@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}, abstractNote={A number of commercially available metal/metal oxide nanoparticles (NPs) such as superparamagnetic iron oxide (SPION) are utilized by the medical field for a wide variety of applications. These NPs may able to induce dermal toxicity via their physical nature and reactive surface properties. We hypothesize that SPION may be toxic to skin via the ability of particles to be internalized and thereby initiate oxidative stress, inducing redox-sensitive transcription factors affecting/leading to inflammation. Due to the skin's susceptibility to UV radiation, it is also of importance to address the combined effect of UVB and NPs co-exposure. To test this hypothesis, the effects of dextran-coated SPION of different sizes (15-50 nm) and manufacturers (MicroMod, Rostock-Warnemunde, Germany and KTH-Royal Institute of Technology, Stockholm, Sweden) were evaluated in two cell lines: normal human epidermal keratinocytes (HEK) and murine epidermal cells (JB6 P(+)). HEK cells exposed to 20 nm (KTH and MicroMod) had a decrease in viability, while the 15 and 50 nm particles were not cytotoxic. HEK cells were also capable of internalizing the KTH particles (15 and 20 nm) but not the MicroMod SPION (20 and 50 nm). IL-8 and IL-6 were also elevated in HEK cells following exposure to SPION. Exposure of JB6 P(+) cells to all SPIONs evaluated resulted in activation of AP-1. Exposure to SPION alone was not sufficient to induce NF-κB activation; however, co-exposure with UVB resulted in significant NF-κB induction in cells exposed to 15 and 20 nm KTH SPION and 50 nm MicroMod particles. Pre-exposure of JB6 P(+) cells to UVB followed by NPs induced a significant depletion of glutathione, release of cytokines, and cell damage as assessed by release of lactate dehydrogenase. Altogether, these data indicate that co-exposure to UVB and SPIONs was associated with induction of oxidative stress and release of inflammatory mediators. These results verify the need to thoroughly evaluate the adverse effects of UVB when evaluating dermal toxicity of engineered NPs on skin.}, 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} }
 @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={ABSTRACT}, 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={Abstract 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{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{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} }
 @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={Abstract}, 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{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{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={Abstract}, 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{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{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{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{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} }
 @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 μl/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} }
 @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{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"]}, DOI={10.1023/A:1010944529387}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} To assess the effects of selective lipid extraction and tape stripping on transepidermal water loss (TEWL) at three body regions in the pig. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Lipids were extracted from the abdominal, inguinal. and back regions using three different solvent extraction procedures or cellophane tape stripping (15x) on Yorkshire pigs. Three solvent extraction stages were I, cyclohexane (5 ml for three, 1-min extractions): II, cyclohexane/ethanol (4:1) (5 ml for three, 1-min extractions): and III, cyclohexane/ethanol (1:4) (5 ml for three, 3-min extractions) extracted as follows: Site A, Stage I: Site B, Stage I and II; Site C, Stage I, II and III. Erythema, edema, and TEWL were assessed in control, tape-stripped, and extracted sites at 0, 6, and 24 h. The extracted lipids were analyzed by thin layer chromatography and quantified by densitometry for ceramide, cholesterol, cholesterol esters, fatty acids, and triglycerides. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} The change in TEWL (delta TEWL) in 14 of the 15 sites was the highest at 24 h and generally increased with each additional extraction. The greatest changes were present in the back. Each extraction stage removed specific lipids in reproducible quantities that caused the delta TEWL to increase from 0 to 24 h. Lipid removal was verified by transmission electron microscopy. The mean total lipid concentration depended on extraction solvents and body region, and was reproducible across sites and regions at equivalent stages of lipid extraction. Relative proportions of individual lipids extracted were similar across all body regions. Higher concentrations of total lipids were extracted from the back. CONCLUSIONS. These studies demonstrate that extraction of lipids increased the delta TEWL to a level similar to repeated tape stripping at all body sites in the pig. This study suggested that strategies that could biochemically alter epidermal lipid composition may increase absorption of simultaneously administered topical compounds and may be useful to enhance drug delivery.}, 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={Abstract}, 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 μl/site). Exposure to phenol was followed by one of 10 different decontamination procedures: 1-, 5-, 15-, and 30-min water wash; Ivory1 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} }
 @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; 8 h HD SD from the 8 h EtOH); and in the dermis with NSE (1 h HD SD from the 1 h EtOH). ALP staining was found to be the most sensitive of the enzyme biomarkers in this study, since its intensity increases in response to mild insult and decreases in response to a more severe exposure.}, number={2}, journal={TOXICOLOGY METHODS}, author={Monteiro-Riviere, NA and Inman, AO}, year={2000}, pages={127–142} }
 @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{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{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 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. Microsc. Res. Tech., 37:172–179, 1997. © 1997 Wiley‐Liss, Inc.}, 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{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} }
 @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 μl 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 intercellular 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. Microsc. Res. Tech., 37:229–241, 1997. © 1997 Wiley‐Liss, Inc.}, number={3}, journal={MICROSCOPY RESEARCH AND TECHNIQUE}, author={MonteiroRiviere, NA and Inman, AO}, year={1997}, month={May}, pages={229–241} }
 @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"]}, 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} }
 @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{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_riviere_1994, title={Development and characterization of a novel skin model for cutaneous phototoxicology}, journal={Photodermatology, Photoimmunology & Photomedicine}, author={Monteiro-Riviere, N. A. and Inman, A. O. and Riviere, J. E.}, year={1994}, pages={235–243} }
 @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"]}, DOI={10.1023/A:1018907508501}, abstractNote={Although electrically assisted transdermal drug delivery has recently achieved a great deal of research attention, the precise anatomical pathway followed by these drugs through the stratum corneum has not been clearly defined. Pigs are an accepted model for studying iontophoretic drug delivery in humans. The purpose of this investigation was to visualize the pathway of ion transport by iontophoresing mercuric chloride. Weanling Yorkshire swine were dosed with 7.4% mercuric chloride in the positive electrode at a current density of 200 microAmp/cm2 applied for 1 hr. Biopsies were immediately taken, exposed to 25% ammonium sulfide vapor to precipitate and localize the mercury, fixed, and processed for light and transmission electron microscopy. The presence of mercury, which appeared as a black precipitate, was confirmed using energy-dispersive X-ray microanalysis. Although some compound penetrated the skin through appendageal pathways, the electron micrographs clearly revealed that mercuric chloride traversed the intact stratum corneum via an intercellular route. Precipitate was also localized in the outer membrane of the mitochondria in the viable epidermal cells, dermal fibroblasts, and capillaries, demonstrating transdermal delivery and systemic exposure to the mercury. These findings have implications for iontophoretic drug delivery, since they allow visualization of the functional "pores" predicted by mathematical models.}, number={2}, journal={PHARMACEUTICAL RESEARCH}, author={MONTEIRORIVIERE, NA and INMAN, AO and RIVIERE, JE}, year={1994}, month={Feb}, pages={251–256} }
 @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} }
 @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{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}, abstractNote={The mechanism of the topical delivery of piroxicam, a nonsteroidal antiinflammatory drug, has been controversial as to whether systemic absorption is required for topical efficacy. This study, using in vivo pigs treated with topical 3H-piroxicam gel, was designed to assess the role of systemic absorption on its delivery to deep tissues. Further, the role of the structure of the cutaneous vasculature (e.g., direct cutaneous or musculocutaneous) was studied. Finally, piroxicam delivery was measured using in vitro diffusion cells with pig skin obtained from the same sites to determine inherent permeability independent of vascular anatomy. These studies showed that penetration of the radiolabel occurred in subcutaneous and muscle tissue only under the dosed sites and not at the remote sites, ruling out systemic absorption as a prerequisite for local delivery. Tissue penetration in vivo was enhanced at the musculocutaneous compared to the direct cutaneous sites. In contrast, in vitro flux was identical in skin harvested from the two vascular sites, suggesting that the vasculature plays a pivotal role in deep tissue penetration of piroxicam. In conclusion, local delivery of topical drugs occurs independent of systemic absorption and the nature of the cutaneous vasculature at different sites must be taken into consideration for optimal delivery.}, 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{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}, abstractNote={The purpose of this study was to investigate the effect of vasoactive drugs on transdermal lidocaine inotophoresis by measuring the concentrations of radiolabeled lidocaine which has penetrated the skin. Previous studies had demonstrated that coinotophoresis of vasoactive drugs could modulate the transcutaneous flux of lidocaine and suggested that a dermal depot of lidocaine was involved. To address this, lidocaine hydrochloride (14C) was iontophoresed in vivo in anesthetized weanling pigs either alone or with the vasodilator tolazoline or the vasoconstrictor norepinephrine. Tissue cores under the active electrode were then collected, quick-frozen, and sectioned on a cryostat, and then the radioactivity was determined in each 40-microns section. Coiontophoresis with norepinephrine resulted in increased concentrations of lidocaine in skin up to a depth of 3 mm. These concentrations decreased to lidocaine-alone levels after a 4-hr washout. Tolazoline decreased tissue concentrations of lidocaine. Concentrations were intermediate when lidocaine alone was administered. These studies support the hypothesis that coiontophoresis of vasoactive drugs modulates the transdermal delivery of lidocaine, in part by altering the cutaneous "depot."}, 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={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} }