-Riviere, N.A.}, year={2010}, pages={111–122} }
 @article{boozer_mariani_campbell_dillard_early_gallagher_mackillop_munana_niman_olby_et al._2010, title={EVALUATION OF CYTOKINE AND CHEMOKINE LEVELS IN CANINE INTRACRANIAL NEOPLASIA}, volume={24}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000277416600264&KeyUID=WOS:000277416600264}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Boozer, L. B. and Mariani, C. L. and Campbell, J. and Dillard, S. and Early, P. J. and Gallagher, R. and MacKillop, E. and Munana, K. R. and Niman, Z. E. and Olby, N. J. and et al.}, year={2010}, pages={741} }
 @inbook{thomas_monteiro-riviere_warheit_savage_2010, place={Oxford}, title={Evaluating the risks associated with nanomaterials}, volume={III}, booktitle={The Oxford Handbook of Nanoscience and Technology, Frontiers and Advances}, publisher={Oxford University Press}, author={Thomas, K. and Monteiro-Riviere, N. and Warheit, D. and Savage, N.}, editor={Narlikar, Eds A.V. and Du, Y.Y.Editors}, year={2010}, pages={888–906,} }
 @article{samberg_oldenburg_monteiro-riviere_2010, title={Evaluation of Silver Nanoparticle Toxicity in Skin in Vivo and Keratinocytes in Vitro}, volume={118}, ISSN={["1552-9924"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000275449500034&KeyUID=WOS:000275449500034}, DOI={10.1289/ehp.0901398}, abstractNote={IntroductionProducts using the antimicrobial properties of silver nanoparticles (Ag-nps) may be found in health and consumer products that routinely contact skin.ObjectivesThis study was designed to assess the potential cytotoxicity of Ag-nps in human epidermal keratinocytes (HEKs) and their inflammatory and penetrating potential into porcine skin in vivo.Materials and MethodsWe used eight different Ag-nps in this study [unwashed/uncoated (20, 50, and 80 nm particle diameter), washed/uncoated (20, 50, and 80 nm), and carbon-coated (25 and 35 nm)]. Skin was dosed topically for 14 consecutive days. HEK viability was assessed by MTT, alamarBlue (aB), and CellTiter 96 AQueous One (96AQ). Release of the proinflammatory mediators interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were measured.ResultsThe effect of the unwashed Ag-nps on HEK viability after a 24-hr exposure indicated a significant dose-dependent decrease (p < 0.05) at 0.34 μg/mL with aB and 96AQ and at 1.7 μg/mL with MTT. However, both the washed Ag-nps and carbon-coated Ag-nps showed no significant decrease in viability at any concentration assessed by any of the three assays. For each of the unwashed Ag-nps, we noted a significant increase (p < 0.05) in IL-1β, IL-6, IL-8, and TNF-α concentrations. We observed localization of all Ag-nps in cytoplasmic vacuoles of HEKs. Macroscopic observations showed no gross irritation in porcine skin, whereas microscopic and ultrastructural observations showed areas of focal inflammation and localization of Ag-nps on the surface and in the upper stratum corneum layers of the skin.ConclusionThis study provides a better understanding Ag-nps safety in vitro as well as in vivo and a basis for occupational and risk assessment. Ag-nps are nontoxic when dosed in washed Ag-nps solutions or carbon coated.}, number={3}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Samberg, Meghan E. and Oldenburg, Steven J. and Monteiro-Riviere, Nancy A.}, year={2010}, month={Mar}, pages={407–413} }
 @article{leavens_xia_lee_monteiro-riviere_brooks_riviere_2010, title={Evaluation of perfused porcine skin as a model system to quantitate tissue distribution of fullerene nanoparticles}, volume={197}, ISSN={["1879-3169"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000279989500001&KeyUID=WOS:000279989500001}, DOI={10.1016/j.toxlet.2010.03.1119}, abstractNote={Nanomaterials are increasingly playing a role in society for uses ranging from biomedicine to microelectronics, however pharmacokinetic studies, which will be necessary for human health risk assessments, are limited. Tissue distribution, one component of pharmacokinetics, can be assessed by quantifying arterial extraction of materials in an isolated perfused porcine skin flap (IPPSF). The objective of this study was to assess the IPPSF as a model system to quantitate the distribution of fullerene nanoparticles (nC60) from the vascular space into tissues. IPPSFs were perfused for 4 h with 0.885 μg/mL nC60 in media with immunoglobulin G present (IgG+) or absent (IgG−) followed by a 4 h perfusion with media only during a washout phase. Arterial and venous concentrations of nC60 were measured in the media by HPLC–UV/vis chromatography. Steady state differences in the arterial and venous nC60 concentrations were compared to determine extraction from the vascular space of the IPPSF, and the venous nC60 concentration versus time profiles were used to calculate compartmental pharmacokinetic parameters. The steady state differences in the arterial and venous concentrations in the IPPSF were small with extraction percentages (mean ± sd) of 8.2 ± 5.7% and 4.2 ± 6.7% for IgG+ and IgG− media, respectively, and were not significantly different between the types of media. The venous concentrations of nC60 in both types of media were best fit with a 2 compartment model with terminal half lives (harmonic mean) of 17.5 and 28.0 min for IgG+ and IgG− media, respectively. The apparent volumes of distribution at steady state were 0.12 ± 0.047 and 0.10 ± 0.034 L/kg, for IgG+ and IgG− media, respectively. By 4 h following infusion of nC60, the recovery of nC60 in the venous effluent was 94 ± 5.5% and 97 ± 6.8% of the infused nC60 for IgG+ and IgG− media, respectively. Based on the apparent volume of distribution, the low extraction during the perfusion, and the high percentage recovery following the washout phase, there was limited distribution of nC60 from the vascular space into the extracellular space and negligible intracellular uptake of nC60 in this system.}, number={1}, journal={TOXICOLOGY LETTERS}, author={Leavens, Teresa L. and Xia, Xin Rui and Lee, Hyun A. and Monteiro-Riviere, Nancy A. and Brooks, James D. and Riviere, Jim E.}, year={2010}, month={Aug}, pages={1–6} }
 @article{doraiswamy_ovsianikov_gittard_monteiro-riviere_crombez_montalvo_shen_chichkov_narayan_2010, title={Fabrication of Microneedles Using Two Photon Polymerization for Transdermal Delivery of Nanomaterials}, volume={10}, ISSN={["1533-4899"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000280361400003&KeyUID=WOS:000280361400003}, DOI={10.1166/jnn.2010.2636}, abstractNote={Microneedle devices for transdermal delivery of nanoscale pharmacologic agents were fabricated out of organically-modified ceramic (Ormocer) materials using two photon polymerization. Out-of-plane hollow microneedle arrays with various aspect ratios were fabricated using this rapid prototyping process. Human epidermal keratinocyte (HEK) viability on Ormocer surfaces fabricated using two photon polymerization was similar to that on control surfaces. Nanoindentation studies were performed to determine hardness and Young's modulus values for Ormocer materials. Microneedies were shown to enable more rapid distribution of the PEG-amine quantum dot solution to the deep epidermis and dermis layers of porcine skin than topical administration. Our results suggest that two photon polymerization may be used to create microneedle arrays for transdermal delivery of nanoscale pharmacologic agents.}, number={10}, journal={JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY}, author={Doraiswamy, Anand and Ovsianikov, Aleksandr and Gittard, Shaun D. and Monteiro-Riviere, Nancy A. and Crombez, Rene and Montalvo, Eva and Shen, Weidian and Chichkov, Boris N. and Narayan, Roger J.}, year={2010}, month={Oct}, pages={6305–6312} }
 @article{haslauer_springer_harrysson_loboa_monteiro-riviere_marcellin-little_2010, title={In vitro biocompatibility of titanium alloy discs made using direct metal fabrication}, volume={32}, ISSN={["1873-4030"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000279857300014&KeyUID=WOS:000279857300014}, DOI={10.1016/j.medengphy.2010.04.003}, abstractNote={Custom orthopedic implants may be generated using free-form fabrication methods (FFF) such as electron beam melting (EBM). EBM FFF may be used to make solid metal implants whose surface is often polished using CNC machining and porous scaffolds that are usually left unpolished. We assessed the in vitro biocompatibility of EBM titanium–6 aluminum–4 vanadium (Ti6Al4V) structures by comparing the cellular response to solid polished, solid unpolished, and porous EBM discs to the cellular response to discs made of commercially produced Ti6Al4V. The discs were seeded with 20,000 human adipose-derived adult stem cells (hASCs) and assessed for cell viability, proliferation, and release of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8). Cell viability was assessed with Live/Dead staining 8 days after seeding. Cell proliferation was assessed using alamarBlue assays at days 0, 1, 2, 3, and 7. The hASCs were alive on all discs after 8 days. Cellular proliferation on porous EBM discs was increased at days 2, 3, and 7 compared to discs made of commercial Ti6Al4V. Cellular proliferation on porous EBM discs was also increased compared to solid polished and unpolished EBM discs. IL-6 and IL-8 releases at day 7 were lower for porous EBM discs than for other discs. Solid polished, unpolished, and porous EBM Ti6Al4V discs exhibited an acceptable biocompatibility profile compared to solid Ti6Al4V discs from a commercial source. EBM FFF may be considered as an option for the fabrication of custom orthopedic implants.}, number={6}, journal={MEDICAL ENGINEERING & PHYSICS}, author={Haslauer, Carla Maria and Springer, Jessica Collins and Harrysson, Ola L. A. and Loboa, Elizabeth G. and Monteiro-Riviere, Nancy A. and Marcellin-Little, Denis J.}, year={2010}, month={Jul}, pages={645–652} }
 @article{monteiro-riviere_oldenburg_inman_2010, title={Interactions of aluminum nanoparticles with human epidermal keratinocytes}, volume={30}, ISSN={["0260-437X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000277524000012&KeyUID=WOS:000277524000012}, DOI={10.1002/jat.1494}, abstractNote={Aluminum nanoparticles (Al NP) have been used in applications as diverse as drug delivery, material surface coatings and an ingredient for solid rocket fuel in military explosives and artillery. Although Al NP are used in many civilian and military applications, the health and safety implications of these nanosize particles are not known. To understand the interactions and biological activity of Al NP in human cells, cultured human neonatal epidermal keratinocytes (HEK) were exposed for 24 h to 50 and 80 nm Al NP in concentrations from 4.0 to 0.0004 mg ml(-1) to assess the cytotoxicity and inflammatory potential. UV-Vis measurements and nanoparticle controls revealed that the Al NP interact with the assay dyes. Viability did not decrease in HEK exposed to both the 50 and the 80 nm Al NP at all treatment concentrations with MTT, CellTiter 96 AQueous One (96 AQ) and alamar Blue (aB) viability assays. The 96 AQ and aB assays interact with the Al NP less than MTT, and proved to be the best assays to use with these Al NP. TEM depicted Al NP localized within the cytoplasmic vacuoles of the cells. Cytokine data was variable, indicating possible nanoparticle interactions with the cytokine assays. These studies illustrate the difficulties involved in assessing the biological safety of nanomaterials such as Al NP due to media- and temperature-dependent particle agglomeration and nanoparticle interactions with biomarkers of cytotoxicity.}, number={3}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Monteiro-Riviere, Nancy A. and Oldenburg, Steven J. and Inman, Alfred O.}, year={2010}, month={Apr}, pages={276–285} }
 @article{xia_monteiro-riviere_riviere_2010, title={Intrinsic biological property of colloidal fullerene nanoparticles (nC(60)): Lack of lethality after high dose exposure to human epidermal and bacterial cells}, volume={197}, ISSN={["1879-3169"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000280052200010&KeyUID=WOS:000280052200010}, DOI={10.1016/j.toxlet.2010.05.010}, abstractNote={Colloidal fullerene nanoparticles (nC60) were reported to be toxic to fish brains, human cells and microorganisms, while new observations suggest that the observed toxicity may be due to tetrahydrofuran (THF) solvent or its oxidative by-products in nC60 preparations. Here, we report a novel method for preparing nC60 nanoparticles that does not use THF solvent, but provides nC60 with an average particle size of 43.8 nm and a yield approximately 100 times higher than the THF method. The prepared nC60 showed a similar antioxidant capacity compared to a water-soluble vitamin E analog. No mortality to human epidermal keratinocytes was observed at a concentration 170 times higher than the reported LC50 values for other human cell lines. No toxicity was observed to E. coli or B. subtilis at up to 342 μg/mL nC60 for 16 h, which was hundred times higher than the reported minimum inhibitory concentrations of nC60 prepared using THF method for these two bacteria. When E. coli was exposed to 85.5 μg/mL nC60 with daily passage for 4 days, the stationary phase populations at different passages were not statistically different (p = 0.05) from the control without nC60 nanoparticles. These results reveal that the intrinsic biological property of nC60 is non-toxic, confirming the prior non-toxic reports when using nC60 prepared with non-THF methods.}, number={2}, journal={TOXICOLOGY LETTERS}, author={Xia, Xin R. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2010}, month={Aug}, pages={128–134} }
 @article{zhang_monteiro-riviere_2010, title={Lectins modulate multi-walled carbon nanotubes cellular uptake in human epidermal keratinocytes}, volume={24}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000275991700026&KeyUID=WOS:000275991700026}, DOI={10.1016/j.tiv.2009.11.007}, abstractNote={The development of nanomaterials for biomedical applications has attracted a great deal of attention. Carbon nanotubes may interact and cross cell membranes and serve as potential carriers for drug delivery studies. The reflection mode in the confocal laser scanning microscope was used to image multi-walled carbon nanotubes (MWCNT) in human neonatal epidermal keratinocytes (HEK) stained with the cytoskeleton protein F-actin. Scanning electron microscopy depicted tight binding of MWCNT on the plasma membrane of HEK, while some MWCNT were located in the cell. Since keratinocytes normally engulf melanosomes, we hypothesized that the melanocyte transfer pathway could be a potential route of entry into keratinocytes. Lectins are inhibitors of the melanosome transfer pathway was used to study the uptake of MWCNT in keratinocytes, to see if they played a role in reducing the cellular uptake of MWCNT in HEK. Three different lectins, Pisum sativum (PS), Lycopersicon esculentum (LE), and Tetragonolobus purpureas (TP) were used as a cocktail. The maximal concentrations of lectins that would be non-toxic to the HEK was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. These studies confirmed that lectin cocktails (PS 5mug/ml, LE 25mug/ml and TP 25mug/ml) decreased MWCNT interaction at the cell surface and uptake. F-actin, a cytoskeleton protein, was used to visualize how the MWCNT interacted with the cytoskeleton in the cells. MWCNT traversed through the cells' cytoskeleton and the plasma membrane into adjacent keratinocytes.}, number={2}, journal={TOXICOLOGY IN VITRO}, author={Zhang, Leshuai W. and Monteiro-Riviere, Nancy A.}, year={2010}, month={Mar}, pages={546–551} }
 @inbook{monteiro-riviere_baroli_2010, title={Nanomaterial penetration}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77958477177&partnerID=MN8TOARS}, booktitle={Toxicology of the Skin}, author={Monteiro-Riviere, N.A. and Baroli, B.}, year={2010}, pages={333–346} }
 @inbook{monteiro riviere_baroli_2010, place={New York, NY}, series={Target organ toxicology series}, title={Nanomaterials Penetration}, booktitle={Toxicology of the Skin}, publisher={Informa Healthcare}, author={Monteiro Riviere, N.A. and Baroli, B}, editor={Monteiro-Riviere, N.A.Editor}, year={2010}, pages={333–346}, collection={Target organ toxicology series} }
 @inbook{grissom_abernathy_monteiro-riviere_2010, place={New York, NY}, series={Target organ toxicology series}, title={Potential Arsenic Exposure Through Dermal Penetration}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85056392662&partnerID=MN8TOARS}, booktitle={Toxicology of the Skin}, publisher={Informa Healthcare}, author={Grissom, R.E. and Abernathy, C.O. and Monteiro-Riviere, N.A.}, editor={Monteiro-Riviere), N.A.Editor}, year={2010}, pages={347–360}, collection={Target organ toxicology series} }
 @book{monteiro-riviere_2010, title={Preface}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85060190964&partnerID=MN8TOARS}, journal={Toxicology of the Skin}, author={Monteiro-Riviere, N.A.}, year={2010}, pages={v} }
 @article{xia_monteiro-riviere_riviere_2010, title={Skin penetration and kinetics of pristine fullerenes (C-60) topically exposed in industrial organic solvents}, volume={242}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000272434800004&KeyUID=WOS:000272434800004}, DOI={10.1016/j.taap.2009.09.011}, abstractNote={Pristine fullerenes (C60) in different solvents will be used in many industrial and pharmaceutical manufacturing and derivatizing processes. This report explores the impact of solvents on skin penetration of C60 from different types of industrial solvents (toluene, cyclohexane, chloroform and mineral oil). Yorkshire weanling pigs (n=3) were topically dosed with 500 microL of 200 microg/mL C60 in a given solvent for 24 h and re-dosed daily for 4 days to simulate the worst scenario in occupational exposures. The dose sites were tape-stripped and skin biopsies were taken after 26 tape-strips for quantitative analysis. When dosed in toluene, cyclohexane or chloroform, pristine fullerenes penetrated deeply into the stratum corneum, the primary barrier of skin. More C60 was detected in the stratum corneum when dosed in chloroform compared to toluene or cyclohexane. Fullerenes were not detected in the skin when dosed in mineral oil. This is the first direct evidence of solvent effects on the skin penetration of pristine fullerenes. The penetration of C60 into the stratum corneum was verified using isolated stratum corneum in vitro; the solvent effects on the stratum corneum absorption of C60 were consistent with those observed in vivo. In vitro flow-through diffusion cell experiments were conducted in pig skin and fullerenes were not detected in the receptor solutions by 24 h. The limit of detection was 0.001 microg/mL of fullerenes in 2 mL of the receptor solutions.}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Xia, Xin R. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2010}, month={Jan}, pages={29–37} }
 @inbook{monteiro-riviere_2010, place={New York, NY}, series={Target organ toxicology series}, title={Structure and Function of Skin}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85056380325&partnerID=MN8TOARS}, number={apter 1}, booktitle={Toxicology of the Skin}, publisher={Informa Healthcare}, author={Monteiro-Riviere, N.A.}, editor={Monteiro-Riviere, N.A.Editor}, year={2010}, pages={1–18,}, collection={Target organ toxicology series} }
 @book{monteiro-riviere_2010, place={New York, NY}, series={Target organ toxicology series}, title={Toxicology of the skin}, publisher={Informa Healthcare}, year={2010}, collection={Target organ toxicology series} }
 @book{monteiro-riviere_2010, title={Toxicology of the skin}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84868687035&partnerID=MN8TOARS}, journal={Toxicology of the Skin}, author={Monteiro-Riviere, N.A.}, year={2010}, pages={1–437} }
 @article{gittard_ovsianikov_akar_chichkov_monteiro-riviere_stafslien_chisholm_shin_shih_lin_et al._2010, title={Two Photon Polymerization-Micromolding of Polyethylene Glycol-Gentamicin Sulfate Microneedles}, volume={12}, ISSN={["1438-1656"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000277655500011&KeyUID=WOS:000277655500011}, DOI={10.1002/adem.200980012}, abstractNote={The use of microneedles for transdermal drug delivery is limited due to the risk of infection associated with formation of channels through the stratum corneum layer of the epidermis. The risk of infection associated with use of microneedles may be reduced by imparting these devices with antimicrobial properties. In this study, a photopolymerization-micromolding technique was used to fabricate microneedle arrays from a photosensitive material containing polyethylene glycol 600 diacrylate, gentamicin sulfate, and a photoinitiator. Scanning electron microscopy indicated that the photopolymerization-micromolding process produced microneedle arrays that exhibited good microneedle-to-microneedle uniformity. An agar plating assay revealed that microneedles fabricated with polyethylene glycol 600 diacrylate containing 2 mg mL(-1) gentamicin sulfate inhibited growth of Staphylococcus aureus bacteria. Scanning electron microscopy revealed no platelet aggregation on the surfaces of platelet rich plasma-exposed undoped polyethylene glycol 600 diacrylate microneedles and gentamicin-doped polyethylene glycol 600 diacrylate microneedles. These efforts will enable wider adoption of microneedles for transdermal delivery of pharmacologic agents.}, number={4}, journal={ADVANCED ENGINEERING MATERIALS}, author={Gittard, Shaun D. and Ovsianikov, Aleksandr and Akar, Hasan and Chichkov, Boris and Monteiro-Riviere, Nancy A. and Stafslien, Shane and Chisholm, Bret and Shin, Chun-Che and Shih, Chun-Ming and Lin, Shing-Jong and et al.}, year={2010}, month={Apr}, pages={B77–B82} }
 @article{monteiro-riviere_zhang_linkov_steevens_2009, title={ASSESSMENT OF QUANTUM DOT PENETRATION INTO SKIN IN DIFFERENT SPECIES UNDER DIFFERENT MECHANICAL ACTIONS}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000262985800003&KeyUID=WOS:000262985800003}, DOI={10.1007/978-1-4020-9491-0_3}, abstractNote={Skin penetration is one of the major routes of exposure for nanoparticles to gain access to a biological system. QD nanoparticles have received a great deal of attention due to their fluorescent characteristics and potential use in medical applications. However, little is known about their permeability in skin. This study focuses on three types of quantum dots (QD) with different surface coatings and concentrations on their ability to penetrate skin. QD621 (polyethylene glycol coated, PEG) was studied for 24 h in porcine skin flow-through diffusion cells. QD565 and QD655 coated with carboxylic acid were studied for 8 and 24 h in flow-through diffusion cells with flexed, tape stripped and abraded rat skin to determine if these mechanical actions could perturb the barrier and affect penetration. Confocal microscopy depicted QD621 penetration through the uppermost layers of the stratum corneum (SC) and fluorescence was found in the SC and near hair follicles. QD621 were found in the intercellular lipid layers of the SC by transmission electron microscopy (TEM). QD565 and 655 with flexed and tape-stripped skin did not show penetration; only abraded skin showed penetration in the viable dermal layers. In all QD studies, inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD did not detect Cd or fluorescence signal in the perfusate at any time point, concentration or type of QD. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, while QD565 and 655 penetrated into the dermis of abraded skin. The anatomical complexity of skin and species differences should be taken into consideration when selecting an animal model to study nanoparticle absorption/penetration. These findings are of importance to risk assessment for nanoscale materials because it indicates that if skin barrier is altered such as in wounds, scrapes, or dermatitis conditions could affect nanoparticle penetration deeper into the dermal layers and skin is an important organ and can serve as a potential route of exposure and should not be overlooked.}, journal={Nanomaterials: Risks and Benefits}, author={Monteiro-Riviere, N. A. and Zhang, L. W. and Linkov, I and Steevens, J}, year={2009}, pages={43–52} }
 @article{gittard_perfect_monteiro-riviere_wei_jin_narayan_2009, title={Assessing the antimicrobial activity of zinc oxide thin films using disk diffusion and biofilm reactor}, volume={255}, ISSN={["1873-5584"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000263893800027&KeyUID=WOS:000263893800027}, DOI={10.1016/j.apsusc.2009.01.009}, abstractNote={The electronic and chemical properties of semiconductor materials may be useful in preventing growth of microorganisms. In this article, in vitro methods for assessing microbial growth on semiconductor materials will be presented. The structural and biological properties of silicon wafers coated with zinc oxide thin films were evaluated using atomic force microscopy, X-ray photoelectron spectroscopy, and MTT viability assay. The antimicrobial properties of zinc oxide thin films were established using disk diffusion and CDC Biofilm Reactor studies. Our results suggest that zinc oxide and other semiconductor materials may play a leading role in providing antimicrobial functionality to the next-generation medical devices.}, number={11}, journal={APPLIED SURFACE SCIENCE}, author={Gittard, Shaun D. and Perfect, John R. and Monteiro-Riviere, Nancy A. and Wei, Wei and Jin, Chunming and Narayan, Roger J.}, year={2009}, month={Mar}, pages={5806–5811} }
 @article{narayan_monteiro-riviere_brigmon_pellin_elam_2009, title={Atomic layer deposition of TiO2 thin films on nanoporous alumina templates: Medical applications}, volume={61}, ISSN={["1543-1851"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000266911200002&KeyUID=WOS:000266911200002}, DOI={10.1007/s11837-009-0081-z}, number={6}, journal={JOM}, author={Narayan, Roger J. and Monteiro-Riviere, Nancy A. and Brigmon, Robin L. and Pellin, Michael J. and Elam, Jeffrey W.}, year={2009}, month={Jun}, pages={12–16} }
 @article{lee_leavens_mason_monteiro-riviere_riviere_2009, title={Comparison of Quantum Dot Biodistribution with a Blood-Flow-Limited Physiologically Based Pharmacokinetic Model}, volume={9}, ISSN={1530-6984 1530-6992}, url={http://dx.doi.org/10.1021/nl803481q}, DOI={10.1021/nl803481q}, abstractNote={A physiologically based pharmacokinetic model with partition coefficients estimated from quantum dot (QD) 705 biodistribution was compared with the biodistribution of other QDs in mice and rats to determine the model's predictive ability across QD types, species, and exposure routes. The model predicted the experimentally observed persistence of QDs in tissues but not early time profiles or different QD biodistribution. Therefore, more complex models will be needed to better predict QD biodistribution in vivo.}, number={2}, journal={Nano Letters}, publisher={American Chemical Society (ACS)}, author={Lee, Hyun A. and Leavens, Teresa L. and Mason, Sharon E. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2009}, month={Jan}, pages={794–799} }
 @article{lee_leavens_mason_monteiro-riviere_riviere_2009, title={Comparison of quantum dot biodistribution with a blood-flow-limited physiologically based pharmacokinetic model}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-63649101776&partnerID=MN8TOARS}, DOI={10.1021/n1803481q}, number={2}, journal={Nano Letters}, author={Lee, H.A. and Leavens, T.L. and Mason, S.E. and Monteiro-Riviere, N.A. and Riviere, J.E.}, year={2009}, pages={794–799} }
 @misc{riviere_monteiro-riviere_2009, title={Cutaneous Toxicology}, ISBN={9780470723272 9780470744307}, url={http://dx.doi.org/10.1002/9780470744307.gat055}, DOI={10.1002/9780470744307.gat055}, abstractNote={Skin is one of the largest organs in the body and is both a route for systemic absorption as well as a direct target after topical exposure in dermatologic formulations, cosmetics or occupational incidents. Compounds cross the stratum corneum epidermal barrier by passive diffusion through the intercellular lipids. Toxicity to this organ is manifested by alteration to one of its biological functions including loss of barrier, damage to the underlying dermis, hair loss, damage to adnexial structures, carcinogenic transformation to cellular constituents or activation of its resident immune system. Factors that result in absorption through or toxicity to skin will be reviewed.}, journal={General and Applied Toxicology}, publisher={John Wiley & Sons, Ltd}, author={Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2009}, month={Dec} }
 @article{zhang_yang_barron_monteiro-riviere_2009, title={Endocytic mechanisms and toxicity of a functionalized fullerene in human cells}, volume={191}, ISSN={["1879-3169"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000272760200007&KeyUID=WOS:000272760200007}, DOI={10.1016/j.toxlet.2009.08.017}, abstractNote={Derivatized fullerenes could be used in biomedical applications and be suitable vectors for drug delivery due to their small size, large surface area and solubility. However, the interactions of derivatized fullerenes with biological systems and cells are not well understood. A water-soluble fullerene-substituted phenylalanine (Bucky amino acid, Baa) poly-lysine derivative with a FITC label (Baa-Lys(FITC)-(Lys)(8)-OH) was characterized by dynamic light scattering, transmission electron microscopy with negative staining, gel electrophoresis, zeta-potential, and UV/vis spectroscopy. Viability assays depicted the cytotoxicity was time, concentration and assay dependent. A decrease in ATP and glutathione at the high concentrations suggests that reactive oxygen species may be involved. Baa-Lys(FITC)-(Lys)(8)-OH was present near the cell membrane at 15 min and entered into the cytoplasm by 30 min but did not localize in the lysosomes. Endocytic inhibitors were used to investigate the uptake mechanism. These results showed that the endocytic pathways could be mediated by caveolae/lipid rafts and cytoskeletal components. A scavenger receptor inhibitor completely blocked the uptake of Baa-Lys(FITC)-(Lys)(8)-OH, suggesting a specific endocytic pathway was strongly involved in Baa-Lys(FITC)-(Lys)(8)-OH cellular uptake.}, number={2-3}, journal={TOXICOLOGY LETTERS}, author={Zhang, Leshuai W. and Yang, Jianzhong and Barron, Andrew R. and Monteiro-Riviere, Nancy A.}, year={2009}, month={Dec}, pages={149–157} }
 @article{sumanasinghe_pfeiler_monteiro-riviere_loboa_2009, title={Expression of Proinflammatory Cytokines by Human Mesenchymal Stem Cells in Response to Cyclic Tensile Strain}, volume={219}, ISSN={["1097-4652"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000263572000009&KeyUID=WOS:000263572000009}, DOI={10.1002/jcp.21653}, abstractNote={Mesenchymal stem cells produce proinflammatory cytokines during their normal growth. Direct or indirect regulation of bone resorption by these cytokines has been reported. However, the effects of osteogenic conditions—chemical and/or mechanical—utilized during in vitro bone tissue engineering on expression of cytokines by hMSCs have not been studied. In this study, we investigated the effects of cyclic tensile strain, culture medium (with and without dexamethasone), and culture duration on the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) by bone marrow derived human mesenchymal stem cells (hMSCs). Human MSCs seeded in three-dimensional Type I collagen matrices were subjected to 0%, 10%, and 12% uniaxial cyclic tensile strains at 1 Hz for 4 h/day for 7 and 14 days in complete growth or dexamethasone-containing osteogenic medium. Viability of hMSCs was maintained irrespective of strain level and media conditions. Expression of either TNF-α or IL-1β was not observed in hMSCs under any of the conditions investigated in this study. Expression of IL-6 was dependent on culture medium. An increase in IL-6 expression was caused by both 10% and 12% strain levels. Both 10% and 12% strain levels caused an increase in IL-8 production by hMSCs that was dependent on the presence of dexamethasone. IL-6 and IL-8 expressions by hMSCs were induced by cyclic tensile strain and osteogenic differentiating media, indicating that IL-6 and IL-8 may be functioning as autocrine signals during osteogenic differentiation of hMSCs. J. Cell. Physiol. 219: 77–83, 2009. © 2008 Wiley-Liss, Inc.}, number={1}, journal={JOURNAL OF CELLULAR PHYSIOLOGY}, author={Sumanasinghe, Ruwan D. and Pfeiler, T. Wayne and Monteiro-Riviere, Nancy A. and Loboa, Elizabeth G.}, year={2009}, month={Apr}, pages={77–83} }
 @article{gittard_ovsianikov_monteiro-riviere_lusk_morel_minghetti_lenardi_chichkov_narayan_2009, title={Fabrication of Polymer Microneedles Using a Two-Photon Polymerization and Micromolding Process}, volume={3}, ISSN={1932-2968 1932-2968}, url={http://dx.doi.org/10.1177/193229680900300211}, DOI={10.1177/193229680900300211}, abstractNote={Background: Microneedle-mediated drug delivery is a promising method for transdermal delivery of insulin, incretin mimetics, and other protein-based pharmacologic agents for treatment of diabetes mellitus. One factor that has limited clinical application of conventional microneedle technology is the poor fracture behavior of microneedles that are created using conventional materials and methods. In this study polymer microneedles for transdermal delivery were created using a two-photon polymerization (2PP) microfabrication and subsequent polydimethylsiloxane (PDMS) micromolding process. Methods: Solid microneedle arrays, fabricated by means of 2PP, were used to create negative molds from PDMS. Using these molds microneedle arrays were subsequently prepared by molding eShell 200, a photo-reactive acrylate-based polymer that exhibits water and perspiration resistance. Results: The eShell 200 microneedle array demonstrated suitable compressive strength for use in transdermal drug delivery applications. Human epidermal keratinocyte viability on the eShell 200 polymer surfaces was similar to that on polystyrene control surfaces. In vitro studies demonstrated that eShell 200 microneedle arrays fabricated using the 2PP microfabrication and PDMS micromolding process technique successfully penetrated human stratum corneum and epidermis. Conclusions: Our results suggest that a 2PP microfabrication and subsequent PDMS micromolding process may be used to create microneedle structures with appropriate structural, mechanical, and biological properties for transdermal drug delivery of insulin and other protein-based pharmacologic agents for treatment of diabetes mellitus.}, number={2}, journal={Journal of Diabetes Science and Technology}, publisher={SAGE Publications}, author={Gittard, Shaun D. and Ovsianikov, Aleksandr and Monteiro-Riviere, Nancy A. and Lusk, Jason and Morel, Pierre and Minghetti, Paola and Lenardi, Cristina and Chichkov, Boris N. and Narayan, Roger J.}, year={2009}, month={Mar}, pages={304–311} }
 @misc{elder_lynch_grieger_chan-remillard_gatti_gnewuch_kenawy_korenstein_kuhlbusch_linker_et al._2009, title={Human Health Risks of Engineered Nanomaterials}, ISBN={9781402094903 9781402094910}, ISSN={1874-6519}, url={http://dx.doi.org/10.1007/978-1-4020-9491-0_1}, DOI={10.1007/978-1-4020-9491-0_1}, abstractNote={There are currently hundreds of available consumer products that contain nanoscale materials. Human exposure is, therefore, likely to occur in occupational and environmental settings. Mounting evidence suggests that some nanomaterials exert toxicity in cultured cells or following in vivo exposures, but this is dependent on the physicochemical characteristics of the materials and the dose. This Working Group report summarizes the discussions of an expert scientific panel regarding the gaps in knowledge that impede effective human health risk assessment for nanomaterials, particularly those that are suspended in a gas or liquid and, thus, deposit on skin or in the respiratory tract. In addition to extensive descriptions of material properties, the Group identified as critical research areas: external and internal dose characterization, mechanisms of response, identification of sensitive subpopulations, and the development of screening strategies and technology to support these investigations. Important concepts in defining health risk are reviewed, as are the specific kinds of studies that will quickly reduce the uncertainties in the risk assessment process.}, journal={Nanomaterials: Risks and Benefits}, publisher={Springer Netherlands}, author={Elder, A. and Lynch, I. and Grieger, K. and Chan-Remillard, S. and Gatti, A. and Gnewuch, H. and Kenawy, E. and Korenstein, R. and Kuhlbusch, T. and Linker, F. and et al.}, year={2009}, pages={3–29} }
 @inbook{linkov_steevens_2009, title={Human health risks of engineered nanomaterials}, ISBN={9781402094897}, booktitle={Nanomaterials: Risks and benefits}, publisher={Dordrecht, Holland: Springer}, year={2009}, pages={1–28} }
 @article{monteiro-riviere_riviere_2009, title={Interaction of nanomaterials with skin: Aspects of absorption and biodistribution}, volume={3}, ISSN={1743-5390 1743-5404}, url={http://dx.doi.org/10.1080/17435390902906803}, DOI={10.1080/17435390902906803}, abstractNote={Skin is an important route of exposure to chemicals after occupational, environmental and consumer product usage, routes also pertinent to nanomaterial exposure. Knowledge of the rate and extent of absorption is required for risk assessments to be made. The primary barrier to chemical absorption is the stratum corneum. The basic question to be answered is how nanomaterial absorption compares to existing paradigms of chemical absorption. Initial studies using topically applied quantum dots suggest that absorption is minimal, yet particle characteristics and species differences exist. If nanomaterial is absorbed via any route of administration, distribution to skin may also occur as was demonstrated in isolated perfused skin studies. Research is beginning to be conducted to define the mechanistic framework describing nanomaterials biodistribution using pharmacokinetic models.}, number={3}, journal={Nanotoxicology}, publisher={Informa UK Limited}, author={Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2009}, month={Jan}, pages={188–193} }
 @article{monteiro-riviere_inman_zhang_2009, title={Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line}, volume={234}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000262761600008&KeyUID=WOS:000262761600008}, DOI={10.1016/j.taap.2008.09.030}, abstractNote={Single-walled carbon nanotubes (SWCNT), fullerenes (C(60)), carbon black (CB), nC(60), and quantum dots (QD) have been studied in vitro to determine their toxicity in a number of cell types. Here, we report that classical dye-based assays such as MTT and neutral red (NR) that determine cell viability produce invalid results with some NM (nanomaterials) due to NM/dye interactions and/or NM adsorption of the dye/dye products. In this study, human epidermal keratinocytes (HEK) were exposed in vitro to CB, SWCNT, C(60), nC(60), and QD to assess viability with calcein AM (CAM), Live/Dead (LD), NR, MTT, Celltiter 96 AQueous One (96 AQ), alamar Blue (aB), Celltiter-Blue (CTB), CytoTox Onetrade mark (CTO), and flow cytometry. In addition, trypan blue (TB) was quantitated by light microscopy. Assay linearity (R(2) value) was determined with HEK plated at concentrations from 0 to 25,000 cells per well in 96-well plates. HEK were treated with serial dilutions of each NM for 24 h and assessed with each of the viability assays. TB, CAM and LD assays, which depend on direct staining of living and/or dead cells, were difficult to interpret due to physical interference of the NM with cells. Results of the dye-based assays varied a great deal, depending on the interactions of the dye/dye product with the carbon nanomaterials (CNM). Results show the optimal high throughput assay for use with carbon and noncarbon NM was 96 AQ. This study shows that, unlike small molecules, CNM interact with assay markers to cause variable results with classical toxicology assays and may not be suitable for assessing nanoparticle cytotoxicity. Therefore, more than one assay may be required when determining nanoparticle toxicity for risk assessment.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Monteiro-Riviere, N. A. and Inman, A. O. and Zhang, L. W.}, year={2009}, month={Jan}, pages={222–235} }
 @article{zhang_monteiro-riviere_2009, title={Mechanisms of Quantum Dot Nanoparticle Cellular Uptake}, volume={110}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000267227800013&KeyUID=WOS:000267227800013}, DOI={10.1093/toxsci/kfp087}, abstractNote={Due to the superior photoemission and photostability characteristics, quantum dots (QD) are novel tools in biological and medical applications. However, the toxicity and mechanism of QD uptake are poorly understood. QD nanoparticles with an emission wavelength of 655 nm are ellipsoid in shape and consist of a cadmium/selenide core with a zinc sulfide shell. We have shown that QD with a carboxylic acid surface coating were recognized by lipid rafts but not by clathrin or caveolae in human epidermal keratinocytes (HEKs). QD were internalized into early endosomes and then transferred to late endosomes or lysosomes. In addition, 24 endocytic interfering agents were used to investigate the mechanism by which QD enter cells. Our results showed that QD endocytic pathways are primarily regulated by the G-protein–coupled receptor associated pathway and low density lipoprotein receptor/scavenger receptor, whereas other endocytic interfering agents may play a role but with less of an inhibitory effect. Lastly, low toxicity of QD was shown with the 20nM dose in HEK at 48 h but not at 24 h by the live/dead cell assay. QD induced more actin filaments formation in the cytoplasm, which is different from the actin depolymerization by cadmium. These findings provide insight into the specific mechanism of QD nanoparticle uptake in cells. The surface coating, size, and charge of QD nanoparticles are important parameters in determining how nanoparticle uptake occurs in mammalian cells for cancer diagnosis and treatment, and drug delivery.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Zhang, Leshuai W. and Monteiro-Riviere, Nancy A.}, year={2009}, month={Jul}, pages={138–155} }
 @article{adrian t. o'neill_monteiro-riviere_walker_2009, title={Microfabricated curtains for controlled cell seeding in high throughput microfluidic systems}, volume={9}, ISSN={["1473-0189"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000266616000016&KeyUID=WOS:000266616000016}, DOI={10.1039/b819622b}, abstractNote={A microfabricated cell curtain is presented that facilitates cellular assays. The cell curtain is defined as a poly(dimethylsiloxane) (PDMS) wall that extends from the ceiling of a cell culture microchamber to within microns of the chamber floor. Curtain use is demonstrated by observing monolayer human epidermal keratinocyte (HEK) colonies for 48 h longer than possible with non-curtained microfluidic chambers. The curtains were further characterized by integrating them into a 96 chamber high throughput microfluidic cell culture device. As proof of concept, this device was used to assay a range of ethanol dilutions spanning 0-22% in cell culture medium. Cells exposed to 12% ethanol or less for 30 min would recover to 85% viability at 24 h, while cells exposed to higher concentrations had viabilities below 10%. The data also showed that cells exposed to 6% ethanol or less grew in population size, 8% ethanol exposure stunted growth, and higher concentrations led to population loss. Curtain use permitted high initial cell seeding densities and increased the amount of time cells can be cultured compared to multi-well plates.}, number={12}, journal={LAB ON A CHIP}, author={Adrian T. O'Neill and Monteiro-Riviere, Nancy A. and Walker, Glenn M.}, year={2009}, pages={1756–1762} }
 @article{adiga_jin_curtiss_monteiro-riviere_narayan_2009, title={Nanoporous membranes for medical and biological applications}, volume={1}, ISSN={1939-5116}, url={http://dx.doi.org/10.1002/wnan.50}, DOI={10.1002/wnan.50}, abstractNote={Synthetic nanoporous materials have numerous potential biological and medical applications that involve sorting, sensing, isolating, and releasing biological molecules. Nanoporous systems engineered to mimic natural filtration systems are actively being developed for use in smart implantable drug delivery systems, bioartificial organs, and other novel nano-enabled medical devices. Recent advances in nanoscience have made it possible to precisely control the morphology as well as physical and chemical properties of the pores in nanoporous materials that make them increasingly attractive for regulating and sensing transport at the molecular level. In this work, an overview of nanoporous membranes for biomedical applications is given. Various in vivo and in vitro membrane applications, including biosensing, biosorting, immunoisolation, and drug delivery, are presented. Different types of nanoporous materials and their fabrication techniques are discussed with an emphasis on membranes with ordered pores. Desirable properties of membranes used in implantable devices, including biocompatibility and antibiofouling behavior, are discussed. The use of surface modification techniques to improve the function of nanoporous membranes is reviewed. Despite the extensive research carried out in fabrication, characterization, and modeling of nanoporous materials, there are still several challenges that must be overcome in order to create synthetic nanoporous systems that behave similarly to their biological counterparts. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants}, number={5}, journal={Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology}, publisher={Wiley}, author={Adiga, Shashishekar P. and Jin, Chunmin and Curtiss, Larry A. and Monteiro-Riviere, Nancy A. and Narayan, Roger J.}, year={2009}, month={Jul}, pages={568–581} }
 @article{gittard_narayan_jin_ovsianikov_chichkov_monteiro-riviere_stafslien_chisholm_2009, title={Pulsed laser deposition of antimicrobial silver coating on Ormocer (R) microneedles}, volume={1}, ISSN={["1758-5090"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000278118300001&KeyUID=WOS:000278118300001}, DOI={10.1088/1758-5082/1/4/041001}, abstractNote={One promising option for transdermal delivery of protein- and nucleic acid-based pharmacologic agents involves the use of microneedles. However, microneedle-generated pores may allow microorganisms to penetrate the stratum corneum layer of the epidermis and cause local or systemic infection. In this study, microneedles with antimicrobial functionality were fabricated using two-photon polymerization-micromolding and pulsed laser deposition.The antibacterial activity of the silver-coated organically modified ceramic (Ormocer)microneedles was demonstrated using an agar diffusion assay. Human epidermal keratinocyte viability on the Ormocer surfaces coated with silver was similar to that on uncoated Ormocer surfaces. This study indicates that coating microneedles with silver thin films using pulsed laser deposition is a useful and novel approach for creating microneedles with antimicrobial functionality.}, number={4}, journal={BIOFABRICATION}, author={Gittard, S. D. and Narayan, R. J. and Jin, C. and Ovsianikov, A. and Chichkov, B. N. and Monteiro-Riviere, N. A. and Stafslien, S. and Chisholm, B.}, year={2009}, month={Dec} }
 @article{gittard_narayan_jin_ovsianikov_chichkov_monteiro-riviere_stafslien_chisholm_2009, title={Pulsed laser deposition of antimicrobial silver coating on Ormocer microneedles.}, volume={1}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=MEDLINE&KeyUT=MEDLINE:20661316&KeyUID=MEDLINE:20661316}, number={4}, journal={Biofabrication}, author={Gittard, S D and Narayan, R J and Jin, C and Ovsianikov, A and Chichkov, B N and Monteiro-Riviere, N A and Stafslien, S and Chisholm, B}, year={2009}, pages={041001} }
 @article{gittard_narayan_lusk_morel_stockmans_ramsey_laverde_phillips_monteiro-riviere_ovsianikov_et al._2009, title={Rapid prototyping of scaphoid and lunate bones}, volume={4}, ISSN={1860-6768 1860-7314}, url={http://dx.doi.org/10.1002/biot.200800233}, DOI={10.1002/biot.200800233}, abstractNote={In this study, a novel rapid prototyping technology was used to fabricate scaphoid and lunate bone prostheses, two carpal bones that are prone to avascular necrosis. Carpal prostheses were fabricated with an Envisiontec Perfactory SXGA stereolithography system using Envisiontec eShell 200 photocurable polymer. Fabrication was guided using 3-D models, which were generated using Mimics software (Materialise NV, Leuven, Belgium) from patient computer tomography data. The prostheses were fabricated in a layer-by-layer manner; approximately 50-microm thick layers were observed in the prostheses. Hardness and Young's modulus values of polymerized eShell 200 material were 93.8 +/- 7.25 MPa and 3050 +/- 90 MPa, respectively. The minimum compressive force required for fracture was 1360 N for the scaphoid prosthesis and 1248 N for the lunate prosthesis. Polymerized Envisiontec eShell material exhibited high human neonatal epidermal keratinocyte cell viability rate in an MTT assay. The results of this study indicate that small bone prostheses fabricated by stereolithography using eShell 200 polymer may have suitable geometry, mechanical properties, and cytocompatibility properties for in vivo use.}, number={1}, journal={Biotechnology Journal}, publisher={Wiley}, author={Gittard, Shaun D. and Narayan, Roger and Lusk, Jason and Morel, Pierre and Stockmans, Filip and Ramsey, Michael and Laverde, Claire and Phillips, Jack and Monteiro-Riviere, Nancy A. and Ovsianikov, Aleksandr and et al.}, year={2009}, month={Jan}, pages={129–134} }
 @book{eaton_philbert_akexeeff_bahadori_balbus_bawendi_biswas_colvin_klaine_maynard_et al._2009, place={Washington, DC}, title={Review of Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research}, ISBN={9780309116992 9780309185837}, url={http://dx.doi.org/10.17226/12559}, DOI={10.17226/12559}, publisher={National Academies Press}, author={Eaton, D.L. and Philbert, M.A. and Akexeeff, G.V. and Bahadori, T. and Balbus, J.M. and Bawendi, M.G. and Biswas, P. and Colvin, V.L. and Klaine, S.J. and Maynard, A.D. and et al.}, year={2009} }
 @article{boehm_narayan_aggarwal_monteiro-riviere_lacour_2009, title={Stretchable diamond-like carbon microstructures for biomedical applications}, volume={61}, ISSN={["1543-1851"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000269953700010&KeyUID=WOS:000269953700010}, DOI={10.1007/s11837-009-0134-3}, number={9}, journal={JOM}, author={Boehm, Ryan and Narayan, Roger J. and Aggarwal, Ravi and Monteiro-Riviere, Nancy A. and Lacour, Stephanie P.}, year={2009}, month={Sep}, pages={53–58} }
 @inbook{monteiro-riviere_2008, title={Anatomical factors that affect barrier function}, ISBN={9780849397738}, booktitle={Dematotoxicology (7th ed.)}, publisher={Boca Raton: Wiley & Sons}, author={Monteiro-Riviere, N. A.}, editor={H. Zhai, K. P. Wilhelm and Maibach, H. I.Editors}, year={2008}, pages={39–50} }
 @inbook{monteiro-riviere_baynes_riviere_2008, place={New York}, edition={2nd}, title={Animal skin morphology and dermal absorption}, ISBN={0849375916}, booktitle={Dermal absorption and toxicity assessment}, publisher={Informa Healthcare}, author={Monteiro-Riviere, N. A. and Baynes, R. E. and Riviere, J. E.}, editor={Roberts, M.S. and Walters, K.A.Editors}, year={2008}, pages={17–35} }
 @article{zhang_monteiro-riviere_2008, title={Assessment of quantum dot penetration into intact, tape-stripped, abraded and flexed rat skin}, volume={21}, ISSN={["1660-5535"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000256798700006&KeyUID=WOS:000256798700006}, DOI={10.1159/000131080}, abstractNote={Quantum dot (QD) nanoparticles have received attention due to their fluorescent characteristics and potential use in medical applications. Skin penetration is one of the major routes of exposure for nanoparticles to gain access to a biological system. QD655 and QD565 coated with carboxylic acid were studied for 8 and 24 h in flow-through diffusion cells with flexed, tape-stripped and abraded rat skin to determine if these mechanical actions could perturb the barrier and affect penetration. Nonflexed skin did not show QD penetration at 8 or 24 h. Flexed skin showed an increase in QD on the surface of skin but no penetration at 8 and 24 h. Tape-stripped skin depicted QD only on the surface of the viable epidermis. QD655 penetrated into the viable dermal layers of abraded skin at both 8 and 24 h, while QD565 was present only at 24 h. QD were not detected in the perfusate by fluorescence and inductively coupled plasma-optical emission spectroscopy analysis for cadmium at any time point. These results indicate that the rat skin penetration of QD655 and QD565 is primarily limited to the uppermost stratum corneum layers of intact skin. Barrier perturbation by tape stripping did not cause penetration, but abrasion allowed QD to penetrate deeper into the dermal layers.}, number={3}, journal={SKIN PHARMACOLOGY AND PHYSIOLOGY}, author={Zhang, L. W. and Monteiro-Riviere, N. A.}, year={2008}, pages={166–180} }
 @article{zhang_yu_colvin_monteiro-riviere_2008, title={Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes}, volume={228}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000255494300008&KeyUID=WOS:000255494300008}, DOI={10.1016/j.taap.2007.12.022}, abstractNote={Quantum dots nanoparticles have novel optical properties for biomedical applications and electronics, but little is known about their skin permeability and interaction with cells. QD621 are nail-shaped nanoparticles that contain a cadmium/selenide core with a cadmium sulfide shell coated with polyethylene glycol (PEG) and are soluble in water. QD were topically applied to porcine skin flow-through diffusion cells to assess penetration at 1 microM, 2 microM and 10 microM for 24 h. QD were also studied in human epidermal keratinocytes (HEK) to determine cellular uptake, cytotoxicity and inflammatory potential. Confocal microscopy depicted the penetration of QD621 through the uppermost stratum corneum (SC) layers of the epidermis and fluorescence was found primarily in the SC and near hair follicles. QD were found in the intercellular lipid bilayers of the SC by transmission electron microscopy (TEM). Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD both did not detect Cd nor fluorescence signal in the perfusate at any time point or concentration. In HEK, viability decreased significantly (p<0.05) from 1.25 nM to 10 nM after 24 h and 48 h. There was a significant increase in IL-6 at 1.25 nM to 10 nM, while IL-8 increased from 2.5 nM to 10 nM after 24 h and 48 h. TEM of HEK treated with 10 nM of QD621 at 24 h depicted QD in cytoplasmic vacuoles and at the periphery of the cell membranes. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, yet if the skin were damaged allowing direct QD exposure to skin or keratinocytes, an inflammatory response could be initiated.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Zhang, Leshuai W. and Yu, William W. and Colvin, Vicki L. and Monteiro-Riviere, Nancy A.}, year={2008}, month={Apr}, pages={200–211} }
 @article{monteiro-riviere_inman_2008, title={COLL 95-Assessment of quantum dot nanoparticle penetration in human skin}, volume={236}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000270256303852&KeyUID=WOS:000270256303852}, journal={Abstracts of Papers of the American Chemical Society}, author={Monteiro-Riviere, Nancy A. and Inman, A. O.}, year={2008} }
 @article{adrian t. o'neill_monteiro-riviere_walker_2008, title={Characterization of microfluidic human epidermal keratinocyte culture}, volume={56}, ISSN={["0920-9069"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000257370900007&KeyUID=WOS:000257370900007}, DOI={10.1007/s10616-008-9149-9}, abstractNote={Human epidermal keratinocytes (HEK) are skin cells of primary importance in maintaining the body’s defensive barrier and are used in vitro to assess the irritation potential and toxicity of chemical compounds. Microfluidic systems hold promise for high throughput irritant and toxicity assays, but HEK growth kinetics have yet to be characterized within microscale culture chambers. This research demonstrates HEK patterning on microscale patches of Type I collagen within microfluidic channels and maintenance of these cells under constant medium perfusion for 72 h. HEK were shown to maintain 93.0%–99.6% viability at 72 h under medium perfusion ranging from 0.025–0.4 μl min−1. HEK maintained this viability while ∼100% confluent—a level not possible in 96 well plates. Microscale HEK cultures offer the ability to precisely examine the morphology, behavior and viability of individual cells which may open the door to new discoveries in toxicological screening methods and wound healing techniques.}, number={3}, journal={CYTOTECHNOLOGY}, author={Adrian T. O'Neill and Monteiro-Riviere, Nancy A. and Walker, Glenn M.}, year={2008}, month={Mar}, pages={197–207} }
 @article{rouse_haslauer_loboa_monteiro-riviere_2008, title={Cyclic tensile strain increases interactions between human epidermal keratinocytes and quantum dot nanoparticles}, volume={22}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000254694500024&KeyUID=WOS:000254694500024}, DOI={10.1016/j.tiv.2007.10.010}, abstractNote={The effects of quantum dots (QD) on cell viability have gained increasing interest due to many recent developments utilizing QD for pharmaceutical and biomedical applications. The potential use of QD nanoparticles as diagnostic, imaging, and drug delivery agents has raised questions about their potential for cytotoxicity. The objective of this study was to investigate the effects of applied strain on QD uptake by human epidermal keratinocytes (HEK). It was hypothesized that introduction of a 10% average strain to cell cultures would increase QD uptake. HEK were seeded at a density of 150,000 cells/mL on collagen-coated Flexcell culture plates (Flexcell Intl.). QD were introduced at a concentration of 3 nM and a 10% average strain was applied to the cells. After 4 h of cyclic strain, the cells were examined for cell viability, QD uptake, and cytokine production. The results indicate that addition of strain results in an increase in cytokine production and QD uptake, resulting in irritation and a negative impact on cell viability. Application of physiological load conditions can increase cell membrane permeability, thereby increasing the concentration of QD nanoparticles in cells.}, number={2}, journal={TOXICOLOGY IN VITRO}, author={Rouse, Jillian G. and Haslauer, Carla M. and Loboa, Elizabeth G. and Monteiro-Riviere, Nancy A.}, year={2008}, month={Mar}, pages={491–497} }
 @inbook{monteiro-riviere_2008, title={Dermatotoxicology}, ISBN={9780470102114}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84889338262&partnerID=MN8TOARS}, DOI={10.1002/9780470285251.ch35}, booktitle={Molecular and biochemical toxicology (4th ed.)}, publisher={Hoboken, NJ: John Wiley}, author={Monteiro-Riviere, N.A.}, editor={Smart, R. C. and Hodgson, E.Editors}, year={2008}, pages={851–880} }
 @article{inman_monteiro-riviere_riviere_2008, title={Inhibition of jet fuel aliphatic hydrocarbon induced toxicity in human epidermal keratinocytes}, volume={28}, ISSN={["1099-1263"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000256028900016&KeyUID=WOS:000256028900016}, DOI={10.1002/jat.1309}, abstractNote={Jet propellant (JP)-8, the primary jet fuel used by the U.S. military, consists of hydrocarbon-rich kerosene base commercial jet fuel (Jet-A) plus additives DC1-4A, Stadis 450 and diethylene glycol monomethyl ether. Human epidermal keratinocytes (HEK) were exposed to JP-8, aliphatic hydrocarbon (HC) fuel S-8 and aliphatic HC pentadecane (penta), tetradecane (tetra), tridecane (tri) and undecane (un) for 5 min. Additional studies were conducted with signal transduction pathway blockers parthenolide (P; 3.0 microm), isohelenin (I; 3.0 microm), SB 203580 (SB; 13.3 microm), substance P (SP; 3.0 microm) and recombinant human IL-10 (rHIL-10; 10 ng ml(-1)). In the absence of inhibitors, JP-8 and to a lesser extent un and S-8, had the greatest toxic effect on cell viability and inflammation suggesting, as least in vitro, that synthetic S-8 fuel is less irritating than the currently used JP-8. Each inhibitor significantly (P < 0.05) decreased HEK viability. DMSO, the vehicle for P, I and SB, had a minimal effect on viability. Overall, IL-8 production was suppressed at least 30% after treatment with each inhibitor. Normalizing data relative to control indicate which inhibitors suppress HC-mediated IL-8 to control levels. P was the most effective inhibitor of IL-8 release; IL-8 was significantly decreased after exposure to un, tri, tetra and penta but significantly increased after JP-8 exposure compared with controls. Inhibitors were not effective in suppressing IL-8 release in JP-8 exposures to control levels. This study shows that inhibiting NF-kappa B, which appears to play a role in cytokine production in HC-exposed HEK in vitro, may reduce the inflammatory effect of HC in vivo.}, number={4}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Inman, A. O. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={2008}, month={May}, pages={543–553} }
 @article{narayan_aggarwal_wei_jin_monteiro-riviere_crombez_shen_2008, title={Mechanical and biological properties of nanoporous carbon membranes}, volume={3}, ISSN={["1748-605X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000258916500020&KeyUID=WOS:000258916500020}, DOI={10.1088/1748-6041/3/3/034107}, abstractNote={Implantable blood glucose sensors have inadequate membrane-tissue interfaces for long term use. Biofouling and inflammation processes restrict biosensor membrane stability. An ideal biosensor membrane material must prevent protein adsorption and exhibit cell compatibility. In addition, a membrane must exhibit high porosity and low thickness in order to allow the biosensor to respond to analyte fluctuations. In this study, the structural, mechanical and biological properties of nanoporous alumina membranes coated with diamond-like carbon thin films were examined using scanning probe microscopy, nanoindentation and MTT viability assay. We anticipate that this novel membrane material could find use in immunoisolation devices, kidney dialysis membranes and other medical devices encountering biocompatibility issues that limit in vivo function.}, number={3}, journal={BIOMEDICAL MATERIALS}, author={Narayan, Roger J. and Aggarwal, Ravi and Wei, Wei and Jin, Chunming and Monteiro-Riviere, Nancy A. and Crombez, Rene and Shen, Weidian}, year={2008}, month={Sep} }
 @article{karakoti_monteiro-riviere_aggarwal_davis_narayan_self_mcginnis_seal_2008, title={Nanoceria as antioxidant: Synthesis and biomedical applications}, volume={60}, ISSN={["1543-1851"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000253852900008&KeyUID=WOS:000253852900008}, DOI={10.1007/s11837-008-0029-8}, abstractNote={The therapeutic application of nanomaterials has been a focus of numerous studies in the past decade. Due to its unique redox properties, cerium oxide (ceria) is finding widespread use in the treatment of medical disorders caused by the reactive oxygen intermediates (ROI). The radical-scavenging role of ceria nanoparticles (nanoceria) have been established, as well as the autocatalytic ability of nanoceria to regenerate under various environmental conditions. The synthesis of nanoceria in biocompatible media has also been reported along with cell viability in order to determine the potential use of nanoceria in biomedical applications.}, number={3}, journal={JOM}, author={Karakoti, A. S. and Monteiro-Riviere, N. A. and Aggarwal, R. and Davis, J. P. and Narayan, R. J. and Self, W. T. and McGinnis, J. and Seal, S.}, year={2008}, month={Mar}, pages={33–37} }
 @inbook{roberts_gierden_riviere_monteiro-riviere_2008, title={Solvents and vehicle effects on the skin}, ISBN={9780849375910}, booktitle={Dermal absorption and toxicity assessment. (2nd ed.)}, publisher={New York: Informa Healthcare}, author={Roberts, M. S. and Gierden, A. and Riviere, J. E. and Monteiro-Riviere, N. A.}, editor={Roberts, M. S. and Walters, K. A.Editors}, year={2008}, pages={433–447} }
 @article{lin_tournas_burch_monteiro-riviere_zielinski_2008, title={Topical isoflavones provide effective photoprotection to skin}, volume={24}, ISSN={["1600-0781"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000254054600002&KeyUID=WOS:000254054600002}, DOI={10.1111/j.1600-0781.2008.00329.x}, abstractNote={Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone-mediated photoprotection with the pig skin model, a more human-resembling model.The pig skin was treated with five well-known isoflavone compounds (genistein, equol, daidzein, biochanin A, and formononetin) and one antioxidant combination solution of 15% vitamin C and 1% vitamin E and 0.5% ferulic acid (CEF) daily for 4 days. Skin was irradiated with solar-simulated UV irradiation, 1 to 5 minimal erythema dose (MED) at 1-MED intervals. Evaluation was carried out 24 h later by colorimeter-measured erythema and sunburn cell numbers.Topical application of 0.5% solutions of three individual phytoestrogens - genistein, daidzein, biochanin A - are better than similar solutions of equol or formononetin in protecting pig skin from solar-simulated ultraviolet (SSUV)-induced photodamage, as measured by sunburn cell formation and/or erythema. However, the protection was less than that provided by a topical combination antioxidant standard containing 15% L-ascorbic acid, 1%alpha-tocopherol, and 0.5% ferulic acid.Isoflavones provide effective photoprotection and are good candidate ingredients for protection against ultraviolet (UV) photodamage.}, number={2}, journal={PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE}, author={Lin, Jing-Yi and Tournas, Joshua A. and Burch, James A. and Monteiro-Riviere, Nancy A. and Zielinski, Jan}, year={2008}, month={Apr}, pages={61–66} }
 @inbook{monteiro-riviere_orsiere_2008, title={Toxicological impacts of nanomaterials}, ISBN={0071477500}, booktitle={Environmental nanotechnology: Applications and impacts of nanomaterials}, publisher={New York: McGraw-Hill}, author={Monteiro-Riviere, N. A. and Orsiere, T.}, editor={Wiesner, M. R. and Bottero, J. Y.Editors}, year={2008}, pages={395–444} }
 @article{walker_monteiro-riviere_rouse_adrian t. o'neill_2007, title={A linear dilution microfluidic device for cytotoxicity assays}, volume={7}, ISSN={["1473-0189"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000244616300011&KeyUID=WOS:000244616300011}, DOI={10.1039/b608990a}, abstractNote={A two-layer polymer microfluidic device is presented which creates nine linear dilutions from two input fluid streams mixed in varying volumetric proportions. The linearity of the nine dilutions is conserved when the flow rate is held constant at 1.0 microl min(-1) (R(2) = 0.9995) and when it is varied from 0.5-16 microl min(-1) (R(2) = 0.9998). An analytical expression is presented for designing microfluidic devices with arbitrary numbers of linear dilutions. To demonstrate the efficacy of this device, primary human epidermal keratinocytes (HEK) were stained with nine dilutions of calcein, resulting in a linear spread of fluorescent intensities (R(2) = 0.94). The operating principles of the device can be scaled up to incorporate any number of linear dilutions. This scalability, coupled with an intrinsic ability to create linear dilutions under a variety of operating conditions, makes the device applicable to high throughput screening applications such as combinatorial chemistry or cytotoxicity assays.}, number={2}, journal={LAB ON A CHIP}, author={Walker, Glenn M. and Monteiro-Riviere, Nancy and Rouse, Jillian and Adrian T. O'Neill}, year={2007}, pages={226–232} }
 @article{xia_baynes_monteiro-riviere_riviere_2007, title={A system coefficient approach for quantitative assessment of the solvent effects on membrane absorption from chemical mixtures}, volume={18}, ISSN={["1062-936X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000249294000006&KeyUID=WOS:000249294000006}, DOI={10.1080/10629360701428540}, abstractNote={A system coefficient approach is proposed for quantitative assessment of the solvent effects on membrane absorption from chemical mixtures. The complicated molecular interactions are dissected into basic molecular interaction forces via Abraham's linear solvation energy relationship (LSER). The molecular interaction strengths of a chemical are represented by a set of solute descriptors, while those of a membrane/chemical mixture system are represented by a set of system coefficients. The system coefficients can be determined by using a set of probe compounds with known solute descriptors. Polydimethylsiloxane (PDMS) membrane-coated fibres and 32 probe compounds were used to demonstrate the proposed approach. When a solvent was added into the chemical mixture, the system coefficients were altered and detected by the system coefficient approach. The system coefficients of the PDMS/water system were (0.09, 0.49, -1.11, -2.36, -3.78, 3.50). When 25% ethanol was added into the PDMS/water system, the system coefficients were altered significantly (0.38, 0.41, -1.18, -2.07, -3.40, 2.81); and the solvent effect was quantitatively described by the changes in the system coefficients (0.29, -0.08, -0.07, 0.29, 0.38, -0.69). The LSER model adequately described the experimental data with a correlation coefficient (r(2)) of 0.995 and F-value of 1056 with p-value less than 0.0001.}, number={5-6}, journal={SAR AND QSAR IN ENVIRONMENTAL RESEARCH}, author={Xia, X. R. and Baynes, R. E. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={2007}, pages={579–593} }
 @article{xia_baynes_monteiro-riviere_riviere_2007, title={An experimentally based approach for predicting skin permeability of chemicals and drugs using a membrane-coated fiber array}, volume={221}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000247278800007&KeyUID=WOS:000247278800007}, DOI={10.1016/j.taap.2007.03.026}, abstractNote={A membrane-coated fiber (MCF) array approach is proposed for predicting the percutaneous absorption of chemicals and drugs from chemical or biological mixtures. Multiple MCFs were used to determine the partition coefficients of compounds (logKMCF). We hypothesized that one MCF will characterize one pattern of molecular interactions and therefore the skin absorption process can be simulated by a multiple MCF array having diverse patterns of molecular interactions. Three MCFs, polydimethylsiloxane (PDMS), polyacrylate (PA) and CarboWax (Wax), were used to determine the logKMCF values for a set of calibration compounds. The skin permeability log(kp) of the compounds was measured by diffusion experiments using porcine skin. The feasibility of the MCF array approach for predicting skin permeability was demonstrated with the three MCFs. A mathematical model was established by multiple linear regression analysis of the log(kp) and logKMCF data set: log(kp) = − 2.34–0.124 logKpdms + 1.91 logKpa − 1.17 logKwax (n = 25, R2 = 0.93). The MCF array approach is an alternative animal model for skin permeability measurement. It is an experimentally based, high throughput approach that provides high prediction confidence and does not require literature data nor molecular structure information in contrast to the existing predictive models.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Xia, Xin-Rui and Baynes, Ronald E. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2007}, month={Jun}, pages={320–328} }
 @inbook{monteiro-riviere_baynes_riviere_2007, title={Animal skin morphology and dermal absorption}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77952889776&partnerID=MN8TOARS}, booktitle={Dermal Absorption and Toxicity Assessment, Second Edition}, author={Monteiro-Riviere, N.A. and Baynes, R.E. and Riviere, J.E.}, year={2007}, pages={17–36} }
 @article{lee_imran_monteiro-riviere_colvin_yu_rivlere_2007, title={Biodistribution of quantum dot nanoparticles in perfused skin: Evidence of coating dependency and periodicity in arterial extraction}, volume={7}, ISSN={["1530-6992"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000249501900058&KeyUID=WOS:000249501900058}, DOI={10.1021/nl071563c}, abstractNote={Arterial extraction of quantum dots (QD) assayed by fluorescence or inductively coupled plasma (ICP) emission spectrometry were studied after infusion into isolated perfused skin. Extraction was mathematically modeled using three linear differential equations. COOH-coated QD had greater tissue deposition, assessed both by model prediction and laser confocal scanning microscopy, than did QD-PEG. Both QD had a unique periodicity in arterial extraction never observed with drug infusions, suggesting a potentially important nanomaterial behavior that could affect systemic disposition.}, number={9}, journal={NANO LETTERS}, author={Lee, Hyun A. and Imran, Mudassar and Monteiro-Riviere, Nancy A. and Colvin, Vicki L. and Yu, William W. and Rivlere, Jim E.}, year={2007}, month={Sep}, pages={2865–2870} }
 @article{zhang_zeng_barron_monteiro-riviere_2007, title={Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes}, volume={26}, ISSN={["1092-874X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000245792700002&KeyUID=WOS:000245792700002}, DOI={10.1080/10915810701225133}, abstractNote={Carbon nanotube–based nanovectors, especially functionalized nanotubes, have shown potential for therapeutic drug delivery. 6-Aminohexanoic acid–derivatized single-wall carbon nanotubes (AHA-SWNTs) are soluble in aqueous stock solutions over a wide range of physiologically relevant conditions; however, their interactions with cells and their biological compatibility has not been explored. Human epidermal keratinocytes (HEKs) were dosed with AHA-SWNTs ranging in concentration from 0.00000005 to 0.05 mg/ml. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability decreased significantly ( p < .05) from 0.00005 to 0.05 mg/ml after 24 h. The proinflammatory mediators of inflammation cytokines interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, IL-10, and IL-1 β were also assessed. Cytokine analysis did not show a significant increase in IL-6 and IL-8 in the medium containing 0.000005 mg/ml of AHA-SWNTs from 1 to 48 h. IL-6 increased in cells treated with 0.05 mg/ml of AHA-SWNTs from 1 to 48 h, whereas IL-8 showed a significant increase at 24 and 48 h. No significant difference ( p < .05) was noted with TNF- α, IL-10, and IL-1 β expression at any time point. Transmission electron microscopy of HEKs treated with 0.05 mg/ml AHA-SWNTs for 24 h depicted AHA-SWNTs localized within intracytoplasmic vacuoles in HEKs. Treatment with the surfactant 1% Pluronic F127 caused dispersion of the AHA-SWNT aggregates in the culture medium and less toxicity. These data showed that the lower concentration of 0.000005 mg/ml of AHA-SWNTs maintains cell viability and induces a mild cytotoxicity, but 0.05 mg/ml of AHA-SWNTs demonstrated an irritation response by the increase in IL-8.}, number={2}, journal={INTERNATIONAL JOURNAL OF TOXICOLOGY}, author={Zhang, Leshuai W. and Zeng, Liling and Barron, Andrew R. and Monteiro-Riviere, Nancy A.}, year={2007}, pages={103–113} }
 @article{wei_sethuraman_jin_monteiro-riviere_narayan_2007, title={Biological properties of carbon nanotubes}, volume={7}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000245142200012&KeyUID=WOS:000245142200012}, DOI={10.1166/jnn.2007.655}, abstractNote={Carbon nanotubes are novel materials with unique physical and chemical properties, and have been considered for use in numerous technological applications. More recently, attention has turned to the unique biological and medical properties of these materials. In this review, the processing, chemical properties, physical properties, nucleic acid interaction, cell interaction, and toxicologic properties of nanotubes are described. Finally, future directions in this area are discussed.}, number={4-5}, journal={Journal of Nanoscience and Nanotechnology}, author={Wei, W. and Sethuraman, A. and Jin, C. and Monteiro-Riviere, N. A. and Narayan, R. J.}, year={2007}, pages={1284–1297} }
 @inbook{monteiro-riviere_2007, title={Dermal effects of nanomaterials}, ISBN={1420045148}, booktitle={Nanotoxicology: Characterization, dosing, and health effects}, publisher={New York: Informa Healthcare}, author={Monteiro-Riviere, N. A.}, editor={N. A. Monteiro-Riviere and Tran, C. L.Editors}, year={2007}, pages={317–337} }
 @inbook{monteiro-riviere_inman_ryman-rasmussen_2007, title={Dermal effects of nanomaterials}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-41549113687&partnerID=MN8TOARS}, booktitle={Nanotoxicology: Characterization, Dosing and Health Effects}, author={Monteiro-Riviere, N.A. and Inman, A.O. and Ryman-Rasmussen, J.P.}, year={2007}, pages={317–337} }
 @article{monteiro-riviere_2007, title={Dermal exposure to nanomaterials.}, volume={48}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000248865500032&KeyUID=WOS:000248865500032}, number={7}, journal={Environmental and Molecular Mutagenesis}, author={Monteiro-Riviere, N.}, year={2007}, pages={533} }
 @article{mccullen_stano_stevens_roberts_monteiro-riviere_clarke_gorga_2007, title={Development, optimization, and characterization of electrospun poly(lactic acid) nanofibers containing multi-walled carbon nanotubes}, volume={105}, ISSN={["1097-4628"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000247576000079&KeyUID=WOS:000247576000079}, DOI={10.1002/app.26288}, abstractNote={Electrospinning of poly (L-D-lactic acid) (PLA) was investigated with the addition of multi-walled carbon nanotubes (MWNT) for development of a scaffold for tissue engineering. Through this experiment, it was determined that the optimal concentration of PLA with weight average molecular weight (Mw) 250,000 g/mol is � 20 wt % as indicated by scanning electron microscopy. This concentration produces fibers with no beading or film formation. The preferred solvent system is a combination of chloroform and dimethyl formamide to alleviate the vol- atile action of chloroform. The optimum processing param- eters for PLA are an electric field of 1 kV/cm which was determined by a surface response plot to minimize fiber diameter based on the applied voltage, working distance, and addition of MWNT. Fourier Transform infrared spec- troscopy has indicated the removal of the solvent system. With the addition of MWNT, the fiber diameter was dras- tically reduced by 70% to form fibers with a mean diame- ter of 700 nm. This is believed to be due to an increased surface charge density for the MWNT/polymer solution. Transmission electron microscopy validated the alignment of the MWNT within the fibers. MWNT loading exhibited an increase in the conductance of the scaffold and the ten- sile modulus at an optimal loading level of 0.25 wt %. 2007 Wiley Periodicals, Inc. J Appl Polym Sci 105: 1668-1678, 2007}, number={3}, journal={JOURNAL OF APPLIED POLYMER SCIENCE}, author={McCullen, Seth D. and Stano, Kelly L. and Stevens, Derrick R. and Roberts, Wesley A. and Monteiro-Riviere, Nancy A. and Clarke, Laura I. and Gorga, Russell E.}, year={2007}, month={Aug}, pages={1668–1678} }
 @inbook{witzmann_monteiro-riviere_2007, title={Effect of carbon nanotube exposure on keratinocyte protein expression}, ISBN={9781420045147}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882791035&partnerID=MN8TOARS}, booktitle={Nanotoxicology: Characterization, Dosing and Health Effects}, publisher={New York: Informa Healthcare}, author={Witzmann, F.A. and Monteiro-Riviere, N.A.}, editor={Monteiro-Riviere, N. A. and Tran, C. L.Editors}, year={2007}, pages={197–224} }
 @article{rouse_yang_ryman-rasmussen_barron_monteiro-riviere_2007, title={Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin}, volume={7}, ISSN={["1530-6992"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000243381300027&KeyUID=WOS:000243381300027}, DOI={10.1021/nl062464m}, abstractNote={Dermatomed porcine skin was fixed to a flexing device and topically dosed with 33.5 mg·mL-1 of an aqueous solution of a fullerene-substituted phenylalanine (Baa) derivative of a nuclear localization peptide sequence (Baa-Lys(FITC)-NLS). Skin was flexed for 60 or 90 min or left unflexed (control). Confocal microscopy depicted dermal penetration of the nanoparticles at 8 h in skin flexed for 60 and 90 min, whereas Baa-Lys(FITC)-NLS did not penetrate into the dermis of unflexed skin until 24 h. TEM analysis revealed fullerene-peptide localization within the intercellular spaces of the stratum granulosum.}, number={1}, journal={NANO LETTERS}, author={Rouse, Jillian G. and Yang, Jianzhong and Ryman-Rasmussen, Jessica P. and Barron, Andrew R. and Monteiro-Riviere, Nancy A.}, year={2007}, month={Jan}, pages={155–160} }
 @article{balbus_maynard_colvin_castranova_daston_denison_dreher_goering_goldberg_kulinowski_et al._2007, title={Meeting report: Hazard assessment for nanoparticles - Report from an interdisciplinary workshop}, volume={115}, ISSN={["1552-9924"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000250769700034&KeyUID=WOS:000250769700034}, DOI={10.1289/chp.10327}, number={11}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Balbus, John M. and Maynard, Andrew D. and Colvin, Vicki L. and Castranova, Vincent and Daston, George P. and Denison, Richard A. and Dreher, Kevin L. and Goering, Peter L. and Goldberg, Alan M. and Kulinowski, Kristen M. and et al.}, year={2007}, month={Nov}, pages={1654–1659} }
 @article{balbus_maynard_colvin_castranova_daston_denison_dreher_goering_goldberg_kulinowski_et al._2007, title={Meeting report: Hazard assessment for nanoparticles-report from an interdisciplinary workshop}, volume={115}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-38449088295&partnerID=MN8TOARS}, DOI={10.1289/ehp.10327}, abstractNote={In this report we present the findings from a nanotoxicology workshop held 6–7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders.}, number={11}, journal={Environmental Health Perspectives}, author={Balbus, J.M. and Maynard, A.D. and Colvin, V.L. and Castranova, V. and Daston, G.P. and Denison, R.A. and Dreher, K.L. and Goering, P.L. and Goldberg, A.M. and Kulinowski, K.M. and et al.}, year={2007}, pages={1654–1659} }
 @book{nanotoxicology: characterization, dosing and health effects_2007, ISBN={1420045148}, publisher={New York: Informa Healthcare}, year={2007} }
 @book{monteiro-riviere_tran_2007, title={Nanotoxicology: Characterization, dosing and health effects}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84907389735&partnerID=MN8TOARS}, journal={Nanotoxicology: Characterization, Dosing and Health Effects}, author={Monteiro-Riviere, N.A. and Tran, C.L.}, year={2007}, pages={1–435} }
 @book{monteiro-riviere_tran_2007, title={Preface}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85057430652&partnerID=MN8TOARS}, journal={Nanotoxicology: Characterization, Dosing and Health Effects}, author={Monteiro-Riviere, N.A. and Tran, C.L.}, year={2007}, pages={iii-iv} }
 @book{riviere_monteiro-riviere_baynes_xia_2007, title={Quantitating the absorption, partitioning and toxicity of hydrocarbon components of JP-8 jet fuel}, number={FA9550-04-1-0376}, author={Riviere, J. E. and Monteiro-Riviere, N. A. and Baynes, R. E. and Xia, X. R.}, year={2007} }
 @inbook{roberts_gierden_riviere_monteiro-riviere_2007, title={Solvent and vehicle effects on the skin}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85056948070&partnerID=MN8TOARS}, booktitle={Dermal Absorption and Toxicity Assessment, Second Edition}, author={Roberts, M.S. and Gierden, A. and Riviere, J.E. and Monteiro-Riviere, N.A.}, year={2007}, pages={433–448} }
 @article{ryman-rasmussen_riviere_monteiro-riviere_2007, title={Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes}, volume={127}, ISSN={["1523-1747"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000243192200021&KeyUID=WOS:000243192200021}, DOI={10.1038/sj.jid.5700508}, abstractNote={Quantum dot (QD) nanoparticles have potential applications in nanomedicine as drug delivery vectors and diagnostic agents, but the skin toxicity and irritation potential of QDs are unknown. Human epidermal keratinocytes (HEKs) were used to assess if QDs with different surface coatings would cause differential effects on HEK cytotoxicity, proinflammatory cytokine release, and cellular uptake. Commercially available QDs of two different sizes, QD 565 and QD 655, with neutral (polyethylene glycol (PEG)), cationic (PEG-amine), or anionic (carboxylic acid) coatings were utilized. Live cell imaging and transmission electron microscopy were used to determine that all QDs localized intracellularly by 24 hours, with evidence of QD localization in the nucleus. Cytotoxicity and release of the proinflammatory cytokines IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α were assessed at 24 and 48 hours. Cytotoxicity was observed for QD 565 and QD 655 coated with carboxylic acids or PEG-amine by 48 hours, with little cytotoxicity observed for PEG-coated QDs. Only carboxylic acid-coated QDs significantly increased release of IL-1β, IL-6, and IL-8. These data indicate that QD surface coating is a primary determinant of cytotoxicity and immunotoxicity in HEKs, which is consistent across size. However, uptake of QDs by HEKs is independent of surface coating. Quantum dot (QD) nanoparticles have potential applications in nanomedicine as drug delivery vectors and diagnostic agents, but the skin toxicity and irritation potential of QDs are unknown. Human epidermal keratinocytes (HEKs) were used to assess if QDs with different surface coatings would cause differential effects on HEK cytotoxicity, proinflammatory cytokine release, and cellular uptake. Commercially available QDs of two different sizes, QD 565 and QD 655, with neutral (polyethylene glycol (PEG)), cationic (PEG-amine), or anionic (carboxylic acid) coatings were utilized. Live cell imaging and transmission electron microscopy were used to determine that all QDs localized intracellularly by 24 hours, with evidence of QD localization in the nucleus. Cytotoxicity and release of the proinflammatory cytokines IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α were assessed at 24 and 48 hours. Cytotoxicity was observed for QD 565 and QD 655 coated with carboxylic acids or PEG-amine by 48 hours, with little cytotoxicity observed for PEG-coated QDs. Only carboxylic acid-coated QDs significantly increased release of IL-1β, IL-6, and IL-8. These data indicate that QD surface coating is a primary determinant of cytotoxicity and immunotoxicity in HEKs, which is consistent across size. However, uptake of QDs by HEKs is independent of surface coating. Hank's balanced salt solution human epidermal keratinocyte keratinocyte growth medium-2 polyethylene glycol quantum dot transmission electron microscopy 3-[4,5]dimethylthiazol-2,5 dephenyltetrazolium bromide Semiconductor nanocrystals, or quantum dots (QDs) have great potential for use as drug delivery, diagnostic, and imaging agents in biomedicine and as semiconductors in the electronics industry. QDs are a diverse class of engineered nanostructures that are highly variable in chemical composition, size, and shape and are frequently multi-layered. The center is comprised of a heterogeneous, colloidal core of inorganic atoms (e.g., CdSe, CdTe, InAs, GaN) that is frequently surrounded by a shell or “cap”, such as ZnS, that can reduce leaching of core metals (Derfus et al., 2004Derfus A.M. Chan W.C.W. Bhatia S. Probing the cytotoxicity of semiconductor nanocrystals.Nano Lett. 2004; 4: 11-18Google Scholar) and attenuate fluorescence intermittency, or “blinking” (Nirmal et al., 1996Nirmal M. Dabbousi B.O. Bawendi M.G. Macklin J.J. Trautman J.K. Harris T.D. et al.Fluorescence intermittency in single cadmium selenide naocrystals.Nature. 1996; 383: 802-804Google Scholar). Surface coatings in one or more layers are often applied to the core/shell complex to customize QDs for different applications, such as increased solubility in biological media or bioconjugation to antibodies or receptor ligands for “targeted” drug delivery and diagnostics (Michalet et al., 2005Michalet X. Pinaud F.F. Bentolila L.A. Tsay J.M. Doose S. Li J.J. et al.Quantum dots for live cells, in vivo imaging, and diagnostics.Science. 2005; 307: 538-544Google Scholar). Nanoscale materials possess novel properties as a direct consequence of size. This may have unique consequences for toxicology (Monteiro-Riviere and Ryman-Rasmussen, 2006Monteiro-Riviere N.A. Ryman-Rasmussen J.P. Toxicology of nanomaterials.in: Riviere J.E. Biological concepts and techniques in toxicology: an integrated approach. Taylor & Francis, London2006: 217-233Google Scholar). The hallmark nanoscale property of QDs is quantum confinement, in which the distance between an excited electron in the conduction band and the corresponding vacant hole in the valence band (the “Bohr radius”) is greater than the size of the nanocrystal core, which results in fluorescence at size-dependent wavelengths. The excitation range of QDs is broad but the fluorescence is discreet and resistant to photobleaching, making QDs easily detectable and amenable to multicolor imaging studies and tracking in live cells. A seminal study demonstrated that targeted CdSe core/ZnS shell QDs could be internalized by HeLa cells and tracked in live cells for more than 10 days with no morphological signs of toxicity (Jaiswal et al., 2003Jaiswal J.K. Mattoussi H. Mauro J.M. Simon S.M. Long-term multiple color imaging of live cells using quantum dot bioconjugates.Nat Biotechnol. 2003; 21: 47-51Google Scholar). This study fueled a great deal of optimism that QDs were non-toxic at doses suitable for long-term imaging studies and drug delivery. Therefore, many synthetic efforts were focused in these directions. There are increasing reports of QD cytotoxicity in the literature (Hardman, 2006Hardman R. A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors.Environ Health Perspect. 2006; 114: 165-172Google Scholar), none of which address skin. Recently, we reported that exposure of skin to commercially available QDs differing in core/shell shape, hydrodynamic size, and surface coatings resulted in the penetration of the intact stratum corneum barrier with localization of QDs in the underlying epidermal and dermal layers as early as 8 hours after topical application (Ryman-Rasmussen et al., 2006Ryman-Rasmussen J.P. Riviere J.E. Monterio-Riviere N.A. Penetration of intact skin by quantum dots with diverse physicochemical properties.Toxicol Sci. 2006; 91: 159-165Google Scholar). This indicated that skin is a potential route of exposure to QDs. The present study utilized primary human neonatal epidermal keratinocytes (HEKs), an established in vitro model for epidermal toxicity, to determine the cytotoxic and inflammatory potential of QDs in skin. This study was designed to test the hypothesis that QDs would be differentially taken up by HEKs and cause cytotoxicity and inflammatory cytokine release in a manner dependent on surface coating. Soluble QDs of two sizes, QD 565 and QD 655, were obtained from a single, commercial source. Both QD 565 and QD 655 were obtained with three different surface coatings: polyethylene glycol (PEG), PEG-amines, or carboxylic acids. We used laser scanning confocal microscopy of live keratinocytes and transmission electron microscopy (TEM) to verify QD uptake 24 hours after administration. Cytotoxicity was assessed by cell viability assays with thiazolyl blue tetrazolium bromide (3-[4,5]dimethylthiazol-2,5 dephenyltetrazolium bromide (MTT)) at 24 and 48 hours. Inflammatory potential was assessed at 24 and 48 hours by measuring the release of the proinflammatory cytokines IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α that are often used as markers for cutaneous irritation. We observed no overlap in the emission channels for QD 565 (green) and QD 655 (red) in trials with fixed keratinocytes treated with 2 nm QD 565 or QD 655, which indicated that dual-label imaging experiments were valid at this concentration, and autofluorescence in the absence of QDs was negligible (data not shown). QDs of both sizes and all coatings were localized intracellularly by 24 hours (Figure 1). Punctate staining of PEG-coated QD 565 and QD 655 (Figure 1, top row) was observed in the cytoplasm, at the periphery of the nucleus, and in the nucleus (QD 565). There was no evidence of PEG-coated QD 565 and QD 655 colocalization (orange), although there were instances of individual cells that contained both green and red punctae. Approximately 50% of HEK cells in any visual field contained PEG-coated QDs. PEG-amine-coated QD 565 and QD 655 (Figure 1, middle row) were observed as very large green (QD 565) or red (QD 655) punctae in the cytoplasm. PEG-amine-QD-treated cells contained QD 565 or QD 655, QD 565 and QD 655 in separate regions of the same cell, or colocalized QD 565 and QD 655 (orange). Staining for PEG-amine-coated QD 565 and QD 655 was sporadic, as the majority of HEK cells in the culture dishes did not stain. Carboxylic acid-coated QD 565 and QD 655 demonstrated very different patterns of cytoplasmic localization than QDs coated with PEG or PEG-amines (Figure 1, bottom row). A majority of cells throughout the culture dish demonstrated diffuse, punctate, staining for both QD 565 and QD 655, with large and discrete punctae containing colocalized QD 565 and QD 655 (orange). Intranuclear staining of carboxylic acid-coated QD 565 and QD 655 was also observed. QDs of both sizes and all coatings were intracellularly localized by 24 hours. In all cases, QDs were usually found agglomerated, both in membrane-bound, vacuolar compartments (Figure 2a) or free in the cytoplasm (Figure 2b). Occasionally with the PEG and PEG-amine-coated QD 565, we observed lipid droplets that were peppered with QDs in the interior and more dense along the periphery (Figure 2c). We also observed several instances for PEG-coated QD 565 and QD 655 and carboxylic acid-coated QD 565 in which QDs were agglomerated within the intranuclear region of the cells. (Figure 2d). No effects of 5% (v/v) borate vehicle of pH 8.3 or 9.0 were seen on HEK viability at 24 or 48 hours (Figure 3a). No differences in HEK viability were observed for three concentrations of PEG-coated QD 565 at 24 or 48 hours (Figure 3b). No differences were observed for PEG-coated QD 655 at 24 hours. At 48 hours, however, there was a moderate (20%) but significant decrease in MTT viability at 20 nm compared to vehicle-treated controls and lower concentrations. No differences in viability at any of the three concentrations were observed for PEG-amine-coated QD 565 at 24 hours (Figure 3c). At 48 hours, however, viability decreased by 40% at the highest concentration compared to vehicle-treated controls and lower concentrations. As cytotoxicity was present at 48 hours but not 24 hours, we statistically compared viability at 24 and 48 hours at 20 nm and found a significant effect of time on viability. Similarly, for QD 655 coated with PEG-amine, there were no dose-dependent differences in viability at 24 hours. However, at 48 hours, viability at 20 nm was decreased to 40% compared to vehicle-treated controls and lower concentrations. There was also a significant effect of time on the cytotoxicity of PEG-amine-coated QD 655 at 20 nm between 24 and 48 hours. Unlike QD 565 coated with PEG or PEG-amines, there were significant differences in HEK viability at 24 hours for carboxylic acid-coated QD 565 (Figure 3d). HEKs treated at the highest of the three concentrations (20 nm) showed a 40% decrease in viability compared to vehicle-treated controls and lower concentrations. These differences remained at 48 hours. Similarly, QD 655 coated with carboxylic acids decreased HEK viability by 40% at 24 hours compared to vehicle-treated controls and lower concentrations. These differences remained at 48 hours, where viability was decreased by another 30%. This decrease in viability between 24 and 48 hours was significant and indicated an effect of time on cytotoxicity. As the decrease in viability between 24 and 48 hours for carboxylic acid-coated QD 565 was smaller than QD 655, we conducted statistical comparisons to see if there was an effect of size on the cytotoxicity. Comparison at 24 hours revealed no size differences. However, viability for QD 655 was significantly decreased relative to QD 565 at 48 hours, indicating a modulatory role for size in cytotoxicity. For all detectable cytokines, there were no effects of 5% (v/v) borate vehicle pH 8.3 or 9.0 at 24 or 48 hours. IL-10 and tumor necrosis factor-α release were not detectable for QD 565 and QD 655 of any coating at 24 or 48 hours within the low range of the multiplex assay, which had a threshold of 0.78 pg/ml. The basal, control levels of IL-1β in the culture medium at 24 hours averaged 1.1±0.2 and 2.6±0.7 pg/ml at maximal response to QDs. Basal levels at 48 hours averaged 2.6±0.6 and 12.2±2.6 pg/ml at maximal response to QDs (data not shown). Effects of dose and coating on IL-1β release were observed for QD 565. At 24 hours, there was over a 2-fold, dose-dependent increase in IL-1β release for carboxylic acid-coated QD 565 (Figure 4b). IL-1β release for this coating was also significantly elevated compared to PEG and PEG-amine coatings at either dose. These differences remained at 48 hours (Figure 4c). The magnitude of IL-1β release for carboxylic acid-coated QD 565 did not change between 24 and 48 hours (Figure 4d). Effects of coating and time on IL-1β release were observed for QD 655. At 24 hours, there was over a 3-fold, dose-dependent increase in IL-1β release for carboxylic acid-coated QD 655 (Figure 4b). This was significantly elevated compared to QD 655 coated with PEG or PEG-amines. At 48 hours, the magnitude of IL-1β release carboxylic acid-coated QD 655 at the highest dose exceeded controls, the lower dose, and other coatings by over 5-fold (Figure 4c). Comparison of IL-1β levels for 20 nm carboxylic acid-coated QD 655 at 24 and 48 hours revealed a significant effect of time on the magnitude of IL-1β release for this coating and dose (Figure 4d). At 48 hours, the difference in IL-1β release for 20 nm carboxylic acid-coated QD 655 and QD 565 was greater than 2-fold (Figure 4c). Statistical analysis confirmed that this difference was significant, revealing an effect of size on IL-1β release. The basal, control levels of IL-6 in the culture medium at 24 hours averaged 110±30 and 220±80 pg/ml at maximal response to QDs. Basal levels at 48 hours averaged 130±50 and 260±70 at maximal response to QDs (data not shown). Effects of dose and coating were observed for QD 565. At 24 hours, IL-6 release for carboxylic acid-coated QD 565 at 20 nm was over 50% greater than control and the lower dose (Figure 5b). At 48 hours, 20 nm carboxylic acid-coated QD 565 was elevated 2-fold compared to controls, the lower dose, and PEG coating at either dose (Figure 5c). There was also a slight but significant dose-dependent elevation in IL-6 release for 20 nm PEG-amine-coated QD 565 compared to controls and the lower dose. IL-6 release for carboxylic acid-coated QD 565 did not significantly differ between 24 and 48 hours (Figure 5d). IL-6 release for QD 655 was dependent on dose, coating, and time. Unlike QD 565, there were no effects of coating or concentration on IL-6 release for QD 655 at 24 hours (Figure 5b). However, significant differences were apparent at 48 hours (Figure 5c). Carboxylic acid-coated QD 655 at the highest dose was elevated 2-fold compared to vehicle-treated controls, the lower dose, and PEG and PEG-amine-coated QD 655 at both doses. Comparison of the magnitude of IL-6 release for 20 nm carboxylic acid-coated QD 655 at 24 and 48 hours revealed a significant effect of time (Figure 5d). The significant increase in IL-6 release at 24 hours for 20 nm carboxylic acid-coated QD 565 but not QD 655 indicated an effect of QD size on IL-6 release at 24 hours (Figure 5b). This effect was confirmed by statistical comparison. In contrast, at 48 hours, IL-6 release for carboxylic acid-coated QD 565 and QD 655 did not significantly differ (Figure 5c). The basal, control levels of IL-8 in the culture medium at 24 hours averaged 1,300±430 and 3,000±600 pg/ml at maximal response to QDs. Basal levels at 48 hours averaged 1,400±140 and 2,800±480 pg/ml at maximal response to QDs (data not shown). Effects of dose and coating were observed for QD 565. At 24 hours, IL-8 release for 20 nm carboxylic acid-coated QD 565 was 2-fold greater than for vehicle-treated controls, the lower dose, and PEG and PEG-amine coatings at either concentration (Figure 6b). Forty-eight hours after treatment, the magnitude of IL-8 release for 20 nm carboxylic acid-coated QD 565 was unchanged (Figure 6d). Also, there was a slight but significant, dose-dependent increase in IL-8 release for 20 nm PEG-amine-coated QD 565 (Figure 6c). Effects of coating, dose, and time on IL-8 release were observed in response to QD 655. There were no effects of coating or dose on IL-8 release for QD 655 at 24 hours (Figure 6b). By 48 hours, however, significant differences were apparent. IL-8 release for carboxylic acid-coated QD 655 at the highest dose was elevated over 2-fold compared to vehicle-treated controls, the lower dose, and PEG and PEG-amine-coatings at either dose. Also, there was a slight but significant dose-dependent increase in IL-8 release for 20 nm PEG-amine-coated QDs. Comparison of IL-8 levels for 20 nm carboxylic acid-coated QD 655 at 24 and 48 hours revealed a significant effect of time on IL-8 release (Figure 6d). An effect of size on IL-8 release for 20 nm carboxylic acid-coated QDs at 24 hours was indicated by the significant increase in the release of this cytokine for QD 565 but not QD 655 (Figure 6b). This effect was confirmed by statistical comparison. However, this effect of size did not extend to 48 hours, at which time the magnitude of IL-8 release for carboxylic acid-coated QD 565 and QD 655 did not differ (Figure 6c). We used commercially available CdSe core/ZnS shell QDs of two sizes (QD 565 and QD 655) and three different surface coatings (PEG, PEG-amines, and carboxylic acids) to test the hypothesis that QDs would be differentially taken up by HEKs and cause cytotoxicity and inflammatory cytokine release depending on surface coating. We controlled for potential core-related effects by restricting these studies to QDs of the same core material with defined sizes and surface coatings. We found that all QDs tested localized to the interior of HEKs by 24 hours. However, cytotoxicity and proinflammatory cytokine release were dependent up surface coating, a robust finding consistent across QDs of two different sizes (Table 1).Table 1Summary of QD effects in HEK.CytotoxicityIL-1βIL-6IL-8QD 565PEG 24 hNSNSNSNS 48 hNSNSNSNSQD 565PEG - NH2 24 hNSNSNSNS 48 h+++NS++QD 565COOH 24 h+++++++++++ 48 h+++++++++++QD 655PEG 24 hNSNSNSNS 48 h+NSNSNSQD 655PEG - NH2 24 hNSNSNSNS 48 h+++NSNS+QD 655COOH 24 h++++++NSNS 48 h++++++++++++++HEK, human epidermal keratinocytes; NS, not significant; QD, quantum dots.Relative degree of effect within each column indicated by (+) or NS. Effects range from (+): statistically significant, but small in magnitude to (++++): statistically significant and large in magnitude. Open table in a new tab HEK, human epidermal keratinocytes; NS, not significant; QD, quantum dots. Relative degree of effect within each column indicated by (+) or NS. Effects range from (+): statistically significant, but small in magnitude to (++++): statistically significant and large in magnitude. Previously, we reported that multi-walled carbon nanotubes were intracellularly localized in cytoplasmic vacuoles of HEKs (Monteiro-Riviere et al., 2005bMonteiro-Riviere N.A. Nemanich R.J. Inman A.O. Wang Y.Y. Riviere J.E. Multi-walled carbon nanotube interactions with human epidermal keratinocytes.Toxicol Lett. 2005; 155: 377-384Google Scholar). The present study is the first to determine that a similar phenomenon extends to QDs in HEKs. Live cell imaging that eliminates fixation artifacts was used in conjunction with confocal laser scanning microscopy for this purpose. A low (2 nm), non-cytotoxic concentration of QDs was chosen to minimize uptake attributable to cell damage. All QDs localized intracellularly by 24 hours, which was surprising because these QDs were not “targeted” for cellular delivery. No evidence of colocalization was seen for QD 565 and QD 655 coated with PEG, which indicates that QDs with the same coating, but different core sizes, are differentially trafficked in HEKs. This result is consistent with a previous study, which showed that core size can influence the intracellular localization of QDs with the same coating (Lovric et al., 2005aLovric J. Bazzi H.S. Cuie Y. Fortin G.R. Winnik F.M. Maysinger D. Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots.J Mol Med. 2005; 83: 377-385Google Scholar). In contrast, QD 565 and QD 655 coated with carboxylic acids or PEG-amines exhibited colocalization, which indicates cellular uptake and/or intracellular trafficking of QD 565 and QD 655 of the same coating by the same mechanisms. The result that QDs of different sizes and coatings localized to the interior of HEKs is of importance because it suggests a mechanism by which QDs may lodge in the avascular epidermis and escape removal by resident macrophages (Monteiro-Riviere and Inman, 2005Monteiro-Riviere N.A. Inman A.O. Challenges for assessing carbon nanomaterial toxicity to the skin.Carbon. 2005; 44: 1070-1078Google Scholar). We also observed nuclear localization of carboxylic acid and PEG-coated QDs by live cell confocal laser scanning microscopy, which was confirmed by TEM. Presently, it is not known if nuclear access of the QDs examined in this study would cause genetic damage in HEKs. There is one report, however, that CdSe core/ZnS shell QDs coated with biotin can nick supercoiled DNA in an in vitro, cell-free assay (Green and Howman, 2005Green M. Howman E. Semiconductor quantum dots and free radical induced DNA nicking.Chem Commun (Cambridge). 2005; 1: 121-123Google Scholar). Agglomeration and/or adsorption of proteins in the culture medium could modulate QD uptake into cells. TEM revealed agglomeration of QDs within HEKs. Agglomeration may occur in the culture medium as a result of nanoparticle interaction with media salts or proteins (Borm et al., 2006Borm P. Klaessig F.C. Landry T.D. Moudgil B. Pauluhn J. Thomas K. et al.Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles.Toxicol Sci. 2006; 90: 23-32Google Scholar), which in the case of partially defined keratinocyte growth medium-2 (KGM-2) medium are human epidermal growth factor, insulin, transferrin and peptide hormones, and proteins from bovine pituitary extract. Alternatively, agglomeration may take place in cytoplasmic vacuoles. However, where agglomeration occurs, QDs were clearly available to the cell for uptake, as evidenced by the presence of these agglomerates in vacuoles and free in the cytoplasm for all QDs. Observation of free QDs in the cytoplasm is an important result, suggesting that QDs can escape cytoplasmic vacuoles or elude sequestration, which might allow interactions with cellular organelles or access to the nucleus. Occasionally, we noted the presence of lipid droplets peppered with electron-dense, PEG- and PEG-amine-coated QDs within the interior and along the periphery of the lipid droplet. Such lipids droplets are normally present in HEKs. Cell viability dose–response assays showed significant cytotoxicity for PEG-amine- and carboxylic acid-coated QDs, but not PEG-coated QDs. These results were consistent for QDs of both sizes. PEG-coated QD 565 and QD 655 exhibited no appreciable cytotoxicity over 48 hours, but PEG-amine and carboxylic acid-coated QD 565 and QD 655 exhibited significant cytotoxicity within 48 hours at the highest dose. A modulatory role for exposure time in QD cytotoxicity was demonstrated by comparison of PEG-amine-coated QD 565 and QD 655 at 24 and 48 hours. No decreases in cell viability were observed at 24 hours, but cell viability had decreased significantly by 48 hours in both cases. We also observed a modest but significant effect of QD size on cytotoxicity when carboxylic acid-coated QD 655 exhibited an increase in cytotoxicity between 24 and 48 hours that was greater in magnitude than that observed for QD 565 with the same coating. The cytotoxicity of compositionally diverse QDs has been investigated in multiple cell lines and at multiple end points (Hardman, 2006Hardman R. A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors.Environ Health Perspect. 2006; 114: 165-172Google Scholar; Monteiro-Riviere and Ryman-Rasmussen, 2006Monteiro-Riviere N.A. Ryman-Rasmussen J.P. Toxicology of nanomaterials.in: Riviere J.E. Biological concepts and techniques in toxicology: an integrated approach. Taylor & Francis, London2006: 217-233Google Scholar). Assessment of QD cytotoxicity at the MTT end point has been reported in several cell lines (Derfus et al., 2004Derfus A.M. Chan W.C.W. Bhatia S. Probing the cytotoxicity of semiconductor nanocrystals.Nano Lett. 2004; 4: 11-18Google Scholar; Shiosahara et al., 2004Shiosahara A. Hoshino A. Hanaki K. Suzuki K. Yamamoto K. On the cytotoxicity caused by quantum dots.Microbiol Immunol. 2004; 48: 669-675Google Scholar; Lovric et al., 2005aLovric J. Bazzi H.S. Cuie Y. Fortin G.R. Winnik F.M. Maysinger D. Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots.J Mol Med. 2005; 83: 377-385Google Scholar, Lovric et al., 2005bLovric J. Cho S.J. Winnik F.M. Maysinger D. Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death.Chem Biol. 2005; 12: 1227-1234Google Scholar), but the mechanisms underlying cytotoxicity have not been defined. Hypothesized mechanisms include oxidative stress as a result of QD-mediated reactive oxygen species production (Lovric et al., 2005bLovric J. Cho S.J. Winnik F.M. Maysinger D. Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death.Chem Biol. 2005; 12: 1227-1234Google Scholar) and leaching of core metals into the culture medium (Derfus et al., 2004Derfus A.M. Chan W.C.W. Bhatia S. Probing the cytotoxicity of semiconductor nanocrystals.Nano Lett. 2004; 4: 11-18Google Scholar). Metal leaching from the core is an unlikely mechanism of toxicity in the present study because core composition was controlled (i.e. these QDs differed only in surface coating) and the CdSe core of all QDs were “capped” with ZnS, which has been shown to attenuate leaching (Derfus et al., 2004Derfus A.M. Chan W.C.W. Bhatia S. Probing the cytotoxicity of semiconductor nanocrystals.Nano Lett. 2004; 4: 11-18Google Scholar). Oxidative stress as a result of reactive oxygen species production cannot be ruled out, but does not directly address the clear effect of QD coating on HEK viability that we observed. Before this work, inflammatory responses to QDs had not been explored. QDs and other nano-sized structures are expected to have high inflammatory potential owing to a large surface area to volume ratio (Oberdorster et al., 2005Oberdorster G. Oberdorster E. Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles.Environ Health Perspect. 2005; 113: 823-839Google Scholar). This expectation is based upon immune responses of the lung following exposure to airborne particulate matter, which has shown the greatest infiltration of immune cells for ultrafine (nano-sized) versus larger particles (Oberdorster, 2001Oberdorster G. Pulmonary effects of inhaled ultrafine particles.Int Arch Occup Environ Health. 2001; 74: 1-8Google Scholar). Immune responses of skin are substantially mediated by epidermal keratinocytes, which upon activation by environmental stimuli, secrete proinflammatory cytokines (Barker et al., 1991Barker J.N. Mitra R.S. Griffiths C.E. Dixit V.M. Nickoloff B.J. Keratinocytes as initiators of inflammation.Lancet. 1991; 337: 211-214Google Scholar; Nickoloff, 1991Nickoloff B.J. The cytokine network in psoriasis.Arch Dermatol. 1991; 127: 871-884Google Scholar). Previous studies in our laboratory have shown that IL-8 is a suitable biomarker for cutaneous inflammation in response to diverse chemicals and chemical mixtures (Allen et al., 2000Allen D.G. Riviere J.E. Monteiro-Riviere N.A. Identification of early biomarkers of inflammation produced by keratinocytes exposed to jet fuels jet A, JP-8, and JP-8(100).J Biochem Mol Toxicol. 2000; 14: 231-237Google Scholar, Allen et al., 2001Allen D.G. Riviere J.E. Monteiro-Riviere N.A. Analysis of interleukin-8 release from normal human epidermal keratinocytes exposed to aliphatic hydrocarbons: delivery of hydrocarbons to cell cultures via complexation with alpha-cyclodextrin.Toxicol In vitro. 2001; 15: 663-669Google Scholar; Chou et al., 2002Chou C.C. Riviere J.E. Monteiro-Riviere N.A. Differential relationship between the carbon chain length of jet fuel aliphatic hydrocarbons and their ability to induce cytotoxicity vs. interleukin-8 release in human epidermal keratinocytes.Toxicol Sci. 2002; 69: 226-233Google Scholar; Chou et al., 2003Chou C.C. Riviere J.E. Monteiro-Riviere N.A. The cytotoxicity of jet fuel aromatic hydrocarbons and dose-related interleukin-8 release from human epidermal kerati}, number={1}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Ryman-Rasmussen, Jessica P. and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2007}, month={Jan}, pages={143–153} }
 @article{leduc_wong_ferreira_groff_haslinger_koonce_lee_love_mccammon_monteiro-riviere_et al._2007, title={Towards an in vivo biologically inspired nanofactory}, volume={2}, ISSN={["1748-3387"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000243902900002&KeyUID=WOS:000243902900002}, DOI={10.1038/nnano.2006.180}, number={1}, journal={NATURE NANOTECHNOLOGY}, author={LeDuc, Philip R. and Wong, Michael S. and Ferreira, Placid M. and Groff, Richard E. and Haslinger, Kiryn and Koonce, Michael P. and Lee, Woo Y. and Love, J. Christopher and McCammon, J. Andrew and Monteiro-Riviere, Nancy A. and et al.}, year={2007}, month={Jan}, pages={3–7} }
 @article{ovsianikov_chichkov_mente_monteiro-riviere_doraiswamy_narayan_2007, title={Two photon polymerization of polymer-ceramic hybrid materials for transdermal drug delivery}, volume={4}, ISSN={["1744-7402"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000243791400003&KeyUID=WOS:000243791400003}, DOI={10.1111/j.1744-7402.2007.02115.x}, abstractNote={Three-dimensional microneedle devices were created by femtosecond laser two photon polymerization (2PP) of organically modified ceramic (Ormocer®) hybrid materials. Arrays of in-plane and out-of-plane hollow microneedles (microneedle length=800 μm, microneedle base diameter=150–300 μm) with various aspect ratios were fabricated. The fracture and penetration properties of the microneedle arrays were examined using compression load testing. In these studies, the microneedle arrays penetrated cadaveric porcine adipose tissue without fracture. Human epidermal keratinocyte viability on the Ormocer® surfaces polymerized using 2PP was similar to that on control surfaces. These results suggest that 2PP is able to create microneedle structures for transdermal drug delivery with a larger range of geometries than conventional microfabrication techniques.}, number={1}, journal={INTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY}, author={Ovsianikov, A. and Chichkov, B. and Mente, P. and Monteiro-Riviere, N. A. and Doraiswamy, A. and Narayan, R. J.}, year={2007}, pages={22–29} }
 @article{ryman-rasmussen_riviere_monteiro-riviere_2007, title={Variables influencing interactions of untargeted quantum dot nanoparticles with skin cells and identification of biochemical modulators}, volume={7}, ISSN={["1530-6992"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000246313000041&KeyUID=WOS:000246313000041}, DOI={10.1021/nl070375j}, abstractNote={Skin cells (NHEK) take up untargeted quantum dots (QD) with surface polyethylene glycol (PEG), amines, and carboxylic acids, but the mechanisms are unknown. Time courses of QD-NHEK interactions were determined and effects of QD surface coating, temperature, culture medium supplements and inhibitors of the cell cycle and endocytosis identified. The magnitude of QD-NHEK interactions was coating dependent. Low-temperature or unsupplemented medium decreased QD-NHEK interactions. Biochemical inhibitors were identified that attenuate and potentiate QD-NHEK interactions. These results are important for understanding and controlling interactions of untargeted QD with cells.}, number={5}, journal={NANO LETTERS}, author={Ryman-Rasmussen, Jessica P. and Riviere, Jim E. and Monteiro-Riviere, Nancy A.}, year={2007}, month={May}, pages={1344–1348} }
 @article{merwe_brooks_gehring_baynes_monteiro-riviere_riviere_2006, title={A physiologically based pharmacokinetic model of organophosphate dermal absorption}, volume={89}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000233991000018&KeyUID=WOS:000233991000018}, DOI={10.1093/toxsci/kfj014}, abstractNote={The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to toxic chemicals and for the development of topically applied drugs, barriers, insect repellents, and cosmetics. In vitro flow-through cells offer a convenient method for the study of dermal absorption that is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model developed to simulate the absorption of organophosphate pesticides, such as parathion, fenthion, and methyl parathion through porcine skin with flow-through cells. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Three parameters were optimized based on experimental dermal absorption data, including solvent evaporation rate, diffusivity, and a mass transfer factor. Diffusion cell studies were conducted to validate the model under a variety of conditions, including different dose ranges (6.3–106.9 μg/cm2 for parathion; 0.8–23.6 μg/cm2 for fenthion; 1.6–39.3 μg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5–120 μl for ethanol; 20–80 μl for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools that may be used for in silico hypotheses generation and limited hypotheses testing. The similarity between the overall shapes of the experimental and model-predicted flux/time curves and the successful simulation of altered system conditions for this series of small, lipophilic compounds indicated that the absorption processes that were described in the model successfully simulated important aspects of dermal absorption in flow-through cells. These data have direct relevance to topical organophosphate pesticide risk assessments.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Merwe, D and Brooks, JD and Gehring, R and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2006}, month={Jan}, pages={188–204} }
 @inproceedings{o’neill_monteiro-riviere_walker_2006, title={A serial dilution microfluidic device for cytotoxicity assays}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34047116480&partnerID=MN8TOARS}, DOI={10.1109/IEMBS.2006.259270}, abstractNote={A novel microfluidic device is presented which creates a linear serial dilution of two input fluid streams. This platform facilitates higher productivity as a component of a high throughput cytotoxicity testing strategy. A modeling solution is presented to create custom linear dilution schemes. The featured device creates a serial dilution of two solutions in the range of 1:9 through 9:1 across nine discrete dilutions. It has been validated to create a highly linear progression of dilutions with an R2 value of 0.9993. The device functions equivalently over a wide range of flow rates. The standard deviation of dilution values averages 0.76% over six flow rates spanning 0.5 to 16 microl min(-1).}, booktitle={Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings}, author={O’Neill, A.T. and Monteiro-Riviere, N. and Walker, G.M.}, year={2006}, pages={2836–2839} }
 @inbook{o'neill_monteiro-riviere_walker_2006, title={A serial dilution microfluidic device for cytotoxicity assays}, booktitle={28th annual International Conference of the IEEE Engineering in Medicine and Biology Society}, publisher={Piscataway, NJ: IEEE}, author={O'Neill, A. T. and Monteiro-Riviere, N. A. and Walker, G. M.}, year={2006}, pages={2836–2839} }
 @article{o’neill_monteiro-riviere_walker_ieee_2006, title={A serial dilution microfluidic device for cytotoxicity assays}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000247284703129&KeyUID=WOS:000247284703129}, journal={2006 28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-15}, author={O’Neill, Adrian T. and Monteiro-Riviere, Nancy and Walker, Glenn M. and IEEE}, year={2006}, pages={3038–3041} }
 @article{monteiro-riviere_inman_2006, title={Challenges for assessing carbon nanomaterial toxicity to the skin}, volume={44}, ISSN={["1873-3891"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000236683800007&KeyUID=WOS:000236683800007}, DOI={10.1016/j.carbon.2005.11.004}, abstractNote={This manuscript reviews a number of issues that must be dealt with to assess carbon nanomaterial interactions with the skin in the context of potential toxicity. The potential pathway for dermal absorption of carbon nanomaterials is discussed. The few existing studies assessing carbon nanomaterial toxicity to skin are reviewed. This paper addresses potential confounding factors in dealing with the experimental design of nanomaterial toxicity studies and their interpretation. Certain standard cytotoxicity assays that are well suited to assess chemical toxicity may generate conflicting results when carbon materials are assessed. This was demonstrated in an experimental study comparing carbon effects on human keratinocyte cytotoxicity assessed by transmission electron microscopy, neutral red and MTT cell viability assays, as well as irritation assessed by release of the cytokine IL-8. Four sources of carbon black particles were assessed. Conflicting results were obtained across all cytotoxicity endpoints potentially secondary to the adsorbing properties of carbon interfering with viability markers in the assay systems. These data suggest that a single cytotoxicity assay should not be relied upon in assessing carbon nanomaterial toxicity and that carbon black may not be optimal control particles for assessing nanomaterial toxicity in epidermal cell culture systems due to the wide range of responses seen between the carbon black varieties.}, number={6}, journal={CARBON}, author={Monteiro-Riviere, NA and Inman, AO}, year={2006}, month={May}, pages={1070–1078} }
 @article{monteiro-riviere_inman_hedgpeth_mosteller_piedrahita_2006, title={Dermatological effects of chronic exposure to 7,12-dimethylbenz[a]anthracene (DMBA) or N-methyl-N-nitrosoguanidine (MNNG) in swine}, volume={25}, ISSN={["1556-9527"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000238451100004&KeyUID=WOS:000238451100004}, DOI={10.1080/15569520600695546}, abstractNote={Purpose: To determine whether chronic exposure to DMBA or MNNG in combination with or without UVB exposure would induce skin carcinomas in swine. Methods: Eight gilts were exposed to 100 mJ of UVB in their left side, allowed to recuperate, and divided into two groups. Each gilt received identical high doses (DMBA 50 µM; MNNG 250 mM), low doses (DMBA 500 nM; MNNG 2.5 mM), carrier (DMSO), or nothing added treatments in the UVB and non-UVB sides. Animals were exposed weekly for 30 weeks and skin samples collected at 10, 20, and 30 weeks from initiation of exposure. An additional sample was collected 16 weeks following cessation of exposure. All samples were scored for dermal morphology, including intracellular epidermal edema, intercellular epidermal edema, papillary dermal edema, perivascular infiltrates, pyknotic stratum basale cells, collagen necrosis, and epidermal-dermal separation, and the data were analyzed by ANOVA. MNNG and UVB light had a significant effect on epidermal thickness and the number of cell layers. The greatest increase in epidermal thickness occurred from 20 weeks to 30 weeks in the UVB plus MNNG treatment. Treatment with MNNG resulted in intracellular and intercellular epidermal edema, dermal edema, and dermal inflammation at both the low and high doses of MNNG. In contrast, all the morphological evaluations of the DMBA treatments were less severe than the MNNG. Conclusion: Our findings show that although chronic exposure to MNNG and DMBA, with or without UVB exposure, caused severe to mild dermatopathological changes, neither resulted in the development of skin carcinomas. These results indicate that at least with respect to responses to DMBA and MNNG, the swine model mimics more closely the responses seen in human skin.}, number={2}, journal={CUTANEOUS AND OCULAR TOXICOLOGY}, author={Monteiro-Riviere, N and Inman, A and Hedgpeth, V and Mosteller, B and Piedrahita, J}, year={2006}, pages={103–119} }
 @article{monteiro-riviere_inman_barlow_baynes_2006, title={Dermatotoxicity of cutting fluid mixtures: In vitro and in vivo studies}, volume={25}, ISSN={["1556-9535"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000242997200001&KeyUID=WOS:000242997200001}, DOI={10.1080/15569520601013137}, abstractNote={Cutting fluids are widely used in the metal-machining industry to lubricate and reduce heat generation when metals are cut by a metal-cutting tool. These cutting fluids have caused occupational irritant contact dermatitis (OICD), and many of the additives used in these cutting fluid mixtures are thought to be responsible for OICD in workers. The purpose of this study was to assess single or various combinations of these additives in initiating the OICD response following an acute 8-hour exposure in porcine skin in vivo and in vitro using the isolated perfused porcine skin flap (IPPSF) and human epidermal keratinocytes (HEK). Pigs (n = 4) were exposed to 5% mineral oil (MO) or 5% polyethylene glycol (PEG) aqueous mixtures containing various combinations of 2% triazine (TRI), 5% triethanolamine (TEA), 5% linear alkylbenzene sulfonate (LAS), or 5% sulfurized ricinoleic acid (SRA). Erythema and edema were evaluated and skin biopsies for histopathology were obtained at 4 and 8 hours. IPPSFs (n = 4) were exposed to control MO or PEG mixtures and complete MO or PEG mixtures, and perfusate samples were collected hourly to determine interleukin- (IL-) 8 release. The only significant (p < 0.05) mixture effects observed in IPPSFs were with SRA + MO that caused an increase in IL-8 release after 1 or 2 hours' exposure. In vivo exposure to TRI alone appeared to increase erythema, edema, and dermal inflammation compared to the other additives, while SRA alone was least likely to initiate a dermal inflammatory response. In 2-component mixture exposures, the presence of TRI appeared to increase the dermal inflammatory response at 4 and 8 hours especially with the PEG mixtures. In the 3- and 4-component mixtures, MO mixtures are more likely to incite an inflammatory response than PEG mixtures. TRI exhibited the highest toxicity toward HEK, which correlates well to the in vivo irritation and morphology results. In summary, these preliminary studies suggest that the biocide, TRI, is the more potent of the 4 performance additives in causing dermal irritation, and this may vary depending on whether the worker is exposed to a synthetic (PEG)- or MO-based fluid. These findings will however require further clinical studies to validate these acute dermal effects as well as human cumulative irritation following exposure to similar cutting fluid formulations in the workplace.}, number={4}, journal={CUTANEOUS AND OCULAR TOXICOLOGY}, author={Monteiro-Riviere, Nancy A. and Inman, Alfred O. and Barlow, Beth M. and Baynes, Ronald E.}, year={2006}, pages={235–247} }
 @article{chou_yang_chen_monteiro-riviere_li_chen_2006, title={Expression profiling of human epidermal keratinocyte response following 1-minute JP-8 exposure}, volume={25}, ISSN={["1556-9527"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000238451100007&KeyUID=WOS:000238451100007}, DOI={10.1080/15569520600695728}, abstractNote={The cDNA microarray analysis of 9600 expressed sequence tags was performed to examine the gene expression changes in human epidermal keratinocytes after 1-minute JP-8 exposure; 151 genes were identified as JP-8 responsive and classified into 8 clusters by self organization map. Genes involved in basal transcription and translations were up-regulated, whereas genes related to DNA repair, metabolism, and keratin were mostly down-regulated. Genes encoded for growth factors, apoptosis, signal transduction, and adhesion were also altered. These results indicated that human keratinocyte responds to a single dose of JP-8 insult and revealed several cellular processes previously not associated with jet fuel exposure.}, number={2}, journal={CUTANEOUS AND OCULAR TOXICOLOGY}, author={Chou, CC and Yang, JH and Chen, SD and Monteiro-Riviere, NA and Li, HN and Chen, JJW}, year={2006}, pages={141–153} }
 @article{rouse_yang_barron_monteiro-riviere_2006, title={Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes}, volume={20}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000242136100006&KeyUID=WOS:000242136100006}, DOI={10.1016/j.tiv.2006.04.004}, abstractNote={The functionalization of C60 with such complexes as amino acids has the potential to provide greater interaction between the fullerene and the biological environment yielding potential new medical and pharmacological applications. Although scientific research in the past decade has revealed much about the chemical and physical properties of C60, the biological activities of this compound and its derivatives are still relatively unclear. In an attempt to understand the biological activity of functionalized C60, human epidermal keratinocytes (HEK) were exposed to fullerene-based amino acid (Baa) solutions ranging in concentrations of 0.4–0.00004 mg/mL in a humidified 5% CO2 atmosphere at 37 °C. MTT cell viability after 48 h significantly decreased (p < 0.05) for concentrations of 0.4 and 0.04 mg/mL. In an additional study, human cytokines IL-6, IL-8, TNF-α, IL-1β, and IL-10 were assessed for concentrations ranging from 0.4–0.004 mg/mL. Media was harvested at 1, 4, 8, 12, 24 and 48 h for cytokine analysis. IL-8 concentrations for the 0.04 mg/mL treatment were significantly greater (p < 0.05) than all other concentrations at 8, 12, 24, and 48 h. IL-6 and IL-1β activities were greater at the 24 h and 48 h for 0.4 and 0.04 mg/mL. No significant TNF-α or IL-10 activity existed at any time points for any of the concentrations. These results indicate that concentrations lower than 0.04 mg/mL initiate less cytokine activity and maintain cell viability. In HEK, Baa concentrations of 0.4 and 0.04 mg/mL decrease cell viability and initiate a pro-inflammatory response.}, number={8}, journal={TOXICOLOGY IN VITRO}, author={Rouse, Jillian G. and Yang, Jianzhong and Barron, Andrew R. and Monteiro-Riviere, Nancy A.}, year={2006}, month={Dec}, pages={1313–1320} }
 @article{witzmann_monteiro-riviere_2006, title={Multi-walled carbon nanotube exposure alters protein expression in human keratinocytes}, volume={2}, ISSN={["1549-9642"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33748746916&partnerID=MN8TOARS}, DOI={10.1016/j.nano.2006.07.005}, abstractNote={Carbon nanotubes have widespread applications, although little is known about their toxicity or interaction with cells. Recent studies in skin and lung reveal that carbon nanoparticles can cause toxicity. To generate a preliminary protein profile of nanotube exposure, we analyzed human epidermal keratinocytes (HEKs) exposed to multi-walled carbon nanotubes (MWCNTs) in cell culture using large-format, two-dimensional (2D) gel electrophoresis and mass spectrometry (MS). Compared with controls, 24 hours of MWCNT exposure altered the expression of 36 proteins (P < .01), whereas 106 were altered at 48 hours. At both time points, roughly 67% of the affected proteins were significantly down-regulated. Peptide mass fingerprinting identified most of the differentially expressed proteins, and the various protein identities reflected a complex cellular response to MWCNT exposure. In addition to proteins associated with metabolism, cell signaling, and stress, we observed a consistent effect on the expression of cytoskeletal elements and vesicular trafficking components. These data clearly show that MWCNTs are capable of altering protein expression in a target epithelial cell that constitutes a primary route of occupational exposure for manufactured nanotubes.}, number={3}, journal={NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE}, author={Witzmann, Frank A. and Monteiro-Riviere, Nancy A.}, year={2006}, month={Sep}, pages={158–168} }
 @article{monteiro-riviere_2006, title={Nanomaterials and the skin}, volume={2}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV200700229001&KeyUID=BIOSIS:PREV200700229001}, DOI={10.1016/j.nano.2006.10.109}, number={4}, journal={Nanomedicine-Nanotechnology Biology and Medicine}, author={Monteiro-Riviere, N. A.}, year={2006}, pages={303} }
 @article{wei_lyubchenko_ghandehari_hanes_stebe_mao_haynie_tomalia_foldvari_monteiro-riviere_et al._2006, title={New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (part I)}, volume={2}, ISSN={["1549-9642"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33845341465&partnerID=MN8TOARS}, DOI={10.1016/j.nano.2006.11.001}, abstractNote={The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Acadmy of Science Building in Washinton, DC, September 9–10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research.}, number={4}, journal={NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE}, author={Wei, Chiming and Lyubchenko, Yuri L. and Ghandehari, Hamid and Hanes, Justin and Stebe, Kathleen J. and Mao, Hai-Quan and Haynie, Donald T. and Tomalia, Donald A. and Foldvari, Marianna and Monteiro-Riviere, Nancy and et al.}, year={2006}, month={Dec}, pages={253–263} }
 @article{ryman-rasmussen_riviere_monteiro-riviere_2006, title={Penetration of intact skin by quantum dots with diverse physicochemical properties}, volume={91}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000236808200018&KeyUID=WOS:000236808200018}, DOI={10.1093/toxsci/kfj122}, abstractNote={Skin is the largest organ of the body and is a potential route of exposure to engineered nanomaterials, but the permeability of the skin to these nanomaterials is unknown. We selected commercially available quantum dots (QD) of two core/shell sizes and shapes and three different surface coatings to determine if QD could penetrate intact skin in a size- or coating-dependent manner. Spherical 4.6 nm core/shell diameter QD 565 and ellipsoid 12 nm (major axis) by 6 nm (minor axis) core/shell diameter QD 655 with neutral (polyethylene glycol), anionic (carboxylic acids) or cationic (polyethylene glycol-amine) coatings were topically applied to porcine skin in flow-through diffusion cells at an occupationally relevant dose for 8 h and 24 h. Confocal microscopy revealed that spherical QD 565 of each surface coating penetrated the stratum corneum and localized within the epidermal and dermal layers by 8 h. Similarly, polyethylene glycol- and polyethylene glycol-amine-coated ellipsoid QD 655 localized within the epidermal layers by 8 h. No penetration of carboxylic acid-coated QD 655 was evident until 24 h, at which time localization in the epidermal layers was observed. This study showed that quantum dots of different sizes, shapes, and surface coatings can penetrate intact skin at an occupationally relevant dose within the span of an average-length work day. These results suggest that skin is surprisingly permeable to nanomaterials with diverse physicochemical properties and may serve as a portal of entry for localized, and possibly systemic, exposure of humans to QD and other engineered nanoscale materials.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Ryman-Rasmussen, JP and Riviere, JE and Monteiro-Riviere, NA}, year={2006}, month={May}, pages={159–165} }
 @article{monteiro-riviere_riviere_2006, title={Skin penetration, cytotoxicity, proteomic analyses, and inflammatory potential of nanomaterials; fullerenes, multi-walled carbon nanotubes and quantum dots}, volume={29}, number={Sup. 1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Monteiro-Riviere, N. A. and Riviere, J. E.}, year={2006}, pages={196–197} }
 @inbook{monteiro-riviere_2006, title={Structure and function of skin}, ISBN={0415700361}, booktitle={Dermal absorption models in toxicology and pharmacology}, publisher={Boca Raton: Taylor & Francis}, author={Monteiro-Riviere, N. A.}, year={2006}, pages={1–19} }
 @inbook{monteiro-riviere_2006, title={The integument}, ISBN={0781741483}, booktitle={Dellmann's textbook of veterinary histology}, publisher={Ames, IA: Blackwell Publishing}, author={Monteiro-Riviere, N. A.}, editor={J. A. Eurell and Frappier, B. L.Editors}, year={2006}, pages={320–349} }
 @article{yang_lee_monteiro-riviere_riviere_tsang_chou_2006, title={Toxicity of jet fuel aliphatic and aromatic hydrocarbon mixtures on human epidermal keratinocytes: evaluation based on in vitro cytotoxicity and interleukin-8 release}, volume={80}, ISSN={["1432-0738"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000238665800007&KeyUID=WOS:000238665800007}, DOI={10.1007/s00204-006-0069-1}, number={8}, journal={ARCHIVES OF TOXICOLOGY}, author={Yang, Jen-Hung and Lee, Chia-Hue and Monteiro-Riviere, Nancy A. and Riviere, Jim E. and Tsang, Chau-Loong and Chou, Chi-Chung}, year={2006}, month={Aug}, pages={508–523} }
 @inbook{monteiro-riviere_ryman-rasmussen_2006, title={Toxicology of Nanomaterials}, ISBN={082472979X}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33845739533&partnerID=MN8TOARS}, booktitle={Biological Concepts and Techniques in Toxicology: An Integrated Approach}, publisher={New York: Taylor & Francis}, author={Monteiro-Riviere, N.A. and Ryman-Rasmussen, J.P.}, year={2006}, pages={217–233} }
 @article{xia_monteiro-riviere_riviere_2006, title={Trace analysis of fullerenes in biological samples by simplified liquid-liquid extraction and high-performance liquid chromatography}, volume={1129}, ISSN={["0021-9673"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000240879200008&KeyUID=WOS:000240879200008}, DOI={10.1016/j.chroma.2006.07.030}, abstractNote={Fullerene (C60) has several potential biomedical and industrial applications. While pure fullerene is not soluble in water, nanoparticles of the fullerene aggregates (nano-C60) can be prepared in water solutions. The concentration of nano-C60 in biological media after systemic exposure could be very low and requires trace analytical methods to be developed for the toxicological and pharmacokinetic studies of the nanomaterial. A serious drop in extraction efficiency was observed when the concentration was under 0.5 μg/mL using traditional liquid–liquid extraction (LLE) protocols. The evaporation of the solvent extract to dryness was found to be the main reason for the efficiency drop and an improved evaporation method was proposed to overcome this problem. Optimal proportion of glacial acetic acid (GAA) was used to solublize the proteins and surfactants in the biological samples, so that the emulsion problem was eliminated during LLE. Magnesium perchlorate was used to destabilize the nano-C60 particles in the water solution and promoted the solvent extraction. A simplified LLE method was developed for high throughput while preserved the advantages of the traditional LLE. The developed method was used for trace analysis of fullerenes in protein containing media and tape-stripped skin samples. Under optimal experimental conditions, the detection limit was 0.34 ng/mL and the recovery was in the range of 94–100% (n = 5) at a concentration of 10 ng/mL nano-C60 in the biological media.}, number={2}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Xia, Xin-Rui and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2006}, month={Oct}, pages={216–222} }
 @misc{tournas_lin_burch_selim_monteiro-riviere_zielinski_pinnell_2006, title={Ubiquinone, idebenone, and kinetin provide ineffective photoprotection to skin when compared to a topical antioxidant combination of vitamins C and E with ferulic acid}, volume={126}, ISSN={["0022-202X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000238968700039&KeyUID=WOS:000238968700039}, DOI={10.1038/sj.jid.5700232}, abstractNote={minimal erythema dose sunburn cell TO THE EDITOR Ubiquinone (Coenzyme Q10) is an important lipophilic antioxidant synthesized by the body and critical for protection of mitochondrial membranes (Crane, 2001Crane F.L. Biochemical functions of coenzyme Q10.J Am College Nutr. 2001; 20: 591-598Crossref PubMed Scopus (690) Google Scholar; Dallner and Sindelar, 2000Dallner G. Sindelar P.J. Regulation of ubiquinone metabolism.Free Radic Biol Med. 2000; 29: 285-294Crossref PubMed Scopus (180) Google Scholar). Idebenone is a synthetic derivative of ubiquinone with a shorter carbon side chain and subsequent increased solubility (Wieland et al., 1995Wieland E. Schutz E. Armstrong V.W. Kuthe F. Heller C. Oellerich M. Idebenone protects hepatic microsomes against oxygen radical-mediated damage in organ preservation solutions.Transplantation. 1995; 60: 444-451Crossref PubMed Scopus (24) Google Scholar). Both have been suggested as topical antioxidant ingredients for the protection of skin from oxidative damage caused by UV irradiation and pollution. Kinetin (N6-furfuryladenine) is a member of the cytokinin plant growth hormone family. Cytokinins are growth promoters, which positively affect cell number and division rate in both plants and animals (Vesely et al., 1985Vesely D.L. Hudson J.L. Pipkin Jr, J.L. Pack L.D. Meiners S.E. Plant growth-promoting hormones activate mammalian guanylate cyclase activity.Endocrinology. 1985; 116: 1887-1892Crossref PubMed Scopus (10) Google Scholar). In vitro studies have shown that kinetin has antioxidant effects, preventing oxidative damage to DNA (Olsen et al., 1999Olsen A. Siboska G.E. Clark B.F. Rattan S.I. N(6)-Furfuryladenine, kinetin, protects against Fenton reaction-mediated oxidative damage to DNA.Biochem Biophys Res Comm. 1999; 265: 499-502Crossref PubMed Scopus (88) Google Scholar). Topical kinetin has been shown to improve skin texture and reduce the appearance of fine rhytides in humans (McCullough and Weinstein, 2002McCullough J. Weinstein G. Clinical study of safety and efficacy of using topical kinetin 0.1% to treat photodamaged skin.Cosmetic Dermatol. 2002; 15: 9Google Scholar) and in animals (Kimura and Doi, 2004Kimura T. Doi K. Depigmentation and rejuvenation effects of kinetin on the aged skin of hairless descendants of Mexican hairless dogs.Rejuvenation Res. 2004; 7: 32-39Crossref PubMed Scopus (25) Google Scholar). We have previously reported effective photoprotection properties of an antioxidant solution containing 15% l-ascorbic acid, 1% α-tocopherol, and 0.5% ferulic acid (C+E+ferulic acid) (Lin et al., 2005Lin F.H. Lin J.Y. Gupta R.D. Tournas J.A. Burch J.A. Selim M.A. et al.Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin.J Invest Dermatol. 2005; 125: 826-832Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar). In this study, we use the same model to evaluate the antioxidant potential of ubiquinone, idebenone, and kinetin by measuring their photoprotective value. The treatment protocol and experimental design has been published in detail elsewhere (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. et al.UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar), but will be summarized here in brief. Of each of the following, 250 μl (solution) or 250 mg (cream) were applied to 7.5 × 10 cm patches of pig skin daily for 4 days: a solution containing 15% l-ascorbic acid, 1% α-tocopherol, and 0.5% ferulic acid (C+E+ferulic acid), solutions containing 1.0% ubiquinone, 1.0% idebenone, and 0.5% kinetin as well as commercial creams containing 0.1% kinetin (Kinerase, Valeant Pharmaceuticals, Costa Mesa, CA), 1.0% idebenone (Prevage, Allergan Inc., Irvine, CA), 0.5% idebenone (TRUE Youth Revealing Complex, TRUE Cosmetics, San Francisco, CA). A 1000 W solar simulator (Lightning Cure 200, Hamamatsu, Hamamatsu City, Japan) was used to deliver the UV radiation at an intensity of 5 mW/cm2 of UVB and approximately 40 mW/cm2 of UVA, as measured by a research radiometer (IL1700, International Light, Newburyport, MA). Patches were irradiated with solar-simulated UV as described above in triplicate from 1 to 5 × minimal erythema dose (MED) in 1 × MED multiples. Evaluation was conducted 24 hours later. All experimental methods were conducted within the guidelines of and with approval by the North Carolina State University Institutional Animal Care and Use Committee. A computerized colorimetry algorithm using digital photographs (Tournas JA and Pinnell SR (2005) A computerized method for skin erythema measurement. J Investig Dermatol 124(S4): A136 (abstract)) and a Microsoft Excel (Microsoft Inc., Redmond, WA) spreadsheet were used to measure and calculate the a* (redness) values of the experimental spots, as well as to compile the statistics and graph the results. After photography, 8 mm punch biopsy sections were taken of each experimental spot and fixed in formalin. Sections were embedded and sectioned for hematoxylin and eosin (H+E) staining. The H+E-stained sections were then examined for the presence of apoptotic “sunburn cells” (SBCs). The full 8 mm width of each section was counted and the result expressed as SBC density/mm of skin. Microsoft Excel was used to determine the mean and standard deviation of the SBC densities at each UV dosage and to graph the results. Thymine dimer analysis was carried out as in the work of Mitchell et al., 2001Mitchell D.L. Volkmer B. Breitbart E.W. Byrom M. Lowery M.G. Greinert R. Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage.J Invest Dermatol. 2001; 117: 590-595Crossref PubMed Google Scholar. An Olympus BX41 fluorescence microscope with a Q-Fire camera (Olympus America Inc., Melville, NY) was employed to obtain the immunofluorescence images. The results for erythema (a*) and SBC density are expressed as mean±SD (n=6). The P-values were calculated by two-tailed Student's t-test. Figure 1a shows the erythema response of skin treated with C+E+ferulic acid, 1.0% ubiquinone, 1.0% idebenone, and the 1.0 and 0.5% idebenone creams (Commercial Creams 1 and 2, respectively), and Figure 1b shows the erythema response of skin treated with C+E+ferulic acid, 0.5% kinetin solution, and the 0.1% kinetin cream. It can be seen that while C+E+ferulic acid is protective at 5 × MED, ubiquinone, idebenone, and kinetin do not provide protection. The computerized colorimetric measurements show that at all UV dosage levels from 1 to 5 × MED, erythema is significantly reduced (P<0.05) when skin is treated with C+E+ferulic acid compared to control, or skin treated with any of the antioxidant solutions or the commercial creams. Additionally, none of the preparations other than C+E+ ferulic acid were significantly different from control at any UV dosage from 1 to 5 × MED. Quantitatively, the a* values for the C+E+ferulic acid-treated area were decreased by 98, 99, 91, 87, and 83% from 1 to 5 × MED, respectively. Figure 2a and b show the SBC density in skin treated with the test solutions after UV irradiation from 1 × to 5 × MED. As with the erythema, SBC density was significantly reduced in skin treated with C+E+ferulic acid as compared to control and the other solutions and creams. The 0.5% idebenone cream showed slight benefit in terms of SBC reduction, though it should be noted that this preparation also contains sunscreen in an unknown amount. Quantitatively, the mean SBC reduction afforded by C+E+ferulic acid over control was 86, 93, 95, 92, and 93% from 1 to 5 × MED, respectively. Additional experiments performed but not shown graphically showed that adding 1% idebenone to C+E+ferulic acid did not increase its photoprotective benefit in terms of both erythema and SBCs. Thymine dimer immunohistochemistry also revealed that only C+E+ferulic acid was completely protective at 4 × MED. The 0.5% idebenone cream afforded slight protection, and the other preparations were not protective. The results of this study show that ubiquinone, idebenone, and kinetin offer little to no photoprotective value in comparison to more established therapies. In addition, the slight photoprotective effect seen with commercial creams containing idebenone may be due to the sunscreen ingredients that they contain. Idebenone specifically does not increase the photoprotective value of an established antioxidant combination of C+E+ferulic acid. The results of this study also validate an earlier study showing that C+E+ferulic acid offers eight-fold UV photoprotection to skin (Lin et al., 2005Lin F.H. Lin J.Y. Gupta R.D. Tournas J.A. Burch J.A. Selim M.A. et al.Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin.J Invest Dermatol. 2005; 125: 826-832Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar). Joshua Tournas is on the speaker's board for SkinCeuticals Inc., Garland, TX, USA. This research was supported in part by Grant R43CA83538 from the National Institutes of Health. This research was presented in part as a poster at the 66th Annual Meeting of the Society of Investigative Dermatology, St Louis, MO 5/4-5/7/2005. We Thank Connie Engle, RVT of the North Carolina State University College of Veterinary Medicine for her expertise in conducting the experiments, and to Doren Madey, PhD, for her assistance in preparing the manuscript. This work was done in Durham, North Carolina, USA.}, number={5}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Tournas, Joshua A. and Lin, Fu-Hsiung and Burch, James A. and Selim, M. Angelica and Monteiro-Riviere, Nancy A. and Zielinski, Jan E. and Pinnell, Sheldon R.}, year={2006}, month={May}, pages={1185–1187} }
 @article{tournas_lin_burch_selim_monteiro-riviere_zielinski_pinnell_2005, title={A topical antioxidant solution containing 15% 1-ascorbic acid, 1% alpha-tocopherol and 0.5% ferulic acid provides superior photoprotection to skin compared to 1% idebenone or 1% ubiquinone}, volume={124}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000228179901354&KeyUID=WOS:000228179901354}, number={4}, journal={Journal of Investigative Dermatology}, author={Tournas, JA and Lin, FH and Burch, A and Selim, MA and Monteiro-Riviere, NA and Zielinski, JE and Pinnell, SR}, year={2005}, pages={A136} }
 @inproceedings{tournas_lin_burch_selim_monteiro-riviere_zielinski_pinnell_2005, title={A topical antioxidant solution containing 15% L-ascorbic acid, 1%a-tocopherol and 0.5% ferulic acid (C+E+Ferulic) provides superiorphotoprotection to skin compared to 1% idebenone or 1% ubiquinone}, volume={19}, number={Supplement 2}, booktitle={Journal of the European Academy of Dermatology & Venereology}, author={Tournas, J.A. and Lin, F.H. and Burch, J.A. and Selim, M.A. and Monteiro-Riviere, N.A. and Zielinski, J.E. and Pinnell, S.R.}, year={2005}, pages={47,} }
 @inbook{ferreira_groff_haslinger_koonce_le duc_lee_love_mcgammon_monteiro-riviere_rotello_et al._2005, title={An in vivo nanofactory: The medicine of the future}, ISBN={0309096685}, booktitle={Designing nanostructures at the interface between biomedical and physical systems}, publisher={Washington, DC: National Academies Press}, author={Ferreira, P. and Groff, R. and Haslinger, K. and Koonce, M. and Le Duc, P. and Lee, W. and Love, C. and McGammon, A. and Monteiro-Riviere, N. and Rotello, V. and et al.}, year={2005}, pages={53–60} }
 @article{muhammad_monteiro-riviere_riviere_2005, title={Comparative in vivo toxicity of topical JP-8 jet fuel and its individual hydrocarbon components: Identification of tridecane and tetradecane as key constituents responsible for dermal irritation}, volume={33}, ISSN={["1533-1601"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000227438200007&KeyUID=WOS:000227438200007}, DOI={10.1080/01926230590908222}, abstractNote={Despite widespread exposure to military jet fuels, there remains a knowledge gap concerning the actual toxic entities responsible for irritation observed after topical fuel exposure. The present studies with individual hydrocarbon (HC) constituents of JP-8 jet fuel shed light on this issue. To mimic occupational scenarios, JP-8, 8 aliphatic HC (nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane) and 6 aromatic HC (ethyl benzene, o-xylene, trimethyl benzene, cyclohexyl benzene, naphthalene, dimethyl naphthalene) soaked cotton fabrics were topically exposed to pigs for 1 day and with repeated daily exposures for 4 days. Erythema, epidermal thickness, and epidermal cell layers were quantitated. No erythema was noted in 1-day in vivo HC exposures but significant erythema was observed in 4-day tridecane, tetradecane, pentadecane, and JP-8 exposed sites. The aromatic HCs did not produce any macroscopic lesions in 1 or 4 days of in vivo exposures. Morphological observations revealed slight intercellular and intracellular epidermal edema in 4-day exposures with the aliphatic HCs. Epidermal thickness and number of cell layers significantly increased (p < 0.05) in tridecane, tetradecane, pentadecane, and JP-8-treated sites. No significant differences were observed in the aromatic HC-exposed sites. Subcorneal microabscesses containing inflammatory cells were observed with most of the long-chain aliphatic HCs and JP-8 in 4-day exposures. Ultrastructural studies depicted that jet fuel HC-induced cleft formation within intercellular lipid lamellar bilayers of the stratum corneum. The degree of damage to the skin was proportional to the length of in vivo HC exposures. These data coupled with absorption and toxicity studies of jet fuel HC revealed that specific HCs (tridecane and tetradecane) might be the key constituents responsible for jet fuel-induced skin irritation.}, number={2}, journal={TOXICOLOGIC PATHOLOGY}, author={Muhammad, F and Monteiro-Riviere, NA and Riviere, JE}, year={2005}, pages={258–266} }
 @article{xia_baynes_monteiro-riviere_riviere_2005, title={Determination of the partition coefficients and absorption kinetic parameters of chemicals in a lipophilic membrane/water system by using a membrane-coated fiber technique}, volume={24}, ISSN={["0928-0987"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000226717800002&KeyUID=WOS:000226717800002}, DOI={10.1016/j.ejps.2004.09.004}, abstractNote={The absorption kinetics of chemicals in a lipophilic membrane/water system was studied with a membrane-coated fiber (MCF) technique, in which the partition coefficient, membrane diffusivity and boundary layer adjacent to the membrane were taken into account. The cumulative amount permeated into the membrane was expressed as a function of absorption time in an exponential equation. Two constants were introduced into the model. Both of them were clearly defined by the physiochemical parameters of the system and were obtained by regression of the experimental data sampled over a limited time. The partition and diffusion coefficients, as well as the thickness of the boundary layer, were calculated from the two constants. The kinetic model adequately described the absorption kinetics of the MCF technique. All of the theoretical predictions were supported by the experimental results. The measured partition coefficients correlated well with the published octanol/water partition coefficient (R(2)=0.91). The thickness of the boundary layer was 5.2 microm in a solution stirred at 400 rpm. An inference of the kinetic model revealed that the contribution of the boundary layer to the absorption kinetics is significant for lipophilic chemicals by a lipophilic membrane. It suggested that the absorption rate of a very lipophilic compound could be controlled by the boundary layer even though the diffusivity of the compound in the membrane is lower than that in the solution. It was demonstrated that the MCF technique could be used to determine the partition, diffusion and permeation coefficients, as well as the thickness of the boundary layer in a lipophilic membrane/water system.}, number={1}, journal={EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2005}, month={Jan}, pages={15–23} }
 @article{witzmann_monteiro-riviere_inman_kimpel_pedrick_ringham_riviere_2005, title={Effect of JP-8 jet fuel exposure on protein expression in human keratinocyte cells in culture}, volume={160}, ISSN={["1879-3169"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000233341800002&KeyUID=WOS:000233341800002}, DOI={10.1016/j.toxlet.2005.06.001}, abstractNote={Dermal exposure to jet fuel is a significant occupational hazard. Previous studies have investigated its absorption and disposition in skin, and the systemic biochemical and immunotoxicological sequelae to exposure. Despite studies of JP-8 jet fuel components in murine, porcine or human keratinocyte cell cultures, proteomic analysis of JP-8 exposure has not been investigated. This study was conducted to examine the effect of JP-8 administration on the human epidermal keratinocyte (HEK) proteome. Using a two-dimensional electrophoretic approach combined with mass spectrometric-based protein identification, we analyzed protein expression in HEK exposed to 0.1% JP-8 in culture medium for 24 h. JP-8 exposure resulted in significant expression differences (p<0.02) in 35 of the 929 proteins matched and analyzed. Approximately, a third of these alterations were increased in protein expression, two-thirds declined with JP-8 exposure. Peptide mass fingerprint identification of effected proteins revealed a variety of functional implications. In general, altered proteins involved endocytotic/exocytotic mechanisms and their cytoskeletal components, cell stress, and those involved in vesicular function.}, number={1}, journal={TOXICOLOGY LETTERS}, author={Witzmann, FA and Monteiro-Riviere, NA and Inman, AO and Kimpel, MA and Pedrick, NM and Ringham, HN and Riviere, JE}, year={2005}, month={Dec}, pages={8–21} }
 @article{muhammad_monteiro-riviere_baynes_riviere_2005, title={Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents}, volume={68}, ISSN={["1087-2620"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000229475900004&KeyUID=WOS:000229475900004}, DOI={10.1080/15287390590925456}, abstractNote={The percutaneous absorption of topically applied jet fuel hydrocarbons (HC) through skin previously exposed to jet fuel has not been investigated, although this exposure scenario is the occupational norm. Pigs were exposed to JP-8 jet fuel-soaked cotton fabrics for 1 and 4 d with repeated daily exposures. Preexposed and unexposed skin was then dermatomed and placed in flow-through in vitro diffusion cells. Five cells with exposed skin and four cells with unexposed skin were dosed with a mixture of 14 different HC consisting of nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethyl benzene, o-xylene, trimethyl benzene (TMB), cyclohexyl benzene (CHB), naphthalene, and dimethyl naphthalene (DMN) in water + ethanol (50:50) as diluent. Another five cells containing only JP-8-exposed skin were dosed solely with diluent in order to determine the skin retention of jet fuel HC. The absorption parameters of flux, diffusivity, and permeability were calculated for the studied HC. The data indicated that there was a two-fold and four-fold increase in absorption of specific aromatic HC like ethyl benzene, o-xylene, and TMB through 1- and 4-dJP-8 preexposed skin, respectively. Similarly, dodecane and tridecane were absorbed more in 4-d than 1-dJP-8 preexposed skin experiments. The absorption of naphthalene and DMN was 1.5 times greater than the controls in both 1- and 4-d preexposures. CHB, naphthalene, and DMN had significant persistent skin retention in 4-d preexposures as compared to 1-d exposures that might leave skin capable of further absorption several days postexposure. The possible mechanism of an increase in HC absorption in fuel preexposed skin may be via lipid extraction from the stratum corneum as indicated by Fourier transform infrared (FTIR) spectroscopy. This study suggests that the preexposure of skin to jet fuel enhances the subsequent in vitro percutaneous absorption of HC, so single-dose absorption data for jet fuel HC from naive skin may not be optimal to predict the toxic potential for repeated exposures. For certain compounds, persistent absorption may occur days after the initial exposure.}, number={9}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Muhammad, F and Monteiro-Riviere, NA and Baynes, RE and Riviere, JE}, year={2005}, month={May}, pages={719–737} }
 @article{lin_lin_gupta_tournas_burch_selim_monteiro-riviere_grichnik_zielinski_pinnell_et al._2005, title={Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin}, volume={125}, ISSN={["1523-1747"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000232556700029&KeyUID=WOS:000232556700029}, DOI={10.1111/j.0022-202X.2005.23768.x}, abstractNote={Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15% L-ascorbic acid and 1% α-tocopherol improved chemical stability of the vitamins (C+E) and doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer. Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15% L-ascorbic acid and 1% α-tocopherol improved chemical stability of the vitamins (C+E) and doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer. minimal erythema dose ultraviolet Ultraviolet (UV) radiation generates oxidative stress in skin creating photodamage. Mechanistically, a photon of radiation interacts with trans-urocanic acid in skin generating singlet oxygen (Hanson and Simon, 1998Hanson K.M. Simon J.D. Epidermal trans-urocanic acid and the UV-A-induced photoaging of the skin.Proc Natl Acad Sci USA. 1998; 95: 10576-10578Google Scholar). This reaction occurs maximally at about 345 nm. Singlet oxygen can generate the entire oxygen free radical cascade with oxidation of nucleic acids, proteins, and lipids, resulting in skin cancer and photoaging changes. The body deals with oxidative stress by employing a series of low molecular weight antioxidants that neutralize the reactive oxygen species before they can produce oxidative changes in tissues (Podda and Grundmann-Kollmann, 2001Podda M. Grundmann-Kollmann M. Low molecular weight antioxidants and their role in skin ageing.Clin Exp Dermatol. 2001; 26: 578-582Google Scholar). In skin the predominant antioxidant is vitamin C; vitamin C protects the fluids of the body (Shindo et al., 1994Shindo Y. Witt E. Han D. Epstein W. Packer L. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin.J Invest Dermatol. 1994; 102: 122-124Google Scholar). The lipid phase including cell membranes and stratum corneum is protected by vitamin E (Thiele, 2001Thiele J.J. Oxidative targets in the stratum corneum. A new basis for antioxidative strategies.Skin Pharmacol Appl Skin Physiol. 2001; 14: 87-91Google Scholar). Plants make vitamins E and C to protect themselves from sunlight (Smirnoff et al., 2001Smirnoff N. Conklin P.L. Loewus F.A. Biosynthesis of ascorbic acid in plants: A renaissance.Annu Rev Plant Physiol Plant Mol Biol. 2001; 52: 437-467Google Scholar; Munne-Bosch and Alegre, 2002Munne-Bosch S. Alegre L. The function of tocopherols and tocotrienols in plants.Crit Rev Plant Sci. 2002; 21: 31-57Google Scholar). Most animals make vitamin C but humans have lost this ability; a necessary gene is mutated (Nishikimi et al., 1994Nishikimi M. Fukuyama R. Minoshima S. Shimizu N. Yagi K. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man.J Biol Chem. 1994; 269: 13685-13688Google Scholar). Therefore, humans typically get vitamins C and E from diet and/or vitamin supplements. Body controls related to absorption, metabolism, and distribution, however, limit the amounts that can eventually be delivered into skin (Herrera and Barbas, 2001Herrera E. Barbas C. Vitamin E: Action, metabolism and perspectives.J Physiol Biochem. 2001; 57: 43-56Google Scholar; Padayatty et al., 2003Padayatty S.J. Katz A. Wang Y. et al.Vitamin C as an antioxidant: Evaluation of its role in disease prevention.J Am Coll Nutr. 2003; 22: 18-35Google Scholar). Moreover, when these vitamins neutralize oxidative stress in skin, they are used up (Darr et al., 1992Darr D. Combs S. Dunston S. Manning T. Pinnell S. Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage.Br J Dermatol. 1992; 127: 247-253Google Scholar). With daily oral supplements of 3 g vitamin C and 2 g vitamin E, protection against photodamage in skin is increased approximately 1.5 times; either vitamin alone is ineffective (Fuchs and Kern, 1998Fuchs J. Kern H. Modulation of UV-light-induced skin inflammation by D-α-tocopherol and L-ascorbic acid: A clinical study using solar simulated radiation.Free Rad Biol Med. 1998; 25: 1006-1012Google Scholar). New formulation methods make it possible to augment protection in skin against photodamage using topical vitamins C and E, achieving significantly greater protection than ever was possible by ingestion. We have previously reported that a stable aqueous solution of 15% vitamin C (L-ascorbic acid) and 1% vitamin E (α-tocopherol) when applied topically to skin can provide 4-fold photoprotection for skin (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874Google Scholar). The solution must be formulated at a pH of 3.5 or lower for the vitamin C to be absorbed into skin: at this pH the vitamin C is protonated and the molecule is uncharged (Pinnell et al., 2001Pinnell S.R. Yang H.S. Omar M. et al.Topical L-ascorbic acid: Percutaneous absorption studies.Dermatol Surg. 2001; 27: 137-142Google Scholar). The formulation concentrations were maximized for percutaneous absorption. Fifteen percent L-ascorbic acid saturates skin in 3 d; its tissue half life is about 4 d (Pinnell et al., 2001Pinnell S.R. Yang H.S. Omar M. et al.Topical L-ascorbic acid: Percutaneous absorption studies.Dermatol Surg. 2001; 27: 137-142Google Scholar). Once inside skin it cannot be removed by washing or rubbing. Vitamins C and E interact synergistically to protect each other and increase overall effectiveness (Pinnell et al., 2001Pinnell S.R. Yang H.S. Omar M. et al.Topical L-ascorbic acid: Percutaneous absorption studies.Dermatol Surg. 2001; 27: 137-142Google Scholar). In an attempt to improve the stability of this solution of vitamins C and E, we explored the effectiveness of a series of known low molecular weight antioxidants that are available in chemically pure form. Chemical stability was determined after 1 mo at 45°C. We have learned that addition of ferulic acid, a ubiquitous plant antioxidant, provided stability of more than 90% for L-ascorbic acid and 100% for α-tocopherol (Zielinski and Pinnell, 2004Zielinski J.E. Pinnell S.R. Stabilized ascorbic acid compositions and methods thereof.2004Google Scholar). A concentration of 0.5% gave the best combination of formulation stability and effectiveness. We were surprised to find that in addition to improving stability, adding 0.5% ferulic acid to the solution of 15% L-ascorbic acid and 1% α-tocopherol doubled photoprotection when applied topically to skin from 4- to 8-fold. In this article, we detail these photoprotection experiments, show reduction in thymine dimer formation generated by UV radiation and demonstrate reduction of apoptosis in keratinocytes with lowered caspase-3 and caspase-7 generation. Antioxidant protection factor is designed to reflect relative photoprotection to solar-simulated radiation provided by daily topical applications of the solution for 4 consecutive days. Both 0.5% ferulic acid alone and 15% L-ascorbic acid +1% α-tocopherol together provided about 4-fold protection (Figure 1a,b). Similar photoprotection has been previously reported for 15% L-ascorbic acid +1% α-tocopherol (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874Google Scholar). The combination of 15% L-ascorbic acid, 1% α-tocopherol, 0.5% ferulic acid provided approximately 8-fold protection and was statistically different than ferulic acid alone or the combination of vitamins C and E (Figure 1a,b). These observations were confirmed by colorimetric measurements of erythema (Figure 1c) and sunburn cell counts (Figure 1d). Colorimetric measurements of combination of vitamins C, E, and ferulic acid were statistically different from control and vehicle at all minimal erythema dose (MED) tested; different from ferulic acid alone at 2 ×, 6 ×, and 8 × MED; and different from combination vitamins C+E at 4 × and 6 × MED. Sunburn cell counts of combination of vitamins C, E, and ferulic acid were statistically different from control and vehicle at all MED tested and different from ferulic acid alone as well as from the combination of vitamins C+E at 2 ×, 4 ×, 6 ×, and 8 × MED. In an effort to explore the mechanism of apoptosis in these experiments, western blots were carried out to determine levels of caspase-3 and its downstream effector, caspase-7. Figure 2a reveals protection by antioxidant solutions of activation of caspase-3 by 4 × and 8 × MED of solar-simulated radiation. Figure 2b shows relative quantification of antioxidant protection of solar-simulated radiation. With 8 × MED of irradiation, protection of vitamin C, E, and ferulic acid is almost complete and is better than vitamin C and E or ferulic acid alone. Figure 2c shows activation of caspase-7 by 4 × and 8 × MED of solar-simulated radiation and protection by antioxidant solutions. Figure 2d shows relative antioxidant protection, which is virtually complete by vitamins C, E and ferulic acid. Figure 3 shows immunohistochemistry of activation of caspase-3 by 4 × MED of solar-simulated light. Activation occurs in both epidermis and dermis (Figure 3a–c); in epidermis, activation is particularly strong in the basal layer. Ferulic acid alone (3b) and vitamins C+E (3c) provide partial protection but vitamins C, E, and ferulic acid (3d) provides virtually complete protection.Figure 3Immunochemistry of activated caspase-3 after solar-simulated irradiation. Skin was pretreated with 0.5% ferulic acid, 15% vitamin C and 1% vitamin E, or 15% vitamin C and 1% vitamin E, and 0.5% ferulic acid and exposed to 4 × minimal erythema dose. After 24 h formalin-fixed tissues were stained with antibodies to activated caspase-3. (a) Vehicle-treated irradiated skin; (b) 0.5% ferulic acid-treated irradiated skin. (c): 15% vitamin C and 1% vitamin E-treated irradiated skin; (d) 15% vitamin C and 1% vitamin E, and 0.5% ferulic acid-treated irradiated skin.View Large Image Figure ViewerDownload (PPT) We have previously demonstrated that topical vitamins C+E could prevent UV-induced thymine dimer formation (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874Google Scholar). In order to determine whether the addition of ferulic acid augmented this protection, we investigated the relative dose–response protection of these formulations (Figure 4). With 4 × MED of solar-simulated irradiation, both control and vehicle-treated skin showed virtually uniform nuclear fluorescence in both epidermis and papillary dermis (Figure 4a). After 4 × MED, ferulic acid-treated skin was still positive in approximately 25% of both epidermis and dermis (data not shown). As previously reported, vitamins C+E almost completely protected skin irradiated with 4 × MED (data not shown). After 8 × MED, ferulic acid-treated skin was about one third positive (Figure 4b) and vitamin C+E-treated skin was about 15% positive and fluorescence was less intense (Figure 4c). Skin treated with vitamins C, E, and ferulic acid was completely negative (Figure 4d). Ferulic acid not only provides increased stability to a solution of vitamins C+E, but also adds a substantial synergistic photoprotection, essentially doubling its efficacy. Moreover it provides additional protection against thymine dimer formation that should prove useful for prevention of skin cancer. These studies support the hypotheses that UV radiation produces apoptosis by triggering the caspase cascade in both epidermis and dermis, and topical vitamins C, E, and ferulic acid can protect against caspase activation. Ferulic acid is a potent phenolic antioxidant found ubiquitously and at high concentrations in plants (Graf, 1992Graf E. Antioxidant potential of ferulic acid.Free Rad Biol Med. 1992; 13: 435-448Google Scholar; Rice-Evans et al., 1996Rice-Evans C.A. Miller N.J. Paganga G. Structure–antioxidant activity relationships of flavonoids and phenolic acids.Free Rad Biol Med. 1996; 20: 933-956Google Scholar; Ou and Kwok, 2004Ou S. Kwok K.-C. Ferulic acid: Pharmaceutical functions, preparation and applications in foods.J Sci Food Agric. 2004; 84: 1261-1269Google Scholar). It serves to cross-link polysaccharides and proteins during lignin cell wall synthesis (Wallace and Fry, 1994Wallace G. Fry S.C. Phenolic components of the plant cell wall.Int Rev Cytol. 1994; 151: 229-267Google Scholar; Mathew and Abraham, 2004Mathew S. Abraham T.E. Ferulic acid: An antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications.Crit Rev Biotechnol. 2004; 24: 59-83Google Scholar) and may be important for the health effects of bran; corn bran contains 3.1% ferulic acid (Mathew and Abraham, 2004Mathew S. Abraham T.E. Ferulic acid: An antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications.Crit Rev Biotechnol. 2004; 24: 59-83Google Scholar). It is abundant in the diet and has low toxicity (Ou and Kwok, 2004Ou S. Kwok K.-C. Ferulic acid: Pharmaceutical functions, preparation and applications in foods.J Sci Food Agric. 2004; 84: 1261-1269Google Scholar; Zhao et al., 2004Zhao Z. Egashira Y. Sanada H. Ferulic acid is quickly absorbed from rat stomach as the free form and then conjugated mainly in liver.J Nutr. 2004; 134: 3083-3088Google Scholar). Ferulic acid is a potent antioxidant with synergistic interactions with ascorbic acid (Trombino et al., 2004Trombino S. Serini S. Di Nicuolo F. et al.Antioxidant effect of ferulic acid in isolated membranes and intact cells: Synergistic interactions with alpha-tocopherol, beta-carotene, and ascorbic acid.J Agric Food Chem. 2004; 52: 2411-2420Google Scholar). It readily forms a resonance stabilized phenoxy radical which accounts for its potent antioxidant potential (Graf, 1992Graf E. Antioxidant potential of ferulic acid.Free Rad Biol Med. 1992; 13: 435-448Google Scholar). Ferulic acid protected membranes from lipid peroxidation and neutralized alkoxyl and peroxyl radicals (Trombino et al., 2004Trombino S. Serini S. Di Nicuolo F. et al.Antioxidant effect of ferulic acid in isolated membranes and intact cells: Synergistic interactions with alpha-tocopherol, beta-carotene, and ascorbic acid.J Agric Food Chem. 2004; 52: 2411-2420Google Scholar). It protected against iron-induced oxidative damage (Hynes and O'Coinceanainn, 2004Hynes M.J. O'Coinceanainn M. The kinetics and mechanisms of reactions of iron(III) with caffeic acid, chlorogenic acid, sinapic acid, ferulic acid and naringin.J Inorg Biochem. 2004; 98: 1457-1464Google Scholar). Ferulic acid scavenged hydroxyl radical (Ogiwara et al., 2002Ogiwara T. Satoh K. Kadoma Y. et al.Radical scavenging activity and cytotoxicity of ferulic acid.Anticancer Res. 2002; 22: 2711-2717Google Scholar; Wenk et al., 2004Wenk G.L. McGann-Gramling K. Hauss-Wegrzyniak B. et al.Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid.J Neurochem. 2004; 89: 484-493Google Scholar), nitric oxide (Wenk et al., 2004Wenk G.L. McGann-Gramling K. Hauss-Wegrzyniak B. et al.Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid.J Neurochem. 2004; 89: 484-493Google Scholar), peroxynitrite (Pannala et al., 1998Pannala A.S. Razaq R. Halliwell B. Singh S. Rice-Evans C.A. Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamate: Nitration or electron donation?.Free Rad Biol Med. 1998; 24: 594-606Google Scholar; Dinis et al., 2002Dinis T.C. Santosa C.L. Almeida L.M. The apoprotein is the preferential target for peroxynitrite-induced LDL damage protection by dietary phenolic acids.Free Rad Res. 2002; 36: 531-543Google Scholar), and superoxide radical (Kaul and Khanduja, 1999Kaul A. Khanduja K.L. Plant polyphenols inhibit benzoyl peroxide-induced superoxide anion radical production and diacylglyceride formation in murine peritoneal macrophages.Nutr Cancer. 1999; 35: 207-211Google Scholar; Kikuzaki et al., 2002Kikuzaki H. Hisamoto M. Hirose K. Akiyama K. Taniguchi H. Antioxidant properties of ferulic acid and its related compounds.J Agric Food Chem. 2002; 50: 2161-2168Google Scholar). It was antimutagenic (Yamada and Tomita, 1996Yamada J. Tomita Y. Antimutagenic activity of caffeic acid and related compounds.Biosci Biotech Biochem. 1996; 60: 328-329Google Scholar; Ferguson et al., 2003Ferguson L.R. Lim I.F. Pearson A.E. Ralph J. Harris P.J. Bacterial antimutagenesis by hydroxycinnamic acids from plant cell walls.Mutat Res. 2003; 542: 49-58Google Scholar), protected against menadione-induced oxidative DNA damage (Burdette et al., 2002Burdette J.E. Chen S.N. Lu Z.Z. et al.Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: Bioassay-directed isolation and characterization of active principles.J Agric Food Chem. 2002; 50: 7022-7028Google Scholar) and demonstrated anticarcinogenic effects in animal models of pulmonary (Lesca, 1983Lesca P. Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice.Carcinogenesis. 1983; 4: 1651-1653Google Scholar) and colon carcinoma (Kawabata et al., 2000Kawabata K. Yamamoto T. Hara A. et al.Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats.Cancer Lett. 2000; 157: 15-21Google Scholar; Wargovich et al., 2000Wargovich M.J. Jimenez A. McKee K. et al.Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression.Carcinogenesis. 2000; 21: 1149-1155Google Scholar). Topical application inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase activity and decreased TPA-induced skin tumor formation (Huang et al., 1988Huang M.T. Smart R.C. Wong C.Q. Conney A.H. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate.Cancer Res. 1988; 48: 5941-5946Google Scholar). Topical application of ferulic acid inhibited UVB-induced erythema (Saija et al., 2000Saija A. Tomaino A. Trombetta D. et al.In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents.Int J Pharmaceut. 2000; 199: 39-47Google Scholar). In a mouse model of multiple sclerosis, oral ferulic acid had a striking effect on syncytin-mediated inflammation and death of oligodendrocytes induced by redox reactants (Antony et al., 2004Antony J.M. van Marle G. Opii W. et al.Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination.Nat Neurosci. 2004; 7: 1088-1095Google Scholar). Ferulic acid absorbs UV radiation with an absorption maximum at 307 nm (log e=4.19) (Graf, 1992Graf E. Antioxidant potential of ferulic acid.Free Rad Biol Med. 1992; 13: 435-448Google Scholar). Theoretically this absorption could result in a sunscreen effect providing topical protection against UV radiation. Our studies revealed no evidence of a dose–response effect to support a sunscreen mechanism (Figure 5). The mechanism of ferulic acid's stabilizing effect on vitamins C and E is unknown. It would not be expected to directly protect these vitamins since its redox potential (0.595) is appreciably higher than vitamin C (0.282) or vitamin E (0.48) (Lu and Liu, 2002Lu C. Liu Y. Interactions of lipoic acid radical cations with vitamins C and E analogue and hydroxycinnamic acid derivatives.Arch Biochem Biophys. 2002; 406: 78-84Google Scholar). Since it provides protection against vitamin C degradation, it may preferentially interact with pro-oxidative intermediates, or serve as a sacrificial substrate. It is also possible that its interactions may be enhanced at the low pH of the formulation. Ferulic acid's effect on photoprotection is most likely related to its antioxidant activity. It had no appreciable effect on ascorbic acid absorption (data not shown). Ferulic acid augments the protection of vitamins C+E previously demonstrated to prevent UV-induced thymine dimer formation when applied topically to skin (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874Google Scholar). A recent study of actinic keratoses and squamous cell carcinomas of skin using laser capture microdissection reveals 8-oxo guanine mutations in the basal germinative layer and thymine dimer mutations at suprabasal locations (Agar et al., 2004Agar N.S. Halliday G.M. Barnetson R.S. Ananthaswamy H.N. Wheeler M. Jones A.M. The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: A role for UVA in human skin carcinogenesis.Proc Natl Acad Sci USA. 2004; 101: 4954-4959Google Scholar). The results support the hypothesis that UVA-induced oxidative DNA modifications are responsible for the carcinogenic mutations in stem cells and UVB-induced mutations promote the carcinogenic process. The hypothesis fits with the superficial penetration of UVB and the deeper penetration of UVA into skin. Although we have not yet been able to measure the effect of antioxidants on UV-induced 8-oxo guanine formation, protection would be predicted. The demonstrated protection of topical application of vitamins C, E, and ferulic acid against UV-induced thymine dimer formation supports its use for the prevention of skin cancer. Recent studies substantiating the shortcomings of sunscreen protection support the need for a different approach to photoprotection. Sun protection factor is measured at 2 mg per cm2, yet in actual use, sunscreen application is only 0.4–0.5 mg per cm2 (Wulf et al., 1997Wulf H.C. Stender I.M. Lock-Andersen J. Sunscreens used at the beach do not protect against erythema: A new definition of SPF is proposed.Photodermatol Photoimmunol Photomed. 1997; 13: 129-132Google Scholar; Autier et al., 2001Autier P. Boniol M. Severi G. Dore J.F. European Organization for Research and Treatment of Cancer Melanoma Co: Quantity of sunscreen used by European students.Br J Dermatol. 2001; 144: 288-291Google Scholar). Since SPF is an exponential measurement, at reduced levels, relative photoprotection of any sunscreen is no more than 3–4-fold. In addition, SPF is a measurement of UVB only and reveals nothing about UVA photoprotection, protection necessary to protect against oxidative stress. Indeed a recent study of three high SPF broad-screen sunscreens revealed that at 2 mg per cm2 application, UVA-induced free radical formation was reduced only 55% with even worse protection when application levels were decreased (Haywood et al., 2003Haywood R. Wardman P. Sanders R. Linge C. Sunscreens inadequately protect against ultraviolet-A-induced free radicals in ski: Implications for skin aging and melanoma? Journal of Investigative Dermatology.. 2003; 121: 862-868Google Scholar). Sunscreens are designed to be shields for the skin, protecting the skin by absorbing harmful UV radiation. Since they work at the surface of the skin, they are easily removed by washing or rubbing. Antioxidants, in contrast, are designed to work not only at the skin's surface but also inside skin. Following topical application, once the skin is saturated with L-ascorbic acid, it remains with a half-life of about 4 d (Pinnell et al., 2001Pinnell S.R. Yang H.S. Omar M. et al.Topical L-ascorbic acid: Percutaneous absorption studies.Dermatol Surg. 2001; 27: 137-142Google Scholar). Approximately one third of UVA-induced oxidative stress in skin occurs at the surface of skin (Ou-Yang et al., 2004Ou-Yang H. Stamatas G. Saliou C. Kollias N. A chemiluminescence study of UVA-induced oxidative stress in human skin in vivo.J Invest Dermatol. 2004; 122: 1020-1029Google Scholar). Vitamin E is delivered to the surface of skin through sebum to protect the stratum corneum from this oxidative insult (Thiele, 2001Thiele J.J. Oxidative targets in the stratum corneum. A new basis for antioxidative strategies.Skin Pharmacol Appl Skin Physiol. 2001; 14: 87-91Google Scholar). Direct topical application of antioxidants would be expected to facilitate this protection. Using both a properly formulated topical combination antioxidant product containing vitamins C and E with ferulic acid, and also a broad-spectrum sunscreen, would be expected to provide optimal photoprotection. Since they work by different mechanisms, they should be supplemental (Darr et al., 1996Darr D. Dunston S. Faust H. Pinnell S. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.Acta Derm Venereol. 1996; 76: 264-268Google Scholar). L-ascorbic acid, DL-α-tocopherol, and trans ferulic acid were purchased from Sigma (St Louis, Missouri). Aqueous solutions were prepared in a vehicle containing diethylene glycol monoethyl ether, 1,2-propanediol, Brij-35, and phenoxyethanol at pH 3. The experimental design has previously been published in detail (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874Google Scholar). Experiments were performed on weanling white Yorkshire pigs in accord with the guidelines prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council (National Institutes of Health, publication No. 86–23, revised 1996). Unless otherwise noted, 500 μL aliquots of vehicle; 0.5% trans ferulic acid; 15% L-ascorbic acid, 1% DL-α-tocopherol, and 15% L-ascorbic acid, 1% DL-α-tocopherol, 0.5% trans ferulic acid were applied to patches of back skin (7.5 × 10 cm) daily for 4 d. A 1000 W solar simulator (Lightning Cure 200, Hamamatsu, Japan) fitted with a WG295 Schott filter to eliminate wavelengths less than 295 nm delivered UV radiation to the skin's surface through a liquid light guide at an intensity of 5 mW per cm2 of UVB and about 40 mW per cm2 of UVA as measured by a radiometer (IL1700, International Light, Newburyport, Mississippi). MED was determined as the lowest dose resulting in erythema with perceptible borders (40 mJ per cm2 of UVB). Each patch was given solar-simulated irradiation in triplicate from 2 × to 10 × MED at 2 × MED intervals. Evaluation was carried out 24 h later. Antioxidant protection factor was calculated as the ratio of the MED in antioxidant-treated skin in comparison with untreated skin. Erythema was measured by colorimeter evaluation in the “a” mode (ColorMouse Too, Color Savvy Systems Ltd, Springboro, Ohio) of 8 × 12 in enlargements of skin photographs. Each spot and adjacent unirradiated skin was measured in triplicate. The difference between irradiated and unirradiated skin determined the erythema. Sunburn cells were determined in formalin-fixed 8 mm punch biopsy sections stained with hematoxylin and eosin. When irradiation damage was extensive, the number 35 sunburn cells per mm were used as an upper limit. For western blotting, cell protein was extracted from freeze-fractured skin in a solution containing 1% NP-40%, 1% sodium deoxycholate, 0.3% SDS, 0.15 M NaCl, 2 mM EDTA, 50 mM sodium fluoride, 10 mM sodium phosphate, pH 7.2, and a pre-formed protease inhibitor mixture (Sigma). Protein extract (50 μg) mixed with mercaptoethanol and SDS-PAGE sample buffer was heated at 100°C for 5 min, and separated on 12% SDS-polyacrylamide gel, electrotransferred to PVDF membrane (Millipore, Bedford, Massachusetts), blocked in TBS (100 mM Tris-HCl, pH 7.5, and 150 mM NaCl) containing 0.1% Tween-20% and 5% milk for 1 h at room temperature and incubated with primary antibody: rabbit anti-human cleaved caspase-3, or cleaved caspase-7 diluted 1:1000 (Cell Signaling Technology, Beverly, Massachusetts) overnight at 4°C. After reaction with horseradish peroxidase-conjugated goat anti-rabbit IgG, immunocomplexes were visualized using ECL (Amersham Pharmacia Biotech, Piscataway, New Jersey). For internal control, the blots were stripped and reprobed with anti-α tubulin monoclonal antibody (Santa Cruz Biotechnology, Santa Cruz, California). Densitometry was performed using Kodak ID image analysis software (Kodak, Rochester, New York). Formalin-fixed skin was prepared for caspase-3 or caspase-7 immunocytochemistry by following manufacturer's protocol. Briefly, sections were deparaffinized/hydrated, heated in 10 mM sodium citrate buffer (pH 6) for antigen unmasking, incubated in 1% hydrogen peroxide, followed by incubation with 5% horse serum. Sections were incubated with primary antibody solution (1:200 dilution) overnight at 4°C, followed by biotin-labeled anti-rabbit IgG secondary antibody according to ABC biotin/avidin method (Vector Laboratories, Burlingame, California). Finally, sections were incubated in peroxidase substrate solution (DAB, Vector Laboratories), and counterstained with hematotoxylin. The procedure was modified from the method described byMitchell et al., 2001Mitchell D.L. Volkmer B. Breitbart E.W. Byrom M. Lowery M.G. Greinert R. Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage.J Invest Dermatol. 2001; 117: 590-595Google Scholar. Briefly, sections were deparaffined/rehydrated and washed with phosphate-buffered saline (PBS), denatured in 0.1 N NaOH/70% EtOH for 5 min, dehydrated in EtOH, air dried, and incubated with protease XXV (Labvision, Fremont, California) at 37°C for 7 min. After washing with PBS, sections were blocked with 5% goat serum for 20 min, washed, incubated with anti-thymine dimer, clone KTM53 diluted 1:200 (Kamiya Biomedical Company, Seattle, Washington) at 37°C for 1 h, followed by anti-mouse IgG conjugated with fluorescein isothiocyanate diluted 1:200 at 37°C for 30 min. Sections were visualized using Olympus BX41fluorescence microscope coupled with a Q-Fire camera. Results are expressed as mean±SD. The p-values were calculated by two-tailed Student's t-test. This research was supported in part by NIH Grant R43CA83538. This research was presented in part as posters at the 65th Annual Meeting of the Society of Investigative Dermatology, Providence, Rhode Island 4/28-5/1 2004. Thanks to Doren Madey, PhD for help in preparation of the manuscript. Sheldon Pinnell is a consultant for SkinCeuticals, Garland, Texas. Jan Zielinski, PhD is president of Zielinski Laboratory, San Diego, California.}, number={4}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Lin, FH and Lin, JY and Gupta, RD and Tournas, JA and Burch, JA and Selim, MA and Monteiro-Riviere, NA and Grichnik, JM and Zielinski, J and Pinnell, SR and et al.}, year={2005}, month={Oct}, pages={826–832} }
 @inproceedings{pinnell_lin_monteiro-riviere_grichnik_zielinski_2005, title={Ferulic acid, a potent plant antioxidant, stabilizes an antioxidant solution containing vitamins C+ E and increases skin photoprotection to eightfold}, volume={21}, number={3}, booktitle={Photodermatology, Photoimmunology & Photomedicine}, author={Pinnell, S.R. and Lin, F-Y and Monteiro-Riviere, N.A. and Grichnik, J.M. and Zielinski, J.E.}, year={2005}, pages={170} }
 @article{tournas_lin_burch_selim_monteiro-riviere_zielinski_pinnell_2005, title={Kinetin (N6-furfuryladenine) provides only mild photoprotection when compared to a topical antioxidant formulation containing 15% L-ascorbic acid, 1% alpha-tocopherol and 0.5% ferulic acid}, volume={124}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000228179901353&KeyUID=WOS:000228179901353}, number={4}, journal={Journal of Investigative Dermatology}, author={Tournas, JA and Lin, F and Burch, JA and Selim, MA and Monteiro-Riviere, NA and Zielinski, JE and Pinnell, SR}, year={2005}, pages={A136} }
 @inproceedings{tournas_lin_burch_selim_monteiro-riviere_zielinski_pinnell_2005, title={Kinetin (N6-furfuryladenine) provides only mild photoprotection whencompared to a topical antioxidant formulation containing 15%L-ascorbic acid, 1% a-tocopherol and 0.5% ferulic acid (C+E+Ferulic)}, volume={19}, number={Supplement 2}, booktitle={Journal of the European Academy of Dermatology & Venereology}, author={Tournas, J.A. and Lin, F.H. and Burch, J.A. and Selim, M.A. and Monteiro-Riviere, N.A. and Zielinski, J.E. and Pinnell, S.R.}, year={2005}, pages={48} }
 @article{xia_baynes_monteiro-riviere_riviere_2005, title={Membrane uptake kinetics of jet fuel aromatic hydrocarbons from aqueous solutions studied by a membrane-coated fiber technique}, volume={15}, ISSN={["1537-6524"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000230827300008&KeyUID=WOS:000230827300008}, DOI={10.1080/15376520590968888}, abstractNote={The absorption of aromatic hydrocarbons from aqueous media is a critical step involved in many biological processes after occupational and environmental exposures to jet fuel. A membrane-coated fiber (MCF) technique was used to study the uptake kinetics. A flow-through system was used to provide a constant concentration for the prolonged permeation experiments. Polydimethylsiloxane (PDMS) and polyacrylate (PA) MCFs were used to study the differential absorptivity of the aromatic compounds between the two membrane materials. The equilibrium absorption amount and a kinetic parameter describing the absorption kinetics were obtained by the regression of the permeation profiles of the aromatic compounds with a mathematical model. The partition coefficients, uptake, and elimination rate constants were determined for six benzene and three naphthalene derivatives. The PDMS/water partition coefficients of the benzene and naphthalene derivatives were linearly correlated with their logK(o/w) (LogK(pdms/w) = 0.871LogK(o/w) - 0.241, R(2) = 0.995). The PA/water partition coefficients of the benzene derivatives and the naphthalene derivatives were correlated differently with their logK(o/w). The correlation equations for benzene and naphthalene derivatives were LogK(pa/w) = 0.865LogK(o/w) + 0.0045, R(2) = 0.997 and LogK(pa/w) = 0.763LogK(o/w) + 0.911, R(2) = 1.00, respectively. These results suggest that the MCF technique can detect subtle differences in molecular interactions of the two group derivatives between the two membrane/water systems and may be used to study the absorption and permeation properties of closely related compounds. Finally, the regression method is a particularly useful tool to determine partition coefficients of very lipophilic compounds.}, number={4}, journal={TOXICOLOGY MECHANISMS AND METHODS}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2005}, pages={307–316} }
 @article{monteiro-riviere_2005, title={Multi-walled carbon nanotube exposure in human epidermal keratinocytes: Localization and proteomic analysis.}, volume={229}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000228177706461&KeyUID=WOS:000228177706461}, journal={Abstracts of Papers of the American Chemical Society}, author={Monteiro-Riviere, NA}, year={2005}, pages={U911–U912} }
 @article{monteiro-riviere_nemanich_inman_wang_riviere_2005, title={Multi-walled carbon nanotube interactions with human epidermal keratinocytes}, volume={155}, ISSN={["1879-3169"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000226645800005&KeyUID=WOS:000226645800005}, DOI={10.1016/j.toxlet.2004.11.004}, abstractNote={Carbon nanotubes have widespread applications in multiple engineering disciplines. However, little is known about the toxicity or interaction of these particles with cells. Carbon nanotube films were grown using a microwave plasma enhanced chemical vapor deposition system. Human epidermal keratinocytes (HEK) were exposed to 0.1, 0.2, and 0.4 mg/ml of multi-walled carbon nanotubes (MWCNT) for 1, 2, 4, 8, 12, 24 and 48 h. HEK were examined by transmission electron microscopy for the presence of MWCNT. Here we report that chemically unmodified MWCNT were present within cytoplasmic vacuoles of the HEK at all time points. The MWCNT also induced the release of the proinflammatory cytokine interleukin 8 from HEKs in a time dependent manner. These data clearly show that MWCNT, not derivatized nor optimized for biological applications, are capable of both localizing within and initiating an irritation response in a target epithelial cell that composes a primary route of occupational exposure for manufactured nanotubes.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Monteiro-Riviere, NA and Nemanich, RJ and Inman, AO and Wang, YYY and Riviere, JE}, year={2005}, month={Mar}, pages={377–384} }
 @article{oberdörster_maynard_donaldson_castranova_fitzpatrick_ausman_carter_karn_kreyling_lai_et al._2005, title={Principles for characterizing the potential human health effects from exposure to nanomaterials: Elements of a screening strategy}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33845214358&partnerID=MN8TOARS}, DOI={10.1186/1743-8977-2-8}, abstractNote={Abstract The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered. Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies.}, number={8}, journal={Particle and Fibre Toxicology}, author={Oberdörster, G. and Maynard, A. and Donaldson, K. and Castranova, V. and Fitzpatrick, J. and Ausman, K. and Carter, J. and Karn, B. and Kreyling, W. and Lai, D. and et al.}, year={2005}, pages={1–35} }
 @article{holsapple_farland_landry_monteiro-riviere_carter_walker_thomas_2005, title={Research strategies for safety evaluation of nanomaterials, part II: Toxicological and safety evaluation of nanomaterials, current challenges and data needs}, volume={88}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000232428300003&KeyUID=WOS:000232428300003}, DOI={10.1093/toxsci/kfi293}, abstractNote={This article summarizes a roundtable discussion held at the 2005 Society of Toxicology Annual Meeting in New Orleans, LA. The purpose of the roundtable was to review the current challenges and data needs for conducting toxicological and safety evaluations for nanomaterials, with the goals of presenting the current state-of-the science on the safety of nanomaterials and bringing together scientists representing government, academia, and industry to identify priorities for developing data to facilitate risk assessments for these materials. In this summary, the unique physicochemical properties associated with nanomaterials are reviewed in the context of the difficulties associated with measuring and characterizing them. In addition, the development of appropriate hazard data, the collection of accurate human and environmental exposure information, and the development of a better fundamental understanding of the modes of action for nanomaterials are discussed as factors that will impact the development of comprehensive toxicological and safety evaluations.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Holsapple, MP and Farland, WH and Landry, TD and Monteiro-Riviere, NA and Carter, JM and Walker, NJ and Thomas, KV}, year={2005}, month={Nov}, pages={12–17} }
 @article{monteiro-riviere_inman_wang_nemanich_2005, title={Surfactant effects on carbon nanotube interactions with human keratinocytes}, volume={1}, ISSN={["1549-9642"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33745481652&partnerID=MN8TOARS}, DOI={10.1016/j.nano.2005.10.007}, abstractNote={Interactions of multiwalled carbon nanotubes (MWCNTs) with human epidermal keratinocytes (HEKs) were studied with respect to the effect of surfactant on dispersion of MWCNT aggregates and cytotoxicity. Our earlier studies had shown that the unmodified MWCNTs were localized within the cytoplasmic vacuoles of HEKs and elicited an inflammatory response. However, MWCNTs in solution tend to aggregate and, therefore, cells are exposed to large MWCNT aggregates. The purpose of this study was to find a surfactant that prevents the formation of large aggregates of MWCNTs without being toxic to the HEKs. HEKs were exposed to serial dilutions (10% to 0.1%) of L61, L92, and F127 Pluronic and 20 or 60 Tween for 24 hours. HEK viability, proportional to surfactant concentration, ranged from 27.1% to 98.5% with Pluronic F127; viability with the other surfactants was less than 10%. Surfactants dispersed and reduced MWCNT aggregation in medium. MWCNTs at 0.4 mg/mL in 5% or 1% Pluronic F127 were incubated with HEKs and assayed for interleukin 8 (IL-8). MWCNTs were cytotoxic to HEKs independent of surfactant exposure. In contrast, MWCNT-induced IL-8 release was reduced when exposed to 1% or 5% Pluronic F127 (P < .05). However, both MWCNTs and surfactant, alone or in combination, increased IL-8 release compared with control exposures at 12 and 24 hours. These results suggest that the surfactant-MWCNT interaction is more complex than simple dispersion alone and should be investigated to determine the mode of interaction.}, number={4}, journal={NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE}, author={Monteiro-Riviere, Nancy A. and Inman, Alfred O. and Wang, Yunyu Y. and Nemanich, Robert J.}, year={2005}, month={Dec}, pages={293–299} }
 @inbook{monteiro-riviere_2005, title={The pig as a model for human skin research}, booktitle={Swine in biomedical research: Update on animal models}, publisher={Sinclair Research Center}, author={Monteiro-Riviere, N. A.}, editor={Swindle, M. and Bouchard, G. F.Editors}, year={2005}, pages={17–22} }
 @inproceedings{monteiro-riviere_riviere_2005, title={The pig as a model for human skin research}, volume={56}, booktitle={Swine in Biomedical Research: Update on Animal Models. Sinclair Research Center. 56th AALAS National Meeting}, author={Monteiro-Riviere, N. A. and Riviere, J. E.}, year={2005}, pages={17–22} }
 @article{linder_shin_monteiro-riviere_2005, title={Toll-like receptor gene expression in purified porcine skin dendritic cells}, volume={124}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000228179901270&KeyUID=WOS:000228179901270}, number={4}, journal={Journal of Investigative Dermatology}, author={Linder, K and Shin, K and Monteiro-Riviere, N}, year={2005}, pages={A122} }
 @article{xia_baynes_monteiro-riviere_riviere_2004, title={A Compartment Model for the Membrane-Coated Fiber Technique Used for Determining the Absorption Parameters of Chemicals into Lipophilic Membranes}, volume={21}, ISSN={0724-8741}, url={http://dx.doi.org/10.1023/b:pham.0000036907.02901.f7}, DOI={10.1023/B:PHAM.0000036907.02901.f7}, number={8}, journal={Pharmaceutical Research}, publisher={Springer Science and Business Media LLC}, author={Xia, Xin-Rui and Baynes, Ronald E. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2004}, month={Aug}, pages={1345–1352} }
 @article{lin_monteiro-riviere_grichnik_zielinski_pinnell_2004, title={A topical antioxidant solution containing vitamin C, vitamin E, and ferulic acid prevents ultraviolet radiation-induced caspase-3 induction in skin}, volume={122}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000220660500931&KeyUID=WOS:000220660500931}, number={3}, journal={Journal of Investigative Dermatology}, author={Lin, J and Monteiro-Riviere, NA and Grichnik, JM and Zielinski, JE and Pinnell, SR}, year={2004}, pages={A148} }
 @inbook{monteiro-riviere_2004, title={Anatomical factors affecting barrier function}, ISBN={0415288622}, booktitle={Dematoxicology. (6th ed.)}, publisher={Washington, DC: CRC Press}, author={Monteiro-Riviere, N. A.}, editor={Zhai, H. and Maibach, H. I.Editors}, year={2004}, pages={42–70} }
 @article{xia_baynes_monteiro-riviere_riviere_2004, title={Characterization of polyacrylate membrane-coated fibers used in chemical absorption studies with programmed thermal treatment and FT-IR microscopy}, volume={76}, ISSN={["0003-2700"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000222706400053&KeyUID=WOS:000222706400053}, DOI={10.1021/ac0355146}, abstractNote={A polyacrylate (PA) film was coated onto a fused-silica fiber as a permeation membrane in a membrane-coated fiber (MCF) technique and a solid-phase microextraction technique. The molecular changes of the PA membrane after different temperature treatments were studied with FT-IR microscopy. The absorption bands of the PA aliphatic backbone at 2902, 2795, and 2740 cm-1 remained unchanged over the elevated thermal treatments, indicating that the polymer backbone was stable over these conditions. The spectra of the PA membrane remained unchanged when the thermal treatment temperature was under 150 °C. When the temperature was 250 °C, the O−H stretching band in the −COOH groups of the poly(acrylic acid) at 3315 cm-1 was significantly reduced. When the temperature was higher than 280 °C, this O−H band disappeared. These evidences suggested that the PA membrane underwent dehydroxyl reaction to form an anhydride when the thermal treatments were higher than 250 °C. Thermal treatments of a deuterated PA MCF confirmed the anhydride formation mechanism. The anhydride formation explained the absorption property of PA MCFs in GC applications where they must be preconditioned at 300 °C. The absorption data suggest that a PA fiber does not preferably absorb polar compounds (with permanent dipole moment); instead, it absorbs preferably aromatic compounds.}, number={14}, journal={ANALYTICAL CHEMISTRY}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2004}, month={Jul}, pages={4245–4250} }
 @article{muhammad_baynes_monteiro-riviere_xia_riviere_2004, title={Dose related absorption of JP-8 jet fuel hydrocarbons through porcine skin with quantitative structure permeability relationship analysis}, volume={14}, ISSN={["1537-6524"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000220690300003&KeyUID=WOS:000220690300003}, DOI={10.1080/15376520490429319}, abstractNote={The effects of dosage on the percutaneous absorption of jet fuel hydrocarbons is not clear, yet is essential for human risk assessment. The present study is an ongoing approach to assess the dose-related percutaneous absorption of a number of aliphatic and aromatic hydrocarbons. The first treatment (1X) was comprised of mixtures containing undecane (4.1%), dodecane (4.7%), tridecane (4.4%), tetradecane (3%), pentadecane (1.6%), naphthalene (1.1%), and dimethyl naphthalene (1.3% of jet fuels) in hexadecane solvent using porcine skin flow through diffusion cell. Other treatments (n = 4 cells) were 2X and 5X concentrations. Perfusate samples were analyzed with gas chromatography-flame ionization detector (GC-FID) using head space solid phase micro-extraction fiber technique. We have standardized the assay to have a good linear correlation for all the tested components in media standards. Absorption parameters including diffusivity, permeability, steady state flux, and percent dose absorbed were estimated for all the tested hydrocarbons. This approach provides a baseline to access component interactions among themselves and with the diluent (solvents). A quantitative structure permeability relationship (QSPR) model was derived to predict the permeability of unknown jet fuel hydrocarbons in this solvent system by using their physicochemical parameters. Our findings suggested a dose related increase in absorption for naphthalene and dimethyl naphthalene (DMN).}, number={3}, journal={TOXICOLOGY MECHANISMS AND METHODS}, author={Muhammad, F and Baynes, RE and Monteiro-Riviere, NA and Xia, XR and Riviere, JE}, year={2004}, pages={159–166} }
 @article{lin_lin_burch_grichnik_gupta_monteiro-riviere_zielinski_pinnell_2004, title={Ferulic acid stabilizes a topical solution containing vitamins C & E and doubles its photoprotection for skin}, volume={122}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000220660500934&KeyUID=WOS:000220660500934}, number={3}, journal={Journal of Investigative Dermatology}, author={Lin, JY and Lin, F and Burch, J and Grichnik, JM and Gupta, R and Monteiro-Riviere, NA and Zielinski, JA and Pinnell, SR}, year={2004}, pages={A148} }
 @article{udomkusonsri_noga_monteiro-riviere_2004, title={Pathogenesis of acute ulceration response (AUR) in hybrid striped bass}, volume={61}, ISSN={["1616-1580"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000226275200003&KeyUID=WOS:000226275200003}, DOI={10.3354/dao061199}, abstractNote={DAO Diseases of Aquatic Organisms Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsSpecials DAO 61:199-213 (2004) - doi:10.3354/dao061199 Pathogenesis of acute ulceration response (AUR) in hybrid striped bass Pareeya Udomkusonsri1,2, Edward J. Noga1,*, Nancy A. Monteiro-Riviere1 1Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27607, USA2Present address: Faculty of Veterinary Medicine, Department of Pharmacology, Kasetsart University, 50 Phahonyothin Road, Chatuchak, Bangkok 10900, Thailand *Corresponding author. Email: ed_noga@ncsu.edu ABSTRACT: In a previous study, we discovered that acute confinement stress causes rapid ulceration of the fins of hybrid striped bass Morone saxatilis female × M. chrysops male (Noga et al. 1998. Vet Pathol 35:102–107). In this paper, we report the development of a reproducible model for studying this phenomenon in juvenile hybrid striped bass. We also determined how quickly ulceration could develop in acutely stressed fish and documented the sequential light microscopic and ultrastructural changes associated with this response. When hybrid striped bass were subjected to a standardized confinement protocol, the pathological response was extremely rapid (fin ulceration began to develop within 15 min of confinement). Grossly, the distal edges of the fins became blanched, and melanophores aggregated near the basement membrane and dermis after 15 min of confinement. Microscopically, the earliest detectable change in the fins, which occurred within 15 min of confinement, was swelling and loss of microridges of the outermost epidermal cells; this was followed by epidermal erosion. After 30 min of stress, epidermal ulceration developed at the distal edges of the fins. At this time, both necrotic and apoptotic epidermal cells were present. The middle and basal epidermal layers were severely spongiotic and the dermis and hypodermis were edematous. Over longer periods (up to 2 h), lesions were similar but increasingly more severe, progressing from the distal edge of the fin towards the base. The response to acute stress showed a significant correlation between confinement period and severity of the pathological changes (epidermal degeneration, epidermal ulceration and leukocyte infiltration). Also, we demonstrated that epidermal damage was not restricted to the fins but also affected the body skin and eyes. The ventral area of the body and the corneal epithelium of stressed fish were ulcerated; however, skin on the head and operculum was not affected, suggesting a site-specific mode of damage. In stressed fish, epidermal ulceration was found in 67 to 97% of all fins, 88% of skin on the ventrum, and 67% of corneas, while control fish had only very mild epidermal ulceration in the few fish in which it was present (on 5 to 10% of the fins, but not on the ventral skin or corneas). Due to the widespread damage to epidermal tissues of the body surface, we have named this the acute ulceration response (AUR). Our study indicates that acute confinement can rapidly cause significant damage to epidermal and ocular epithelium. AUR might be a primary cause of morbidity in acutely stressed fish. KEY WORDS: Skin ulceration · Striped bass · Acute stress · Pathology Full article in pdf format PreviousNextExport citation Mail this link - Contents Mailing Lists - RSS Facebook - Tweet - linkedIn Cited by Published in DAO Vol. 61, No. 3. Online publication date: November 05, 2004 Print ISSN: 0177-5103; Online ISSN: 1616-1580 Copyright © 2004 Inter-Research.}, number={3}, journal={DISEASES OF AQUATIC ORGANISMS}, author={Udomkusonsri, P and Noga, EJ and Monteiro-Riviere, NA}, year={2004}, month={Nov}, pages={199–213} }
 @article{monteiro-riviere_inman_riviere_2004, title={Skin toxicity of jet fuels: ultrastructural studies and the effects of substance P}, volume={195}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000220284800009&KeyUID=WOS:000220284800009}, DOI={10.1016/j.taap.2003.07.013}, abstractNote={Topical exposure to jet fuel is a significant occupational hazard. Recent studies have focused on dermal absorption of fuel and its components, or alternatively, on the biochemical or immunotoxicological sequelae to exposure. Surprisingly, morphological and ultrastructural analyses have not been systematically conducted. Similarly, few studies have compared responses in skin to that of the primary target organ, the lung. The focus of the present investigation was 2-fold: first, to characterize the ultrastructural changes seen after topical exposure to moderate doses (335 or 67 microl/cm2) of jet fuels [Jet A, Jet Propellant (JP)-8, JP-8+100] for up to 4 days in pigs, and secondly, to determine if co-administration of substance P (SP) with JP-8 jet fuel in human epidermal keratinocyte cell cultures modulates toxicity as it does to pulmonary toxicity in laboratory animal studies. The primary change seen after exposure to all fuels was low-level inflammation accompanied by formation of lipid droplets in various skin layers, mitochondrial and nucleolar changes, cleft formation in the intercellular lipid lamellar bilayers, as well as disorganization in the stratum granulosum-stratum corneum interface. An increased number of Langerhans cells were also noted in jet fuel-treated skin. These changes suggest that the primary effect of jet fuel exposure is damage to the stratum corneum barrier. SP administration decreased the release of interleukin (IL)-8 normally seen in keratinocytes after JP-8 exposure, a response similar to that reported for SP's effect on JP-8 pulmonary toxicity. These studies provide a base upon which biochemical and immunological data collected in other model systems can be compared.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Monteiro-Riviere, NA and Inman, AO and Riviere, JE}, year={2004}, month={Mar}, pages={339–347} }
 @misc{lin_lin_burch_selim_monteiro-riviere_grichnik_pinnell_2004, title={alpha-Lipoic acid is ineffective as a topical antioxidant for photoprotection of skin}, volume={123}, ISSN={["1523-1747"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000224347000029&KeyUID=WOS:000224347000029}, DOI={10.1111/j.0022-202x.2004.23446.x}, abstractNote={To the Editor: α-lipoic acid is synthesized in mitochondria of cells (Morikawa et al., 2001Morikawa T. Yasuno R. Wada H. Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria.FEBS Lett. 2001; 498: 16-21https://doi.org/10.1016/S0014-5793(01)02469-3Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar) and covalently attached through lysyl residues to α-keto acid dehydrogenase complexes (Biewenga et al., 1997Biewenga G.P. Haenen G.R. Bast A. The pharmacology of the antioxidant lipoic acid.Gen Pharmacol. 1997; 29: 315-331Crossref PubMed Scopus (728) Google Scholar). The attached α-lipoic acid is a cofactor for the enzyme and together with dihydrolipoic acid, its reduction derivative, serve as a redox couple carrying electrons from the substrate of the enzyme to NAD+. Despite the fact that there is little or no free α-lipoic acid normally in tissues (Hermann et al., 1996Hermann R. Niebch G. Borbe H.O. et al.Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers.Eur J Pharm Sci. 1996; 4: 167-174https://doi.org/10.1016/0928-0987(95)00045-3Crossref Scopus (99) Google Scholar), α-lipoic acid has been proposed as an antioxidant for topical application to skin to protect the skin against ultraviolet photodamage including skin cancer and photoaging changes (Podda et al., 2001Podda M. Zollner T.M. Grundmann-Kollmann M. Thiele J.J. Packer L. Kaufmann R. Activity of alpha-lipoic acid in the protection against oxidative stress in skin.Curr Problems Dermatol. 2001; 29: 43-51Crossref PubMed Google Scholar). We have previously studied topical combination vitamin C (L-ascorbic acid) and vitamin E (α-tocopherol) in skin and demonstrated synergistic photoprotection (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874https://doi.org/10.1067/mjd.2003.425Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar). In this study, we use the same model to evaluate topical α-lipoic acid formulations. The experimental design has previously been published in detail (Lin et al., 2003Lin J.Y. Selim M.A. Shea C.R. Grichnik J.M. Omar M.M. Monteiro-Riviere N.A. Pinnell S.R. UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol. 2003; 48: 866-874https://doi.org/10.1067/mjd.2003.425Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar). Experiments were performed on weanling white Yorkshire pigs in accord with the guidelines prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council (National Institutes of Health, publication no. 86-23, revised 1996). Five percent DL-α-lipoic acid (Pharmline, Florida, New York) was dissolved in 50% ethanol. A commercial formulation containing 15%L-ascorbic acid (vitamin C) and 1%DL-α-tocopherol (vitamin E) (Primacy C+E, SkinCeuticals, Garland, Texas) and a commercial formulation of á-lipoic acid (Face Firming Activator with DMAE, N.V. Perricone, Meriden, Connecticut) were purchased and opened immediately prior to use. Antioxidant solutions (500 μL) were applied to patches of shaved back skin (7.5 × 10 cm) daily for 4 days. A 1000-W solar simulator (Lightning Cure 200, Hamamatsu, Japan) fitted with a WG295 Schott filter to eliminate wavelengths less than 295 nm delivered ultraviolet irradiation to the skin's surface through a liquid light guide at an intensity of 5 mW per cm2 of UVB and about 40 mW per cm2 of UVA as measured by a radiometer (IL1700, International Light, Newburyport, Mississippi). MED was determined as the lowest dose resulting in erythema with perceptible borders (40 mJ per cm2 of UVB). Each patch was given solar-simulated irradiation in triplicate from 0.5 × to 2.5 × MED at 0.5 × MED intervals or 1 × to 5 × MED at 1 × MED intervals. Evaluation was carried out 24 hours later. Erythema was measured by colorimeter evaluation in the “a” mode (ColorMouse Too, Color Savvy Systems, Springboro, Ohio) of 8 × 12-in photographic enlargements of skin. Each spot, together with adjacent unirradiated skin, was measured in triplicate. The difference between irradiated and unirradiated skin determined the erythema measurement. Sunburn cells were determined in formalin-fixed 8 mm punch biopsy sections stained with hematoxylin and eosin. When irradiation damage was extensive, the figure 35 sunburn cells per mm was used as an upper limit. Results are expressed as mean±SD (n=3). The p-values were calculated by Student's t test. No significant protection could be detected either by reduction of erythema (Figure 1a) or by sunburn cell (Figure 1b) analysis when untreated skin was compared to skin treated by 5%α-lipoic acid or a commercial formulation of α-lipoic acid. As previously reported, a formulation combining 15%L-ascorbic acid and 1%α-tocopherol provided meaningful photoprotection against solar-simulated irradiation as revealed by erythema (Figure 2a) or sunburn cells (Figure 2b). Adding 5%α-lipoic acid to the vitamin C and E solution provided no additional photoprotection (Figure 2a and b).Figure 2Topical α-lipoic acid does not supplement photoprotection provided by topica vitamins C+E. Colorimeter (a) and sunburn cell (b) data from untreated skin, skin treated with 5% vitamin C and 1% vitamin E, or skin treated with 5% vitamin C and 1% vitamin E and 5%α lipoic acid.View Large Image Figure ViewerDownload (PPT) Although α-lipoic acid has antioxidant properties, its potential as an antioxidant has been thought to depend on reduction to the more potent dihydrolipoic acid. Although small amounts of dihydrolipoic acid have been measured in murine skin following topical application of α-lipoic acid (Podda et al., 1996Podda M. Rallis M. Traber M.G. Packer L. Maibach H.I. Kinetic study of cutaneous and subcutaneous distribution following topical application of [7,8-14C]rac-alpha-lipoic acid onto hairless mice.Biochem Pharmacol. 1996; 52: 627-633https://doi.org/10.1016/0006-2952(96)00337-1Crossref PubMed Scopus (40) Google Scholar), this reaction is very inefficient. Reduction of α-lipoic acid to dihydrolipoic acid can be achieved with the mitochondrial enzyme dihydrolipoamide dehydrogenase, but it is not clear whether free α-lipoic acid has ready access to the mitochondrial compartment (Biewenga et al., 1996Biewenga G.P. Dorstijn M.A. Verhagen J.V. Haenen G.R. Bast A. Reduction of lipoic acid by lipoamide dehydrogenase.Biochem Pharmacol. 1996; 51: 233-238Crossref PubMed Scopus (44) Google Scholar). Glutathione reductase also can carry out the reduction, but the rate of the reaction is slow (Pick et al., 1995Pick U. Haramaki N. Constantinescu A. Handelman G.J. Tritschler H.J. Packer L. Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for alpha-lipoic acid enantiomers.Biochem Biophys Res Commun. 1995; 206: 724-730https://doi.org/10.1006/bbrc.1995.1102Crossref PubMed Scopus (84) Google Scholar). Several studies have shown that the reaction rate constant of dihydrolipoic acid with reactive oxygen species is slower than that of α-lipoic acid (Bisby and Parker, 1998Bisby R.H. Parker A.W. Antioxidant reactions of dihydrolipoic acid and lipoamide with triplet duroquinone.Biochem Biophys Res Commun. 1998; 244 ([erratum appears in Biochem Biophys Res Commun 1998 Aug 10;249(1):297].): 263-267Crossref PubMed Scopus (18) Google Scholar;Lu and Liu, 2002Lu C. Liu Y. Interactions of lipoic acid radical cations with vitamins C and E analogue and hydroxycinnamic acid derivatives.Arch Biochem Biophys. 2002; 406: 78-84https://doi.org/10.1016/S0003-9861(02)00411-3Crossref PubMed Scopus (39) Google Scholar;Trujillo and Radi, 2002Trujillo M. Radi R. Peroxynitrite reaction with the reduced and the oxidized forms of lipoic acid: New insights into the reaction of peroxynitrite with thiols.Arch Biochem Biophys. 2002; 397: 91-98https://doi.org/10.1006/abbi.2001.2619Crossref PubMed Scopus (166) Google Scholar). Moreover, dihydrolipoic acid may be pro-oxidant (Scott et al., 1994Scott B.C. Aruoma O.I. Evans P.J. et al.Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.Free Radical Res. 1994; 20: 119-133Crossref PubMed Scopus (282) Google Scholar). Once α-lipoic acid is oxidized after reaction with a free radical, its one-electron oxidation product is strongly pro-oxidant potentially causing free radical damage to cellular and tissue components(Lu and Liu, 2002Lu C. Liu Y. Interactions of lipoic acid radical cations with vitamins C and E analogue and hydroxycinnamic acid derivatives.Arch Biochem Biophys. 2002; 406: 78-84https://doi.org/10.1016/S0003-9861(02)00411-3Crossref PubMed Scopus (39) Google Scholar). In contrast, for example, ascorbyl radical has a relatively low pro-oxidant potential (De Tullio and Arrigoni, 2004De Tullio M.C. Arrigoni O. Hopes, disillusions and more hopes from vitamin C. [Review] [103 refs].Cell Mol Life Sci. 2004; 61: 209-219https://doi.org/10.1007/s00018-003-3203-8Crossref PubMed Scopus (67) Google Scholar). In fact, it prefers to react with itself and disproportionate rather than attacking other substrates. It is not clear whether free α-lipoic acid provides much physiologic antioxidant activity. In mitochondria it is covalently attached to mitochondrial enzymes through lysyl residues. Although available in the diet in tissues with high metabolic activity (e.g., heart), proteolytic enzymes do not effectively cleave the linkage between α-lipoic acid and lysine (Biewenga et al., 1997Biewenga G.P. Haenen G.R. Bast A. The pharmacology of the antioxidant lipoic acid.Gen Pharmacol. 1997; 29: 315-331Crossref PubMed Scopus (728) Google Scholar). Free α-lipoic acid is not normally detected in plasma (Hermann et al., 1996Hermann R. Niebch G. Borbe H.O. et al.Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers.Eur J Pharm Sci. 1996; 4: 167-174https://doi.org/10.1016/0928-0987(95)00045-3Crossref Scopus (99) Google Scholar) or in skin (Podda et al., 1994Podda M. Tritschler H.J. Ulrich H. Packer L. Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency.Bioch Biophys Res Commun. 1994; 204: 98-104https://doi.org/10.1006/bbrc.1994.2431Crossref PubMed Scopus (100) Google Scholar). Following oral or parenteral infusion, it remains in plasma only about 30 minutes and is cleared by liver during first pass (Hermann et al., 1996Hermann R. Niebch G. Borbe H.O. et al.Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers.Eur J Pharm Sci. 1996; 4: 167-174https://doi.org/10.1016/0928-0987(95)00045-3Crossref Scopus (99) Google Scholar;Teichert et al., 2003Teichert J. Hermann R. Ruus P. Preiss R. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers.J Clin Pharmacol. 2003; 43: 1257-1267https://doi.org/10.1177/0091270003258654Crossref PubMed Scopus (132) Google Scholar). Similar rapid clearance may also occur after percutaneous absorption. In summary, we have tested α-lipoic acid at high doses topically to skin to determine if it provides photoprotection against solar-simulated radiation. We were unable to detect protection using α-lipoic acid alone or together with vitamins C and E. In addition, a commercial formulation of α-lipoic acid provided no protection. Although we are unable to explain this lack of effect, it seems reasonable that α-lipoic acid absorbs ultraviolet light in the UVA spectrum—it has an absorption spectrum at 330 nm (Matsugo et al., 1996Matsugo S. Han D. Tritschler H.J. Packer L. Decomposition of alpha-lipoic acid derivatives by photoirradiation-formation of dihydrolipoic acid from alpha-lipoic acid.Biochem Mol Biol Int. 1996; 38: 51-59PubMed Google Scholar)—and is oxidized to its free radical and subsequently destroyed (Podda et al., 1997Podda M. Traber M.G. Packer L. Alpha-lipoate: Antioxidant properties and effects on skin.in: Fuchs J. Packer L. Zimmer G. Lipoic Acid in Health and Disease. Dekker, New York1997: 163-180Google Scholar). Conversion to dihydrolipoic acid is inefficient resulting in little interaction with vitamins C and E to augment their photoprotection. This research was supported in part by NIH grant R43CA83538. Solutions were prepared by Mostafa M. Omar, PhD of Phytoceuticals, Elmwood Park, New Jersey. Thanks to Doren Madey, PhD for help in preparation of the manuscript. Sheldon Pinnell is a consultant for SkinCeuticals, Garland, Texas.}, number={5}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={Lin, JY and Lin, FH and Burch, JA and Selim, MA and Monteiro-Riviere, NA and Grichnik, JM and Pinnell, SR}, year={2004}, month={Nov}, pages={996–998} }
 @article{xia_baynes_monteiro-riviere_riviere_2003, title={A mathematical model of the permeation kinetics of the membrane-coated fiber technique accounting for partition, diffusion and boundary layer factors.}, volume={72}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000181518501848&KeyUID=WOS:000181518501848}, journal={Toxicological Sciences}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2003}, pages={379} }
 @article{xia_baynes_monteiro-riviere_leidy_shea_riviere_2003, title={A novel in-vitro technique for studying percutaneous permeation with a membrane-coated fiber and gas chromatography/mass spectrometry: Part I. Performances of the technique and determination of the permeation rates and partition coefficients of chemical mixtures}, volume={20}, ISSN={["0724-8741"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000180830200019&KeyUID=WOS:000180830200019}, DOI={10.1023/A:1022287524024}, number={2}, journal={PHARMACEUTICAL RESEARCH}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Leidy, RB and Shea, D and Riviere, JE}, year={2003}, month={Feb}, pages={275–282} }
 @article{muhammad_baynes_monteiro-riviere_xia_riviere_2003, title={Absorption through porcine skin exposed to various doses of jet fuel marker components determined with GC-FID using head space SPME fiber.}, volume={72}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000181518501865&KeyUID=WOS:000181518501865}, journal={Toxicological Sciences}, author={Muhammad, F and Baynes, RE and Monteiro-Riviere, NA and Xia, XR and Riviere, JE}, year={2003}, pages={383} }
 @article{jacobs_wester_auletta_ryan_monteiro-riviere_2003, title={Cutaneous toxicity current methods and concepts in safety evaluation and relevance to human exposure.}, volume={72}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000181518500007&KeyUID=WOS:000181518500007}, journal={Toxicological Sciences}, author={Jacobs, AC and Wester, RC and Auletta, CS and Ryan, CA and Monteiro-Riviere, NA}, year={2003}, pages={1–2} }
 @article{monteiro-riviere_chou_riviere_2003, title={Dose-related interleukin-8 release from epidermal keratinocytes after exposure to jet fuel aromatic hydrocarbons.}, volume={26}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV200300446377&KeyUID=BIOSIS:PREV200300446377}, number={Supplement 1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Monteiro-Riviere, N. A. and Chou, C. C. and Riviere, J. E.}, year={2003}, pages={162} }
 @article{monteiro-riviere_van miller_simon_joiner_brooks_riviere_2003, title={In vitro percutaneous absorption of nonylphenol (NP) and nonylphenol ethoxylates (NPE-4 and NPE-9) in isolated perfused skin}, volume={22}, ISSN={["0731-3829"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000182704200001&KeyUID=WOS:000182704200001}, DOI={10.1081/CUS-120019325}, abstractNote={Skin contact with nonylphenol ethoxylates (NPE), a group of widely used surfactants, is the primary source of human exposure. Previous studies have shown that the absorption of NPE through human and animal skin in vitro is limited (<1% over 8 hr) [Monteiro-Riviere et al. Toxicol Indust Health 2000; 16:49–57]. The purpose of this study was to examine the percutaneous absorption of NPE and the chemical precursor, nonylphenol (NP), in the isolated perfused porcine skin flap (IPPSF) model for comparison to the in vitro porcine skin flow through (PSFT) diffusion studies. The IPPSF model is considered to accurately predict absorption of chemicals through human skin. The IPPSF was dosed with 100 μl of 1% 14C ring-labeled NP, 14C ring-labeled NPE-4, or 14C ring-labeled NPE-9 in aqueous polyethylene glycol (PEG-400) solution and perfused for 8 hr. All three chemicals were minimally absorbed, with only approximately 0.1% of the applied dose found in the perfusate over the 8-hr collection. This absorbed material rep...}, number={1-2}, journal={JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY}, author={Monteiro-Riviere, NA and Van Miller, JP and Simon, GS and Joiner, RL and Brooks, J and Riviere, JE}, year={2003}, pages={1–11} }
 @article{riviere_baynes_brooks_yeatts_monteiro-riviere_2003, title={Percutaneous Absorption of Topical N , N -Diethyl- m -Toluamide (Deet): Effects of Exposure Variables and Coadministered Toxicants}, volume={66}, ISSN={1528-7394 1087-2620}, url={http://dx.doi.org/10.1080/15287390306400}, DOI={10.1080/15287390306400}, abstractNote={Exposure to N,N-diethyl-m-toluamide (DEET) commonly occurs in the general population and has been implicated as a contributory factor to the Gulf War Illness. The focus of the present studies was to determine the effect of coexposure factors, potentially encountered in a military environment, that could modulate transdermal flux of topically applied DEET. Factors investigated were vehicle, dose, coexposure to permethrin, low-level sulfur mustard, occlusion, and simultaneous systemic exposure to pyridostigmine bromide and the nerve agent stimulant diisopropylfluorophosphate (DFP). Studies were conducted using the isolated perfused porcine skin flap (IPPSF), with a few mechanistically oriented studies conducted using in vitro porcine skin and silastic membrane diffusion cells. DEET was quantitated using high-performance liquid chromatography. The vehicle-control transdermal DEET flux in the IPPSF was approximately 2 micrograms/cm2/h for both 7.5 and 75% DEET concentrations, a value similar to that reported in humans. DEET absorption was enhanced by coinfusion of pyridostigmine bromide and DFP, by the presence of sulfur mustard, or by dosing under complete occlusion. The greatest increase in baseline flux was fivefold. In vitro diffusion cell studies indicated that silastic membranes had two orders of magnitude greater permeability than porcine skin, and showed vehicle effects on flux that were not detected in the IPPSF. These results suggest that coexposure to a number of chemicals that potentially could be encountered in a military environment may modulate the percutaneous absorption of topically applied DEET beyond that seen for normal vehicles at typically applied concentrations.}, number={2}, journal={Journal of Toxicology and Environmental Health, Part A}, publisher={Informa UK Limited}, author={Riviere, Jim and Baynes, Ronald and Brooks, James and Yeatts, James and Monteiro-Riviere, Nancy}, year={2003}, month={Jan}, pages={133–151} }
 @article{inman_carpenter_briggs_brooks_monteiro-riviere_2003, title={Percutaneous absorption of 2,6-di-tert-butyl-4-nitrophenol (DBNP) in isolated per-fused porcine skin.}, volume={72}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000181518501864&KeyUID=WOS:000181518501864}, journal={Toxicological Sciences}, author={Inman, AO and Carpenter, RL and Briggs, B and Brooks, JD and Monteiro-Riviere, NA}, year={2003}, pages={383} }
 @article{inman_still_jederberg_carpenter_riviere_brooks_monteiro-riviere_2003, title={Percutaneous absorption of 2,6-di-tert-butyl-4-nitrophenol (DBNP) in isolated perfused porcine skin}, volume={17}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000183738100006&KeyUID=WOS:000183738100006}, DOI={10.1016/S0887-2333(03)00015-8}, abstractNote={DBNP (2,6-di-tert-butyl-4-nitrophenol) has been reported as a potential contaminant in submarines. This yellow substance forms when lubrication oil mist containing the antioxidant additive 2,6-di-tert-butylphenol passes through an electrostatic precipitator and is nitrated. Percutaneous absorption of 14C-DBNP was assessed in the isolated perfused porcine skin flap (IPPSF). Four treatments were studied (n=4 flaps/treatment): 40.0 μg/cm2 in 100% ethanol; 40.0 μg/cm2 in 85% ethanol/15% H2O; 4.0 μg/cm2 in 100% ethanol; and 4.0 μg/cm2 in 85% ethanol/15% water. DBNP absorption was minimal across all treatment groups, with the highest absorption detected being only 1.08% applied dose in an aqueous ethanol group. The highest mass of 14C-DBNP absorbed was only 0.5 μg. The majority of the applied dose remained on the surface of the skin. This suggests that there is minimal dermal exposure of DBNP when exposed topically to skin.}, number={3}, journal={TOXICOLOGY IN VITRO}, author={Inman, AO and Still, KR and Jederberg, WW and Carpenter, RL and Riviere, JE and Brooks, JD and Monteiro-Riviere, NA}, year={2003}, month={Jun}, pages={289–292} }
 @article{riviere_baynes_brooks_yeatts_monteiro-riviere_2003, title={Percutaneous absorption of topical N,N-diethyl-m-toluamide (DEET): Effects of exposure variables and coadministered toxicants}, volume={66}, DOI={10.1080/15287390390155796}, number={2}, journal={Journal of Toxicology and Environmental Health. Part A}, author={Riviere, J. E. and Baynes, R. E. and Brooks, J. D. and Yeatts, J. L. and Monteiro-Riviere, N.A.}, year={2003}, pages={133–151} }
 @article{monteiro-riviere_baynes_riviere_2003, title={Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused porcine skin}, volume={183}, ISSN={["0300-483X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000180799100002&KeyUID=WOS:000180799100002}, DOI={10.1016/s0300-483x(02)00421-3}, abstractNote={Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic treatment against organophosphate nerve agent exposure, and were exposed to the insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET). The purpose of this study was to assess the effects of PB to modulate release of inflammatory biomarkers after topical chemical exposure to chemical mixtures containing permethrin and DEET applied in ethanol or water vehicles. Treatments were topically applied to isolated perfused porcine skin flaps (IPPSFs). Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential inflammatory effects after complex mixture application. IPPSFs (n=4/treatment) were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB. Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate low level organophosphate nerve agent exposure. Timed IPPSF venous effluent samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2) release. Effects on TNF-alpha were vehicle dependent. To probe the potential mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these studies suggest that systemic exposure to PB suppressed IL-8 release at multiple time points in two skin model systems. This interaction merits further study.}, number={1-3}, journal={TOXICOLOGY}, author={Monteiro-Riviere, NA and Baynes, RE and Riviere, JE}, year={2003}, month={Feb}, pages={15–28} }
 @article{chou_riviere_monteiro-riviere_2003, title={The cytotoxicity of jet fuel aromatic hydrocarbons and dose-related interleukin-8 release from human epidermal keratinocytes}, volume={77}, ISSN={0340-5761 1432-0738}, url={http://dx.doi.org/10.1007/s00204-003-0461-z}, DOI={10.1007/s00204-003-0461-z}, number={7}, journal={Archives of Toxicology}, publisher={Springer Science and Business Media LLC}, author={Chou, C. C. and Riviere, J. E. and Monteiro-Riviere, N. A.}, year={2003}, month={Jul}, pages={384–391} }
 @article{lin_selim_shea_grichnik_omar_monteiro-riviere_pinnell_2003, title={UV photoprotection by combination topical antioxidants vitamin C and vitamin E}, volume={48}, ISSN={["0190-9622"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000183594900009&KeyUID=WOS:000183594900009}, DOI={10.1067/mjd.2003.425}, abstractNote={Background: Virtually all plants and animals protect themselves from the sun using vitamins C and E. Objective: The purpose of this study was to see if a combination of topical vitamins C and E is better for UV protection to skin than an equivalent concentration of topical vitamin C or E alone. Methods: We developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1% α-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5× minimal erythema dose) control- and antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter. On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and thymine dimers. Results: The combination of 15% L-ascorbic acid and 1% α-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% α-tocopherol alone also was protective but the combination was superior. Application during 4 days provided progressive protection that yielded an antioxidant protection factor of 4-fold. In addition, the combination of vitamins C and E provided protection against thymine dimer formation. Conclusion: Appreciable photoprotection can be obtained from the combination of topical vitamins C and E. We suggest that these natural products may protect against skin cancer and photoaging. (J Am Acad Dermatol 2003;48:866-74.)}, number={6}, journal={JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY}, author={Lin, JY and Selim, MA and Shea, CR and Grichnik, JM and Omar, MM and Monteiro-Riviere, NA and Pinnell, SR}, year={2003}, month={Jun}, pages={866–874} }
 @article{chou_riviere_monteiro-riviere_2002, title={Differential relationship between the carbon chain length of jet fuel aliphatic hydrocarbons and their ability to induce cytotoxicity vs. interleukin-8 release in human epidermal keratinocytes}, volume={69}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000177996800025&KeyUID=WOS:000177996800025}, DOI={10.1093/toxsci/69.1.226}, abstractNote={Jet fuels are complex mixtures of hydrocarbons known to cause dermal toxicity and to increase the release of proinflammatory cytokines by human epidermal keratinocytes (HEK). However, the dermatotoxic effects of individual hydrocarbons remain unclear. Since aliphatic hydrocarbons make up more than 80% of the hydrocarbons formulated in jet fuels, the objective of this study was to assess acute cytotoxicity and IL-8 release induced by individual aliphatic hydrocarbons without a vehicle. Ten aliphatic hydrocarbons with carbon (C) chain lengths ranging from 6 to 16 were dosed neat on HEK grown on 96-well plates. Acute exposure (1, 5, and 15 min) to aliphatic hydrocarbons significantly increased HEK mortality such that the increase in cytotoxicity corresponded with the decrease in carbon chain length. Extended exposure time did not increase cytotoxicity significantly until 15 min of exposure by short-chain hydrocarbons (C < or = 11). There were differences between the aliphatic hydrocarbons with respect to their effects on IL-8 release. IL-8 concentration was increased significantly by 3- to 10-fold, with the highest increase found after exposure to hydrocarbons in the C9-C13 range. These studies indicated that individual aliphatic hydrocarbons are toxic to HEK cells and are capable of inducing proinflammatory cytokines. Higher cytotoxicity by shorter-chain aliphatic hydrocarbons did not correlate to increased ability to stimulate IL-8 release, which peaked at mid-chain lengths, suggesting a different structure-activity relationship for these two toxicological endpoints in keratinocyte cell cultures.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Chou, CC and Riviere, JE and Monteiro-Riviere, NA}, year={2002}, month={Sep}, pages={226–233} }
 @article{riviere_monteiro-riviere_baynes_2002, title={Gulf War related exposure factors influencing topical absorption of 14C-permethrin}, volume={135}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/s0378-4274(02)00239-4}, DOI={10.1016/S0378-4274(02)00239-4}, abstractNote={Topical exposure to permethrin has often been implicated as a mitigating factor in the illnesses reported in Gulf War veterans. These studies were designed to assess the effect of co-exposure to low level sulfur mustard, JP-8 jet fuel, N,N-diethyl-m-toluamide (DEET) and fabric occlusion on the percutaneous absorption and skin disposition of topically applied 14C-permethrin (40 μg/cm2) in the isolated perfused porcine skin flap (IPPSF) model. Extent of dermal absorption in vehicle controls in the IPPSF was comparable to literature values for humans. These studies demonstrated a two-fold increased 14C-permethrin percutaneous absorption and almost three-fold increased penetration when JP-8 was present, compared to a one-third decreased permethrin flux in the presence of sulfur mustard. Complete occlusion slightly increased 14C-permethrin absorption, while occlusion with fabric showed no significant effect. A previously noted effect of DEET to inhibit permethrin absorption was still seen in the presence of sulfur mustard exposure. These studies suggest that co-exposure to JP-8 or sulfur mustard may modulate transdermal flux of 14C-permethrin. However, the JP-8 increase in absorption and penetration was less than the five-fold increase previously seen with arterial infusion of pyridostigmine bromide and diisopropylfluorophosphate in the IPPSF. The toxicologic significance of this moderate increase in permethrin absorption remains unclear.}, number={1-2}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Riviere, Jim E and Monteiro-Riviere, Nancy A and Baynes, Ronald E}, year={2002}, month={Sep}, pages={61–71} }
 @article{baynes_monteiro-riviere_riviere_2002, title={Pyridostigmine bromide modulates the dermal disposition of [C-14]permethrin}, volume={181}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000176540200002&KeyUID=WOS:000176540200002}, DOI={10.1006/taap.2002.9412}, abstractNote={The cause of the Gulf War Syndrome may be related to soldiers being exposed to insecticides (e.g., permethrin (P)), insect repellents (e.g., N,N-diethyl-m-toluamide (DEET)), an organophosphate nerve agent simulant (e.g., diisopropyl fluorpohosphate (DFP)), and/or prophylactic treatment (e.g., pyridostigmine bromide (PB)) against potential nerve gas attacks. The purpose of this study was to assess the dermal disposition of [14C]permethrin in ethanol or ethanol:water (3:2) in the isolated perfused porcine skin flap (IPPSF) model with simultaneous dermal exposure to DEET or DFP. These IPPSFs were also simultaneously perfused arterially with or without PB, DFP, or DFP + PB. The results indicated that DFP + PB significantly increased [14C]permethrin absorption compared to controls (1.06% dose vs 0.14% dose). PB significantly increased [14C]permethrin disposition in the stratum corneum (SC) in aqueous mixtures only (9.40 vs 3.35% dose), while topical DEET or topical DFP reduced [14C]permethrin levels in the SC especially in nonaqueous mixtures. PB also significantly enhanced [14C]permethrin penetration into all skin tissues and perfusate in aqueous mixtures, while DEET reversed this effect. PB appeared to influence [14C]permethrin disposition in flowthrough diffusion cells, suggesting that the mechanism of this interaction may be associated predominantly with epidermal permeability, although muscarinic effects in the vasculature in IPPSFs should not be ruled out and requires further investigation. These experiments suggest that intraarterial perfusion of PB and/or DFP and topical application of DFP or DEET can alter the disposition of [14C]permethrin in skin and possibly its bioavailability in soldiers simultaneously exposed to these chemicals.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2002}, month={Jun}, pages={164–173} }
 @article{rhyne_pirone_riviere_monteiro-riviere_2002, title={The use of enzyme histochemistry in detecting cutaneous toxicity of three topically applied jet fuel mixtures}, volume={12}, DOI={10.1080/10517230252875877}, number={1}, journal={Toxicology Mechanisms and Methods}, author={Rhyne, B. N. and Pirone, J. R. and Riviere, J. E. and Monteiro-Riviere, N.A.}, year={2002}, pages={17–34} }
 @article{rhyne_pirone_riviere_monteiro-riviere_2002, title={The use of enzyme histochemistry in detecting cutaneous toxicity of three topically applied jet fuel mixtures}, volume={12}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000175434900002&KeyUID=WOS:000175434900002}, DOI={10.1080/1537-650291895748}, number={1}, journal={Toxicology Mechanisms and Methods}, author={Rhyne, BN and Pirone, JR and Riviere, JE and Monteiro-Riviere, NA}, year={2002}, pages={17–34} }
 @article{allen_riviere_monteiro-riviere_2001, title={Analysis of interleukin-8 release from normal human epidermal keratinocytes exposed to aliphatic hydrocarbons: delivery of hydrocarbons to cell cultures via complexation with alpha-cyclodextrin}, volume={15}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000172508300009&KeyUID=WOS:000172508300009}, DOI={10.1016/S0887-2333(01)00075-3}, abstractNote={While inhalation exposures represent the predominant route for jet fuel toxicity, increased concern has been placed on topical exposures due to reports of severe contact dermatitis among military personnel. All three of the predominant aviation fuels currently used by the commercial and military sectors have been demonstrated experimentally to induce the production of interleukin-8 (IL-8), a proinflammatory cytokine, in normal human epidermal keratinocytes (NHEK). The objective of this study was to examine the effects of individual hydrocarbon components found in these fuels on IL-8 production by NHEK. In order to circumvent the extreme hydrophobicity of these compounds, inclusion complexes were formed between alpha-cyclodextrin/aliphatic hydrocarbons by adding 2 mM hydrocarbons to 4 mM alpha-cyclodextrin. NHEK were exposed to four aliphatic hydrocarbons (undecane, dodecane, tridecane, hexadecane) for 24 h at concentrations of 7.8-500 microM. These hydrocarbons caused a peak in IL-8 release at a concentration of 31.2 microM, with the exception of dodecane which peaked at 62.5 microM. Subtoxic concentrations of the aliphatic hydrocarbons were those < 62.5 microM. These studies demonstrate that the etiology of proinflammatory cytokine expression due to jet fuel exposure may be due in large part to the aliphatic hydrocarbon components. Furthermore, these studies provide additional evidence that hydrocarbons can be successfully delivered to cells in culture by encapsulating them in cyclodextrin inclusion complexes.}, number={6}, journal={TOXICOLOGY IN VITRO}, author={Allen, DG and Riviere, JE and Monteiro-Riviere, NA}, year={2001}, month={Dec}, pages={663–669} }
 @article{allen_riviere_monteiro-riviere_2001, title={Cytokine induction as a measure of cutaneous toxicity in primary and immortalized porcine keratinocytes exposed to jet fuels, and their relationship to normal human epidermal keratinocytes}, volume={119}, ISSN={["1879-3169"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000167667000005&KeyUID=WOS:000167667000005}, DOI={10.1016/S0378-4274(00)00316-7}, abstractNote={The purpose of this study was to identify biomarkers of toxicity in primary porcine keratinocytes (PKC) and an immortalized porcine keratinocyte cell line (MSK3877) exposed to jet fuels Jet A, JP-8, and JP-8+100. Cells were exposed to 0.1% jet fuels and assayed for interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) mRNA using the TaqMan real time quantitative reverse transcriptase PCR assay. IL-8 and TNF-alpha protein release was measured using an ELISA. PKC exposed to jet fuels caused a slight upregulation of TNF-alpha mRNA at early time points, but no significant differences in TNF-alpha protein production were detected. IL-8 mRNA was increased at 4 h following exposure, and IL-8 protein was increased at 8 h. In MSK 3877 cells, jet fuels were shown to increase the production and expression of TNF-alpha mRNA and protein at 30 min and 1 h following exposure, respectively. IL-8 mRNA was only slightly induced compared to control. IL-8 protein release was suppressed by jet fuel exposure. These results were compared with those of a previous study in our laboratory to evaluate the utility of using porcine cells in lieu of normal human epidermal keratinocytes (NHEK). Similarities exist between PKC and NHEK with respect to both TNF-alpha and IL-8 production. The expression profile of TNF-alpha in MSK3877 cells mimics that of NHEK. In contrast, the profile of IL-8 expression opposes that of PKC and NHEK. These results suggest that porcine keratinocytes are susceptible to jet fuel toxicity. However, the responses of immortalized cells may vary from those of PKC and NHEK necessitating cautious interpretation of such data.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Allen, DG and Riviere, JE and Monteiro-Riviere, NA}, year={2001}, month={Mar}, pages={209–217} }
 @book{baynes_riviere_smith_monteiro-riviere_freeman_2001, title={Dermal absorption cutting fluids}, journal={Annual report 1R010H03669-01A2}, author={Baynes, R. E. and Riviere, J. E. and Smith, C. E. and Monteiro-Riviere, N. A. and Freeman, B.}, year={2001}, month={May} }
 @inbook{monteiro-riviere_2001, title={Dermatotoxicology}, volume={21}, ISBN={0471333344}, booktitle={Introduction to biochemical toxicology (3rd ed.)}, publisher={NY: John Wiley & Sons}, author={Monteiro-Riviere, N. A.}, editor={E. Hodgson and Smart, R.Editors}, year={2001}, pages={509–537} }
 @article{monteiro-riviere_inman_mak_wertz_riviere_2001, title={Effect of selective lipid extraction from different body regions on epidermal barrier function}, volume={18}, ISSN={["0724-8741"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000170027500014&KeyUID=WOS:000170027500014}, DOI={10.1023/A:1010944529387}, number={7}, journal={PHARMACEUTICAL RESEARCH}, author={Monteiro-Riviere, NA and Inman, AO and Mak, V and Wertz, P and Riviere, JE}, year={2001}, month={Jul}, pages={992–998} }
 @article{monteiro-riviere_inman_riviere_2001, title={Effects of short-term high-dose and low-dose dermal exposure to Jet A, JP-8 and JP-8 + 100 jet fuels}, volume={21}, ISSN={0260-437X 1099-1263}, url={http://dx.doi.org/10.1002/jat.785}, DOI={10.1002/jat.785}, abstractNote={Occupational and environmental exposures to jet fuel recently have become a source of public and regulatory concern. This study investigates the cutaneous toxicity of three fuels used in both civilian and military aircraft. Pigs, an accepted animal model for human skin, were exposed to low-dose (25 microl or 7.96 microl cm(-2)) or high-dose (335 microl or 67 microl cm(-2)) Jet A, JP-8 and JP-8 + 100 under occluded (Hill Top) chamber or cotton fabric) and non-occluded conditions for 5 h, 24 h and 5 days. To mimic occupational exposure, fuel-soaked fabric (high dose) was used. Erythema, edema, transepidermal water loss (TEWL) and epidermal thickness were quantified. High-dose fabric occluded sites had slight erythema at 5 h with increased erythema at 5 days. No erythema was noted in any of the occluded (Hill Top) or non-occluded sites at any of the time points. Morphological assessments depicted slight intracellular epidermal edema at all time points. An increase in change in TEWL (DeltaTEWL) was observed at the 5-h and 24-h fabric and Hill Top occluded treatments and a decrease at the 5-day fabric and Hill Top occluded sites. In all 5-day JP-8 + 100 fabric sites, intracorneal microabscesses filled with inflammatory cells were observed. Epidermal thickening was significant (P < 0.05) in all three jet fuels at the high-dose fabric sites, with JP-8 + 100 being the thickest. The epidermal rete peg depth increased significantly (P < 0.05) at 24 h and 5 days with Jet A, JP-8, and JP-8 + 100 in the fabric sites. No significant differences were noted in the 5-day non-occluded fabric and Hill Top occluded and non-occluded sites. Jet fuel JP-8 + 100 tended to have the greatest proliferative response. In conclusion, the high-dose fabric-soaked exposure at 5 days to Jet A, JP-8 and JP-8 + 100 fuels caused the greatest increase in cutaneous erythema, edema, epidermal thickness and rete peg depth compared with high-dose non-occluded or low-dose exposure under Hill Top occluded and non-occluded conditions.}, number={6}, journal={Journal of Applied Toxicology}, publisher={Wiley}, author={Monteiro-Riviere, Nancy and Inman, Alfred and Riviere, Jim}, year={2001}, pages={485–494} }
 @article{monteiro-riviere_inman_jackson_dunn_dimond_2001, title={Efficacy of topical phenol decontamination strategies on severity of acute phenol chemical burns and dermal absorption: in vitro and in vivo studies in pig skin}, volume={17}, ISSN={["0748-2337"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000179568300001&KeyUID=WOS:000179568300001}, DOI={10.1191/0748233701th095oa}, abstractNote={Pure phenol is colorless and used in the manufacture of phenolic resins, plastics, explosives, fertilizers, paints, rubber, textiles, adhesives, pharmaceuticals, paper, soap, and wood preservatives. The purpose of this study was to compare the efficacy of several phenol decontamination strategies following dermal exposure using the pig as a model for human exposure, and then assess the effect of the two best treatments on phenol absorption in the isolated perfused porcine skin flap (IPPSF). Six anesthetized Yorkshire pigs were exposed to 89% aqueous phenol for 1 min using Hilltop chambers (10 skin sites/pig; 400 microl/site). Exposure to phenol was followed by one of 10 different decontamination procedures: 1-, 5-, 15-, and 30-min water wash; Ivory soap solution; polyethylene glycol (PEG 400); PEG 400/industrial methylated spirits (IMS); PEG 400/ethanol (EtOH); polyvinyl pyrrolidone (PVP)/70% isopropanol (IPA); and 70% IPA. For each of the last five strategies, 1-min treatment washes were repeatedly alternated with 1-min water washes for a total of 15 min. Evaluation was based on scoring of erythema, edema, and histological parameters such as intracellular and intercellular epidermal edema, papillary dermal edema, perivascular infiltrates, pyknotic stratum basale cells, and epidermal-dermal separation. It was concluded that PEG 400 and 70% IPA were superior to the other treatments investigated and equally efficacious in the reduction of phenol-induced skin damage. In addition, phenol absorption was assessed utilizing the two most effective in vivo treatments in the IPPSF. The assessment of percutaneous absorption of phenol found the PEG 400, 70% IPA, and 15-min water treatments significantly (P < 0.05) reduced phenol absorption relative to no treatment.}, number={4}, journal={TOXICOLOGY AND INDUSTRIAL HEALTH}, author={Monteiro-Riviere, NA and Inman, AO and Jackson, H and Dunn, B and Dimond, S}, year={2001}, month={May}, pages={95–104} }
 @article{inman_olivry_dunston_monteiro-riviere_gatto_2001, title={Electron microscopic observations of stratum corneum intercellular lipids in normal and atopic dogs}, volume={38}, ISSN={["1544-2217"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000172330100017&KeyUID=WOS:000172330100017}, DOI={10.1354/vp.38-6-720}, abstractNote={The barrier function of mammalian skin is maintained by intercellular stratum corneum lipids. In human patients with atopic dermatitis, an abnormal lipid barrier results in dry skin and increased transepidermal water loss. At this time, it is not known if a defective lipid barrier is present in atopic dogs. Normal and atopic canine skin were postfixed in ruthenium tetroxide and studied using transmission electron microscopy to determine structural differences within stratum corneum lipids. Intercellular lipid lamellae were graded on a semiquantitative scale. The deposition of stratum corneum lipid lamellae in atopic canine skin appeared markedly heterogeneous compared with that seen in normal canine skin. When present, the lamellae often exhibited an abnormal structure. The continuity and thickness of the intercellular lipid lamellae were significantly less in nonlesional atopic than in normal canine skin. These preliminary observations suggest that the epidermal lipid barrier is defective in atopic canine skin. Additional studies are needed to further characterize the biochemical defect and to possibly correct it with nutritional and/or pharmacologic intervention.}, number={6}, journal={VETERINARY PATHOLOGY}, author={Inman, AO and Olivry, T and Dunston, SM and Monteiro-Riviere, NA and Gatto, H}, year={2001}, month={Nov}, pages={720–723} }
 @inbook{monteiro-riviere_argenzio_2001, title={The excretory system}, volume={13}, booktitle={Biology of the domestic pig}, publisher={Ithaca, NY: Comstock Pub. Associates/Cornell University Press}, author={Monteiro-Riviere, N. A. and Argenzio, R. A.}, editor={W. G. Pond, H. J. MersmannEditor}, year={2001}, pages={585–624} }
 @inbook{monteiro-riviere_2001, title={The integument}, volume={14}, ISBN={0801434688}, booktitle={Biology of the domestic pig}, publisher={Comstock Publishing Assoc.}, author={Monteiro-Riviere, N. A.}, editor={W. G. Pond and Mersmann, H. J.Editors}, year={2001}, pages={625–652} }
 @article{pinnell_yang_omar_riviere_debuys_walker_wang_levine_2001, title={Topical L-ascorbic acid: Percutaneous absorption studies}, volume={27}, ISSN={["1524-4725"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000167170000008&KeyUID=WOS:000167170000008}, DOI={10.1046/j.1524-4725.2001.00264.x}, abstractNote={Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults.This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir.L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery.L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid.Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics.}, number={2}, journal={DERMATOLOGIC SURGERY}, author={Pinnell, SR and Yang, HS and Omar, M and Riviere, NM and DeBuys, HV and Walker, LC and Wang, YH and Levine, M}, year={2001}, month={Feb}, pages={137–142} }
 @article{pinnell_debuys_omar_walker_monteiro-riviere_dawson_waalkes_2001, title={Topical zinc sulphate - An antioxidant for skin}, volume={117}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000170668300728&KeyUID=WOS:000170668300728}, number={2}, journal={Journal of Investigative Dermatology}, author={Pinnell, S and DeBuys, H and Omar, M and Walker, L and Monteiro-Riviere, N and Dawson, T and Waalkes, M}, year={2001}, pages={506} }
 @article{shea_selim_monteiro-riviere_pinnell_2001, title={Ultraviolet A exposure induces irradiance-dependent vascular injury in pig skin}, volume={117}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000170668300736&KeyUID=WOS:000170668300736}, number={2}, journal={Journal of Investigative Dermatology}, author={Shea, C and Selim, M and Monteiro-Riviere, N and Pinnell, S}, year={2001}, pages={507} }
 @article{riviere_smith_budsaba_brooks_olajos_salem_monteiro-riviere_2001, title={Use of methyl salicylate as a simulant to predict the percutaneous absorption of sulfur mustard}, volume={21}, ISSN={["1099-1263"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000167916500002&KeyUID=WOS:000167916500002}, DOI={10.1002/jat.718}, abstractNote={Exposure to chemical vesicants such as sulfur mustard (HD) continues to be a threat to military forces requiring protectant strategies to exposure to be evaluated. Methyl salicylate (MS) has historically been the simulant of choice to assess HD exposure. The purpose of this study was to compare the percutaneous absorption and skin deposition of MS to HD in the isolated perfused porcine skin flap (IPPSF). The HD data were obtained from a previously published study in this model wherein 400 microg cm(-2) of ](14)C[-MS or ](14)C[-HD in ethanol were topically applied to 16 IPPSFs and experiments were terminated at 2, 4 or 8 h. Perfusate was collected at increasing time intervals throughout perfusion. Radioactivity was determined in perfusate and skin samples. Perfusate flux profiles were fitted to a bi-exponential model Y(t) = A(e(-bt) - e(-dt)) and the area under the curve (AUC), peak flux and time to peak flux were determined. Sulfur mustard had more pronounced and rapid initial flux parameters (P < 0.05). The AUCs determined from observed and model-predicted parameters were not statistically different, although the mean HD AUC was 40--50% greater than MS. The HD skin and fat levels were up to twice those seen with MS, but had lower stratum corneum and residual skin surface concentrations (P < 0.05). Compared with other chemicals studied in this model, HD and MS cutaneous disposition were very similar, supporting the use of MS as a dermal simulant for HD exposure.}, number={2}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Riviere, JE and Smith, CE and Budsaba, K and Brooks, JD and Olajos, EJ and Salem, H and Monteiro-Riviere, NA}, year={2001}, pages={91–99} }
 @inbook{monteiro-riviere_2000, title={Apparato tegumentario}, booktitle={Istologia e anatomia microscopica veterinaria (2a ed.)}, publisher={Milano: Casa Editrice Ambrosiana}, author={Monteiro-Riviere, N. A.}, editor={H. D. Dellmann, J. A. Eurell and Bortolami, R.Editors}, year={2000}, pages={408–444} }
 @article{monteiro-riviere_inman_2000, title={Characterization of sulfur mustard-induced toxicity by enzyme histochemistry in porcine skin}, volume={10}, ISSN={["1051-7235"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033671104&partnerID=MN8TOARS}, DOI={10.1080/10517230050083366}, abstractNote={The isolated perfused porcine skin flap (IPPSF) has been validated as an invitro model to study the cutaneous toxicology of numerous compounds, including sulfur mustard (bis(2-chloroethyl)sulfide; HD). Enzyme histochemistry of alkaline phosphatase (ALP), acid phosphatase (ACP), and nonspecific esterase (NSE) was performed on skin dosed with HD from the IPPSF. Flaps from the dose response study were treated with 10.0 (n = 5), 5.0 (n = 4), 2.5 (n = 4), 1.25 (n = 3), 0.5 (n = 3), and 0.2 (n = 4) mg/mL HD in absolute ethanol (EtOH) and perfused for 8 h. Flaps from the time response study were treated with 10.0 mg/mL HD in EtOH or the EtOH vehicle and perfused for 1 (n = 4), 3 (n = 4), 5 (n = 4), and 8 h (n = 3). In the time response study, significant differences (SD) (p <. 05) were found in the stratum basale with ALP (3 h HD SD from the 3 h EtOH; 3 h HD SD from the 8 h HD), ACP (3 h HD SD from the 3 h EtOH), and NSE (8 h HD SD from the 8 h EtOH); in the stratum spinosum with NSE (1 h HD SD from the 1 h EtOH...}, number={2}, journal={TOXICOLOGY METHODS}, author={Monteiro-Riviere, NA and Inman, AO}, year={2000}, pages={127–142} }
 @article{monteiro-riviere_miller_simon_joiner_brooks_riviere_2000, title={Comparative in vitro percutaneous absorption of nonylphenol and nonylphenol ethoxylates (NPE-4 and NPE-9) through human, porcine and rat skin}, volume={16}, DOI={10.1191/074823300678827654}, number={2}, journal={Toxicology and Industrial Health}, author={Monteiro-Riviere, N.A. and Miller, J. P. Van and Simon, G. and Joiner, R. L. and Brooks, J. D. and Riviere, J. E.}, year={2000}, pages={49–57} }
 @article{monteiro-riviere_van miller_simon_joiner_brooks_riviere_2000, title={Comparative in vitro percutaneous absorption of nonylphenol and nonylphenol ethoxylates (NPE-4 and NPE-9) through human, porcine and rat skin}, volume={16}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000086751400001&KeyUID=WOS:000086751400001}, DOI={10.1177/074823370001600201}, abstractNote={The purpose of this study was to assess the percutaneous absorption of nonylphenol (NP) and the nonylphenol ethoxylates, NPE-4 and NPE-9, in human, porcine and rat skin. In vitro studies with the NPEs were conducted for 8 h in flowthrough diffusion cells using topical solutions of 0.1, 1.0 and 10% in PEG-400 or 1% in water (NPE-9 only). NP absorption was assessed as a 1% solution in PEG-400. All compounds were 14C ring-labeled and radioactivity in perfusate was monitored over time. Skin deposition was measured at the termination of the experiment. Absorption into perfusate and total penetration (compound absorbed plus compound sequestered in skin) were calculated. Absorption of NPE-4, NPE-9 and NP was similar across all species at less than 1% of the applied dose over 8 h. Penetration was generally below 5% of applied dose, the majority located in the stratum corneum. In all species and for both NPEs, the fraction of dose absorbed was highest for the lowest applied dose. Absorptions expressed as actual mass absorbed over 8 h were similar (approximately 0.3 microg/cm2) across all concentrations. Penetration, but not absorption, was greater from a water vehicle compared to a PEG-400 vehicle, particularly in rat skin. These studies suggest that NP, NPE-4 and NPE-9 were minimally absorbed across skin from all three species. Fractional absorption was concentration-dependent, making the actual absorbed flux constant across all doses.}, number={2}, journal={Toxicology and Industrial Health}, author={Monteiro-Riviere, NA and Van Miller, JP and Simon, G and Joiner, RL and Brooks, JD and Riviere, JE}, year={2000}, pages={49–57} }
 @article{allen_riviere_monteiro-riviere_2000, title={Identification of early biomarkers of inflammation produced by keratinocytes exposed to jet fuels Jet A, JP-8, and JP-8(100)}, volume={14}, ISSN={["1099-0461"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000088822300001&KeyUID=WOS:000088822300001}, DOI={10.1002/1099-0461(2000)14:5<231::AID-JBT1>3.0.CO;2-K}, abstractNote={The purpose of this study was to identify biomarkers of inflammation in normal human epidermal keratinocytes (NHEK) exposed to three jet fuel mixtures, Jet A, JP8, and JP8(100). NHEK were treated over 24 hours with 0.1% jet fuels, and mRNA production and protein release of two proinflammatory cytokines, IL-8 and TNF-alpha, were determined. Using an enzyme-linked immunosorbent assay (ELISA), NHEK were found to release both TNF-alpha and IL-8 in response to exposure to all three jet fuels. IL-8 release was noted within 8 hours and continued to rise through 24 hours compared to controls. Maximal levels of TNF-alpha release were seen at 4 hours and decreased in a time-dependent manner, although these levels remained above control levels at all time points assayed. mRNA for IL-8 was elevated 4 hours following exposure to the fuels, which was detected via a quantitative competitive reverse transcriptase-polymerase chain reaction (RT-PCR). mRNA for TNF-alpha was detected at all time points assayed but was not quantified. These results demonstrate that jet fuels induce the production and release of proinflammatory cytokines in NHEK and thus create the potential for chronic inflammation, which may contribute to the development or progression of disease states in the skin.}, number={5}, journal={JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY}, author={Allen, DG and Riviere, JE and Monteiro-Riviere, NA}, year={2000}, pages={231–237} }
 @article{monteiro-riviere_allen_riviere_2000, title={Use of the pig as a model to assess cutaneous toxicity and inflammation of jet fuels}, volume={23}, number={Suppl. 1 CD}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Monteiro-Riviere, N. A. and Allen, D. A. and Riviere, J. E.}, year={2000}, pages={F12} }
 @article{allen_monteiro-riviere_1999, title={Alteration of cytokeratin expression following transdermal lidocaine hydrochloride iontophoresis}, volume={16}, ISSN={["0724-8741"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000082536800025&KeyUID=WOS:000082536800025}, DOI={10.1023/A:1018979831854}, number={9}, journal={PHARMACEUTICAL RESEARCH}, author={Allen, DG and Monteiro-Riviere, NA}, year={1999}, month={Sep}, pages={1487–1490} }
 @article{riviere_brooks_monteiro-riviere_budsaba_smith_1999, title={Dermal Absorption and Distribution of Topically Dosed Jet Fuels Jet-A, JP-8, and JP-8(100)}, volume={160}, ISSN={0041-008X}, url={http://dx.doi.org/10.1006/taap.1999.8744}, DOI={10.1006/taap.1999.8744}, abstractNote={Dermal exposure to jet fuels has received increased attention with the recent release of newer fuels with novel performance additives. The purpose of these studies was to assess the percutaneous absorption and cutaneous disposition of topically applied (25 μl/5 cm2) neat Jet-A, JP-8, and JP-8(100) jet fuels by monitoring the absorptive flux of the marker components 14C naphthalene and 3H dodecane simultaneously applied nonoccluded to isolated perfused porcine skin flaps (IPPSF) (n = 4). Absorption of 14C hexadecane was estimated from JP-8 fuel. Absorption and disposition of naphthalene and dodecane were also monitored using a nonvolatile JP-8 fraction reflecting exposure to residual fuel that might occur 24 h after a jet fuel spill. In all studies, perfusate, stratum corneum, and skin concentrations were measured over 5 h. Naphthalene absorption had a clear peak absorptive flux at less than 1 h, while dodecane and hexadecane had prolonged, albeit significantly lower, absorption flux profiles. Within JP-8, the rank order of absorption for all marker components was (mean ± SEM % dose) naphthalene (1.17 ± 0.07) > dodecane (0.63 ± 0.04) > hexadecane (0.18 ± 0.08). In contrast, deposition within dosed skin showed the reverse pattern. Naphthalene absorption into perfusate was similar across all fuel types, however total penetration into and through skin was highest with JP-8(100). Dodecane absorption and total penetration was greatest from JP-8. Absorption of both markers from aged JP-8 was lower than other fuels, yet the ratio of skin deposition to absorption was greatest for this treatment group. In most exposure scenarios, absorption into perfusate did not directly correlate to residual skin concentrations. These studies demonstrated different absorption profiles for the three marker compounds, differential effects of jet fuel types on naphthalene and dodecane absorption, and uncoupling of perfusate absorption from skin disposition.}, number={1}, journal={Toxicology and Applied Pharmacology}, publisher={Elsevier BV}, author={Riviere, Jim E. and Brooks, James D. and Monteiro-Riviere, Nancy A. and Budsaba, Kamon and Smith, Charles E.}, year={1999}, month={Oct}, pages={60–75} }
 @article{monteiro-riviere_inman_babin_casillas_1999, title={Immunohistochemical characterization of the basement membrane epitopes in bis(2-chloroethyl) sulfide-induced toxicity in mouse ear skin}, volume={19}, ISSN={["1099-1263"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000082883800003&KeyUID=WOS:000082883800003}, DOI={10.1002/(SICI)1099-1263(199909/10)19:5<313::AID-JAT582>3.0.CO;2-X}, abstractNote={Sulfur mustard (bis(2-chloroethyl) sulfide (HD)), a potent cutaneous vesicant and bifunctional alkylating agent, produces significant time-dependent histopathological changes in the skin of the mouse. The right ears of male CD1 mice were exposed topically to 5.0 μl of 195 mM (0.16 mg) HD in dichloromethane and harvested at 6, 12, 18 and 24 h. The left ear control was dosed with 5.0 μl of dichloromethane. In all controls and HD-treated mouse ear, moderate immunofluorescence staining was seen at the epidermal–dermal junction with bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA) and laminin (Lam), and light staining was observed with bullous pemphigoid 180 (BP180), fibronectin (Fn) and type IV collagen (Coll IV). Mouse anti-human monoclonal antibodies for GB3, L3d and 19-DEJ-1 (Uncein) did not cross-react. In microvesicles, BP, BP180 and Fn showed areas of light focal epidermal staining and homogeneous dermal staining, and EBA, Lam and Coll IV showed moderate dermal staining. Both BP and Fn exhibited weak, inconsistent staining with time. Immunoelectron microscopy (IEM) revealed similar results, with an increase in cell damage from 6 to 24 h, which corresponded to a decrease in staining intensity. Cell proliferation, expressed as the growth fraction of proliferating cell nuclear antigen (PCNA), showed an increase in cell damage. The growth fraction was lower in the inner ear and showed time-dependent differences. The immunofluorescence and IEM results indicate that HD causes an undulating inconsistent separation in the uppermost lamina lucida with focal cleavage into the lower portion of the basal keratinocytes just above the plasma membrane. Although this pattern of separation differs from other in vivo models in which the split occurs exclusively within the lamina lucida, this should not preclude its role as a screening model to study the effects and development of specific prophylactic and therapeutic strategies. Copyright © 1999 John Wiley & Sons, Ltd.}, number={5}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Monteiro-Riviere, NA and Inman, AO and Babin, MC and Casillas, RP}, year={1999}, pages={313–328} }
 @inproceedings{weaver_zewert_pliquett_vanbever_gowrshankar_herndon_martin_vaughan_ilic_handwerker_et al._1999, title={Pathway-enlarging molecules for skin electroporation: The possibility of macromolecule delivery with minimal side effects}, booktitle={Proceedings of the 6th Conference on Perspectives in Percutaneous Penetration}, publisher={Cardiff: STS Publishing}, author={Weaver, J. C. and Zewert, T. E. and Pliquett, U. F. and Vanbever, R. and Gowrshankar, T. R. and Herndon, T. O. and Martin, G. T. and Vaughan, T. E. and Ilic, L. and Handwerker, J. and et al.}, year={1999} }
 @inbook{monteiro riviere_riviere_1999, place={San Diego, CA}, title={Skin Toxicology}, ISBN={9780124732704 9780080543116 9781281028853}, DOI={10.1016/b978-012473270-4/50077-8}, abstractNote={Publisher Summary
This chapter depicts how anatomical structures within the skin can contribute and influence barrier function by providing an overview of the structure and function of the skin, viewed from a multifaceted perspective. The primary function of the skin is to act as a barrier to the external environment. There has also been a surge of interest in the skin as a target organ due in part to the fact that it is experimentally accessible, directly interfaces with the environment, and is an important route of entry for a myriad of environmental toxins. Recent developments in percutaneous absorption and dermal toxicology have considered how anatomical factors may affect the barrier function, thereby altering the rate of absorption. It is the purpose of this chapter to provide an overview of the general principles of percutaneous penetration, metabolism, and cutaneous responses to specific chemicals. In addition, the mechanisms of direct irritation and sensitization are discussed to provide a basis for selecting appropriate biomarkers for evaluating dermal toxicity.}, booktitle={Toxicology}, publisher={Academic Press}, author={Monteiro Riviere, N and Riviere, J}, editor={Marquardt, H. and Schafer, S. and McClellan, R. and Welsch, F.Editors}, year={1999}, pages={439–457} }
 @inproceedings{monteiro-riviere_inman_babin_casillas_1998, title={Assessment of epidermal-dermal junction epitopes in the mouse ear vesicant model}, booktitle={Proceedings of the 1998 Medical Defense Bioscience Review}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={Monteiro-Riviere, N. A. and Inman, A. O. and Babin, M. C. and Casillas, R. P.}, year={1998}, pages={1–13} }
 @article{olivry_fine_dunston_chasse_tenorio_monteiro-riviere_chen_woodley_1998, title={Canine epidermolysis bullosa acquisita: circulating autoantibodies target the aminoterminal noncollagenous (NC1) domain of collagen VII in anchoring fibrils}, volume={9}, ISSN={["0959-4493"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000073123800004&KeyUID=WOS:000073123800004}, DOI={10.1046/j.1365-3164.1998.00067.x}, abstractNote={The classification of autoimmune blistering skin diseases is based on the skin antigen(s) targeted by pathogenic autoantibodies. In humans and dogs, there is increasing evidence that autoimmune subepidermal bullous diseases represent different nosological entities. This study establishes the existence of the canine equivalent of epidermolysis bullosa acquisita (EBA) in humans. Canine EBA, like the inflammatory variant of its human counterpart, is characterized by spontaneous vesicles arising from an inflammatory eruption. Dermo-epidermal separation occurs in association with neutrophilic infiltration in the superficial dermis. Tissue-fixed and circulating IgA and IgG autoantibodies specific for the lower basement membrane zone can be detected by immunofluorescence methods. Using immunoelectron microscopy, autoantibodies are shown to target the distal end of anchoring fibrils in the sublamina densa. ELISA and immunoblotting utilizing eukaryotically expressed recombinant collagen VII subdomains confirm that the circulating autoantibodies are specific for the aminoterminal globular non-collagenous NC1 domain of type VII collagen.}, number={1}, journal={VETERINARY DERMATOLOGY}, author={Olivry, T and Fine, JD and Dunston, SM and Chasse, D and Tenorio, AP and Monteiro-Riviere, NA and Chen, M and Woodley, DT}, year={1998}, month={Mar}, pages={19–31} }
 @inproceedings{monteiro-riviere_riviere_1998, title={Frontiers in in vitro and in vivo assessment of cutaneous toxicity models for risk assessment}, number={1998 Mar.}, booktitle={Continuing education course syllabus for the 37th annual meeting of the Society of Toxicology, Seattle, WA, March, 1998}, author={Monteiro-Riviere, N. A. and Riviere, J. E.}, year={1998} }
 @inproceedings{monteiro-riviere_riviere_ed._1998, title={In vitro and in vivo assessment of cutaneous toxicity models}, volume={37}, booktitle={Continuing Education Course Syllabus for the 37th Annual Meeting of the Society of Toxicology}, author={Monteiro-Riviere, N. A. and Riviere, J. E. and ed.}, year={1998} }
 @inbook{monteiro-riviere_1998, title={The Integument}, ISBN={0683301683}, booktitle={Textbook of veterinary histology. (5th ed.)}, publisher={Baltimore: Williams & Wilkins}, author={Monteiro-Riviere, N. A.}, editor={H. D. Dellmann and Eurell, J. A.Editors}, year={1998}, pages={303–332} }
 @article{zhang_fine_monteiro-riviere_1998, title={Uncein may be a potential target for sulfur mustard alkylation}, volume={8}, ISSN={["1051-7235"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000074183400004&KeyUID=WOS:000074183400004}, DOI={10.1080/105172398243014}, abstractNote={Severe blister formation in theepidermal and dermal junction is one of the characteristic cutaneous lesions caused by bis-2-chloroethyl sulfide (sulfur mustard, HD), a bifunctional alkylating agent. Uncein is a newly discovered anchoring filament-associated antigen that has been shown to be undetectable in all forms of junctional epidermolysis bullosa, therefore suggesting its role in maintaining the integrity of the epidermal-dermal basement membrane zone. To test uncein as a potential target for HD alkylation in HD-induced vesication, uncein was biosynthetically labeled with 35 S-methionine and purified by immunoprecipitation with a 19-DEJ-1 monoclonal antibody from the medium of normal human keratinocyte (NHEK) cultures. The 3 5 S-labeled uncein was incubated with 50 muL of 10.0 mg/mL of HD in ethanol (ETOH) or ETOH, which served as the control in 50 mM Tris-Cl buffer (pH 7.4) for 2 h. In addition, 10.0 mg/mL of HD was incubated with uncein pretreated with 3 mM sodium thiosulfate, an HD scavenger. Uncein treated with HD was fractionated by reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Uncein with no HD showed the typical profile of three subunit bands at 165, 130, and 100 kD. HD treatment reduced the intensity of uncein bands. Further, new higher molecular weight bands appeared at the top of the gel, and at the positions of 145 kD as well as 135 kD after HD treatment, suggesting that HD might cross-link uncein. In addition, sodium thiosulfate prevented the appearance of HD-crosslinked bands. Finally, monolayers of NHEK grown on cover slips were treated with 10.0 mg/mL of HD in ETOH or ETOH alone as control. Then, uncein was stained with a 19-DEJ-1 antibody and examined under immunofluorescence microscopy. In the control, uncein staining was localized intracellularly and was absent from the intercellular regions. Although the staining pattern did not change, the intensity of uncein staining was reduced after HD treatment, indicating that HD chemically modified uncein antigenic epitopes. These results suggest that HD alkylation of uncein may be ultimately responsible for weakening the epidermal-dermal junction, thereby contributing this chemical-induced subepidermal blister formation.}, number={1}, journal={TOXICOLOGY METHODS}, author={Zhang, ZL and Fine, JD and Monteiro-Riviere, NA}, year={1998}, pages={27–36} }
 @article{monteiroriviere_inman_snider_blank_hobson_1997, title={Comparison of an in vitro skin model to normal human skin for dermatological research}, volume={37}, ISSN={["1059-910X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1997WX21300002&KeyUID=WOS:A1997WX21300002}, DOI={10.1002/(SICI)1097-0029(19970501)37:3<172::AID-JEMT2>3.0.CO;2-Q}, abstractNote={EpiDerm, an in vitro human skin equivalent (HSE), was compared to normal human breast skin (NHS) to morphologically and biochemically assess its feasibility for dermatological research. Intralot and interlot variability was studied in day 0, 1, 2, and 3 in vitro cultures and in day 0, 3, 5, and 7 NHS. For NHS, light microscopy (LM) at day 0 showed stratified epidermis which exhibited an increase in vacuoles and dark basal cells as storage increased to 3, 5, and 7 days. Transmission electron microscopy (TEM) revealed typical organelles in the epidermis and a convoluted basement membrane at day 0. With increased storage, vacuoles and paranuclear clefts became numerous, necrosis increased, tonofilaments became less organized, and overall cellular integrity decreased. Biochemical data showed consistent MTT and glucose utilization (GU) through day 5, while lactate production decreased to 75% by day 3. By LM, day 0 HSE consisted of a thick, compact, stratum corneum that sent projections between the stratum granulosum cells. By TEM, the configuration organization, differentiation, distribution, and frequency of the organelles differed slightly from NHS. In addition, the basement membrane of the HSE was not completely differentiated, and the dermis was thin and acellular. Although day 1 and 2 cultures showed little change, day 3 exhibited an overall degeneration. Biochemical analysis showed GU and the lactate production decreased through day 3. In conclusion, the EpiDerm HSE, although exhibiting slight differences, was morphologically and biochemically similar to normal human epidermis and may be a valuable model in assessing the toxicology, metabolism, or pharmacology of nonvesicating compounds.}, number={3}, journal={MICROSCOPY RESEARCH AND TECHNIQUE}, author={MonteiroRiviere, NA and Inman, AO and Snider, TH and Blank, JA and Hobson, DW}, year={1997}, month={May}, pages={172–179} }
 @article{zhang_monteiroriviere_1997, title={Comparison of integrins in human skin, pig skin, and perfused skin: An in vitro skin toxicology model}, volume={17}, ISSN={["0260-437X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1997XR71500007&KeyUID=WOS:A1997XR71500007}, DOI={10.1002/(SICI)1099-1263(199707)17:4<247::AID-JAT437>3.3.CO;2-J}, number={4}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Zhang, ZL and MonteiroRiviere, NA}, year={1997}, pages={247–253} }
 @article{zhang_monteiro-riviere_1997, title={Comparison of integrins in human skin, pig skin, and perfused skin: An in vitro skin toxicology model}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030818144&partnerID=MN8TOARS}, DOI={10.1002/(SICI)1099-1263(199707)17:4<247::AID-JAT437>3.0.CO;2-S}, abstractNote={Integrins alpha2beta1, alpha3beta1, and alpha6beta4 are expressed in the epidermis, and play an important role in wound healing and/or epidermal-dermal interaction. These integrins may provide a new perspective into the understanding of wound healing and vesication. The isolated perfused porcine skin flap (IPPSF) has been shown to be an in vitro model for chemical-induced vesication. In order to determine whether the IPPSF could be utilized to study skin diseases mediated by integrins, the expression of integrins alpha2beta1, alpha3beta1, and alpha6beta4 was studied in human skin, pig skin, and the IPPSF using immunohistochemical staining. Immunostaining of both alpha2beta1 and alpha3beta1 was primarily located at the periphery of the basal keratinocytes in human skin. Similarly, alpha2beta1 was expressed in the stratum basale layer of the epidermis in both pig skin and the IPPSF after 8 h of perfusion. These antibodies defined the periphery of the pig basal keratinocytes more diffusely than that of human cells. However, the alpha3 antibody outlined the keratinocytes in all epidermal layers of the IPPSF and in the pig skin. In human skin, pig skin, and the IPPSF, alpha6beta4 stained exclusively at the basal pole of the basal keratinocytes, and showed a continuous linear labeling along the epidermal-dermal junction. The IPPSF showed stronger immunoreactivity with the antibody against beta4. Furthermore, the distribution of alpha6beta4 in 5.0 mg/ml of bis-(2-chloroethyl) sulfide (sulfur mustard, HD)-induced blisters was examined in the IPPSF. The alpha6beta4 staining was exclusively located on the epidermal side (roof) of the blister. In addition, alpha6beta4 staining was not linear but disrupted and patchy. These findings suggest that any destruction of alpha6beta4 may weaken the epidermal-dermal junction, thereby leading to HD-induced vesication. This study demonstrates that the IPPSF expresses similar integrins to those of human skin, and the distribution of alpha6beta4 in the IPPSF blisters caused by HD is comparable to that of some human basement membrane blistering diseases. Therefore, the pig and the IPPSF prove to be ideal models to study the role of integrins in wound healing and blistering diseases occurring at the epidermal-dermal junction.}, number={4}, journal={Journal of Applied Toxicology}, author={Zhang, Z. and Monteiro-Riviere, N.A.}, year={1997}, pages={247–253} }
 @article{baynes_monteiro-riviere_qiao_riviere_1997, title={Cutaneous toxicity of the benzidine dye direct red 28 applied as mechanistically-defined chemical mixtures (MDCM) in perfused porcine skin}, volume={93}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/s0378-4274(97)00083-0}, DOI={10.1016/S0378-4274(97)00083-0}, abstractNote={Complex chemical mixtures at hazardous waste sites can potentially consist of a marker chemical and several other chemicals, each of which can have different modulating actions on the dermatotoxicity of the marker chemical and/or other components in the mixture. A total of 16 mixtures, consisting of a marker chemical direct red 28 (DR28), a solvent (80% acetone or DMSO in water), a surfactant (0 or 10% sodium lauryl sulfate, SLS), a vasodilator (0 or 180 microg methyl nicotinate, MN) and a reducing agent (0 or 2% stannous chloride, SnCl2) were selected. Isolated perfused porcine skin flaps (IPPSFs), which have been proven to be an in vitro model for assessing absorption and toxicity, were utilized. These mixtures did not cause severe dermatotoxicity. However, light microscopic observations depicted minor alterations (intracellular and intercellular epidermal edema) with DMSO mixtures than with acetone mixtures. The presence of SLS caused an alteration in the stratum corneum. Enzyme histochemical staining for alkaline phosphatase (ALP) and nonspecific esterase (NSE) revealed no significant treatment effects, but increased staining for acid phosphatase (ACP) in the stratum basale was significant when associated with SLS or SLS + MN in DMSO mixtures. At 8 h post-dose, only DMSO mixtures containing SL + MN, SL + SnCl2, or SLS + MN + SnCl2 significantly increased transepidermal water loss. In conclusion, this study demonstrated that various mixtures, especially those containing SLS alter the epidermal barrier differently with complex interactions occurring simultaneously.}, number={2-3}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Baynes, Ronald E and Monteiro-Riviere, Nancy A and Qiao, Gui L and Riviere, Jim E}, year={1997}, month={Dec}, pages={159–169} }
 @article{allen_potts_tamada_lee_monteiro-riviere_1997, title={Enzyme histochemical evaluation of current application in pig skin}, volume={14}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199800104918&KeyUID=BIOSIS:PREV199800104918}, number={11 SUPPL.}, journal={Pharmaceutical Research (New York)}, author={Allen, D. G. and Potts, R. O. and Tamada, J. A. and Lee, S. and Monteiro-Riviere, N. A.}, year={1997}, pages={S307} }
 @article{monteiro-riviere_baynes_riviere_1997, title={Epidermal cytotoxicity of topically-applied chemical mixtures in perfused porcine skin}, volume={20}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199799683390&KeyUID=BIOSIS:PREV199799683390}, number={SUPPL. 1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Monteiro-Riviere, N. and Baynes, R. and Riviere, J.}, year={1997}, pages={255–256} }
 @article{smoak_blanton_monteiro-riviere_1997, title={Glut-1: Cardiac expression during organogenesis and its role in glucose uptake in embryonic mouse heart}, volume={11}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33750120598&partnerID=MN8TOARS}, number={3}, journal={FASEB Journal}, author={Smoak, I.W. and Blanton, M.R. and Monteiro-Riviere, N.A.}, year={1997} }
 @article{monteiroriviere_1997, title={Introduction to histological aspects of dermatotoxicology}, volume={37}, ISSN={["1097-0029"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1997WX21300001&KeyUID=WOS:A1997WX21300001}, DOI={10.1002/(SICI)1097-0029(19970501)37:3<171::AID-JEMT1>3.0.CO;2-R}, abstractNote={Microscopy Research and TechniqueVolume 37, Issue 3 p. 171-171 Topical Paper Introduction to histological aspects of dermatotoxicology Nancy A. Monteiro-Riviere Ph.D., Corresponding Author Nancy A. Monteiro-Riviere Ph.D. Investigative Dermatology and Toxicology, North Carolina State University, Raleigh, North CarolinaInvestigative Dermatology and Toxicology, North Carolina State University, Raleigh, North CarolinaSearch for more papers by this author Nancy A. Monteiro-Riviere Ph.D., Corresponding Author Nancy A. Monteiro-Riviere Ph.D. Investigative Dermatology and Toxicology, North Carolina State University, Raleigh, North CarolinaInvestigative Dermatology and Toxicology, North Carolina State University, Raleigh, North CarolinaSearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1097-0029(19970501)37:3<171::AID-JEMT1>3.0.CO;2-RCitations: 12AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume37, Issue31 May 1997Pages 171-171 RelatedInformation}, number={3}, journal={MICROSCOPY RESEARCH AND TECHNIQUE}, author={MonteiroRiviere, NA}, year={1997}, month={May}, pages={171–171} }
 @book{riviere_brooks_qiao_monteiro-riviere_1997, title={Percutaneous absorption of volatile chemicals}, DOI={10.21236/ada332910}, abstractNote={Abstract : The purpose of this project was to assess the percutaneous absorption of two volatile organic compounds, chloropentafluorobenzene (CPFB) and dichlorobenzene (DCB) in the isolated perfused porcine skin flap (IPPSF) model. An independent theoretical goal was to begin to develop a mathematical framework to assess vehicle-compound interactions which occur during dermal exposure. Assessment of the percutaneous absorption and penetration of volatile compounds is difficult. The process of studying these compounds involved 5 steps: (1) development of an IPPSF cradle chamber to trap the evaporated compound in the area next to the skin, (2) assessment of the mass of CPFB that was absorbed into the perfusate from CPFB which was evaporated from excised skin, (3) exposure of the IPPSF to neat test compounds and test compounds in a vehicle, (4) assessment of the mass of the test compound in the perfusate is a result of exposure to the volatile compound vapor, and (5) development of a dosing dome that allowed dosing a vapor without vapor uptake directly into the perfusate. Relevant absorption parameters were then determined. These studies demonstrated dose-dependent absorption of CPFB and DCB in skin which was further modulated by concomitant exposure to vehicle. The data obtained could be used as direct input into a systemic risk assessment model.}, journal={(NTIS report AFOSR G49620-95-1-0017)}, institution={Bethesda, MD: Cambridge Scientific Abstracts}, author={Riviere, J. E. and Brooks, J. D. and Qiao, G. L. and Monteiro-Riviere, N.A.}, year={1997}, pages={1–23} }
 @article{riviere_monteiro-riviere_inman_1997, title={The effect of altered media flow and glucose concentration on sulfur mustard toxicity in the Isolated Perfused Porcine Skin Flap}, volume={10}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030818496&partnerID=MN8TOARS}, number={2}, journal={In Vitro and Molecular Toxicology: Journal of Basic and Applied Research}, author={Riviere, J.E. and Monteiro-Riviere, N.A. and Inman, A.O.}, year={1997}, pages={169–181} }
 @article{riviere_monteiro-riviere_inman_1997, title={The effects of altered media flow and glucose concentration on sulfur mustard toxicity in isolated perfused skin}, volume={10}, number={2}, journal={In Vitro Toxicology}, author={Riviere, J. E. and Monteiro-Riviere, N. A. and Inman, A. O.}, year={1997}, pages={169–181} }
 @inbook{potts_bommannan_wong_tamada_riviere_monteiro-riviere_1997, title={Transdermal peptide delivery using electroporation}, DOI={10.1007/0-306-46803-4_8}, booktitle={Protein delivery: Physical systems}, publisher={New York: Plenum Press}, author={Potts, R. O. and Bommannan, D. and Wong, O. and Tamada, J. A. and Riviere, J. E. and Monteiro-Riviere, N.A.}, editor={L. M. Sanders and Hendren, R. W.Editors}, year={1997}, pages={213–238} }
 @article{potts_bommannan_wong_tamada_riviere_monteiro-riviere_1997, title={Transdermal peptide delivery using electroporation.}, volume={10}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=MEDLINE&KeyUT=MEDLINE:9160374&KeyUID=MEDLINE:9160374}, journal={Pharmaceutical biotechnology}, author={Potts, R O and Bommannan, D and Wong, O and Tamada, J A and Riviere, J E and Monteiro-Riviere, N A}, year={1997}, pages={213–38} }
 @article{monteiroriviere_inman_1997, title={Ultrastructural characterization of sulfur mustard-induced vesication in isolated perfused porcine skin}, volume={37}, ISSN={["1097-0029"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1997WX21300008&KeyUID=WOS:A1997WX21300008}, DOI={10.1002/(SICI)1097-0029(19970501)37:3<229::AID-JEMT8>3.0.CO;2-I}, abstractNote={The isolated perfused porcine skin flap (IPPSF) is a novel alternative, humane in vitro model consisting of a viable epidermis and dermis with a functional microvasculature. For this study, 200 microliters of either 10.0, 5.0, 2.5, 1.25, 0.50, or 0.20 mg/ml of bis (2-chloroethyl) sulfide (HD) in ethanol or ethanol control was topically applied to a 5.0 cm2 dosing area of the IPPSF and perfused for 8 h with recirculating media. HD dermatotoxicity was assessed in the flap by cumulative glucose utilization (CGU), vascular resistance (VR), light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). HD produced a statistically significant dose relationship for gross blisters and microvesicles. The HD-treated IPPSFs were also characterized by a decrease in CGU and an increase in VR. Light microscopic changes included mild intracellular and slight intracellular epidermal edema, multifocal epidermal-dermal separation, and dark basal cells. Ultrastructural alterations consisted of cytoplasmic vacuoles, pyknotic basal cells, nucleolar segregation, and epidermal-dermal separation occurring between the lamina lucida and lamina densa of the basement membrane. The severity of these changes increased in a dose-dependent manner. Morphologically, the IPPSF appeared similar to human skin exposed to HD with the formation of macroscopic blisters and microscopic vesicles. In conclusion, the IPPSF appears to be an appropriate in vitro model with which to study the pathogenesis of vesicant-induced toxicity.}, number={3}, journal={MICROSCOPY RESEARCH AND TECHNIQUE}, author={MonteiroRiviere, NA and Inman, AO}, year={1997}, month={May}, pages={229–241} }
 @inbook{monteiro-riviere_1996, title={Anatomical factors affecting percutaneous absorption}, ISBN={1560323566}, booktitle={Dermatotoxicology (5th ed.)}, publisher={Washington, DC: Taylor & Francis}, author={Monteiro-Riviere, N. A.}, editor={F. N. Marzulli and Maibach, H. I.Editors}, year={1996}, pages={3–17} }
 @inproceedings{monteiro-riviere_zhang_riviere_1996, title={Integrated biochemical and molecular mechanisms of sulfur mustard vesication in skin: vascular and basement membrane targets}, booktitle={Proceedings of the 1996 Medical Defense Bioscience Review}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={Monteiro-Riviere, N. A. and Zhang, Z. and Riviere, J. E.}, year={1996}, pages={977–986} }
 @misc{riviere_rogers_monteiro-riviere_1996, title={Iontophoretic electrode}, volume={5540654}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Riviere, J. E. and Rogers, R. A. and Monteiro-Riviere, N. A.}, year={1996} }
 @inbook{murtaugh_monteiro-riviere_panepinto_1996, title={Swine research breeds, methods, and biomedical models}, ISBN={0306454955}, DOI={10.1007/978-1-4615-5885-9_1}, booktitle={Advances in swine in biomedical research}, publisher={New York: Plenum Press}, author={Murtaugh, M. P. and Monteiro-Riviere, N.A. and Panepinto, L.}, editor={M. E. Tumbleson and Schook, L. B.Editors}, year={1996}, pages={423–424} }
 @article{gordon_gray_monteiro-riviere_yang_miller_1996, title={Temperature regulation in adult hamsters and rats exposed perinatally to dioxin}, volume={10}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199698763275&KeyUID=BIOSIS:PREV199698763275}, number={3}, journal={FASEB Journal}, author={Gordon, C. J. and Gray, L. E. and Monteiro-Riviere, N. A. and Yang, Y. and Miller, D. B.}, year={1996}, pages={A4} }
 @inbook{monteiro-riviere_riviere_1996, title={The pig as a model for cutaneous pharmacology and toxicology research}, ISBN={0306454955}, DOI={10.1007/978-1-4615-5885-9_2}, booktitle={Advances in swine in biomedical research}, publisher={New York: Plenum Press}, author={Monteiro-Riviere, N.A. and Riviere, J. E.}, editor={M. E. Tumbleson and Schook, L. B.Editors}, year={1996}, pages={425–458} }
 @article{qiao_brooks_baynes_monteiroriviere_williams_riviere_1996, title={The use of mechanistically defined chemical mixtures (MDCM) to assess component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals .1. Studies with parathion mixtures in isolated perfused porcine skin}, volume={141}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1996WC22200015&KeyUID=WOS:A1996WC22200015}, DOI={10.1006/taap.1996.0313}, abstractNote={Recently, attention has been directed to the risk assessment of cutaneous exposure to chemical mixtures rather than to only a single compound since this is the exposure scenario in the environment, residence, and work place. Using acetone or dimethylsulfoxide (DMSO) (80% in water) as a vehicle, percutaneous absorption and cutaneous disposition of parathion (PA) were studied following PA (40 μg/cm2) dosing on isolated perfused porcine skin as mechanistically defined chemical mixtures (MDCM) consisting of the surfactant sodium lauryl sulfate (SLS), the rubefacient methyl nicotinate (MNA), and the reducing agent stannous chloride (SnCl2). A full 2 × 4 factorial design was used to asses treatment effects and potential interactions. More radiolabel was absorbed with DMSO than with acetone albeit an earlier peak flux time but lower peak flux was observed with acetone than with DMSO. The absorption flux rate profiles with DMSO continued increasing but bipeak-featured profiles were observed with acetone. SLS enhanced PA absorption with both DMSO and acetone. The presence of MNA in both vehicles blunted the absorption rate curves without significantly changing total absorption. SnCl2blocked PA absorption and increased residue level on the skin surface and in the stratum corneum (SC). The venous flux profiles were mixture-dependent and highly reproducible within treatment groups. Higher level interactions were also noted. This study indicated multiple levels of interactive effects on PA absorption which must be incorporated into any effort to identify critical mechanisms which affect risk assessment of topically exposed mixtures. It was suggested that the chemicals selected in a topically applied mixture may have significant effects on the penetration/distribution pattern and percutaneous absorption profile of a toxicant/drug in the mixture. The MDCM approach may be useful in a screening or triage approach to identify mixture components which affect marker chemical absorption as well as identify potential mechanisms which deserve further attention. Risk assessment efforts could then be focused on those mixtures, containing these critical components, which would be expected to have the greatest penetration and absorption.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Qiao, GL and Brooks, JD and Baynes, RE and MonteiroRiviere, NA and Williams, PL and Riviere, JE}, year={1996}, month={Dec}, pages={473–486} }
 @article{williams_thompson_qiao_monteiro-riviere_baynes_riviere_1996, title={The use of mechanistically defined chemical mixtures (MDCM) to assess mixture component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals .2. Development of a general dermatopharmacokinetic model for use in risk assessment}, volume={141}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1996WC22200016&KeyUID=WOS:A1996WC22200016}, DOI={10.1006/taap.1996.0314}, abstractNote={We present a conceptual approach to a general comprehensive mathematical model to quantify percutaneous absorption of topically applied chemicals in complex mixtures on the basis of biophysical parameters estimated or measured using in vitro and ex vivo perfused skin preparations. This model addresses mechanistically defined chemical mixtures (MDCM) which consist of components selected because of their potential to modulate by various mechanisms the absorption of a marker toxic penetrant. This model accounts for observed toxicodynamic general and specific effects of chemicals, acting single or in concert, on the absorption of any or all components in a defined mixture. We have also included experimental data from an isolated perfused porcine skin flap study with topically applied parathion as the marker penetrant and acetone or DMSO as solvent, with methyl nicotinate as a potential rubefacient, sodium laurel sulfate as a surfactant, and stannous chloride as a reducing agent in order to provide an illustration of the application and performance of the model. This model supports the MDCM concept that defining and then simulating those components of a complex mixture that could have a significant impact on the absorption of a marker toxic compound would be a useful screening approach in the risk assessment of topical chemical mixtures. It may also be used to identify critical pathways where chemical mixture component interactions significantly modify the absorption of the penetrant of interest.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Williams, P. L. and Thompson, D. and Qiao, G. L. and Monteiro-Riviere, N.A. and Baynes, R. L. and Riviere, J. E.}, year={1996}, month={Dec}, pages={487–496} }
 @article{zhang_peters_monteiroriviere_1995, title={ASSESSMENT OF SULFUR MUSTARD INTERACTION WITH BASEMENT-MEMBRANE COMPONENTS}, volume={11}, ISSN={["1573-6822"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995RM25300003&KeyUID=WOS:A1995RM25300003}, DOI={10.1007/bf00767494}, number={2}, journal={CELL BIOLOGY AND TOXICOLOGY}, author={ZHANG, Z and PETERS, BP and MONTEIRORIVIERE, NA}, year={1995}, month={Apr}, pages={89–101} }
 @article{spoo_monteiroriviere_riviere_1995, title={DETECTION OF SULFUR MUSTARD BIS(2-CHLOROETHYL) SULFIDE AND METABOLITES AFTER TOPICAL APPLICATION IN THE ISOLATED-PERFUSED PORCINE SKIN FLAP}, volume={56}, ISSN={["0024-3205"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995QM83700002&KeyUID=WOS:A1995QM83700002}, DOI={10.1016/0024-3205(95)00102-6}, abstractNote={The purpose of this study was to develop an assay to study the flux of sulfur mustard (HD) through the skin and determine if metabolites are formed due to the epidermal metabolism of HD after topical exposure of the isolated perfused porcine skin flap (IPPSF) to 14C-HD. Four IPPSFs were topically dosed with 2.85 mg of 14C-HD in ethanol. Venous perfusate samples were collected and added to a 34% solution of NaCl and snap-frozen to inhibit the metabolism of HD until time for assay. Perfusate samples were extracted using a solid-phase extraction cartridge with ethyl acetate and then assayed using gas chromatography. Two of the 4 IPPSFs showed detectable levels of HD in the venous perfusate 15 min after dosing, with 1 of these 2 IPPSFs showing detectable levels of HD in the perfusate 2 hours after dosing. All 4 IPPSFS had no more than 3 metabolites of HD appearing in the perfusate throughout the 2 hr experiment, with one of the these metabolites identified as thiodiglycol. These experiments showed that little, if any, HD appears in the venous perfusate intact after percutaneous absorption and that epidermal metabolism of HD does occur to a significant degree in the IPPSF.}, number={17}, journal={LIFE SCIENCES}, author={SPOO, JW and MONTEIRORIVIERE, NA and RIVIERE, JE}, year={1995}, month={Mar}, pages={1385–1394} }
 @article{chang_brooks_monteiroriviere_riviere_1995, title={ENHANCING OR BLOCKING EFFECT OF FENVALERATE ON THE SUBSEQUENT PERCUTANEOUS-ABSORPTION OF PESTICIDES IN-VITRO}, volume={51}, ISSN={["0048-3575"]}, DOI={10.1006/pest.1995.1021}, abstractNote={The percutaneous absorption of pesticides has been receiving much research attention. However, most work is conducted with single exposures and potential interactions of previous pesticide exposure have received little attention. In the present study, the effect of in vivo pretreatment of the skin with a 3% fenvalerate in ethanol or a 3% parathion in ethanol solution on carbaryl, fenvalerate, lindane, and parathion absorption was studied in vitro using weanling pig skin in a flowthrough diffusion cell system. Concentrations of 40 or 400 μg/cm2 of carbaryl, fenvalerate, lindane, and parathion in ethanol were applied topically. Environmental conditions of air and perfusate temperature (37°C), relative humidity (60%), flow rate (4 ml/hr), and Kreb′s-Ringer bicarbonate buffer with 4.5% bovine serum albumin medium were controlled. The total absorption of these pesticides, both ethanol control and fenvalerate or parathion pretreated, increased proportionally with the dose; however, the absorption efficiency (fraction of applied dose absorbed) decreased as the dose increased. At both doses, fenvalerate pretreatment had little or no effect on carbaryl and fenvalerate absorption; however, parathion absorption was significantly decreased in fenvalerate-pretreated skin (P < 0.05). There was no significant difference (P ≥ 0.05) of parathion absorption between the parathion pretreatment and the fenvalerate pretreatment. Lindane absorption increased at the 40-μg dose and significantly increased at the 400-μg dose (P < 0.05) following fenvalerate pretreatment. Carbaryl absorption was higher than other pesticides at the dose of 40 μg/cm2 Furthermore, comparing ethanol control data with previous results indicates that prolonged skin treatment with ethanol significantly increases parathion absorption (P < 0.05). This study suggests that the absorption data from a single parent compound alone were not adequate to determine the rate of absorption of pesticide under mixture exposure conditions. Pesticide interactions may significantly affect the percutaneous absorption, interpretation, and assessment of risk.}, number={3}, journal={PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY}, author={CHANG, SK and BROOKS, JD and MONTEIRORIVIERE, NA and RIVIERE, JE}, year={1995}, month={Mar}, pages={214–219} }
 @article{zhang_riviere_monteiroriviere_1995, title={EVALUATION OF PROTECTIVE EFFECTS OF SODIUM THIOSULFATE, CYSTEINE, NIACINAMIDE AND INDOMETHACIN ON SULFUR MUSTARD-TREATED ISOLATED-PERFUSED PORCINE SKIN}, volume={96}, ISSN={["0009-2797"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995RA80300004&KeyUID=WOS:A1995RA80300004}, DOI={10.1016/0009-2797(94)03596-Z}, abstractNote={Sulfur mustard (bis(2-chloroethyl)sulfide, HD), a bifunctional alkylating agent, causes severe cutaneous injury, including cell death, edema and vesication. However, the mechanisms underlying HD-induced cutaneous toxicity remain undefined. The isolated perfused porcine skin flap (IPPSF) has been utilized to investigate dermal toxic compounds and pharmacological intervention. In this study, 4 compounds with different pharmacological mechanisms were tested for their ability to prevent the dark basal cell formation, vesication and vascular response charcteristic of exposure to HD in the IPPSF. Reduction of HD-induced dark basal cells was observed in IPPSFs perfused with sodium thiosulfate and cysteine, which are HD scavengers; niacinamide, a possible NAD+ stabilizer and an inhibitor of poly (ADP-ribose) polymerase; or indomethacin, a cyclooxygenase inhibitor, respectively. Treatments with niacinamide and indomethacin, but not sodium thiosulfate or cysteine, resulted in an inhibition of the vascular response in IPPSF exposed to HD. Microvesicles caused by HD were only partially prevented in the indomethacin-perfused IPPSFs. These data suggest that none of these agents alone would be successful antivesicant agents and different mechanisms are involved in production of HD-induced dark basal cells, microvesicles and the vascular response; unfortunately, blocking of the cellular toxicity as evidenced by dark basal cell formation did not prevent vesication, suggesting that other mechanisms must be operative and that there is a multistep, biochemical process that leads to a final lesion.}, number={3}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={ZHANG, ZL and RIVIERE, JE and MONTEIRORIVIERE, NA}, year={1995}, month={Jun}, pages={249–262} }
 @article{monteiroriviere_inman_1995, title={INDIRECT IMMUNOHISTOCHEMISTRY AND IMMUNOELECTRON MICROSCOPY DISTRIBUTION OF 8 EPIDERMAL-DERMAL JUNCTION EPITOPES IN THE PIG AND IN ISOLATED-PERFUSED SKIN TREATED WITH BIS (2-CHLOROETHYL) SULFIDE}, volume={23}, ISSN={["0192-6233"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995RD37200008&KeyUID=WOS:A1995RD37200008}, DOI={10.1177/019262339502300308}, abstractNote={Sulfur mustard (bis [2-chloroethyl] sulfide, HD) is a potent cutaneous vesicant that causes gross blisters by separation of the epidermal-dermal junction (EDJ). The EDJ of the skin is a highly specialized and complex structure composed of several components and plays a major role in the integrity of the skin. The isolated perfused porcine skin flap (IPPSF) was dosed with 0.2 mg/ml (n = 4), 5.0 mg/ml (n = 4), and 10.0 mg/ml (n = 5) HD or ethanol (n = 4) for 8 hr (dose-response study) and 10.0 mg/ml HD or ethanol for 1, 3, 5, and 8 hr (n = 4/treatment) (time-response study). Successful EDJ mapping was carried out in normal pig skin (NPS), ethanol-treated IPPSFs, and HD-treated IPPSFs using the following antibodies: laminin, type IV collagen, fibronectin, GB3 (Nicein), bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). Two mouse anti-human monoclonal antibodies, L3d and 19-DEJ-l (Uncein), did not cross-react with the EDJ of the pig. Antibody staining in NPS, ranging from very intense for laminin and type IV collagen to weak for fibronectin, was generally more discrete than in the IPPSF. No differences in staining were noted between the ethanol and nonblistered areas of the HD-treated IPPSFs. In HD-blistered areas, BP stained only the epidermal hemidesmosomes, and laminin, fibronectin, and GB3 stained primarily the dermis with fragments attached to the basal pole of the stratum basale cells, while type IV collagen and EBA stained only the dermis. Mapping of these epitopes determined that the precise plane of EDJ separation in the HD-treated skin occurred beneath the hemidesmosomes within the upper portion of the lamina lucida. The conservation of human epitopes in the EDJ of the pig further emphasizes the similarities between human skin and pig skin. Therefore, pig skin and the IPPSF may be used to study HD-induced vesication and blistering diseases.}, number={3}, journal={TOXICOLOGIC PATHOLOGY}, author={MONTEIRORIVIERE, NA and INMAN, AO}, year={1995}, pages={313–325} }
 @article{riviere_monteiro-riviere_williams_1995, title={Isolated perfused porcine skin flap as an in vitro model for predicting transdermal pharmacokinetics}, volume={41}, journal={European Journal of Pharmaceutics and Biopharmaceutics}, author={Riviere, J. E. and Monteiro-Riviere, N. A. and Williams, P. L.}, year={1995}, pages={152–162} }
 @book{monteiro-riviere_zhang_inman_riviere_1995, title={Mechanisms of cutaneous vesication}, volume={161}, journal={DAMD17-92-C-2071; NTIS, ADA305800}, institution={DAMD 17-92C-2071, NTIS Report, ADA 305800}, author={Monteiro-Riviere, N. A. and Zhang, J. Z. and Inman, A. O. and Riviere, J. E.}, editor={NTISEditor}, year={1995}, pages={1–161} }
 @article{riviere_monteiroriviere_rogers_bommannan_tamada_potts_1995, title={PULSATILE TRANSDERMAL DELIVERY OF LHRH USING ELECTROPORATION - DRUG-DELIVERY AND SKIN TOXICOLOGY}, volume={36}, ISSN={["0168-3659"]}, DOI={10.1016/0168-3659(95)00036-8}, number={3}, journal={JOURNAL OF CONTROLLED RELEASE}, author={RIVIERE, JE and MONTEIRORIVIERE, NA and ROGERS, RA and BOMMANNAN, D and TAMADA, JA and POTTS, RO}, year={1995}, month={Oct}, pages={229–233} }
 @article{francoeur_monteiro-riviere_riviere_1995, title={Piroxicam: Evidence for local delivery following topical application}, volume={41}, journal={European Journal of Pharmaceutics and Biopharmaceutics}, author={Francoeur, M. L. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={1995}, pages={175–183} }
 @article{gordon_gray_monteiroriviere_miller_1995, title={TEMPERATURE REGULATION AND METABOLISM IN RATS EXPOSED PERINATALLY TO DIOXIN - PERMANENT CHANGE IN REGULATED BODY-TEMPERATURE}, volume={133}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995RH95400019&KeyUID=WOS:A1995RH95400019}, DOI={10.1006/taap.1995.1138}, abstractNote={2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lower thyroxine levels and cause hypothermia in the adult rat; however, there is little known regarding the perinatal effects of TCDD on metabolism and temperature regulation of the offspring. To address this issue, thermoregulatory responses were assessed in adult male rat offspring exposed perinatally to 1.0 micrograms TCDD/kg body wt by gavage on Gestational Day 15. Individual castrated offspring were placed in a gradient-layer calorimeter for 5 hr during their nocturnal period while ambient temperature (Ta) was maintained at 10, 16, 24, or 28 degrees C. Metabolic rate (M), as measured from the total heat loss in the calorimeter, was determined along with evaporative heat loss (EHL), dry thermal conductance, and body core temperature (Tc). Animals exposed to TCDD had a significantly lower body temperature at TaS of 10, 16, and 24 degrees C and a higher thermal conductance. M was unaffected by TCDD, indicating that TCDD did not impair the effector to regulate Tc during cold exposure. EHL was also unaffected by TCDD. Skin blood flow of the interscapular area was measured in anesthetized rats with laser Doppler velocimetry and found to be the same in control and TCDD groups. The reduction in body temperature over a wide range of TaS concomitant with normal thermoregulatory effector function suggests that perinatal exposure to TCDD results in a reduction in the regulated body temperature (i.e., decrease in set-point).}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={GORDON, CJ and GRAY, LE and MONTEIRORIVIERE, NA and MILLER, DB}, year={1995}, month={Jul}, pages={172–176} }
 @article{riviere_brooks_williams_monteiroriviere_1995, title={TOXICOKINETICS OF TOPICAL SULFUR MUSTARD PENETRATION, DISPOSITION, AND VASCULAR TOXICITY IN ISOLATED-PERFUSED PORCINE SKIN}, volume={135}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995TD76100004&KeyUID=WOS:A1995TD76100004}, DOI={10.1006/taap.1995.1205}, abstractNote={Sulfur mustard bis(2-chloroethyl) sulfide (HD) is a bifunctional alkylating agent that causes cutaneous vesication. The isolated perfused porcine skin flap is an in vitro model that has been used to study this toxic response. The purpose of this study was to formulate a toxicokinetic model of HD penetration and cutaneous disposition as an aid in correlating critical steps in the pathogenesis of vesication to HD concentrations in different regions of skin. [14C]HD was dosed topically in ethanol at 10.0 mg/ml in a 7.5-cm2 dosing site and venous efflux samples were collected over 2, 4, or 8 hr. At the termination of the experiment, stratum corneum tape strips, core biopsies for serial sections, and the entire skin flap were collected for radioassay. Peak 14C-radiolabel flux occurred within 5 to 60 min in all skin flaps, much earlier than signs of HD-induced toxicity. A toxicokinetic model was used to quantitate the time profile of HD disposition in different skin compartments. Estimates of vascular and extracellular volume changes due to topical HD toxicity were estimated using radiolabeled albumin and inulin infusions. A second toxicokinetic model, with a time-variant distribution rate, was used to simulate volume changes. In order to accurately predict HD disposition, it was necessary to add another compartment as a reservoir for slowly released metabolites of HD. This model provides a quantitative profile of the time course of HD (or metabolites) disposition within skin which would aid in the interpretation of mechanistic studies of vesication as well as in designing interventive antivesicant drug strategies.}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={RIVIERE, JE and BROOKS, JD and WILLIAMS, PL and MONTEIRORIVIERE, NA}, year={1995}, month={Nov}, pages={25–34} }
 @article{zhang_riviere_monteiro-riviere_1995, title={Topical sulfur mustard induces changes in prostaglandins and interleukin-1-alpha in isolated perfused porcine skin}, volume={8}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199598461660&KeyUID=BIOSIS:PREV199598461660}, number={2}, journal={In Vitro Toxicology}, author={Zhang, Z. and Riviere, J. E. and Monteiro-Riviere, N. A.}, year={1995}, pages={149–158} }
 @article{williams_brooks_inman_monteiroriviere_riviere_1994, title={DETERMINATION OF PHYSICOCHEMICAL PROPERTIES OF PHENOL, P-NITROPHENOL, ACETONE AND ETHANOL RELEVANT TO QUANTITATING THEIR PERCUTANEOUS-ABSORPTION IN PORCINE SKIN}, volume={83}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1994MV05600006&KeyUID=WOS:A1994MV05600006}, number={1}, journal={Research Communications in Chemical Pathology and Pharmacology}, author={WILLIAMS, PL and BROOKS, JD and INMAN, AO and MONTEIRORIVIERE, NA and RIVIERE, JE}, year={1994}, pages={61–75} }
 @article{monteiroriviere_inman_riviere_1994, title={DEVELOPMENT AND CHARACTERIZATION OF A NOVEL SKIN MODEL FOR CUTANEOUS PHOTOTOXICOLOGY}, volume={10}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1994QF67500002&KeyUID=WOS:A1994QF67500002}, number={6}, journal={Photodermatology Photoimmunology & Photomedicine}, author={MONTEIRORIVIERE, NA and INMAN, AO and RIVIERE, JE}, year={1994}, pages={235–243} }
 @article{william_brooks_inman_monteiro-riviere_riviere_1994, title={Determination of physicochemical properties of phenol, p-nitrophenol, acetone and ethanol relevant to quantitating their percutaneous absorption in porcine skin}, volume={83}, journal={Research Communications in Chemical Pathology and Pharmacology}, author={William, P. L. and Brooks, J. D. and Inman, A. O. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={1994}, pages={61–75} }
 @article{monteiro-riviere_inman_tamada_potts_riviere_1994, title={Histological evaluation of transdermal electroporation and iontophoresis of LHRH delivery in porcine skin}, volume={11}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199598020099&KeyUID=BIOSIS:PREV199598020099}, number={10 SUPPL.}, journal={Pharmaceutical Research (New York)}, author={Monteiro-Riviere, N. A. and Inman, A. O. and Tamada, J. and Potts, R. O. and Riviere, J. E.}, year={1994}, pages={S191} }
 @article{monteiroriviere_inman_riviere_1994, title={IDENTIFICATION OF THE PATHWAY OF IONTOPHORETIC DRUG-DELIVERY - LIGHT AND ULTRASTRUCTURAL STUDIES USING MERCURIC-CHLORIDE IN PIGS}, volume={11}, ISSN={["0724-8741"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1994MW65100011&KeyUID=WOS:A1994MW65100011}, DOI={10.1023/A:1018907508501}, number={2}, journal={PHARMACEUTICAL RESEARCH}, author={MONTEIRORIVIERE, NA and INMAN, AO and RIVIERE, JE}, year={1994}, month={Feb}, pages={251–256} }
 @article{king_peters_monteiroriviere_1994, title={LAMININ IN THE CUTANEOUS BASEMENT-MEMBRANE AS A POTENTIAL TARGET IN LEWISITE VESICATION}, volume={126}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1994NL85400021&KeyUID=WOS:A1994NL85400021}, DOI={10.1006/taap.1994.1103}, abstractNote={The epidermal-dermal junction has a complex molecular architecture, with numerous components playing key roles in adhesion of the epidermis to the dermis. The purpose of this study was to examine structural components of the epidermal-dermal junction as potential targets for toxicity by lewisite (dichloro(2-chlorovinyl)arsine). This was accomplished by (1) immunocytochemical mapping of laminin, type IV collagen, and bullous pemphigoid antigen (BPA) in lewisite-treated isolated perfused porcine skin flaps (IPPSF), (2) evaluation of protease activity in IPPSF blister fluid against laminin substrate from murine EHS tumor and human keratinocytes, and (3) examination of human keratinocyte laminin for direct chemical modification by lewisite. Lewisite-induced epidermal-dermal separation was localized to the lamina lucida. Localization of the separation suggested that laminin, a cysteine-rich and highly protease-sensitive adhesive glycoprotein, is a potential target for lewisite action. It was hypothesized that chemical modification of laminin directly (via chemical alkylation of laminin thiols by the arsenical) or indirectly (due to lewisite-induced cytotoxic release of proteases) could result in blister formation. Employing sensitive methodology, no evidence of proteolytic activity against EHS tumor laminin or human keratinocyte laminin was identified in the blister fluid. In addition, no evidence for direct chemical modification of laminin by lewisite was demonstrated. However, up to 36% of the thiol groups in human keratinocyte laminin immunoprecipitates was potentially available for reaction with alkylating agents. While these studies did not demonstrate a lewisite-induced chemical modification of laminin, they do not rule out the possibility that other adhesive molecules of the basement membrane are targets for lewisite action. Further evaluation of the molecular role that these binding modalities play in vesicant-induced separation may provide new insights into therapeutic and prophylactic strategies against the toxicity of such compounds and contribute to a better understanding of basement membrane biochemistry.}, number={1}, journal={Toxicology and Applied Pharmacology}, author={KING, JR and PETERS, BP and MONTEIRORIVIERE, NA}, year={1994}, pages={164–173} }
 @article{king_peters_a._1994, title={Matrix molecules of the epidermal basement membrane as targets for chemical vesication with lewisite}, volume={126}, journal={Toxicology and Applied Pharmacology}, author={King, J. R. and Peters, B. P. and A., Monteiro-Riviere N.}, year={1994}, pages={164–173} }
 @book{monteiro-riviere_zhang_inman_brooks_riviere_1994, title={Mechanisms of cutaneous vesication}, volume={114}, journal={DAMD17-92-C-2071; NTIS, ADA283085}, institution={DAMD 17-92-C-2071, NTIS Report, ADA 283085}, author={Monteiro-Riviere, N. A. and Zhang, J. Z. and Inman, A. O. and Brooks, J. D. and Riviere, J. E.}, year={1994}, pages={1–114} }
 @article{meyer_kim_moser_monteiroriviere_smart_1994, title={SYNERGISTIC INTERACTION BETWEEN THE NONPHORBOL ESTER-TYPE PROMOTER MIREX AND 12-O-TETRADECANOYLPHORBOL-13-ACETATE IN MOUSE SKIN TUMOR PROMOTION}, volume={15}, ISSN={["0143-3334"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1994MR10300009&KeyUID=WOS:A1994MR10300009}, DOI={10.1093/carcin/15.1.47}, abstractNote={Mirex, an organochlorine pesticide and non-genotoxic rodent hepatocarcinogen, is also a potent non-phorbol ester-type promoter of mouse skin tumors. Mirex, unlike most other skin tumor promoters, is not a significant epidermal hyperplasiogen even at a maximally promoting dose (200 nmol). Experiments described here examined whether tumor promotion by mirex and 12-O-tetradecanoylphorbol-13-acetate (TPA) are mediated through different mechanisms as indicated by their additivity when co-applied to 7,12-dimethyl-benz[a]anthracene (DMBA, 200 nmol)-initiated female CD-1 mouse skin. Instead of the additive response of 14 plus 5 tumors/mouse predicted from mice promoted for 20 weeks (2x/week) with either mirex (200 nmol) or TPA (2 nmol) respectively, their co-application yielded 35 tumors/mouse. This synergy with TPA was specific to mirex since a structurally related compound, chlordecone (Kepone) was inactive. Mirex plus TPA-promoted papillomas contained a c-Ha-ras A182-->T mutation as frequently (13/14) as those promoted by mirex or TPA alone, suggesting that these DMBA-initiated/co-promoted papillomas were not atypical in this genotypic marker. Promotional synergy with mirex was only observed with a submaximal promoting dose of 2 nmol TPA; 5 or 8 nmol TPA plus mirex gave additive or less tumor multiplicities. This synergistic multiplicity with mirex plus 2 nmol TPA (35 tumors/mouse) approximated the sum of individual responses to 200 nmol mirex (14 tumors/mouse) and the maximally promoting dose of TPA (12 nmol), 24 tumors/mouse, suggesting that mirex potentiated the promotional activity of TPA, as well as promoted through a mirex-specific mechanism. Epidermal DNA synthesis induced by 2 nmol TPA was potentiated by mirex, further supporting a role for mirex in potentiation of epidermal TPA activity. Collectively, these studies suggest that mirex affects two possibly related responses: (i) promotion through a distinct mirex-specific mechanism, and (ii) potentiation of a mechanism mediating the promotional activity of TPA.}, number={1}, journal={CARCINOGENESIS}, author={MEYER, SA and KIM, TW and MOSER, GJ and MONTEIRORIVIERE, NA and SMART, RC}, year={1994}, month={Jan}, pages={47–52} }
 @article{heit_monteiro-riviere_jayes_riviere_1994, title={Transdermal iontophoretic delivery of luteinizing hormone releasing hormone (LHRH): Effect of repeated administration}, volume={11}, ISSN={["1573-904X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1994NW46700012&KeyUID=WOS:A1994NW46700012}, DOI={10.1023/A:1018983303842}, number={7}, journal={Pharmaceutical Research}, author={Heit, M.C. and Monteiro-Riviere, N.A. and Jayes, F.L. and Riviere, J.E.}, year={1994}, pages={1000–1003} }
 @article{spoo_rogers_monteiro-riviere_1993, title={Effects of formaldehyde, DMSO, benzoyl peroxide, and sodium lauryl sulfate on isolated perfused porcine skin}, volume={5}, journal={In Vitro Toxicology}, author={Spoo, J. W. and Rogers, R. A. and Monteiro-Riviere, N. A.}, year={1993}, pages={251–260} }
 @book{a_w_l_1993, title={INTEGUMENT}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199243095656&KeyUID=BIOSIS:PREV199243095656}, journal={Dellmann, H.-D. Textbook of Veterinary Histology, Fourth Edition. Ix+351p. Lea and Febiger: Malvern, Pennsylvania, Usa. Illus}, author={A, MONTEIRO-RIVIERE N and W, STINSON A and L, CALHOUN M}, year={1993}, pages={285–312} }
 @article{meyer_moser_monteiroriviere_smart_1993, title={MINIMAL ROLE OF ENHANCED CELL-PROLIFERATION IN SKIN TUMOR PROMOTION BY MIREX - A NONPHORBOL ESTER-TYPE PROMOTER}, volume={101}, ISSN={["0091-6765"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1993NB89100044&KeyUID=WOS:A1993NB89100044}, DOI={10.2307/3431879}, number={Suppl. 5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={MEYER, SA and MOSER, GJ and MONTEIRORIVIERE, NA and SMART, RC}, year={1993}, month={Dec}, pages={265–269} }
 @inbook{riviere_monteiro-riviere_1993, title={Porcine Skin Flaps}, ISBN={9780124612013}, url={http://dx.doi.org/10.1016/b978-0-12-461201-3.50051-7}, DOI={10.1016/b978-0-12-461201-3.50051-7}, booktitle={In Vitro Biological Systems}, publisher={Elsevier}, author={Riviere, J. Edmond and Monteiro-Riviere, Nancy A.}, year={1993}, pages={515–524} }
 @inproceedings{monteiro-riviere_inman_spoo_rogers_riviere_1993, title={Studies on the pathogenesis of bis (2-chloroethyl) sulfide (HD) induced vesication in porcine skin}, booktitle={Proceedings of the Eighth Medical Defense Bioscience Review  U.S. Army Medical Research Institute of Chemical Defense}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={Monteiro-Riviere, N. A. and Inman, A. O. and Spoo, J. W. and Rogers, R. A. and Riviere, J. E.}, year={1993}, pages={31–40} }
 @article{monteiroriviere_inman_riviere_mcneill_francoeur_1993, title={TOPICAL PENETRATION OF PIROXICAM IS DEPENDENT ON THE DISTRIBUTION OF THE LOCAL CUTANEOUS VASCULATURE}, volume={10}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1993LV52400013&KeyUID=WOS:A1993LV52400013}, number={9}, journal={Pharmaceutical Research}, author={MONTEIRORIVIERE, NA and INMAN, AO and RIVIERE, JE and MCNEILL, SC and FRANCOEUR, ML}, year={1993}, pages={1326–1331} }
 @article{monteiro-riviere_inman_riviere_mcneil_francoeur_1993, title={Topical penetration of piroxicam is dependent on the distribution of the local cutaneous vasculature}, volume={10}, DOI={10.1023/A:1018973814456}, journal={Pharmaceutical Research}, author={Monteiro-Riviere, N.A. and Inman, A. O. and Riviere, J. E. and McNeil, S. C. and Francoeur, M. L.}, year={1993}, pages={1326–1331} }
 @article{monteiro-riviere_iman_riviere_mcneill_francoeur_1992, title={A new hypothesis for the mechanism of local enhanced delivery of topically applied drugs to the underlying musculature}, volume={9}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199344034170&KeyUID=BIOSIS:PREV199344034170}, number={10 SUPPL.}, journal={Pharmaceutical Research (New York)}, author={Monteiro-Riviere, N. A. and Iman, A. O. and Riviere, J. E. and McNeill, S. C. and Francoeur, M. L.}, year={1992}, pages={S169} }
 @article{king_riviere_monteiroriviere_1992, title={CHARACTERIZATION OF LEWISITE TOXICITY IN ISOLATED PERFUSED SKIN}, volume={116}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1992JR70900005&KeyUID=WOS:A1992JR70900005}, DOI={10.1016/0041-008X(92)90298-7}, abstractNote={Lewisite (L) is a potent organic arsenical that causes rapid onset of pain and severe vesication on contact with epithelial tissues. The isolated perfused porcine skin flap (IPPSF) is an in vitro model that has shown potential as a model for cutaneous vesicant research. The objective of this study was to characterize IPPSF responses after topical exposure to six concentrations of L ranging from 0.07 to 5.0 mg/ml (n = 4/treatment plus controls). Biochemical markers of viability (glucose utilization (CGU) and lactate dehydrogenase (LDH) release), vascular resistance (VR), venous arsenic flux, and morphological parameters (light and electron microscopy) were evaluated. In addition, lewisite lesions were characterized at 1, 3, 5, and 8 hr after exposure (n = 4/time plus controls) using these morphological parameters, as well as enzyme histochemistry. Macroscopic and microscopic lesions caused by L exposure were dose related. Mild decreases in CGU were noted with the higher concentrations of L, while generally increased responses in LDH release and VR were seen. Marked increases in LDH activity were noted in the blister fluid of IPPSFs treated with 5.0 mg/ml of L. Also, significant cutaneous arsenic flux was noted at the 5.0 mg/ml dose of L. The formation of gross blisters, the location and characterization of epidermal-dermal junction separation, and the time course of lesion production paralleled the description of L-induced lesions in humans. The sensitivity of the IPPSF to L exposure and the similarity of lesions to those described for humans suggests that this model provides a relevant in vitro model with which to study mechanisms of chemical vesication and arsenic toxicity, as well as protective and therapeutic intervention for vesicant exposure.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={KING, JR and RIVIERE, JE and MONTEIRORIVIERE, NA}, year={1992}, month={Oct}, pages={189–201} }
 @article{srikrishna_riviere_monteiroriviere_1992, title={CUTANEOUS TOXICITY AND ABSORPTION OF PARAQUAT IN PORCINE SKIN}, volume={115}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1992JC47400012&KeyUID=WOS:A1992JC47400012}, DOI={10.1016/0041-008X(92)90371-X}, abstractNote={Paraquat, a commonly used herbicide, has been shown to be toxic in exposed field workers. The objectives of this study were to (a) assess the cutaneous toxicity of paraquat in vivo in pig skin and in vitro in the isolated perfused porcine skin flap (IPPSF) and (b) quantitate its absorption in the IPPSF. The amounts of 3, 24, and 200 mg of paraquat were topically applied (5 cm2 surface area) on the ventral abdomen of pigs and biopsied after 6-8 hr for light microscopy (LM) and transmission electron microscopy (TEM). IPPSFs were topically dosed with the same concentrations and perfused for 8 hr (n = 4/treatment). The dosed area of the skin was sampled for LM, TEM, and enzyme histochemistry. IPPSFs were also treated topically with [14C]paraquat dichloride at the aforementioned concentrations (n = 4/dose) and hourly perfusate samples were collected for radiolabel determination and assessment of biochemical and physiological parameters. The epidermal changes were similar both in vivo and in vitro. The changes included epidermal intercellular edema which increased with dose and epidermal-dermal separation at the 200-mg dose. Acid phosphatase and nonspecific esterase activities were increased in the upper layers of the epidermis, while alkaline phosphatase showed a greater activity in the stratum basale layer. Glucose utilization of all treated IPPSFs was lower than that of the controls and a variation in the vascular resistance profiles was seen in all the treated flaps. Radiotracer studies indicated that a majority of the compound remained on top of the application site and minimal absorption or penetration into skin was observed. Thus, at high concentrations and prolonged exposure, paraquat may have deleterious effects on epidermal morphology in the absence of significant percutaneous absorption.}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={SRIKRISHNA, V and RIVIERE, JE and MONTEIRORIVIERE, NA}, year={1992}, month={Jul}, pages={89–97} }
 @article{riviere_monteiroriviere_inman_1992, title={DETERMINATION OF LIDOCAINE CONCENTRATIONS IN SKIN AFTER TRANSDERMAL IONTOPHORESIS - EFFECTS OF VASOACTIVE DRUGS}, volume={9}, ISSN={["0724-8741"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1992HC29100010&KeyUID=WOS:A1992HC29100010}, DOI={10.1023/a:1018985323001}, number={2}, journal={PHARMACEUTICAL RESEARCH}, author={RIVIERE, JE and MONTEIRORIVIERE, NA and INMAN, AO}, year={1992}, month={Feb}, pages={211–214} }
 @article{venkatesh_levi_inman_monteiroriviere_misra_hodgson_1992, title={ENZYMATIC AND IMMUNOHISTOCHEMICAL STUDIES ON THE ROLE OF CYTOCHROME-P450 AND THE FLAVIN-CONTAINING MONOOXYGENASE OF MOUSE SKIN IN THE METABOLISM OF PESTICIDES AND OTHER XENOBIOTICS}, volume={43}, ISSN={["1095-9939"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1992HV42800007&KeyUID=WOS:A1992HV42800007}, DOI={10.1016/0048-3575(92)90019-V}, abstractNote={Abstract The cytochrome P450 (P450) content, the cytochrome c reductase activity, the metabolism of a variety of P450 substrates, and the presence and role of flavin-containing monooxygenase (FMO) in xenobiotic metabolism were studied in skin microsomes and compared to those of liver. The cytochrome P450 content of skin as determined by CO-dithionite-reduced minus CO-oxidized spectra was approximately 6.8% of the liver P450 content. By comparison, cytochrome c reductase activity in skin microsomes was high, being equivalent to approximately one-third of the liver microsomal enzyme activity. Skin microsomes metabolized several known P450 substrates and, depending upon the substrate used, the specific activity ranged from 2.5 to 13.4% of the corresponding rates seen in liver microsomes. Skin microsomes exhibited the highest enzymatic activity with benzo[ a ]pyrene and ethoxyresorufin, moderate activity with parathion and aldrin, and low activity with benzphetamine and ethoxycoumarin. Skin microsomes also metabolized the triazine herbicides atrazine, simazine, and terbutryn, with the activity being 2 to 5% of the liver microsomal activity. FMO activity in skin microsomes with thiobenzamide and methimazole as substrates ranged from 10 to 20% of the liver FMO activity. Immunohistochemical studies using antibodies to mouse liver FMO showed localization primarily in the epidermis. Additional studies using pig skin showed a similar distribution pattern. Antibodies developed to mouse liver FMO and the constitutive liver P450 isozyme, 1A2, showed cross-reactivity on Western blots with proteins in skin microsomes that appeared identical to the cross-reacting proteins present in liver microsomes. The relative contribution of P450 and FMO in mouse skin to the sulfoxidation of phorate was investigated and compared to that of liver microsomes. Several procedures were employed to selectively inhibit either P450 or FMO to determine the role of each monooxygenase system in the absence of the other system. In liver microsomes, P450 was responsible for 68 to 85% of the phorate sulfoxidation activity. In contrast, in skin microsomes 66 to 69% of the phorate sulfoxidation activity was due to FMO, while P450 was responsible for the remainder of the activity. Thus, although the overall phorate sulfoxidation rate in mouse skin microsomes was only 3 to 4% of the rate seen in liver, FMO appears to assume a greater relative role to P450 in the metabolic processes in skin.}, number={1}, journal={PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY}, author={VENKATESH, K and LEVI, PE and INMAN, AO and MONTEIRORIVIERE, NA and MISRA, R and HODGSON, E}, year={1992}, month={May}, pages={53–66} }
 @inproceedings{bristol_riviere_monteiro-riviere_brooks_rogers_1992, title={Effect of vehicle and application site on absorption of chemicals through equine skin}, volume={38}, booktitle={Proceedings, 38th Annual Convention of the American Association of Equine Practitioners}, author={Bristol, D. G. and Riviere, J. E. and Monteiro-Riviere, N. A. and Brooks, J. D. and Rogers, R. A.}, year={1992}, pages={725} }
 @article{monteiroriviere_1992, title={LANGERHANS CELL GRANULES IN PORCINE EPIDERMIS}, volume={180}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1992JK80100018&KeyUID=WOS:A1992JK80100018}, journal={Journal of Anatomy}, author={MONTEIRORIVIERE, NA}, year={1992}, pages={555–556} }
 @inbook{monteiro-riviere_stinson_calhoun_1992, title={The integument}, ISBN={0812115538}, booktitle={Textbook of veterinary histology. (4th ed.)}, publisher={Philadelphia: Lea & Febiger}, author={Monteiro-Riviere, N. A. and Stinson, A. W. and Calhoun, H. L.}, year={1992}, pages={285–312} }
 @article{monteiro-riviere_1992, title={The use of isolated perfused skin in dermatotoxicology}, volume={5}, journal={In Vitro Toxicology}, author={Monteiro-Riviere, N. A.}, year={1992}, pages={219–233} }
 @article{manning_monteiroriviere_bristol_riviere_1991, title={CUTANEOUS LASER-DOPPLER VELOCIMETRY IN 9 ANIMAL SPECIES}, volume={52}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1991GT51300007&KeyUID=WOS:A1991GT51300007}, number={12}, journal={American Journal of Veterinary Research}, author={MANNING, TO and MONTEIRORIVIERE, NA and BRISTOL, DG and RIVIERE, JE}, year={1991}, pages={1960–1964} }
 @inproceedings{king_monteiro-riviere_riviere_1991, title={Characterization of lewisite vesication in isolated perfused porcine skin}, booktitle={Proceedings of the 1991 Medical Defense Bioscience Review}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={King, J. R. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={1991}, pages={167–170} }
 @inproceedings{riviere_king_monteiro-riviere_1991, title={Characterization of the cutaneous vascular response to topically applied sulfur mustard and lewisite}, booktitle={Proceedings of the 1991 Medical Defense Bioscience Review}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={Riviere, J. E. and King, J. R. and Monteiro-Riviere, N. A.}, year={1991}, pages={163–166} }
 @inbook{monteiro-riviere_1991, title={Comparative anatomy, physiology, and biochemistry of mammalian skin}, ISBN={0849388112}, booktitle={Dermal and ocular toxicology: Fundamentals and methods}, publisher={Boca Raton, FL: CRC Press}, author={Monteiro-Riviere, N. A.}, year={1991}, pages={3–71} }
 @book{monteiro-riviere_riviere_1991, title={Cutaneous toxicity of mustard and lewisite on the isolated perfused porcine skin flap}, journal={DAMD17-87-C-7139; NTIS, ADA254419}, author={Monteiro-Riviere, N. A. and Riviere, J. E.}, year={1991}, pages={1–140} }
 @article{bowman_monteiroriviere_riviere_1991, title={DEVELOPMENT OF SURGICAL TECHNIQUES FOR PREPARATION OF INVITRO-ISOLATED PERFUSED PORCINE SKIN FLAPS FOR PERCUTANEOUS-ABSORPTION STUDIES}, volume={52}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1991ER42900016&KeyUID=WOS:A1991ER42900016}, number={1}, journal={American Journal of Veterinary Research}, author={BOWMAN, KF and MONTEIRORIVIERE, NA and RIVIERE, JE}, year={1991}, pages={75–82} }
 @article{king_monteiro-riviere_1991, title={Effects of organic solvent vehicles on the viability and morphology of isolated perfused porcine skin}, volume={69}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1991GH30900002&KeyUID=WOS:A1991GH30900002}, DOI={10.1016/0300-483x(91)90149-u}, abstractNote={Although many organic solvents are known tio be cutaneous irritants, they are commonly utilized as vehicles in percutaneous absorption and toxicity studies. The isolated perfused porcine skin flap (IPPSF) is an alternative animal model that has been used to study percutaneous absoprtion and cutaneous toxicity. The purpose of this study was to evaluate the effect of five organic solvents (ethanol, acetone, dimethyl sulfoxide (DMSO), toluene, and cyclohexane) on biochemical viability parameters, vascular response, and epidermal morphology of the OPPSF. Cumulative glucose utilization (CGU), the ratio of lactate production/glucose utilization (L/CGU ratio),a nd the leakage of lactate dehydrogenase (LDH) were used as biochemical indicators of alterations in glucose metabolism and flap viability. Only ethanol resulted in a statistically sigficantly decrease in the average rate of CGU over the perfusion. All of the solvent treatments resulted in slight in LDH release versus the control. Vascular resistance (VR) was measured to examine the response of the cutaneous vasculature to these solvents,a nd most treatments resulted in a decreased VR in the terminal phases of perfusion. Ethanol was the only solvent to cause an apparent increase in terminal VR. Light micriscopy demonstrated a modelrate increase in intracellular edema in the DMSO, toluene, and acetone flaps. Ultrastructural evaluation showed focal bledding of the nuclear envelope amd vesiculation of the rough endoplasmic reticulum in cells of the stratum basale and styratum spinosum layers with DMSO treatment. The IPPSF allowed the evaluation of subtle biochemical, vascular, and morphological changes associated with non-occlusive topical exposure to these organic solvents. These findings support the necessity of documenting vehicle efefcts which might mask or other wise alter subtle,but potentially important, compound-specific responses.}, number={1}, journal={Toxicology (Amsterdam, Netherlands)}, author={King, J. R. and Monteiro-Riviere, N.A.}, year={1991}, pages={11–26} }
 @article{a_o_e_1991, title={IDENTIFICATION OF THE PATHWAY OF TRANSDERMAL IONTOPHORETIC DRUG DELIVERY ULTRASTRUCTURAL STUDIES USING MERCURIC CHLORIDE IN-VIVO IN PIGS}, volume={8}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199242016040&KeyUID=BIOSIS:PREV199242016040}, number={10 SUPPL}, journal={Pharmaceutical Research (New York)}, author={A, MONTEIRO-RIVIERE N and O, INMAN A and E, RIVIERE J}, year={1991}, pages={S141} }
 @article{monteiroriviere_banks_birnbaum_1991, title={LASER DOPPLER MEASUREMENTS OF CUTANEOUS BLOOD-FLOW IN AGING MICE AND RATS}, volume={57}, ISSN={["0378-4274"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1991GC02800010&KeyUID=WOS:A1991GC02800010}, DOI={10.1016/0378-4274(91)90207-M}, abstractNote={Laser Doppler velocimetry (LDV) is a non-invasive technique that measures capillary blood perfusion parameters (blood flow, volume and velocity) and can be used non-invasively to evaluate the effects of ageing on cutaneous blood perfusion. Male Fischer-344 rats (R) of 1, 2, 3, 8, 12, 16, 20 and 24 months and C57BL/6N mice (M) 1, 2, 3, 9, 15, 19 and 22 months (n=6/mo) were used. Animals were anesthetized with ketamine/xylazine and LDV-measured blood flow was made on the backs of all animals. Five readings for each parameter were recorded in order to obtain a mean value of the individual. Skin biopsies (4 mm) were removed after LDV for assessing epidermal and dermal thickness and number of epidermal cell layers. The number of viable epidermal layers in M remained constant while in R it decreased with age. Epidermal thickness in both M and R decreased from 2–3 months and then remained constant. Dermal thickness decreased from 3 to 22 months in M, and increased in R from 1 to 2 months and remained constant. Blood flow of M increased between 1 and 2 months, remained constant to 19 months, then increased at 22 months; flow in R was constant except at 2 months. Thus age differences in epidermal and dermal thickness, and blood flow of M and R occur and should be considered when evaluating cutaneous toxicity studies in different-aged animals. These changes may potentially alter dermal absorption and/or distribution of xenobiotics.}, number={3}, journal={TOXICOLOGY LETTERS}, author={MONTEIRORIVIERE, NA and BANKS, YB and BIRNBAUM, LS}, year={1991}, month={Aug}, pages={329–338} }
 @inproceedings{monteiro-riviere_king_riviere_1991, title={Mustard induced vesication in isolated perfused skin: Biochemical, physiological, and morphological studies}, booktitle={Proceedings of the 1991 Medical Defense Bioscience Review}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={Monteiro-Riviere, N. A. and King, J. R. and Riviere, J. E.}, year={1991}, pages={159–162} }
 @article{v_a_1991, title={THE EFFECTS OF SODIUM HYDROXIDE AND HYDROCHLORIC ACID ON ISOLATED PERFUSED SKIN}, volume={4}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV199293071955&KeyUID=BIOSIS:PREV199293071955}, number={3}, journal={In Vitro Toxicology}, author={V, SRIKRISHNA and A, MONTEIRO-RIVIERE N}, year={1991}, pages={207–216} }
 @article{bristol_riviere_monteiroriviere_bowman_rogers_1991, title={THE ISOLATED PERFUSED EQUINE SKIN FLAP - PREPARATION AND METABOLIC PARAMETERS}, volume={20}, ISSN={["0161-3499"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1991GP81300010&KeyUID=WOS:A1991GP81300010}, DOI={10.1111/j.1532-950X.1991.tb00351.x}, abstractNote={A model for the study of equine cutaneous physiology, pharmacology, and toxicology was developed. Four 4 x 12 cm and twenty-one 6 x 12 cm single-pedicle axial pattern skin flaps based on the caudal superficial epigastric artery, and eight 6 x 12 cm flaps based on the saphenous artery and medial saphenous vein, were raised and sutured in a tubed configuration. On day 2, each flap was removed, the artery was cannulated, and the flap was perfused with a modified Krebs-Ringer's albumin-based medium for at least 6 hours. Flap viability was assessed by glucose use, lactate production, and histologic examination at the end of the perfusion period. The 4 x 12 cm flaps had evidence of skin necrosis, but the 6 x 12 cm flaps remained histologically viable. Results were compared to those previously reported from perfusion of porcine skin flaps based on the caudal superficial epigastric artery. While the ratios of glucose use to lactate production were similar, equine flaps used less glucose and produced less lactate per gram of tissue than similar pig flaps. Equine skin flaps perfused by saphenous vessels used more glucose and produced more lactate than flaps perfused by caudal superficial epigastric vessels. These results indicate that conclusions drawn from cutaneous physiology studies should not be extrapolated across species lines and that site-specific skin should be used for cutaneous physiology, pharmacology, and toxicology studies. The identified skin flaps may have applications in equine reconstructive surgery.}, number={6}, journal={VETERINARY SURGERY}, author={BRISTOL, DG and RIVIERE, JE and MONTEIRORIVIERE, NA and BOWMAN, KF and ROGERS, RA}, year={1991}, pages={424–433} }
 @misc{riviere_monteiroriviere_1991, title={THE ISOLATED PERFUSED PORCINE SKIN FLAP AS AN INVITRO MODEL FOR PERCUTANEOUS-ABSORPTION AND CUTANEOUS TOXICOLOGY}, volume={21}, ISSN={["1547-6898"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1991GC88700002&KeyUID=WOS:A1991GC88700002}, DOI={10.3109/10408449109019570}, abstractNote={The isolated perfused porcine skin flap (IPPSF) is a new perfused skin model which allows in vitro cutaneous pharmacology and toxicology studies to be conducted in a viable skin preparation which has a normal anatomical structure and a functional microcirculation. The purpose of this review is to (1) outline the background of this field which indicated the need for this type of model; (2) outline the surgical procedures needed to create and harvest viable preparations; (3) overview the criteria (biochemical, physiological, and histological) used to assess viability during an experiment; (4) present results of percutaneous absorption, cutaneous metabolism, transdermal delivery (passive and active), and skin distribution experiments conducted to date; (5) present the strategy developed to quantitate percutaneous absorption and cutaneous drug distribution using compartmental and physiological-based pharmacokinetic models; (6) assess the correlation of IPPSF data to in vivo results; (7) define the biochemical, physiological and histological (LM, TEM, enzyme histochemistry) response of the IPPSF to topically applied cutaneous vesicants; (8) overview where this type of in vitro model fits into the overall framework of cutaneous toxicology and pharmacology research; and (9) outline possible paths for future development. This review should provide the reader with an appreciation of some unique problems in this field which require an in vitro model that is closely integrated in structure and function to the in vivo setting.}, number={5}, journal={CRITICAL REVIEWS IN TOXICOLOGY}, author={RIVIERE, JE and MONTEIRORIVIERE, NA}, year={1991}, pages={329–344} }
 @article{srikrishna_monteiro-riviere_1991, title={The effects of sodium hydroxide and hydrochloric acid on isolated perfused skin}, volume={4}, journal={In Vitro Toxicology}, author={Srikrishna, V. and Monteiro-Riviere, N. A.}, year={1991}, pages={207–215} }
 @article{monteiroriviere_1990, title={ALTERED EPIDERMAL MORPHOLOGY SECONDARY TO LIDOCAINE IONTOPHORESIS - INVIVO AND INVITRO STUDIES IN PORCINE SKIN}, volume={15}, ISSN={["0272-0590"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1990DP30100020&KeyUID=WOS:A1990DP30100020}, DOI={10.1016/0272-0590(90)90174-I}, abstractNote={Iontophoresis is the process of delivering ionic drugs across the skin using electric current. Iontophoresis of lidocaine hydrochloride in 30 pigs in vivo and in 112 in vitro isolated perfused porcine skin flap (IPPSF) preparations produced a drug-specific alteration in the epidermis greater than or equal to 10 min after dosing. By light microscopy, this change was characterized by the appearance of flattened dark basophilic staining nuclei oriented parallel to the stratum corneum in the stratum granulosum and spinosum layers. In severe cases, this alteration extended into the deeper usually vacuolated stratum basale. The stratum corneum appeared normal. This unique morphological alteration showed an abrupt change from the stratum basale to stratum granulosum. An immune-mediated etiology can be ruled out since this alteration is observed both in vivo and in vitro. The severity of this change, graded on a scale of 0-3 (no change to severe), was best correlated to total transcutaneous lidocaine flux as estimated in IPPSF studies and to flux as estimated by current (mA-hr) in vivo. Electron microscopic changes following iontophoresis showed specific alterations in the tonofilaments of the epidermal cells. The tonofilaments appeared unrecognizable and resembled an amorphous matrix. In pigs followed through 10 days to study the resolution of this alteration, the epidermis reverted to normal within 6 days with no additional manifestations. In conclusion, lidocaine iontophoresis can induce in swine a unique dose-dependent non-immune-mediated epidermal alteration which is expected to have minimal toxicological significance.}, number={1}, journal={FUNDAMENTAL AND APPLIED TOXICOLOGY}, author={MONTEIRORIVIERE, NA}, year={1990}, month={Jul}, pages={174–185} }
 @article{king_monteiroriviere_1990, title={CUTANEOUS TOXICITY OF 2-CHLOROETHYL METHYL SULFIDE IN ISOLATED PERFUSED PORCINE SKIN}, volume={104}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1990DJ59700017&KeyUID=WOS:A1990DJ59700017}, DOI={10.1016/0041-008X(90)90292-3}, abstractNote={Previous research has shown the isolated perfused porcine skin flap (IPPSF) to be a novel in vitro experimental model for investigating xenobiotic percutaneous absorption. In this study, the IPPSF was used to biochemically and morphologically assess the dermatotoxicity of 2-chloroethyl methyl sulfide (CEMS), a monofunctional analog of the vesicant, sulfur mustard. IPPSFs were perfused in a recirculating perfusion system and were treated with 97% CEMS (n = 4) or served as controls (n = 4). Additional IPPSFs were perfused in a nonrecirculating perfusion system and were treated with CEMS (n = 4) or were controls (n = 4). After dosing, each IPPSF was perfused for 8 hr. Cumulative glucose utilization (GU) and lactate production/glucose utilization ratio (L/GU ratio) were used as viability parameters. The average rate of GU for CEMS was significantly lower than control (p less than 0.05) in the recirculating and nonrecirculating IPPSFs. The L/GU ratio for CEMS was not significantly different (p greater than 0.05) from control for either perfusion system. CEMS resulted in a marked increase in vascular resistance versus control in both perfusion systems. Gross vesicles and bullae formation occurred in six of the CEMS-treated IPPSFs. Light microscopy revealed subepidermal vesicle formation above the basement membrane and extensive basal cell pyknosis in all IPPSFs treated with CEMS. No macroscopic or microscopic lesions were noted in the control flaps. Transmission electron microscopy revealed separation between the lamina lucida and the lamina densa of the basal lamina, with intracellular vacuolization and mitochondrial swelling occurring in the stratum basale and stratum spinosum cells of IPPSFs treated with CEMS. These lesions are similar to those described after human exposure to sulfur mustard. Full characterization of the morphological and biochemical changes seen after topical exposure of the IPPSF to vesicants may shed light on the pathogenesis of cutaneous toxicity of these compounds in vivo and serve as a relevant model to assess protective strategies against vesicant exposure.}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={KING, JR and MONTEIRORIVIERE, NA}, year={1990}, month={Jun}, pages={167–179} }
 @book{monteiro-riviere_king_riviere_1990, title={Cutaneous toxicity of mustard and lewisite on the isolated perfused porcine skin flap}, journal={DAMD17-87-C-7139; NTIS, ADA 229922}, institution={NTIS}, author={Monteiro-Riviere, N. A. and King, J. R. and Riviere, J. E.}, year={1990}, pages={1–144} }
 @article{hansen_monteiroriviere_smart_1990, title={DIFFERENTIAL DOWN-REGULATION OF EPIDERMAL PROTEIN-KINASE-C BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE AND DIACYLGLYCEROL - ASSOCIATION WITH EPIDERMAL HYPERPLASIA AND TUMOR PROMOTION}, volume={50}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1990DY41800007&KeyUID=WOS:A1990DY41800007}, number={18}, journal={Cancer Research}, author={HANSEN, LA and MONTEIRORIVIERE, NA and SMART, RC}, year={1990}, pages={5740–5745} }
 @article{monteiroriviere_bristol_manning_rogers_riviere_1990, title={INTERSPECIES AND INTERREGIONAL ANALYSIS OF THE COMPARATIVE HISTOLOGIC THICKNESS AND LASER DOPPLER BLOOD-FLOW MEASUREMENTS AT 5 CUTANEOUS SITES IN 9 SPECIES}, volume={95}, ISSN={["0022-202X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1990EJ41400018&KeyUID=WOS:A1990EJ41400018}, DOI={10.1111/1523-1747.ep12505567}, abstractNote={Studies in dermatology, cutaneous pharmacology, and toxicology utilize skin from different animal species and body sites. However, regional differences exist in topical chemical percutaneous absorption studies in man and in animal. The objective of this study was to compare epidermal thickness and number of cell layers across species and body sites using both formalin-fixed paraffin and frozen sections. Cutaneous blood flow determined by laser Doppler velocimetry (LDV) was compared to histologic data. Six animals of each of the following species were used: monkeys, pigs, dogs, cats, cows, horses, rabbits, rats, and mice. Cutaneous blood flow was determined and 6-mm skin biopsies were taken directly from the following sites: buttocks, ear, humeroscapular joint, thoracolumbar junction, and abdominal area. When the two histologic methods were compared across all species and body sites, the thickness of the epidermis was significantly greater, and the thickness of the stratum corneum significantly less, in paraffin sections versus frozen sections (p less than 0.05). There were no differences in the number of viable cell layers determined by both methods. The values for LDV-determined blood flow did not significantly correlate (p greater than 0.05) to epidermal or stratum corneum thickness. However, regional and species differences were noted in all these parameters. In conclusion, these data indicate that thickness and LDV blood flow are independent and must be evaluated separately when comparisons are made between species and body sites. This work provides a data base for future comparative studies in which a knowledge of skin thickness or blood flow might be important variables.}, number={5}, journal={JOURNAL OF INVESTIGATIVE DERMATOLOGY}, author={MONTEIRORIVIERE, NA and BRISTOL, DG and MANNING, TO and ROGERS, RA and RIVIERE, JE}, year={1990}, month={Nov}, pages={582–586} }
 @inbook{riviere_monteiro-riviere_1990, title={Percutaneous absorption of pesticides in the isolated perfused porcine skin flap (IPPSF)}, ISBN={0080419976}, booktitle={Advances in veterinary dermatology. Vol. 1}, publisher={London: Balliere-Tindall}, author={Riviere, J. E. and Monteiro-Riviere, N. A.}, editor={Halliwell, R. E. W. and Tscharner, C.Editors}, year={1990}, pages={299–307} }
 @inbook{monteiro-riviere_1990, title={Specialized technique: Isolated perfused porcine skin flap}, ISBN={0849346517}, booktitle={Methods for skin absorption}, publisher={Boca Raton, FL: CRC Press}, author={Monteiro-Riviere, N. A.}, editor={Kemppainen, B. W. and Reifenrath, W. G.Editors}, year={1990}, pages={175–189} }
 @article{riviere_sage_monteiroriviere_1989, title={TRANSDERMAL LIDOCAINE IONTOPHORESIS IN ISOLATED PERFUSED PORCINE SKIN}, volume={8}, ISSN={["0731-3829"]}, DOI={10.3109/15569528909062953}, abstractNote={AbstractThe isolated perfused porcine skin flap (IPPSF) is an alternative animal model for quantitatively assessing percutaneous drug absorption. The ability to place drugs or chemicals on the surface of viable skin with a functional microcirculation maintained in a controlled ambient environment, coupled with the measurement of arterial and venous drug concentrations, makes this model well suited for modeling percutaneous drug flux after transder-mal delivery. Lidocaine hydrochloride was used as the model drug to investigate the dynamics of transdermal delivery using iontophoresis. Total lidocaine flux (bioavailability) was a function of lidocaine concentration, current density, and duration of application. Rate of transdermal flux was a function of concentration, current density, and the presence or absence of coadministered epinephrine (reduced) or tolazoline (increased). The presence of vasodilators significantly affected the magnitude of peak venous}, number={4}, journal={JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY}, author={RIVIERE, JE and SAGE, BH and MONTEIRORIVIERE, NA}, year={1989}, pages={493–504} }
 @inproceedings{monteiro-riviere_king_1989, title={The dermatotoxicity of 2- chloroethyl methyl sulfide and solvent vehicles in isolated perfused porcine skin}, booktitle={Proceedings of the 1989 Medical Defense Bioscience Review}, publisher={Aberdeen, MD: U.S. Army Medical Research Institute of Chemical Defense}, author={Monteiro-Riviere, N. A. and King, J. R.}, year={1989}, pages={53–56} }
 @article{smart_huang_monteiroriviere_wong_mills_conney_1988, title={COMPARISON OF THE EFFECT OF SN-1,2-DIDECANOYLGLYCEROL AND 12-O-TETRADECANOYLPHORBOL-13-ACETATE ON CUTANEOUS MORPHOLOGY, INFLAMMATION AND TUMOR PROMOTION IN CD-1 MICE}, volume={9}, ISSN={["0143-3334"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1988R257800013&KeyUID=WOS:A1988R257800013}, DOI={10.1093/carcin/9.12.2221}, abstractNote={Since sn-1,2-didecanoylglycerol mimics 12-O-tetradecanoylphorbol-13-acetate (TPA) by inducing ornithine decarboxylase activity and stimulating DNA synthesis in mouse epidermis [Smart, R.C., Huang, M.-T. and Conney, A.H. Carcinogenesis, 7, 1865 (1986)], we have investigated morphological changes induced by TPA and sn-1,2-didecanoylglycerol in the epidermis and we have also examined sn-1,2-didecanoylglycerol as a possible complete tumor promoter. It was determined that topical application of 2.5 or 10 mumol of sn-1,2-didecanoylglycerol induced epidermal ornithine decarboxylase activity to about the same extent as the application of 1 or 2 nmol of TPA respectively. Therefore, these doses of TPA and sn-1,2-didecanoylglycerol were used in most of our studies. Single or multiple application (2 X/week for 4 weeks) of 1, 2 or 5 nmol of TPA to the skin of CD-1 mice produced a dose-dependent increase in the number of epidermal non-cornified cell layers, epidermal thickness, leukocyte infiltration and intracellular edema. In contrast, neither single nor multiple application (2 X/week for 4 weeks) of 2.5 or 10 mumol sn-1,2-didecanoylglycerol produced any of these responses. However, when 5 mumol sn-1,2-didecanoylglycerol was applied topically twice a day (10 mumol/day) for 5 days there was a significant increase in the number of epidermal non-cornified cell layers and epidermal thickness. The effects of TPA and sn-1,2-didecanoylglycerol were compared using the mouse ear inflammation model. Application of TPA caused edema, but sn-1,2-didecanoylglycerol had little or no effect. sn-1,2-Didecanoylglycerol was then evaluated as a complete tumor promoter utilizing the mouse skin two-stage model. CD-1 mice were initiated with 200 nmol 7,12-dimethylbenz[a]anthracene and then treated with 1 nmol TPA or 2.5 mumol sn-1,2-didecanoylglycerol twice a week for 28 weeks. A 28 weeks, 28% of the mice treated with TPA had developed tumors, while none of the mice treated with 2.5 mumol sn-1,2-didecanoylglycerol developed tumors. The data indicate that topical application of 2.5 mumol sn-1,2-didecanoylglycerol induced ornithine decarboxylase activity to the same extent as a tumor-promoting dose of 1 nmol TPA, but it did not cause morphological changes in the epidermis when applied once or when applied twice a week for 4 weeks and did not function as a complete tumor promoter when applied twice a week for 28 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)}, number={12}, journal={CARCINOGENESIS}, author={SMART, RC and HUANG, MT and MONTEIRORIVIERE, NA and WONG, CQ and MILLS, KJ and CONNEY, AH}, year={1988}, month={Dec}, pages={2221–2226} }
 @article{shehatakaram_monteiroriviere_guthrie_1988, title={INVITRO PENETRATION OF PESTICIDES THROUGH HUMAN NEWBORN FORESKIN}, volume={40}, ISSN={["0378-4274"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1988M439900006&KeyUID=WOS:A1988M439900006}, DOI={10.1016/0378-4274(88)90046-X}, abstractNote={The in vitro dermal penetration of 14C-labelled parathion, fenvalerate, carbofuran, and lindane through fresh full-thickness human newborn foreskin was determined at 1, 6, 24, and 48 h. The pesticides were applied to a constant dosing area (0.031 cm2), and a fixed dose (1.18 microgram), for each of the compounds studied. 90%, or greater, of the labelled pesticides were recovered in all cases. Carbofuran showed the greatest mean penetration of 82% followed by parathion and lindane with mean penetrations of 79 and 66%, respectively. Fenvalerate exhibited a mean penetration of 9% which is significantly lower than that of the other three compounds. No difference was noted in the penetration of pesticides through human skin from blacks and whites.}, number={3}, journal={TOXICOLOGY LETTERS}, author={SHEHATAKARAM, H and MONTEIRORIVIERE, NA and GUTHRIE, FE}, year={1988}, month={Mar}, pages={233–239} }
 @article{grissom_monteiroriviere_guthrie_1987, title={A METHOD FOR PREPARING MOUSE SKIN FOR ASSESSING INVITRO DERMAL PENETRATION OF XENOBIOTICS}, volume={36}, ISSN={["0378-4274"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1987H440100007&KeyUID=WOS:A1987H440100007}, DOI={10.1016/0378-4274(87)90193-7}, abstractNote={A method is described for preparing mouse skin for assessment of in vitro penetration of dermally applied compounds. Separation of the epidermis from the dermis was attempted using a dermatome, heat, trypsin and collagenase. When mouse skin was incubated in a collagenase solution and separated using water, the hypodermis and part of the dermis were separated from the epidermis while leaving the hair follicles and hair shafts intact. Morphologically, the skins prepared for in vitro use appeared to offer similar barriers to topically applied compounds as those found in vivo.}, number={3}, journal={TOXICOLOGY LETTERS}, author={GRISSOM, RE and MONTEIRORIVIERE, NA and GUTHRIE, FE}, year={1987}, month={May}, pages={251–258} }
 @book{riviere_monteiro-riviere_bowman_1987, title={Development of in vitro isolated perfused porcine skin flaps for study of percutaneous absorption of xenobiotics}, DOI={10.21236/ada204615}, journal={DAMD17-84-C-4103, NTIS, ADA 204615}, institution={NTIS}, author={Riviere, J. E. and Monteiro-Riviere, N.A. and Bowman, K. F.}, year={1987}, pages={1–126} }
 @misc{riviere_bowman_monteiroriviere_1987, title={ON THE DEFINITION OF VIABILITY IN ISOLATED PERFUSED SKIN PREPARATIONS}, volume={116}, ISSN={["0007-0963"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1987H242000020&KeyUID=WOS:A1987H242000020}, DOI={10.1111/j.1365-2133.1987.tb05911.x}, number={5}, journal={BRITISH JOURNAL OF DERMATOLOGY}, author={RIVIERE, JE and BOWMAN, KF and MONTEIRORIVIERE, NA}, year={1987}, month={May}, pages={739–741} }
 @inproceedings{riviere_carver_monteiro-riviere_1987, title={Percutaneous absorption of organophosphates, steroids, caffeine and benzoic acid in vivo and in vitro using the isolated perfused porcine skin flap (IPPSF)}, booktitle={Proceedings of the 6th Medical Chemical Defense Bioscience Review}, publisher={Aberdeen, MD: Aberdeen Proving Ground}, author={Riviere, J. E. and Carver, M. P. and Monteiro-Riviere, N. A.}, year={1987}, pages={763–766} }
 @article{a_f_j_e_1987, title={THE ISOLATED PERFUSED PORCINE SKIN FLAP IPPSF II. ULTRASTRUCTURAL AND HISTOLOGICAL CHARACTERIZATION OF EPIDERMAL VIABILITY}, volume={1}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV198886033485&KeyUID=BIOSIS:PREV198886033485}, number={4}, journal={In Vitro Toxicology}, author={A, MONTEIRO-RIVIERE N and F, BOWMAN K and J, SCHEIDT V and E, RIVIERE J}, year={1987}, pages={241–252} }
 @inproceedings{monteiro-riviere_manning_1987, title={The effects of different fixatives on the porcine integument}, booktitle={45th Annual Proceedings, Electron Microscopy Society of America}, publisher={San Francisco: San Francisco Press}, author={Monteiro-Riviere, N. A. and Manning, T. O.}, year={1987}, pages={948–949} }
 @article{monteiro-riviere_bowman_scheidt_riviere_1987, title={The isolated perfused porcine skin flap (IPPSF). II. Ultrastructural and histological characterization of epidermal viability}, volume={1}, journal={In Vitro Toxicology}, author={Monteiro-Riviere, N. A. and Bowman, K. F. and Scheidt, V. J. and Riviere, J. E.}, year={1987}, pages={241–252} }
 @book{development of in vitro isolated perfused porcine skin flaps for study of percutaneous absorption of xenobiotics_1986, DOI={10.21236/ada198960}, abstractNote={Abstract : This report describes an in vitro alternative animal model for dermatology and cutaneous toxicology. An anatomically intact, viable, isolated perfused skin preparation would be a useful model for studying percutaneous drug absorption because venous and arterial perfusate concentrations could be assessed independently of confounding systemic processes. A single-pedicle, axial-pattern, island-tubed skin flap was created in crossbred Yorkshire weanling pigs in one surgical procedure, then transferred 2 or 6 days later to a perfusion chamber for 10-12 hour studies. The development of this two stage surgical procedure is fully described. Pig skin was used because of its recognized similarity to human skin. Viability was assessed by glucose utilization, lactate production, and an absence of significant concentrations of the intracellular enzyme lactate dehydrogenase in the perfusate. Light and electron microscopy was used to develop a morphological viability index and to differentiate degenerative lesions from normal surgery or perfusion changes or lesions from exogenously applied toxins. Based on these criteria, biochemically viable skin flaps could be maintained for 12 hrs without significantly abnormal morphology. The research resulted in a reproducible perfusion model optimized for the xenobiotic absorption studies to be conducted in the second year. This preparation would be an humane alternative animal model for studies in cutaneous toxicology, physiology, oncology, and percutaneous drug absorption and metabolism.}, journal={DAMD17-84-C-4103, NTIS, ADA 198960}, institution={Bethesda, MD: NTIS}, year={1986}, pages={1–23} }
 @article{riviere_bowman_monteiroriviere_dix_carver_1986, title={THE ISOLATED PERFUSED PORCINE SKIN FLAP (IPPSF) .1. A NOVEL INVITRO MODEL FOR PERCUTANEOUS-ABSORPTION AND CUTANEOUS TOXICOLOGY STUDIES}, volume={7}, ISSN={["0272-0590"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1986E389600010&KeyUID=WOS:A1986E389600010}, DOI={10.1016/0272-0590(86)90094-1}, abstractNote={This article describes the development of a novel in vitro alternative animal model for dermatology and cutaneous toxicology. A single-pedicle, axial-pattern, island-tubed skin flap was created in crossbred Yorkshire weanling pigs in one surgical procedure, then transferred 2 or 6 days later to a computer-controlled temperature-regulated perfusion chamber for 10-to 12-hr studies. Perfusate consisted of Krebs-Ringer bicarbonate buffer (pH 7.4) containing albumin and glucose. Viability was assessed by glucose utilization, lactate production, an absence of significant concentrations of the intracellular enzyme lactate dehydrogenase in the perfusate, and light and electron microscopy. A mean lactate to glucose ratio of 1.6 for flaps harvested 2 days after surgery and 1.8 for flaps taken 6 days after surgery suggested primarily anaerobic glycolysis. This preparation would be a humane alternative animal model for studies in cutaneous toxicology, physiology, oncology, and percutaneous drug absorption and metabolism.}, number={3}, journal={FUNDAMENTAL AND APPLIED TOXICOLOGY}, author={RIVIERE, JE and BOWMAN, KF and MONTEIRORIVIERE, NA and DIX, LP and CARVER, MP}, year={1986}, month={Oct}, pages={444–453} }
 @inbook{riviere_bowman_monteiro-riviere_1986, title={The isolated perfused porcine skin flap: A novel animal for cutaneous toxicologic research}, ISBN={0306424142}, booktitle={Swine in biomedical research}, publisher={New York: Plenum Press}, author={Riviere, J. E. and Bowman, K. F. and Monteiro-Riviere, N. A.}, year={1986}, pages={657–666} }
 @article{monteiroriviere_popp_1986, title={ULTRASTRUCTURAL EVALUATION OF ACUTE NASAL TOXICITY IN THE RAT RESPIRATORY EPITHELIUM IN RESPONSE TO FORMALDEHYDE GAS}, volume={6}, ISSN={["0272-0590"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1986A361700007&KeyUID=WOS:A1986A361700007}, DOI={10.1016/0272-0590(86)90238-1}, abstractNote={Ultrastructural lesions were induced by formaldehyde (HCHO) gas in the rat nasal respiratory epithelium. Male F-344 rats, 7-9 weeks old, were exposed to 0.5 or 2 ppm (6 hr/day) for 1 or 4 days and to 6 ppm (6 hr/day) of HCHO for 1 day and sacrificed immediately or 18 hr after 1, 2, or 4 days of exposure. Other groups were exposed to 15 ppm (6 hr/day) of HCHO for 1 and 2 days. Ultrastructural changes to 0.5 or 2 ppm were limited to altered cilia with wing-like projections occasionally seen on the tips of the ciliary shafts. Autophagic vacuoles were present in some of the basal cells while neutrophils were seen in the basal and suprabasal layers after 1 day exposure to 6 ppm of formaldehyde. Hypertrophy of goblet and ciliated cells were noted in animals exposed to 6 ppm of formaldehyde and sacrificed 18 hours after 1, 2, or 4 days of exposure. Some nonciliated cells formed apical blebs containing an abundance of SER. Ciliated-mucous cells were observed after 2 and 4 days of exposure to 6 ppm of formaldehyde. Nonkeratinized squamous cells containing microfilaments were seen as early as 4 days after exposure to 6 ppm and at 1 and 2 days after exposure to 15 ppm. Loss of microvilli in ciliated cells occurred in all exposure levels. At 15 ppm for 1 and 2 days, nucleolar segregation was observed in basal and cuboidal cells and internalized cilia were noted. These results demonstrate that short-term exposure to 6 or 15 ppm of HCHO caused respiratory epithelial injury which was not cell specific, but was dose related in severity.}, number={2}, journal={FUNDAMENTAL AND APPLIED TOXICOLOGY}, author={MONTEIRORIVIERE, NA and POPP, JA}, year={1986}, month={Feb}, pages={251–262} }
 @book{a_a_t_1986, title={ULTRASTRUCTURE OF THE RAT NASAL MUCOSA}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV198732045635&KeyUID=BIOSIS:PREV198732045635}, journal={Barrow, C. S. (Ed.). Chemical Industry Institute of Toxicology Series: Toxicology of the Nasal Passages; Seventh Ciit (Chemical Industry Institute Toxicology) Conference on Toxicology, Raleigh, N.c., USA, Feb. 22-23, 1984. Xvii+317p. Hemisphere Publishing Corp.: New York, N.y., USA (Dist. Outside the United States By Mcgraw-Hill International Book Co.: Auckland, N.z., Australia.)}, author={A, POPP J and A, MONTEIRO-RIVIERE N and T, MARTIN J}, year={1986}, pages={37–50} }
 @article{monteiroriviere_jiang_1986, title={USE OF MIXED GLYCOSIDASE FOR THE REMOVAL OF MUCUS FROM THE RAT NASAL EPITHELIUM IN SEM STUDIES}, volume={3}, ISSN={["0741-0581"]}, DOI={10.1002/jemt.1060030405}, abstractNote={The surface layer of mucus, which obscures the epithelium from view, is a major obstacle when performing scanning electron microscopic studies of the nasal mucosa. Samples treated with a 1% mixed glycosidase solution for 1 or 2 minutes, followed by agitation, removed most of the mucus from the conchae without damaging the underlying epithelium. Removal of mucus allows the complete evaluation of the underlying epithelium in normal animals and the localization and characterization of lesions in animals exposed to nasal toxicants.}, number={4}, journal={JOURNAL OF ELECTRON MICROSCOPY TECHNIQUE}, author={MONTEIRORIVIERE, NA and JIANG, XZ}, year={1986}, pages={407–411} }
 @inbook{monteiro-riviere_1986, title={Ultrastructural evaluation of the porcine integument}, ISBN={0306424142}, booktitle={Swine in biomedical research}, publisher={New York: Plenum Press}, author={Monteiro-Riviere, N. A.}, year={1986}, pages={641–655} }
 @inbook{popp_monteiro-riviere_1986, title={Ultrastructure of the rat nasal mucosa}, ISBN={0891163972}, booktitle={Toxicology of the nasal passages}, publisher={Washington: Hemisphere Publishing Corp.}, author={Popp, J. A. and Monteiro-Riviere, N. A.}, year={1986}, pages={37–49} }
 @article{carver_monteiroriviere_brown_riviere_1985, title={DOSE-RESPONSE STUDIES OF GENTAMICIN-NEPHROTOXICITY IN RATS WITH EXPERIMENTAL RENAL DYSFUNCTION .2. POLYVINYL-ALCOHOL GLOMERULOPATHY}, volume={80}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1985APK3800010&KeyUID=WOS:A1985APK3800010}, DOI={10.1016/0041-008X(85)90083-3}, abstractNote={Animal studies involving concurrent pathophysiologic states, including experimental renal dysfunction, are useful for a proper understanding of the mechanisms of gentamicin nephrotoxicity and acute renal failure. This study examined gentamicin nephrotoxicity in a model of glomerular dysfunction in rats. Administration of medium molecular weight polyvinyl alcohol (PVA) produced a glomerulopathy, with characteristic accumulation of macromolecular PVA in the glomerular mesangium without altering glomerular filtration or causing proteinuria. Subsequent daily doses of gentamicin ranging from 0 to 120 mg/kg elicited a dose-response nephrotoxicity in both control and PVA-pretreated rats after 6 or 12 days of drug. Based on statistical analysis of renal clearances of creatinine, urea, sodium, and potassium; serum creatinine and urea nitrogen; urinary N-acetyl-β-d-glucosaminidase excretion (6 days only); in vitro renal cortical transport of tetraethylammonium (TEA) (6 days); and quantified light-microscopic data (12 days), PVA induced an early (6 days) sensitivity to gentamicin nephrotoxicity. By 12 days, there were no differences in the responses of control and PVA rats to gentamicin. Single-dose gentamicin clearance, volume of distribution, and half-life were not altered by PVA and renal concentrations at 6 days were generally lower in these rats. Results of TEA transport studies tend to rule out PVA-induced metabolic lesions in the proximal tubular epithelium as the mechanism for the early sensitivity. This investigation demonstrates altered gentamicin nephrotoxicity in rats with an otherwise benign glomerulopathy and, combined with similar conclusions from a related study in subtotally nephrectomized rats, presents further evidence that the underlying pathophysiologic state of the kidney is an important factor in the renal response to nephrotoxins.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={CARVER, MP and MONTEIRORIVIERE, NA and BROWN, TT and RIVIERE, JE}, year={1985}, pages={264–273} }
 @book{riviere_bowman_monteiro-riviere_1985, title={Development of in vitro isolated perfused porcine skin flaps for study of percutaneous absorption of xenobiotics}, journal={DAMD17-84-C-4103, NTIS, ADA 183580}, institution={Bethesda, MD: NTIS}, author={Riviere, J. E. and Bowman, K. F. and Monteiro-Riviere, N. A.}, year={1985}, pages={1–32} }
 @inproceedings{development of surgical techniques for in vitro isolated perfused skin flaps for percutaneous absorption of xenobiotics_1985, volume={App III}, booktitle={Proceedings of the Fifth Annual Chemical Defense Bioscience Review.  USAMRICD Report #SP 85-051}, publisher={Columbia, MD: USAMRICD Report SP85 05}, year={1985}, pages={A927–939} }
 @book{a_a_1985, title={MACROSCOPIC MICROSCOPIC AND ULTRASTRUCTURAL ANATOMY OF THE NASAL CAVITY RAT}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV198529049025&KeyUID=BIOSIS:PREV198529049025}, journal={Jones, T. C., U. Mohr and R. D. Hunt (Ed.). Monographs on Pathology of Laboratory Animals. Respiratory System. Xv+240p. Springer-Verlag: Berlin, West Germany; New York, N.y., Usa. Illus}, author={A, POPP J and A, MONTEIRO-RIVIERE N}, year={1985}, pages={3–10} }
 @inproceedings{riviere_bowman_monteiro-riviere_1985, title={The isolated perfused porcine skin flap: A novel in vitro animal model system for drug and xenobiotic percutaneous absorption}, booktitle={Proceedings of the Fifth Annual Chemical Defense Bioscience Review.  USAMRICD Report #SP 85-051}, publisher={Columbia, MD}, author={Riviere, J. E. and Bowman, K. F. and Monteiro-Riviere, N. A.}, year={1985}, pages={A911–926} }
 @article{monteiro-riviere_stromberg_1985, title={ULTRASTRUCTURE OF THE INTEGUMENT OF THE DOMESTIC PIG SUS-SCROFA FROM 1-14 WEEKS OF AGE}, volume={14}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV198580068231&KeyUID=BIOSIS:PREV198580068231}, DOI={10.1111/j.1439-0264.1985.tb00270.x}, abstractNote={The biopsies of normal lumbar and dorsal thoracic pig epidermis and dermis are described ultrastructurally at one, three, five, seven, nine and fourteen weeks and compared to the human integument. In the epidermis, basal cell projections extended into the dermis and increased slightly with age. Intraepidermal axons were seen. The basal lamina thickened opposite the hemidesmosomes of the epidermal-dermal junction. Small anchoring fibrils extended from the basal lamina into the dermis. Mitochondria were concentrated beneath the cellular nuclei of the stratum basale. Upper stratum spinosum and stratum granulosum cells contained membrane coating granules. The stratum corneum contained cells of varying density. The only intraepidermal nonkeratinocytes observed were melanocytes and Langerhans-like cells. Both were similar to those of humans. In the dermis, the interfollicular muscle resembled the arrector pili and smooth muscle found in other body areas. Nerve fibers were similar to those described in humans except subepidermal nerve endings contained mitochondria. One unexpected finding was the presence of mast cells which were enveloped by a zone of loose floccular material which stained positive with PAS from seven through fourteen weeks of age. Mast cell population density peaked at seven weeks and was greater in the papillary dermis than in the reticular dermis. Generally, the pig integument is morphologically similar to that of man and would serve as a useful animal model when age changes are accounted for.}, number={2}, journal={Anatomia Histologia Embryologia}, author={MONTEIRO-RIVIERE, N A and STROMBERG, M W}, year={1985}, pages={97–115} }
 @article{monteiroriviere_popp_1984, title={ULTRASTRUCTURAL CHARACTERIZATION OF THE NASAL RESPIRATORY EPITHELIUM IN THE RAT}, volume={169}, ISSN={["0002-9106"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1984SA55800002&KeyUID=WOS:A1984SA55800002}, DOI={10.1002/aja.1001690103}, abstractNote={This ultrastructural study of the respiratory epithelium of the rat nasal mucosa revealed six morphologically distinct cell types: goblet cells, basal cells, ciliated cells, nonciliated columnar cells, cuboidal cells, and brush cells. The latter three have not been previously characterized in the rat nasal mucosa by transmission electron microscopy. Cuboidal cells observed on the conchae and lateral wall had short apical microvilli which were less dense than the microvilli of the nonciliated columnar cells. Nonciliated columnar cells also identified on the conchae and lateral wall had short microvilli and an extensive network of smooth endoplasmic reticulum in the apical region. The brush cell had distinct ultrastructural features; it was pear-shaped, with the broad base adjacent to the basement membrane and large microvilli on the surface. Microfilaments, microtubules, vesicles, and paired cisternae were found in the apical cytoplasm. Brush cells occurred singly on the conchae and lateral wall but were not identified in the respiratory epithelium of the nasal septum. These findings indicate the complexity of cell types composing the rat nasal respiratory epithelium.}, number={1}, journal={AMERICAN JOURNAL OF ANATOMY}, author={MONTEIRORIVIERE, NA and POPP, JA}, year={1984}, pages={31–43} }
 @article{popp_monteiro-riviere_1984, title={Ultrastructural studies of the rat nasal mucosa}, volume={4}, journal={Activities (Chemical Industry Institute of Toxicology)}, author={Popp, J. A. and Monteiro-Riviere, N. A.}, year={1984}, pages={1–4} }
 @article{a_w_1982, title={ULTRASTRUCTURAL STUDY OF SKIN INNERVATION OF THE DOMESTICATED PIG}, volume={202}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=BIOSIS&KeyUT=BIOSIS:PREV198324046718&KeyUID=BIOSIS:PREV198324046718}, number={3}, journal={Anatomical Record}, author={A, MONTEIRO-RIVIERE N and W, STROMBERG M}, year={1982}, pages={132A} }
 @article{monteiroriviere_stromberg_1982, title={ULTRASTRUCTURE OF LANGERHANS CELLS IN THE DOMESTICATED PIG}, volume={202}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1982MZ03000064&KeyUID=WOS:A1982MZ03000064}, number={1}, journal={Anatomical Record}, author={MONTEIRORIVIERE, NA and STROMBERG, MW}, year={1982}, pages={161} }
 @article{stromberg_hwang_monteiroriviere_1981, title={INTERFOLLICULAR SMOOTH-MUSCLE IN THE SKIN OF THE DOMESTICATED PIG (SUS-SCROFA)}, volume={201}, ISSN={["0003-276X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1981MP53200001&KeyUID=WOS:A1981MP53200001}, DOI={10.1002/ar.1092010302}, abstractNote={An interfollicular smooth muscle that spans the triad of hair follicles has been identified in the skin of the domesticated pig (Sus scrofa). This muscle has been previously noted by other investigators and identified as an arrector pili muscle. However, it cannot be interpreted as such for the following reasons: (1) It lies opposite the arrector pili muscle on the follicle; (2) the orientation of its fibers is perpendicular to those of the arrector pili; (3) the two muscles are not continuous; their attachments are different; and (4) contraction of the interfollicular muscle would have little effect on erection of the hairs. Based on structural evidence, it is postulated that upon contraction the muscle draws the base of the three aligned follicles together into a triangular conformation. In so doing, it may rotate the outer two follicles of the triad. Its specific functional role is unknown.}, number={3}, journal={ANATOMICAL RECORD}, author={STROMBERG, MW and HWANG, YC and MONTEIRORIVIERE, NA}, year={1981}, pages={455–462} }
 @article{monteiroriviere_hwang_stromberg_1981, title={LIGHT MICROSCOPIC MORPHOLOGY OF LOW RESISTANCE SKIN POINTS IN THE GUINEA-PIG}, volume={9}, ISSN={["0192-415X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1981NL85300007&KeyUID=WOS:A1981NL85300007}, DOI={10.1142/S0192415X81000196}, abstractNote={This study compares the light microscopic structure of low resistance skin points (LRSP) to high resistance skin points (HRSP) of the guinea pig, Previously, LRSP have been shown to coincide with acupuncture loci. Epidermal nuclei and dermal nuclei were counted at both LRSP and at control points or HRSP. In addition, hair follicles, blood vessels, and sebaceous nuclei were likewise quantitated. This data, collected in a blind manner, was then subjected to statistical analysis using a nested analysis of variance and a Student's "t" test. The former test indicated an increase in density of hair follicles at LRSP, while both demonstrated a decrease in dermal nuclei at LRSP. An interesting finding is that the epidermis at both LRSP and HRSP is indistinguishable at the light microscopic level. This was indicated by both statistical procedures. Finding of a Haarscheibe, an aggregation of Merkel cell-neurite complexes, only at HRSP tends to preclude its role as an acupuncture neurotransducer. Finally, there appeared to be no obvious qualitative differences between LRSP and HRSP observable at the light microscopic level.}, number={2}, journal={AMERICAN JOURNAL OF CHINESE MEDICINE}, author={MONTEIRORIVIERE, NA and HWANG, YC and STROMBERG, MW}, year={1981}, pages={155–163} }
 @article{monteiroriviere_hwang_stromberg_1980, title={A QUALITATIVE AND QUANTITATIVE MICROSCOPIC STUDY OF LOW RESISTANCE SKIN POINTS OF THE GUINEA-PIG}, volume={196}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1980JR59000086&KeyUID=WOS:A1980JR59000086}, number={2}, journal={Anatomical Record}, author={MONTEIRORIVIERE, NA and HWANG, YC and STROMBERG, MW}, year={1980}, pages={269} }
 @misc{wei_sethuraman_jin_monteiro-riviere_narayan, title={Biological properties of carbon nanotubes}, volume={7}, number={4-5}, journal={Journal of Nanoscience and Nanotechnology}, author={Wei, W. and Sethuraman, A. and Jin, C. and Monteiro-Riviere, N. A. and Narayan, R. J.}, pages={1284–1297} }
 @article{monteiro-riviere_baynes_riviere, title={Epidermal cytotoxicity of topically-applied chemical mixtures in porcine skin}, volume={20}, number={1997}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Monteiro-Riviere, N. A. and Baynes, R. and Riviere, J.}, pages={255–256} }
 @misc{riviere_xia_baynes_monteiro-riviere, title={Method and apparatus for determining a molecular descriptor of absorption for a candidate compound}, volume={7,517,693}, number={2009 Apr. 14}, author={Riviere, J. E. and Xia, X. R. and Baynes, R. E. and Monteiro-Riviere, N. A.} }
 @book{riviere_monteiro-riviere_baynes, title={Percutaneous absorption of chemical mixtures relevant to the Gulf War}, journal={Technical report USAMRMC DAMD 17-99C-9047}, author={Riviere, J. E. and Monteiro-Riviere, N. A. and Baynes, R. E.}, pages={1–162} }
 @book{riviere_baynes_monteiro-riviere, title={Percutaneous absorption of chemical mixtures relevant to the Gulf War}, journal={USAMRMC, DAMD17-99C-9047. Technical Report ADB253401}, author={Riviere, J. E. and Baynes, R. E. and Monteiro-Riviere, N. A.}, pages={1–30} }
 @book{riviere_baynes_monteiro-riviere, title={Percutaneous absorption of chemical mixtures relevant to the Gulf War. II.}, journal={Technical report ADB, USAMRMC, DAMD17-99-C-9047}, author={Riviere, J. E. and Baynes, R. E. and Monteiro-Riviere, N. A.}, pages={1–34} }
 @book{riviere_baynes_monteiro-riviere, title={Quantitating absorption of complex chemical mixtures}, journal={Final report, CDC OH 007555}, institution={Atlanta: Center for Disease Control}, author={Riviere, J. E. and Baynes, R. E. and Monteiro-Riviere, N. A.}, pages={1–27} }
 @book{riviere_baynes_smith_monteiro-riviere, title={Quantitating the percutaneous absorption of mechanistically defined chemical mixtures}, journal={NTIS report, AFOSR GF 49620-98-1-0105}, author={Riviere, J. E. and Baynes, R. E. and Smith, C. E. and Monteiro-Riviere, N. A.}, pages={1–109} }
 @book{riviere_montiero-riviere_baynes_xia_smith, title={Quantitating the percutaneous absorption of mechanistically-defined chemical mixtures}, volume={34}, author={Riviere, J. E. and Montiero-Riviere, N. A. and Baynes, R. E. and Xia, X. R. and Smith, C. E.}, pages={1} }