@article{gerard_blikslager_marais_2023, title={A novel case of tracheal injury secondary to gunshot trauma in a white rhinoceros (Ceratotherium simum)}, volume={261}, ISSN={["1943-569X"]}, DOI={10.2460/javma.23.05.0254}, abstractNote={To describe a case of tracheal injury secondary to gunshot trauma in a rhinoceros.5-year-old female white rhinoceros (Ceratotherium simum).The rhinoceros was found alive with an apparent bullet entry wound cranial to the left shoulder. The rhinoceros was agitated and had bilateral epistaxis and increased respiratory noise. Immobilization of the animal facilitated closer examination and initiation of medical therapy. Radiographs obtained of the neck region at this first examination were nondiagnostic. Subsequent immobilization events allowed for further diagnostics and treatment.Initial treatment included a broad-spectrum antibiotic and a corticosteroid. Five days following the injury, the rhinoceros was considered stable, and the animal was immobilized to investigate the cause of the epistaxis and respiratory signs. Tracheoscopy revealed a full-thickness penetrating wound in the mid to caudal region of the trachea, and the surface of a metallic projectile was viewed within the wound. Medical treatment was continued and the rhinoceros was managed conservatively. At 14 days, radiographs of the neck made with a more powerful unit revealed tissue emphysema dorsal to the trachea. A subsequent tracheoscopy 54 days after injury revealed a granulated wound. Follow-up at 4 years after injury determined that the rhinoceros was reported to be behaving normally and had successfully calved.Gunshot wounds associated with poaching are a prevalent problem in rhinoceros in Africa. Although more aggressive therapy including surgery may likely be considered in zoo or domestic animals, limited conservative treatment was successful in this wild-managed rhinoceros.}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Gerard, Mathew P. and Blikslager, Anthony T. and Marais, H. Johan}, year={2023}, month={Oct} }
 @article{rivera_bilton_burclaff_czerwinski_liu_trueblood_hinesley_breau_deal_joshi_et al._2023, title={Hypoxia Primes Human ISCs for Interleukin-Dependent Rescue of Stem Cell Activity}, volume={16}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2023.07.012}, abstractNote={Hypoxia in the intestinal epithelium can be caused by acute ischemic events or chronic inflammation in which immune cell infiltration produces inflammatory hypoxia starving the mucosa of oxygen. The epithelium has the capacity to regenerate after some ischemic and inflammatory conditions suggesting that intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of hypoxia on human ISC (hISC) function has not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs from healthy donors and test the hypothesis that prolonged hypoxia modulates how hISCs respond to inflammation-associated interleukins (ILs).hISCs were exposed to <1.0% oxygen in the MPS for 6, 24, 48, and 72 hours. Viability, hypoxia-inducible factor 1a (HIF1a) response, transcriptomics, cell cycle dynamics, and response to cytokines were evaluated in hISCs under hypoxia. HIF stabilizers and inhibitors were screened to evaluate HIF-dependent responses.The MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs maintain viability until 72 hours and exhibit peak HIF1a at 24 hours. hISC activity was reduced at 24 hours but recovered at 48 hours. Hypoxia induced increases in the proportion of hISCs in G1 and expression changes in 16 IL receptors. Prolyl hydroxylase inhibition failed to reproduce hypoxia-dependent IL-receptor expression patterns. hISC activity increased when treated IL1β, IL2, IL4, IL6, IL10, IL13, and IL25 and rescued hISC activity caused by 24 hours of hypoxia.Hypoxia pushes hISCs into a dormant but reversible proliferative state and primes hISCs to respond to a subset of ILs that preserves hISC activity. These findings have important implications for understanding intestinal epithelial regeneration mechanisms caused by inflammatory hypoxia.}, number={5}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Rivera, Kristina R. and Bilton, R. Jarrett and Burclaff, Joseph and Czerwinski, Michael J. and Liu, Jintong and Trueblood, Jessica M. and Hinesley, Caroline M. and Breau, Keith A. and Deal, Halston E. and Joshi, Shlok and et al.}, year={2023}, pages={823–846} }
 @article{ruff_zetterstrom_boone_hofmeister_smith_epstein_blikslager_fogle_burke_2023, title={Retrospective analysis of postoperative complications following surgical treatment of ileal impaction in horses managed with manual decompression compared to jejunal enterotomy}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1156678}, abstractNote={The objective of this study was to compare the occurrence of post-operative complications and survival to discharge in horses with ileal impactions resolved by manual decompression compared with jejunal enterotomy.A total of 121 client-owned horses undergoing surgical correction of an ileal impaction at three teaching hospitals.Data from the medical records of horses undergoing surgical correction of an ileal impaction was retrospectively collected. Post-operative complications, survival to discharge, or post-operative reflux present were evaluated as dependent variables and pre-operative PCV, surgery duration, pre-operative reflux, and type of surgery were evaluated as independent variables. Type of surgery was divided into manual decompression (n = 88) and jejunal enterotomy (n = 33).There were no significant differences in development of minor complications, development of major complications, presence of post-operative reflux, amount of post-operative reflux, and survival to discharge between horses that were treated with manual decompression and those treated with distal jejunal enterotomy. Pre-operative PCV and surgery duration were significant predictors of survival to discharge.This study showed that there are no significant differences in post-operative complications and survival to discharge in horses undergoing distal jejunal enterotomy versus manual decompression for correction of ileal impaction. Pre-operative PCV and duration of surgery were found to be the only predictive factors of survival to discharge. Based on these findings, distal jejunal enterotomy should be considered earlier in horses with moderate to severe ileal impactions identified at surgery.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Ruff, Jennifer and Zetterstrom, Sandra and Boone, Lindsey and Hofmeister, Erik and Smith, Caitlin and Epstein, Kira and Blikslager, Anthony and Fogle, Callie and Burke, Megan}, year={2023}, month={Apr} }
 @article{hepworth-warren_erwin_moore_talbot_young_neault_haugland_robertson_blikslager_2023, title={Risk factors associated with an outbreak of equine coronavirus at a large farm in North Carolina}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1060759}, abstractNote={Equine coronavirus (ECoV) leads to outbreaks with variable morbidity and mortality. Few previous reports of risk factors for infection are available in the literature.To describe unique clinical findings and risk factors for infection and development of clinical disease.135 horses on a farm affected by ECoV outbreak.Retrospective cohort study. Data obtained included age, breed, gender, activity level, housing, and feed at the onset of the outbreak. Factors were evaluated for assessment of risk of infection using simple logistic regression or Fisher's exact test. Significance was set at p ≤ 0.05.Forty-three of 54 (79.6%) horses tested on the farm were positive on fecal PCR for ECoV, and 17 horses (12.6%) developed clinical signs consistent with ECoV. Out of 17 horses in which the presence or absence of signs of colic was noted, 6 of 17 (35.3%) showed signs of colic. Three of these horses had small colon impactions, 2 of which required surgical intervention. Significant risk factors for having positive PCR results included being primarily stalled (OR 167.1, 95% CI 26.4-1719), housing next to a positive horse (OR 7.5, 95% CI 3.1-19.0), being in work (OR 26.9, 95% CI 4.6-281.9), being fed rationed hay vs. ad libitum (OR 1,558, 95% CI 130.8-15,593), and being fed alfalfa hay (OR 1,558, 95% CI 130.8-15,593).This report describes risk factors for ECoV infection many of which were associated with intensive management of show horses. Clinicians should be aware that clinical signs vary and can include severe colic.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Hepworth-Warren, Kate L. and Erwin, Sara J. and Moore, Caroline B. and Talbot, James R. and Young, Kimberly A. S. and Neault, Michael J. and Haugland, Jennifer C. and Robertson, James B. and Blikslager, Anthony T.}, year={2023}, month={Mar} }
 @article{cortes_brodsky_chen_pridgen_odle_snider_cruse_putikova_masuda_doyle_et al._2022, title={Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis}, volume={3}, ISSN={["2673-6101"]}, DOI={10.3389/falgy.2022.1029184}, abstractNote={Eosinophilic esophagitis (EoE) is a chronic allergy-mediated condition with an increasing incidence in both children and adults. Despite EoE's strong impact on human health and welfare, there is a large unmet need for treatments with only one recently FDA-approved medication for EoE. The goal of this study was to establish swine as a relevant large animal model for translational biomedical research in EoE with the potential to facilitate development of therapeutics. We recently showed that after intraperitoneal sensitization and oral challenge with the food allergen hen egg white protein (HEWP), swine develop esophageal eosinophilia-a hallmark of human EoE. Herein, we used a similar sensitization and challenge treatment and evaluated immunological and pathological markers associated with human EoE. Our data demonstrate that the incorporated sensitization and challenge treatment induces (i) a systemic T-helper 2 and IgE response, (ii) a local expression of eotaxin-1 and other allergy-related immune markers, (iii) esophageal eosinophilia (>15 eosinophils/0.24 mm2), and (iv) esophageal endoscopic findings including linear furrows and white exudates. Thereby, we demonstrate that our sensitization and oral challenge protocol not only induces the underlying immune markers but also the micro- and macro-pathological hallmarks of human EoE. This swine model for EoE represents a novel relevant large animal model that can drive translational biomedical research to develop urgently needed treatment strategies for EoE.}, journal={FRONTIERS IN ALLERGY}, author={Cortes, Lizette M. and Brodsky, David and Chen, Celine and Pridgen, Tiffany and Odle, Jack and Snider, Douglas B. and Cruse, Glenn and Putikova, Arina and Masuda, Mia Y. and Doyle, Alfred D. and et al.}, year={2022}, month={Nov} }
 @article{boger_sheridan_ziegler_blikslager_2022, title={Mechanisms and modeling of wound repair in the intestinal epithelium}, volume={6}, ISSN={["2168-8370"]}, url={https://doi.org/10.1080/21688370.2022.2087454}, DOI={10.1080/21688370.2022.2087454}, abstractNote={The intestinal epithelial barrier is susceptible to injury from insults, such as ischemia or infectious disease. The epithelium’s ability to repair wounded regions is critical to maintaining barrier integrity. Mechanisms of intestinal epithelial repair can be studied with models that recapitulate the in vivo environment. This review focuses on in vitro injury models and intestinal cell lines utilized in such systems. The formation of artificial wounds in a controlled environment allows for the exploration of reparative physiology in cell lines modeling diverse aspects of intestinal physiology. Specifically, the use of intestinal cell lines, IPEC-J2, Caco-2, T-84, HT-29, and IEC-6, to model intestinal epithelium is discussed. Understanding the unique systems available for creating intestinal injury and the differences in monolayers used for in vitro work is essential for designing studies that properly capture relevant physiology for the study of intestinal wound repair.}, journal={TISSUE BARRIERS}, author={Boger, Kasey D. and Sheridan, Ana E. and Ziegler, Amanda L. and Blikslager, Anthony T.}, year={2022}, month={Jun} }
 @article{erwin_clark_dechant_aitken_hassel_blikslager_ziegler_2022, title={Multi-Institutional Retrospective Case-Control Study Evaluating Clinical Outcomes of Foals with Small Intestinal Strangulating Obstruction: 2000-2020}, volume={12}, ISSN={["2076-2615"]}, url={https://www.mdpi.com/2076-2615/12/11/1374}, DOI={10.3390/ani12111374}, abstractNote={Lower survival has been reported in foals than adults with small intestinal strangulating obstruction (SISO), but age-dependent outcomes have not been examined directly. Hospital records were collected from five US academic referral hospitals. It was hypothesized that foals would exhibit lower survival than case-matched adults. Foal cases 6-months-of-age or younger, and adult cases between 2- and 20-years-of-age were collected. Data revealed 24 of 25 (96.0%) foals and 66 of 75 (88.0%) adults that were recovered from surgery for SISO survived to hospital discharge. Sixteen of the total 41 (39.0%) foals studied were euthanized intraoperatively, whereas 30 of 105 (28.6%) adults were euthanized intraoperatively. Common lesions in foals that were recovered from surgery were volvulus (n = 13) and intussusception (n = 5), whereas common lesions in adults were volvulus (n = 25) and strangulating lipoma (n = 23). This study was limited by incomplete medical records, relatively small sample size, and lack of long-term follow-up. Unexpectedly, short-term survival tended to be higher in foals than adults and may have been partly driven by case selection prior to referral or surgery or decision-making intraoperatively. More optimism toward surgical treatment of foals with SISO may be warranted.}, number={11}, journal={ANIMALS}, publisher={MDPI AG}, author={Erwin, Sara J. and Clark, Marley E. and Dechant, Julie E. and Aitken, Maia R. and Hassel, Diana M. and Blikslager, Anthony T. and Ziegler, Amanda L.}, year={2022}, month={Jun} }
 @article{jacobs_schnabel_mcilwraith_blikslager_2022, title={Non-steroidal anti-inflammatory drugs in equine orthopaedics}, volume={2}, ISSN={["2042-3306"]}, DOI={10.1111/evj.13561}, abstractNote={Summary Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non‐steroidal anti‐inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non‐selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examines new and future avenues for the management of inflammation in equine orthopaedics.}, journal={EQUINE VETERINARY JOURNAL}, author={Jacobs, Carrie C. and Schnabel, Lauren V. and McIlwraith, C. Wayne and Blikslager, Anthony T.}, year={2022}, month={Feb} }
 @misc{rose_blikslager_ziegler_2022, title={Porcine Models of the Intestinal Microbiota: The Translational Key to Understanding How Gut Commensals Contribute to Gastrointestinal Disease}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.834598}, abstractNote={In the United States, gastrointestinal disorders account for in excess of $130 billion in healthcare expenditures and 22 million hospitalizations annually. Many of these disorders, including necrotizing enterocolitis of infants, obesity, diarrhea, and inflammatory bowel disease, are associated with disturbances in the gastrointestinal microbial composition and metabolic activity. To further elucidate the pathogenesis of these disease syndromes as well as uncover novel therapies and preventative measures, gastrointestinal researchers should consider the pig as a powerful, translational model of the gastrointestinal microbiota. This is because pigs and humans share striking similarities in their intestinal microbiota as well as gastrointestinal anatomy and physiology. The introduction of gnotobiotic pigs, particularly human-microbial associated pigs, has already amplified our understanding of many gastrointestinal diseases that have detrimental effects on human health worldwide. Continued utilization of these models will undoubtedly inform translational advancements in future gastrointestinal research and potential therapeutics.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Rose, Elizabeth C. and Blikslager, Anthony T. and Ziegler, Amanda L.}, year={2022}, month={Mar} }
 @article{erwin_blikslager_ziegler_2021, title={Age-Dependent Intestinal Repair: Implications for Foals with Severe Colic}, volume={11}, ISSN={["2076-2615"]}, url={https://www.mdpi.com/2076-2615/11/12/3337}, DOI={10.3390/ani11123337}, abstractNote={Colic is a leading cause of death in horses, with the most fatal form being strangulating obstruction which directly damages the intestinal barrier. Following surgical intervention, it is imperative that the intestinal barrier rapidly repairs to prevent translocation of gut bacteria and their products and ensure survival of the patient. Age-related disparities in survival have been noted in many species, including horses, humans, and pigs, with younger patients suffering poorer clinical outcomes. Maintenance and repair of the intestinal barrier is regulated by a complex mucosal microenvironment, of which the ENS, and particularly a developing network of subepithelial enteric glial cells, may be of particular importance in neonates with colic. Postnatal development of an immature enteric glial cell network is thought to be driven by the microbial colonization of the gut and therefore modulated by diet-influenced changes in bacterial populations early in life. Here, we review the current understanding of the roles of the gut microbiome, nutrition, stress, and the ENS in maturation of intestinal repair mechanisms after foaling and how this may influence age-dependent outcomes in equine colic cases.}, number={12}, journal={ANIMALS}, author={Erwin, Sara J. and Blikslager, Anthony T. and Ziegler, Amanda L.}, year={2021}, month={Dec} }
 @article{enomoto_yeatts_carbajal_krishnan_madan_laumas_blikslager_messenger_2021, title={In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model}, volume={16}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0249179}, abstractNote={There is no FDA approved therapy for the treatment of celiac disease (CeD), aside from avoidance of dietary gluten. Larazotide acetate (LA) is a first in class oral peptide developed as a tight junction regulator, which is a lead candidate for management of CeD. A delayed release formulation was tested in vitro and predicted release in the mid duodenum and jejunum, the target site of CeD. The aim of this study was to follow the concentration versus time profile of orally administered LA in the small intestine using a porcine model. A sensitive liquid chromatography/tandem mass spectrometry method was developed to quantify LA concentrations in porcine intestinal fluid samples. Oral dosing of LA (1 mg total) in overnight fasted pigs resulted in time dependent appearance of LA in the distal duodenum and proximal jejunum. Peak LA concentrations (0.32-1.76 μM) occurred at 1 hour in the duodenum and in proximal jejunum following oral dosing, with the continued presence of LA (0.02-0.47 μM) in the distal duodenum and in proximal jejunum (0.00-0.43 μM) from 2 to 4 hours following oral dosing. The data shows that LA is available in detectable concentrations at the site of CeD.}, number={4}, journal={PLOS ONE}, author={Enomoto, Hiroko and Yeatts, James and Carbajal, Liliana and Krishnan, B. Radha and Madan, Jay P. and Laumas, Sandeep and Blikslager, Anthony T. and Messenger, Kristen M.}, year={2021}, month={Apr} }
 @article{slifer_hernandez_pridgen_carlson_messenger_madan_krishnan_laumas_blikslager_2021, title={Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions}, volume={16}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0250165}, abstractNote={Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions. Larazotide acetate (LA), a small peptide studied in Phase III clinical trials for treatment of celiac disease, regulates tight junctions (TJs). We hypothesized that LA would dose-dependently hasten recovery of intestinal ischemic injury via modulation of TJs. Ischemia-injured tissue from 6-8-week-old pigs was recovered in Ussing chambers for 240-minutes in the presence of LA. LA (1 μM but not 0.1 μM or 10 μM) significantly enhanced transepithelial electrical resistance (TER) above ischemic injured controls and significantly reduced serosal-to-mucosal flux LPS ( P<0 . 05 ). LA (1 μM) enhanced localization of the sealing tight junction protein claudin-4 in repairing epithelium. To assess for the possibility of fragmentation of LA, an in vitro enzyme degradation assay using the brush border enzyme aminopeptidase M, revealed generation of peptide fragments. Western blot analysis of total protein isolated from uninjured and ischemia-injured porcine intestine showed aminopeptidase M enzyme presence in both tissue types, and mass spectrometry analysis of samples collected during ex vivo analysis confirmed formation of LA fragments. Treatment of tissues with LA fragments had no effect alone, but treatment with a fragment missing both amino-terminus glycines inhibited barrier recovery stimulated by 1 μM LA. To reduce potential LA inhibition by fragments, a D-amino acid analog of larazotide Analog #6, resulted in a significant recovery response at a 10-fold lower dose (0.1 μM) similar in magnitude to that of 1 μM LA. We conclude that LA stimulates repair of ischemic-injured epithelium at the level of the tight junctions, at an optimal dose of 1 μM LA. Higher doses were less effective because of inhibition by LA fragments, which could be subverted by chirally-modifying the molecule, or microdosing LA.}, number={4}, journal={PLOS ONE}, author={Slifer, Zachary M. and Hernandez, Liliana and Pridgen, Tiffany A. and Carlson, Alexandra R. and Messenger, Kristen M. and Madan, Jay and Krishnan, B. Radha and Laumas, Sandeep and Blikslager, Anthony T.}, year={2021}, month={Apr} }
 @misc{slifer_krishnan_madan_blikslager_2021, title={Larazotide acetate: a pharmacological peptide approach to tight junction regulation}, volume={320}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00386.2020}, abstractNote={Larazotide acetate (LA) is a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function. LA is currently being studied in phase III clinical trials and is orally administered to adult patients with celiac disease as an adjunct therapeutic to enhance intestinal barrier function that has been disrupted by gliadin-induced immune reactivity. Mechanistically, LA is thought to act as a zonulin antagonist to reduce zonulin-induced increases in barrier permeability and has been associated with the redistribution and rearrangement of tight junction proteins and actin filaments to restore intestinal barrier function. More recently, LA has been linked to inhibition of myosin light chain kinase, which likely reduces tension on actin filaments, thereby facilitating tight junction closure. Small (rodent) and large (porcine) animal studies have been conducted that demonstrate the importance of LA as a tight junction regulatory peptide in conditions other than celiac disease, including collagen-induced arthritis in mice and intestinal ischemic injury in pigs.}, number={6}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Slifer, Zachary M. and Krishnan, B. Radha and Madan, Jay and Blikslager, Anthony T.}, year={2021}, month={Jun}, pages={G983–G989} }
 @misc{hellstrom_ziegler_blikslager_2021, title={Postoperative Ileus: Comparative Pathophysiology and Future Therapies}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.714800}, abstractNote={Postoperative ileus (POI), a decrease in gastrointestinal motility after surgery, is an important problem facing human and veterinary patients. 37.5% of horses that develop POI following small intestinal (SI) resection will not survive to discharge. The two major components of POI pathophysiology are a neurogenic phase which is then propagated by an inflammatory phase. Perioperative care has been implicated, namely the use of opioid therapy, inappropriate fluid therapy and electrolyte imbalances. Current therapy for POI variably includes an early return to feeding to induce physiological motility, reducing the inflammatory response with agents such as non-steroidal anti-inflammatory drugs (NSAIDs), and use of prokinetic therapy such as lidocaine. However, optimal management of POI remains controversial. Further understanding of the roles of the gastrointestinal microbiota, intestinal barrier function, the post-surgical inflammatory response, as well as enteric glial cells, a component of the enteric nervous system, in modulating postoperative gastrointestinal motility and the pathogenesis of POI may provide future targets for prevention and/or therapy of POI.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Hellstrom, Emily A. and Ziegler, Amanda L. and Blikslager, Anthony T.}, year={2021}, month={Sep} }
 @article{rose_odle_blikslager_ziegler_2021, title={Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function}, volume={22}, ISSN={1422-0067}, url={http://dx.doi.org/10.3390/ijms22136729}, DOI={10.3390/ijms22136729}, abstractNote={Disruptions in the intestinal epithelial barrier can result in devastating consequences and a multitude of disease syndromes, particularly among preterm neonates. The association between barrier dysfunction and intestinal dysbiosis suggests that the intestinal barrier function is interactive with specific gut commensals and pathogenic microbes. In vitro and in vivo studies demonstrate that probiotic supplementation promotes significant upregulation and relocalization of interepithelial tight junction proteins, which form the microscopic scaffolds of the intestinal barrier. Probiotics facilitate some of these effects through the ligand-mediated stimulation of several toll-like receptors that are expressed by the intestinal epithelium. In particular, bacterial-mediated stimulation of toll-like receptor-2 modulates the expression and localization of specific protein constituents of intestinal tight junctions. Given that ingested prebiotics are robust modulators of the intestinal microbiota, prebiotic supplementation has been similarly investigated as a potential, indirect mechanism of barrier preservation. Emerging evidence suggests that prebiotics may additionally exert a direct effect on intestinal barrier function through mechanisms independent of the gut microbiota. In this review, we summarize current views on the effects of pro- and prebiotics on the intestinal epithelial barrier as well as on non-epithelial cell barrier constituents, such as the enteric glial cell network. Through continued investigation of these bioactive compounds, we can maximize their therapeutic potential for preventing and treating gastrointestinal diseases associated with impaired intestinal barrier function and dysbiosis.}, number={13}, journal={International Journal of Molecular Sciences}, publisher={MDPI AG}, author={Rose, Elizabeth C. and Odle, Jack and Blikslager, Anthony T. and Ziegler, Amanda L.}, year={2021}, month={Jun}, pages={6729} }
 @article{prasher_shrivastava_dahl_sharma-huynh_maturavongsadit_pridgen_schorzman_zamboni_ban_blikslager_et al._2021, title={Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis}, volume={13}, ISSN={["2073-4360"]}, url={https://www.mdpi.com/2073-4360/13/4/557}, DOI={10.3390/polym13040557}, abstractNote={Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test "entero-test" and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.}, number={4}, journal={POLYMERS}, author={Prasher, Alka and Shrivastava, Roopali and Dahl, Denali and Sharma-Huynh, Preetika and Maturavongsadit, Panita and Pridgen, Tiffany and Schorzman, Allison and Zamboni, William and Ban, Jisun and Blikslager, Anthony and et al.}, year={2021}, month={Feb} }
 @article{blikslager_mair_2021, title={Trends in the management of horses referred for evaluation of colic: 2004-2017}, ISBN={2042-3292}, DOI={10.1111/eve.13244}, abstractNote={Summary The financial crisis of 2008 had effects on veterinary practice, with falling turnovers associated with reluctance of owners to spend money on veterinary care. There were anecdotal reports that fewer horses were undergoing colic surgery. The aims of this study were to document the numbers of horses with colic being referred to, and undergoing surgery and/or euthanasia, at two equine hospitals (a university based equine hospital in the United States [NC State] and a private equine hospital in the UK [Bell Equine]) over a 14‐year period (2004–2017). There was a trend of declining total yearly equine accessions at NC State starting in 2009, followed by an increase starting in 2012. At Bell Equine, total accessions showed an increasing trend from 2004 to 2015, followed by a slight decline in 2016 and 2017. The proportion of equine accessions that were colics varied from around 15% to 20% at both hospitals and did not show any notable variations over the time period studied. Both practices showed a trend of decreasing colic admissions undergoing and recovering from surgery starting from 2007 to 2008. The numbers and percentages of colic admissions that were subjected to euthanasia increased from 2004/2005 to 2014/2015 in both hospitals; there was a greater increase in numbers being subjected to euthanasia at surgery at NC State, compared to a greater increase in numbers being subjected to euthanasia without surgery at Bell Equine. At both hospitals, there was a trend of increasing mean invoice totals over the study period. The results show that there has been a trend of decreasing numbers of horses undergoing surgical treatment for colic since 2004/2005. This is likely to be, at least partly, due to the financial crisis of 2008, although other factors, including the high costs of surgery and the ageing equine population may also be important.}, journal={Equine Veterinary Education}, author={Blikslager, A. T. and Mair, T. S.}, year={2021}, month={Apr} }
 @article{mitchell_dasilva_rosenbaum_blikslager_edwards_2021, title={Ultrasound findings in tendons and ligaments of lame sport horses competing or training in South Florida venues during the winter seasons of 2007 through 2016}, volume={33}, ISSN={["2042-3292"]}, DOI={10.1111/eve.13298}, abstractNote={Summary Knowledge of common soft tissue lesions in sport horses in training should prove beneficial for evaluating lameness and developing training and management regimens to avoid injury and aid rehabilitation. Medical records were reviewed from 2007 to 2016 to describe tendon/ligament lesions in lame sport horses training and competing at the same venues during the winter show circuit and identified by lameness and ultrasonographic examinations. Season, discipline, breed, age, gender, limb and ultrasound findings were recorded. Descriptive statistics were used to describe the population of horses. Significance of association of gender, discipline and limb with lesion type was evaluated using chi‐squared analyses. Values were considered significant at P ≤ 0.05. Lesions were identified in 296 horses: 176 dressage and 120 hunter/jumpers. Ninety‐two horses (31%) had multiple lesions. Suspensory ligament lesion locations (n = 281) were categorised as proximal (n = 144), body (n = 22) and branches (n = 115). Superficial digital flexor tendon (SDFT; n = 37), deep digital flexor tendon (DDFT; n = 27), inferior check ligament (ICL; n = 34), digital flexor tendon sheath (n = 17), distal sesamoidean ligament (n = 10), lower limb collateral ligament (n = 14), carpal sheath (n = 2), superior check ligament (n = 2) and tarsal sheath (n = 1) lesions were noted. Remaining lesions identified were medial branch SDFT (n = 2), lateral branch SDFT (n = 2), palmar annular ligament (n = 3), lateral plantar ligament (n = 2) and inter‐sesamoidean ligament (n = 1). Rear limb proximal suspensory abnormalities, specifically the right hindlimb (n = 68), were significantly over‐represented (P = 0.03). Suspensory origin, suspensory branch, ICL, SDFT and DDFT accounted for 82% of the abnormal findings identified. SDFT, DDFT and ICL lesions were most often identified in the front limb. The lesion type and location may provide insight in assessing training regimens, patient monitoring and rehabilitation guidelines.}, number={6}, journal={EQUINE VETERINARY EDUCATION}, author={Mitchell, R. D. and DaSilva, D. D. and Rosenbaum, C. F. and Blikslager, A. T. and Edwards, R. B., III}, year={2021}, month={Jun}, pages={306–309} }
 @article{sheridan_pridgen_odle_van landeghem_blikslager_ziegler_2020, title={A Glial Cell Inhibitor Blocks Epithelial Barrier Repair in a Pig Model of Intestinal Ischemia}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.02030}, abstractNote={The gut epithelium functions as a barrier against toxic luminal contents which can repair efficiently after injury to prevent systemic illness and death. However, we have shown that repair is severely hindered in neonates as compared to juveniles in our translational pig model of intestinal ischemia. The subepithelial enteric glial cell (EGC) network is known to promote epithelial repair by paracrine signaling mechanisms. This EGC network develops postnatally; therefore, we believe this repair defect in neonates is due to an underdeveloped EGC network. In support of this, we hypothesize that EGC inhibition in juveniles will block epithelial barrier repair after ischemic injury mimicking the neonatal phenotype. Ischemia-injured jejunum of juvenile pigs was recovered ex vivo with and without fluoroacetate (FA), a glial inhibitor. Transepithelial electrical resistance (TEER) was monitored as a measure of barrier function, and tissues were collected for imaging analysis and primary EGC culture. FA inhibited TEER recovery at all tested concentrations (P<0.0001). Histology showed 500μM FA optimally inhibits epithelial repair (P=0.0196) without directly damaging the epithelium (P=0.5509). Cellular metabolism marker c-fos has been optimized for immunofluorescence in control tissues and ongoing imaging work will validate selective inhibition of EGC metabolism by 500μM FA. In addition, pig EGC isolation and culture has been optimized, so that future work will confirm inhibitory effects of FA on EGC signaling functions in vitro. Understanding the development of glial-epithelial crosstalk in barrier repair will ultimately guide novel clinical solutions to improve outcomes in neonatal patients affected by intestinal injury. Support or Funding Information UNC CGIBD Large Animal Models Core (P30 DK034987), UNC CGIBD Basic Science Research Training Fellowship (NIH T32 5T32DK007737), UNC CGIBD Pilot Feasibility Grant (P30 DK034987), USDA National Institute of Food and Agriculture (Projects 1007263 and 07985)}, number={S1}, journal={FASEB JOURNAL}, publisher={Wiley}, author={Sheridan, Ana and Pridgen, Tiffany and Odle, Jack and Van Landeghem, Laurianne and Blikslager, Anthony and Ziegler, Amanda}, year={2020}, month={Apr} }
 @article{ziegler_blikslager_2020, title={Effects of Environmental Acclimation versus Transport Stress on Barrier Recovery in a Pig Model of Intestinal Ischemia and Repair}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.09380}, abstractNote={The pig is a powerful model for intestinal barrier studies, and it is important to carefully plan animal care and handling for optimal study design as psychological and physiological stressors significantly impact mucosal barrier function. Here, we report the effects of a period of environmental acclimation versus acute transport stress on mucosal barrier repair after intestinal ischemic injury. Jejunal ischemia was induced for 30-minutes in 8–10-week-old pigs which had been transported and allowed to acclimate to a biomedical research housing environment for 3-days prior to injury or been transported immediately prior to injury. Jejunal mucosa was then allowed to recover ex vivo in Ussing chambers while transepithelial electrical resistance (TEER) and mannitol flux were measured, and epithelial integrity was assessed by histomorphometry. In uninjured mucosa, there was no difference in basal TEER (P=0.8801) or epithelial integrity on histology between groups (P=0.5686), however, acclimated pigs had increased flux as compared to transported pigs during the first hour of ex vivo incubation (P=0.0186). Ischemia-injured mucosa of acclimated pigs had less robust TEER recovery ex vivo (P=0.0101) as compared to transported pigs, but an increased initial flux in this group was significantly reduced during recovery (P=0.0025). Ischemia induced greater epithelial loss in transported pigs as compared to acclimated pigs (68.5% versus 87.8% epithelial coverage, P<0.0001), yet both groups restored control levels of epithelial coverage after 120-minutes ex vivo recovery. These results indicate that acute transport stress on the day of experimental intestinal injury modeling may increase mucosal susceptibility to epithelial loss, but also prime the tissue for a more robust barrier repair response. Brief environmental acclimation, on the other hand, appears to increase intestinal permeability to molecular flux in the absence of injury, while possibly having a protective effect on epithelial loss during injury. These are important considerations for appropriate study design when utilizing highly translational pig models for intestinal barrier research. Support or Funding Information NIH K01 OD 028207, NIH P30 DK 034987, NIH-NICHD R01 HD095876, USDA-NIFA VMCG-0065, USDA-NIFA 1007263.}, journal={FASEB JOURNAL}, author={Ziegler, Amanda and Blikslager, Anthony}, year={2020}, month={Apr} }
 @article{shapiro_ziegler_odle_van landeghem_blikslager_2020, title={Effects of Oligosaccharide Supplementation on Intestinal Morphology and Enteric Glial Cell Marker Expression in a Neonatal Pig Model}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.09457}, abstractNote={We have shown that oligosaccharide supplementation can modulate the gut flora in neonates, and the microbiome is known to drive the maturation of the enteric glial cell (EGC) network postnatally. Here, we test the effects of dietary oligosaccharides on postnatal changes in the EGC network and intestinal morphology in a neonatal pig model.After suckling colostrum for 24-hours, one-day-old pigs were grouped onto one of three formula-based diets: control, high oligosaccharide (1:1 mixture of galactooligosaccharide and polydextrose, 8g/L), or low oligosaccharide (4g/L). Small intestine and colon samples were collected at 1- 7- 14- and 21- days-of-age for western blot and histological analysis. Preliminary histological results indicate a trend toward a decreased small intestinal villus length in the high oligosaccharide group at 7-days-of-age, indicative of accelerated intestinal maturity. Expression of the EGC marker glial fibrillary acidic protein is increased in the small intestinal mucosa at 7- and 14-days-of-age in the high oligosaccharide group based on a preliminary western blot (n=1). Following ongoing work to assess crypt morphology and quantify additional EGC markers S100B, PLP-1, Sox10 in the small intestine and colon, we expect to find increased mucosal expression of EGC markers earlier in postnatal development in the high oligosaccharide group, as well as histological changes consistent with enhanced rates of gut maturation in pigs fed a high oligosaccharide diet. Understanding how dietary inputs drive intestinal development postnatally may improve practices for managing optimal gut heath early in life. Support or Funding Information NIH K01 OD 028207, NIH P30 DK 034987, NIH-NICHD R01 HD095876, USDA-NIFA VMCG-0065}, number={S1}, journal={FASEB JOURNAL}, publisher={Wiley}, author={Shapiro, Lindsey and Ziegler, Amanda and Odle, Jack and Van Landeghem, Laurianne and Blikslager, Anthony}, year={2020}, month={Apr} }
 @article{ziegler_pridgen_blikslager_2020, title={Environmental stressors affect intestinal permeability and repair responses in a pig intestinal ischemia model}, volume={8}, ISSN={["2168-8370"]}, url={https://doi.org/10.1080/21688370.2020.1832421}, DOI={10.1080/21688370.2020.1832421}, abstractNote={The pig is a powerful model for intestinal barrier studies, and it is important to carefully plan animal care and handling for optimal study design as psychological and physiological stressors significantly impact intestinal mucosal barrier function. Here, we report the effects of a period of environmental acclimation versus acute transport stress on mucosal barrier repair after intestinal ischemic injury. Jejunal ischemia was induced in young pigs which had been allowed to acclimate to a biomedical research housing environment or had been transported immediately prior to experimental injury (non-acclimated). Mucosa was then incubated ex vivo on Ussing chambers. In uninjured mucosa, there was no difference in transepithelial electrical resistance (TEER) or epithelial integrity between groups. However, acclimated pigs had increased macromolecular flux as compared to non-acclimated pigs during the first hour of ex vivo incubation. Ischemia induced greater epithelial loss in non-acclimated pigs as compared to acclimated pigs, yet this group achieved greater wound healing during recovery. Non-acclimated pigs had more robust TEER recovery ex vivo following injury versus acclimated pigs. The expression pattern of the tight junction protein claudin-4 was disrupted in acclimated pigs following recovery but showed enhanced localization to the apical membrane in non-acclimated pigs following recovery. Acute transport stress increases mucosal susceptibility to epithelial loss but also primes the tissue for a more robust barrier repair response. Alternatively, environmental acclimation increases leak pathway and diminishes barrier repair responses after ischemic injury.}, number={4}, journal={TISSUE BARRIERS}, publisher={Informa UK Limited}, author={Ziegler, Amanda L. and Pridgen, Tiffany A. and Blikslager, Anthony T.}, year={2020}, month={Oct} }
 @misc{blikslager_2020, title={Letter to the Editor: Post-operative reflux - a surgeon's perspective}, volume={32}, ISSN={["2042-3292"]}, DOI={10.1111/eve.13116}, abstractNote={Equine Veterinary EducationVolume 32, Issue 1 p. 52-53 Correspondence Letter to the Editor: Post-operative reflux – a surgeon's perspective A. T. Blikslager, Corresponding Author A. T. Blikslager anthony_blikslager@ncsu.edu orcid.org/0000-0002-0867-7310 Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this author A. T. Blikslager, Corresponding Author A. T. Blikslager anthony_blikslager@ncsu.edu orcid.org/0000-0002-0867-7310 Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this author First published: 25 April 2019 https://doi.org/10.1111/eve.13116Citations: 1Read the full textAboutPDF ToolsExport 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 onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue1January 2020Pages 52-53 RelatedInformation}, number={1}, journal={EQUINE VETERINARY EDUCATION}, author={Blikslager, A. T.}, year={2020}, month={Jan}, pages={52–53} }
 @article{kruger_pridgen_taylor_garman_blikslager_2020, title={Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus}, volume={318}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00086.2019}, abstractNote={Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett’s esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue ( P < 0.05). Evaluation of the interepithelial tight junctions showed well-defined membrane localization of occludin in lubiprostone-treated injured tissues. Pretreatment of tissues with the Na + -K + -2Cl − cotransporter inhibitor bumetanide blocked lubiprostone-induced increases in short-circuit current and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of ClC-2 with ZnCl 2 blocked the effects of lubiprostone. We conclude that ClC-2 contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target. NEW & NOTEWORTHY This research is the first to describe the presence of anion channels ClC-2 and CFTR localized to the basal epithelia of porcine esophageal mucosa and the esophageal submucosal glands. In the setting of ex vivo acid exposure, the ClC-2 agonist lubiprostone reduced acid-related injury and enhanced recovery of the epithelial barrier. This work may ultimately provide an alternate mechanism for treating gastroesophageal reflux disease.}, number={4}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Kruger, Leandi and Pridgen, Tiffany A. and Taylor, Ellie R. and Garman, Katherine S. and Blikslager, Anthony T.}, year={2020}, month={Apr}, pages={G613–G623} }
 @inbook{marshall_blikslager_2020, place={St. Louis, MO}, edition={6th edition}, title={Surgical disorders of the large intestine}, booktitle={Large Animal Internal Medicine}, publisher={Elsevier}, author={Marshall, J.M. and Blikslager, A.T.}, editor={Smith, B.P. and Van Metre, D.C. and Pusterla, N.Editors}, year={2020} }
 @inbook{blikslager_marshall_2020, place={St. Louis}, edition={6th edition}, title={Surgical disorders of the small intestine}, booktitle={Large Animal Internal Medicine}, publisher={Elsevier}, author={Blikslager, A.T. and Marshall, J.M.}, editor={Smith, B.P. and Van Metre, D.C. and Pusterla, N.Editors}, year={2020} }
 @article{slifer_blikslager_2020, title={The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium}, url={https://www.mdpi.com/1422-0067/21/3/972}, DOI={10.3390/ijms21030972}, abstractNote={The intestinal epithelial monolayer forms a transcellular and paracellular barrier that separates luminal contents from the interstitium. The paracellular barrier consists of a highly organized complex of intercellular junctions that is primarily regulated by apical tight junction proteins and tight junction-associated proteins. This homeostatic barrier can be lost through a multitude of injurious events that cause the disruption of the tight junction complex. Acute repair after injury leading to the reestablishment of the tight junction barrier is crucial for the return of both barrier function as well as other cellular functions, including water regulation and nutrient absorption. This review provides an overview of the tight junction complex components and how they link to other plasmalemmal proteins, such as ion channels and transporters, to induce tight junction closure during repair of acute injury. Understanding the components of interepithelial tight junctions and the mechanisms of tight junction regulation after injury is crucial for developing future therapeutic targets for patients experiencing dysregulated intestinal permeability.}, journal={International Journal of Molecular Sciences}, author={Slifer, Zachary and Blikslager, Anthony}, year={2020}, month={Feb} }
 @article{jin_blikslager_2020, title={The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases}, url={https://www.mdpi.com/1422-0067/21/10/3550}, DOI={10.3390/ijms21103550}, abstractNote={The intestinal epithelial apical junctional complex, which includes tight and adherens junctions, contributes to the intestinal barrier function via their role in regulating paracellular permeability. Myosin light chain II (MLC-2), has been shown to be a critical regulatory protein in altering paracellular permeability during gastrointestinal disorders. Previous studies have demonstrated that phosphorylation of MLC-2 is a biochemical marker for perijunctional actomyosin ring contraction, which increases paracellular permeability by regulating the apical junctional complex. The phosphorylation of MLC-2 is dominantly regulated by myosin light chain kinase- (MLCK-) and Rho-associated coiled-coil containing protein kinase- (ROCK-) mediated pathways. In this review, we aim to summarize the current state of knowledge regarding the role of MLCK- and ROCK-mediated pathways in the regulation of the intestinal barrier during normal homeostasis and digestive diseases. Additionally, we will also suggest potential therapeutic targeting of MLCK- and ROCK-associated pathways in gastrointestinal disorders that compromise the intestinal barrier.}, journal={International Journal of Molecular Sciences}, author={Jin, Younggeon and Blikslager, Anthony}, year={2020}, month={May} }
 @article{erwin_touvron_odle_van landeghem_blikslager_ziegler_2020, title={iDISCO Allows Complete Visualization and Analysis of Postnatal Enteric Nervous System Development in a Comparative Pig Model}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fasebj.2020.34.s1.03991}, abstractNote={The enteric nervous system consists of a dense, complex network of neurons and glia which are instrumental in the maturation of normal intestinal physiology after birth. Our lab uses a comparative pig model to study the postnatal development of the enteric glial network and its role in regulating intestinal barrier functions in neonates. Immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs (iDISCO) is a method of preparing tissue samples for volume imaging with a light sheet microscope. iDISCO has been optimized for use in primarily mouse organs and embryos for the study of early development and offers a more complete picture of the tissue than traditional histological analysis. Our objective was to optimize the iDISCO protocol for use in porcine intestinal tissue to allow complete qualitative and quantitative analysis of postnatal development of the enteric glial network in our comparative pig model. Antibodies against glial cell markers S100b, Sox10, and glial fibrillary acidic protein (GFAP) were used to triple-stain fixed full-thickness 3mm by 5mm samples of porcine jejunum using the iDISCO protocol. Samples were imaged with a light-sheet microscope (Ultra-II, LaVision BioTec®) using three different fluorescent channels and datasets were visualized and analyzed in 3D with Imaris software (Oxford Instruments®). The percent volume of GFAP+ glial cells was quantified by manually masking individual intestinal villi and optimizing a surface algorithm to identify glial network structures within those villi. Antibodies against all three markers tested produced the predicted staining pattern with minimal non-specific staining. Percent of jejunal villus volume occupied by GFAP+ glia is higher in 6-week-old versus 2-week-old pig (0.49% versus 0.23%, *P≤0.05). Ongoing work will optimize quantification techniques for S100b and Sox10, and assess co-localization patterns of these glial markers in the jejunum at discrete timepoints postnatally. iDISCO is a powerful imaging modality which will allow our lab to directly assess the expansion, complexity, and localization of glial cell subtypes by marker co-expression analysis at discrete postnatal timepoints, and will be utilized in future studies to explore effects of disease and external interventions on the enteric glial network. Support or Funding Information NIH P30 DK034987 UNC CGIBD Pilot Feasibility; NIH T32 5T32DK007737-22 UNC Basic Science GI Research Training Fellowship; USDA National Institute of Food and Agriculture, Animal Health Projects 1007263 and 07985; 2017 NC State CMI TPP Seed Grant}, number={S1}, journal={FASEB JOURNAL}, publisher={Wiley}, author={Erwin, Sara and Touvron, Melissa and Odle, Jack and Van Landeghem, Laurianne and Blikslager, Anthony and Ziegler, Amanda}, year={2020}, month={Apr} }
 @inbook{marshall_blikslager_2019, title={Colic}, ISBN={9780323484206}, url={http://dx.doi.org/10.1016/b978-0-323-48420-6.00033-8}, DOI={10.1016/b978-0-323-48420-6.00033-8}, booktitle={Equine Surgery}, publisher={Elsevier}, author={Marshall, John F. and Blikslager, Anthony T.}, year={2019}, pages={521–528} }
 @misc{blikslager_2019, title={Colic Prevention to Avoid Colic Surgery: A Surgeon's Perspective}, volume={76}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2019.02.023}, abstractNote={Management factors associated with colic, particularly related to stall confinement and nutrition, have been linked to alterations in gastrointestinal mucosal transport, motility, and microbiome, which in turn creates conditions that induce colic. In particular, meal feeding creates large changes in water movement in and out of the colon and alters the microbiome. These conditions may in turn result in colic conditions such as large colon impaction or large colon volvulus. In addition, a range of management and nutritional factors have been found to place horses at risk of select colic conditions such as ileal impaction. Other specific colic conditions, such as strangulating lipomas, may be related to fat metabolism in geldings and ponies, although the association with nutrition and the endocrine system are less well defined. It has long been understood that parasites are associated with colic, and with the advent of highly effective anthelmintics, parasite-induced colic has been markedly reduced. Nonetheless, equine mangers and veterinarians have to be aware of changes in parasite resistance or patterns of activity, such as the resurgence of large strongyles with surveillance-based management of parasites. Overall, understanding management risk factors can lead to recommendations that prevent colic in horses. Additional study of these factors may ultimately lead to reductions in the prevalence of colic by suggesting optimal management practices.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Blikslager, Anthony T.}, year={2019}, month={May}, pages={1–5} }
 @article{manship_blikslager_elfenbein_2019, title={Disease features of equine coronavirus and enteric salmonellosis are similar in horses}, volume={33}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.15386}, DOI={10.1111/jvim.15386}, abstractNote={Background Equine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those of Salmonella infections. Objectives Compare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses. Animals Forty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV and Salmonella spp . Methods Medical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive, Salmonella‐ positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set at P < .05. Results Most common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses with Salmonella . Horses with Salmonella had significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable. Conclusions and Clinical Importance Equine coronavirus and Salmonella infections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Manship, Arlie J. and Blikslager, Anthony T. and Elfenbein, Johanna R.}, year={2019}, month={Jan}, pages={912–917} }
 @article{ziegler_fogle_burke_blikslager_2019, title={Letter to the Editor: Bias in statistics or bias in equine veterinary medicine?}, volume={51}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/evj.13081}, DOI={10.1111/evj.13081}, abstractNote={See Correspondence by Freeman}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Ziegler, A. L. and Fogle, C. A. and Burke, M. and Blikslager, A. T.}, year={2019}, month={Feb}, pages={423–423} }
 @article{gonzalez_stewart_freund_kucera_dekaney_magness_blikslager_2019, title={Preservation of reserve intestinal epithelial stem cells following severe ischemic injury}, volume={316}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00262.2018}, DOI={10.1152/ajpgi.00262.2018}, abstractNote={Intestinal ischemia is an abdominal emergency with a mortality rate >50%, leading to epithelial barrier loss and subsequent sepsis. Epithelial renewal and repair after injury depend on intestinal epithelial stem cells (ISC) that reside within the crypts of Lieberkühn. Two ISC populations critical to epithelial repair have been described: 1) active ISC (aISC; highly proliferative; leucine-rich-repeat-containing G protein-coupled receptor 5 positive, sex determining region Y-box 9 positive) and 2) reserve ISC [rISC; less proliferative; homeodomain only protein X (Hopx) + ]. Yorkshire crossbred pigs (8–10 wk old) were subjected to 1–4 h of ischemia and 1 h of reperfusion or recovery by reversible mesenteric vascular occlusion. This study was designed to evaluate whether ISC-expressing biomarkers of aISCs or rISCs show differential resistance to ischemic injury and different contributions to the subsequent repair and regenerative responses. Our data demonstrate that, following 3–4 h ischemic injury, aISC undergo apoptosis, whereas rISC are preserved. Furthermore, these rISC are retained ex vivo in spheroids in which cell populations are enriched in the rISC biomarker Hopx. These cells appear to go on to provide a proliferative pool of cells during the recovery period. Taken together, these data indicate that Hopx + cells are resistant to injury and are the likely source of epithelial renewal following prolonged ischemic injury. It is therefore possible that targeting reserve stem cells will lead to new therapies for patients with severe intestinal injury. NEW & NOTEWORTHY The population of reserve less-proliferative intestinal epithelial stem cells appears resistant to injury despite severe epithelial cell loss, including that of the active stem cell population, which results from prolonged mesenteric ischemia. These cells can change to an activated state and are likely indispensable to regenerative processes. Reserve stem cell targeted therapies may improve treatment and outcome of patients with ischemic disease.}, number={4}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Gonzalez, Liara M. and Stewart, Amy Stieler and Freund, John and Kucera, Cecilia Renee and Dekaney, Christopher M. and Magness, Scott T. and Blikslager, Anthony T.}, year={2019}, month={Apr}, pages={G482–G494} }
 @inbook{cook_blikslager_marshall_2019, title={Principles of Intestinal Injury and Determination of Intestinal Viability}, ISBN={9780323484206}, url={http://dx.doi.org/10.1016/b978-0-323-48420-6.00034-x}, DOI={10.1016/b978-0-323-48420-6.00034-x}, abstractNote={Intestinal injury, although typically associated with ischemic lesions, occurs during any obstructive intestinal disease to varying degrees depending on the type of obstruction and the extent of vascular compromise. In addition, in some instances, the intestinal lumen is patent, but there is vascular compromise—for example, in nonstrangulating infarctions. Intestinal obstructive lesions are classified as either simple or strangulating obstructions. A great deal of work has been done to assess the level of injury encountered with these lesions at surgery and during the postsurgical phase following correction and subsequent reperfusion of these lesions. Although more is known about mucosal injury than about injury encountered in other intestinal layers, it is clear that substantial injury also occurs at the levels of the serosa and the muscularis, which very likely contributes to postoperative complications such as adhesion formation and ileus. Understanding the pathophysiology of these lesions allows the surgeon to more adequately perform surgical and postoperative procedures to optimize patient survival. For example, attention has been focused on the development of intestinal injury during reperfusion, and the possibility of inhibiting these lesions with various treatments. Furthermore, to combat the postoperative complication of serosal inflammation and secondary adhesion formation, surgeons have adopted a number of new treatments.}, booktitle={Equine Surgery}, publisher={Elsevier}, author={Cook, Vanessa L. and Blikslager, Anthony T. and Marshall, John F.}, year={2019}, pages={529–536} }
 @inbook{blikslager_wilson_2019, title={Stomach and Duodenum}, ISBN={9780323484206}, url={http://dx.doi.org/10.1016/b978-0-323-48420-6.00031-4}, DOI={10.1016/b978-0-323-48420-6.00031-4}, booktitle={Equine Surgery}, publisher={Elsevier}, author={Blikslager, Anthony T. and Wilson, David A.}, year={2019}, pages={496–505} }
 @inbook{prange_blikslager_rakestraw_2019, title={Transverse and Small Colon}, ISBN={9780323484206}, url={http://dx.doi.org/10.1016/b978-0-323-48420-6.00038-7}, DOI={10.1016/b978-0-323-48420-6.00038-7}, booktitle={Equine Surgery}, publisher={Elsevier}, author={Prange, Timo and Blikslager, Anthony T. and Rakestraw, Peter C.}, year={2019}, pages={621–631} }
 @article{jin_blikslager_2018, title={138 - Knockout of CLC-2 Reveals Critical Functions of Adherens Junctions in Colonic Homeostasis and Tumorigenicity}, volume={154}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(18)30596-1}, DOI={10.1016/S0016-5085(18)30596-1}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Jin, Younggeon and Blikslager, Anthony T.}, year={2018}, month={May}, pages={S-37-S-38} }
 @article{burke_blikslager_2018, title={Advances in Diagnostics and Treatments in Horses with Acute Colic and Postoperative Ileus}, volume={34}, ISSN={0749-0739}, url={http://dx.doi.org/10.1016/j.cveq.2017.11.006}, DOI={10.1016/j.cveq.2017.11.006}, abstractNote={Differentiating between medical and surgical causes of colic is one of the primary goals of the colic workup, because early surgical intervention improves prognosis in horses requiring surgery. Despite the increasing availability of advanced diagnostics (hematologic analyses, abdominal ultrasound imaging, etc), the most accurate indicators of the need for surgery remain the presence of moderate to severe signs of abdominal pain, recurrence of pain after appropriate analgesic therapy, and the absence of intestinal borborygmi. Investigation of novel biomarkers, which may help to differentiate surgical lesions from those that can be managed medically, continues to be an active area of research.}, number={1}, journal={Veterinary Clinics of North America: Equine Practice}, publisher={Elsevier BV}, author={Burke, Megan and Blikslager, Anthony}, year={2018}, month={Apr}, pages={81–96} }
 @article{lisowski_pirie_blikslager_lefebvre_hume_hudson_2018, title={An update on equine post-operative ileus: Definitions, pathophysiology and management}, volume={50}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12801}, DOI={10.1111/evj.12801}, abstractNote={Post-operative ileus (POI) is a serious condition which any horse undergoing abdominal surgery is at risk of developing, leading to increased hospitalisation time and resulting costs. Advances in the understanding of the development of equine POI are mainly based on human and rodent literature, where manipulation-induced inflammation has been identified as a trigger, with activation of resident muscularis externa macrophages playing a crucial role in the pathophysiology. Despite many pharmacological trials in all species, there is no single completely successful treatment for POI, highlighting that the condition is multifactorial in cause and requires a multimodal approach to minimise its incidence.}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Lisowski, Z. M. and Pirie, R. S. and Blikslager, A. T. and Lefebvre, D. and Hume, D. A. and Hudson, N. P. H.}, year={2018}, month={Jan}, pages={292–303} }
 @article{hill_lascelles_blikslager_2018, title={Effect of sucralfate on gastric permeability in an ex vivo model of stress-related mucosal disease in dogs}, volume={32}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.15076}, DOI={10.1111/jvim.15076}, abstractNote={Sucralfate is a gastroprotectant with no known systemic effects. The efficacy of sucralfate for prevention and treatment of stress-related mucosal diseases (SRMD) in dogs is unknown.To develop a canine ex vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier function in this model.Gastric antral mucosa was collected immediately postmortem from 29 random-source apparently healthy dogs euthanized at a local animal control facility.Randomized experimental trial. Sucralfate (100 mg/mL) was applied to ex vivo canine gastric mucosa concurrent with and after acid injury. Barrier function was assessed by measurement of transepithelial electrical resistance (TER) and radiolabeled mannitol flux.Application of acidified Ringers solution to the mucosal side of gastric antrum caused a reduction in gastric barrier function, and washout of acidified Ringers solution allowed recovery of barrier function (TER: 34.0 ± 2.8% of control at maximum injury, 71.3 ± 5.5% at recovery, P < .001). Sucralfate application at the time of injury or after injury significantly hastened recovery of barrier function (TER: 118.0 ± 15.2% of control at maximum injury, P < .001 and 111.0 ± 15.5% at recovery, P = .35).Sucralfate appeared effective at restoring defects in gastric barrier function induced by acid and accelerating repair of tissues subjected to acid in this model, suggesting that sucralfate could have utility for the treatment and prevention of SRMD in dogs.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Hill, Tracy L. and Lascelles, B. Duncan X. and Blikslager, Anthony T.}, year={2018}, month={Feb}, pages={670–678} }
 @article{ziegler_pridgen_mills_gonzalez_van landeghem_odle_blikslager_2018, title={Epithelial restitution defect in neonatal jejunum is rescued by juvenile mucosal homogenate in a pig model of intestinal ischemic injury and repair}, volume={13}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0200674}, DOI={10.1371/journal.pone.0200674}, abstractNote={Intestinal ischemic injury results sloughing of the mucosal epithelium leading to host sepsis and death unless the mucosal barrier is rapidly restored. Volvulus and neonatal necrotizing enterocolitis (NEC) in infants have been associated with intestinal ischemia, sepsis and high mortality rates. We have characterized intestinal ischemia/repair using a highly translatable porcine model in which juvenile (6-8-week-old) pigs completely and efficiently restore barrier function by way of rapid epithelial restitution and tight junction re-assembly. In contrast, separate studies showed that younger neonatal (2-week-old) pigs exhibited less robust recovery of barrier function, which may model an important cause of high mortality rates in human infants with ischemic intestinal disease. Therefore, we aimed to further refine our repair model and characterize defects in neonatal barrier repair. Here we examine the defect in neonatal mucosal repair that we hypothesize is associated with hypomaturity of the epithelial and subepithelial compartments. Following jejunal ischemia in neonatal and juvenile pigs, injured mucosa was stripped from seromuscular layers and recovered ex vivo while monitoring transepithelial electrical resistance (TEER) and 3H-mannitol flux as measures of barrier function. While ischemia-injured juvenile mucosa restored TEER above control levels, reduced flux over the recovery period and showed 93±4.7% wound closure, neonates exhibited no change in TEER, increased flux, and a 11±23.3% increase in epithelial wound size. Scanning electron microscopy revealed enterocytes at the wound margins of neonates failed to assume the restituting phenotype seen in restituting enterocytes of juveniles. To attempt rescue of injured neonatal mucosa, neonatal experiments were repeated with the addition of exogenous prostaglandins during ex vivo recovery, ex vivo recovery with full thickness intestine, in vivo recovery and direct application of injured mucosal homogenate from neonates or juveniles. Neither exogenous prostaglandins, intact seromuscular intestinal layers, nor in vivo recovery enhanced TEER or restitution in ischemia-injured neonatal mucosa. However, ex vivo exogenous application of injured juvenile mucosal homogenate produced a significant increase in TEER and enhanced histological restitution to 80±4.4% epithelial coverage in injured neonatal mucosa. Thus, neonatal mucosal repair can be rescued through direct contact with the cellular and non-cellular milieu of ischemia-injured mucosa from juvenile pigs. These findings support the hypothesis that a defect in mucosal repair in neonates is due to immature repair mechanisms within the mucosal compartment. Future studies to identify and rescue specific defects in neonatal intestinal repair mechanisms will drive development of novel clinical interventions to reduce mortality in infants affected by intestinal ischemic injury.}, number={8}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Ziegler, Amanda L. and Pridgen, Tiffany A. and Mills, Juliana K. and Gonzalez, Liara M. and Van Landeghem, Laurianne and Odle, Jack and Blikslager, Anthony T.}, editor={Karhausen, JörnEditor}, year={2018}, month={Aug}, pages={e0200674} }
 @article{blikslager_gonzalez_2018, title={Equine Intestinal Mucosal Pathobiology}, volume={6}, ISSN={2165-8102 2165-8110}, url={http://dx.doi.org/10.1146/annurev-animal-030117-014748}, DOI={10.1146/annurev-animal-030117-014748}, abstractNote={The equine intestinal mucosa is intimately involved in maintaining homeostasis both on a systemic level by controlling extracellular fluid movement and at the local level to maintain barrier function. Horses are particularly susceptible to the clinical syndrome of colic, with the most severe cases involving strangulating obstruction that induces ischemia. Because of the mucosal vascular architecture, the mucosal epithelium is particularly susceptible to ischemic injury. The potential for reperfusion injury has been investigated and found to play a minimal role. However, inflammation does affect mucosal repair. Mechanisms of repair, including villus contraction, epithelial restitution, and tight junction closure, are critical to reforming the mucosal barrier. Nonsteroidal anti-inflammatory drugs have an impact on this repair, particularly at the level of the tight junctions. Completion of mucosal regeneration requires proliferation, which is now being actively studied in equine enteroids. All of these aspects of equine mucosal pathobiology are reviewed in depth.}, number={1}, journal={Annual Review of Animal Biosciences}, publisher={Annual Reviews}, author={Blikslager, Anthony and Gonzalez, Liara}, year={2018}, month={Feb}, pages={157–175} }
 @article{blikslager_gonzalez_2018, title={Equine intestinal mucosal pathobiology}, volume={6}, journal={Annual review of animal biosciences, vol 6}, author={Blikslager, A. and Gonzalez, L.}, year={2018}, pages={157–175} }
 @article{burke_tomlinson_blikslager_johnson_dallap-schaer_2018, title={Evaluation of digital cryotherapy using a commercially available sleeve style ice boot in healthy horses and horses receiving i.v. endotoxin}, volume={50}, ISSN={["2042-3306"]}, url={https://doi.org/10.1111/evj.12842}, DOI={10.1111/evj.12842}, abstractNote={Continuous digital cryotherapy experimentally prevents development and reduces severity of sepsis-associated laminitis. A sleeve style ice boot where ice is in direct contact with the skin, and water drains from the boot is being used clinically for distal limb cryotherapy. The degree of cooling achieved by this boot is unknown.Evaluate skin and lamellar cooling after application of the ice sleeve in healthy horses, and the same horses during an endotoxaemia model.Prospective study, crossover design.In eight healthy horses thermocouples were inserted into dorsal lamellae of both front feet, and under skin on both metacarpi. One forelimb received cryotherapy using sleeve style ice boot, with contralateral limb as control. Temperature was recorded on data logging devices at 5 min intervals during each cryotherapy session. Day 1: temperature data was collected for healthy horses. Day 2: data was collected for the same horses during i.v. administration of endotoxin.In healthy and endotoxaemic horses, the sleeve style ice boot significantly decreased mean skin (7.2°C and 5.8°C respectively) and lamellar (10.8°C and 9.6°C respectively) temperatures compared with control limbs (P<0.001). Skin and lamellar temperatures in endotoxaemic horses undergoing cryotherapy were significantly colder than in healthy horses (P = 0.01).Order of treatment not randomised.The boot caused significant decreases in lamellar temperatures compared with untreated control limbs in all horses. Endotoxaemic horses had significantly colder lamellae and skin than healthy horses. This study is the first to show that a sleeve style boot, where ice does not cover the hoof, can cause significant decreases in lamellar temperatures through cooling of blood as it travels to the foot.}, number={6}, journal={EQUINE VETERINARY JOURNAL}, author={Burke, M. J. and Tomlinson, J. E. and Blikslager, A. T. and Johnson, A. L. and Dallap-Schaer, B. L.}, year={2018}, month={Nov}, pages={848–853} }
 @article{gerard_glyphis_crawford_blikslager_marais_2018, title={IDENTIFICATION OF A NASOCONCHAL PARANASAL SINUS IN THE WHITE RHINOCEROS (CERATOTHERIUM SIMUM)}, volume={49}, ISSN={["1937-2825"]}, DOI={10.1638/2017-0185.1}, abstractNote={African rhinoceros are poached for their horns using indiscriminate and aggressive methods. Rhinoceros that survive these attacks often have severe facial trauma, and treatment is limited by a lack of understanding and published information of the normal anatomy. This study was performed to investigate and describe the anatomy of the most commonly injured area of the head of the white rhinoceros (Ceratotherium simum). Two white rhinoceros cadaver heads were imaged by computed tomography and grossly dissected. A combined dorsal conchal sinus and nasal sinus (named the nasoconchal sinus) was identified and confirmed to be readily exposed by horn removal. The nasoconchal sinus communicates via a relatively large opening with the middle nasal meatus of the nasal cavity. Awareness of the combined sinus space and its single communicating pathway will assist with accurate assessment and treatment of trauma to the dorsal facial region of the white rhinoceros.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Gerard, Mathew R. and Glyphis, Zoe G. and Crawford, Christine and Blikslager, Anthony T. and Marais, JOhan}, year={2018}, month={Jun}, pages={444–449} }
 @article{stieler stewart_freund_blikslager_gonzalez_2018, title={Intestinal Stem Cell Isolation and Culture in a Porcine Model of Segmental Small Intestinal Ischemia}, volume={5}, ISSN={1940-087X}, url={http://dx.doi.org/10.3791/57647}, DOI={10.3791/57647}, abstractNote={Intestinal ischemia remains a major cause of morbidity and mortality in human and veterinary patients. Many disease processes result in intestinal ischemia, when the blood supply and therefore oxygen is decreased to the intestine. This leads to intestinal barrier loss and damage to the underlying tissue. Intestinal stem cells reside at the base of the crypts of Lieberkühn and are responsible for intestinal renewal during homeostasis and following injury. Ex vivo cell culture techniques have allowed for the successful study of epithelial stem cell interactions by establishing culture conditions that support the growth of three-dimensional epithelial organ-like systems (termed "enteroids" and "colonoids" from the small and large intestine, respectively). These enteroids are composed of crypt and villus-like domains and mature to contain all of the cell types found within the epithelium. Historically, murine models have been utilized to study intestinal injury. However, a porcine model offers several advantages including similarity of size as well as gastrointestinal anatomy and physiology to that of humans. By utilizing a porcine model, we establish a protocol in which segmental loops of intestinal ischemia can be created within a single animal, enabling the study of differing time points of ischemic injury and repair in vivo. Additionally, we describe a method to isolate and culture the intestinal stem cells from the ischemic loops of intestine, allowing for the continued study of epithelial repair, modulated by stem cells, ex vivo.}, number={135}, journal={Journal of Visualized Experiments}, publisher={MyJove Corporation}, author={Stieler Stewart, Amy and Freund, John M and Blikslager, Anthony T and Gonzalez, Liara M}, year={2018}, month={May} }
 @article{jin_ibrahim_magness_blikslager_2018, title={Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity}, volume={315}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00087.2018}, DOI={10.1152/ajpgi.00087.2018}, abstractNote={Adherens junctions (AJs), together with tight junctions (TJs), form an apical junctional complex that regulates intestinal epithelial cell-to-cell adherence and barrier homeostasis. Within the AJ, membrane-bound E-cadherin binds β-catenin, which functions as an essential intracellular signaling molecule. We have previously identified a novel protein in the region of the apical junction complex, chloride channel protein-2 (ClC-2), that we have used to study TJ regulation. In this study, we investigated the possible effects of ClC-2 on the regulation of AJs in intestinal mucosal epithelial homeostasis and tumorigenicity. Mucosal homeostasis and junctional proteins were examined in wild-type (WT) and ClC-2 knockout (KO) mice as well as associated colonoids. Tumorigenicity and AJ-associated signaling were evaluated in a murine colitis-associated tumor model and in a colorectal cancer cell line (HT-29). Colonic tissues from ClC-2 KO mice had altered ultrastructural morphology of intercellular junctions with reduced colonocyte differentiation, whereas jejunal tissues had minimal changes. Colonic crypts from ClC-2 KO mice had significantly higher numbers of less-differentiated forms of colonoids compared with WT. Furthermore, the absence of ClC-2 resulted in redistribution of AJ proteins and increased β-catenin activity. Downregulation of ClC-2 in colorectal cells resulted in significant increases in proliferation associated with disruption of AJs. Colitis-associated tumors in ClC-2 KO mice were significantly increased, associated with β-catenin transcription factor activation. The absence of ClC-2 results in less differentiated colonic crypts and increased tumorigenicity associated with colitis via dysregulation of AJ proteins and activation of β-catenin-associated signaling. NEW & NOTEWORTHY Disruption of adherens junctions in the absence of chloride channel protein-2 revealed critical functions of these junctional structures, including maintenance of colonic homeostasis and differentiation as well as driving tumorigenicity by regulating β-catenin signaling.}, number={6}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Jin, Younggeon and Ibrahim, Dina and Magness, Scott T. and Blikslager, Anthony T.}, year={2018}, month={Dec}, pages={G966–G979} }
 @article{kruger_pridgen_garman_blikslager_2018, title={Mo1169 - Role of Cftr and Clc-2 in Esophageal Barrier Function}, volume={154}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(18)32450-8}, DOI={10.1016/S0016-5085(18)32450-8}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Kruger, Leandi and Pridgen, Tiffany and Garman, Katherine S. and Blikslager, Anthony T.}, year={2018}, month={May}, pages={S-694} }
 @article{ziegler_freeman_fogle_burke_davis_cook_southwood_blikslager_2018, title={Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction}, volume={51}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/evj.13013}, DOI={10.1111/evj.13013}, abstractNote={Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin meglumine.We hypothesised that treatment of post-surgical SISO horses with firocoxib (COX-2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control.Blinded randomised clinical trial.In addition to clinical monitoring, preoperative and 12-, 24- and 48-h post-operative plasma samples were assessed for prostaglandin E2 (PGE2 ), thromboxane B2 (TXB2 ), TNF⍺ and soluble CD14 (sCD14).In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post-operative period in three university hospitals from 2015 to 2017. COX-2 selectivity was confirmed by a relative lack of inhibition of the COX-1 prostanoid TXB2 by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX-2 prostanoid PGE2 . There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23-fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia.Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine.In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Ziegler, A. L. and Freeman, C. K. and Fogle, C. A. and Burke, M. J. and Davis, J. L. and Cook, V. L. and Southwood, L. L. and Blikslager, A. T.}, year={2018}, month={Sep}, pages={329–335} }
 @article{hernandez_carlson_pridgen_messenger_prior_laumas_madan_krishnan_blikslager_2018, title={Sa1183 - Larazotide Stimulates Recovery of Ischemic-Injured Intestine in a Dose-Dependent Manner Associated with Restoration of Tight Junctions}, volume={154}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(18)31264-2}, DOI={10.1016/S0016-5085(18)31264-2}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Hernandez, Liliana and Carlson, Alexandra and Pridgen, Tiffany and Messenger, Kristen and Prior, Christopher P. and Laumas, Sandeep and Madan, Jay and Krishnan, B Radha and Blikslager, Anthony T.}, year={2018}, month={May}, pages={S-270} }
 @article{hernandez_carlson_pridgen_messenger_prior_laumas_madan_krishnan_blikslager_2018, title={Su2039 - Larazotide Stimulates Recovery of Ischemic-Injured Intestine in the Presence of the Non-Steroidal Anti-Inflammatory Drug (NSAID) Indomethacin Related to Recovery of Tight Junctions}, volume={154}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(18)34463-9}, DOI={10.1016/S0016-5085(18)34463-9}, number={6}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Hernandez, Liliana and Carlson, Alexandra and Pridgen, Tiffany and Messenger, Kristen and Prior, Christopher P. and Laumas, Sandeep and Madan, Jay and Krishnan, B Radha and Blikslager, Anthony T.}, year={2018}, month={May}, pages={S-1365} }
 @article{dellon_joshi_blikslager_gonzalez_pridgen_whitlow_ivanovic_slaughter_garman_karp_et al._2017, title={A Novel Inflammation-Activated Drug Delivery System Using Self-Assembling Hydrogel Doubles Esophageal Dwell Time in an Esophageal Injury Porcine Model}, volume={152}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(17)32956-6}, DOI={10.1016/S0016-5085(17)32956-6}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Dellon, Evan S. and Joshi, Nitin and Blikslager, Anthony and Gonzalez, Liara M. and Pridgen, Tiffany and Whitlow, Ann and Ivanovic, Marija and Slaughter, Kai and Garman, Katherine S. and Karp, Jeffrey M. and et al.}, year={2017}, month={Apr}, pages={S859–S860} }
 @article{krüger_gonzalez_pridgen_mccall_furstenberg_harnden_carnighan_cox_blikslager_garman_et al._2017, title={Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair}, volume={313}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00036.2017}, DOI={10.1152/ajpgi.00036.2017}, abstractNote={Esophageal injury is a risk factor for diseases such as Barrett’s esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair. NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given the anatomical and physiological similarities between pigs and humans.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Krüger, Leandi and Gonzalez, Liara and Pridgen, Tiffany A. and McCall, Shannon J. and Furstenberg, Richard J. and Harnden, Ivan and Carnighan, Gwendolyn E. and Cox, Abigail M. and Blikslager, Anthony and Garman, Katherine S. and et al.}, year={2017}, month={Sep}, pages={G180–G191} }
 @article{shin_ferguson_2017, title={Exploring Product Solution Differences Due to Choice Model Selection in the Presence of Noncompensatory Decisions With Conjunctive Screening Rules}, volume={139}, ISSN={["1050-0472"]}, DOI={10.1115/1.4035051}, abstractNote={Research in market-based product design has often used compensatory preference models that assume an additive part-worth rule. These additive models have a simple, usable form and their parameters can be estimated using existing software packages. However, marketing research literature has demonstrated that consumers sometimes use noncompensatory-derived heuristics to simplify their choice decisions. This paper explores the quality of optimal solution obtained to a product line design search when using a compensatory model in the presence of noncompensatory choices and a noncompensatory model with conjunctive screening rules. Motivation for this work comes from the challenges posed by Bayesian-based noncompensatory models: the need for screening rule assumptions, probabilistic representations of noncompensatory choices, and discontinuous choice probability functions. This paper demonstrates how respondents making noncompensatory choices with conjunctive rules can lead to compensatory model estimations with distinct respondent segmentation and relative, large absolute part-worth values. Results from a product design problem suggest that using a compensatory model can provide benefits of smaller design errors and reduced computational costs. Product design optimization problems using real choice data confirm that the compensatory model and the noncompensatory model with conjunctive rules provide comparable solutions that have similar likelihoods of not being screened out when using a consideration set verifier. While many different noncompensatory heuristic rules exist, the presented study is limited to conjunctive screening rules.}, number={2}, journal={JOURNAL OF MECHANICAL DESIGN}, author={Shin, Jaekwan and Ferguson, Scott}, year={2017}, month={Feb} }
 @article{shrauner_blikslager_davis_campbell_law_lustgarten_prange_2017, title={Feasibility and safety of lumbosacral epiduroscopy in the standing horse}, volume={49}, ISSN={["2042-3306"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84978052421&partnerID=MN8TOARS}, DOI={10.1111/evj.12591}, abstractNote={The large size of the adult horse prevents the use of advanced imaging modalities in most areas of the axial skeleton, including the lumbosacral vertebral column. Traditional imaging techniques are frequently unable to pinpoint the underlying pathology in horses with caudal back pain. In man, lumbosacral epiduroscopy is used to diagnose and treat subjects with chronic back and leg pain. This technique may close the diagnostic gap in horses with similar clinical signs.To evaluate the safety and feasibility of lumbosacral epiduroscopy in the standing adult horse.Descriptive, experimental study.Seven adult horses weighing 504-578 kg were sedated and restrained in stocks in preparation for aseptic surgery. Vascular dilators of increasing size were inserted cranial to the first moveable vertebra caudal to the sacrum to facilitate a minimally invasive approach into the epidural space. A flexible video-endoscope was introduced and advanced as far as its 60-cm working length permitted. Pre-, intra- and post-operative plasma cortisol samples were collected, and neurological and lameness examinations were performed prior to and during the 2 weeks following the procedure. Post-mortem examinations were conducted in 5 of the 7 horses.Standing lumbosacral epiduroscopy was well tolerated by all horses. The anatomic structures in the epidural space (dura mater, spinal nerve roots, fat and blood vessels) were followed as far cranial as the thoracolumbar region. No complications related to the procedure were noted in the 2-week monitoring period following epiduroscopy. Small, organised haematomas were identified in the sacral epidural space during necropsy in one horse. No abnormalities were seen in the other 4 animals.Lumbosacral epiduroscopy can be performed safely in sedated standing horses. The procedure may become a valuable diagnostic tool in horses with caudal back or hindlimb pain of unknown origin.}, number={3}, journal={EQUINE VETERINARY JOURNAL}, author={Shrauner, B. and Blikslager, A. and Davis, J. and Campbell, N. and Law, M. and Lustgarten, M. and Prange, T.}, year={2017}, month={May}, pages={322–328} }
 @article{ziegler_blikslager_2017, title={Impaired intestinal barrier function and relapsing digestive disease: Lessons from a porcine model of early life stress}, volume={29}, ISSN={1350-1925}, url={http://dx.doi.org/10.1111/nmo.13216}, DOI={10.1111/nmo.13216}, abstractNote={Within this issue of Neurogastroenterology and Motility, an article by Pohl et al highlights new insights from a powerful porcine model of the link between early life adversity and relapsing functional gastrointestinal disorders. Early weaning stress closely mimics the early life psychosocial stressors that have been linked to adult onset gastrointestinal dysfunction. This early weaning model provides reproducible and highly translatable outcomes in young stress-challenged pigs. Due to the convincingly comparable neurological and gastroenterological anatomy and physiology between pigs and human beings, gastrointestinal stress and injury studies utilizing swine models will provide invaluable insights to improve our understanding and treatment of gastrointestinal disease in human beings. Future studies to examine mechanisms underlying this link between early life adversity and functional gastrointestinal disorders will explore the roles of gender and hypomaturity in gastrointestinal responses to stress.}, number={11}, journal={Neurogastroenterology & Motility}, publisher={Wiley}, author={Ziegler, A. L. and Blikslager, A. T.}, year={2017}, month={Oct}, pages={e13216} }
 @inbook{blikslager_2017, title={Pathophysiology of Gastrointestinal Obstruction and Strangulation}, ISBN={9781119063254 9781119063216}, url={http://dx.doi.org/10.1002/9781119063254.ch11}, DOI={10.1002/9781119063254.ch11}, abstractNote={The intestine may be subjected to simple obstruction, in which only the lumen is obstructed, strangulating obstruction, in which both the lumen and vasculature are obstructed, or infarction, in which only the vasculature is obstructed. Each of these may injure intestinal tissues, particularly with interruption of blood flow and subsequent ischemic injury. This can also occur in simple obstruction as the luminal pressure causes collapse of the vasculature within the intestinal wall. Once reperfused, ischemic-injured mucosa may undergo reperfusion injury, depending on the circumstances. This relates to the level of reactive oxygen metabolite generation and infiltration of neutrophils. More recently, repair of the mucosa has been studied in depth, including villus contraction (in the small intestine), epithelial restitution, tight junction closure, and mucosal proliferation. Other layers of the intestine are also injured, particularly the serosa, which can lead to inflammation and development of adhesions.}, booktitle={The Equine Acute Abdomen}, publisher={John Wiley & Sons, Inc.}, author={Blikslager, Anthony T.}, year={2017}, month={Sep}, pages={102–118} }
 @article{von furstenberg_li_stolarchuk_feder_campbell_kruger_gonzalez_blikslager_cardona_mccall_et al._2017, title={Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation}, volume={4}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2017.07.005}, DOI={10.1016/j.jcmgh.2017.07.005}, abstractNote={Although cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model.We evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2'-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs.Marked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor-dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+) and hollow/ductal (cytokeratin 7+). Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts.Our results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous) or abnormally (columnar epithelium). This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for Biotechnology Information Gene Expression Omnibus (accession number: GSE100543).}, number={3}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={von Furstenberg, Richard J. and Li, Joy and Stolarchuk, Christina and Feder, Rachel and Campbell, Alexa and Kruger, Leandi and Gonzalez, Liara M. and Blikslager, Anthony T. and Cardona, Diana M. and McCall, Shannon J. and et al.}, year={2017}, month={Nov}, pages={385–404} }
 @article{kucera_stranahan_hughes_blikslager_gonzalez_2017, title={Protein biomarker of cell proliferation determines survival to discharge in cases of equine large colon volvulus}, volume={50}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12767}, DOI={10.1111/evj.12767}, abstractNote={Progenitor cells play critical roles in epithelial repair following ischaemic injury. Protein biomarkers have been used to identify intestinal progenitor cell subpopulations. This study aims to determine if a critical number of intestinal progenitor cells can predict tissue viability and survival to discharge of large colon volvulus (LCV) cases.The objectives were to 1) identify intestinal progenitor cell subpopulations using biomarkers: proliferating cell nuclear antigen (PCNA), sex determining region Y box 9 (SOX9), phospho-histone H3 (PHH3) and Ki-67, 2) define cut-off values for critical numbers of positive cells and 3) determine if survival to discharge is associated with cut-off values.Retrospective cohort study.Adult horses admitted to the Farm and Equine Veterinary Medical Center at NC State's Veterinary Hospital and Peterson and Smith Equine Hospital between 2006 and 2016 that underwent an exploratory coeliotomy with a diagnosis of LCV of ≥360 degrees, had pelvic flexure biopsy and that recovered from general anaesthesia were selected for inclusion in the study. Immunohistochemical analyses were performed and positive cells were counted. Optimal cut-off values were determined using receiver operator curves. A Fisher's exact test was used to associate cut-off values with survival to discharge.In this study, 23 cases of LCV ≥360° were included. Of 23 horses, 13 (57%) survived to discharge. A cut-off value of <2.1 PHH3 positive cells per crypt correctly predicted death with 100% sensitivity (95% CI; 69.15-100%) and 84.62% specificity (95% CI; 54.55-98.08%). LCV cases with <2.1 PHH3 positive cells per crypt were 96.6 times more likely to die (95% CI; 4.14-2255 and P < 0.0001). Biomarkers PCNA, SOX9 and Ki-67 did not predict short-term survival.The population size was small.PHH3 immunohistochemical analysis may assist in more accurate prediction of survival to hospital discharge of LCV cases. The summary is available in Spanish - see Supporting Information.}, number={4}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Kucera, C. R. and Stranahan, L. W. and Hughes, F. and Blikslager, A. T. and Gonzalez, L. M.}, year={2017}, month={Nov}, pages={452–456} }
 @misc{blikslager_2017, title={Reply to Dr Freeman: Keep your surgical options open}, volume={29}, ISSN={["2042-3292"]}, DOI={10.1111/eve.12710}, number={7}, journal={EQUINE VETERINARY EDUCATION}, author={Blikslager, A. T.}, year={2017}, month={Jul}, pages={404–405} }
 @inbook{blikslager_2017, title={Small Intestinal Function}, ISBN={9781119063254 9781119063216}, url={http://dx.doi.org/10.1002/9781119063254.ch4}, DOI={10.1002/9781119063254.ch4}, abstractNote={Digestion and absorption of nutrients take place predominantly in the proximal half of the small intestine so that the ileum is exposed to a relatively low nutrient load. The digestive/absorptive units of the small intestinal mucosa are finger-like projections of the epithelial surface, the villi, whereas secretory function is largely confined to the crypts. Villus height and crypt depth decline from the proximal to the distal segments of the intestine. As enterocytes move up the crypt–villus axis, they progressively differentiate to take on absorptive and digestive functions. For example, there is a gradient of RNA abundance from the villus base to the tip with six times more of the D-glucose transporter SGLT1 being present in mature cells near the tip than in the immature cells at the base. A similar gradient for amino acid absorption has been demonstrated by autoradiographic methods in equine jejunum. Although the crypts of both small and large intestines have zones of proliferation, migration, and differentiation, only the small intestine has villi with unique digestive and absorptive capabilities.}, booktitle={The Equine Acute Abdomen}, publisher={John Wiley & Sons, Inc.}, author={Blikslager, Anthony T.}, year={2017}, month={Sep}, pages={27–40} }
 @article{lima_lin_jacobi_man_sommer_flowers_blikslager_gonzalez_odle_2017, title={Supplementation of Maternal Diets with Docosahexaenoic Acid and Methylating Vitamins Impacts Growth and Development of Fetuses from Malnourished Gilts}, volume={2}, ISSN={2475-2991}, url={http://dx.doi.org/10.3945/cdn.117.001958}, DOI={10.3945/cdn.117.001958}, abstractNote={Like many species, pregnant swine mobilize and repartition body nutrient stores during extreme malnutrition to support fetal development.The objective of this study was to model chronic human maternal malnutrition and measure effects of methylating-vitamins (MVs, containing choline, folate, B-6, B-12, and riboflavin) and docosahexaenoic acid (DHA) supplementation on fetal growth and development.Pregnant gilts (n = 24) were either fully nourished (2.0 kg/d) with a corn-plus-isolated-soy-protein basal diet (control) supplemented with MVs and DHA or nourishment was restricted throughout gestation. Basal diet fed to malnourished gilts was reduced progressively from 50% to 70% restriction (1.0 to 0.6 kg/d) and was supplemented following a 2 (±MVs) x 2 (±DHA) factorial design. Full-term c-sections were performed to assess impacts on low and normal birth weight (LBW/NBW) fetuses (n = 238).Body weight gain of malnourished gilts was 10% of full-fed control dams (P < 0.05), but offspring birth weight, length, girth, and percentage of LBW fetuses were not different between treatments. The number of pigs per litter was reduced by 30% in malnourished control dams. Fetal brain weights were reduced by 7% compared to positive controls (P < 0.05). Micronutrient supplementation to malnourished dams increased fetal brain weights back to full-fed control levels. Dams with DHA produced offspring with higher DHA concentrations in brain and liver (P < 0.05). Plasma choline concentration was 4-fold higher in fetuses from unsupplemented malnourished dams (P < 0.0001). Global DNA methylation status of fetuses from restricted dams was higher than in control fetuses, including brain, liver, heart, muscle, and placenta tissues (P < 0.05). Addition of DHA increased methylation in LBW fetal brains (P < 0.05).Despite the mobilization of maternal stores, malnourished litters displayed reduced brain development that was fully mitigated by micronutrient supplementation. Severe maternal malnutrition increased global DNA methylation in several fetal tissues that was unaltered by choline and B-vitamin supplementation.}, number={3}, journal={Current Developments in Nutrition}, publisher={Oxford University Press (OUP)}, author={Lima, Hope K and Lin, Xi and Jacobi, Sheila K and Man, Caolai and Sommer, Jeffrey and Flowers, William and Blikslager, Anthony and Gonzalez, Liara and Odle, Jack}, year={2017}, month={Dec} }
 @book{libraries_2017, title={The Equine Acute Abdomen}, ISBN={9781119063254 9781119063216}, url={http://dx.doi.org/10.1002/9781119063254}, DOI={10.1002/9781119063254}, abstractNote={Providing coverage of the diseases producing equine acute abdomen or colic, this text covers diagnosis, treatment, anaesthesia, surgery and intensive care.}, publisher={John Wiley & Sons, Inc.}, author={Libraries, NC State University}, editor={Blikslager, Anthony T. and White, Nathaniel A., II and Moore, James N. and Mair, Tim S.Editors}, year={2017}, month={Oct} }
 @article{zhang_ke_blikslager_fujita_yoo_2017, title={Type III Interferon Restriction by Porcine Epidemic Diarrhea Virus and the Role of Viral Protein nsp1 in IRF1 Signaling}, volume={92}, ISSN={0022-538X 1098-5514}, url={http://dx.doi.org/10.1128/JVI.01677-17}, DOI={10.1128/jvi.01677-17}, abstractNote={ABSTRACT Type III interferons (IFNs) play a vital role in maintaining the antiviral state of the mucosal epithelial surface in the gut, and in turn, enteric viruses may have evolved to evade the type III IFN responses during infection. To study the possible immune evasion of the type III IFN response by porcine epidemic diarrhea virus (PEDV), a line of porcine intestinal epithelial cells was developed as a cell model for PEDV replication. IFN-λ1 and IFN-λ3 inhibited PEDV replication, indicating the anti-PEDV activity of type III IFNs. Of the 21 PEDV proteins, nsp1, nsp3, nsp5, nsp8, nsp14, nsp15, nsp16, open reading frame 3 (ORF3), E, M, and N were found to suppress type III IFN activities, and IRF1 (interferon regulatory factor 1) signaling mediated the suppression. PEDV specifically inhibited IRF1 nuclear translocation. The peroxisome is the innate antiviral signaling platform for the activation of IRF1-mediated IFN-λ production, and the numbers of peroxisomes were found to be decreased in PEDV-infected cells. PEDV nsp1 blocked the nuclear translocation of IRF1 and reduced the number of peroxisomes to suppress IRF1-mediated type III IFNs. Mutational studies showed that the conserved residues of nsp1 were crucial for IRF1-mediated IFN-λ suppression. Our study for the first time provides evidence that the porcine enteric virus PEDV downregulates and evades IRF1-mediated type III IFN responses by reducing the number of peroxisomes. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus that emerged in swine in the United States and has caused severe economic losses. PEDV targets intestinal epithelial cells in the gut, and intestinal epithelial cells selectively induce and respond to the production of type III interferons (IFNs). However, little is known about the modulation of the type III IFN response by PEDV in intestinal epithelial cells. In this study, we established a porcine intestinal epithelial cell model for PEDV replication. We found that PEDV inhibited IRF1-mediated type III IFN production by decreasing the number of peroxisomes in porcine intestinal epithelial cells. We also demonstrated that the conserved residues in the PEDV nsp1 protein were crucial for IFN suppression. This study for the first time shows PEDV evasion of the type III IFN response in intestinal epithelial cells, and it provides valuable information on host cell-virus interactions not only for PEDV but also for other enteric viral infections in swine.}, number={4}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Zhang, Qingzhan and Ke, Hanzhong and Blikslager, Anthony and Fujita, Takashi and Yoo, Dongwan}, year={2017}, month={Nov}, pages={JVI.01677–17} }
 @article{ziegler_fogle_blikslager_2017, title={Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses}, volume={250}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.250.11.1271}, DOI={10.2460/javma.250.11.1271}, abstractNote={Abstract Nonsteroidal anti-inflammatory drugs work through inhibition of cyclooxygenase (COX) and are highly effective for the treatment of pain and inflammation in horses. There are 2 clinically relevant isoforms of COX. Cyclooxygenase-1 is constitutively expressed and is considered important for a variety of physiologic functions, including gastrointestinal homeostasis. Thus, NSAIDs that selectively inhibit COX-2 while sparing COX-1 may be associated with a lower incidence of adverse gastrointestinal effects. Various formulations of firocoxib, a COX-2-selective NSAID, labeled for use in horses are available in the United States. Equine practitioners should know that the FDA limits the use of firocoxib to formulations labeled for horses, regardless of price concerns. In addition, practitioners will benefit from understanding the nuances of firocoxib administration, including the importance of correct dosing and the contraindications of combining NSAIDs. Together with knowledge of the potential advantages of COX-2 selectivity, these considerations will help veterinarians select and treat patients that could benefit from this new class of NSAID.}, number={11}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Ziegler, Amanda and Fogle, Callie and Blikslager, Anthony}, year={2017}, month={Jun}, pages={1271–1274} }
 @article{simpson_gonzalez_chung_blikslager_magness_piedrahita_2016, title={27 AN IMPROVED LARGE ANIMAL MODEL FOR THE STUDY OF ADULT STEM CELLS}, volume={28}, ISSN={1031-3613}, url={http://dx.doi.org/10.1071/RDV28N2AB27}, DOI={10.1071/RDV28N2AB27}, abstractNote={Murine models for the study of adult stem cell populations have broadened the understanding of previously uncharacterized stem cell niches. The development of murine reporter lines for the leucine-rich repeat-containing G-protein-coupled receptor-5 (Lgr5) has highlighted the importance of this gene as a stem cell marker in the stomach, intestine, hair follicle, liver, and kidney in mice. These models however have significant limitations in terms of translational applications because of anatomical and physiological differences between humans and mice. In order to overcome these limitations, we have sought to develop a porcine LGR5 reporter line. We report the generation of a porcine stem cell reporter line using the combination of transcription activator-like effector nucleases and somatic cell NT. Transcription activator-like effector nuclease-mediated homologous recombination was used to drive the integration of an internal ribosome entry site green fluorescent protein fusion into the 3′ untranslated region of the LGR5 locus in porcine fetal fibroblast cells. Multiple cell lines were developed and screened for the proper integration event. Upon confirmation of proper integration by genomic DNA sequencing, these lines were used as donors for somatic cell NT. Transfer of the somatic cell NT reconstructed embryos to a surrogate gilt resulted in 3 live births, and the establishment of a founder line of LGR5-green fluorescent protein reporter pigs. We have begun to characterise these lines, having observed fluorescent labelling of putative stem cell populations in the intestinal crypts and hair follicles from these animals. Many of these observations parallel the expression patterns observed in similar murine models. We have confirmed the fluorescent reporter signal by immunohistochemistry using an anti-green fluorescent protein antibody, and are working towards colocalization studies using anti-LGR5 antibodies and RNA in situ hybridization, as well as the characterisation of additional stem cell populations in the pig. The development of this line of transgenic pigs represents significant progress toward the study of adult stem cells, their progenitors, and the stem cell niche, using a large animal model with an anatomy, physiology, and ability to recapitulate human disease that overcomes the current limitations of rodent models. Funding was provided by NIH R21OD019738.}, number={2}, journal={Reproduction, Fertility and Development}, publisher={CSIRO Publishing}, author={Simpson, S. and Gonzalez, L. and Chung, J. and Blikslager, A. and Magness, S. and Piedrahita, J.}, year={2016}, pages={143} }
 @article{ziegler_pridgen_carnighan_odle_blikslager_2016, title={784 Neonates Have a Reduced Ability to Repair Jejunal Mucosal Injury As Compared to Juveniles in a Pig Model of Ischemia/ Reperfusion Injury}, volume={150}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(16)30639-4}, DOI={10.1016/S0016-5085(16)30639-4}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Ziegler, Amanda L. and Pridgen, Tiffany and Carnighan, Gwendolyn and Odle, Jack and Blikslager, Anthony}, year={2016}, month={Apr}, pages={S163} }
 @article{fogle_jacob_blikslager_edwards_wagner_dean_fogle_2016, title={Comparison of lipopolysaccharides and soluble CD14 measurement between clinically endotoxaemic and nonendotoxaemic horses}, volume={49}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12582}, DOI={10.1111/evj.12582}, abstractNote={Summary Reasons for performing study Clinically useful biomarkers are needed for early identification of endotoxaemic horses. Soluble CD14 (sCD14) is amplified early in response to inflammatory signals, including bacterial lipopolysaccharide (LPS), and may prove a useful biomarker for clinical endotoxaemia. Objectives The aim of this study was to determine if sCD14 could serve as a more reliable biomarker of the clinical signs of endotoxaemia, compared to measuring LPS alone. Study design Prospective observational study in horses at a veterinary teaching hospital. Methods Plasma samples were collected from 20 healthy horses and 35 horses presenting for emergency evaluation. Horses were classified as clinically endotoxaemic, using previously established criteria, if they had a heart rate >70 beats/min, packed cell volume >45% and/or a lesion likely to result in endotoxaemia. Soluble CD14 was measured using a cytometric bead‐based assay and LPS was measured using a Limulus amoebocyte lysate (LAL) assay. Results Soluble CD14 was higher in horses classified as clinically endotoxaemic (median 1102 ng/ml, interquartile range 439 ng/ml), compared to clinically nonendotoxaemic (median 692 ng/ml, interquartile range 455 ng/ml, P = 0.03. There was no difference in LPS concentrations between clinically nonendotoxaemic (median 5.4 endotoxin units [EU]/ml, interquartile range 5 EU/ml) and endotoxaemic horses (median 7.2 EU/ml, interquartile range 17 EU/ml, P = 0.2). There was no correlation between sCD14 and LPS values in paired serum samples. LPS and sCD14 values were used to generate a receiver operating characteristic curve. The area under the curve for LPS and sCD14 was <0.7, suggesting that sCD14 and LPS were poor predictors of clinical endotoxaemia for the horses in this study. Conclusions Further investigation is warranted to assess the utility of sCD14 measurement as a clinically useful biomarker to identify endotoxaemia in horses.}, number={2}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Fogle, J. and Jacob, M. and Blikslager, A. and Edwards, A. and Wagner, B. and Dean, K. and Fogle, C.}, year={2016}, month={May}, pages={155–159} }
 @article{partlow_blikslager_matthews_law_daniels_baker_labens_2016, title={Effect of topically applied Saccharomyces boulardii on the healing of acute porcine wounds: A preliminary study}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84963811981&partnerID=MN8TOARS}, DOI={10.1186/s13104-016-2012-8}, abstractNote={Normal wound healing progresses through a series of interdependent physiological events: inflammation, angiogenesis, re-epithelialization, granulation tissue formation and extracellular matrix remodeling. Alterations in this process as well as the bacterial type and load on a wound may alter the wound healing rate. The purpose of this study was to evaluate the effect of topical Saccharomyces boulardii on the healing of acute cutaneous wounds, using a prospective, controlled, experimental study, with six purpose bred landrace pigs. All wounds healed without apparent complications. Comparison of the mean 3D and 2D wound surface area measurements showed no significant difference between treatment groups as wounds decreased similarly in size over the duration of the study. A significant reduction in wound surface area was identified sooner using 3D assessments (by day 9) compared to 2D assessments (by day 12) (P < 0.001). There was no significant effect of treatment group on the number of multiple isolates or the most common isolates obtained relative to control wounds. There was no histologically appreciable difference between the wounds of the different groups. Topical application of Saccharomyces boulardii does not hasten wound healing or change the wounds’ microbiome under the conditions reported in this study.}, number={1}, journal={BMC Research Notes}, author={Partlow, J. and Blikslager, A. and Matthews, C. and Law, M. and Daniels, J. and Baker, R. and Labens, R.}, year={2016} }
 @article{prange_shrauner_blikslager_2016, title={Epiduroscopy of the lumbosacral vertebral canal in the horse: Technique and endoscopic anatomy}, volume={48}, ISSN={["2042-3306"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84939825449&partnerID=MN8TOARS}, DOI={10.1111/evj.12470}, abstractNote={Reasons for performing study Back pain is a common cause of gait alterations and poor performance in horses, but the available imaging modalities are frequently insufficient to isolate the underlying pathology. In human patients, epidural endoscopy (epiduroscopy) is successfully used to diagnose and treat challenging cases of lower back pain. Endoscopy of the cervical epidural space has previously been reported in anaesthetised horses. Objectives To develop a technique for lumbosacral epiduroscopy in standing horses and to describe the endoscopic anatomy of the lumbosacral epidural space. Study design Pilot study to assess the feasibility of lumbosacral epiduroscopy in 5 horse cadavers. Methods The cadavers of 5 horses, weighing 457–694 kg (mean, 570 kg), were suspended in an upright position. Vascular dilators of increasing size were inserted between the first 2 moveable vertebrae caudal to the sacrum to create a minimally invasive approach into the epidural space. A flexible videoendoscope was introduced and advanced as far cranially as the length of the endoscope permitted. The lumbosacral epidural space underwent gross necropsy examination following the procedure. Results The endoscope was successfully inserted into the epidural space in all horses. Saline injection through the working channel of the endoscope allowed the following anatomical structures to be seen: dura mater, left and right lumbosacral spinal nerves, cauda equina, epidural fat, connective tissue and blood vessels. Using the 60 cm working length of the endoscope, the epidural space could be examined as far cranial as L3–T18, depending on the size of the horse. No gross damage to epidural neurovascular structures was observed on necropsy examination. Conclusion Lumbosacral epiduroscopy is technically feasible in standing horses and may become a valuable diagnostic tool in horses with caudal back or limb pain of unknown origin. Studies in live horses will be necessary to evaluate the safety of the procedure.}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Prange, T. and Shrauner, B. D. and Blikslager, A. T.}, year={2016}, month={Jan}, pages={125–129} }
 @misc{prange_shrauner_blikslager_2016, title={Epiduroscopy of the lumbosacral vertebral canal in the horse: Technique and endoscopic anatomy Response}, volume={48}, ISSN={["2042-3306"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84949784656&partnerID=MN8TOARS}, DOI={10.1111/evj.12494}, abstractNote={See correspondence by Josephson and article by Prange et al.}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Prange, T. and Shrauner, B. D. and Blikslager, A. T.}, year={2016}, month={Jan}, pages={131–131} }
 @article{thakre-nighot_blikslager_2016, title={Indomethacin induces increase in gastric epithelial tight junction permeability via redistribution of occludin and activation of p38 MAPK in MKN-28 Cells}, volume={4}, ISSN={2168-8370}, url={http://dx.doi.org/10.1080/21688370.2016.1187325}, DOI={10.1080/21688370.2016.1187325}, abstractNote={Tight Junctions (TJ) create a paracellular barrier that is compromised when nonsteriodal anti-inflammatory drugs (NSAIDs) injure the gastric epithelium, leading to increased permeability. However, the mechanism of NSAID-induced gastric injury is unclear. Here, we examined the effect of indomethacin on barrier function and TJ in gastric MKN-28 cells. In concentration response studies, 500 µm indomethacin induced a significant decrease in transepithelial resistance (TER; 380 vs. 220 Ω·cm(2) for control and indomethacin-treated cells respectively, p < 0.05), and increased dextran permeability by 0.2 vs 1.2 g/l (p < 0.05). These changes in barrier function were completely ameliorated by the p38 MAPK inhibitor (SB-203580) but not by JNK inhibitor (SP-600125) or MEK/ERK inhibitor (PD-98059). SiRNA knock down of p38 MAPK prevented the loss of barrier function caused by indomethacin in MKN-28 cells. Western analyses of TJ proteins revealed that expression of occludin was reduced by indomethacin, whereas there was no change in other TJ proteins. The loss of occludin expression induced by indomethacin was prevented by inhibition of p38 MAPK but not JNK or ERK and also by siRNA of p38 MAPK. Immunofluorescence revealed disruption of occludin localization at the site of the tight junction in indomethacin-treated cells, and this was attenuated by inhibition of p38 MAPK. NSAID injury to murine gastric mucosa on Ussing chambers revealed that indomethacin caused a significant drop in TER and increased paracellular permeability. Pretreatment with the p38 MAPK inhibitor significantly attenuated the disruption of barrier function, but JNK and MEK/ERK inhibition had no effect. Western blot analysis on gastric mucosa reveled loss of TJ protein occludin by indomethacin, which was prevented by inhibition of p38 MAPK. This data suggests that indomethacin compromises the gastric epithelial barrier via p38 MAPK inducing occludin alterations in the TJs.}, number={3}, journal={Tissue Barriers}, publisher={Informa UK Limited}, author={Thakre-Nighot, Meghali and Blikslager, Anthony T.}, year={2016}, month={May}, pages={e1187325} }
 @article{jin_blikslager_2016, title={Intestinal Ischemia–Reperfusion: Rooting for the SOCS?}, volume={62}, ISSN={0163-2116 1573-2568}, url={http://dx.doi.org/10.1007/s10620-016-4328-6}, DOI={10.1007/s10620-016-4328-6}, abstractNote={Ischemia–reperfusion (IR) injury of the intestine occurs when blood flow is temporarily interrupted, which occurs during interventions such as surgery for an abdominal aortic aneurysm, small bowel transplantation, strangulating hernias, and neonatal necrotizing enterocolitis. It can also occur as a result of collapse of the systemic circulation during conditions such as hemorrhagic shock following trauma, septic shock, or heat stress [1]. At the cellular level, the initial intestinal ischemic injury reduces cellular mitochondrial ATP generation, activates hydrolases, reduces cell membrane selective permeability, and increases calcium influx into ischemic cells. Reperfusion may exacerbate the extent of injury through the activation of an intense systemic inflammatory response [2] such as marked pro-inflammatory cytokine release, production of reactive oxygen species (ROS), increased expression of nitric oxide (NO), Toll-like receptor (TLR)-4 signaling, and activation of inflammatory transcription factors, among other pro-inflammatory mechanisms [3]. IR injury is therefore difficult to manage clinically with consequent high morbidity and mortality [4]. Ischemic preconditioning is an alternative strategy to reduce IR injury among therapeutic interventions aimed at reducing IR injury by inhibiting the activation of inflammatory cells [4]. Ischemic preconditioning consists of a brief episode of ischemia preceding the major ischemic event, an intervention that activates tissue-adaptive mechanisms. Ischemic preconditioning can be induced mechanically or pharmacologically; mechanical preconditioning, in which the target organ is exposed to a brief ischemic episode by mechanically compromising its blood supply prior to prolonged ischemia, has the benefit of reducing IR injury, but it has the principal disadvantage of traumatizing major vessels and stressing the target organ. Alternatively, the identification of the signaling pathways underlying ischemic preconditioning has created the possibility of using pharmacological agents that confer protection against IR injury [5]. Ischemic preconditioning increases the generation of endogenous antioxidants such as glutathione, superoxide dismutase, and hemoxygenase-1 (HO-1). Nuclear transcription factors such as nuclear factor-kappa B (NFjB) and NO are also affected by ischemic preconditioning, reducing the generation of pro-inflammatory cytokines, and preserving blood flow, oxygenation, and mitochondrial function [3, 6]. Clinically, ischemic preconditioning may be applied to patients prior to a planned surgical procedure such as cardiac, hepatic, or pulmonary surgery, in order to reduce the potential adverse effects of IR injury in the postoperative period. In this issue of Digestive Diseases and Sciences, Liu et al. [7] report that ischemic preconditioning-induced suppressor of cytokine signaling-1 (SOCS-1) activation protects the intestine from IR injury via downregulation of the Toll-like receptor 4 (TLR4) pathway (Fig. 1). Among the molecular mechanisms integral to the pathogenesis of IR injury, the authors focused on TLR4 signaling and its downstream signaling intermediate tumor necrosis factor receptor-associated factor 6 (TRAF6), which has been understudied in IR injury. Additionally, the investigators also studied the contribution of receptor interacting protein 1 (RIP1), a key regulator of cellular apoptosis, regulated by tumor necrosis factor (TNF) signaling. SOCS-1 is a key regulator of inflammatory responses, including the TLR4 signaling pathway, thereby putatively inhibiting & Anthony T. Blikslager anthony_blikslager@ncsu.edu}, number={1}, journal={Digestive Diseases and Sciences}, publisher={Springer Nature}, author={Jin, Younggeon and Blikslager, Anthony T.}, year={2016}, month={Nov}, pages={4–6} }
 @article{ziegler_gonzalez_blikslager_2016, title={Large Animal Models: The Key to Translational Discovery in Digestive Disease Research}, volume={2}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2016.09.003}, DOI={10.1016/j.jcmgh.2016.09.003}, abstractNote={Gastrointestinal disease is a prevalent cause of morbidity and mortality and the use of animal models have been instrumental in studying mechanisms of digestive pathophysiology. As investigators attempt to translate the wealth of basic science information developed from rodent, models, large animal models provide a number of translational advantages. The pig, in particular, is arguably one of the most powerful models of human organ systems, including the gastrointestinal tract. The pig has provided important tools and insight into intestinal ischemia/reperfusion injury, intestinal mucosal repair, as well as new insights into esophageal injury and repair. Porcine model development has taken advantage of the size of the animal, allowing increased surgical and endoscopic access. In addition, cellular tools such as the intestinal porcine epithelial cell line and porcine enteroids are providing the methodology to translate basic science findings using in-depth mechanistic analyses. Further opportunities in porcine digestive disease modeling include developing additional transgenic pig strains. Collectively, porcine models hold great promise for the future of clinically relevant digestive disease research.}, number={6}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Ziegler, Amanda and Gonzalez, Liara and Blikslager, Anthony}, year={2016}, month={Nov}, pages={716–724} }
 @article{kruger_gonzalez_von furstenberg_henning_blikslager_garman_2016, title={Mo1253 Ductular and Proliferative Response of Esophageal Submucosal Glands in a Porcine Model of Esophageal Injury and Repair}, volume={150}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(16)32312-5}, DOI={10.1016/S0016-5085(16)32312-5}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Kruger, Leandi and Gonzalez, Liara M. and von Furstenberg, Richard J. and Henning, Susan J. and Blikslager, Anthony and Garman, Katherine S.}, year={2016}, month={Apr}, pages={S679–S680} }
 @article{stewart_freund_magness_lund_blikslager_gonzalez_2016, title={Mo1298 Critical Contribution of Intestinal Stem Cells in the Repair of Ischemia Reperfusion Injury}, volume={150}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(16)32355-1}, DOI={10.1016/S0016-5085(16)32355-1}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Stewart, Amy S. and Freund, John and Magness, Scott and Lund, Pauline K. and Blikslager, Anthony and Gonzalez, Liara M.}, year={2016}, month={Apr}, pages={S691} }
 @article{jin_blikslager_2016, title={Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury}, volume={311}, ISSN={0363-6143 1522-1563}, url={http://dx.doi.org/10.1152/ajpcell.00113.2016}, DOI={10.1152/ajpcell.00113.2016}, abstractNote={Intestinal anoxia/reoxygenation (A/R) injury induces loss of barrier function followed by epithelial repair. Myosin light chain kinase (MLCK) has been shown to alter barrier function via regulation of interepithelial tight junctions, but has not been studied in intestinal A/R injury. We hypothesized that A/R injury would disrupt tight junction barrier function via MLCK activation and myosin light chain (MLC) phosphorylation. Caco-2BBe1 monolayers were subjected to anoxia for 2 h followed by reoxygenation in 21% O 2 , after which barrier function was determined by measuring transepithelial electrical resistance (TER) and FITC-dextran flux. Tight junction proteins and MLCK signaling were assessed by Western blotting, real-time PCR, or immunofluorescence microscopy. The role of MLCK was further investigated with select inhibitors (ML-7 and peptide 18) by using in vitro and ex vivo models. Following A/R injury, there was a significant increase in paracellular permeability compared with control cells, as determined by TER and dextran fluxes ( P < 0.05). The tight junction protein occludin was internalized during A/R injury and relocalized to the region of the tight junction after 4 h of recovery. MLC phosphorylation was significantly increased by A/R injury ( P < 0.05), and treatment with the MLCK inhibitor peptide 18 attenuated the increased epithelial monolayer permeability and occludin endocytosis caused by A/R injury. Application of MLCK inhibitors to ischemia-injured porcine ileal mucosa induced significant increases in TER and reduced mucosal-to-serosal fluxes of 3 H-labeled mannitol. These data suggest that MLCK-induced occludin endocytosis mediates intestinal epithelial barrier dysfunction during A/R injury. Our results also indicate that MLCK-dependent occludin regulation may be a target for the therapeutic treatment of ischemia/reperfusion injury.}, number={6}, journal={American Journal of Physiology-Cell Physiology}, publisher={American Physiological Society}, author={Jin, Younggeon and Blikslager, Anthony T.}, year={2016}, month={Dec}, pages={C996–C1004} }
 @article{meliopoulos_marvin_freiden_moser_nighot_ali_blikslager_reddivari_heath_koci_et al._2016, title={Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea
                    In Vivo}, volume={7}, ISSN={2150-7511}, url={http://dx.doi.org/10.1128/mBio.01494-16}, DOI={10.1128/mBio.01494-16}, abstractNote={ABSTRACT The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction. IMPORTANCE Acute gastroenteritis, with its sequela diarrhea, is one of the most important causes of childhood morbidity and mortality worldwide. A variety of infectious agents cause gastroenteritis, and in many cases, an enterotoxin produced by the agent is involved in disease manifestations. Although we commonly think of bacteria as a source of toxins, at least one enteric virus, rotavirus, produces a protein with enterotoxigenic activity during viral replication. In these studies, we demonstrate that oral administration of the turkey astrovirus 2 (TAstV-2) structural (capsid) protein induces acute diarrhea, increases barrier permeability, and causes relocalization of NHE3 in the small intestine, suggesting that rotavirus may not be alone in possessing enterotoxigenic activity.}, number={6}, journal={mBio}, publisher={American Society for Microbiology}, author={Meliopoulos, Victoria A. and Marvin, Shauna A. and Freiden, Pamela and Moser, Lindsey A. and Nighot, Prashant and Ali, Rizwana and Blikslager, Anthony and Reddivari, Muralidhar and Heath, Richard J. and Koci, Matthew D. and et al.}, year={2016}, month={Nov} }
 @inproceedings{chapman_jenkins_bryant_2016, title={Parametric study of a fluidic artificial muscle actuated electrohydraulic system}, DOI={10.1115/smasis2016-9044}, abstractNote={Fluidic artificial muscles have the potential for a wide range of uses; from injury rehabilitation to high-powered hydraulic systems. Their modeling to date has largely been quasi-static and relied on the operator to adjust pressure so as to control force output and utilization while little work has been done to analyze the kinematics of the driving-systems involved in their operation. This paper utilizes an established electro-hydraulic model to perform a study of the components of a fluidic artificial muscle actuated climbing robot. Its purpose is to determine the effect of the robotic subsystems on function and efficiency for a small-scale system in order to extrapolate more general design and analysis schemes for future use. Its results indicate that important aspects to consider in design of the hydraulic system are system payload, operating pressure, pump selection, and FAM construction.}, booktitle={Proceedings of the asme conference on smart materials adaptive}, author={Chapman, E. and Jenkins, T. and Bryant, M.}, year={2016} }
 @article{blikslager_2016, title={The paradox of diarrhoeal disease and small colon obstruction}, volume={28}, ISSN={["2042-3292"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84949257020&partnerID=MN8TOARS}, DOI={10.1111/eve.12504}, abstractNote={Summary

The interesting finding of stenosis in a case series of 3 foals that initially presented with diarrhoeal disease is suggestive of an inflammatory and fibrotic event that is more frequently reported in people with inflammatory bowel disease. In man, stenosis is believed to occur because of inflammation and excessive production of scar tissue in the absence of a normal reparative response. However, this is typically a chronic process, whereas in the foals, stenosis occurred within weeks to months. Other diseases of horses, particularly right dorsal colitis and small colon impaction preceded by diarrhoeal disease, have some similarities to the focal disease described for foals. Collectively, equine studies are increasingly pointing toward complex interactions in the intestinal tract between the mucosa, the microbiome, management factors such as diet, and reparative responses to inflammatory insult.}, number={8}, journal={EQUINE VETERINARY EDUCATION}, author={Blikslager, A. T.}, year={2016}, month={Aug}, pages={424–425} }
 @article{gonzalez_moeser_blikslager_2015, title={Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research}, volume={308}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00112.2013}, DOI={10.1152/ajpgi.00112.2013}, abstractNote={Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Gonzalez, Liara M. and Moeser, Adam J. and Blikslager, Anthony T.}, year={2015}, month={Jan}, pages={G63–G75} }
 @article{gonzalez_kinnin_blikslager_2015, title={Characterization of discrete equine intestinal epithelial cell lineages}, volume={76}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.76.4.358}, DOI={10.2460/ajvr.76.4.358}, abstractNote={Abstract OBJECTIVE To characterize epithelial cells of the small intestine and colon in horses without clinical gastrointestinal abnormalities with an emphasis on the stem cell niche constituents. SAMPLE Mucosal biopsy specimens from small and large intestines obtained from 12 horses euthanized for reasons unrelated to gastrointestinal disease or systemic disease. PROCEDURES Intestinal biopsy specimens were collected by sharp dissection immediately following euthanasia. Specimens were prepared for immunohistochemical, immunofluorescence, and transmission electron microscopic imaging to detect and characterize each epithelial cell type. Antibodies against protein biomarkers for cellular identification were selected on the basis of expression in other mammalian species. RESULTS Intestinal epithelial cell types were identified by means of immunostaining and morphological characterization with transmission electron microscopy. Some differences in biomarker expression and antibody cross-reactivity were identified in equine tissue, compared with other species. However, each known type of mucosal epithelial cell was identified in equine tissue. CONCLUSIONS AND CLINICAL RELEVANCE The methodology used can enhance detection of stem cells and progenitor cells as well as postmitotic cell lineages in equine intestinal tissues. Results may have relevance to regenerative potential of intestinal mucosa and survival in horses with colic.}, number={4}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gonzalez, Liara M. and Kinnin, Leslie A. and Blikslager, Anthony T.}, year={2015}, month={Apr}, pages={358–366} }
 @article{jin_blikslager_2015, title={ClC-2 regulation of intestinal barrier function: Translation of basic science to therapeutic target}, volume={3}, ISSN={2168-8370}, url={http://dx.doi.org/10.1080/21688370.2015.1105906}, DOI={10.1080/21688370.2015.1105906}, abstractNote={The ClC-2 chloride channel is a member of the voltage-gated chloride channel family. ClC-2 is involved in various physiological processes, including fluid transport and secretion, regulation of cell volume and pH, maintaining the membrane potential of the cell, cell-to-cell communication, and tissue homeostasis. Recently, our laboratory has accumulated evidence indicating a critical role of ClC-2 in the regulation of intestinal barrier function by altering inter-epithelial tight junction composition. This review will detail the role of ClC-2 in intestinal barrier function during intestinal disorders, including experimental ischemia/reperfusion injury and dextran sodium sulfate (DSS)-induced inflammatory bowel disease. Details of pharmacological manipulation of ClC-2 via prostone agonists will also be provided in an effort to show the potential therapeutic relevance of ClC-2 regulation, particularly during intestinal barrier disruption.}, number={4}, journal={Tissue Barriers}, publisher={Informa UK Limited}, author={Jin, Younggeon and Blikslager, Anthony T}, year={2015}, month={Oct}, pages={e1105906} }
 @article{lefebvre_hudson_elce_blikslager_divers_handel_tremaine_pirie_2015, title={Clinical features and management of equine post operative ileus (POI): Survey of Diplomates of the American Colleges of Veterinary Internal Medicine (ACVIM), Veterinary Surgeons (ACVS) and Veterinary Emergency and Critical Care (ACVECC)}, volume={48}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12520}, DOI={10.1111/evj.12520}, abstractNote={A recent survey of European Colleges (European College of Equine Internal Medicine [ECEIM] and European College of Veterinary Surgeons [ECVS]) revealed the different strategies implemented by, and some of the challenges facing, European clinicians presented with cases of post operative ileus (POI). It was concluded that further comparative analysis of opinions, canvassed from additional colleges of equine veterinary specialism worldwide, would provide valuable additional insight into current POI knowledge on a more global scale.To report and compare the current strategies favoured by American veterinary specialists when managing POI in horses that underwent emergency colic surgery.Cross-sectional survey.Electronic invitations were sent to 814 Large Animal specialists, including 3 colleges: the American College of Veterinary Internal Medicine (ACVIM), American College of Veterinary Surgeons (ACVS) and the American College of Veterinary Emergency and Critical Care (ACVECC).The response rate was 14% (115/814). The majority of respondents (68%) reported an estimated prevalence range of POI of 0-20%. The presence of reflux on nasogastric intubation was the main criterion used to define POI. A lesion involving the small intestine was considered the main risk factor for POI. Anti-inflammatory drugs, intravenous (i.v.) fluids and antimicrobial drugs were the primary strategies used when managing POI. Flunixin meglumine and i.v. lidocaine were the drugs most commonly used in the treatment of horses with POI. Supplementary management strategies targeted mainly the prevention of post operative adhesions, infection and inflammation.There is a lack of consensus on the clinical definition of POI. Prospective and objective clinical assessment of the effectiveness of the different strategies contained within this and the European survey is necessary in order to identify a standardised approach to the management of equine POI.}, number={6}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Lefebvre, D. and Hudson, N. P. H. and Elce, Y. A. and Blikslager, A. and Divers, T. J. and Handel, I. G. and Tremaine, W. H. and Pirie, R. S.}, year={2015}, month={Dec}, pages={714–719} }
 @article{blikslager_2015, title={Gastric impaction and large colon volvulus: Can one lead to the other?}, volume={27}, ISSN={["2042-3292"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84938313234&partnerID=MN8TOARS}, DOI={10.1111/eve.12417}, abstractNote={Summary The possibility of stomach impaction resulting in large colon volvulus is raised by authors reporting the findings of both lesions in 7 horses. Although this combination of lesions has not been reported before, it is interesting to consider the effect of a gastric impaction compressing the colon as the stomach increases in size with firm ingesta. Anatomically, the stomach is dorsal to the colon, and might therefore compress the colon. As to how this might result in volvulus, it is interesting to speculate on the possible roles of gas accumulation or other changes in the intracolonic environment, such as composition in microbiota. The report of 7 horses also highlights the need to thoroughly explore any horse taken to surgery because of intractable colic in case there is more than one lesion.}, number={9}, journal={EQUINE VETERINARY EDUCATION}, author={Blikslager, A. T.}, year={2015}, month={Sep}, pages={460–461} }
 @article{nighot_nighot_ma_malinowska_shull_cuppoletti_blikslager_2015, title={Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion}, volume={10}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0138174}, DOI={10.1371/journal.pone.0138174}, abstractNote={The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84–95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.}, number={9}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Nighot, Meghali P. and Nighot, Prashant K. and Ma, Thomas Y. and Malinowska, Danuta H. and Shull, Gary E. and Cuppoletti, John and Blikslager, Anthony T.}, editor={Guerrero-Hernandez, AgustínEditor}, year={2015}, month={Sep}, pages={e0138174} }
 @article{jin_pridgen_blikslager_2015, title={Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis}, volume={21}, ISSN={1078-0998}, url={http://dx.doi.org/10.1097/MIB.0000000000000550}, DOI={10.1097/mib.0000000000000550}, abstractNote={We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2 mice.We administered lubiprostone to wild-type or ClC-2 mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid-induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry.Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid-induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2 mice, the protective effect against DSS colitis was limited.This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.}, number={12}, journal={Inflammatory Bowel Diseases}, publisher={Oxford University Press (OUP)}, author={Jin, Younggeon and Pridgen, Tiffany A. and Blikslager, Anthony T.}, year={2015}, month={Dec}, pages={2747–2757} }
 @article{gonzalez_moeser_blikslager_2015, title={Porcine models of digestive disease: the future of large animal translational research}, volume={166}, ISSN={1931-5244}, url={http://dx.doi.org/10.1016/j.trsl.2015.01.004}, DOI={10.1016/j.trsl.2015.01.004}, abstractNote={There is increasing interest in nonrodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia-reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine and mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine.}, number={1}, journal={Translational Research}, publisher={Elsevier BV}, author={Gonzalez, Liara M. and Moeser, Adam J. and Blikslager, Anthony T.}, year={2015}, month={Jul}, pages={12–27} }
 @inbook{marshall_blikslager_2015, place={St. Louis, MO}, edition={5th edition}, title={Surgical disorders of the large intestine}, booktitle={Large Animal Internal Medicine}, publisher={Elsevier}, author={Marshall, J.M. and Blikslager, A.T.}, editor={Smith, B.P.Editor}, year={2015}, pages={715–718} }
 @inbook{blikslager_marshall_2015, place={St. Louis, MO}, edition={5th edition}, title={Surgical disorders of the small intestine}, booktitle={Large Animal Internal Medicine}, publisher={Elsevier}, author={Blikslager, A.T. and Marshall, J.M.}, editor={Smith, B.P.Editor}, year={2015}, pages={703–707} }
 @article{petschow_blikslager_weaver_campbell_polo_shaw_burnett_klein_rhoads_2014, title={Bovine immunoglobulin protein isolates for the nutritional management of enteropathy}, volume={20}, ISSN={1007-9327}, url={http://dx.doi.org/10.3748/wjg.v20.i33.11713}, DOI={10.3748/wjg.v20.i33.11713}, abstractNote={The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.}, number={33}, journal={World Journal of Gastroenterology}, publisher={Baishideng Publishing Group Inc.}, author={Petschow, B.W. and Blikslager, A.T. and Weaver, E.M. and Campbell, J.M. and Polo, J. and Shaw, A.L. and Burnett, B.P. and Klein, G.L. and Rhoads, J.M.}, year={2014}, pages={11713} }
 @article{gonzalez_magness_lund_blikslager_2014, title={Mo1960 Intestinal Epithelial Cells Expressing Biomarkers of Crypt Base Columnar or Reserve Stem Cells Show Differential Resistance to Ischemia-Reperfusion Injury}, volume={146}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(14)62550-6}, DOI={10.1016/S0016-5085(14)62550-6}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Gonzalez, Liara M. and Magness, Scott T. and Lund, Pauline K. and Blikslager, Anthony}, year={2014}, month={May}, pages={S-702} }
 @article{gonzalez_fogle_baker_hughes_law_motsinger-reif_blikslager_2014, title={Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013}, volume={47}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12273}, DOI={10.1111/evj.12273}, abstractNote={There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus.To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus.Retrospective cohort study.Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson and Smith and Chino Valley Equine Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitium-to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital).Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be associated significantly with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified measurement of haemorrhage area strengthened the association of haemorrhage with nonsurvival in cases of large colon volvulus.Histomorphometric measurements of interstitium-to-crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons' prognostic capabilities in horses with large colon volvulus.}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Gonzalez, L. M. and Fogle, C. A. and Baker, W. T. and Hughes, F. E. and Law, J. M. and Motsinger-Reif, A. A. and Blikslager, A. T.}, year={2014}, month={May}, pages={279–284} }
 @article{holland_fogle_blikslager_curling_barlow_schirmer_davis_2014, title={Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses}, volume={38}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12177}, DOI={10.1111/jvp.12177}, abstractNote={The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE 2 and TXB 2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher C max , shorter T max , and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE 2 was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC 50 of approximately 27 ng/mL and an IC 80 of 108 ng/ mL for COX2 inhibition. Inhibition of TXB 2 production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Holland, B. and Fogle, C. and Blikslager, A. T. and Curling, A. and Barlow, B. M. and Schirmer, J. and Davis, J. L.}, year={2014}, month={Nov}, pages={249–256} }
 @article{nighot_nighot_ma_blikslager_2014, title={Su1947 Genetic Absence of Chloride Channel CLC-2 Results in Disruption of Organization and Function of Murine Gastric Glands}, volume={146}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(14)61827-8}, DOI={10.1016/S0016-5085(14)61827-8}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Meghali P. and Nighot, Prashant K. and Ma, Thomas Y. and Blikslager, Anthony}, year={2014}, month={May}, pages={S-505-S-506} }
 @article{hill_lascelles_m. law_blikslager_2014, title={The Effect of Tramadol and Indomethacin Coadministration on Gastric Barrier Function in Dogs}, volume={28}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12345}, DOI={10.1111/jvim.12345}, abstractNote={Background Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti‐inflammatory drugs ( NSAID s). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown. Hypothesis/Objectives That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid‐injured, indomethacin‐treated, and tramadol‐treated mucosa. Animals Gastric mucosa of 10 humanely euthanized shelter dogs. Methods Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified. Results Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E 2 (acid‐injured PGE 2 : 509.3 ± 158.3 pg/mL, indomethacin + acid injury PGE 2 : 182.9 ± 93.8 pg/mL, P < .001) and thromboxane B 2 (acid‐injured TXB 2 : 233.2 ± 90.7 pg/mL, indomethacin + acid injury TXB 2 : 37.9 ± 16.8 pg/mL, P < .001), whereas tramadol had no significant effect ( PGE 2 P = .713, TXB 2 P = .194). Neither drug had an effect on cyclooxygenase expression ( COX ‐1 P = .743, COX ‐2 P = .705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration. Conclusions and Clinical Importance There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Hill, T.L. and Lascelles, B.D.X. and M. Law, J. and Blikslager, A.T.}, year={2014}, month={Mar}, pages={793–798} }
 @article{cook_blikslager_2014, title={The use of nonsteroidal anti-inflammatory drugs in critically ill horses}, volume={25}, ISSN={1479-3261}, url={http://dx.doi.org/10.1111/vec.12271}, DOI={10.1111/vec.12271}, abstractNote={Abstract Objective To review the physiology of the cyclooxygenase (COX) enzymes with reference to the beneficial effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) related to their analgesic and antiendotoxic properties as well as the mechanisms responsible for adverse gastrointestinal, renal, and coagulation effects. Data Sources Human and veterinary peer reviewed literature Veterinary Data Synthesis NSAIDs are frequently administered to critically ill horses for their analgesic and anti‐inflammatory effects. However, NSAIDs have significant side effects principally on the gastrointestinal mucosa and kidneys. These side effects may be exacerbated in critically ill horses if they have gastrointestinal damage or are volume depleted Conclusions This review provides important information for equine veterinarians and criticalists on the advantages and disadvantages of using traditional NSAIDs and newer equine COX‐2 selective NSAIDs for the management of different conditions in critically ill horses.}, number={1}, journal={Journal of Veterinary Emergency and Critical Care}, publisher={Wiley}, author={Cook, Vanessa L. and Blikslager, Anthony T.}, year={2014}, month={Dec}, pages={76–88} }
 @article{jin_pridgen_blikslager_2014, title={Tu2028 Lubiprostone reduces murine colitis principally in a ClC-2-dependent manner.}, volume={146}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(14)63275-3}, DOI={10.1016/S0016-5085(14)63275-3}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Jin, Younggeon and Pridgen, Tiffany and Blikslager, Anthony}, year={2014}, month={May}, pages={S-901} }
 @article{jacobi_moeser_blikslager_rhoads_corl_harrell_odle_2013, title={Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets}, volume={19}, ISSN={1007-9327}, url={http://dx.doi.org/10.3748/wjg.v19.i31.5094}, DOI={10.3748/wjg.v19.i31.5094}, abstractNote={To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses.Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P < 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol.Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.}, number={31}, journal={World Journal of Gastroenterology}, publisher={Baishideng Publishing Group Inc.}, author={Jacobi, S.K. and Moeser, A.J. and Blikslager, A.T. and Rhoads, J.M. and Corl, B.A. and Harrell, R.J. and Odle, J.}, year={2013}, month={Aug}, pages={5094–5102} }
 @article{gonzalez_williamson_piedrahita_blikslager_magness_2013, title={Cell Lineage Identification and Stem Cell Culture in a Porcine Model for the Study of Intestinal Epithelial Regeneration}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0066465}, DOI={10.1371/journal.pone.0066465}, abstractNote={Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC) driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM) and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA), Minichromosome Maintenance Complex 2 (MCM2), Bromodeoxyuridine (BrdU) and phosphorylated Histone H3 (pH3) distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/‘reserve’ stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2); enteroendocrine cells by Chromogranin A (CGA), Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII) and sucrase isomaltase (SIM). Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease.}, number={6}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Gonzalez, Liara M. and Williamson, Ian and Piedrahita, Jorge A. and Blikslager, Anthony T. and Magness, Scott T.}, editor={Singh, Shree RamEditor}, year={2013}, month={Jun}, pages={e66465} }
 @article{nighot_young_nighot_rawat_sung_maharshak_plevy_ma_blikslager_2013, title={Chloride Channel ClC-2 is a Key Factor in the Development of DSS-induced Murine Colitis}, volume={19}, ISSN={1078-0998}, url={http://dx.doi.org/10.1097/MIB.0b013e3182a82ae9}, DOI={10.1097/mib.0b013e3182a82ae9}, abstractNote={Previously, it was shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury. The role of ClC-2 was investigated in TJ barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2 knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was measured electrophysiologically and by transepithelial mannitol fluxes. Selected TJ and associated proteins were Western blotted, cytokines were measured using quantitative PCR, and human colonic biopsies were examined with immunohistochemistry. ClC-2−/− mice had a higher disease activity index, higher histological scores, and increased paracellular permeability compared with wild-type mice when treated with DSS. DSS-treated ClC-2−/− mice had increased claudin-2 expression, greater loss of occludin in the membrane, increased association of occludin with caveolin-1, and significantly increased tumor necrosis factor-α and interleukin-1β messenger RNA. ClC-2 knockdown in human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance in the event of epithelial injury. The restoration of colonic barrier function after DSS colitis was delayed in ClC-2−/− mice. In human colonic biopsies, the protein and messenger RNA expression of ClC-2 was found to be reduced in patients with ulcerative colitis. ClC-2 plays a critical role in experimental colitis in that its absence increases disease activity, reduces barrier function and recovery, and perturbs TJs. Furthermore, ClC-2 expression is markedly reduced in the colon of human patients with ulcerative colitis.}, number={13}, journal={Inflammatory Bowel Diseases}, publisher={Oxford University Press (OUP)}, author={Nighot, Prashant and Young, Karen and Nighot, Meghali and Rawat, Manmeet and Sung, Eui J. and Maharshak, Nitsan and Plevy, Scott E. and Ma, Thomas and Blikslager, Anthony}, year={2013}, month={Dec}, pages={2867–2877} }
 @article{labens_lascelles_charlton_ferrero_van wettere_xia_blikslager_2013, title={Ex vivo effect of gold nanoparticles on porcine synovial membrane}, volume={1}, ISSN={2168-8370}, url={http://dx.doi.org/10.4161/tisb.24314}, DOI={10.4161/tisb.24314}, abstractNote={Gold nanoparticles (AuNPs) have great potential as carriers for local drug delivery and as a primary therapeutic for treatment of inflammation. Here we report on the AuNP-synovium interaction in an ex vivo model of intra-articular application for treatment of joint inflammation. Sheets of porcine femoropatellar synovium were obtained post mortem and each side of the tissue samples was maintained in a separate fluid environment. Permeability to AuNPs of different sizes (5−52 nm) and biomarker levels of inflammation were determined to characterize the ex vivo particle interaction with the synovium. Lipopolysaccharide or recombinant human interleukin-1β were added to fluid environments to assess the ex vivo effect of pro-inflammatory factors on permeability and biomarker levels. The synovium showed size selective permeability with only 5 nm AuNPs effectively permeating the entire tissues’ width. This process was further governed by particle stability in the fluid environment. AuNPs reduced matrix metalloproteinase and lactate dehydrogenase activity and hyaluronic acid concentrations but had no effect on prostaglandin E2 levels. Exposure to pro-inflammatory factors did not significantly affect AuNP permeation or biomarker levels in this model. Results with ex vivo tissue modeling of porcine synovium support an anti-inflammatory effect of AuNPs warranting further investigation.}, number={2}, journal={Tissue Barriers}, publisher={Informa UK Limited}, author={Labens, Raphael and Lascelles, B. Duncan X. and Charlton, Anna N. and Ferrero, Nicole R. and Van Wettere, Arnaud J. and Xia, Xin-Riu and Blikslager, Anthony T.}, year={2013}, month={Apr}, pages={e24314} }
 @article{blikslager_2013, title={Feeding intravenously saves the patient but starves the gut: consequences for the intestinal barrier}, volume={591}, ISSN={0022-3751}, url={http://dx.doi.org/10.1113/jphysiol.2013.260703}, DOI={10.1113/jphysiol.2013.260703}, abstractNote={During the late 1960s, the medical breakthrough of providing a patient's complete daily nutritional requirement via intravenous catheter was successfully developed (Dudrick, 2009). When coupled with a growing understanding of the role of optimal nutrition in the recovery of patients unable to consume food, total parenteral nutrition (TPN) has saved numerous lives. However, as with any advanced medical therapy, TPN comes with a number of important complications, many of which are life-threatening. One specific consequence of TPN is gut mucosal atrophy, in which the intestinal mucosa is reduced in thickness because of the importance of luminal nutrients on mucosal growth. Furthermore, there is an associated breakdown in intestinal barrier function, which is critical because the mucosal barrier is the most important line of defence against microorganisms within the intestinal lumen. Bacterial translocation can in turn trigger sepsis, an important cause of mortality in gravely ill patients. However, the mechanisms of intestinal barrier breakdown in patients on TPN are poorly understood.

The intestinal mucosal barrier is composed of a single layer of columnar epithelial cells attached side-by-side by a series of interepithelial junctions, including the apical-most tight junctions. Over the last 10–15 years, tight junctions have been the subject of intensive study because although they are ‘tight’ they are also the weakest link in the barrier. Tight junctions are composed of interdigitating extracytoplasmic loops of junctional proteins, including occludin, claudins and junction adhesion molecules. Loss of barrier function at the level of the tight junctions is thought to be a pivotal event in the pathophysiology of a number of important disease syndromes, including infectious diarrhoeal disease, ischaemia/reperfusion injury and inflammatory bowel disease (Hering et al. 2012). However, the mechanisms whereby intestinal barrier function is pathologically altered in intestinal disease are not well defined.

In this issue of The Journal of Physiology, Feng & Teitelbaum (2013) have built on their previous findings of barrier disruption in experimental animals on TPN by showing that a complex interplay of tumour necrosis factor (TNFα) and its two receptors (TNFR1 and TNFR2) is responsible for the breakdown of intestinal epithelial tight junctions. Experiments using mutant mice in which TNFR1, TNFR2, or both receptors were knocked out revealed that the absence of either TNF receptor partially prevented the effects of TPN on tight junctions. Additionally, genetic deletion of both TNF receptors prevented any notable effect of TPN on intestinal barrier function. This is interesting not only to researchers studying the mechanisms of TPN-induced barrier disruption, but also to others who have focused on mechanisms whereby cytokines such as TNFα disrupt epithelial barrier function. The TPN model is particularly interesting because it involves selective loss of tight junction integrity independent of inflammatory cell infiltration. In this way, TPN models may allow more precise studies assessing the effect of select factors on tight junction integrity in vivo which are complicated in many models by inflammation.

From cell studies, it is well known that cytokines, including TFNα, interferon-γ and interleukin-1-β, can disrupt epithelial barrier function. For example, initial studies assessing the role of cytokines in cell culture models revealed that TNFα dose-dependently reduced epithelial barrier function associated with morphological disruption of tight junctions using electron microscopy (Schmitz et al. 1999). With advancing technology, studies of specific tight junction proteins have shown that TNFα induces endocytosis of occludin as a consequence of activation of the cytoskeletal-associated enzyme myosin light chain kinase (MLCK). Interestingly, Feng et al. noted increased phosphorylation of myosin light chain by MLCK in their TPN mouse model. MLCK has a physiological role in ‘opening’ tight junctions in response to sodium-coupled glucose intestinal epithelial transport, but has more recently been closely linked to pathological states involving disruption of tight junctions. TNFα has also been shown to have alternate mechanisms of barrier disruption. For example, recent studies have shown that TNFα disrupts the highly controlled process of cell shedding of the most superficial surface epithelium resulting in excessive cell loss that can be seen in patients with inflammatory bowel disease (Watson et al. 2012). Such cell loss is also associated with perturbation of tight junctions, allowing cell detachment. Which of the actions of TNFα is critical to loss of barrier function in TPN-treated mice is not entirely clear, although the tight junctions and MLCK are certainly involved.

As far as the translational relevance of TNFα in disruption of the gut barrier is concerned, Feng & Teitelbaum (2013) have additionally shown that the TNFα inhibitor etanercept prevents loss of barrier function in TPN-infused mice. Etanercept is a TNFR fusion protein that was originally studied for the treatment of shock (Fisher et al. 1996) and has been marketed for the treatment of select autoimmune diseases. Considering the fact that placement of a patient on TPN is elective, there may be the opportunity to intervene prior to onset of intestinal barrier disruption.}, number={15}, journal={The Journal of Physiology}, publisher={Wiley}, author={Blikslager, Anthony T.}, year={2013}, month={Jul}, pages={3673–3673} }
 @book{hill_lascelles_blikslager_2013, title={Gastroduodenal Ulceration}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84926197069&partnerID=MN8TOARS}, DOI={10.1002/9781118997505.ch36}, journal={Small Animal Soft Tissue Surgery}, publisher={John Wiley & Sons, Ltd}, author={Hill, Tracy L. and Lascelles, B. Duncan X. and Blikslager, Anthony}, year={2013}, pages={329–340} }
 @article{gonzalez_blikslager_piedrahita_magness_2013, title={Su1099 A Translational Porcine Model of Intestinal Stem Cells}, volume={144}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(13)61466-3}, DOI={10.1016/S0016-5085(13)61466-3}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Gonzalez, Liara and Blikslager, Anthony and Piedrahita, Jorge A. and Magness, Scott T.}, year={2013}, month={May}, pages={S-398} }
 @article{nighot_nighot_young_edwards_blikslager_moeser_2013, title={Tu1641 Effects of Lubiprostone in a Porcine Model of Stress-Induced Intestinal Barrier Injury}, volume={144}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(13)63010-3}, DOI={10.1016/S0016-5085(13)63010-3}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Meghali P. and Nighot, Prashant K. and Young, Karen and Edwards, Laura and Blikslager, Anthony and Moeser, Adam J.}, year={2013}, month={May}, pages={S-812-S-813} }
 @article{labens_redding_desai_orde_mansmann_blikslager_2013, title={Validation of a photogrammetric technique for computing equine hoof volume}, volume={197}, ISSN={["1532-2971"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84884983213&partnerID=MN8TOARS}, DOI={10.1016/j.tvjl.2013.04.005}, abstractNote={Assessment of equine foot conformation is often based on linear and angular measurements performed on lateral digital photographs. However, quantification of external foot conformation requires more comprehensive assessments to capture the shape of the entire foot. Volumetric measurements of the hoof capsule represent a summary measure quantifying foot shape. The aim of this study was to develop a method for computation of virtual foot models from digital foot images allowing precise and accurate volumetric measurements. This photogrammetric technique was then assessed for the characterization of foot volume changes associated with foot trimming. Using the technique, three different photographers imaged feet from 18 cadavers at different time points and one analyst processed their images to generate virtual computer models. Volumetric measurements were obtained from these models to determine their precision in the context of 'Photographer', 'Time' and the effect of 'Trimming'. Computed tomographic (CT) imaging was used to assess the accuracy of the photogrammetric method. Pre-trim photogrammetric measurements showed excellent precision and accuracy and the results did not depend on the person acquiring the images. The accuracy of post-trim photogrammetric measurements deteriorated in comparison with the average differences measured by CT imaging (19 cm(3)). Precise volumetric measurements were obtained using the photogrammetric method, but average differences in foot volume after trimming as measured by CT imaging are likely too small to be detected with confidence.}, number={3}, journal={VETERINARY JOURNAL}, author={Labens, R. and Redding, W. R. and Desai, K. K. and Orde, K. Vom and Mansmann, R. A. and Blikslager, A. T.}, year={2013}, month={Sep}, pages={625–630} }
 @article{nighot_young_blikslager_2012, title={211 Chloride Channel CLC-2 Mediated Tight Junction Barrier Function Modulates DSS-Induced Murine Colitis}, volume={142}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(12)60200-5}, DOI={10.1016/S0016-5085(12)60200-5}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Young, Karen and Blikslager, Anthony}, year={2012}, month={May}, pages={S-52} }
 @article{meyerhoff_nighot_ali_blikslager_koci_2012, title={Characterization of turkey inducible nitric oxide synthase and identification of its expression in the intestinal epithelium following astrovirus infection}, volume={35}, ISSN={0147-9571}, url={http://dx.doi.org/10.1016/j.cimid.2011.10.002}, DOI={10.1016/j.cimid.2011.10.002}, abstractNote={The inducible nitric oxide synthase (iNOS) enzyme has long been recognized as a key mediator of innate immune responses to infectious diseases across the phyla. Its role in killing or inactivating bacterial, parasitic, and viral pathogens has been documented in numerous host systems. iNOS, and its innate immune mediator NO has also been described to have negative consequence on host tissues as well; therefore understanding the pathogenesis of any infectious agent which induces iNOS expression requires a better understanding of the role iNOS and NO play in that disease. Previous studies in our laboratory and others have demonstrated evidence for increased levels of iNOS and activity of its innate immune mediator NO in the intestine of turkeys infected with astrovirus. To begin to characterize the role iNOS plays in the innate immune response to astrovirus infection, we identified, characterized, developed tkiNOS specific reagents, and demonstrated that the intestinal epithelial cells induce expression of iNOS following astrovirus infection. These data are the first to our knowledge to describe the tkiNOS gene, and demonstrate that astrovirus infection induces intestinal epithelial cells to express iNOS, suggesting these cells play a key role in the antiviral response to enteric infections.}, number={1}, journal={Comparative Immunology, Microbiology and Infectious Diseases}, publisher={Elsevier BV}, author={Meyerhoff, R. Ryan and Nighot, Prashant K. and Ali, Rizwana A. and Blikslager, Anthony T. and Koci, Matthew D.}, year={2012}, month={Jan}, pages={63–69} }
 @article{nighot_blikslager_2012, title={Chloride channel ClC-2 modulates tight junction barrier function via intracellular trafficking of occludin}, volume={302}, ISSN={0363-6143 1522-1563}, url={http://dx.doi.org/10.1152/ajpcell.00072.2011}, DOI={10.1152/ajpcell.00072.2011}, abstractNote={Previously, we have demonstrated that the chloride channel ClC-2 modulates intestinal mucosal barrier function. In the present study, we investigated the role of ClC-2 in epithelial barrier development and maintenance in Caco-2 cells. During early monolayer formation, silencing of ClC-2 with small interfering (si)RNA led to a significant delay in the development of transepithelial resistance (TER) and disruption of occludin localization. Proteomic analysis employing liquid chromatography-mass spectrometry /mass spectrometry revealed association of ClC-2 with key proteins involved in intracellular trafficking, including caveolin-1 and Rab5. In ClC-2 siRNA-treated cells, occludin colocalization with caveolin-1 was diffuse and in the subapical region. Subapically distributed occludin in ClC-2 siRNA-treated cells showed marked colocalization with Rab5. To study the link between ClC-2 and trafficking of occludin in confluent epithelial monolayers, a Caco-2 cell clone expressing ClC-2 short hairpin (sh)RNA was established. Disruption of caveolae with methyl-β-cyclodextrin (MβCD) caused a marked drop in TER and profound redistribution of caveolin-1-occludin coimmunofluorescence in ClC-2 shRNA cells. In ClC-2 shRNA cells, focal aggregations of Rab5-occludin coimmunofluorescence were present within the cytoplasm. Wortmannin caused an acute fall in TER in ClC-2 shRNA cells and subapical, diffuse redistribution of Rab5-occludin coimmunofluorescence in ClC-2 shRNA cells. An endocytosis and recycling assay for occludin revealed higher basal rate of endocytosis of occludin in ClC-2 shRNA cells. Wortmannin significantly reduced the rate of recycling of occludin in ClC-2 shRNA cells. These data clearly indicate that ClC-2 plays an important role in the modulation of tight junctions by influencing caveolar trafficking of the tight junction protein occludin.}, number={1}, journal={American Journal of Physiology-Cell Physiology}, publisher={American Physiological Society}, author={Nighot, Prashant K. and Blikslager, Anthony T.}, year={2012}, month={Jan}, pages={C178–C187} }
 @book{marshall_blikslager_2012, title={Colic: Diagnosis, Surgical Decision, and Preoperative Management}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882594941&partnerID=MN8TOARS}, DOI={10.1016/B978-1-4377-0867-7.00033-8}, journal={Equine Surgery}, author={Marshall, J.F. and Blikslager, A.T.}, year={2012}, pages={402–407} }
 @article{cuppoletti_blikslager_chakrabarti_nighot_malinowska_2012, title={Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors}, volume={12}, ISSN={1471-2210}, url={http://dx.doi.org/10.1186/1471-2210-12-3}, DOI={10.1186/1471-2210-12-3}, abstractNote={Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Comparison with effects of lubiprostone, known to promote repair of barrier function was carried out. In ischemia-damaged pig jejunum, using measurements of transepithelial resistance, 3H-mannitol fluxes, short-circuit current (Cl− secretion) and occludin localization, active linaclotide failed to effectively promote repair of the epithelial barrier or recovery of short-circuit current, whereas lubiprostone promoted barrier repair and increased short-circuit current. In control pig jejunum, 1 μM linaclotide and 1 μM lubiprostone both caused similar increases in short-circuit current (Cl− secretion). In T84 cells, using measurements of transepithelial resistance, fluxes of fluorescent macromolecules, occludin and mitochondrial membrane potential, active linaclotide was virtually ineffective against damage caused by interferon-γ and tumor necrosis factor-α, while lubiprostone protected or promoted repair of epithelial barrier and cell function. Barrier protection/repair by lubiprostone was inhibited by methadone, a ClC-2 inhibitor. Linaclotide, but not lubiprostone increased [cGMP]i as expected and [Ca2+]i and linaclotide depolarized while lubiprostone hyperpolarized the T84 plasma membrane potential suggesting that lubiprostone may lead to greater cellular stability compared to linaclotide. In T84 cells, as found with linaclotide but not with lubiprostone, transepithelial resistance was slightly but significantly decreased by guanylin, STa and 8-bromo cGMP and fluorescent dextran fluxes were increased by guanylin. However the physiological implications of these small but statistically significant changes remain unclear. Considering the physiological importance of epithelial barrier function and cell integrity and the known impact of stressors, the finding that lubiprostone, but not active linaclotide, exhibits the additional distinct property of effective protection or repair of the epithelial barrier and cell function after stress suggests potential clinical importance for patients with impaired or compromised barrier function such as might occur in IBS.}, number={1}, journal={BMC Pharmacology}, publisher={Springer Nature}, author={Cuppoletti, John and Blikslager, Anthony T and Chakrabarti, Jayati and Nighot, Prashant K and Malinowska, Danuta H}, year={2012}, month={May} }
 @article{jacobi_moeser_corl_harrell_blikslager_odle_2012, title={Dietary Long-Chain PUFA Enhance Acute Repair of Ischemia-Injured Intestine of Suckling Pigs}, volume={142}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.111.150995}, DOI={10.3945/jn.111.150995}, abstractNote={Infant formula companies have been fortifying formulas with long-chain PUFA for 10 y. Long-chain PUFA are precursors of prostanoids, which stimulate recovery of intestinal barrier function. Supplementation of milk with PUFA increases the content of arachidonic acid (ARA) in enterocyte membranes; however, the effect of this enrichment on intestinal repair is not known. The objective of these experiments was to investigate the effect of supplemental ARA on intestinal barrier repair in ischemia-injured porcine ileum. One-day-old pigs (n= 24) were fed a milk-based formula for 10 d. Diets contained no PUFA (0% ARA), 0.5% ARA, 5% ARA, or 5% EPA of total fatty acids. Following dietary enrichment, ilea were subjected to in vivo ischemic injury by clamping the local mesenteric blood supply for 45 min. Following the ischemic period, control (nonischemic) and ischemic loops were mounted on Ussing chambers. Transepithelial electrical resistance (TER) was measured over a 240-min recovery period. Ischemia-injured ileum from piglets fed 5% ARA (61.0 ± 14%) exhibited enhanced recovery compared with 0% ARA (16 ± 14) and 0.5% ARA (22.1 ± 14)-fed pigs. Additionally, ischemia-injured ileum from 5% EPA (51.3 ± 14)-fed pigs had enhanced recovery compared with 0% ARA-fed pigs (P< 0.05). The enhanced TER recovery response observed with ischemia-injured 5% ARA supplementation was supported by a significant reduction in mucosal-to-serosal flux of3H-mannitol and14C-inulin compared with all other ischemia-injured dietary groups (P< 0.05). A histological evaluation of ischemic ilea from piglets fed the 5% ARA showed reduced histological lesions after ischemia compared with the other dietary groups (P< 0.05). These data demonstrate that feeding elevated levels of long-chain PUFA enhances acute recovery of ischemia-injured porcine ileum.}, number={7}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Jacobi, Sheila K. and Moeser, Adam J. and Corl, Benjamin A. and Harrell, Robert J. and Blikslager, Anthony T. and Odle, Jack}, year={2012}, month={May}, pages={1266–1271} }
 @article{hill_blikslager_2012, title={Effect of a zincl-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo}, volume={73}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.73.5.659}, DOI={10.2460/ajvr.73.5.659}, abstractNote={To examine whether a zinc L-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa.Gastric mucosa from 6 healthy dogs.Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc L-carnosine compound, or zinc L-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti-active caspase-3 antibody as an indicator of apoptosis.Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc L-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc L-carnosine compound did not protect against development of apoptosis.Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc L-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.}, number={5}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Hill, Tracy L. and Blikslager, Anthony T.}, year={2012}, month={May}, pages={659–663} }
 @article{nighot_moeser_ueno_blikslager_2012, title={Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa}, volume={18}, ISSN={1007-9327}, url={http://dx.doi.org/10.3748/wjg.v18.i34.4684}, DOI={10.3748/wjg.v18.i34.4684}, abstractNote={To evaluate the protective properties of novel prostone ClC-2 agonist SPI-8811 in porcine model of gastric acid injury.Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH = 1.5) with or without SP1-8811 (1 μmol/L), cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172, 10 μmol/L, apical) and ClC-2 inhibitor ZnCl₂, 300 μmol/L, apical), on the apical surface of tissues. Transepithelial resistance and mucosal-to-serosal ³H-mannitol fluxes were measured over a 90-min period. Tissues were analyzed by morph metric techniques, Immunofluorescence and by western blots.Compared with control tissues, acid exposure decreased transepithelial electrical resistance (TER) and increased ³H-mannitol flux. Pretreatment of gastric mucosa with SPI-8811 was protective against acid-induced decreases in TER (TER, 50 Ω.cm² vs 100 Ω.cm²) and abolished increases in flux (³H-mannitol flux, 0.10 μmol/L.cm² vs 0.04 μmol/L.cm²). Evidence of histological damage in the presence of acid was markedly attenuated by SPI-0811. Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811. Pretreatment with the ClC-2 inhibitor ZnCl₂, but not the selective CFTR inhibitor 172, attenuated SPI-8811-mediated mucosal protection, suggesting a role for ClC-2. Prostone may serve both protective and reparative roles in injured tissues.ClC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach.}, number={34}, journal={World Journal of Gastroenterology}, publisher={Baishideng Publishing Group Inc.}, author={Nighot, M. and Moeser, A. and Ueno, R. and Blikslager, A.}, year={2012}, pages={4684–4692} }
 @article{blikslager_2012, title={Misoprostol: Is it safety or a lack of understanding that prevents its more frequent usage?}, volume={45}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12017}, DOI={10.1111/evj.12017}, abstractNote={Equine Veterinary JournalVolume 45, Issue 1 p. 8-8 Editorial Misoprostol: Is it safety or a lack of understanding that prevents its more frequent usage? A. T. BLIKSLAGER, A. T. BLIKSLAGER College of Veterinary Medicine, North Carolina State University, USASearch for more papers by this author A. T. BLIKSLAGER, A. T. BLIKSLAGER College of Veterinary Medicine, North Carolina State University, USASearch for more papers by this author First published: 10 December 2012 https://doi.org/10.1111/evj.12017Citations: 7Read the full textAboutPDF 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 No abstract is available for this article.Citing Literature Volume45, Issue1January 2013Pages 8-8 RelatedInformation}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Blikslager, A. T.}, year={2012}, month={Dec}, pages={8–8} }
 @article{nugent_blikslager_ferencz_2012, title={Pain management in horses | Schmerzmanagement beim Pferd}, volume={93}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879328604&partnerID=MN8TOARS}, number={3}, journal={Praktische Tierarzt}, author={Nugent, D. and Blikslager, A. and Ferencz, T.}, year={2012}, pages={223–226} }
 @article{labens_blikslager_2012, title={Precision of a photogrammetric method to perform 3D wound measurements compared to standard 2D photographic techniques in the horse}, volume={45}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2011.00538.x}, DOI={10.1111/j.2042-3306.2011.00538.x}, abstractNote={Summary Reasons for performing study: Methods of 3D wound imaging in man play an important role in monitoring of healing and determination of the prognosis. Standard photographic assessments in equine wound management consist of 2D analyses, which provide little quantitative information on the wound bed. Hypotheses: 3D imaging of equine wounds is feasible using principles of stereophotogrammetry. 3D measurements differ significantly and are more precise than results with standard 2D assessments. Methods: Repeated specialised photographic imaging of 4 clinical wounds left to heal by second intention was performed. The intraoperator variability in measurements due to imaging and 3D processing was compared to that of a standard 2D technique using descriptive statistics and multivariate repeated measures ANOVA. Results: Using a custom made imaging system, 3D analyses were successfully performed. Area and circumference measurements were significantly different between imaging modalities. The intraoperator variability of 3D measurements was up to 2.8 times less than that of 2D results. On average, the maximum discrepancy between repeated measurements was 5.8% of the mean for 3D and 17.3% of the mean for 2D assessments. Conclusions: The intraoperator repeatability of 3D wound measurements based on principles of stereophotogrammetry is significantly increased compared to that of a standard 2D photographic technique indicating it may be a useful diagnostic and monitoring tool. Potential relevance: The equine granulation bed plays an important role in equine wound healing. When compared to 2D analyses 3D monitoring of the equine wound bed allows superior quantitative characterisation, contributing to clinical and experimental investigations by offering potential new parameters.}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Labens, R. and Blikslager, A.}, year={2012}, month={Jan}, pages={41–46} }
 @book{blikslager_marshall_2012, title={Principles of Intestinal Injury and Determination of Intestinal Viability}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882569232&partnerID=MN8TOARS}, DOI={10.1016/B978-1-4377-0867-7.00035-1}, journal={Equine Surgery}, author={Blikslager, A.T. and Marshall, J.F.}, year={2012}, pages={411–416} }
 @article{davis_fogle_gerard_levine_blikslager_2012, title={Return to use and performance following exploratory celiotomy for colic in horses: 195 cases (2003-2010)}, volume={45}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2012.00615.x}, DOI={10.1111/j.2042-3306.2012.00615.x}, abstractNote={There are few objective data on return to use and performance in horses following colic surgery.To investigate return to functional use of horses following colic surgery and factors associated with a negative outcome.The North Carolina State University Equine Colic Database was reviewed for horses that underwent exploratory celiotomy for colic (2003-2010). Horses were excluded from the study if they survived <6 months, had no intended use preoperatively, or if further data were not available at attempted follow-up. Information retrieved included history, background, use, and selected pre-, intra-, and post operative factors. Telephone interviews were used to obtain follow-up data. Logistic regression was used to investigate associations between clinical data and outcome, reported as odds ratios with a 95% confidence interval and corresponding P value.Of patients surviving to 6 months, 133/195 (68%) were performing their intended use and 85/156 (54%) were at or above preoperative performance. At one year, 145/190 (76%) horses were performing their intended use and 101/153 (66%) were at or above preoperative performance. Animals were significantly less likely to return to use/performance if they had a previous celiotomy, stall rest for an orthopaedic condition, a nonstrangulating lesion type, incisional hernia, diarrhoea or laminitis.The overall prognosis for return to use and performance following colic surgery is fair to good. Multiple pre- and post operative factors may affect the likelihood of return to use and performance.Targeted owner education regarding preoperative lameness, post operative rehabilitation and treatment for complications, such as incisional hernioplasty, may help inform owners about their horse's potential for return to use and performance following colic surgery.}, number={2}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Davis, W. and Fogle, C. A. and Gerard, M. P. and Levine, J. F. and Blikslager, A. T.}, year={2012}, month={Aug}, pages={224–228} }
 @book{wilson_blikslager_2012, title={Stomach and Spleen}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882624044&partnerID=MN8TOARS}, DOI={10.1016/B978-1-4377-0867-7.00032-6}, journal={Equine Surgery}, author={Wilson, D.A. and Blikslager, A.T.}, year={2012}, pages={388–402} }
 @article{hill_blikslager_lascelles_2012, title={Su1738 Misoprostol Protects Gastric Barrier Function After Acid Injury in an Ex Vivo Canine Model}, volume={142}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(12)61879-4}, DOI={10.1016/S0016-5085(12)61879-4}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Hill, Tracy L. and Blikslager, Anthony and Lascelles, Duncan}, year={2012}, month={May}, pages={S-492} }
 @article{nighot_ueno_blikslager_2012, title={Su1751 The CLC-2 Agonist SPI-0811 Protects Against Indomethacin-Induced Epithelial Barrier Dysfunction in Human Gastric Epithelial Cells}, volume={142}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(12)61893-9}, DOI={10.1016/S0016-5085(12)61893-9}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Meghali P. and Ueno, Ryuji and Blikslager, Anthony}, year={2012}, month={May}, pages={S-495} }
 @article{blikslager_2011, title={Cecal impaction in horses}, volume={33}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84861449526&partnerID=MN8TOARS}, number={7}, journal={Compendium on Continuing Education for the Practising Veterinarian}, author={Blikslager, A.}, year={2011}, month={Jul}, pages={E1–4} }
 @article{blikslager_2011, title={Cecal impaction in horses.}, volume={33}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879314118&partnerID=MN8TOARS}, number={7}, journal={Compendium (Yardley, PA)}, author={Blikslager, A.}, year={2011} }
 @article{nighot_young_blikslager_2011, title={Chloride Channel CLC-2 Modulates Susceptibility to DSS-Induced Murine Colitis: Implications for the Role of the Tight Junction in IBD}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)62079-9}, DOI={10.1016/S0016-5085(11)62079-9}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Young, Karen and Blikslager, Anthony}, year={2011}, month={May}, pages={S-502} }
 @article{messenger_papich_blikslager_2011, title={Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs}, volume={35}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2011.01338.x}, DOI={10.1111/j.1365-2885.2011.01338.x}, abstractNote={The objective of this study was to determine the pharmacokinetics (PK) of enrofloxacin in pigs and compare to the tissue interstitial fluid (ISF). Six healthy, young pigs were administered 7.5 mg/kg enrofloxacin subcutaneously (SC). Blood and ISF samples were collected from preplaced intravenous catheters and ultrafiltration sampling probes placed in three different tissue sites (intramuscular, subcutaneous, and intrapleural). Enrofloxacin concentrations were measured using high-pressure liquid chromatography with fluorescence detection, PK parameters were analyzed using a one-compartment model, and protein binding was determined using a microcentrifugation system. Concentrations of the active metabolite ciprofloxacin were negligible. The mean ± SD enrofloxacin plasma half-life, volume of distribution, clearance, and peak concentration were 26.6 ± 6.2 h (harmonic mean), 6.4 ± 1.2 L/kg, 0.18 ± 0.08 L/kg/h, and 1.1 ± 0.3 μg/mL, respectively. The half-life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 μg/mL. Tissue penetration, as measured by a ratio of area-under-the-curve (AUC), was 139% (± 69%). Plasma protein binding was 31.1% and 37.13% for high and low concentrations, respectively. This study demonstrated that the concentration of biologically active enrofloxacin in tissues exceeds the concentration predicted by the unbound fraction of enrofloxacin in pig plasma. At a dose of 7.5 mg/kg SC, the high tissue concentrations and long half-life produce an AUC/MIC ratio sufficient for the pathogens that cause respiratory infections in pigs.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Messenger, K. M. and Papich, M. G. and Blikslager, A. T.}, year={2011}, month={Sep}, pages={452–459} }
 @article{marshall_bhatnagar_bowman_howard_morris_skorich_redding_blikslager_2011, title={Evaluation of the cyclooxygenase selectivity of robenacoxib and its effect on recovery of ischemia-injured jejunal mucosa in horses}, volume={72}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.72.2.226}, DOI={10.2460/ajvr.72.2.226}, abstractNote={Abstract Objective —To determine the cyclooxygenase (COX) selectivity of robenacoxib and its effect on recovery of jejunal mucosa following ischemic injury in horses. Animals —12 healthy horses. Procedures —Half the maximal inhibition (EC 50 ) of robenacoxib for COX-1 and COX-2 activity was established in bloods samples from 6 horses via measurement of thromboxane B 2 (TXB 2 ) and prostaglandin E 2 concentrations, respectively; COX selectivity was subsequently calculated. Six other horses were anesthetized, and ischemia was induced in the jejunum for 2 hours. Control and ischemia-injured mucosa were collected and incubated with Ringer's solution (control treatment), flunixin meglumine (2.7 × 10 −5 M), or robenacoxib (2.7 × 10 −5 M). Transepithelial electrical resistance and mannitol flux were measured over a 4-hour recovery period. Bathing solution TXB 2 and prostaglandin E metabolite concentrations were measured to assess COX-1 and COX-2 function, respectively. Results —The mean ± SD EC 50 value of robenacoxib for COX-1 and COX-2 was 11.46 ± 4.46μM and 0.19 ± 0.07μM, respectively, resulting in a COX selectivity ratio of 61.01. The transepithelial electrical resistance of ischemia-injured jejunum treated with flunixin meglumine was significantly lower than that of control and robenacoxib-treated tissues. A significant increase in concentrations of prostaglandin E metabolites and TXB 2 was detected in control and robenacoxib-treated tissues but not flunixin meglumine—treated tissues. Conclusions and Clinical Relevance —Robenacoxib selectively inhibited COX-2 and allowed recovery of barrier function in ischemia-injured equine jejunal tissue in vitro.}, number={2}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Marshall, John F and Bhatnagar, Adria S. and Bowman, Susan G. and Howard, Christina M. and Morris, Natalie N. and Skorich, Dinah A. and Redding, Caitlyn D. and Blikslager, Anthony T.}, year={2011}, month={Feb}, pages={226–232} }
 @article{brown_blikslager_2011, title={Hypoxia Disrupts Recovery of Injured Non-Transformed Small Intestinal Cells, but Not Transformed Cells}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)62902-8}, DOI={10.1016/S0016-5085(11)62902-8}, abstractNote={occluding superior mesenteric artery (SMA) for 45 min. Inflammatory response in the smallintestine(jejunum)wasassessed4hfollowingreperfusionbymeasuringtissuelevelsofTNF-alpha protein (ELISA), histology (Hematoxylin-Eosin stain), iNOS and HO-1 localization(immunohistochemistry), adhesion molecules E-selectin and ICAM-1 (Western blot), NF-kappaB activation (EMSA), and polymorphonuclear neutrophil (PMN) tissue accumulation(MPO assay). iNOS and HO-1 were localized in the epithelium and infiltrated PMN. Theobtained results indicated that tissue levels of TNF-alpha, E-selectin and ICAM-1 proteinexpression, activation of NF-kappaB, and subsequent accumulation of PMN were elevatedin I/R-challenged WT jejunum. The above changes were significantly attenuated in I/R-challenged Bach1 deficient jejunum. Taken together these findings indicate that disruptionof the Bach1 gene resulted in attenuation of I/R-challenged intestinal injury, indicating thatinhibitionofBach1maybeanoveltherapeuticstrategyforthetreatmentagainstI/R-mediatedintestinal injury.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Brown, Mary A. and Blikslager, Anthony}, year={2011}, month={May}, pages={S-699} }
 @article{hill_blikslager_2011, title={Indomethacin Decreases Recovery of Gastric Barrier Function After Acid Injury in a Novel Ex Vivo Canine Model}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)61288-2}, DOI={10.1016/S0016-5085(11)61288-2}, abstractNote={rhage and edema; dilation and repletion of venules, aggregation of blood cells, clots. Microvascular abnormalities started in 2-5min after application of 5-HT and lasted 30-40min. IL-1β 40pg/gtissue, TNF-α 35±3pg/gtissue, IFN-γ 50±6pg/gtissue. The 3rd group (acute ulcer): narrowing of arteries and arterioles, dilation of venules, clots of blood, increased number of capillaries, edema of surrounding tissue. The 4th group no changes. Conclusion: Disturbances in microcirculatory system reduce the tolerance of gastric mucosa. The damage to exchange vessels and veins lead to severe injury of gastric mucosa. Gastric mucosa is more stable to supply vessels damage. Determination of microcirculatory changes In Vivo in human is possible during conventional endoscopic procedure by using Lazma system and it helps to point out the initial stages of damage to the gastric mucosa.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Hill, Tracy L. and Blikslager, Anthony}, year={2011}, month={May}, pages={S-319} }
 @article{nighot_blikslager_2011, title={Indomethacin Induces Gastric Epithelial Barrier Dysfunction via a p38 MAPK-Dependent Mechanism in MKN-28 Cells}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)61271-7}, DOI={10.1016/S0016-5085(11)61271-7}, abstractNote={Background and AimsIL-33 is an IL-1 related cytokine and like IL-1a has been suggested to amplify the immune response during tissue injury. IL-33 is expressed in endothelium and mucosal epithelium and is a ligand for the receptor ST2. Recently IL-33 has been shown to be a crucial amplifier of immunity that can modulate the response in a number of models of innate-type mucosal immunity. Significantly IL-33 is involved in the development of DSS induced colitis. Additionally we have demonstrated that IL-11, a member of the IL-6 family of cytokines, is also important in DSS induced colitis and others have demonstrated an antiinflammatory role for IL-11 in intestinal inflammation. Here we examine the effects of IL11 on the normal colon and establish that IL-11 is upstream of Bmp1 and IL-33, and that it regulates mucosal proliferation via Reg3β in a STAT3-dependent manner. MethodsNormal mice were treated with 5 ug of recombinant human IL-11 (rhIL-11) every 6 hours and culled either 6 hours, 24 hours of 5 days after the initial dose. Colons were removed for mRNA and protein analysis. ResultsIL-11 is a ligand for gp130 and should initiate both the Ras/MAPK/ERK and STAT1/STAT3 signalling pathways. Chronic IL-11 treatment of normal mice activates STAT3 (Tyr705) but not ERK1/2 (Thr202/Tyr204), and acute IL-11 caused a drop in ERK1/2 activation. This is a very similar to the signalling outcome downstream of IL-11 in the gastric mucosa, where signalling emanating from gp130 activation by IL-11 is skewed towards STAT3. Expression of SOCS3, a bona fide STAT3 responsive gene, is also increased in the colon following IL-11 treatment. In the gastric antrum IL-11 treatment is pro-proliferative. The same is true of the colonic response to IL-11 with a 1.6 fold increase in the expression of the proliferation marker PCNA by immunoblot. IL-11 also caused an increase in the expression of the pro-proliferative gene Reg3β and the mRNAs involved in BMP signalling Bmp1 and Bmp1rb. However, most significantly IL-11 treatment caused a large and significant increase in the expression of IL-33 and other mediators of the innate immune response in the absence of any significant damage to the mucosa. ConclusionsColonic tissue responds to IL-11 largely by activation of STAT3 signalling. There are three major outcomes resulting from this signalling; 1) increased proliferation and expression of pro-proliferative genes, 2) increased expression of components of BMP signalling and 3) activation of IL-33 and the innate immune system.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Meghali P. and Blikslager, Anthony}, year={2011}, month={May}, pages={S-315} }
 @article{vainio_sykes_blikslager_2011, title={Primary gastric impaction in horses: A retrospective study of 20 cases (2005-2008)}, volume={23}, ISSN={["0957-7734"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952467016&partnerID=MN8TOARS}, DOI={10.1111/j.2042-3292.2010.00153.x}, abstractNote={Primary gastric impaction is an uncommon condition. Furthermore, the factors associated with gastric impaction and the optimal method of treatment are not clear. The aim of this article is to describe the clinical findings, treatment and outcome of horses with a primary gastric impaction. Medical records of horses that presented with a primary gastric impaction between 2005 and 2008 were reviewed and 20 horses with a primary gastric impaction identified. Diagnosis of a primary gastric impaction was made if the horse had been fasted for a minimum of 16 h, a concretion of ingesta precluded visualisation of the margo plicatus and there was no evidence of concurrent intestinal pathology. Thirteen of 20 (65%) horses were presented on an emergency basis. The most common complaint was inappetence (50%) followed by acute colic (35%) and recurrent colic (35%). On initial examination for colic, all horses had a normal heart rate and 7 of 20 (35%) had decreased gastrointestinal borborygmi. All horses were treated with enteral fluid therapy. The median dose of fluids administered per day was 5 doses (range 1–8 doses) of 2–10 l of isotonic electrolyte solution. The median length of treatment until resolution was 2 days (range 1–5 days). Eighteen of 20 (90%) horses survived to discharge. Primary gastric impaction appears to be a condition with clinical signs of inappetence and mild abdominal discomfort. This is the largest group of horses reported that were treated with enteral fluid therapy for a gastric impaction and it was concluded that enteral fluid therapy was of value in this study.}, number={4}, journal={EQUINE VETERINARY EDUCATION}, author={Vainio, K. and Sykes, B. W. and Blikslager, A. T.}, year={2011}, month={Apr}, pages={186–190} }
 @article{nighot_blikslager_2011, title={The Chloride Channel CLC-2 Modulates Tight Junction Barrier Function via Intracellular Trafficking}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)62083-0}, DOI={10.1016/S0016-5085(11)62083-0}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Blikslager, Anthony}, year={2011}, month={May}, pages={S-503} }
 @article{nighot_blikslager_nighot_2011, title={The Chloride Channel CLC-2 is Involved in Organization of Murine Gastric Glands}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)60379-X}, DOI={10.1016/S0016-5085(11)60379-X}, abstractNote={BACKGROUND: Primary cilia are necessary for Hedgehog (Hh) signaling and other pathways. Anterograde ciliary transport is mediated by kinesin-II, a heterotrimeric protein composed of two motor subunits, KIF3A, KIF3B, and a non-motor subunit KAP3. Intraflagellar transport protein 88 (IFT88) participates in protein transport along the cilia. Conventional null mice for KIF3A and IFT88 are not viable. Sonic hedgehog (Shh) is highly expressed in gastric epithelial cells of the corpus compared to the antrum. Therefore we examined the stomach of mice conditionally null for KIF3A and IFT88 to define the role of primary cilia in this organ. METHODS: KIF3A and IFT88 mice harboring one null allele and loxP sites on the other allele on a ROSA26 reporter background were crossed to Shh-Cre mice (KIF3A-/ FL and IFT88-/FL respectively.) KIF3A+/FL, IFT88+/FL, and wild type (WT) littermates were analyzed at 6 and 8 months. Cell lineages were identified by immunohistochemistry in paraffin-sections, and by β-galactosidase (β-gal) staining for the Cre-expressing cells. Acetylated-α-tubulin was used as the marker for cilia. RESULTS: Epithelial cells in the antrum and corpus expressed primary cilia. β-gal staining confirmed variegated glandular Cre expression in all epithelial cells. Gastric epithelial cells did not express cilia in the IFT88-/FL mice, while KIF3A-/FL mice showed reduced numbers of cilia in the corpus versus controls (0.59+0.04 cilia/gland, N=8 vs. 0.72+0.06 cilia/gland, N=14), but no changes in the antrum (0.94+0.05 vs. 1.08+0.09 cilia/gland.) KIF3A-/FL and IFT88-/FL mice exhibited different phenotypes. By 6 months, KIF3A-/FL mice showed mucous pit hyperplasia in the corpus. Mucous neck and zymogenic lineages were not expanded, but parietal cells were still present. The KIF3A-/FL mice phenotype resembled the mucous pit hyperplasia observed in the Shh conditionally null mice generated with H+K+ATPase-Cre. In contrast, the phenotype of the IFT88-/FL mice showed parietal cell atrophy, and proximal corpus hyperplasia due to expansion of the mucous neck cell compartment assessed by TFF2 expression (SPEM) by 4 months of age. We have previously observed that gastrinand ghrelin-secreting cells exhibit primary cilia, but none of the mouse models showed differences in the number of these endocrine cells.CONCLUSION:The IFT88-/FLmice exhibited amore severe phenotype than the KIF3A-/FL mice even though both molecules affect primary cilia function. The phenotype of these two mouse models suggests that Hh signaling is necessary for the maintenance of the corpus epithelium. Also, gastric epithelial cilia might be important for the function but not differentiation of gastrinand ghrelin-secreting cells.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Meghali P. and Blikslager, Anthony and Nighot, Prashant K.}, year={2011}, month={May}, pages={S-93} }
 @article{marshall_blikslager_2011, title={The effect of nonsteroidal anti-inflammatory drugs on the equine intestine}, volume={43}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2011.00398.x}, DOI={10.1111/j.2042-3306.2011.00398.x}, abstractNote={Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the response of the large and small intestines to injury and NSAID treatment have been identified. Flunixin meglumine has been shown in the small intestine to inhibit barrier function recovery and increase permeability to lipopolysaccharide (LPS). A range of NSAIDs has been examined in the small intestine and experimental evidence suggests that those NSAIDs with cyclooxygenase independent anti-inflammatory effects or a COX-2 selective mode of action may offer significant advantages over traditional NSAIDs.}, number={SUPPL.39}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Marshall, J. F. and Blikslager, A. T.}, year={2011}, month={Jul}, pages={140–144} }
 @article{marshall_bhatnagar_bowman_morris_skorich_redding_blikslager_2011, title={The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo}, volume={43}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2011.00401.x}, DOI={10.1111/j.2042-3306.2011.00401.x}, abstractNote={Summary Reasons for performing study: Flunixin meglumine is used for treatment of equine colic despite evidence of inhibited recovery of mucosal barrier function following small intestinal ischaemic injury. This study aimed to characterise an alternative treatment (AHI‐805) for abdominal pain in the horse. Objective: To determine the effect of AHI‐805, an aza‐thia‐benzoazulene derivative, on the cyclooxygenase enzymes and the recovery of mucosal barrier function following ischaemic injury. Methods: Effect of AHI‐805 on in vitro COX‐1 and COX‐2 activity was determined by measuring coagulation‐induced thromboxane B 2 (TXB 2 ) and lipopolysaccharide‐stimulated prostaglandin E 2 concentrations in equine whole blood. Horses (n = 6) were anaesthetised and jejunum subjected to ischaemia for 2 h. Control and ischaemia injured mucosa was placed in Ussing chambers and treated with Ringer's solution containing control treatment (DMSO), flunixin meglumine (27 µmol/l), or AHI‐805 (27 µmol/l). Transepithelial electrical resistance (TER), mucosal‐to‐serosal flux of 3 H‐mannitol, and bathing solution TXB 2 and prostaglandin E metabolites (PGEM) were measured over a 4 h recovery period. Results: Treatment with AHI‐805 had no significant effect on TXB 2 production but significantly inhibited production of PGE 2 at a concentration of 1 µmol/l or greater. TER of flunixin or AHI‐805 treated ischaemia‐injured jejunum was significantly lower than control treated injured tissue over the recovery period. Mannitol flux and grade of histological damage were significantly increased by ischaemic injury only. There was a significant increase in PGEM and TXB 2 in control tissues over the 240 min recovery period, but not in flunixin or AHI‐805 treated tissues. Conclusions: Flunixin meglumine and AHI‐805 inhibit recovery of barrier function in ischaemic‐injured equine jejunum in vitro through inhibition of the COX enzymes. Potential relevance: The novel compound AHI‐805 may not be suitable for the treatment of equine colic associated with ischaemic injury.}, number={SUPPL.39}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Marshall, J. F. and Bhatnagar, A. S. and Bowman, S. G. and Morris, N. N. and Skorich, D. A. and Redding, C. D. and Blikslager, A. T.}, year={2011}, month={Jul}, pages={106–111} }
 @article{davis_marshall_papich_blikslager_campbell_2011, title={The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses}, volume={34}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2010.01185.x}, DOI={10.1111/j.1365-2885.2010.01185.x}, abstractNote={Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap. 34 , 12–16. The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life ( t 1/2 k 10 ) of 12.49 ± 1.84 h. The average maximum plasma concentration (C max ) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC 50 and IC 80 , respectively. Dosing simulations showed that concentrations above the IC 80 for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC 50 following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Marshall, J. F. and Papich, M. G. and Blikslager, A. T. and Campbell, N. B.}, year={2011}, month={Jan}, pages={12–16} }
 @article{grosche_morton_graham_sanchez_blikslager_polyak_freeman_2011, title={Ultrastructural changes in the equine colonic mucosa after ischaemia and reperfusion}, volume={43}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2011.00402.x}, DOI={10.1111/j.2042-3306.2011.00402.x}, abstractNote={Summary Reason for performing study: Ultrastructural changes in the epithelium can provide information on early changes in barrier properties, repair and inflammation in equine colon after ischaemia and reperfusion (I/R). Objectives: To describe the morphology and ultrastructure of the epithelium in equine large colonic mucosa after I/R, and the response of inflammatory cells to injury. Methods: Ischaemia was induced for 1 h followed by 4 h of reperfusion in a 40 cm segment of the pelvic flexure in 6 horses. Mucosal biopsies before and after ischaemia, and after 1, 2 and 4 h of reperfusion were fixed in glutaraldehyde/paraformaldehyde and osmium tetroxide, and embedded in epon. Morphological and ultrastructural changes were evaluated in toluidine blue‐stained semithin sections by light microscopy and in thin sections stained with uranyl acetate/lead citrate by transmission electron microscopy. Results: Ischaemia caused swelling of epithelial cells and their organelles, opening of tight junctions, detachment from the basement membrane, early apoptosis and single cell necrosis. Autophagy was a prominent feature in epithelial cells after ischaemia. Reperfusion was characterised by apoptosis, epithelial regeneration and restoration of apical cell junctions. Phagocytic‐like vacuoles containing cellular debris and bacteria were evident in epithelial cells after reperfusion. Paracellular and subepithelial clefts formed, accompanied by infiltration of neutrophils, lymphocytes and eosinophils into the epithelium. Subepithelial macrophages and luminal neutrophils had increased phagocytic activity. Conclusions: Ischaemia caused ultrastructural damage to the colonic epithelium, but epithelial cells recovered during reperfusion. Potential relevance: Transmission electron microscopy can demonstrate subtle ultrastructural damage to epithelial cells and evidence of recovery after I/R in equine colon.}, number={SUPPL.39}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Grosche, A. and Morton, A. J. and Graham, A. S. and Sanchez, L. C. and Blikslager, A. T. and Polyak, M. M. R. and Freeman, D. E.}, year={2011}, month={Jul}, pages={8–15} }
 @article{nighot_lee_blikslager_2010, title={580 Intestinal Epithelial Barrier Alterations in CLC-2−/− Mice are Partially Regulated by MLCK}, volume={138}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(10)60375-7}, DOI={10.1016/S0016-5085(10)60375-7}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Lee, Sung H. and Blikslager, Anthony T.}, year={2010}, month={May}, pages={S-82} }
 @article{schramme_hunter_campbell_blikslager_smith_2010, title={A surgical tendonitis model in horses: Technique, clinical, ultrasonographic and histological characterisation}, volume={23}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77956158773&partnerID=MN8TOARS}, DOI={10.3415/VCOT-09-10-0106}, abstractNote={Tendon injuries are common in all athletic activities in both humans and horses. Research of treatment modalities for this disease has typically been performed on a model of collagenase-induced tendonitis. This model has several disadvantages. Our hypothesis was that a reproducible core lesion could be created surgically in superficial digital flexor tendons (SDFT), which could then be evaluated consistently using ultrasonography.Four horses free of forelimb lameness were used in this study. Each horse underwent general anaesthesia and a synovial resector was used to create a core lesion in the SDFT of each forelimb. Sonographic examination was conducted weekly using 2 cm intervals between a section 7 and 25 cm distal to the accessory carpal bone. At two, four, eight, and 12 weeks after injury, a horse was euthanatized. Histopathological evaluation of the SDFT was performed at the same levels as the sonographic examination.Only mild clinical signs of tendonitis were observed. Ultrasonographic core lesions were 10-16 cm long and had a mean maximum cross-sectional area (CSA) of 18.25 +/- 5.91% occurring at 17-23 cm distal to the accessory carpal bone, and a mean volume of 1.86 +/- 0.26 cm(3). Mean duration taken to achieve maximum lesion CSA and lesion volume was 35 +/- 7 days. Histologically, the lesions were characterised by mild inflammation followed by fibroplasia.The reported surgical technique resulted in core lesions that were consistent in size and location, were readily evaluated with ultrasonography, and showed similarities with the ultrasonographic and histological progression of naturally occurring tendonitis lesions.}, number={4}, journal={Veterinary and Comparative Orthopaedics and Traumatology}, author={Schramme, M. and Hunter, S. and Campbell, N. and Blikslager, A. and Smith, R.}, year={2010}, pages={231–239} }
 @inbook{blikslager_2010, place={Philadelphia, PA}, edition={2nd}, title={Alimentary diseases}, ISBN={9780702027925}, url={http://dx.doi.org/10.1016/b978-0-7020-2792-5.00007-3}, DOI={10.1016/b978-0-7020-2792-5.00007-3}, booktitle={Diagnostic Techniques in Equine Medicine}, publisher={W.B. Saunders, Elsevier}, author={Blikslager, A.T.}, editor={Taylor, F.G.R. and Brazil, T. and Hillyer, M.H.Editors}, year={2010}, pages={27–72} }
 @book{blikslager_2010, title={Alimentary diseases}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84905885831&partnerID=MN8TOARS}, journal={Diagnostic Techniques in Equine Medicine: Second Edition}, author={Blikslager, A.T.}, year={2010}, pages={28–72} }
 @article{nighot_moeser_ali_blikslager_koci_2010, title={Astrovirus infection induces sodium malabsorption and redistributes sodium hydrogen exchanger expression}, volume={401}, ISSN={0042-6822}, url={http://dx.doi.org/10.1016/j.virol.2010.02.004}, DOI={10.1016/j.virol.2010.02.004}, abstractNote={Astroviruses are known to be a leading cause of diarrhea in infants and the immunocompromised; however, our understanding of this endemic pathogen is limited. Histological analyses of astrovirus pathogenesis demonstrate clinical disease is not associated with changes to intestinal architecture, inflammation, or cell death. Recent studies in vitro have suggested that astroviruses induce actin rearrangement leading to loss of barrier function. The current study used the type-2 turkey astrovirus (TAstV-2) and turkey poult model of astrovirus disease to examine how astrovirus infection affects the ultrastructure and electrophysiology of the intestinal epithelium. These data demonstrate that infection results in changes to the epithelial ultrastructure, rearrangement of F-actin, decreased absorption of sodium, as well as redistribution of the sodium/hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm. Collectively, these data suggest astrovirus infection induces sodium malabsorption, possibly through redistribution of specific sodium transporters, which results in the development of an osmotic diarrhea.}, number={2}, journal={Virology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Moeser, Adam and Ali, Rizwana A. and Blikslager, Anthony T. and Koci, Matthew D.}, year={2010}, month={Jun}, pages={146–154} }
 @article{nighot_blikslager_2010, title={ClC-2 regulates mucosal barrier function associated with structural changes to the villus and epithelial tight junction}, volume={299}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00520.2009}, DOI={10.1152/ajpgi.00520.2009}, abstractNote={We have previously shown an important role of the chloride channel ClC-2 in orchestrating repair of tight junctions in ischemia-injured mucosa. In this study, we examined the role of ClC-2 in regulating barrier function of normal murine intestinal mucosa. Ex vivo, ClC-2-/- ileal mucosa mounted in Ussing chambers had significantly higher transepithelial electrical resistance (TER) and reduced [(3)H]mannitol mucosal-to-serosal flux compared with wild-type (WT) mouse mucosa. We also noted that ileum from ClC-2-/- mice had a significantly reduced in vivo [(3)H]mannitol blood-to-lumen clearance compared with WT animals. By scanning electron microscopy, flat leaflike villi were found to have tapering, rounded apical tips in ClC-2-/- mucosa. By transmission electron microscopy, the apical intercellular tight junctions in ClC-2-/- intestine revealed lateral membranes that were less well defined but closely aligned compared with electron-dense and closely apposed tight junctions in WT mucosa. The width of apical tight junctions was significantly reduced in ClC-2-/- intestine. Such an alteration in tight junction ultrastructure was also noted in the testicular tissue from ClC-2-/- mice. The ClC-2-/- intestinal mucosa had reduced expression of phospho-myosin light chain (MLC), and inhibition of myosin light chain kinase (MLCK) in WT mucosa partially increased TER toward the TER in ClC-2-/- intestine. Contrary to our prior work on the reparative role of ClC-2 in injured mucosa, this study indicates that ClC-2 reduces barrier function in normal mucosa. The mechanisms underlying these differing roles are not entirely clear, although ultrastructural morphology of tight junctions and MLCK appear to be important to the function of ClC-2 in normal mucosa.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Nighot, Prashant K. and Blikslager, Anthony T.}, year={2010}, month={Aug}, pages={G449–G456} }
 @article{bowman_marshall_blikslager_2010, title={Demographic characteristics of horses donated to the North Carolina State University Equine Health Center, 1996–2008}, volume={236}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.236.12.1334}, DOI={10.2460/javma.236.12.1334}, abstractNote={To determine demographic characteristics of horses donated to the North Carolina State University Equine Health Center (EHC) between 1996 and 2008.Retrospective cohort study.122 horses donated to the EHC between January 1996 and December 2008, and 246 horses offered for donation to the EHC between January 2007 and December 2008.Telephone and medical records were examined. Data were collected in 5 categories: age, sex, breed, reason for donation, and use prior to donation.From January 1996 through December 2008, 122 horses were donated to the EHC (median, 3 horses/y; range, 0 to 39 horses/y). There were 131 and 115 horses offered for donation during 2007 and 2008, respectively, of which 38 and 23 were accepted. Mean +/- SD age of horses offered for donation during 2007 and 2008 was 12.7 +/- 6.7 years, with 75 of the 246 (30.5%) horses between 6 and 10 years old. Musculoskeletal disease was the most commonly listed reason horses were offered for donation (115/240 [47.9%]).Results indicated that unwanted horses donated to the EHC between 1996 and 2008 spanned a wide range of ages and breeds and included both males and females. The most common reason given for unwanted horses offered for donation during 2007 and 2008 was musculoskeletal disease, with degenerative joint disease, lameness of undetermined cause, laminitis, and navicular disease being the most common musculoskeletal conditions.}, number={12}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Bowman, Susan G. and Marshall, John F. and Blikslager, Anthony T.}, year={2010}, month={Jun}, pages={1334–1337} }
 @article{blikslager_christley_jeffcott_silver_weeren_2010, title={Dr Peter Rossdale, OBE, Editor Equine Veterinary Journal 1980-2010}, volume={43}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/j.2042-3306.2010.00347.x}, DOI={10.1111/j.2042-3306.2010.00347.x}, abstractNote={Equine Veterinary JournalVolume 43, Issue 1 p. 2-2 Dr Peter Rossdale, OBE, Editor Equine Veterinary Journal 1980–2010 Anthony Blikslager, Anthony Blikslager North Carolina State University, USASearch for more papers by this authorRob Christley, Rob Christley University of Liverpool, UKSearch for more papers by this authorLeo Jeffcott, Leo Jeffcott University of Sydney, AustraliaSearch for more papers by this authorIan Silver, Ian Silver Bristol University, UKSearch for more papers by this authorRené van Weeren, René van Weeren Utrecht University, The NetherlandsSearch for more papers by this author Anthony Blikslager, Anthony Blikslager North Carolina State University, USASearch for more papers by this authorRob Christley, Rob Christley University of Liverpool, UKSearch for more papers by this authorLeo Jeffcott, Leo Jeffcott University of Sydney, AustraliaSearch for more papers by this authorIan Silver, Ian Silver Bristol University, UKSearch for more papers by this authorRené van Weeren, René van Weeren Utrecht University, The NetherlandsSearch for more papers by this author First published: 10 December 2010 https://doi.org/10.1111/j.2042-3306.2010.00347.xCitations: 2Read the full textAboutPDF 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 Volume43, Issue1January 2011Pages 2-2 RelatedInformation}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Blikslager, Anthony and Christley, Rob and Jeffcott, Leo and Silver, Ian and Weeren, René van}, year={2010}, month={Dec}, pages={2–2} }
 @article{smith_clark_overman_tozel_huang_rivier_blisklager_moeser_2010, title={Early weaning stress impairs development of mucosal barrier function in the porcine intestine}, volume={298}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00081.2009}, DOI={10.1152/ajpgi.00081.2009}, abstractNote={Early life stress is a predisposing factor for the development of chronic intestinal disorders in adult life. Here, we show that stress associated with early weaning in pigs leads to impaired mucosal barrier function. Early weaning (15- to 21-day weaning age) resulted in sustained impairment in intestinal barrier function, as indicated by reductions in jejunal transepithelial electrical resistance and elevations in mucosal-to-serosal flux of paracellular probes [(3)H]mannitol and [(14)C]inulin measured at 5 and 9 wk of age, compared with that shown in late-weaned pigs (23- to 28-day weaning age). Elevated baseline short-circuit current was observed in jejunum from early-weaned pigs and was shown to be mediated via enhanced Cl(-) secretion. Jejunal barrier dysfunction in early-weaned pigs coincided with increased lamina propria immune cell density particularly mucosal mast cells. The mast cell stabilizer drug sodium cromoglycolate ameliorated barrier dysfunction and hypersecretion in early-weaned pigs, demonstrating an important role of mast cells. Furthermore, activation of mast cells ex vivo with c48/80 and corticotrophin-releasing factor (CRF) in pig jejunum mounted in Ussing chambers induced barrier dysfunction and elevations in short-circuit current that were inhibited with mast cell protease inhibitors. Experiments in which selective CRF receptor antagonists were administered to early-weaned pigs revealed that CRF receptor 1 (CRFr1) activation mediates barrier dysfunction and hypersecretion, whereas CRFr2 activation may be responsible for novel protective properties in the porcine intestine in response to early life stress.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Smith, Feli and Clark, Jessica E. and Overman, Beth L. and Tozel, Christena C. and Huang, Jennifer H. and Rivier, Jean E. F. and Blisklager, Anthony T. and Moeser, Adam J.}, year={2010}, month={Mar}, pages={G352–G363} }
 @article{cook_meyer_campbell_blikslager_2010, title={Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum | Wirkung von firocoxib oder flunixin auf die regeneration des ischämisch geschädigtem jejunum beim pferd}, volume={26}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77749270496&partnerID=MN8TOARS}, number={1}, journal={Pferdeheilkunde}, author={Cook, V. and Meyer, C. and Campbell, N. and Blikslager, A.}, year={2010}, pages={100–101} }
 @article{wooten_lascelles_cook_law_blikslager_2010, title={Evaluation of the relationship between lesions in the gastroduodenal region and cyclooxygenase expression in clinically normal dogs}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.6.630}, DOI={10.2460/ajvr.71.6.630}, abstractNote={Abstract Objective —To determine whether clinically normal dogs have lesions in the pylorus and duodenum and to examine the expression of cyclooxygenase (COX) isoforms in the pylorus and duodenum of these dogs. Animals —27 clinically normal dogs. Procedures —Physical examination was performed on clinically normal dogs from animal shelters and research projects; the dogs were then euthanized. After the dogs were euthanized, the pylorus and duodenum were photographed and scored for gross appearance of lesions. Samples were obtained for histologic evaluation and determination of COX expression via western blot analyses. Tissues from the pylorus and duodenum were categorized as normal, inflamed, or eroded on the basis of histologic analysis. Each histologic category of tissue was then evaluated to determine the correlation with gross appearance and COX expression. Results —Of the 27 dogs, 5 had unremarkable histologic findings in the pylorus and duodenum. Inflammation was found in the pylorus of 10 dogs and in the duodenum of 5 dogs. Epithelial erosion was detected in the pylorus of 1 dog and in the duodenum of 3 dogs. Gross appearance was not significantly correlated with histologic appearance. Expression of COX-1 was not upregulated by inflammation, whereas COX-2 expression was increased by inflammation or erosion. Conclusions and Clinical Relevance —Dogs that appear to be clinically normal may have underlying gastroduodenal lesions associated with upregulation of COX-2. Because of the inability to determine this during routine physical examination, practitioners should be aware of this potential situation when prescribing COX inhibitors.}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wooten, Jenna G. and Lascelles, B. Duncan X. and Cook, Vanessa L. and Law, J. Mac and Blikslager, Anthony T.}, year={2010}, month={Jun}, pages={630–635} }
 @inbook{blikslager_2010, place={St. Louis, MO}, edition={3rd edition}, title={Ischemic disorders of the intestinal tract}, booktitle={Equine Internal Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T.}, editor={Reed, S.M. and Bayly, W.M. and Sellon, D.C.Editors}, year={2010}, pages={876–882} }
 @article{mansmann_james_blikslager_orde_2010, title={Long Toes in the Hind Feet and Pain in the Gluteal Region: An Observational Study of 77 Horses}, volume={30}, ISSN={["0737-0806"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78650007012&partnerID=MN8TOARS}, DOI={10.1016/j.jevs.2010.11.007}, abstractNote={This study deals with the relationship between long toes in the hind feet and pain in the gluteal region in horses, and the remedial value of trimming/shoeing that moves the breakover point back at the toe. Seventy seven client-owned horses were studied, 67 shod riding horses retrospectively and 10 barefoot broodmares prospectively. The 10 mares were evaluated twice, and 24 of the 67 riding horses were re-evaluated at the next shoeing, for a total of 111 observations. Each horse underwent gluteal palpation and lateral radiographs of both hind feet. Toe length was quantified as breakover distance (BD), the horizontal distance between the tip of the third phalanx and the dorsalmost point at which the wall/shoe was in contact with the ground. The BD was then shortened with trimming +/− shoeing to a length of ≤15mm (shod horses) or ≤20 mm (barefoot horses). The 24 riding horses were re-evaluated 4-6 weeks later and the 10 broodmares 1 week after trimming. The results showed that of the 67 riding horses, 75% were positive for gluteal pain at initial evaluation. The mean BD for the positive and negative horses was 24.2 ± 1.3 mm and 18.8 ± 2.0 mm, respectively (p = 0.04). At the next shoeing, the mean BD was 10.9 ± 2.3 mm and gluteal pain was improved in all 24 horses; 20 horses (83%) were negative and 4 horses (17%) were now only mildly positive. The 10 broodmares were all positive for gluteal pain initially. The mean BD before and after trimming was 23.7 ± 1.2 mm and 10.9 ± 1.1 mm, respectively. One week later, gluteal pain was improved in all 10 mares; 8 mares (80%) were negative, and the other 2 mares (20%) were only mildly positive. The conclusion is that excessive toe length in the hind feet may be accompanied by pain in the gluteal region and, in our experience, may be associated with gait or performance problems. Shortening the toe can alleviate this pain within days or weeks. Aiming for a BD of between 0 and 20 mm probably is appropriate for the average-size horse.}, number={12}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Mansmann, Richard A. and James, Sarah and Blikslager, Anthony T. and Orde, Kurt}, year={2010}, month={Dec}, pages={720–726} }
 @article{marshall_blikslager_2010, title={M1863 Indomethacin Impedes Recovery From Hypoxia-Reoxygenation in CACO-2 Cells}, volume={138}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(10)62006-9}, DOI={10.1016/S0016-5085(10)62006-9}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Marshall, John and Blikslager, Anthony T.}, year={2010}, month={May}, pages={S-434} }
 @article{blikslager_2010, title={Mucosal epithelial barrier repair to maintain pig health}, volume={133}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77957158589&partnerID=MN8TOARS}, DOI={10.1016/j.livsci.2010.06.062}, abstractNote={Mucosal barrier function is critical to prevent translocation of microorganisms and their toxins. The intestinal barrier is made up of a single layer of columnar epithelium that can be readily breached by enteric infections, but has a tremendous capacity to repair. Thus, mucosal epithelial repair is one of the most critical elements of maintaining an intact barrier. In the small intestine, villous contraction is the initial phase of repair. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. However, restoration of a continuous layer of epithelium is insufficient to restore barrier function. Recent ex vivo studies of porcine small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in porcine tissues to prevent the onset of sepsis.}, number={1-3}, journal={Livestock Science}, author={Blikslager, A.T.}, year={2010}, pages={194–199} }
 @inbook{blikslager_2010, place={St. Louis, MO}, edition={3rd edition}, title={Obstructive disorders of the gastrointestinal tract}, booktitle={Equine Internal Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T.}, editor={Reed, S.M. and Bayly, W.M. and Sellon, D.C.Editors}, year={2010}, pages={882–892} }
 @inbook{blikslager_2010, place={St. Louis, MO}, edition={3rd edition}, title={Pathophysiology of mucosal injury and repair}, booktitle={Equine Internal Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T.}, editor={Reed, S.M. and Bayly, W.M. and Sellon, D.C.Editors}, year={2010}, pages={794–802} }
 @article{nighot_turner_lee_blikslager_2010, title={S1779 The Chloride Channel CLC-2 Modulates Early Barrier Development in CACO-2 Cells}, volume={138}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(10)61250-4}, DOI={10.1016/S0016-5085(10)61250-4}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Turner, Rachel C. and Lee, Sung H. and Blikslager, Anthony T.}, year={2010}, month={May}, pages={S-272} }
 @article{kajino-sakamoto_omori_nighot_blikslager_matsumoto_ninomiya-tsuji_2010, title={TGF-β–Activated Kinase 1 Signaling Maintains Intestinal Integrity by Preventing Accumulation of Reactive Oxygen Species in the Intestinal Epithelium}, volume={185}, ISSN={0022-1767 1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.0903587}, DOI={10.4049/jimmunol.0903587}, abstractNote={The intestinal epithelium is constantly exposed to inducers of reactive oxygen species (ROS), such as commensal microorganisms. Levels of ROS are normally maintained at nontoxic levels, but dysregulation of ROS is involved in intestinal inflammatory diseases. In this article, we report that TGF-β-activated kinase 1 (TAK1) is a key regulator of ROS in the intestinal epithelium. tak1 gene deletion in the mouse intestinal epithelium caused tissue damage involving enterocyte apoptosis, disruption of tight junctions, and inflammation. Disruption of TNF signaling, which is a major intestinal damage inducer, rescued the inflammatory conditions but not apoptosis or disruption of tight junctions in the TAK1-deficient intestinal epithelium, suggesting that TNF is not a primary inducer of the damage noted in TAK1-deficient intestinal epithelium. We found that TAK1 deficiency resulted in reduced expression of several antioxidant-responsive genes and reduced the protein level of a key antioxidant transcription factor NF-E2-related factor 2, which resulted in accumulation of ROS. Exogenous antioxidant treatment reduced apoptosis and disruption of tight junctions in the TAK1-deficient intestinal epithelium. Thus, TAK1 signaling regulates ROS through transcription factor NF-E2-related factor 2, which is important for intestinal epithelial integrity.}, number={8}, journal={The Journal of Immunology}, publisher={The American Association of Immunologists}, author={Kajino-Sakamoto, Rie and Omori, Emily and Nighot, Prashant K. and Blikslager, Anthony T. and Matsumoto, Kunihiro and Ninomiya-Tsuji, Jun}, year={2010}, month={Sep}, pages={4729–4737} }
 @article{moeser_blikslager_tonkonogy_keku_2009, title={665 The Role of the Intestinal Microbiota in Colonic Barrier Dysfunction Induced By Neonatal Stress}, volume={136}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(09)60460-1}, DOI={10.1016/S0016-5085(09)60460-1}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Moeser, Adam J. and Blikslager, Anthony T. and Tonkonogy, Susan L. and Keku, Temitope O.}, year={2009}, month={May}, pages={A-102} }
 @article{cook_jones shults_mcdowell_campbell_davis_marshall_blikslager_2009, title={Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.10.1259}, DOI={10.2460/ajvr.70.10.1259}, abstractNote={To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine.24 horses.Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejunal specimens were collected after the ischemic period and after euthanasia 18 hours later for histologic assessment and determination of cyclooxygenase (COX) expression (via western blot procedures). Plasma samples collected prior to (baseline) and 8 hours after the ischemic period were analyzed for prostanoid concentrations.Immediately after the ischemic period, COX-2 expression in horses treated with lidocaine alone was significantly less than expression in horses treated with SS or flunixin alone. Eighteen hours after the ischemic period, mucosal neutrophil counts in horses treated with flunixin alone were significantly higher than counts in other treatment groups. Compared with baseline plasma concentrations, postischemia prostaglandin E(2) metabolite and thromboxane B(2) concentrations increased in horses treated with SS and in horses treated with SS or lidocaine alone, respectively.In horses with ischemia-injured jejunum, lidocaine administered IV reduced plasma prostaglandin E(2) metabolite concentration and mucosal COX-2 expression. Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts.}, number={10}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Jones Shults, Jennifer and McDowell, Marsha R. and Campbell, Nigel B. and Davis, Jennifer L. and Marshall, John F. and Blikslager, Anthony T.}, year={2009}, month={Oct}, pages={1259–1268} }
 @inbook{blikslager_2009, place={St. Louis}, edition={6th edition}, title={Cecal impaction}, booktitle={Current Therapy in Equine Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T.}, editor={Robinson, N.E. and Sprayberry, K.A.Editors}, year={2009}, pages={405–407} }
 @article{nighot_moeser_ryan_ghashghaei_blikslager_2009, title={ClC-2 is required for rapid restoration of epithelial tight junctions in ischemic-injured murine jejunum}, volume={315}, ISSN={0014-4827}, url={http://dx.doi.org/10.1016/j.yexcr.2008.10.001}, DOI={10.1016/j.yexcr.2008.10.001}, abstractNote={Involvement of the epithelial chloride channel ClC-2 has been implicated in barrier recovery following ischemic injury, possibly via a mechanism involving ClC-2 localization to the tight junction. The present study investigated mechanisms of intestinal barrier repair following ischemic injury in ClC-2−/− mice. Wild type, ClC-2 heterozygous and ClC-2−/− murine jejunal mucosa was subjected to complete ischemia, after which recovery of barrier function was monitored by measuring in vivo blood-to-lumen clearance of 3H-mannitol. Tissues were examined by light and electron microscopy. The role of ClC-2 in re-assembly of the tight junction during barrier recovery was studied by immunoblotting, immunolocalization and immunoprecipitation. Following ischemic injury, ClC-2−/− mice had impaired barrier recovery compared to wild type mice, defined by increases in epithelial paracellular permeability independent of epithelial restitution. The recovering ClC-2−/− mucosa also had evidence of ultrastructural paracellular defects. The tight junction proteins occludin and claudin-1 shifted significantly to the detergent soluble membrane fraction during post-ischemic recovery in ClC-2−/− mice whereas wild type mice had a greater proportion of junctional proteins in the detergent insoluble fraction. Occludin was co-immunoprecipitated with ClC-2 in uninjured wild type mucosa, and the association between occludin and ClC-2 was re-established during ischemic recovery. Based on immunofluorescence studies, re-localization of occludin from diffuse sub-apical areas to apical tight junctions was impaired in ClC-2−/− mice. These data demonstrate a pivotal role of ClC-2 in recovery of the intestinal epithelium barrier by anchoring assembly of tight junctions following ischemic injury.}, number={1}, journal={Experimental Cell Research}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Moeser, Adam J. and Ryan, Kathleen A. and Ghashghaei, Troy and Blikslager, Anthony T.}, year={2009}, month={Jan}, pages={110–118} }
 @article{cook_meyer_campbell_blikslager_2009, title={Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.8.992}, DOI={10.2460/ajvr.70.8.992}, abstractNote={To determine whether treatment of horses with firocoxib affects recovery of ischemic-injured jejunum, while providing effective analgesia.18 horses.Horses (n = 6 horses/group) received saline (0.9% NaCl) solution (1 mL/50 kg, IV), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or firocoxib (0.09 mg/kg, IV, q 24 h) before 2 hours of jejunal ischemia. Horses were monitored via pain scores and received butorphanol for analgesia. After 18 hours, ischemic-injured and control mucosa were placed in Ussing chambers for measurement of transepithelial resistance and permeability to lipopolysaccharide. Histomorphometry was used to determine denuded villus surface area. Western blots for cyclooxygenase (COX)-1 and COX-2 were performed. Plasma thromboxane B(2) and prostaglandin E(2) metabolite (PGEM) concentrations were determined.Pain scores did not significantly increase after surgery in horses receiving flunixin meglumine or firocoxib. Transepithelial resistance of ischemic-injured jejunum from horses treated with flunixin meglumine was significantly lower than in saline- or firocoxib-treated horses. Lipopolysaccharide permeability across ischemic-injured mucosa was significantly increased in horses treated with flunixin meglumine. Treatment did not affect epithelial restitution. Cyclooxygenase-1 was constitutively expressed and COX-2 was upregulated after 2 hours of ischemia. Thromboxane B(2) concentration decreased with flunixin meglumine treatment but increased with firocoxib or saline treatment. Flunixin meglumine and firocoxib prevented an increase in PGEM concentration after surgery.Flunixin meglumine retarded mucosal recovery in ischemic-injured jejunum, whereas firocoxib did not. Flunixin meglumine and firocoxib were effective visceral analgesics. Firocoxib may be advantageous in horses recovering from ischemic intestinal injury.}, number={8}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Meyer, Colleen T. and Campbell, Nigel B. and Blikslager, Anthony T.}, year={2009}, month={Aug}, pages={992–1000} }
 @article{wooten_blikslager_marks_law_graeber_lascelles_2009, title={Effect of nonsteroidal anti-inflammatory drugs with varied cyclooxygenase-2 selectivity on cyclooxygenase protein and prostanoid concentrations in pyloric and duodenal mucosa of dogs}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.10.1243}, DOI={10.2460/ajvr.70.10.1243}, abstractNote={Abstract Objective —To assess in vivo effects of short-term administration of NSAIDs with varied cyclooxygenase (COX)-2 selectivity on pyloric and duodenal mucosa. Animals —8 healthy dogs. Procedures —Each dog received deracoxib (2 mg/kg, PO, q 24 h for 3 days), firocoxib (5 mg/kg, PO, q 24 h for 3 days), meloxicam (0.2 mg/kg, PO, q 24 h for 1 day followed by 0.1 mg/kg, PO, q 24 h for 2 days), or placebo orally for 3 days; there was a 4-week interval between successive treatments. Prior to and on day 3 of drug administration, pyloric and duodenal mucosae were assessed endoscopically and biopsy specimens obtained for histologic examination. Cyclooxygenase-1 and -2 protein expressions were assessed (western blotting) and prostanoid concentrations measured (ELISAs). Data were analyzed by use of an ANOVA. Results —Drug administration did not significantly affect endoscopic mucosal scores, histologic scores, or COX-1 or -2 protein expression. The COX-1 protein expression was significantly higher in the pylorus than in the duodenum. Total prostaglandin and thromboxane B 2 (TXB 2 ) concentrations were significantly greater in pyloric than in duodenal mucosa. Drug administration had no effect on prostaglandin or TXB 2 concentrations. Conclusions and Clinical Relevance —Prostanoid concentrations in gastric and duodenal tissues, and gross and histologic appearances, were not significantly affected by drugs with varied COX-2 selectivity. These findings suggested that, for these experimental conditions, there were no differences among the preferential and selective COX-2 inhibitors with regard to adverse effects on the gastric and duodenal portions of the gastrointestinal tract of dogs.}, number={10}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wooten, Jenna G. and Blikslager, Anthony T. and Marks, Steve L. and Law, J. Mac and Graeber, Elizabeth C. and Lascelles, B. Duncan X.}, year={2009}, month={Oct}, pages={1243–1249} }
 @article{morton_grosche_rötting_matyjaszek_blikslager_freeman_2009, title={Expression of cyclooxygenase-1 and -2 in the left dorsal colon after different durations of ischemia and reperfusion in horses}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.12.1536}, DOI={10.2460/ajvr.70.12.1536}, abstractNote={Abstract Objective —To identify expression and localization of cyclooxygenase (COX)-1 and COX-2 in healthy and ischemic-injured left dorsal colon of horses. Sample Population —Left dorsal colon tissue samples from 40 horses. Procedures —Tissue samples that were used in several related studies on ischemia and reperfusion were evaluated. Samples were collected during anesthesia, before induction of ischemia, and following 1 hour of ischemia, 1 hour of ischemia and 30 minutes of reperfusion, 2 hours of ischemia, 2 hours of ischemia and 30 minutes of reperfusion, and 2 hours of ischemia and 18 hours of reperfusion. Histomorphometric analyses were performed to characterize morphological injury. Immunohistochemical analyses were performed to characterize expression and localization of COX-1 and COX-2. Results —COX-1 and COX-2 were expressed in control tissues before ischemia was induced, predominantly in cells in the lamina propria. Ischemic injury significantly increased expression of COX-2 in epithelial cells on the colonic surface and in crypts. A similar significant increase of COX-1 expression was seen in the epithelial cells. Conclusions and Clinical Relevance —On the basis of information on the role of COX-2, upregulation of COX-2 in surface epithelium and crypt cells following ischemic injury in equine colon may represent an early step in the repair process.}, number={12}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Morton, Alison J. and Grosche, Astrid and Rötting, Anna K. and Matyjaszek, Sarah A. and Blikslager, Anthony T. and Freeman, David E.}, year={2009}, month={Dec}, pages={1536–1544} }
 @article{nighot_moeser_blikslager_2009, title={M1698 Clc-2 Regulates Mucosal Barrier Function Associated with Structural Changes to the Villus and Early Co-Localization with Occludin}, volume={136}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(09)61898-9}, DOI={10.1016/S0016-5085(09)61898-9}, abstractNote={(45+5 CFU/ml) after 1hr exposure to EIEC. Pretreatment of HT29 cells with either recombinant Muc17/Muc3 cysteine rich domain protein or a crude mucin preparation significantly increased TER by 12.5-25% after EIEC incubation compared with no treatment. Conclusion: Reduction of endogenous MUC17 is associated with reduced cell adherence, aggregation, and migration and increased apoptosis in response to exogenous toxins. This correlated with increased permeability, iNOS and COX2 induction, and bacterial invasion in response to EIEC exposure. Exogenous recombinant MUC17/Muc3 also enhanced cell integrety in response to EIEC. These data suggest that both native and exogenous MUC17 play a role in attachment and invasion of EIEC in colonic cell lines and/or play a role in maintaining elements of epithelial barrier function such as anti-apoptosis or permeability.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Moeser, Adam J. and Blikslager, Anthony T.}, year={2009}, month={May}, pages={A-413} }
 @inbook{blikslager_2009, place={St. Louis, MO}, edition={6th edition}, title={Non-steroidal anti-inflammatory}, booktitle={Current Therapy in Equine Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T.}, editor={Robinson, N.E. and Sprayberry, K.A.Editors}, year={2009}, pages={7–10} }
 @inbook{blikslager_2009, place={Jackson, WY}, title={Pathophysiology of gastrointestinal disease: obstruction and strangulation}, booktitle={The Equine Acute Abdomen}, publisher={Teton New Media}, author={Blikslager, A.T.}, editor={White, N.A. and Moore, J.N. and Mair, T.S.Editors}, year={2009}, pages={100–107} }
 @inbook{blikslager_jones_2009, place={St. Louis, MO}, edition={4th edition}, title={Surgical disorders of the large intestine}, booktitle={Large Animal Internal Medicine}, publisher={Mosby}, author={Blikslager, A.T. and Jones, S.L.}, editor={Smith, B.P.Editor}, year={2009}, pages={750–755} }
 @inbook{blikslager_jones_2009, place={St. Louis, MO}, edition={4th edition}, title={Surgical disorders of the small intestine}, booktitle={Large Animal Internal Medicine}, publisher={Mosby}, author={Blikslager, A.T. and Jones, S.L.}, editor={Smith, B.P.Editor}, year={2009}, pages={732–737} }
 @article{cook_neuder_blikslager_jones_2009, title={The effect of lidocaine on in vitro adhesion and migration of equine neutrophils}, volume={129}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2008.12.017}, DOI={10.1016/j.vetimm.2008.12.017}, abstractNote={The effect of lidocaine on in vitro migration and adhesion of equine neutrophils was evaluated. Neutrophils were isolated from equine whole blood using a Percoll-gradient centrifugation protocol. Purified neutrophils were incubated with lidocaine at concentrations from 0.1 to 1000 microg/ml for 30 min at 37 degrees C, after calcein loading. Neutrophil integrin-mediated adhesion in response to stimulation with 100 nM LTB(4), 100 nM PAF, or 100 ng/ml IL-8, or integrin-mediated migration in response to stimulation with 100 nM LTB(4), 150 nM PAF, or 100 ng/ml IL-8 was assessed. Statistical significance was set at P<0.05. Neutrophil adhesion was significantly increased in response to all three stimulants. IL-8-stimulated adhesion was significantly increased when neutrophils were incubated with 1mg/ml lidocaine, compared to lower lidocaine concentrations. LTB(4)-stimulated adhesion was significantly increased when neutrophils were incubated with 1mg/ml lidocaine compared to that at 5 microg/ml lidocaine. Migration was significantly increased in response to IL-8. IL-8 and LTB(4) stimulated migration was significantly increased when neutrophils were incubated with 1mg/ml lidocaine, compared to lower lidocaine concentrations. In conclusion, lidocaine did not inhibit neutrophil migration or adhesion in vitro at therapeutic concentrations, and increased migration and adhesion at higher concentrations.}, number={1-2}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Cook, Vanessa L. and Neuder, Laura E. and Blikslager, Anthony T. and Jones, Samuel L.}, year={2009}, month={May}, pages={137–142} }
 @article{sheats_cook_jones_blikslager_pease_2009, title={Use of ultrasound to evaluate outcome following colic surgery for equine large colon volvulus}, volume={42}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.2746/042516409X456040}, DOI={10.2746/042516409X456040}, abstractNote={The post operative response of the large colon wall after a surgically corrected large colon volvulus (LCV) has not been investigated.To use transabdominal ultrasound to monitor the post operative change in large colon wall thickness following surgical correction of LCV.A prolonged period to colon wall involution is correlated with an increased rate of post operative morbidity and mortality.A prospective clinical study including horses that presented to the North Carolina State University Veterinary Teaching Hospital for colic between September 2006 and March, 2008, had surgically diagnosed and corrected LCV (at least 360 degrees ) without resection and recovered from anaesthesia. Ultrasound of the ventral large colon was performed at the time of anaesthetic recovery and every 6-8 h until the colon wall returned to normal thickness (< or = 5 mm). Outcome was evaluated using a one-way ANOVA to compare average time to colon wall involution between: 1) survivors and nonsurvivors; and 2) horses that developed multiple organ dysfunction syndrome (MODS) during the post operative period and those that recovered without evidence of MODS.Sixteen horses that recovered without evidence of MODS had a significantly shorter period to colon wall involution (< or = 5 mm) compared to those diagnosed with MODS (mean +/- s.e. 19.6 h +/- 2.5 and 39.7 h +/- 6.7 respectively, P = 0.006). There was no significant difference in mean period to colon wall involution between survivors and nonsurvivors (26.2 +/- 4.9 and 33.2 +/- 7.8 h, respectively).A shorter time to colon wall involution was associated with decreased post operative morbidity in horses presented for surgical correction of large colon volvulus without resection.Ultrasonographic monitoring of colon wall involution after surgical correction of LCV may aid in identifying those cases at risk of MODS. Further investigation of colon wall involution time using a larger number of horses is warranted.}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Sheats, M. K. and Cook, V. L. and Jones, S. L. and Blikslager, A. T. and Pease, A. P.}, year={2009}, month={Dec}, pages={47–52} }
 @article{fogle_gerard_elce_little_morton_correa_blikslager_2008, title={Analysis of Sodium Carboxymethylcellulose Administration and Related Factors Associated with Postoperative Colic and Survival in Horses with Small Intestinal Disease}, volume={37}, ISSN={0161-3499 1532-950X}, url={http://dx.doi.org/10.1111/j.1532-950X.2008.00420.x}, DOI={10.1111/j.1532-950X.2008.00420.x}, abstractNote={To analyze the effect of the intraoperative use of sodium carboxymethylcellulose (CBMC) and related perioperative factors on postoperative colic and survival in horses that had abdominal surgery for colic.Retrospective study.Horses (n=203) that had surgery for small intestinal disease; 33 horses had intraoperative administration of CBMC.Information was obtained from medical records for 170 horses that had surgery for colic before use of CBMC and 33 horses that had intraoperative CBMC. Kaplan-Meier survival curves were used to estimate median survival time and a Cox proportional hazards model was used to estimate the hazard ratio for the effect of CBMC and other perioperative variables on survival.Seventy-five percent of horses administered CBMC survived to 180 days, whereas 75% of untreated horses survived 8 days (median survival time=18 days). Horses not administered CBMC were twice as likely to die compared with horses administered CBMC. Horses that had postoperative ileus (POI) were 1.4 times more likely to die than horses without ileus. Similarly, horses with signs of colic after surgery were 1.3 times more likely to die than horses without postoperative signs of colic.CBMC administration is seemingly protective against death and prolongs survival when used intraoperatively in horses with small intestine disease, particularly horses with postoperative colic or POI. Both POI and colic increased risk of death after surgery.Intraoperative administration of CBMC in horses that have surgery for small intestinal disease may improve survival, possibly by reducing early adhesion formation.}, number={6}, journal={Veterinary Surgery}, publisher={Wiley}, author={Fogle, Callie A. and Gerard, Mathew P. and Elce, Yvonne A. and Little, Dianne and Morton, Alison J. and Correa, Maria T. and Blikslager, Anthony T.}, year={2008}, month={Aug}, pages={558–563} }
 @article{corl_odle_niu_moeser_gatlin_phillips_blikslager_rhoads_2008, title={Arginine Activates Intestinal p70S6k and Protein Synthesis in Piglet Rotavirus Enteritis}, volume={138}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.1093/jn/138.1.24}, DOI={10.1093/jn/138.1.24}, abstractNote={We previously showed that phosphorylation of p70 S6 kinase (p70(S6k)) in the intestine is increased during viral enteritis. In this study, we hypothesized that during rotavirus infection, oral Arg, which stimulates p70(S6k) activation, will further stimulate intestinal protein synthesis and mucosal recovery, whereas the p70(S6k) inhibitor rapamycin (Rapa) will inhibit mucosal recovery. Newborn piglets were fed a standard milk replacer diet supplemented with Arg (0.4 g x kg(-1) x d(-1), twice daily by gavage), Rapa (2 mg x m(-2) x d(-1)), Arg + Rapa, or saline (controls). They were infected on d 6 of life with porcine rotavirus. Three days postinoculation, we measured the piglets' body weight, fecal rotavirus excretion, villus-crypt morphology, epithelial electrical resistance in Ussing chambers, and p70(S6k) activation by Western blotting and immunohistochemistry. We previously showed a 2-fold increase in jejunal protein synthesis during rotavirus diarrhea. In this experiment, Arg stimulated jejunal protein synthesis 1.3-fold above standard medium, and the Arg stimulation was partially inhibited by Rapa. Small bowel stimulation of p70(S6k) phosphorylation and p70(S6k) levels were inhibited >80% by Rapa. Immunohistochemistry revealed a major increase of p70(S6k) and ribosomal protein S6 phosphorylation in the crypt and lower villus of the infected piglets. However, in Arg-treated piglets, p70(S6k) activation occurred over the entire villus. Jejunal villi of the Rapa-treated group showed inactivation of p70(S6k) and a decrease in mucosal resistance (reflecting increased permeability), the latter of which was reversed by Arg. We conclude that, early in rotavirus enteritis, Arg has no impact on diarrhea but augments intestinal protein synthesis in part by p70(S6k) stimulation, while improving intestinal permeability via a mammalian target of rapamycin/p70(S6k)-independent mechanism.}, number={1}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Corl, Benjamin A. and Odle, Jack and Niu, Xiaomei and Moeser, Adam J. and Gatlin, Lori A. and Phillips, Oulayvanh T. and Blikslager, Anthony T. and Rhoads, J. Marc}, year={2008}, month={Jan}, pages={24–29} }
 @article{corl_odle_niu_moeser_gatlin_phillips_blikslager_rhoads_2008, title={Arginine activates intestinal p70S6k and protein synthesis in piglet rotavirus enteritis}, volume={138}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-38149032281&partnerID=MN8TOARS}, number={1}, journal={Journal of Nutrition}, author={Corl, B.A. and Odle, J. and Niu, X. and Moeser, A.J. and Gatlin, L.A. and Phillips, O.T. and Blikslager, A.T. and Rhoads, J.M.}, year={2008}, pages={24–29} }
 @article{cook_shults_mcdowell_campbell_davis_blikslager_2008, title={Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine}, volume={40}, DOI={10.2746/04251640SX293574}, number={4}, journal={Equine Veterinary Journal}, author={Cook, V. L. and Shults, J. J. and McDowell, M. and Campbell, N. B. and Davis, J. L. and Blikslager, Anthony}, year={2008}, pages={353–357} }
 @article{cook_shults_mcdowell_campbell_davis_blikslager_2008, title={Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine}, volume={40}, ISSN={0425-1644}, url={http://dx.doi.org/10.2746/042516408X293574}, DOI={10.2746/042516408x293574}, abstractNote={Reasons for performing study: Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. Hypothesis: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. Methods: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine and lidocaine, with 6 horses allocated randomly to each group. Two sections of jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local blood supply, via a midline celiotomy. Horses were monitored with a behavioural pain score and were subjected to euthanasia 18 h after reversal of ischaemia. Ischaemic-injured and control jejunum was mounted in Ussing chambers for measurement of transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS). Results: In ischaemic-injured jejunum TER was significantly higher in horses treated with saline, lidocaine or lidocaine and flunixin meglumine combined, compared to horses treated with flunixin meglumine. In ischaemic-injured jejunum LPS permeability was significantly increased in horses treated with flunixin meglumine alone. Behavioural pain scores did not increase significantly after surgery in horses treated with flunixin meglumine. Conclusions: Treatment with systemic lidocaine ameliorated the inhibitory effects of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury, when the 2 treatments were combined. The mechanism of lidocaine in improving mucosal repair has not yet been elucidated. Potential relevance: Recovery of ischaemic-injured jejunum in post operative colic cases may be improved when treatment with flunixin meglumine is combined with lidocaine.}, number={4}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Cook, V. L. and Shults, J. Jones and McDowell, M. and Campbell, N. B. and Davis, J. L. and Blikslager, A. T.}, year={2008}, month={Jun}, pages={353–357} }
 @article{moeser_nighot_roerig_ueno_blikslager_2008, title={Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine}, volume={14}, ISSN={1007-9327}, url={http://dx.doi.org/10.3748/wjg.14.6012}, DOI={10.3748/wjg.14.6012}, abstractNote={To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine.Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function.Application of 1 micromol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of (3)H-mannitol and (14)C-inulin.This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.}, number={39}, journal={World Journal of Gastroenterology}, publisher={Baishideng Publishing Group Inc.}, author={Moeser, Adam J and Nighot, Prashant K and Roerig, Birgit and Ueno, Ryuji and Blikslager, Anthony T}, year={2008}, pages={6012} }
 @article{wooten_blikslager_ryan_marks_law_lascelles_2008, title={Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs}, volume={69}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.69.4.457}, DOI={10.2460/ajvr.69.4.457}, abstractNote={Abstract Objective —To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Animals —8 healthy dogs. Procedures —Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Before study commencement (baseline) and on day 3 of each treatment, pyloric and duodenal mucosal appearance was assessed endoscopically and biopsy specimens were obtained for histologic examination. Cyclooxygenase-1 and COX-2 protein expressions were assessed via western blotting, and prostanoid concentrations were measured via ELISAs. An ANOVA was used to analyze data. Results —Treatments had no effect on mucosal appearance and ulceration was not evident histologically. In pyloric and duodenal mucosae, COX-1 expression was unaffected by treatments. Cyclooxygenase-2 expression remained unchanged in pyloric mucosa; in duodenal mucosa, aspirin significantly increased COX-2 expression, compared with effects of deracoxib and carprofen. At baseline, total prostaglandin and thromboxane B 2 concentrations in pyloric mucosa were significantly greater than those in duodenal mucosa. Aspirin significantly decreased both prostanoid concentrations in both mucosal tissues, compared with other treatments. In pyloric mucosa, carprofen administration significantly decreased total prostaglandin and thromboxane B 2 concentrations, compared with deracoxib administration. Conclusions and Clinical Relevance —In dogs, prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of a selective COX-2 NSAID.}, number={4}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wooten, Jenna G. and Blikslager, Anthony T. and Ryan, Kathleen A. and Marks, Steve L. and Law, J. Mac and Lascelles, B. Duncan X.}, year={2008}, month={Apr}, pages={457–464} }
 @article{moeser_blikslager_swanson_2008, title={Determination of minimum alveolar concentration of sevoflurane in juvenile swine}, volume={84}, ISSN={0034-5288}, url={http://dx.doi.org/10.1016/j.rvsc.2007.03.015}, DOI={10.1016/j.rvsc.2007.03.015}, abstractNote={Pigs are important animal models in veterinary and medical research and have been widely used in experiments requiring surgical anesthesia. Sevoflurane is an inhalant anesthetic with unique properties that make it an ideal anesthetic for mask induction and anesthesia maintenance. However, there are relatively few studies reporting the anesthetic requirements for sevoflurane in juvenile swine, an age group that is commonly used in research experiments. Therefore the objective of this study was to determine the Minimum Alveolar Concentration (MAC) for sevoflurane in juvenile swine. Sevoflurane anesthesia was induced in six Yorkshire-cross pigs of approximately 9 weeks-of-age and MAC for sevoflurane was determined. The sevoflurane MAC value was determined to be 3.5+/-0.1% which is notably higher than values reported in the literature for pigs. This discrepancy in MAC values may represent changes in anesthetic requirements between different age groups of pigs and differences in the type of stimulus used to determine MAC.}, number={2}, journal={Research in Veterinary Science}, publisher={Elsevier BV}, author={Moeser, Adam J. and Blikslager, Anthony T. and Swanson, Cliff}, year={2008}, month={Apr}, pages={283–285} }
 @article{hess_corl_lin_jacobi_harrell_blikslager_odle_2008, title={Enrichment of Intestinal Mucosal Phospholipids with Arachidonic and Eicosapentaenoic Acids Fed to Suckling Piglets Is Dose and Time Dependent}, volume={138}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.108.094136}, DOI={10.3945/jn.108.094136}, abstractNote={Infant formula companies began fortifying formulas with long-chain PUFA in 2002, including arachidonic acid (ARA) at ∼0.5% of total fatty acids. The primary objective of this study was to determine the time-specific effects of feeding formula enriched with supra-physiologic ARA on fatty acid composition of intestinal mucosal phospholipids. One-day-old pigs (n = 96) were fed a milk-based formula for 4, 8, or 16 d. Diets contained either no PUFA (0% ARA, negative control), 0.5% ARA, 2.5% ARA, 5% ARA, or 5% eicosapentaenoic acid (EPA) of total fatty acids (wt:wt). Growth (299 ± 21 g/d) and clinical hematology were unaffected by treatment (P > 0.6). Although minimal on d 4, concentrations of ARA in jejunal mucosa were enriched 47, 272 and 428% by d 8 and 144, 356, and 415% by d 16 in pigs fed the 0.5% ARA, 2.5% ARA, and 5% ARA diets, respectively, compared with the 0% ARA control pigs (P < 0.01). On d 16, ARA enrichment increased progressively with increasing dietary ARA supplementation from 0 to 2.5% but plateaued as dietary ARA rose to 5%. A similar pattern of ARA enrichment was observed in ileal mucosal phospholipids, but maximal enrichment in the ileum exceed that in the jejunum by >50%. As ARA increased, linoleic acid content decreased reciprocally. Although maximal enterocyte enrichment with EPA approached 20-fold by d 8, concentrations were only ∼50% of those attained for ARA. Negligible effects on gross villus/crypt morphology were observed. These data demonstrate a dose-dependent response of intestinal mucosal phospholipid ARA concentration to dietary ARA with nearly full enrichment attained within 8 d of feeding formula containing ARA at 2.5% of total fatty acids and that supra-physiologic supplementation of ARA is not detrimental to growth.}, number={11}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Hess, Holly A. and Corl, Benjamin A. and Lin, Xi and Jacobi, Sheila K. and Harrell, Robert J. and Blikslager, Anthony T. and Odle, Jack}, year={2008}, month={Nov}, pages={2164–2171} }
 @article{blikslager_2008, title={Equine colic | La colica degli equini}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70349887661&partnerID=MN8TOARS}, number={3}, journal={Ippologia}, author={Blikslager, A.T.}, year={2008}, pages={21–33} }
 @article{blikslager_2008, title={Life in the Gut Without Oxygen: Adaptive Mechanisms and Inflammatory Bowel Disease}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1053/j.gastro.2007.11.049}, DOI={10.1053/j.gastro.2007.11.049}, abstractNote={See “Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition” by Robinson A, Keely S, Karhausen J, et al on page 145; and “The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis” by Cummins EP, Seeballuck F, Keely SJ, et al on page 156. See “Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition” by Robinson A, Keely S, Karhausen J, et al on page 145; and “The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis” by Cummins EP, Seeballuck F, Keely SJ, et al on page 156. The epithelium that lines the intestine exists in a constant state of hypoxia. In the small intestine, this has classically been explained by a countercurrent exchange mechanism, wherein oxygen from arterial blood entering the villi diffuses across to neighboring venules traveling from the tip down toward the base of the villus.1Shepherd A.P. Local control of intestinal oxygenation and blood flow.Annu Rev Physiol. 1982; 44: 13-27Google Scholar The crucial components of countercurrent exchange are in close proximity of a tubular or vascular supply with components traveling in the opposite direction at a low velocity, a semipermeable membrane, and differing concentrations of a solute. All of these components are present in the small intestine, with resultant countercurrent exchange of oxygen and relatively hypoxic villous tips. However, there appear to be other reasons for intestinal epithelial hypoxia because it is also present in the colon where there are no villi. The easiest explanation for this is the distance of the epithelium from the vascular supply, so that most of the oxygen has been taken up by subepithelial tissues before oxygenated blood reaches the level of the epithelium. Regardless of the mechanism, a steep oxygen gradient has been documented in the gut.1Shepherd A.P. Local control of intestinal oxygenation and blood flow.Annu Rev Physiol. 1982; 44: 13-27Google Scholar This is important, because, without oxygen, transport mechanisms and barrier function become disrupted. In fact, the intestine is one of the most energy-demanding organ systems because of the Na+/K+ ATPase, an epithelial basolateral transporter that is critical to intestinal function. Additional energy is required to fuel maintenance of barrier function, including interepithelial tight junctions, which are heavily laden with signaling molecules. Fortunately, the apical epithelium has developed adaptive mechanisms that allow it to function in an environment without optimal oxygenation. Aside from reduced oxygen availability, the intestinal mucosa has to respond to microorganisms in its lumen in an appropriate way to avoid developing an inflammatory response. Some patients may not respond appropriately to luminal bacteria, possibly resulting in inflammatory bowel disease (IBD), depending on other factors involved in development of disease.2Sartor R.B. Innate immunity in the pathogenesis and therapy of IBD.J Gastroenterol. 2003; 38: 43-47Google Scholar Currently, investigators are attempting to determine which bacteria are likely candidates for triggering IBD under specific circumstances.3Sartor R.B. Blumberg R.S. Braun J. et al.CCFA microbial-host interactions workshop: highlights and key observations.Inflamm Bowel Dis. 2007; 13: 600-619Google Scholar Additional factors may influence the development of IBD, including genetic influences and lifestyle.4Xavier R.J. Podolsky D.K. Unravelling the pathogenesis of inflammatory bowel disease.Nature. 2007; 448: 427-434Google Scholar Furthermore, Robinson et al point out in this issue of Gastroenterology that it has recently been recognized that hypoxia is a feature of IBD, and may in some way influence inflammation.5Robinson A. Keely S. Karhausen J. et al.Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition.Gastroenterology. 2008; 134: 145-155Abstract Full Text Full Text PDF Scopus (288) Google Scholar, 6Karthausen J. Haase V.H. Colgan S.P. Inflammatory hypoxia: role of hypoxia-inducible factor.Cell Cycle. 2005; 4: 256-258Google Scholar Until these mechanisms can be better understood, a number of investigators use simplified murine models of IBD in which injurious agents such as detergents are administered. The most common detergents used are DSS and TNBS, which cause epithelial injury and subsequent inflammation. A critical component of the adaptive response to hypoxia is the regulation of molecules that protect the mucosal epithelium, including hypoxia inducible factor (HIF). However, this transcription factor is degraded by hydroxylation under normal conditions, presumably because of overlapping protective and adaptive mechanisms that allow the gut to continue to transport and maintain a barrier under conditions of “physiologic hypoxia” (a term adopted by Robinson et al5Robinson A. Keely S. Karhausen J. et al.Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition.Gastroenterology. 2008; 134: 145-155Abstract Full Text Full Text PDF Scopus (288) Google Scholar). When the gut is subjected to pathophysiologic levels of hypoxia, HIF is stabilized and helps to protect the intestine from injury.7Kong T. Westerman K.A. Faigle M. et al.HIF-dependent induction of adenosine A2B receptor in hypoxia.FASEB J. 2006; 20: 2242-2250Google Scholar In this issue of Gastroenterology, two groups show that HIF can be used to protect the intestine from detergent-induced IBD in rodents (Figure 1). In the study by Robinson et al and the study by Cummins et al,8Cummins E.P. Seeballuck F. Keely S.J. et al.The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis.Gastroenterology. 2008; 134: 156-165Google Scholar HIF degradation was prevented by pharmacologic inhibitors of hydroxylases, the enzymes that result in inactivation of HIF. Although the hydroxylase inhibitors used were different, the results were similar: an increase in stable HIF-1 levels. This in turn protected mice against colonic injury, inflammation, and clinical signs of IBD. Recent studies have shown that HIF is also protective against other diseases that may be associated with hypoxia. For example, investigators showed that HIF protected the intestine from injury during necrotizing enterocolitis,9Baregamian N. Rychahou P.G. Hawkins H.K. et al.Phosphatidylinositol 3-kinase pathway regulates hypoxia-inducible factor-1 to protect from intestinal injury during necrotizing enterocolitis.Surgery. 2007; 142: 295-302Google Scholar a disease of infants in which a combination of hypoxic and dietary factors seems to play a role in causing loss of epithelial barrier function and subsequent sepsis. The mechanism whereby HIF prevents induction of disease is less clear. In the study by Robinson et al,5Robinson A. Keely S. Karhausen J. et al.Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition.Gastroenterology. 2008; 134: 145-155Abstract Full Text Full Text PDF Scopus (288) Google Scholar increased HIF levels were associated with both reduction of changes in barrier function and inflammation. The authors demonstrate a decrease in the expression of critical proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the presence of increased HIF levels. This may in part explain the beneficial effects of HIF on the intestinal barrier; cytokines such as TNF-α and IFN-γ have been shown to reduce barrier function in cell models.10Utech M. Brüwer M. Nusrat A. Tight junctions and cell-cell interactions.Methods Mol Biol. 2006; 341: 185-195Google Scholar Additional effects of HIF were shown by Cummins et al,8Cummins E.P. Seeballuck F. Keely S.J. et al.The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis.Gastroenterology. 2008; 134: 156-165Google Scholar including decreased levels of a number of proinflammatory interleukins, and evidence for reduced neutrophil infiltration, assessed by myeloperoxidase levels, an enzyme expressed predominantly by neutrophils. In addition to anti-inflammatory mechanisms, the hydroxylase inhibitor that was studied most extensively by Robinson et al (FG-4497)5Robinson A. Keely S. Karhausen J. et al.Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition.Gastroenterology. 2008; 134: 145-155Abstract Full Text Full Text PDF Scopus (288) Google Scholar was also shown to induce marked contraction of collagen in vitro, suggesting that HIF plays a role in wound healing. Marked damage and inflammation, as was produced in both studies in this issue, would require initial wound healing, followed by contraction of the wound and epithelial restitution. Although restoration of barrier function to reduce continued influx of proinflammatory products from the lumen is vital, the role of HIF and fibrosis may be a future area for this research. This might require chronic models of IBD, most likely more subtle in nature than detergent-induced IBD. Alternate rodent models of a more chronic nature include interleukin-10 knockout mice that are susceptible to select luminal bacteria. Typically, these models involve gnotobiotic techniques so that individual bacteria, or a specific group of bacteria, can be introduced to colonize the gut.11Kim S.C. Tonkonogy S.L. Albright C.A. et al.Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria.Gastroenterology. 2005; 128: 891-906Google Scholar, 12Rath H.C. Wilson K.H. Sartor R.B. Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli.Infect Immun. 1999; 67: 2969-2974Crossref Google Scholar The study by Cummins et al8Cummins E.P. Seeballuck F. Keely S.J. et al.The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis.Gastroenterology. 2008; 134: 156-165Google Scholar suggests that inhibition of hydroxylases with dimethyloxalylglycine (DMOG) has a more broad-spectrum effect than stabilization of HIF, as nuclear factor (NF)-κB levels were increased. Although this signaling pathway is typically associated with inflammation, elevated NF-κB levels decrease apoptosis, thereby potentially preserving the intestinal epithelial barrier in DSS-induced colitis. Apoptosis is likely applicable to loss of cells from the luminal surface of the intestine under normal and pathophysiologic conditions. The intestinal epithelium is characterized by rapid turnover of the epithelium, with stem cells located in the base of the crypts, that generated new epithelial cells, which mature as they escalate up the crypt and on to intestinal villi in the small intestinal mucosa and intercrypt epithelium in the colon. Finally, cells undergo apoptosis, and are removed from the intestinal epithelial monolayer in an orderly fashion to limit alteration of barrier function.13Yen T.H. Wright N.A. The gastrointestinal tract stem cell niche.Stem Cell Rev. 2006; 2: 203-212Google Scholar, 14Bullen T.F. Forrest S. Campbell F. et al.Characterization of epithelial cell shedding from human small intestine.Lab Invest. 2006; 86: 1052-1063Google Scholar In other words, the apoptotic cell undergoes cell death in situ, allowing neighboring cells to fill the gap and limit disruption of the epithelial barrier. The work shown in these studies provides evidence for the importance of HIF-1 in protection of and repair of IBD lesions induced in acute and subacute detergent models in rodents. Future directions include the applicability of inhibition of hydroxylases by novel pharmaceutical agents in patients with IBD. In addition, it is difficult to know from these studies which are the most critical mechanisms of HIF-1 activity in IBD: protection from loss of epithelial cells via inhibition of apoptosis, increased wound healing, or inhibition of inflammatory pathways. Conclusive studies, using a range of models that begin to incorporate factors thought to be involved in IBD in patients (the luminal microbial environment and the genetic background of the subject) may be an area for future study; targeting of HIF-1 signaling pathways may provide novel therapeutic regimens. Further clinical trials are required to determine applicability of hydroxylase inhibitors in humans, because rodents do not reflect all of the factors involved in IBD. Staging of disease is also likely to be very important. For example, inhibition of hydroxylases might be critical very early in the onset of IBD, but may have to be used more selectively during chronic disease once inflammation has been established. Importantly, translation of basic science studies like these to patients with differing courses and severity of disease is difficult. However, the findings provided in the studies in this issue of Gastroenterology are striking, particularly given the severity of detergent-induced rodent IBD, and the number of similarities between the findings of two entirely separate groups of investigators. Mucosal Protection by Hypoxia-Inducible Factor Prolyl Hydroxylase InhibitionGastroenterologyVol. 134Issue 1PreviewBackground & Aims: A number of recent studies have implicated tissue hypoxia in both acute and chronic inflammatory diseases, particularly as they relate to mucosal surfaces lined by epithelial cells. In this context, a protective role for the transcriptional regulator hypoxia-inducible factor (HIF) was shown through conditional deletion of epithelial HIF-1α in a murine model of colitis. Here, we hypothesized that pharmacologic activation of HIF would similarly provide a protective adaptation to murine colitic disease. Full-Text PDF The Hydroxylase Inhibitor Dimethyloxalylglycine Is Protective in a Murine Model of ColitisGastroenterologyVol. 134Issue 1PreviewBackground & Aims: Prolyl and asparaginyl hydroxylases are key oxygen-sensing enzymes that confer hypoxic sensitivity to transcriptional regulatory pathways including the hypoxia inducible factor 1 (HIF-1) and nuclear factor-κB (NF-κB). Knockout of either HIF-1 or (IKKβ-dependent) NF-κB pathways in intestinal epithelial cells promotes inflammatory disease in murine models of colitis. Both HIF-1 and NF-κB pathways are repressed by the action of hydroxylases through the hydroxylation of key regulatory molecules. Full-Text PDF}, number={1}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Blikslager, Anthony T.}, year={2008}, month={Jan}, pages={346–348} }
 @article{blikslager_2008, title={Managing pain associated with colic}, volume={3}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Blikslager, A.T.}, year={2008}, pages={294–307} }
 @article{moeser_nighot_ryan_simpson_clarke_blikslager_2008, title={Mice lacking the Na+/H+ exchanger 2 have impaired recovery of intestinal barrier function}, volume={295}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00538.2007}, DOI={10.1152/ajpgi.00538.2007}, abstractNote={Ischemic injury induces breakdown of the intestinal barrier. Recent studies in porcine postischemic tissues indicate that inhibition of NHE2 results in enhanced recovery of barrier function in vitro via a process involving interepithelial tight junctions. To further study this process, recovery of barrier function was assessed in wild-type (NHE2 +/+ ) and NHE2 −/− mice in vivo and wild-type mice in vitro. Mice were subjected to complete mesenteric ischemia in vivo, after which barrier function was measured by blood-to-lumen mannitol clearance over a 3-h recovery period or measurement of transepithelial electrical resistance (TER) in Ussing chambers immediately following ischemia. Tissues were assessed for expression of select junctional proteins. Compared with NHE2 +/+ mice, NHE2 −/− mice had greater intestinal permeability during the postischemic recovery process. In contrast to prior porcine studies, pharmacological inhibition of NHE2 in postischemic tissues from wild-type mice also resulted in significant reductions in TER. Mucosa from NHE2 −/− mice displayed a shift of occludin and claudin-1 expression to the Triton-X-soluble membrane fractions and showed disruption of occludin and claudin-1 localization patterns following injury. This was qualitatively and quantitatively recovered in NHE2 +/+ mice compared with NHE2 −/− mice by the end of the 3-h recovery period. Serine phosphorylation of occludin and claudin-1 was downregulated in NHE2 −/− postischemia compared with wild-type mice. These data indicate an important role for NHE2 in recovery of barrier function in mice via a mechanism involving tight junctions.}, number={4}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Moeser, Adam J. and Nighot, Prashant K. and Ryan, Kathleen A. and Simpson, Janet E. and Clarke, Lane L. and Blikslager, Anthony T.}, year={2008}, month={Oct}, pages={G791–G797} }
 @article{merritt_blikslager_2008, title={Post operative ileus: To be or not to be?}, volume={40}, ISSN={0425-1644}, url={http://dx.doi.org/10.2746/042516408X302537}, DOI={10.2746/042516408X302537}, abstractNote={Equine Veterinary JournalVolume 40, Issue 4 p. 295-296 Post operative ileus: To be or not to be? A. M. MERRITT, A. M. MERRITT College of Veterinary Medicine, University of Florida, Box 100136-0138, Gainesville, Florida 36210, USASearch for more papers by this authorA. T. BLIKSLAGER, A. T. BLIKSLAGER College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this author A. M. MERRITT, A. M. MERRITT College of Veterinary Medicine, University of Florida, Box 100136-0138, Gainesville, Florida 36210, USASearch for more papers by this authorA. T. BLIKSLAGER, A. T. BLIKSLAGER College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this author First published: 05 January 2010 https://doi.org/10.2746/042516408X302537Citations: 24AboutPDF 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 onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume40, Issue4June 2008Pages 295-296 RelatedInformation}, number={4}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Merritt, A. M. and Blikslager, A. T.}, year={2008}, month={Jun}, pages={295–296} }
 @inbook{blikslager_2008, place={Deerfield Beach, FL}, title={Signs of colic}, booktitle={The ultimate horse lover : the best experts' advice for a happy, healthy horse with stories and photos of awe-inspiring equines}, publisher={Health Communications}, author={Blikslager, A.T.}, editor={Becker, M.Editor}, year={2008}, pages={208–210} }
 @article{cook_meyer_campbell_davis_blikslager_2008, title={T1298 Comparison of the Effects of a COX-2 Selective Inhibitor (Firocoxib) and a Traditional NSAID (Flunixin Meglumine) On Recovery of Ischemic-Injured Equine Jejunum}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(08)62455-5}, DOI={10.1016/S0016-5085(08)62455-5}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Cook, Vanessa and Meyer, Colleen T. and Campbell, Nigel and Davis, Jennifer and Blikslager, Anthony T.}, year={2008}, month={Apr}, pages={A-525-A-526} }
 @article{cook_blikslager_2008, title={Use of systemically administered lidocaine in horses with gastrointestinal tract disease}, volume={232}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.232.8.1144}, DOI={10.2460/javma.232.8.1144}, number={8}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Blikslager, Anthony T.}, year={2008}, month={Apr}, pages={1144–1148} }
 @article{nighot_koci_moeser_ali_blikslager_2008, title={W1268 Mechanism of Astrovirus Induced Diarrhea}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(08)63119-4}, DOI={10.1016/S0016-5085(08)63119-4}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Prashant K. and Koci, Matthew D. and Moeser, Adam J. and Ali, Rizwana and Blikslager, Anthony T.}, year={2008}, month={Apr}, pages={A-668} }
 @article{nighot_ueno_roerig_ryan_blikslager_moeser_2008, title={W1738 Gastroprotective Properties of Cobiprostone Against Acid and NSAID-Induced Mucosal Injury in Porcine Gastric Mucosa}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(08)63293-X}, DOI={10.1016/S0016-5085(08)63293-X}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Nighot, Meghali P. and Ueno, Ryuji and Roerig, Birgit and Ryan, Kathleen A. and Blikslager, Anthony T. and Moeser, Adam J.}, year={2008}, month={Apr}, pages={A-705} }
 @article{little_jones_blikslager_2007, title={Cyclooxygenase (COX) Inhibitors and the Intestine}, volume={21}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2007.tb02978.x}, DOI={10.1111/j.1939-1676.2007.tb02978.x}, abstractNote={Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARγ, nuclear factor kB, mitogen activated protein kinases, and heat shock proteins.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Little, Dianne and Jones, Samuel L. and Blikslager, Anthony T.}, year={2007}, month={May}, pages={367–377} }
 @article{little_jones_blikslager_2007, title={Cyclooxygenase (COX) inhibitors and the intestine}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34249297006&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2007)21[367:CCIATI]2.0.CO;2}, abstractNote={Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins.}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Little, D. and Jones, S.L. and Blikslager, A.T.}, year={2007}, pages={367–377} }
 @article{little_brown_campbell_moeser_davis_blikslager_2007, title={Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum}, volume={68}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.68.6.614}, DOI={10.2460/ajvr.68.6.614}, abstractNote={To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.18 horses.Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects.Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Little, Dianne and Brown, S. Aubrey and Campbell, Nigel B. and Moeser, Adam J. and Davis, Jennifer L. and Blikslager, Anthony T.}, year={2007}, month={Jun}, pages={614–624} }
 @article{blikslager_2007, title={Equine colic research: future prospects for an age-old problem}, volume={27}, number={12}, journal={Journal of Equine Veterinary Science}, author={Blikslager, A.T.}, year={2007}, pages={546–547} }
 @article{elce_orsini_blikslager_2007, title={Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses}, volume={68}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.68.1.76}, DOI={10.2460/ajvr.68.1.76}, abstractNote={Abstract Objective —To assess expression of cyclooxygenase (COX)-1 and -2 in naturally occurring squamous cell carcinomas (SCCs) and the analogous normal tissues in horses. Sample Population —Tissue samples collected from 3 conjunctival, 2 vulvar, 4 preputial, and 5 penile SCCs during surgical excision in 14 horses and from corresponding body regions (conjunctiva [n = 5 horses], vulva [2], prepuce [3], and penis [3]) in 5 horses euthanized for reasons unrelated to neoplasia. Procedures —Tissue samples were snap frozen in liquid nitrogen and stored at −80°C until analysis. Protein was extracted from the frozen tissues, and western blot analyses were performed. Nonneoplastic and abnormal tissues from each body region were run on the same blot, and blots were run in triplicate. Molecular-weight markers and COX-1 and 2 ovine standards (positive control samples) were run concurrently on the gels; negative control samples were not used. Results —All tissues, including the nonneoplastic and SCC tissues, expressed both COX-1 and -2 proteins. Conclusions and Clinical Relevance —Results indicated that the expression of COX proteins in both nonneoplastic and SCC-affected tissues in horses is markedly different from that in other species. The reason for the potential benefit of COX-2 inhibitors in horses and other species is unknown. Further research needs to be performed to evaluate the efficacy of COX-2 inhibitors as cancer treatments in horses. Investigation of the mechanisms of tumor development in horses should be performed to increase understanding of this disease and ascertain how the mechanisms differ from those in other animals.}, number={1}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Elce, Yvonne A. and Orsini, James A. and Blikslager, Anthony T.}, year={2007}, month={Jan}, pages={76–80} }
 @article{moeser_ryan_nighot_blikslager_2007, title={Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs}, volume={293}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00304.2006}, DOI={10.1152/ajpgi.00304.2006}, abstractNote={Our previous work has demonstrated that weaning at 19 days of age has deleterious effects on mucosal barrier function in piglet intestine that are mediated through peripheral CRF receptor signaling pathways. The objectives of the present study were to assess the impact of piglet age on weaning-associated intestinal dysfunction and to determine the role that mast cells play in weaning-induced breakdown of mucosal barrier function. Nursing Yorkshire-cross piglets were either weaned at 19 days of age (early-weaned, n = 8) or 28 days of age (late-weaned, n = 8) and housed in nursery pens. Twenty-four hours postweaning, segments of midjejunum and ascending colon from piglets within each weaning age group were harvested and mounted on Ussing chambers for measurements of transepithelial electrical resistance and serosal-to-mucosal [(3)H]mannitol fluxes. Early weaning resulted in reductions in transepithelial electrical resistance and increases in mucosal permeability to [(3)H]mannitol in the jejunum and colon (P < 0.01). In contrast, postweaning reductions in intestinal barrier function were not observed in piglets weaned at 28 days of age. Early-weaned piglet intestinal mucosa had increased expression of CRF receptor 1 protein, increased mucosal mast cell tryptase levels, and evidence of enhanced mast cell degranulation compared with late-weaned intestinal mucosa. Pretreatment of piglets with the mast cell stabilizer drug cromolyn, injected intraperitoneally 30 min prior to weaning, abolished the early-weaning-induced intestinal barrier disturbances. Our results indicate that early-weaning stress induces mucosal dysfunction mediated by intestinal mast cell activation and can be prevented by delaying weaning.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Moeser, Adam J. and Ryan, Kathleen A. and Nighot, Prashant K. and Blikslager, Anthony T.}, year={2007}, month={Aug}, pages={G413–G421} }
 @article{rhoads_corl_harrell_niu_gatlin_phillips_blikslager_moeser_wu_odle_et al._2007, title={Intestinal ribosomal p70(S6K) signaling is increased in piglet rotavirus enteritis}, volume={292}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00468.2006}, DOI={10.1152/ajpgi.00468.2006}, abstractNote={Recent identification of the mammalian target of rapamycin (mTOR) pathway as an amino acid-sensing mechanism that regulates protein synthesis led us to investigate its role in rotavirus diarrhea. We hypothesized that malnutrition would reduce the jejunal protein synthetic rate and mTOR signaling via its target, ribosomal p70 S6 kinase (p70 S6K ). Newborn piglets were artificially fed from birth and infected with porcine rotavirus on day 5 of life. Study groups included infected (fully fed and 50% protein calorie malnourished) and noninfected fully fed controls. Initially, in “worst-case scenario studies,” malnourished infected piglets were killed on days 1, 3, 5, and 11 postinoculation, and jejunal samples were compared with controls to determine the time course of injury and p70 S6K activation. Using a 2 × 2 factorial design, we subsequently determined if infection and/or malnutrition affected mTOR activation on day 3. Western blot analysis and immunohistochemistry were used to measure total and phosphorylated p70 S6K ; [ 3 H]phenylalanine incorporation was used to measure protein synthesis; and lactase specific activity and villus-crypt dimensions were used to quantify injury. At the peak of diarrhea, the in vitro jejunal protein synthetic rate increased twofold (compared with the rate in the uninfected pig jejunum), concomitant with increased jejunal p70 S6K phosphorylation (4-fold) and an increased p70 S6K level (3-fold, P < 0.05). Malnutrition did not alter the magnitude of p70 S6K activation. Immunolocalization revealed that infection produced a major induction of cytoplasmic p70 S6K and nuclear phospho-p70 S6K , mainly in the crypt. A downregulation of semitendinosus muscle p70 S6K phosphorylation was seen at days 1–3 postinoculation. In conclusion, intestinal activation of p70 S6K was not inhibited by malnutrition but was strongly activated during an active state of mucosal regeneration.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Rhoads, J. Marc and Corl, Benjamin A. and Harrell, Robert and Niu, Xiaomei and Gatlin, Lori and Phillips, Oulayvanh and Blikslager, Anthony and Moeser, Adam and Wu, Guoyao and Odle, Jack and et al.}, year={2007}, month={Mar}, pages={G913–G922} }
 @article{moeser_blikslager_2007, title={Mechanisms of porcine diarrheal disease}, volume={231}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.231.1.56}, DOI={10.2460/javma.231.1.56}, abstractNote={JAVMA, Vol 231, No. 1, July 1, 2007 E disease continues to be a substantial problem in the swine industry, contributing to poor growth performance, increased morbidity and mortality rates, compromised welfare, and economic losses. Advances in the understanding of swine management, vaccine technology, and prophylactic antimicrobial regimens have substantially reduced the impact of certain diarrheal diseases of swine, but several pathogens continue to pose major challenges to the swine industry. Intensive management practices and changes in genetics have likely led to increased susceptibility of pigs to common enteric pathogens and the emergence of new pathogens that were once considered commensal. Several of these pathogens have not been fully characterized, or their pathophysiologic features are not well understood. Since a review of the mechanisms of diarrhea by Moon in 1978, the basic understanding of pathophysiologic mechanisms of diarrheal disease has increased considerably. Elucidation of the molecular basics of intestinal ion transport and how these molecular events become dysregulated by enteric pathogens have not only helped us better understand the disease process, but have also provided us with important information aiding in the development of diagnostic, management, and therapeutic strategies to combat these disorders. The objective of this report was to review the current understanding of the basic mechanisms of diarrheal diseases in swine, with particular emphasis on the ability of specific enteric pathogens to alter intestinal ion transport and fluid movement across intestinal epithelium. Although this review is focused on enteric diseases in pigs, basic mechanisms discussed apply to all veterinary species.}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Moeser, Adam J. and Blikslager, Anthony T.}, year={2007}, month={Jul}, pages={56–67} }
 @article{tate_blikslager_papich_2007, title={Performance of the 808-nm diode laser on equine upper airway tissue is enhanced by intravenous administration of indocyanine green}, volume={25}, ISSN={["1557-8550"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-35848961222&partnerID=MN8TOARS}, DOI={10.1089/pho.2007.2107}, abstractNote={Objective: The objective was to develop a protocol whereby 808-nm diode laser irradiation combined with intravenous (IV) indocyanine green (ICG) could be used in non-contact mode with equal surgical efficacy to the Nd:YAG on equine tissues. Background Data: The 808-nm diode laser, delivering 20–40 W of power, has been produced for veterinary medical applications. This laser's power output is less than that of most neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers. ICG is absorbed at a wavelength of 810 nm, which when concentrated in tissue should be an excellent absorber for the energy produced by the 808-nm diode laser. Methods: This study compares the depths and widths of thermal penetration achieved with the 808-nm diode laser in equine respiratory tissue after intravenous injection of ICG. ICG was administered at two doses: 1.5 mg/kg and 3 mg/kg. The 808-nm diode laser and Nd:YAG laser were set to deliver 200 J of energy. The depths and widths of thermal penetration obtained were compared. Results: Lesion depth and width tended to be greater in the ICG + 3 mg/kg group than in the ICG + 1.5 mg/kg group. Even so, the 1.5-mg/kg dose substantially increased the efficacy of the diode laser. Plasma ICG concentrations peaked at 5 min post-administration and then dropped markedly; lesion depth decreased after peaking at 7 min post-administration. Conclusion: This study demonstrated that the 808-nm diode laser, when augmented with intravenous ICG, will be as effective a surgical tool as the Nd:YAG laser on equine upper airway tissues when applied using a non-contact fiber.}, number={5}, journal={PHOTOMEDICINE AND LASER SURGERY}, author={Tate, Lloyd P. and Blikslager, Anthony T. and Papich, Mark G.}, year={2007}, month={Oct}, pages={443–448} }
 @article{davis_papich_morton_gayle_blikslager_campbell_2007, title={Pharmacokinetics of etodolac in the horse following oral and intravenous administration}, volume={30}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2007.00811.x}, DOI={10.1111/j.1365-2885.2007.00811.x}, abstractNote={The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two‐way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3‐week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half‐life ( t 1/2 ) of 2.67 h, volume of distribution ( V d ) of 0.29 L/kg and clearance ( Cl ) of 234.87 mL/h kg. Following oral administration, the average maximum plasma concentration ( C max ) was 32.57 μg/mL with a t 1/2 of 3.02 h. Bioavailability was approximately 77.02%. Results of in vitro COX selectivity assays showed that etodolac was only slightly selective for COX‐2 with a COX‐1/COX‐2 selectivity ratio effective concentration (EC) 50 of 4.32 and for EC 80 of 4.77. This study showed that etodolac is well absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Papich, M. G. and Morton, A. J. and Gayle, J. and Blikslager, A. T. and Campbell, N. B.}, year={2007}, month={Feb}, pages={43–48} }
 @article{garvican_elce_woolard_blikslager_2007, title={Preputial melanoma with systemic metastasis in a pony gelding and disseminated metastatic melanoma in a Thoroughbred gelding}, volume={19}, ISSN={["2042-3292"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34447558345&partnerID=MN8TOARS}, DOI={10.2746/095777307x207646}, number={6}, journal={EQUINE VETERINARY EDUCATION}, author={Garvican, E. R. and Elce, Y. A. and Woolard, K. and Blikslager, A. T.}, year={2007}, month={Jul}, pages={312–315} }
 @article{moeser_nighot_engelke_ueno_blikslager_2007, title={Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone}, volume={292}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00183.2006}, DOI={10.1152/ajpgi.00183.2006}, abstractNote={Previous studies utilizing an ex vivo porcine model of intestinal ischemic injury demonstrated that prostaglandin (PG)E(2) stimulates repair of mucosal barrier function via a mechanism involving Cl(-) secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE(2)-induced mucosal recovery was mediated via type-2 Cl(-) channels (ClC-2). Therefore, the objective of the present study was to directly investigate the role of ClC-2 in mucosal repair by evaluating mucosal recovery in ischemia-injured intestinal mucosa treated with the selective ClC-2 agonist lubiprostone. Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers, and short-circuit current (I(sc)) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01-1 microM lubiprostone to ischemia-injured mucosa induced concentration-dependent increases in TER, with 1 microM lubiprostone stimulating a twofold increase in TER (DeltaTER = 26 Omega.cm(2); P < 0.01). However, lubiprostone (1 microM) stimulated higher elevations in TER despite lower I(sc) responses compared with the nonselective secretory agonist PGE(2) (1 microM). Furthermore, lubiprostone significantly (P < 0.05) reduced mucosal-to-serosal fluxes of (3)H-labeled mannitol to levels comparable to those of normal control tissues and restored occludin localization to tight junctions. Activation of ClC-2 with the selective agonist lubiprostone stimulated elevations in TER and reductions in mannitol flux in ischemia-injured intestine associated with structural changes in tight junctions. Prostones such as lubiprostone may provide a selective and novel pharmacological mechanism of accelerating recovery of acutely injured intestine compared with the nonselective action of prostaglandins such as PGE(2).}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Moeser, Adam J. and Nighot, Prashant K. and Engelke, Kory J. and Ueno, Ryuji and Blikslager, Anthony T.}, year={2007}, month={Feb}, pages={G647–G656} }
 @article{blikslager_moeser_gookin_jones_odle_2007, title={Restoration of Barrier Function in Injured Intestinal Mucosa}, volume={87}, ISSN={0031-9333 1522-1210}, url={http://dx.doi.org/10.1152/physrev.00012.2006}, DOI={10.1152/physrev.00012.2006}, abstractNote={Mucosal repair is a complex event that immediately follows acute injury induced by ischemia and noxious luminal contents such as bile. In the small intestine, villous contraction is the initial phase of repair and is initiated by myofibroblasts that reside immediately beneath the epithelial basement membrane. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. This is a highly regulated event involving signaling via basement membrane integrins by molecules such as focal adhesion kinase and growth factors. Interestingly, however, ex vivo studies of mammalian small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. Additional roles are played by subepithelial cell populations, including neutrophils, related to their role in innate immunity. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian tissues to prevent the onset of sepsis.}, number={2}, journal={Physiological Reviews}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Moeser, Adam J. and Gookin, Jody L. and Jones, Samuel L. and Odle, Jack}, year={2007}, month={Apr}, pages={545–564} }
 @article{fogle_gerard_johansson_breuhaus_blikslager_jones_2007, title={Spontaneous rupture of the guttural pouch as a complication of treatment for guttural pouch empyema}, volume={19}, ISSN={["0957-7734"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34547981740&partnerID=MN8TOARS}, DOI={10.2746/095777307X196900}, abstractNote={Equine Veterinary EducationVolume 19, Issue 7 p. 351-355 Spontaneous rupture of the guttural pouch as a complication of treatment for guttural pouch empyema C. A. Fogle, Corresponding Author C. A. Fogle Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.*Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorM. P. Gerard, M. P. Gerard Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorA. M. Johansson, A. M. Johansson Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorB. A. Breuhaus, B. A. Breuhaus Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorA. T. Blikslager, A. T. Blikslager Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorS. L. Jones, S. L. Jones Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this author C. A. Fogle, Corresponding Author C. A. Fogle Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.*Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorM. P. Gerard, M. P. Gerard Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorA. M. Johansson, A. M. Johansson Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorB. A. Breuhaus, B. A. Breuhaus Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorA. T. Blikslager, A. T. Blikslager Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this authorS. L. Jones, S. L. Jones Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA.Search for more papers by this author First published: 05 January 2010 https://doi.org/10.2746/095777307X196900Citations: 13AboutPDF ToolsExport 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 onFacebookTwitterLinked InRedditWechat Citing Literature Volume19, Issue7August 2007Pages 351-355 RelatedInformation}, number={7}, journal={EQUINE VETERINARY EDUCATION}, author={Fogle, C. A. and Gerard, M. P. and Johansson, A. M. and Breuhaus, B. A. and Blikslager, A. T. and Jones, S. L.}, year={2007}, month={Aug}, pages={351–355} }
 @article{moeser_klok_ryan_wooten_little_cook_blikslager_2007, title={Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig}, volume={292}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00197.2006}, DOI={10.1152/ajpgi.00197.2006}, abstractNote={Weaning in the piglet is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Although stress is thought to play a role in postweaning intestinal disease, the mechanisms by which stress influences intestinal pathophysiology in the weaned pig are not understood. The objectives of these experiments were to investigate the impact of weaning on gastrointestinal health in the pig and to assess the role of stress signaling pathways in this response. Nineteen-day-old pigs were weaned, and mucosal barrier function and ion transport were assessed in jejunal and colonic tissues mounted on Ussing chambers. Weaning caused marked disturbances in intestinal barrier function, as demonstrated by significant ( P < 0.01) reductions in transepithelial electrical resistance and increases in intestinal permeability to [ 3 H]mannitol in both the jejunum and colon compared with intestinal tissues from age-matched, unweaned control pigs. Weaned intestinal tissues exhibited increased intestinal secretory activity, as demonstrated by elevated short-circuit current that was sensitive to treatment with tetrodotoxin and indomethacin, suggesting activation of enteric neural and prostaglandin synthesis pathways in weaned intestinal tissues. Western blot analyses of mucosal homogenates showed increased expression of corticotrophin-releasing factor (CRF) receptor 1 in the jejunum and colon of weaned intestinal tissues. Pretreatment of pigs with the CRF receptor antagonist α-helical CRF(9–41), which was injected intraperitoneally 30 min prior to weaning, abolished the stress-induced mucosal changes. Our results indicate that weaning stress induces mucosal dysfunction mediated by intestinal CRF receptors and activated by enteric nerves and prostanoid pathways.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Moeser, Adam J. and Klok, Carin Vander and Ryan, Kathleen A. and Wooten, Jenna G. and Little, Dianne and Cook, Vanessa L. and Blikslager, Anthony T.}, year={2007}, month={Jan}, pages={G173–G181} }
 @article{blikslager_yin_cochran_wooten_pettigrew_belknap_2006, title={Cyclooxygenase expression in the early stages of equine laminitis: A cytologic study}, volume={20}, DOI={10.1111/j.1939-1676.2006.tb00721.x}, abstractNote={Background:Recent reports indicate increased amounts of mRNA from inflammation-related genes in the prodromal stage of laminitis. Hypothesis:Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) undergo distinct patterns of expression in equine laminae in the developmental stage (DEV) and acute clinical stage (LAM) of laminitis. Animals:Horses selected from an outbred population were placed into 1 of 4 groups: DEV (n = 5), CON-3h (control group for DEV, n = 5), LAM (n = 5) and CON-10h (control group for LAM, n = 5). Methods:Laminar and skin samples were obtained from (1) animals either undergoing leukopenia (DEV) or the onset of clinical signs of laminitis (LAM) after black walnut extract (BWE) administration and (2) animals either 3 (CON-3h) or 10 (CON-10h) hours after administration of water. Real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunohistochemical analysis were performed for COX-1 and COX-2. Results:Upon immunohistochemical analysis of all 4 groups, COX-2 was expressed by most viable epithelial cells in both laminae and skin. COX-1 exhibited similar epithelial expression to COX-2 in skin epidermis, but was expressed exclusively in the basal layer of laminar epidermis. COX-1 protein was not detectable in dermal vasculature of equine skin or laminae, whereas COX-2 was present in endothelial and vascular smooth muscle cells of dermal vasculature in both skin and laminae in all groups. A marked increase in laminar COX-2 protein concentrations was detected on immunoblotting in the DEV group, although a lesser increase was observed in the LAM group. Conclusions and Clinical Importance: COX-2 protein expression is markedly increased in the resident laminar cell types in the developmental stage of BWE-induced laminitis.}, number={5}, journal={Journal of Veterinary Internal Medicine}, author={Blikslager, Anthony and Yin, C. L. and Cochran, A. M. and Wooten, J. G. and Pettigrew, A. and Belknap, J. K.}, year={2006}, pages={1191–1196} }
 @article{blikslager_yin_cochran_wooten_pettigrew_belknap_2006, title={Cyclooxygenase expression in the early stages of equine laminitis: A cytologic study}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33750288395&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2006)20[1191:CEITES]2.0.CO;2}, abstractNote={Recent reports indicate increased amounts of mRNA from inflammation-related genes in the prodromal stage of laminitis.Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) undergo distinct patterns of expression in equine laminae in the developmental stage (DEV) and acute clinical stage (LAM) of laminitis.Horses selected from an outbred population were placed into 1 of 4 groups: DEV (n = 5), CON-3h (control group for DEV, n = 5), LAM (n = 5) and CON-10h (control group for LAM, n = 5).Laminar and skin samples were obtained from (1) animals either undergoing leukopenia (DEV) or the onset of clinical signs of laminitis (LAM) after black walnut extract (BWE) administration and (2) animals either 3 (CON-3h) or 10 (CON-10h) hours after administration of water. Real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunohistochemical analysis were performed for COX-1 and COX-2.Upon immunohistochemical analysis of all 4 groups, COX-2 was expressed by most viable epithelial cells in both laminae and skin. COX-1 exhibited similar epithelial expression to COX-2 in skin epidermis, but was expressed exclusively in the basal layer of laminar epidermis. COX-1 protein was not detectable in dermal vasculature of equine skin or laminae, whereas COX-2 was present in endothelial and vascular smooth muscle cells of dermal vasculature in both skin and laminae in all groups. A marked increase in laminar COX-2 protein concentrations was detected on immunoblotting in the DEV group, although a lesser increase was observed in the LAM group.COX-2 protein expression is markedly increased in the resident laminar cell types in the developmental stage of BWE-induced laminitis.}, number={5}, journal={Journal of Veterinary Internal Medicine}, author={Blikslager, A.T. and Yin, C. and Cochran, A.M. and Wooten, J.G. and Pettigrew, A. and Belknap, J.K.}, year={2006}, pages={1191–1196} }
 @article{blikslager_2006, title={Intestinal mucosal epithelium: The barrier to sepsis}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33751177759&partnerID=MN8TOARS}, DOI={10.1080/17471060600765018}, abstractNote={The intestinal epithelium provides a critical barrier to pathogens and their toxins within the intestinal lumen. The epithelium is capable of directly interacting with intestinal pathogens such as Salmonella species, resulting in a release of cytokines beneath the epithelium that likely play a role in sepsis. More directly, the epithelium expresses Toll-like receptors so that it can directly respond to luminal lipopolysaccharide. Breaching of the epithelial barrier is likely the principal cause of sepsis in patients with compromised intestinal circulation. However, a number of reparative mechanisms have developed to rapidly repair epithelial defects, including epithelial migration (restitution) and closure of injured tight junctions. Therefore, barrier function and prevention of sepsis are related to the ability of the epithelium to react in an appropriate manner to luminal bacteria, prevent passage of bacteria across the barrier, and rapidly repair the barrier when it is damaged.}, number={4}, journal={Journal of Organ Dysfunction}, author={Blikslager, A.T.}, year={2006}, pages={250–253} }
 @article{pease_cook_jones_blikslager_scrivani_erb_2006, title={Letters to the Editor}, volume={228}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.228.7.1011}, DOI={10.2460/javma.228.7.1011}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Pease, A. and Cook, V. and Jones, S. and Blikslager, A. and Scrivani, P. and Erb, H.}, year={2006}, month={Apr}, pages={1011–1012} }
 @article{davis_little_blikslager_papich_2006, title={Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary investigation}, volume={29}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2006.00757.x}, DOI={10.1111/j.1365-2885.2006.00757.x}, abstractNote={Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to develop in vitro / in vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioavailability in the horse. Permeability was ranked as follows: MTZ > FCZ > MAR > CPX. This correlated with the bioavailability ( R 2 = 0.633447), the Log P ( R 2 = 0.648517), as well as the molecular weight ( R 2 = 0.851208) of the drugs. Metronidazole induced a decrease in the tissue transepithelial resistance, suggestive of the possibility of tissue toxicity, which may have falsely increased its permeability. The low permeability of cephalexin across the tissue may indicate a lack of active transporters that are found in other species. From this study, we can conclude that the Ussing chamber is a promising method for determining mucosal permeability in the horse.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Little, D. and Blikslager, A. T. and Papich, M. G.}, year={2006}, month={Oct}, pages={379–385} }
 @article{blikslager_2006, title={North Carolina State University's College of Veterinary Medicine announces plans to expand equine services}, volume={26}, ISSN={["0737-0806"]}, DOI={10.1016/j.jevs.2006.03.008}, number={4}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Blikslager, A}, year={2006}, month={Apr}, pages={148-+} }
 @article{blikslager_2006, title={Peritonitis in the horse}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33745200257&partnerID=MN8TOARS}, DOI={10.1111/j.2042-3292.2006.tb00434.x}, abstractNote={Equine Veterinary EducationVolume 18, Issue 3 p. 143-143 Peritonitis in the horse A. T. Blikslager, A. T. Blikslager Equine Health Program, North Carolina State University, Raleigh, North Carolina 27606, USASearch for more papers by this author A. T. Blikslager, A. T. Blikslager Equine Health Program, North Carolina State University, Raleigh, North Carolina 27606, USASearch for more papers by this author First published: 05 January 2010 https://doi.org/10.1111/j.2042-3292.2006.tb00434.xAboutPDF ToolsExport 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 onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, Issue3June 2006Pages 143-143 RelatedInformation}, number={3}, journal={Equine Veterinary Education}, author={Blikslager, A.T.}, year={2006}, pages={143} }
 @article{frederico_jones_blikslager_2006, title={Predisposing factors for small colon impaction in horses and outcome of medical and surgical treatment: 44 cases (1999–2004)}, volume={229}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.229.10.1612}, DOI={10.2460/javma.229.10.1612}, abstractNote={To identify factors associated with development of small colon impaction in horses and with selection of medical versus surgical treatment and to determine the prognosis for affected horses following medical or surgical management.Retrospective case series.44 horses with primary impaction of the small colon.Medical records were reviewed for signalment, history, clinical findings, treatment (medical vs surgical), hospitalization time, and outcome. For comparison purposes, the same information was collected for 83 horses with primary impaction of the large colon.Diarrhea was the only factor found to be associated with development of small colon impaction. Horses with small colon impaction were 10.8 times as likely to have diarrhea at the time of initial examination as were horses with large colon impaction. Abdominal distension was the only factor associated with use of surgical versus medical treatment. Horses with small colon impaction that were treated surgically were 5.2 times as likely to have had abdominal distension at the time of admission as were horses with small colon impaction that were treated medically. Overall, 21 of 23 (91%) horses treated medically and 20 of 21 (95%) horses treated surgically survived to discharge.Results suggest that diarrhea may be a risk factor for development of small colon impaction and that horses with small colon impaction that have abdominal distension at the time of initial examination are more likely to require surgical than medical treatment.}, number={10}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Frederico, Lisa M. and Jones, Samuel L. and Blikslager, Anthony T.}, year={2006}, month={Nov}, pages={1612–1616} }
 @book{blikslager_2006, title={Principles of Intestinal Injury and Determination of Intestinal Viability}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84860691395&partnerID=MN8TOARS}, DOI={10.1016/B1-41-600123-9/50036-X}, journal={Equine Surgery}, author={Blikslager, A.T.}, year={2006}, pages={395–401} }
 @article{moeser_nighot_ryan_wooten_blikslager_2006, title={Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine}, volume={291}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00380.2005}, DOI={10.1152/ajpgi.00380.2005}, abstractNote={Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl − secretion and inhibition of electroneutral Na + /H + exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current ( I sc ), transepithelial electrical resistance (TER), and isotopic fluxes of 22 Na were measured in response to PGE 2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER ( P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 μM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in I sc and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 μM) or serosal cariporide (25 μM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22 Na + (by ∼35%) compared with nontreated ischemia-injured control tissues ( P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.}, number={5}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Moeser, Adam J. and Nighot, Prashant K. and Ryan, Kathleen A. and Wooten, Jenna G. and Blikslager, Anthony T.}, year={2006}, month={Nov}, pages={G885–G894} }
 @article{alward_corriher_barton_sellon_blikslager_jones_2006, title={Red maple (Acer rubrum) leaf toxicosis in horses: A retrospective study of 32 cases}, volume={20}, ISSN={["0891-6640"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33750326132&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2006)20[1197:RMARLT]2.0.CO;2}, abstractNote={Ingestion of wilted red maple leaves by horses can result in severe hemolytic anemia and methemoglobinemia. Little is known about what factors influence the outcome of red maple leaf toxicosis in horses.Our hypothesis was that physical examination findings, clinicopathologic variables or therapeutic modalities may predict outcome in horses with red maple leaf toxicity.Horses with red maple leaf toxicosis presented to referral hospitals in the southeast region of the United States.A multi-institutional retrospective study was designed to identify factors that predict mortality in horses with red maple toxicosis.Thirty-two horses with red maple toxicosis were identified, 19 of which died. Twenty-nine horses presented with anemia and 24 had clinicopathologic evidence of systemic inflammation. Renal insufficiency was identified in 12/30 (41%) horses. Laminitis (9/28) and colic (13/30) also were identified in horses with red maple toxicosis, but development of these 2 conditions did not have a negative effect on short-term survival. Horses with red maple toxicosis that survived to discharge were likely to have developed pyrexia during hospitalization (P = .030). Horses that were treated with a corticosteroid had a significantly increased likelihood of death (P = .045). There was no significant relationship between initial serum hemoglobin concentration, methemoglobin concentration, or percentage methemoglobin and mortality in this horse series.This study suggests that information obtained on initial examination cannot be used to accurately predict survival in horses with red maple toxicosis, but horses that receive corticosteroids are unlikely to survive.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Alward, Ashley and Corriher, Candice A. and Barton, Michelle H. and Sellon, Debra C. and Blikslager, Anthony T. and Jones, Samuel L.}, year={2006}, pages={1197–1201} }
 @book{blikslager_wilson_2006, title={Stomach and spleen}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67949122235&partnerID=MN8TOARS}, DOI={10.1016/B1-41-600123-9/50034-6}, journal={Equine Surgery}, author={Blikslager, A.T. and Wilson, D.A.}, year={2006}, pages={374–386} }
 @article{pease_cook_jones_blikslager_scrivani_erb_2006, title={Views conclusions in ultrasound study as unsupported [1]}, volume={228}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33645467501&partnerID=MN8TOARS}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Pease, A. and Cook, V. and Jones, S. and Blikslager, A. and Scrivani, P. and Erb, H.}, year={2006} }
 @inproceedings{a guide for calculation of spot size to determine power density for free fiber irradiation of tissue_2005, volume={5686}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-23244456795&partnerID=MN8TOARS}, DOI={10.1117/12.579868}, abstractNote={Transendoscopic laser treatment for upper airway disorders has been performed in the horse for over twenty years. Endoscopic laser transmission utilizing flexible fiber optics is limited to certain discreet wavelengths. Initially, the laser of choice was the Nd: YAG laser (1064nm), but in the early 1990's, diode lasers (810nm, 980nm) were introduced to veterinary medicine and are currently used in private practice and universities. Precise application of laser irradiation is dependent on the user knowing the laser's output as well as the amount of energy that is delivered to tissue. Knowledge of dosimetry is important to the veterinarian for keeping accurate medical records by being able to describe very specific treatment regimes. The applied energy is best described as power density or energy density. Calculation of this energy is dependent upon the users ability to determine the laser's spot size when irradiating tissue in a non-contact mode. The charts derived from this study provide the veterinarian the ability to estimate spot size for a number of commonly used lasers with the fiber positioned at various distances from the target.}, booktitle={Progress in Biomedical Optics and Imaging - Proceedings of SPIE}, year={2005}, pages={606–611} }
 @article{glyde_fitzpatrick_shahar_mccreary_mac giolla ri_staines_rodgers_connery_welsh_mcnair_et al._2005, title={Association of Veterinary Teachers and Research Workers (Irish region) 41th Winter Scientific meeting}, volume={58}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-20144369853&partnerID=MN8TOARS}, number={3}, journal={Irish Veterinary Journal}, author={Glyde, M. and Fitzpatrick, D. and Shahar, R. and McCreary, T. and Mac Giolla Ri, B. and Staines, A. and Rodgers, J.D. and Connery, N.L. and Welsh, M.D. and McNair, J. and et al.}, year={2005}, pages={171–176} }
 @article{schierack_nordhoff_pollmann_weyrauch_amasheh_lodemann_jores_tachu_kleta_blikslager_et al._2005, title={Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine}, volume={125}, ISSN={0948-6143 1432-119X}, url={http://dx.doi.org/10.1007/s00418-005-0067-z}, DOI={10.1007/s00418-005-0067-z}, number={3}, journal={Histochemistry and Cell Biology}, publisher={Springer Science and Business Media LLC}, author={Schierack, Peter and Nordhoff, Marcel and Pollmann, Marion and Weyrauch, Karl Dietrich and Amasheh, Salah and Lodemann, Ulrike and Jores, Jörg and Tachu, Babila and Kleta, Sylvia and Blikslager, Anthony and et al.}, year={2005}, month={Oct}, pages={293–305} }
 @article{tschetter_blikslager_little_howard_woody_beex_crisman_2005, title={Detection of differentially regulated genes in ischaemic equine intestinal mucosa}, volume={37}, ISSN={["0425-1644"]}, DOI={10.2746/0425164054529382}, abstractNote={Reasons for performing study: Colic is a serious disease syndrome in horses. Much of the mortality is associated with ischaemic-injured intestine during strangulating obstruction, yet there is limited understanding of the associated molecular events. Identification of differentially expressed genes during ischaemic injury should expand our understanding of colic and may lead to novel targeted therapeutic approaches in the future. Objective: To isolate and identify differentially expressed genes in equine jejunum following a 2 h ischaemic event compared to normally perfused jejunum. Methods: Suppressive subtractive hybridisation was used to clone genes that are differentially expressed in equine jejunum injured by 2 h of complete ischaemia as compared to time-matched control jejunal tissues. Expression of selected clones was further evaluated by northern blot analysis. Results: Of the 384 clones selected, 157 were confirmed to possess cDNAs corresponding differentially expressed genes by dot blot analysis. Two genes, fatty acid binding protein 2 and calcium-activated chloride channel 4 were further confirmed to be differentially expressed by northern blot analysis. Conclusions: Suppressive subtractive hybridisation can be used to detect changes in expression of a broad array of genes, as confirmed by northern blot analysis of selected genes. Potential relevance: These initial results have identified a pool of equine intestinal epithelial genes that are differentially expressed following a 2 h ischaemic event. In particular, genes indicative of deranged metabolic activity and those potentially involved in early repair events were identified and may ultimately provide clues as to the nature of epithelial ischaemic injury in horses.}, number={4}, journal={EQUINE VETERINARY JOURNAL}, author={Tschetter, JR and Blikslager, AT and Little, D and Howard, RD and Woody, SL and Beex, LM and Crisman, MV}, year={2005}, month={Jul}, pages={319–324} }
 @article{tschetter_blikslager_little_howard_woody_beex_crisman_2005, title={Detection of differentially regulated genes in ischaemic equine intestinal mucosa}, volume={37}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-22144488823&partnerID=MN8TOARS}, number={4}, journal={Equine Veterinary Journal}, author={Tschetter, J.R. and Blikslager, A.T. and Little, D. and Howard, R.D. and Woody, S.L. and Beex, L.M. and Crisman, M.V.}, year={2005}, pages={319–324} }
 @article{tomlinson_blikslager_2005, title={Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum}, volume={37}, ISSN={["2042-3306"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-11844295474&partnerID=MN8TOARS}, DOI={10.2746/0425164054406865}, abstractNote={Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)-2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti-inflammatory drugs in colic patients.To compare the effects of deracoxib, a highly selective canine COX-2 inhibitor, with flunixin on in vitro recovery of ischaemic-injured equine jejunum.Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 240 mins. Transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol were monitored as indices of barrier function in the presence of flunixin or deracoxib.The TER of ischaemic-injured tissue recovered significantly over 240 mins in the presence of no treatment, but not in the presence of flunixin or deracoxib. In addition, flunixin-treated ischaemic jejunum was significantly more permeable to mannitol when compared with untreated tissue by the end of the recovery period, whereas deracoxib treatment did not increase permeability. Addition of the PGE1 analogue misoprostol to flunixin-treated tissue restored recovery of TER.Treatment of horses with ischaemic jejunal disease with flunixin may result in a prolonged permeability defect in recovering mucosa. Addition of misoprostol or replacement of flunixin with deracoxib may ameliorate effects of COX inhibitors on recovering mucosa.}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Tomlinson, JE and Blikslager, AT}, year={2005}, month={Jan}, pages={75–80} }
 @article{blikslager_2005, title={Equine reproductive services at North Carolina State University}, volume={25}, ISSN={["0737-0806"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-29244461404&partnerID=MN8TOARS}, DOI={10.1016/j.jevs.2005.11.007}, number={12}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Blikslager, A}, year={2005}, month={Dec}, pages={501–501} }
 @article{little_white_young_blikslager_2005, title={Faecal bile loss in horses following small intestinal resection}, volume={37}, ISSN={["0425-1644"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-11844295005&partnerID=MN8TOARS}, DOI={10.2746/0425164054406883}, abstractNote={Equine Veterinary JournalVolume 37, Issue 1 p. 92-94 Faecal bile loss in horses following small intestinal resection D. LITTLE, D. LITTLE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorC. E. WHITE, C. E. WHITE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorK. M. YOUNG, K. M. YOUNG Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorA. T. BLIKSLAGER, Corresponding Author A. T. BLIKSLAGER Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USADepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this author D. LITTLE, D. LITTLE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorC. E. WHITE, C. E. WHITE Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorK. M. YOUNG, K. M. YOUNG Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorA. T. BLIKSLAGER, Corresponding Author A. T. BLIKSLAGER Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USADepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this author First published: 05 January 2010 https://doi.org/10.2746/0425164054406883Citations: 3AboutPDF 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 onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume37, Issue1January 2005Pages 92-94 RelatedInformation}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Little, D and White, CE and Young, KM and Blikslager, AT}, year={2005}, month={Jan}, pages={92–94} }
 @article{lascelles_blikslager_fox_reece_2005, title={Gastrointestinal tract perforation in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases (2002-2003)}, volume={227}, ISSN={["1943-569X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-26044462209&partnerID=MN8TOARS}, DOI={10.2460/javma.2005.227.1112}, abstractNote={Abstract Objective —To identify factors associated with gastrointestinal tract perforation in dogs being treated with a selective cyclooxygenase-2 (COX-2) inhibitor (deracoxib). Design —Retrospective study. Animals —29 dogs. Procedure —The Novartis Animal Health pharmacovigilance database was searched for records of dogs treated with deracoxib in which gastrointestinal tract perforation was documented. Results —16 of the 29 (55%) dogs had received deracoxib at a dosage higher than that approved by the FDA for the particular indication being treated, with 25 (86%) dogs having received deracoxib at a dosage > 2 mg/kg/d (0.9 mg/lb/d). Seventeen (59%) dogs had received at least 1 other nonsteroidal anti-inflammatory drug (NSAID) or a corticosteroid in close temporal association (within 24 hours) with deracoxib administration (ie, immediately before or following). In all, 26 (90%) dogs had received deracoxib at a higher-than-approved dosage or had received at least 1 other NSAID or corticosteroid in close temporal association with deracoxib administration. Twenty dogs died or were euthanatized, and 9 survived. Conclusions and Clinical Relevance —In dogs with gastrointestinal tract perforation and that had been treated with deracoxib, perforation was most likely attributable to a number of factors. Deracoxib should only be used at approved dosages. Cortico-steroids and other less selective NSAIDs should not be administered in close temporal association with selective COX-2 inhibitors, including deracoxib. Further study is required to define this problem. ( J Am Vet Med Assoc 2005;227:1112–1117)}, number={7}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Lascelles, BDX and Blikslager, AT and Fox, SM and Reece, D}, year={2005}, month={Oct}, pages={1112–1117} }
 @article{blikslager_jones_2005, title={NSAIDs}, volume={25}, ISSN={["0737-0806"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-14944341260&partnerID=MN8TOARS}, DOI={10.1016/j.jevs.2005.02.004}, abstractNote={Objective pain assessment is important to guide and tailor therapy in clinical practice. This study describes the clinical applicability and validity of two pain scales, the Composite Pain Scale (CPS) and the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) in horses with orthopaedic trauma or after orthopaedic surgery. A cohort follow-up study was performed using 77 adult horses (n = 43 with orthopaedic trauma or injury; n = 34 controls). Composite and facial expression-based pain scores were assessed by direct observations of pairs of two independent observers. All horses were assessed at arrival, and on the first and second day after arrival or after surgery.Both CPS and EQUUS-FAP scores demonstrated high inter-observer reliability (Crohnbach’s alpha = 0.97 for CPS; Crohnbach’s alpha = 0.93 for EQUUS-FAP; P < 0.001), with low bias (0.07 and −0.08 respectively) and limits of agreement of −1.9 to 1.9 for CPS and −1.9 to 1.9 for EQUUS-FAP. Both CPS and EQUUS-FAP scores showed significant differences between control horses and orthopaedic cases (P < 0.001). Trauma cases had significantly higher pain scores compared to postoperative cases for both CPS (P < 0.05) and for EQUUS-FAP (P < 0.01) and both pain scores significantly decreased after nonsteroidal anti-inflammatory drug (NSAID) administration. In accordance with the findings in other types of equine pain, the CPS and FAP proved useful and valid for objective and repeatable assessment of pain in horses with orthopaedic trauma or after orthopaedic surgery. This can further aid treatment of horses in clinical practice and might improve equine welfare.}, number={3}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Blikslager, A and Jones, S}, year={2005}, month={Mar}, pages={98–102} }
 @article{little_tomlinson_blikslager_2005, title={Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia}, volume={37}, ISSN={["0425-1644"]}, DOI={10.2746/0425164054529472}, abstractNote={Post operative ileus (POI) remains an important cause of post operative morbidity and mortality in the horse. However, clinical progression of naturally occurring cases of POI in both horse and man does not entirely support the 'neurogenic' hypothesis as the sole mechanism of POI; and the hypothesis that inflammation plays a major role at 12-24 h after surgery requires validation.An inflammatory infiltrate in the muscularis externa and myenteric plexus of equine jejunum is present 18 h following a period of ischaemia.Samples of normal jejunum, jejunum from the proximal resection margins of clinical cases and jejunum obtained 18 h after 1 or 2 h ischaemia or manipulation alone were evaluated for neutrophil infiltration. Samples obtained 18 h after surgery were additionally evaluated for leucocyte activation using calprotectin immunohistochemistry. Results were evaluated by ANOVA and P < 0.05 was considered significant.Significant neutrophilic inflammation was identified in the samples from the proximal resection margins of clinical cases compared to uninjured jejunum. In experimental cases, neutrophilic inflammation appeared to be increased further by 18 h and was identified through all intestinal layers, particularly in the serosa, fascial planes around circular and longitudinal muscle fibres, and myenteric plexus. This elevated level of neutrophilic inflammation was mirrored by an increased number of calprotectin-positive cells in these intestinal layers, indicating leucocyte activation.Significant neutrophilic inflammation occurs in equine jejunal myenteric layers 18 h after surgery.This neutrophilic inflammation coincides with the clinical time point at which POI is identified and may indicate that inflammatory pathways, rather than solely neurogenic pathways, are responsible for POI in the horse.}, number={4}, journal={EQUINE VETERINARY JOURNAL}, author={Little, D and Tomlinson, JE and Blikslager, AT}, year={2005}, month={Jul}, pages={329–335} }
 @article{little_tomlinson_blikslager_2005, title={Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia}, volume={37}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-22144461056&partnerID=MN8TOARS}, number={4}, journal={Equine Veterinary Journal}, author={Little, D. and Tomlinson, J.E. and Blikslager, A.T.}, year={2005}, pages={329–335} }
 @article{morton_campbell_gayle_redding_blikslager_2005, title={Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis}, volume={78}, ISSN={0034-5288}, url={http://dx.doi.org/10.1016/j.rvsc.2004.07.006}, DOI={10.1016/j.rvsc.2004.07.006}, abstractNote={Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac with the non-selective COX inhibitor phenylbutazone in horses with lipopolysaccharide (LPS)-induced synovitis. Three groups of horses (n=6) received no treatment, phenylbutazone (4.4 mg/kg, IV, q12h), or etodolac (23 mg/kg, IV, q12h), respectively, 2-h following injection of LPS into one middle carpal joint. Synovial fluid was analyzed for white blood cell (WBC) count, and TXB2 and PGE2 levels. Phenylbutazone and etodolac significantly reduced WBC count 6 and 24-h following injection of LPS compared to untreated horses. In addition, both drugs significantly reduced PGE2 levels (P<0.05) 6-h following LPS injection, whereas the probable COX-1 prostanoid TXB2 was significantly reduced by phenylbutazone (P<0.05), but not etodolac. Etodolac may serve as a more selective anti-inflammatory agent than phenylbutazone for treatment of equine synovitis.}, number={2}, journal={Research in Veterinary Science}, publisher={Elsevier BV}, author={Morton, Alison J. and Campbell, Nigel B. and Gayle, J’mai M. and Redding, W. Rich and Blikslager, Anthony T.}, year={2005}, month={Apr}, pages={189–192} }
 @article{rhoads_chen_gookin_wu_fu_blikslager_rippe_argenzio_cance_weaver_et al._2004, title={Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism}, volume={53}, ISSN={0017-5749}, url={http://dx.doi.org/10.1136/gut.2003.027540}, DOI={10.1136/gut.2003.027540}, abstractNote={<b>Background:</b>l-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines. <b>Aims:</b> To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. <b>Methods:</b> We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration. <b>Results:</b> Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates β1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels. <b>Conclusions:</b> These results showed that l-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.}, number={4}, journal={Gut}, publisher={BMJ}, author={Rhoads, J.M. and Chen, W. and Gookin, J. and Wu, G.Y. and Fu, Q. and Blikslager, A.T. and Rippe, R.A. and Argenzio, R.A. and Cance, W.G. and Weaver, E.M. and et al.}, year={2004}, month={Apr}, pages={514–522} }
 @article{moeser_haskell_shifflett_little_schultz_blikslager_2004, title={CIC-2 chloride secretion mediates prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum}, volume={127}, ISSN={["1528-0012"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4444353665&partnerID=MN8TOARS}, DOI={10.1053/j.gastro.2004.06.004}, abstractNote={Ischemia results in the breakdown of the intestinal barrier, predisposing patients to sepsis and multiple organ failure. Prostaglandins play a critical role in mediating recovery of barrier function in ischemia-injured intestine through a mechanism involving stimulation of Cl - secretion. In the present study, we investigated the contributory role of individual Cl - channels in the recovery of barrier function in ischemia-injured porcine ileum.Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers. Short-circuit current (Isc) and transepithelial resistance (TER) were measured in response to prostaglandin E 2 (PGE 2 ) and pharmacologic inhibitors of epithelial Cl - channels. Immunoassays were used to assess the expression and localization of ion channels.Application of PGE 2 to ischemia-injured ileal mucosa stimulated increases in Isc, an indicator of Cl - secretion, that was followed by marked increases in TER, an indicator of barrier function recovery. In vitro studies revealed that although PGE 2 induced Cl - secretion via at least 3 distinct secretory pathways, recovery of barrier function was initiated by Cl - secretion via ClC-2 Cl - channels co-expressed with occludin and localized to tight junctions within restituting epithelium. Intravenous administration of furosemide to pigs subjected to 1 hour of ileal ischemia impaired recovery of barrier function, as evidenced by decreased TER and increased mucosal-to-serosal 3 H-mannitol flux after a 2-hour reperfusion/recovery period, confirming an important role for Cl - secretory pathways in vivo.ClC-2-mediated intestinal Cl - secretion restores TER in ischemia-injured intestine. These data may provide the basis for targeted pharmacologic therapy for diseases associated with impaired barrier function.}, number={3}, journal={GASTROENTEROLOGY}, author={Moeser, AJ and Haskell, MM and Shifflett, DE and Little, D and Schultz, BD and Blikslager, AT}, year={2004}, month={Sep}, pages={802–815} }
 @article{sellon_roberts_blikslager_ulibarri_papich_2004, title={Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy}, volume={18}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2004)18<555:EOCRII>2.0.CO;2}, abstractNote={A randomized, controlled, blinded clinical trial was performed to determine whether butorphanol administered by continuous rate infusion (CRI) for 24 hours after abdominal surgery would decrease pain and surgical stress responses and improve recovery in horses. Thirty-one horses undergoing exploratory celiotomy for abdominal pain were randomly assigned to receive butorphanol CRI (13 microg/kg/h for 24 hours after surgery; treatment) or isotonic saline (control). All horses received flunixin meglumine (1.1 mg/kg IV q12h). There were no significant differences between treatment and control horses in preoperative or operative variables. Treatment horses had significantly lower plasma cortisol concentration compared with control horses at 2, 8, 12, 24, 36, and 48 hours after surgery. Mean weight loss while hospitalized was significantly less for treatment horses than control horses, whether expressed as total decrease in body weight (13.9+/-3.4 and 27.9+/-4.5 kg, respectively) or as a percentage decrease in body weight (2.6+/-0.7 and 6.3+/-1.1%, respectively). Treatment horses were significantly delayed in time to first passage of feces (median times of 15 and 4 hours, respectively). Treatment horses had significantly improved behavior scores during the first 24 hours after surgery, consistent with the conclusion that they experienced less pain during that time. Butorphanol CRI during the immediate postoperative period significantly decreased plasma cortisol concentrations and improved recovery characteristics in horses undergoing abdominal surgery.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Sellon, DC and Roberts, MC and Blikslager, AT and Ulibarri, C and Papich, MG}, year={2004}, pages={555–563} }
 @article{sellon_roberts_blikslager_ulibarri_papich_2004, title={Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4243171425&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2004)18<555:EOCRII>2.0.CO;2}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Sellon, D.C. and Roberts, M.C. and Blikslager, A.T. and Ulibarri, C. and Papich, M.G.}, year={2004}, pages={555–563} }
 @article{tomlinson_wilder_young_blikslager_2004, title={Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia}, volume={65}, ISSN={["1943-5681"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3042571674&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2004.65.761}, abstractNote={Abstract Objective —To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemicinjured equine jejunal mucosa after 18 hours of reperfusion. Animals —24 horses. Procedure —Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, IV, q 12 h), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or etodolac (23 mg/kg, IV, q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithelial flux of tritium-labeled mannitol measured mucosal permeability. Denuded villous surface area and mean epithelial neutrophil count per mm2 were calculated. Western blot analysis for cyclooxygenase (COX)-1 and -2 was performed. Pharmacokinetics of flunixin and etodolac and eicosanoid concentrations were determined. Results —Ischemic-injured tissue from horses treated with flunixin and etodolac had significantly lower TER and increased permeability to mannitol, compared with that from horses treated with saline solution. Epithelial denudation after ischemia and 18 hours after recovery was not significantly different among treatments. Both COX-1 and -2 were expressed in ischemic-injured and nonischemic tissues. Ischemia caused significant upregulation of both COX isoforms. Eicosanoid concentrations were significantly lower in tissues from flunixin and etodolac-treated horses, compared with that from horses treated with saline solution. Conclusions and Clinical Relevance —Flunixin and etodolac treatment retarded recovery of intestinal barrier function in jejunal mucosa after 18 hours of reperfusion, whereas tissues from horses treated with saline solution recovered baseline values of TER and permeability to mannitol. ( Am J Vet Res 2004;65:761–769)}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tomlinson, JE and Wilder, BO and Young, KM and Blikslager, AT}, year={2004}, month={Jun}, pages={761–769} }
 @article{tomlinson_blikslager_2004, title={Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across equine jejunum}, volume={65}, ISSN={["0002-9645"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-5644271864&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2004.65.1377}, abstractNote={Abstract Objective —To determine whether ischemia and flunixin affect in vitro lipopolysaccharide (LPS) absorption in samples of the jejunum of horses. Animals —12 horses. Procedure —Horses were anesthetized, a midline celiotomy was performed, and the jejunum was located. Two 30-cm sections of jejunum (60 cm apart) were selected. One segment was designated as control tissue; ischemia was induced in the other segment for 120 minutes. Horses were then euthanatized. Mucosa from each jejunal segment was mounted on Ussing chambers and treated with or without flunixin. Tissues from 6 horses were used to assess permeability to radiolabeled LPS; mucosal samples from the remaining 6 horses were incubated with fluorescent-labeled LPS (FITC-LPS) and examined histologically. Production of tumor necrosis factor-α (TNF-α) and production of LPS-binding protein (LBP) were assessed as indicators of mucosal response to LPS. Results —Ischemia significantly increased mucosal permeability to LPS, but by 180 minutes, the mucosa was not more permeable than control tissue. Flunixin treatment adversely affected intestinal barrier function throughout the experiment but did not result in increased mucosal permeability to LPS. Compared with control tissues, LBP production was increased by ischemia and reduced by exposure to LPS. In ischemic tissue, FITC-LPS entered the lamina propria but TNF-α was produced on the mucosal side only, indicating little response to the absorbed LPS. Conclusions and Clinical Relevance —Ischemia increased LPS passage across equine jejunal mucosa. Flunixin delayed mucosal recovery but did not exacerbate LPS absorption. Evaluation of the clinical importance of flunixin-associated delayed mucosal recovery requires further in vivo investigation. ( Am J Vet Res 2004;65:1377–1383)}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tomlinson, JE and Blikslager, AT}, year={2004}, month={Oct}, pages={1377–1383} }
 @article{tomlinson_blikslager_2004, title={Interactions between lipopolysaccharide and the intestinal epithelium}, volume={224}, ISSN={["1943-569X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-2442581583&partnerID=MN8TOARS}, DOI={10.2460/javma.2004.224.1446}, abstractNote={I ischemia often results in endotoxemia, and endotoxemia significantly increases postoperative morbidity and mortality rates in patients with ischemic intestinal disease. Even if all grossly ischemic intestine is resected, remaining intestine may be injured as a result of distention. In addition, intestine at the margins of the resection may have evidence of serosal injury and neutrophil infiltration. Endotoxemia is a result of absorption of lipopolysaccharide (LPS) from intestinal gram-negative bacteria. Gram-negative bacteria release LPS during periods of rapid proliferation and cell death. Once absorbed, LPS stimulates host cells, principally monocytes and macrophages, to produce and release endogenous mediators of inflammation, triggering pathophysiologic effects that range from mild fever to fatal septic shock. Although intestinal epithelial cells were once regarded as merely a barrier to LPS, it has recently been determined that these cells interact specifically with LPS molecules. Intestinal epithelial cells are normally exposed to high numbers of intact bacteria and high concentrations of bacterial products and form a barrier to LPS absorption and intestinal microbial invasion. As a result, intestinal epithelial cells must recognize and react to pathologic bacteria but avoid responding to the normal gastrointestinal tract flora. Inappropriate responses to normal gastrointestinal tract flora likely play a role in the development of inflammatory bowel disease. Intestinal epithelial cells are regularly exposed to LPS, and small amounts of LPS may be found in the portal blood of healthy individuals. Kupffer cells in the liver typically remove this LPS before it can reach the systemic circulation. However, if the amount of LPS in the portal blood overwhelms the liver’s mechanisms for LPS removal, then LPS will enter the systemic circulation. Circulating LPS interacts with host cells via specific cell surface receptors, and the intercalation of these molecules is considered to be an important step in the activation cascade.}, number={9}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Tomlinson, JE and Blikslager, AT}, year={2004}, month={May}, pages={1446–1452} }
 @article{shifflett_jones_moeser_blikslager_2004, title={Mitogen-activated protein kinases regulate COX-2 and mucosal recovery in ischemic-injured porcine ileum}, volume={286}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00478.2003}, DOI={10.1152/ajpgi.00478.2003}, abstractNote={Mitogen-activated protein kinase (MAPK) pathways transduce signals from a diverse array of extracellular stimuli. The three primary MAPK-signaling pathways are the extracellular regulated kinases (ERK1/2), p38 MAPK, and c-Jun NH 2 -terminal kinase (JNK). Previous research in our laboratory has shown that COX-2-elaborated prostanoids participate in recovery of mucosal barrier function in ischemic-injured porcine ileum. Because COX-2 expression is regulated in part by MAPKs, we postulated that MAPK pathways would play an integral role in recovery of injured mucosa. Porcine mucosa was subjected to 45 min of ischemia, after which tissues were mounted in Ussing chambers, and transepithelial electrical resistance (TER) was monitored as an index of recovery of barrier function. Treatment of tissues with the p38 MAPK inhibitor SB-203580 (0.1 mM) or the ERK1/2 inhibitor PD-98059 (0.1 mM) abolished recovery. Western blot analysis revealed that SB-203580 inhibited upregulation of COX-2 that was observed in untreated ischemic-injured mucosa, whereas PD-98059 had no effect on COX-2 expression. Inhibition of TER recovery by SB-203580 or PD-98059 was overcome by administration of exogenous prostaglandin E 2 (1 μM). The JNK inhibitor SP-600125 (0.1 mM) significantly increased TER and resulted in COX-2 upregulation. COX-2 expression appears to be positively and negatively regulated by the p38 MAPK and the JNK pathways, respectively. Alternatively, ERK1/2 appear to be involved in COX-2-independent reparative events that remain to be defined.}, number={6}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Shifflett, Donnie E. and Jones, Samuel L. and Moeser, Adam J. and Blikslager, Anthony T.}, year={2004}, month={Jun}, pages={G906–G913} }
 @article{shifflett_bottone_young_moeser_jones_blikslager_2004, title={Neutrophils augment recovery of porcine ischemia-injured ileal mucosa by an IL-1β- and COX-2-dependent mechanism}, volume={287}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00076.2003}, DOI={10.1152/ajpgi.00076.2003}, abstractNote={Polymorphonuclear neutrophils (PMNs) play a critical role in intestinal mucosal injury and repair. To study effects of PMNs on acutely injured mucosa, we applied PMNs isolated from circulation or peritoneal fluid from animals with chemically induced peritonitis to ischemia-injured porcine ileal mucosa. In preliminary experiments, PMNs enhanced recovery of transepithelial electrical resistance (TER), and this action was inhibited by pretreatment with the nonselective cyclooxygenase (COX) inhibitor indomethacin. Because COX-2 is upregulated by inflammatory mediators such as IL-1beta, which is released by PMNs, we postulated that PMNs enhance recovery of ischemia-injured mucosa by a pathway involving IL-1beta and COX-2. Application of 5 x 10(6) PMNs to the serosal surface of ischemia-injured mucosa significantly enhanced recovery of TER (P < 0.05), an effect that was inhibited by the selective COX-2 inhibitor NS-398 (5 microM) and by an IL-1beta receptor antagonist (0.1 mg/ml). Addition of 10 ng/ml IL-1beta to the serosal surface of injured tissues caused a significant increase in TER (P < 0.05) that was inhibited by pretreatment with NS-398. Western blot analysis of mucosal homogenates revealed dramatic upregulation of COX-2 in response to IL-1beta or peritoneal PMNs, and the latter was inhibited by an IL-1beta receptor antagonist. Real-time PCR revealed that increased mRNA COX-2 expression preceded increased COX-2 protein expression in response to IL-1beta. We concluded that PMNs augment recovery of TER in ischemia-injured ileal mucosa via IL-1beta-dependent upregulation of COX-2.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Shifflett, Donnie E. and Bottone, Frank G., Jr. and Young, Karen M. and Moeser, Adam J. and Jones, Samuel L. and Blikslager, Anthony T.}, year={2004}, month={Jul}, pages={G50–G57} }
 @inbook{blikslager_jones_grondhal_merritt_malbert_2004, place={Ames, Iowa}, edition={1st edition}, title={Pathophysiology of the Gastrointestinal Tract}, booktitle={Veterinary Pathophysiology}, publisher={Iowa State Press}, author={Blikslager, A.T. and Jones, S.L. and Grondhal, M.L. and Merritt, A.M. and Malbert, C.H.}, editor={Dunlop, R.H. and Malbert, C.H.Editors}, year={2004}, pages={111–142} }
 @article{campbell_ruaux_shifflett_steiner_williams_blikslager_2004, title={Physiological concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum}, volume={287}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00310.2003}, DOI={10.1152/ajpgi.00310.2003}, abstractNote={We have previously shown rapid in vitro recovery of barrier function in porcine ischemic-injured ileal mucosa, attributable principally to reductions in paracellular permeability. However, these experiments did not take into account the effects of luminal contents, such as bile salts. Therefore, the objective of this study was to evaluate the role of physiological concentrations of deoxycholic acid in recovery of mucosal barrier function. Porcine ileum was subjected to 45 min of ischemia, after which mucosa was mounted in Ussing chambers and exposed to varying concentrations of deoxycholic acid. The ischemic episode resulted in significant reductions in transepithelial electrical resistance (TER), which recovered to control levels of TER within 120 min, associated with significant reductions in mucosal-to-serosal 3 H-labeled mannitol flux. However, treatment of ischemic-injured tissues with 10 −5 M deoxycholic acid significantly inhibited recovery of TER with significant increases in mucosal-to-serosal 3 H-labeled mannitol flux, whereas 10 −6 M deoxycholic acid had no effect. Histological evaluation at 120 min revealed complete restitution regardless of treatment, indicating that the breakdown in barrier function was due to changes in paracellular permeability. Similar effects were noted with the application of 10 −5 M taurodeoxycholic acid, and the effects of deoxycholic acid were reversed with application of the Ca 2+ -mobilizing agent thapsigargin. Deoxycholic acid at physiological concentrations significantly impairs recovery of epithelial barrier function by an effect on paracellular pathways, and these effects appear to be Ca 2+ dependent.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Campbell, Nigel B. and Ruaux, Craig G. and Shifflett, Donnie E. and Steiner, Jöerg M. and Williams, David A. and Blikslager, Anthony T.}, year={2004}, month={Aug}, pages={G399–G407} }
 @article{davis_blikslager_catto_jones_2003, title={A Retrospective Analysis of Hepatic Injury in Horses with Proximal Enteritis (1984-2002)}, volume={17}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2003.tb02530.x}, DOI={10.1111/j.1939-1676.2003.tb02530.x}, abstractNote={The purpose of this study was to test the hypothesis that horses with proximal enteritis (PE) are predisposed to hepatic injury. We also determined whether the presence of liver injury in horses with PE was associated with other clinicopathologic abnormalities or affected outcome. The medical records of all horses admitted for evaluation of colic and gastric reflux between 1984 and 2002 were reviewed. Horses were considered to have PE if the diagnosis was made at surgery or postmortem examination or if they had clinical findings consistent with PE. Horses with a small intestinal strangulating obstruction (SISO) were used as the control group. Historic and clinicopathologic data were collected for each horse. The data were analyzed by descriptive statistics, parametric and nonparametric analyses, and logistic regression. Horses with PE had significantly higher serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities than horses with SISO (P < .05). Horses with PE were 12.1 times more likely to have high GGT activities than were horses with SISO. Horses with PE had an increased risk of at least 1 hepatic enzyme being increased if a high anion gap or large volume of reflux was present. Our conclusion is that horses with PE are more likely to have hepatic injury than horses with SISO. The mechanism of hepatic injury may involve ascending infection from the common bile duct, absorption of endotoxin or inflammatory mediators from the portal circulation, or hepatic hypoxia resulting from systemic inflammation and endotoxemic shock.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Davis, Jennifer L. and Blikslager, Anthony T. and Catto, Katrina and Jones, Samuel L.}, year={2003}, month={Nov}, pages={896–901} }
 @article{davis_blikslager_catto_jones_2003, title={A Retrospective Analysis of Hepatic Injury in Horses with Proximal Enteritis (1984-2002)}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0346994802&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2003)017<0896:ARAOHI>2.3.CO;2}, number={6}, journal={Journal of Veterinary Internal Medicine}, author={Davis, J.L. and Blikslager, A.T. and Catto, K. and Jones, S.L.}, year={2003}, pages={896–901} }
 @article{davis_blikslager_catto_jones_2003, title={A retrospective analysis of hepatic injury in horses with proximal enteritis (1984-2002)}, volume={17}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2003)017<0896:ARAOHI>2.3.CO;2}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Davis, JL and Blikslager, AT and Catto, K and Jones, SL}, year={2003}, pages={896–901} }
 @article{cole_blikslager_hunt_gookin_argenzio_2003, title={Cyclooxygenase blockade and exogenous glutamine  enhance sodium absorption in infected bovine ileum}, volume={284}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00172.2002}, DOI={10.1152/ajpgi.00172.2002}, abstractNote={We have previously shown that prostanoids inhibit electroneutral sodium absorption in Cryptosporidium parvum-infected porcine ileum, whereas glutamine stimulates electroneutral sodium absorption. We postulated that glutamine would stimulate sodium absorption via a cyclooxygenase (COX)-dependent pathway. We tested this hypothesis in C. parvum-infected calves, which are the natural hosts of cryptosporidiosis. Tissues from healthy and infected calves were studied in Ussing chambers and analyzed via immunohistochemistry and Western blots. Treatment of infected tissue with selective COX inhibitors revealed that COX-1 and -2 must be blocked to restore electroneutral sodium absorption, although the transporter involved did not appear to be the expected Na(+)/H(+) exchanger 3 isoform. Glutamine addition also stimulated sodium absorption in calf tissue, but although this transport was electroneutral in healthy tissue, sodium absorption was electrogenic in infected tissue and was additive to sodium transport uncovered by COX inhibition. Blockade of both COX isoforms is necessary to release the prostaglandin-mediated inhibition of electroneutral sodium uptake in C. parvum-infected calf ileal tissue, whereas glutamine increases sodium uptake by an electrogenic mechanism in this same tissue.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Cole, Jeffrey and Blikslager, Anthony and Hunt, Elaine and Gookin, Jody and Argenzio, Robert}, year={2003}, month={Mar}, pages={G516–G524} }
 @book{jones_blikslager_davis_mcconnico_roberts_lester_lohmann_barton_sanchez_zimmel_et al._2003, title={Disorders of the Gastrointestinal System}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84942574154&partnerID=MN8TOARS}, DOI={10.1016/B0-72-169777-1/50015-9}, journal={Equine Internal Medicine: Second Edition}, author={Jones, S.L. and Blikslager, A.T. and Davis, J.L. and McConnico, R.S. and Roberts, M.C. and Lester, G.D. and Lohmann, K.L. and Barton, M.H. and Sanchez, L.C. and Zimmel, D.N. and et al.}, year={2003}, pages={1–181} }
 @inbook{blikslager_jones_2003, place={St. Louis, MO}, edition={2nd edition}, title={Esophageal diseases}, booktitle={Equine Internal Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T. and Jones, S.L.}, editor={Reed, S.M. and Bayly, W.M. and Sellon, D.C.Editors}, year={2003}, pages={913–921} }
 @inbook{blikslager_2003, place={St. Louis, MO}, edition={2nd edition}, title={Ischemic disorders of the intestinal tract}, booktitle={Equine Internal Medicine}, publisher={Saunders Elsevier}, author={Blikslager, A.T.}, editor={Reed, S.M. and Bayly, W.M. and Sellon, D.C.Editors}, year={2003}, pages={802–814} }
 @article{gookin_galanko_blikslager_argenzio_2003, title={PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum}, volume={285}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00532.2002}, DOI={10.1152/ajpgi.00532.2002}, abstractNote={Small bowel epithelium is at the frontline of intestinal barrier function. Restitution is considered to be the major determinant of epithelial repair, because function recovers in parallel with restitution after acute injury. As such, studies of intact mucosa have largely been replaced by migration assays of cultured epithelia. These latter studies fail to account for the simultaneous roles played by villous contraction and paracellular permeability in recovery of barrier function. NSAIDs result in increased intestinal permeability and disease exacerbation in patients with inflammatory bowel disease (IBD). Thus we examined the reparative attributes of endogenous PGs after injury of ileal mucosa by deoxycholate (6 mM) in Ussing chambers. Recovery of transepithelial electrical resistance (TER) from 20-40 Omega.cm2 was abolished by indomethacin (Indo), whereas restitution of 40-100% of the villous surface was unaffected despite concurrent arrest of villous contraction. In the presence of PG, resident crypt and migrating epithelial cells were tightly apposed. In tissues treated with Indo, crypt epithelial cells had dilated intercellular spaces that were accentuated in the migrating epithelium. TER was fully rescued from the effects of Indo by osmotic-driven collapse of the paracellular space, and PG-mediated recovery was significantly impaired by blockade of Cl- secretion. These studies are the first to clearly distinguish the relative contribution of paracellular resistance vs. restitution to acute recovery of epithelial barrier function. Restitution was ineffective in the absence of PG-mediated paracellular space closure. Failure of PG-mediated repair mechanisms may underlie barrier failure resulting from NSAID use in patients with underlying enteropathy.}, number={5}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Gookin, Jody L. and Galanko, Joseph A. and Blikslager, Anthony T. and Argenzio, Robert A.}, year={2003}, month={Nov}, pages={G967–G979} }
 @article{little_dean_young_mckane_martin_jones_blikslager_2003, title={PI3K signaling is required for prostaglandin-induced  mucosal recovery in ischemia-injured porcine ileum}, volume={284}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00121.2002}, DOI={10.1152/ajpgi.00121.2002}, abstractNote={We have previously shown that PGE(2) and PGI(2) induce recovery of transepithelial resistance (TER) in ischemia-injured porcine ileal mucosa, associated with initial increases in Cl(-) secretion. We believe that the latter generates an osmotic gradient that stimulates resealing of tight junctions. Because of evidence implicating phosphatidylinositol 3-kinase (PI3K) in regulating tight junction assembly, we postulated that this signaling pathway is involved in PG-induced mucosal recovery. Porcine ileum was subjected to 45 min of ischemia, after which TER was monitored for a 180-min recovery period. Endogenous PG production was inhibited with indomethacin (5 microM). PGE(2) (1 microM) and PGI(2) (1 microM) stimulated recovery of TER, which was inhibited by serosal application of the osmotic agent urea (300 mosmol/kgH(2)O). The PI3K inhibitor wortmannin (10 nM) blocked recovery of TER in response to PGs or mucosal urea. Immunofluorescence imaging of recovering epithelium revealed that PGs restored occludin and zonula occludens-1 distribution to interepithelial junctions, and this pattern was disrupted by pretreatment with wortmannin. These experiments suggest that PGs stimulate recovery of paracellular resistance via a mechanism involving transepithelial osmotic gradients and PI3K-dependent restoration of tight junction protein distribution.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Little, Dianne and Dean, Rebecca A. and Young, Karen M. and McKane, Shaun A. and Martin, Linda D. and Jones, Samuel L. and Blikslager, Anthony T.}, year={2003}, month={Jan}, pages={G46–G56} }
 @book{blikslager_2003, title={Rectal Tears: Initial Management and Liability}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84888935519&partnerID=MN8TOARS}, DOI={10.1016/B978-0-7216-9540-2.50047-5}, journal={Current Therapy in Equine Medicine: Fifth Edition}, author={Blikslager, A.T.}, year={2003}, pages={150–153} }
 @article{tomlinson_blikslager_2003, title={Role of nonsteroidal anti-inflammatory drugs in gastrointestinal tract injury and repair}, volume={222}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0037377824&partnerID=MN8TOARS}, DOI={10.2460/javma.2003.222.946}, number={7}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Tomlinson, J and Blikslager, A}, year={2003}, month={Apr}, pages={946–951} }
 @book{blikslager_2003, title={Strangulating Obstruction of the Small Intestine}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84902063513&partnerID=MN8TOARS}, DOI={10.1016/B978-0-7216-9540-2.50039-6}, journal={Current Therapy in Equine Medicine: Fifth Edition}, author={Blikslager, A.T.}, year={2003}, pages={124–126} }
 @article{blikslager_2003, title={Treatment of gastrointestinal ischemic injury}, volume={19}, ISSN={["0749-0739"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-1842592080&partnerID=MN8TOARS}, DOI={10.1016/j.cveq.2003.08.004}, abstractNote={Ischemic injury is one of the most important causes of mortality in equine veterinary medicine. Although treatment of reperfusion injury has been attempted in a number of experimental trials to reduce the level of injury subsequent to an ischemic episode, this research has not resulted in the development of useful clinical treatments. Nevertheless, recent studies assessing intraluminal application of solutions containing antioxidants, nutrients, and vasodilators are promising. Furthermore, focusing on improving mucosal recovery after an ischemic event may provide an alternative method of reducing mortality. Potential treatments include administration of basement membrane components like hyaluronic acid, gut-specific nutrients like glutamine, and early return to feeding to stimulate endogenous repair mechanisms. Finally, recent studies evaluating NSAIDs have revealed the potential of flunixin meglumine to retard the mucosal repair process, indicating the need for judicious use of this drug.}, number={3}, journal={VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE}, author={Blikslager, AT}, year={2003}, month={Dec}, pages={715-+} }
 @inproceedings{determination of non-contact penetration parameters of the 60 watt 810 nm diode laser on equine respiratory tissue_2002, volume={4609}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036401997&partnerID=MN8TOARS}, DOI={10.1117/12.431789}, abstractNote={The Neodynium: Yttrium Aluminum Garnet (Nd: YAG) laser was one ofthe first lasers to allow tissue photoablation to be performed transendoscopically in the standing equine patient.1 It became very popular due to the fact that its irradiation can be applied through flexible fiber optic cables. Recently, a number of diode lasers have been marketed to the equine practitioner as replacements for the Nd: YAG laser, specifically the 810nm and 980nm diode lasers. Initially, both of these lasers produced a maximum of 20 watts total power output. Currently, higher power output versions being 50 or 60 watts are available to the practitioner. Producing a high power output means these lasers have the potential to be used in the non-contact configuration, as well as contact, when performing corrections of upper respiratory disorders ofthe horse. Penetration studies have been performed using lower power (20 watt) 810nm and 980nm diode laser which were compared to the depths and widths of penetration produced by the Nd: YAG laser.2,3 The purpose of this investigation was to evaluate the 60 watt 810nm diode lasers penetration delivering 200-600 joules on to equine respiratory tissue. Penetration parameters selected were width and depth of craters and were compared to the Nd: YAG laser set to deliver 200 joules of energy. This study determined that the 810nm diode lasers penetration parameter is close to that of the Nd: YAG laser. As the diode laser power output increased above 200 joules, it significantly penetrated respiratory tissue deeper than the Nd: YAG laser set at 200 joules output. Measurement of the crater depth created by the 810nm diode laser as its output power was increased at 100 joule increments was significantly deeper than the depth of crater formed by the previous power setting. Similarly, the diode laser's crater top and bottom width measurement, at 400 joules and greater, was significantly greater than or equal to that of the Nd: YAG lasers set to deliver 200 joules of energy. This investigation provided evidence that the 60 watt 810nm diode laser produces substantial penetration that can be applied not only in the contact mode successfully, but also in the non-contact mode providing the practitioner with a more versatile laser for transendoscopic application in the equine.}, booktitle={Proceedings of SPIE - The International Society for Optical Engineering}, year={2002}, pages={254–259} }
 @article{cole_gookin_gayle_eisemann_argenzio_blikslager_2002, title={Endoscopy via a gastric cannula to monitor the development of ulcers in the pars esophagea in pigs after consumption of a finely ground feed combined with a period of withholding of feed}, volume={63}, ISSN={["0002-9645"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036702024&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2002.63.1076}, abstractNote={To develop an endoscopic technique for use in monitoring devlopment of gastric ulcers via a gastric cannula during withholding of feed and administration of a finely ground diet to pigs.6 pigs weighing between 60 and 70 kg.A gastric cannula was surgically inserted adjacent to the pars esophagea in each pig. Pigs were fed a finely ground diet for two 7-day periods that were separated by a 48-hour period during which feed was withheld. Endoscopic examination via the gastric cannula was used to monitor development of ulcers in the pars esophageal region of the pigs during the 48-hour period of feed withhold and subsequent 7-day feeding period. An ulcer score was assigned during each endoscopic examination. A final examination was performed during necropsy and compared with results for the final endoscopic examination.Consumption of a finely ground diet for 7 days resulted in progressive erosive damage to the pars esophageal region of the stomach. Further significant increases in ulcerative damage were detected after 24 and 48 hours of withholding of feed. Final examination during necropsy did not reveal significant differences from results obtained during the final endoscopic examination.Endoscopic examination via a gastric cannula was an effective means of monitoring ulcer development in the pars esophagea of pigs. Feeding a finely ground diet and withholding of feed induced endoscopically observable ulcers in the stratified squamous epithelial region of the stomach. Direct visual examination during necropsy confirmed the accuracy of endoscopic examination.}, number={8}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Cole, JT and Gookin, JL and Gayle, JM and Eisemann, JH and Argenzio, RA and Blikslager, AT}, year={2002}, month={Aug}, pages={1076–1082} }
 @inproceedings{evaluation of topical application of indocyanine green (icg) to enhance penetration of the 810nm diode laser on equine respiratory tissue_2002, volume={4609}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036400113&partnerID=MN8TOARS}, DOI={10.1117/12.431788}, abstractNote={The Neodynium: Yttrium Aluminum Garnet (Nd: YAG) laser has been the most frequently used laser in correcting equine upper respiratory disorders.'4 Evaluation of this laser and several other lasers' ability to penetrate tissues is based on in vitro studies using portions of the arytenoid cartilage and the nasal septum.5 The parameters measured have routinely been the depth and width of the crater created by laser irradiation of the tissue.5 Previous studies, now considered the standard, have used a power output of 200 joules to create a measurable crater in order to make comparisons.5'6 The initial method of measurement consists of standard histological preparation followed by microscopic evaluation. This has been compared to computed tomography which has been determined to be as accurate.5'6 In a more recent study, we compared the 980nm and 810nm diode lasers producing a total power output of 20 watts, to the Nd: YAG laser.7 As demonstrated, both diode lasers can potentially be used as a substitute for the Nd: YAG laser.7 Our study also indicated that intravenous administration of indocyanine green (ICG) greatly enhanced the depth and width of crater formation in equine respiratory tissue with the laser set at 200 joules total power output.7 Intravenous administration of ICG was found to be an expensive protocol, therefore, the current study was devised to determine the penetration parameters of ICG after topical administration. The evaluation consisted of comparing depths and widths of penetration measured by computed tomography technique after ICG was topically sprayed on the tissue with solution concentrations ranging from 0. 1 % to 1%. The study's results demonstrated that topical application of ICG greater than or equal to 0.5% solution produced a depth ofpenetration significantly greater (p>0.05) than that ofthe Nd: YAG laser. The width measurements of craters created by the diode laser irradiation were found to be significantly less than those produced by the Nd: YAG laser. It was concluded that topical administration of ICG was more economical than intravenous administration.}, booktitle={Proceedings of SPIE - The International Society for Optical Engineering}, year={2002}, pages={247–253} }
 @article{little_blikslager_2002, title={Factors associated with development of ileal impaction in horses with surgical colic: 78 Cases (1986-2000)}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036637533&partnerID=MN8TOARS}, number={5}, journal={Equine Veterinary Journal}, author={Little, D. and Blikslager, A.T.}, year={2002}, pages={464–468} }
 @article{little_blikslager_2002, title={Factors associated with development of ileal impaction in horses with surgical colic: 78 cases (1986-2000)}, volume={34}, ISSN={["2042-3306"]}, DOI={10.2746/042516402776117773}, abstractNote={Deal impaction is prevalent in the south-eastern USA, where feeding of Coastal Bermuda hay has been implicated as a risk factor. Alternatively, infection with the tapeworm Anoplocephala perfoliata has been identified as a risk factor for ileal impaction in the UK. We hypothesised that feeding Coastal Bermuda hay and failure to administer routinely an anthelmintic with efficacy against tapeworms would place horses at risk of developing ileal impaction in the USA. Seventy-eight horses, with surgically confirmed ileal impaction and 100 horses admitted for colic that did not have an ileal impaction, were selected retrospectively for logistic regression analysis. Using odds ratios (OR) as an index of risk, feeding Coastal Bermuda hay (OR = 2.9) and failure to administer a pyrantel salt within 3 months of admission (OR = 3.1) placed horses at risk of development of ileal impaction. This study confirms the belief that feeding Coastal Bermuda hay places horses at risk of ileal impaction, although the quality of the hay may also play a role. Periodic administration of anthelmintics with efficacy against tapeworms should be considered to reduce risk of ileal impaction.}, number={5}, journal={EQUINE VETERINARY JOURNAL}, author={Little, D and Blikslager, AT}, year={2002}, month={Jul}, pages={464–468} }
 @article{gayle_jones_argenzio_blikslager_surgery_2002, title={Neutrophils increase paracellular permeability of restituted ischemic-injured porcine ileum}, volume={132}, ISSN={["0039-6060"]}, url={http://europepmc.org/abstract/med/12324760}, DOI={10.1067/msy.2002.125320}, abstractNote={Background. We have previously shown minimal evidence of neutrophil infiltration during early reperfusion of porcine ischemic ileum. However, we noted marked neutrophil infiltration 6 to 18 hours after ischemia during mucosal repair. We postulated such neutrophil infiltration would disrupt restituting epithelium. Methods. Pigs were pretreated with anti-CD11/CD18 monoclonal antibody, superoxide dismutase-polyethylene glycol, or saline solution before inducing 1 hour of ischemia. Pigs recovered for up to 18 hours, after which mucosal repair was assessed. Results. One hour of ischemia induced loss of 19 ± 7% of the villous epithelial surface area. Epithelial restitution covered the mucosal defect within 2 hours, although full recovery of mucosal barrier function required 6 hours. By 18 hours, a significant decrease in transepithelial electrical resistance and increase in transmucosal mannitol flux was noted despite the continued presence of complete epithelial coverage. Accumulation of neutrophils within restituting epithelium was noted on histologic examination, associated with electron-microscopic evidence of widened paracellular spaces. Pretreatment with anti-CD11/CD18 monoclonal antibody and superoxide dismutase-polyethylene glycol significantly reduced neutrophil infiltration and normalized transepithelial electrical resistance and mannitol fluxes. Conclusions. Mucosal inflammation during epithelial repair resulted in increased paracellular permeability as neutrophils traversed restituted epithelium. Blocking neutrophil adhesion or scavenging superoxide prevented mucosal dysfunction in recovering tissue. (Surgery 2002;132:461-70.)}, number={3}, journal={SURGERY}, author={Gayle, J. and Jones, S.L. and Argenzio, R.A. and Blikslager, A.T. and Surgery}, year={2002}, month={Sep}, pages={461–470} }
 @article{gayle_jones_argenzio_blikslager_2002, title={Neutrophils increase paracellular permeability of restituted ischemic-injured porcine ileum}, volume={132}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036748181&partnerID=MN8TOARS}, DOI={10.1016/S0039-6060(02)00112-5}, number={3}, journal={Surgery}, author={Gayle, J. and Jones, S.L. and Argenzio, R.A. and Blikslager, A.T.}, year={2002}, pages={461–470} }
 @article{blikslager_zimmel_young_campbell_little_argenzio_2002, title={Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2}, volume={50}, ISSN={0017-5749}, url={http://dx.doi.org/10.1136/gut.50.5.615}, DOI={10.1136/gut.50.5.615}, abstractNote={We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear.To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production.Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity.Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5x10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity.The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.}, number={5}, journal={Gut}, publisher={BMJ}, author={Blikslager, A.T. and Zimmel, D.N. and Young, K.M. and Campbell, N.B. and Little, D. and Argenzio, R.A.}, year={2002}, month={May}, pages={615–623} }
 @misc{jones_blikslager_2002, title={Role of the enteric nervous system in the pathophysiology of secretory diarrhea}, volume={16}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2002)016<0222:ROTENS>2.3.CO;2}, abstractNote={Details of the physiology and pathophysiology of epithelial secretion in the gastrointestinal tract are becoming clear, leading to new models of the mechanisms underlying diarrhea. The enteric nervous system is a critical component of the mechanism regulating fluid secretion in the normal gut and a key element in the pathophysiology of diarrhea. Neural reflex pathways increase epithelial fluid secretion in response to several enteric pathogens of veterinary importance such as Salmonella spp., Cryptosporidium parvum, rotavirus, and Clostridium difficile. Moreover, the enteric nervous system has an important role in epithelial secretion triggered by products of activated leukocytes during inflammation. New approaches targeting the enteric nervous system show promise for the treatment of secretory diarrhea.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Jones, SL and Blikslager, AT}, year={2002}, pages={222–228} }
 @article{jones_blikslager_2002, title={Role of the enteric nervous system in the pathophysiology of secretory diarrhea}, volume={16}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036581818&partnerID=MN8TOARS}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Jones, S.L. and Blikslager, A.T.}, year={2002}, pages={222–228} }
 @article{morton_blikslager_2002, title={Surgical and postoperative factors influencing short-term survival of horses following small intestinal resection: 92 Cases (1994-2001)}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036632826&partnerID=MN8TOARS}, number={5}, journal={Equine Veterinary Journal}, author={Morton, A.J. and Blikslager, A.T.}, year={2002}, pages={450–454} }
 @article{morton_blikslager_2002, title={Surgical and postoperative factors influencing short-term survival of horses following small intestinal resection: 92 cases (1994-2001)}, volume={34}, ISSN={["0425-1644"]}, DOI={10.2746/042516402776117700}, abstractNote={Although short-term survival rates following small intestinal resection reportedly range from 48–88%, there is little information on predicting which horse may or may not survive small intestinal (SI) resection and anastomosis. The aim of this study was to identify factors that contribute to nonsurvival in horses following small intestinal resection. Medical records of horses which recovered from anaesthesia following SI resection were reviewed. Clinical and surgical variables were evaluated for their association with short-term survival using logistic regression and were reported as odds ratios (OR), including the 95% confidence interval (CI), indicating the likelihood of horses not surviving to hospital discharge. Ninety-two records met the criteria for inclusion. Thirty-six (81.8%) of the horses that underwent jejunojejunostomy (JJ) and 34 (70.8%) of the horses that underwent jejunocaecostomy (JC) survived to discharge. Multiple logistic analysis indicated that postoperative ileus (OR = 29.7; 95% CI 2.5–354.6), repeat celiotomy (OR = 18; CI 1.7–187.6), and an elevated heart rate of ≥ 60 beats/min (OR = 5.6; CI 1.5–20.6) were the principal factors associated with nonsurvival. A low total plasma protein of <55 g/l (OR = 1.8; CI 0.5–7.6) was incorporated in the final model because its inclusion improved the overall validity of the model Clinicians should be aware of the factors associated with the greatest likelihood of nonsurvival following small intestinal resection, so that they can institute aggressive treatment and accurately inform owners on the likelihood of survival.}, number={5}, journal={EQUINE VETERINARY JOURNAL}, author={Morton, AJ and Blikslager, AT}, year={2002}, month={Jul}, pages={450–454} }
 @article{campbell_jones_blikslager_2002, title={The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon}, volume={34}, ISSN={["0425-1644"]}, DOI={10.2746/042516402776117737}, abstractNote={A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l deoxycholate for 30 min, after which they were recovered for 4 h in Ussing chambers. Contrary to the proposed hypothesis, recovery of bile-injured colonic mucosa was not affected by flunixin or etodolac, despite significantly depressed prostanoid production. However, treatment of control tissue with flunixin led to increases in mucosal permeability, whereas treatment with etodolac had no significant effect. Therefore, although recovery from bile-induced colonic injury maybe independent of COX-elaborated prostanoids, treatment of control tissues with nonselective COX inhibitors may lead to marked increases in permeability. Alternatively, selective inhibition of COX-2 may reduce the incidence of adverse effects in horses requiring NSAID therapy.}, number={5}, journal={EQUINE VETERINARY JOURNAL}, author={Campbell, NB and Jones, SL and Blikslager, AT}, year={2002}, month={Jul}, pages={493–498} }
 @article{campbell_jones_blikslager_2002, title={The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036634884&partnerID=MN8TOARS}, number={5}, journal={Equine Veterinary Journal}, author={Campbell, N.B. and Jones, S.L. and Blikslager, A.T.}, year={2002}, pages={493–498} }
 @article{gayle_burrell_anderson_redding_blikslager_2001, title={Deep digital flexor tenotomy for treatment of severe laminitis in a cow}, volume={219}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2001.219.644}, abstractNote={A first-calf Guernsey cow was referred for evaluation of severe udder edema, mastitis, metritis, and ketosis. During the course of treatment, the cow became recumbent and was unable to rise. Intensive treatment resulted in the cow being able to stand for short periods with the aid of a sling. However, severe pressure necrosis of the udder and ongoing mastitis made performance of a complete mastectomy necessary. After surgery, the cow's condition improved, although assistance in standing was still required. Radiography of the distal phalanges revealed severe rotation in the right lateral and left medial digits of the hind limbs. The laminitis was nonresponsive to medical management; therefore, a deep digital flexor tenotomy was performed in the affected claws. The procedure provided almost immediate relief of signs of foot pain and resulted in ability to stand without assistance. Deep digital flexor tenotomy should be considered when treating cows with severe laminitis.}, number={5}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Gayle, JM and Burrell, GA and Anderson, KL and Redding, WR and Blikslager, AT}, year={2001}, month={Sep}, pages={644–646} }
 @article{gayle_burrell_anderson_rich redding_blikslager_2001, title={Deep digital flexor tenotomy for treatment of severe laminitis in a cow}, volume={219}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0040621851&partnerID=MN8TOARS}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Gayle, J.M. and Burrell, G.A. and Anderson, K.L. and Rich Redding, W. and Blikslager, A.T.}, year={2001}, pages={644–646+613} }
 @article{blikslager_hunt_guerrant_rhoads_argenzio_2001, title={Glutamine transporter in crypts compensates for loss of villus absorption in bovine cryptosporidiosis}, volume={281}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.2001.281.3.G645}, DOI={10.1152/ajpgi.2001.281.3.g645}, abstractNote={Cryptosporidium parvum infection represents a significant cause of diarrhea in humans and animals. We studied the effect of luminally applied glutamine and the PG synthesis inhibitor indomethacin on NaCl absorption from infected calf ileum in Ussing chambers. Infected ileum displayed a decrease in both mucosal surface area and NaCl absorption. Indomethacin and glutamine or its stable derivative alanyl-glutamine increased the net absorption of Na(+) in infected tissue in an additive manner and to a greater degree than in controls. Immunohistochemical and Western blot studies showed that in control animals neutral amino acid transport system ASC was present in villus and crypts, whereas in infected animals, ASC was strongly present only on the apical border of crypts. These results are consistent with PGs mediating the altered NaCl and water absorption in this infection. Our findings further illustrate that the combined use of a PG synthesis inhibitor and glutamine can fully stimulate Na(+) and Cl(-) absorption despite the severe villous atrophy, an effect associated with increased expression of a Na(+)-dependent amino acid transporter in infected crypts.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Blikslager, Anthony and Hunt, Elaine and Guerrant, Richard and Rhoads, Marc and Argenzio, Robert}, year={2001}, month={Sep}, pages={G645–G653} }
 @article{blikslager_tate_jones_2001, title={Neodymium: yttrium aluminum garnet laser ablation of a urethral web to relieve urinary outflow obstruction in a horse}, volume={218}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2001.218.1970}, DOI={10.2460/javma.2001.218.1970}, abstractNote={An 8-year-old Hanoverian gelding was examined because of urine dribbling and urethral obstruction. Mild proprioceptive deficits of the left hind limb were evident during neurologic examination. Ultrasonography per rectum revealed dilatation of the pelvic portion of the urethra. Endoscopy of the urethra revealed 2 webs of tissue: 1 was located 10 cm proximal to the external urethral opening; the other was located 65 cm proximal to the external urethral opening and prevented passage of the endoscope into the urinary bladder. The mass was ablated with a neodymium:yttrium-aluminum-garnet laser, using a transendoscopic noncontact technique. On follow-up examination 6 months after laser surgery, an endoscope could easily be passed into the bladder, and no urethral web was seen. The horse was able to void a stream of urine but continued to dribble urine intermittently. The proximal location of the urethral lesion in this horse would have made use of traditional surgical methods problematic, whereas transendoscopic laser photoablation was easy and effective.}, number={12}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Blikslager, A.T. and Tate, L.P. and Jones, S.}, year={2001}, month={Jun}, pages={1970–1972} }
 @article{neodymium:yttrium-aluminum-garnet laser ablation of a urethral web to relieve urinary outflow obstruction in a horse_2001, volume={218}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035877844&partnerID=MN8TOARS}, number={12}, journal={Journal of the American Veterinary Medical Association}, year={2001}, pages={1970–1972} }
 @article{blikslager_pell_young_2001, title={PGE2 triggers recovery of transmucosal resistance via EP receptor cross talk in porcine ischemia-injured ileum}, volume={281}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.2001.281.2.G375}, DOI={10.1152/ajpgi.2001.281.2.g375}, abstractNote={16,16-Dimethyl-PGE2 (PGE2) may interact with one of four prostaglandin type E (EP) receptors, which signal via cAMP (via EP2 or EP4 receptors) or intracellular Ca(2+) (via EP1 receptors). Furthermore, EP3 receptors have several splice variants, which may signal via cAMP or intracellular Ca(2+). We sought to determine the PGE2 receptor interactions that mediate recovery of transmucosal resistance (R) in ischemia-injured porcine ileum. Porcine ileum was subjected to 45 min of ischemia, after which the mucosa was mounted in Ussing chambers. Tissues were pretreated with indomethacin (5 microM). Treatment with the EP1, EP2, EP3, and EP4 agonist PGE2 (1 microM) elevated R twofold and significantly increased tissue cAMP content, whereas the EP2 and EP4 agonist deoxy-PGE1 (1 microM) or the EP1 and EP3 agonist sulprostone (1 microM) had no effect. However, a combination of deoxy-PGE1 and sulprostone stimulated synergistic elevations in R and tissue cAMP content. Furthermore, treatment of tissues with deoxy-PGE1 and the Ca(2+) ionophore A-23187 stimulated synergistic increases in R and cAMP, indicating that PGE2 triggers recovery of R via EP receptor cross talk mechanisms involving cAMP and intracellular Ca(2+).}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Pell, Susan M. and Young, Karen M.}, year={2001}, month={Aug}, pages={G375–G381} }
 @inproceedings{l.p._blikslager_campbell_2001, title={Preliminary report: Comparison of 980-nm, 808-nm diode laser enhanced with Indocyanine green to the Nd: YAG laser applied to equine respiratory tissue}, volume={4244}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034935283&partnerID=MN8TOARS}, DOI={10.1117/12.427772}, abstractNote={The Neodynium: Yttrium Aluminum Garnet (Nd:YAG) laser has been the mainstay of performing upper respiratory laser surgery in the equine since 1984. The 808-nm diode laser has also been applied transendoscopically as well as the 980-nm diode laser over recent years. It has been shown that Indocyanine Green (ICG) enhances the performance of the 808- nm laser because it is absorbed at 810 nm of light. The 808- nm laser's tissue interaction combined with ICG is equivalent to or greater than the Nd:YAG laser's cutting ability. The 980-nm diode laser performance was similar to that of the Nd:YAG as determined by the parameters of this study. This study compared the depths and widths of penetration achieved with the 808-nm diode laser after intravenous injection of ICG on equine respiratory tissue. It also compared depths and widths of penetration achieved by the non-contact application of the 980-nm diode laser delivering the same energy of 200 joules. The depths and widths of penetration of both diode lasers were compared to themselves and to the Nd:YAG laser with all factors remaining constant.}, booktitle={Proceedings of SPIE - The International Society for Optical Engineering}, author={L.P., Tate, Jr. and Blikslager, A.T. and Campbell, N.B.}, year={2001}, pages={583–590} }
 @article{little_redding_blikslager_2001, title={Risk factors for reduced postoperative fecal output in horses: 37 cases (1997-1998)}, volume={218}, ISSN={["0003-1488"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035253634&partnerID=MN8TOARS}, DOI={10.2460/javma.2001.218.414}, abstractNote={To determine prevalence and risk factors for development of ileus of the large intestine after surgery in horses, identified by reduced postoperative fecal output (RPFO).Retrospective study.37 horses that developed RPFO after undergoing general anesthesia for reasons unrelated to the gastrointestinal tract.Fecal output was obtained from medical records as number of defecations per 24-hour period after surgery; RPFO was defined as < or = 3 defecations per 24-hour period after surgery. The reference population included 48 horses that defecated > or = 4 times during the same period. Demographic, clinical, and surgical variables were evaluated for their association with development of RPFO by use of logistic regression analysis.Ten (12%) horses, all of which had RPFO, developed signs of colic after surgery. Horses > or = 5 years old that underwent orthopedic procedures of > 60 minutes' duration and that did not receive phenylbutazone after surgery were at significant risk for developing RPFO.Results suggest that after surgery unrelated to the gastrointestinal tract in horses, there is an intermediate clinical phase characterized by reduced fecal output preceding overt signs of colic. Recognition of RPFO may reduce morbidity and mortality of such horses.}, number={3}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Little, D and Redding, WR and Blikslager, AT}, year={2001}, month={Feb}, pages={414–420} }
 @inbook{blikslager_2001, place={St. Louis, MO}, title={Surgical Disorders of the Large Intestine}, booktitle={Large Animal Internal Medicine}, publisher={Mosby}, author={Blikslager, A.T.}, editor={Smith, B.P.Editor}, year={2001}, pages={662–665} }
 @inbook{blikslager_2001, place={St. Louis, MO}, title={Surgical Disorders of the Small Intestine}, booktitle={Large Animal Internal Medicine}, publisher={Mosby}, author={Blikslager, A.T.}, editor={Smith, B.P.Editor}, year={2001}, pages={649–653} }
 @article{jones_blikslager_2001, title={The future of antiinflammatory therapy}, volume={17}, ISSN={["0749-0739"]}, DOI={10.1016/S0749-0739(17)30060-3}, abstractNote={The cells and mediators that make up the inflammatory response have the potential to injure tissues and contribute to the pathophysiology of many inflammatory diseases. Strategies to reduce neutrophil migration into sites of inflammation and subsequent activation by inhibiting integrin-mediated adhesion hold promise for successful treatment of a variety of inflammatory diseases. New pharmacologic agents that specifically target prostanoid mediators of inflammation by specifically inhibiting the activity of cyclooxygenase 2 are potent antiinflammatory agents with fewer gastrointestinal side effects than nonspecific cyclooxygenase inhibitors. These areas of antiinflammatory research are rapidly yielding drugs with diverse future applications in equine medicine.}, number={2}, journal={VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE}, author={Jones, SL and Blikslager, A}, year={2001}, month={Aug}, pages={245-+} }
 @article{jones_blikslager_2001, title={The future of antiinflammatory therapy.}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-1942520108&partnerID=MN8TOARS}, number={2}, journal={The Veterinary clinics of North America. Equine practice}, author={Jones, S.L. and Blikslager, A.}, year={2001} }
 @article{ange_eisemann_argenzio_almond_blikslager_2000, title={Effects of feed physical form and buffering solutes on water disappearance and proximal stomach pH in swine.}, volume={78}, ISSN={0021-8812}, url={http://dx.doi.org/10.2527/2000.7892344x}, DOI={10.2527/2000.7892344x}, abstractNote={The effects of the physical form of feed on water disappearance and the effects of buffered water on proximal stomach pH in swine were determined in two experiments. In Exp. 1, 32 barrows were used to evaluate the water disappearance in pigs fed a finely ground and pelleted diet vs those fed a coarsely ground and mashed diet for ad libitum consumption over a 2-wk interval. There were four replicates with eight pigs per replicate. Average daily water and feed disappearance did not differ (P = 0.06 and P = 0.10, respectively). However, average daily water to feed ratio was higher for pigs on the pelleted diet (4.21+/-0.31 L/kg vs 3.04+/-0.33 L/kg; P = 0.02). The higher ratio for the pelleted diet indicated that this may be the cause of a more fluid digesta allowing reflux of irritants from the distal stomach to damage the pars esophageal region of the proximal stomach. In Exp. 2, four barrows (25+/-2 kg) had gastric cannulas surgically implanted into the proximal region of the stomach. Pigs were given ad libitum access to a finely ground and pelleted diet. The experimental design was a Latin square. Water treatments included water (control), 200 mOsm NaHCO3, 250 mOsm NaHCO3, and 250 mOsm mono-dibasic sodium phosphate. Pigs were given a 4-d adjustment period, and pH measurements began on the morning of the 5th d and continued for 24 h under normal feeding conditions. Feed was removed and measurements were continued for 16 h. Buffered water raised the pH of the proximal region of the stomach compared to the control (P < 0.001). Average pH while consuming the water treatments was 3.65+/-0.11 (n = 4) for water control, 4.86+/-0.11 (n = 4) for the 200 mOsm NaHCO3, 4.63+/-0.11 (n = 4) for the 250 mOsm NaHCO3, and 4.59+/-0.14 (n = 3) for the 250 mOsm mono-dibasic sodium phosphate. Buffers also raised the pH of the proximal region of the stomach for the fed (P < 0.001) and the feed restriction (P < 0.01) phases of the trial. Water disappearance rates in pigs given NaHCO3 were higher than in the control (P < 0.01). Average daily water disappearance for the treatments was 9.13+/-0.74 L for the control, 13.56+/-0.74 L for 200 mOsm NaHCO3, 13.77+/-0.74 L for the 250 mOsm NaHCO3, and 10.33+/-0.95 L for the phosphate buffer. The proximal pH of the stomach was increased by adding buffers to the water supply. Addition of NaHCO3 buffers also caused increased water disappearance.}, number={9}, journal={Journal of Animal Science}, publisher={Oxford University Press (OUP)}, author={Ange, K D and Eisemann, J H and Argenzio, R A and Almond, G W and Blikslager, A T}, year={2000}, pages={2344} }
 @article{blikslager_roberts_young_rhoads_argenzio_2000, title={Genistein augments prostaglandin-induced recovery  of barrier function in ischemia-injured porcine ileum}, volume={278}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.2000.278.2.G207}, DOI={10.1152/ajpgi.2000.278.2.g207}, abstractNote={We have previously shown that PGE(2) enhances recovery of transmucosal resistance (R) in ischemia-injured porcine ileum via a mechanism involving chloride secretion. Because the tyrosine kinase inhibitor genistein amplifies cAMP-induced Cl(-) secretion, we postulated that genistein would augment PGE(2)-induced recovery of R. Porcine ileum subjected to 45 min of ischemia was mounted in Ussing chambers, and R and mucosal-to-serosal fluxes of [(3)H]N-formyl-methionyl-leucyl phenylalanine (FMLP) and [(3)H]mannitol were monitored as indicators of recovery of barrier function. Treatment with genistein (10(-4) M) and PGE(2) (10(-6) M) resulted in synergistic elevations in R and additive reductions in mucosal-to-serosal fluxes of [(3)H]FMLP and [(3)H]mannitol, whereas treatment with genistein alone had no effect. Treatment of injured tissues with genistein and either 8-bromo-cAMP (10(-4) M) or cGMP (10(-4) M) resulted in synergistic increases in R. However, treatment of tissues with genistein and the protein kinase C (PKC) agonist phorbol myristate acetate (10(-5)-10(-6) M) had no effect on R. Genistein augments recovery of R in the presence of cAMP or cGMP but not in the presence of PKC agonists.}, number={2}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Roberts, Malcolm C. and Young, Karen M. and Rhoads, J. Marc and Argenzio, Robert A.}, year={2000}, month={Feb}, pages={G207–G216} }
 @article{rhoads_argenzio_chen_graves_licato_blikslager_smith_gatzy_brenner_2000, title={Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, Raf-independent mechanism}, volume={118}, ISSN={["0016-5085"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033970974&partnerID=MN8TOARS}, DOI={10.1016/S0016-5085(00)70417-3}, abstractNote={Infectious diarrhea caused by viruses plus enterotoxigenic bacteria is often more severe than diarrhea induced by either pathogen alone. We postulated that the increased cell adenosine 3',5'-cyclic monophosphate (cAMP) concentration observed during infection by enterotoxigenic organisms retards the intestinal repair process by blocking activation of mitogen-activated protein kinases (MAPKs) in proliferating intestinal cells.We evaluated the effects of glutamine on MAPK activity, thymidine incorporation, and cell number in glutamine-starved and -sufficient rat intestinal crypt cells (IEC-6).In glutamine-starved cells, 10 mmol/L glutamine in the absence of serum stimulated [(3)H]thymidine incorporation 8-fold. This effect was inhibited by 60% with 8-(4-chlorophenylthio) (8-CPT)-cAMP (100 micromol/L) + isobutyl methylxanthine (100 micromol/L). In cells not starved of glutamine, glutamine stimulated thymidine incorporation by 3-fold, and 8-CPT-cAMP completely blocked the mitogenic effect. Inhibition of proliferation by cAMP persisted for at least 68 hours after cAMP removal. In vitro kinase assays showed that glutamine signaling requires an intact ERK (extracellular signal-related kinase) pathway in unstarved cells. In starved cells, at least one other pathway (JNK) was activated by glutamine, and the mitogenic inhibition by 8-CPT-cAMP was incomplete. Other intestinal fuels (glucose and acetate) were not mitogenic.Increased levels of intracellular cAMP inhibit ERKs but only partially reduce glutamine-stimulated proliferation in enterocytes adapted to low glutamine.}, number={1}, journal={GASTROENTEROLOGY}, author={Rhoads, JM and Argenzio, RA and Chen, WN and Graves, LM and Licato, LL and Blikslager, AT and Smith, J and Gatzy, J and Brenner, DA}, year={2000}, month={Jan}, pages={90–100} }
 @article{blikslager_tate_2000, title={History, instrumentation, and techniques of flexible endoscopic laser surgery in horses}, volume={16}, ISSN={["1558-4224"]}, DOI={10.1016/S0749-0739(17)30103-7}, abstractNote={There are clearly a number of applications for which flexible endoscopic laser surgery has become the state of the art in equine surgery, and the Nd:YAG laser seems to be the most versatile instrument for this type of surgery. Nevertheless, it is critical to understand the advantages and disadvantages of each laser technique. For example, the Nd:YAG laser used in a noncontact fashion seems to be superior when ablation of tissue is required such as treatment of upper airway masses. Conversely, contact Nd:YAG laser techniques have proven themselves to be superior when more precise cutting is advantageous such as treatment of epiglottic entrapment. Ultimately, it seems that a range of lasers is necessary to ensure selection of the most appropriate technique, adding significantly to the expense of equipment but improving the outcome for a range of equine diseases.}, number={2}, journal={VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE}, author={Blikslager, AT and Tate, LP}, year={2000}, month={Aug}, pages={251-+} }
 @article{history, instrumentation, and techniques of flexible endoscopic laser surgery in horses._2000, volume={16}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-2342587507&partnerID=MN8TOARS}, number={2}, journal={The Veterinary clinics of North America. Equine practice}, year={2000}, pages={251–268} }
 @article{gayle_blikslager_bowman_2000, title={Mesenteric rents as a source of small intestinal strangulation in horses: 15 cases (1990-1997)}, volume={216}, ISSN={["0003-1488"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034181105&partnerID=MN8TOARS}, DOI={10.2460/javma.2000.216.1446}, abstractNote={To describe the clinical findings in horses with small intestinal strangulation through mesenteric rents, and to determine the recurrence and survival rates after surgery.Retrospective study.15 horses with small intestinal obstruction via a mesenteric rent.Medical records of horses with obstruction of the small intestine via a mesenteric rent between January 1990 and December 1997 were reviewed. The signalment, history, initial physical examination findings, results of abdominocentesis, and clinical laboratory values were recorded. Surgical findings, including location of the mesenteric rent and surgical procedure performed, were recorded. Short- and long-term survival rates were calculated.Most mesenteric rents were located in the mesentery of the small intestine (13 horses). Two horses had multiple mesenteric defects. Seven horses were euthanatized at surgery because of an inability to reduce the entrapped intestine (3 horses), uncontrollable hemorrhage (2), inability to close the rent (1), and the amount of compromised intestine involved (1). Seven horses required intestinal resection and anastomosis. The median length of intestine resected was 2.6 m (range, 0.6 to 4.5 m). The mesenteric rents created during resection were not closed in 2 horses. One of these 2 horses subsequently developed a strangulating obstruction through the open rent. Seven of 15 horses in our study were discharged from the hospital (i.e., short-term survival rate of 47% [7/15]). Long-term follow-up information was available for 5 of the 7 horses (follow-up duration of 5 months to 9 years), of which 2 died as a result of colic, and 1 horse was euthanatized because of severe arthritis (i.e., long-term survival rate of 40% [2/5]).Inability to reduce the intestinal obstruction, severe hemorrhage from the mesentery, and the length of intestine involved are the main factors that decrease survival rates in horses with small intestinal strangulation caused by mesenteric rents.}, number={9}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Gayle, JM and Blikslager, AT and Bowman, KF}, year={2000}, month={May}, pages={1446–1449} }
 @inproceedings{pilot study: intravenous use of indocyanine green as an enhancer for 808-nm diode laser application in the equine_2000, volume={3907}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033723469&partnerID=MN8TOARS}, booktitle={Proceedings of SPIE - The International Society for Optical Engineering}, year={2000}, pages={454–460} }
 @article{gayle_blikslager_jones_2000, title={Role of neutrophils in intestinal mucosal injury}, volume={217}, ISSN={["0003-1488"]}, url={http://europepmc.org/abstract/med/10953711}, DOI={10.2460/javma.2000.217.498}, number={4}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Gayle, JM and Blikslager, AT and Jones, SL}, year={2000}, month={Aug}, pages={498–500} }
 @article{campbell_blikslager_2000, title={The role of cyclooxygenase inhibitors in repair of ischaemic-injured jejunal mucosa in the horse.}, ISBN={0425-1644}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034207798&partnerID=MN8TOARS}, DOI={10.1111/j.2042-3306.2000.tb05335.x}, abstractNote={Cyclooxygenase inhibitors are administered to horses to prevent endotoxin-induced elaboration of prostaglandins. However, PGE2 and PGI2 stimulate repair of injured intestine. There are 2 isoforms of cyclooxygenase: COX-1, which constitutively produces prostaglandins and COX-2, which is induced by inflammation. We hypothesised that the nonspecific cyclooxygenase inhibitor flunixin meglumine would retard repair of ischaemic intestinal injury by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac, would permit repair as a result of continued COX-1 prostaglandin production. Segments of equine jejunum were subjected to ischaemia for 1 h, and recovered for 4 h in Ussing chambers. In ischaemic tissue, treated with the nonspecific cyclooxygenase inhibitor, flunixin meglumine (2.7 x 10(-5) mol/l), production of PGE2 and PGI2 was inhibited, and there was no evidence of recovery based on measurements of transepithelial resistance. Conversely, untreated ischaemic tissues or tissues treated with the specific COX-2 inhibitor etodolac (2.7 x 10(-5) mol/l) had significant elevations in PGE2 and PGI2, and significant recovery of transepithelial resistance. These studies suggest that specific COX-2 inhibitors may provide an advantageous alternative to nonspecific cyclooxygenase inhibitors in horses with colic.}, number={32}, journal={Equine veterinary journal. Supplement}, author={Campbell, N.B. and Blikslager, A.T.}, year={2000}, pages={59–64} }
 @article{zimmel_blikslager_jones_mcfarlane_young_2000, title={Vaccine-associated anaphylactic-like reaction in a horse}, volume={22}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0348245852&partnerID=MN8TOARS}, number={1}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Zimmel, D.N. and Blikslager, A.T. and Jones, S.L. and McFarlane, D. and Young, K.}, year={2000}, pages={81–84} }
 @article{blikslager_1999, title={Cyclooxygenase-2 Inhibitors in Equine Practice}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0347120540&partnerID=MN8TOARS}, number={6}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Blikslager, A.T.}, year={1999}, pages={548–550} }
 @article{blikslager_rhoads_bristol_roberts_argenzio_1999, title={Glutamine and transforming growth factor-α stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine}, volume={125}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033056065&partnerID=MN8TOARS}, DOI={10.1016/S0039-6060(99)70264-3}, abstractNote={Background: Epidermal growth factor (EGF) signals enterocyte proliferation via extracellular regulated kinases (ERKs). Because glutamine is required for EGF-stimulated proliferation and stimulates ERKs in intestinal cell culture, we hypothesized that glutamine and the EGF-related peptide transforming growth factor–alpha (TGF-α) would synergistically enhance repair associated with stimulation of ERKs. Methods: Thiry-Vella loops were created in juvenile pigs. One half of the loop was subjected to 2 hours of ischemia, and the other half served as control. Loops were infused daily with Ringer's solution containing 140 mmol/L glucose, 140 mmol/L glutamine, 140 mmol/L glucose plus 60 μg/L TGF-α, or 140 mmol/L glutamine plus 60 μg/L TGF-α. Results: After 2 hours of ischemia, complete villous epithelial sloughing was present. By 18 hours, villous epithelium had fully restituted, but villi remained stunted until 144 hours after injury. Glutamine + TGF-α triggered sustained increases in ERK activity compared with glucose-treated tissues (maximal at 18 hours), whereas glutamine alone or glucose + TGF-α caused only transient elevations in ERK activity. By 72 hours, villous surface area had increased to normal values with glutamine plus TGF-α treatment, whereas villi remained stunted with glucose alone, glutamine alone, or glucose plus TGF-α. Conclusions: Glutamine plus TGF-α treatment restored mucosal architecture within 72 hours of severe ischemic injury associated with sustained elevations in ERK activity. (Surgery 1999;125:186-94.)}, number={2}, journal={Surgery}, author={Blikslager, Anthony and Rhoads, J.M. and Bristol, D.G. and Roberts, M.C. and Argenzio, R.A.}, year={1999}, pages={186–194} }
 @inproceedings{hunt_argenzio_blikslager_1999, title={New therapies for calf diarrhea: therapy and prevention for the new millennium}, volume={32}, booktitle={Proceedings of the thirty second annual conference, American Association of Bovine Practitioners: September 23-26, 1999, Nashville, TN}, publisher={Stillwater, OK: American Association of Bovine Practitioners}, author={Hunt, E. and Argenzio, R. and Blikslager, A.}, year={1999}, month={Sep}, pages={118–122} }
 @book{king_1999, place={Cary, NC}, title={Preventing Colic in Horses}, publisher={Paper Horse}, author={King, C.}, editor={Blikslager, A.T.Editor}, year={1999} }
 @article{blikslager_roberts_argenzio_1999, title={Prostaglandin-induced recovery of barrier function  in porcine ileum is triggered by chloride secretion}, volume={276}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.1999.276.1.G28}, DOI={10.1152/ajpgi.1999.276.1.g28}, abstractNote={We have previously shown that PGI 2 and PGE 2 have a synergistic role in restoring electrical transepithelial resistance ( R) in ischemia-injured porcine ileum via the second messengers Ca 2+ and cAMP. Because Ca 2+ and cAMP stimulate Cl − secretion, we assessed the role of PG-induced Cl − secretion in recovery of R. Mucosa from porcine ileum subjected to ischemia for 45 min was mounted in Ussing chambers and bathed in indomethacin and Ringer solution. Addition of PGs stimulated a twofold increase in R, which was preceded by elevations in short-circuit current (increase of 25 μA/cm 2 ). The PG-induced effect on R was partially inhibited with bumetanide, an inhibitor of Cl − secretion. The remaining elevations in R were similar in magnitude to those induced in ischemic tissues by amiloride, an inhibitor of Na + absorption. Treatment with 10 −4 M 8-bromo-cGMP or 300 mosM mucosal urea resulted in elevations in R similar to those attained with PG treatment. PGs signal recovery of Rvia induction of Cl − secretion and inhibition of Na + absorption, possibly by establishing a transmucosal osmotic gradient.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Roberts, Malcolm C. and Argenzio, Robert A.}, year={1999}, month={Jan}, pages={G28–G36} }
 @inbook{berschneider_blikslager_roberts_1999, title={Role of duodenal reflux in nonglandular gastric ulcer disease of the mature horse}, booktitle={Equine gastric ulceration  (Equine veterinary journal supplement)}, publisher={Suffolk, UK: British Equine Veterinary Association}, author={Berschneider, H. M. and Blikslager, A. T. and Roberts, M. C.}, editor={T. S. Mair, P. D. Rossdale and Merritt, A. M.Editors}, year={1999}, month={Apr}, pages={24–29} }
 @article{berschneider_blikslager_roberts_1999, title={Role of duodenal reflux in nonglandular gastric ulcer disease of the mature horse.}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033106966&partnerID=MN8TOARS}, number={29}, journal={Equine veterinary journal. Supplement}, author={Berschneider, H.M. and Blikslager, A.T. and Roberts, M.C.}, year={1999}, pages={24–29} }
 @article{gerard_blikslager_roberts_tate_argenzio_1999, title={The characteristics of intestinal injury peripheral to strangulating obstruction lesions in the equine small intestine}, volume={31}, ISSN={["0425-1644"]}, DOI={10.1111/j.2042-3306.1999.tb03826.x}, abstractNote={Recent studies suggest that horses requiring surgical correction of strangulating intestinal obstruction may develop post operative complications as a result of ischaemia/reperfusion injury. Therefore, the mucosal and serosal margins of resected small intestine from 9 horses with small intestinal strangulating lesions were examined for evidence of ischaemia/reperfusion injury. Severe mucosal injury and marked elevations in myeloperoxidase activity were detected at ileal resection margins (n = 4), whereas the mucosa from proximal jejunal (n = 9) and distal jejunal (n = 5) resection margins was normal. However, the serosa from jejunal resection margins had evidence of haemorrhage and oedema, and the proximal jejunal serosa had significantly increased numbers of neutrophils. Histological injury in ileal stumps is indicative of the inability fully to resect the ileum in horses with distal small intestinal strangulations. One of 4 horses subjected to ileal resection was subjected to euthanasia and found to have a necrotic ileal stump. Evidence of serosal injury and neutrophil infiltration in the proximal jejunal resection margins may predispose horses to post operative adhesions. Four of 8 horses discharged from the hospital suffered from recurrent colic in the post operative period.}, number={4}, journal={EQUINE VETERINARY JOURNAL}, author={Gerard, MP and Blikslager, AT and Roberts, MC and Tate, LP and Argenzio, RA}, year={1999}, month={Jul}, pages={331–335} }
 @article{the characteristics of intestinal injury peripheral to strangulating obstruction lesions in the equine small intestine_1999, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033160429&partnerID=MN8TOARS}, number={4}, journal={Equine Veterinary Journal}, year={1999}, pages={331–335} }
 @article{blikslager_tate_tudor_1999, title={Transendoscopic laser treatment of rostral displacement of the palatopharyngeal arch in four horses}, volume={17}, ISSN={["1044-5471"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032922176&partnerID=MN8TOARS}, DOI={10.1089/clm.1999.17.49}, abstractNote={To document the use and clinical outcome of transendoscopic laser techniques for treatment of rostral displacement of the palatopharyngeal arch (RDPA) in horses.Rostral displacement of the palatopharyngeal arch is a rare cause of upper respiratory noise and exercise intolerance in horses, and may be associated with abnormal laryngeal anatomy. There are few reports of successful treatment of this condition, and no reports of the treatment of RDPA using laser techniques.The diagnosis of RDPA was based on the presence of palatal tissue covering the dorsal aspect of the arytenoid cartilages on endoscopic examination. Either a neodymium:yttrium aluminum garnet (Nd:YAG) laser noncontact technique (1060 nm, 100 W continuous mode) or a diode laser contact technique (808 nm, 14 W, continuous mode) was used.In 3 horses in which the Nd:YAG laser was used, displaced palatal tissue was not fully divided at surgery, but separated after latent thermal necrosis within 3 days. In the horse in which the diode laser was used, tissues were fully divided at the time of surgery. Two horses had abnormal laryngeal anatomy and laryngeal hemiplegia. One of these 2 horses was subjected to arytenoidectomy, and had limited success as a race-horse, while the other was retired as a broodmare. One of 2 horses with no other laryngeal abnormalities raced once unsuccessfully, while the other horse was never raced.Rostral displacement of the palatopharyngeal arch may be corrected in standing horses using transendoscopic surgery, but despite successful ablation of displaced tissue the prognosis for athletic performance is poor.}, number={2}, journal={JOURNAL OF CLINICAL LASER MEDICINE & SURGERY}, author={Blikslager, AT and Tate, LP and Tudor, R}, year={1999}, month={Apr}, pages={49–52} }
 @article{ahdieh_blikslager_bhat_coleman_argenzio_rhoads_1998, title={L-Glutamine and Transforming Growth Factor-α Enhance Recovery of Monoacylglycerol Acyltransferase and Diacylglycerol Acyltransferase Activity in Porcine Postischemic Ileum}, volume={43}, ISSN={0031-3998 1530-0447}, url={http://dx.doi.org/10.1203/00006450-199802000-00012}, DOI={10.1203/00006450-199802000-00012}, abstractNote={Recovery of the ability to digest and absorb lipids is essential to the maintenance of normal nutrition in infants with bowel damage. Two intrinsic microsomal enzymes, monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT), catalyze the major pathway for intestinal triacylglycerol biosynthesis. This study describes the effects of intestinal ischemia on epithelial DGAT and MGAT activities and their recovery in response to two luminal treatments: L-glutamine (Gln), the primary intestinal fuel, and transforming growth factor-alpha (TGF-alpha), a mitogenic hormone similar to epidermal growth factor present in breast milk. Ischemic damage and recovery were analyzed in mucosa from Thiry-Vella loops in the mid-ileum of 7-wk-old pigs. Loops were subjected to 2-h occlusion of local mesenteric arteries, followed by 6 or 72 h of recovery in the presence of luminal glucose (control), Gln, or TGF-alpha. Ischemic tissue followed by 6-h recovery exhibited an approximate 50% decrease in both MGAT and DGAT activities compared with nonischemic loop tissue. At 72 h, MGAT and DGAT recovery in Gln plus TGF-alpha-treated loops was significantly greater than their corresponding 6-h peak damage levels (p < 0.05). From 6 to 72 h, MGAT increased 4-fold and DGAT increased 3.6-fold after Gln plus TGF-alpha treatment. With other treatments, MGAT and DGAT activities increased <2.5-fold from 6 to 72 h. This study shows that intestinal MGAT and DGAT activities decrease after ischemic damage, yet recover rapidly in bowel exposed to Gln and/or TGF-alpha. By stimulating the rate of recovery of the villi and lipid synthesizing enzymes, these treatments could improve the efficacy of enteral feeding in infants recovering from bowel damage.}, number={2}, journal={Pediatric Research}, publisher={Springer Nature}, author={Ahdieh, Navid and Blikslager, Anthony T and Bhat, B Ganesh and Coleman, Rosalind A and Argenzio, Robert A and Rhoads, J Marc}, year={1998}, month={Feb}, pages={227–233} }
 @article{lang_blikslager_regina_eisemann_argenzio_1998, title={Synergistic effect of hydrochloric acid and bile acids on the pars esophageal mucosa of the porcine stomach}, volume={59}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032161874&partnerID=MN8TOARS}, number={9}, journal={American Journal of Veterinary Research}, author={Lang, J. and Blikslager, A. and Regina, D. and Eisemann, J. and Argenzio, R.}, year={1998}, pages={1170–1176} }
 @inproceedings{development of a model to evaluate laser penetration in the equine using nd:yag laser as a standard_1997, volume={3245}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031289667&partnerID=MN8TOARS}, DOI={10.1117/12.312311}, abstractNote={The Nd:YAG laser is a frequently used laser in correcting equine upper respiratory disorders. Evaluation of this laser and several other lasers ability to penetrate tissue has been based on in vitro studies using portions of the arytenoid cartilage. The parameters measured have routinely been depth and width of crater created from irradiation of tissue. This investigation was performed on cadaver acquired tissue with anticipation of developing a model to conduct future in vivo studies of a similar nature to evaluate and compare different lasers. To perform this power setting, tissue selection and means of acquiring measurements needed to be standardized. Due to its accessibility and anatomic similarity to the arytenoid used in previous studies the rostral nasal septum was chosen as the second tissue for comparison with the arytenoid. Evaluation of the selected energies delivered to the tissues by the Nd:YAG laser were evaluated to set a standard by determining depth and top and bottom diameters of the area ablated. Methods of measurement consisting of standard histologic preparation followed by microscopic evaluation was compared to computer tomography acquired determinations. Statistical analysis supported the hypothesis that the nasal septum is a viable substitute for the arytenoid cartilage for future in vivo studies. It is also easily accessible compared to the arytenoid and evaluation of laser induced lesion parameters either in situ or separate from the animal should not be detrimental to the animal.}, booktitle={Proceedings of SPIE - The International Society for Optical Engineering}, year={1997}, pages={407–416} }
 @article{blikslager_roberts_gerard_argenzio_1997, title={How important is intestinal reperfusion injury in horses?}, volume={211}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031451722&partnerID=MN8TOARS}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Roberts, M.C. and Gerard, M.P. and Argenzio, R.A.}, year={1997}, pages={1387–1389} }
 @article{blikslager_roberts_rhoads_argenzio_1997, title={Is reperfusion injury an important cause of mucosal damage after porcine intestinal ischemia?}, volume={121}, ISSN={["0039-6060"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030999624&partnerID=MN8TOARS}, DOI={10.1016/S0039-6060(97)90107-0}, abstractNote={Intestinal ischemic injury is exacerbated by reperfusion in rodent and feline models because of xanthine oxidase-initiated reactive oxygen metabolite formation and neutrophil infiltration. Studies were conducted to determine the relevance of reperfusion injury in the juvenile pig, whose low levels of xanthine oxidase are similar to those of the human being.Ischemia was induced by means of complete mesenteric arterial occlusion, volvulus, or hemorrhagic shock. Injury was assessed by means of histologic examination and measurement of lipid peroxidation. In addition, myeloperoxidase, as a marker of neutrophil infiltration, and xanthine oxidase-xanthine dehydrogenase were measured.Significant ischemic injury was evident after 0.5 to 3 hours of complete mesenteric occlusion or 2 hours of shock or volvulus. In none of these models was the ischemic injury worsened by reperfusion. To maximize superoxide production, pigs were ventilated on 100% O2, but only limited reperfusion injury (1.2-fold increase in histologic grade) was noted. Xanthine oxidase-xanthine dehydrogenase levels were negligible (0.4 +/- 0.4 mU/gm).Reperfusion injury may not play an important role in intestinal injury under conditions of complete mesenteric ischemia and low-flow states in the pig. This may result from low xanthine oxidase-xanthine dehydrogenase levels, which are similar to those found in the human being.}, number={5}, journal={SURGERY}, author={Blikslager, AT and Roberts, MC and Rhoads, JM and Argenzio, RA}, year={1997}, month={May}, pages={526–534} }
 @article{blikslager_roberts_1997, title={Mechanisms of intestinal mucosal repair}, volume={211}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030707695&partnerID=MN8TOARS}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Roberts, M.C.}, year={1997}, pages={1437–1441} }
 @article{blikslager_roberts_1997, title={Nitric oxide and the intestinal epithelial barrier: does it protect or damage the gut?}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031253859&partnerID=MN8TOARS}, number={4}, journal={Journal of pediatric gastroenterology and nutrition}, author={Blikslager, A.T. and Roberts, M.C.}, year={1997}, pages={439–440} }
 @article{argenzio_armstrong_blikslager_rhoads_1997, title={Peptide YY inhibits intestinal Cl- secretion in experimental porcine cryptosporidiosis through a prostaglandin-activated neural pathway}, volume={283}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030832697&partnerID=MN8TOARS}, number={2}, journal={Journal of Pharmacology and Experimental Therapeutics}, author={Argenzio, R.A. and Armstrong, M. and Blikslager, A. and Rhoads, J.M.}, year={1997}, pages={692–697} }
 @article{blikslager_roberts_rhoads_argenzio_1997, title={Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum.}, volume={100}, ISSN={0021-9738}, url={http://dx.doi.org/10.1172/JCI119723}, DOI={10.1172/JCI119723}, abstractNote={Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium, possibly because they enhance mucosal repair. The objective of the present studies was to assess the role of prostaglandins in intestinal repair. Intestinal mucosa from porcine ileum subjected to 1 h of ischemia was mounted in Ussing chambers. Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control. The latter response was blocked by inhibition of prostaglandin synthesis, and restored by addition of both carbacyclin (an analog of PGI2) and PGE2, whereas the addition of each alone had little effect. Histologically, prostaglandins had no effect on epithelial restitution or villous contraction, indicating that elevations in transepithelial resistance were associated with increases in paracellular resistance. Furthermore, prostaglandin-stimulated elevations in resistance were inhibited with cytochalasin D, an agent known to stimulate cytoskeletal contraction. Synergistic elevations in transepithelial resistance, similar to those of carbacyclin and PGE2, were also noted after treatment with cAMP and A23187 (a calcium ionophore). We conclude that PGE2 and PGI2 have a synergistic role in restoration of intestinal barrier function by increasing intracellular cAMP and Ca2+, respectively, which in turn signal cytoskeletal-mediated tight junction closure.}, number={8}, journal={Journal of Clinical Investigation}, publisher={American Society for Clinical Investigation}, author={Blikslager, A T and Roberts, M C and Rhoads, J M and Argenzio, R A}, year={1997}, month={Oct}, pages={1928–1933} }
 @article{cook_blikslager_bristol_1996, title={Colic associated with a jejunal diverticulum in a mature horse}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030537582&partnerID=MN8TOARS}, number={3}, journal={Equine Veterinary Education}, author={Cook, G. and Blikslager, A.T. and Bristol, D.G.}, year={1996}, pages={143–144} }
 @article{blikslager_roberts_mansmann_1996, title={Critical steps in managing equine rectal tears}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0348248969&partnerID=MN8TOARS}, number={10}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Blikslager, A.T. and Roberts, M.C. and Mansmann, R.A.}, year={1996}, pages={1140–1143} }
 @article{jejunocolostomy or ileocolostomy for treatment of cecal impaction in horses: nine cases (1985-1995)_1996, volume={209}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030256305&partnerID=MN8TOARS}, number={7}, journal={Journal of the American Veterinary Medical Association}, year={1996}, pages={1287–1290} }
 @article{blikslager_roberts_1995, title={Accuracy of clinicians in predicting site and type of lesion as well as outcome in horses with colic.}, volume={207}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029446969&partnerID=MN8TOARS}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Roberts, M.C.}, year={1995}, pages={1444–1447} }
 @article{blikslager_bristol_1995, title={Avulsion of the origin of the peroneus tertius tendon in a foal}, volume={204}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Bristol, D.G.}, year={1995}, month={May}, pages={1483–1485} }
 @article{benamou_blikslager_sellon_1995, title={Intestinal Atresia in Horses}, volume={17}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Benamou, A. and Blikslager, A.T. and Sellon, D.}, year={1995}, pages={1510–1517} }
 @article{blikslager_bristol_bowman_engelbert_1995, title={Loop colostomy for treatment of grade-3 rectal tears in horses: seven cases (1983-1994)}, volume={207}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029411076&partnerID=MN8TOARS}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Bristol, D.G. and Bowman, K.F. and Engelbert, T.A.}, year={1995}, pages={1201–1205} }
 @article{blikslager_anderson_bristol_fubini_anderson_1995, title={Repeat laparotomy for gastrointestinal disorders in cattle: 57 cases (1968-1992).}, volume={207}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029391433&partnerID=MN8TOARS}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Anderson, K.L. and Bristol, D.G. and Fubini, S.L. and Anderson, D.E.}, year={1995}, pages={939–943} }
 @article{tate_blikslager_little_1995, title={TRANSENDOSCOPIC LASER TREATMENT OF GUTTURAL POUCH TYMPANITES IN 8 FOALS}, volume={24}, ISSN={["0161-3499"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029364626&partnerID=MN8TOARS}, DOI={10.1111/j.1532-950X.1995.tb01345.x}, abstractNote={Guttural pouch tympanites was diagnosed in eight foals with respiratory stridor and tympanic swelling in the parotid region. Three foals were treated by transendoscopic neodymium:yttrium aluminum garnet (Nd:YAG) laser fenestration of the median septum between the guttural pouches. One foal died of pneumonia, and the other two foals recovered completely, although the fenestration later closed in one foal. Five foals were treated by creating a salpingopharyngeal fistula using transendoscopic laser irradiation: complete resolution of the tympanites occurred. Transendoscopic laser surgery in standing foals may be a reasonable alternative to conventional surgery and general anesthesia for correction of guttural pouch tympanites.}, number={5}, journal={VETERINARY SURGERY}, author={TATE, LP and BLIKSLAGER, AT and LITTLE, EDE}, year={1995}, pages={367–372} }
 @article{blikslager_1995, title={Vagal indigestion}, volume={206}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T.}, year={1995}, month={May}, pages={1528} }
 @article{blikslager_1995, title={Vagal indigestion.}, volume={206}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029644874&partnerID=MN8TOARS}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T.}, year={1995} }
 @article{blikslager_bristol_1994, title={Avulsion of the origin of the peroneus tertius tendon in a foal.}, volume={204}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028434716&partnerID=MN8TOARS}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Bristol, D.G.}, year={1994}, pages={1483–1485} }
 @article{blikslager_bowman_levine_bristol_roberts_1994, title={Evaluation of factors associated with postoperative ileus in horses: 31 cases (1990-1992)}, volume={205}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028774741&partnerID=MN8TOARS}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Bowman, K. and Levine, J. F. and Bristol, D. G. and Roberts, M. C.}, year={1994}, pages={1748–1752} }
 @article{holding power of orthopedic screws in the large metacarpal and metatarsal bones of calves._1994, volume={55}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028390063&partnerID=MN8TOARS}, number={3}, journal={American Journal of Veterinary Research}, year={1994}, pages={415–418} }
 @article{blikslager_bristol_1994, title={Recurrence of avulsion fractures.}, volume={205}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028774119&partnerID=MN8TOARS}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Bristol, D.G.}, year={1994} }
 @article{blikslager_tate_weinstock_1993, title={Effects of Neodymium:Yttnum Aluminum Garnet Laser Irradiation on Endometrium and on Endometrial Cysts in Six Mares}, volume={22}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0027661255&partnerID=MN8TOARS}, DOI={10.1111/j.1532-950X.1993.tb00411.x}, abstractNote={Effects of neodymium:yttrium aluminum garnet (Nd:YAG) laser irradiation on equine endometrium were evaluated In vitro and in six mares with endometrial cysts. The Nd:YAG laser was applied to six endometrial sites, in each of five uterine specimens, with power densities of 5659 to 33,954 J/cm2. Depth of tissue ablation was measured and graded on histologic sections of the tissue lesions. Power density had a significant effect on the depth of tissue ablation (p < .001). Grade 3 lesions (full-thickness ablation of the endometrium) were created with energy densities of 16,977 to 33,954 J/cm2. Six mares had endometrial cysts treated by photoablation. Two of the four mares that were reproductively sound but barren, despite appropriate breeding, produced foals after treatment. One mare remained reproductively unsound after treatment, and another mare that was treated postpartum was bred successfully.}, number={5}, journal={Veterinary Surgery}, author={BLIKSLAGER, A.T. and TATE, L.P. and WEINSTOCK, D.}, year={1993}, pages={351–356} }
 @article{haven_bowman_engelbert_blikslager_1993, title={Surgical management of urolithiasis in small ruminants.}, volume={83}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0027342746&partnerID=MN8TOARS}, number={1}, journal={The Cornell veterinarian}, author={Haven, M.L. and Bowman, K.F. and Engelbert, T.A. and Blikslager, A.T.}, year={1993}, pages={47–55} }
 @article{blikslager_green_macfadden_fagin_johnson_1992, title={EXCRETORY UROGRAPHY AND ULTRASONOGRAPHY IN THE DIAGNOSIS OF BILATERAL ECTOPIC URETERS IN A FOAL}, volume={33}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/j.1740-8261.1992.tb01955.x}, DOI={10.1111/j.1740-8261.1992.tb01955.x}, abstractNote={A 7-week-old Appaloosa filly was admitted for persistent urinary incontinence since birth. Vaginal speculum examination revealed urine flowing from an opening in the right vaginal wall. Cystoscopy demonstrated that the ureters did not terminate at the bladder. The endoscope passed easily from the vagina directly into a dilated right ureter. An excretory urogram confirmed the vaginal termination of at least one ureter, based upon extensive filling of the vagina with contrast media in the absence of bladder filling. Bilateral hydroureter and dilated renal pelves were demonstrated both by excretory urography and by ultrasonography. Euthanasia was requested by the owner in lieu of attempted surgical correction. At necropsy, it was confirmed that the right ureter entered the vagina and the left ureter terminated at the urethra. The diagnosis of bilateral ectopic ureter in this foal was suggested by the history and clinical signs, supported by endoscopy and ultrasonography, and confirmed by excretory urography and necropsy. This case establishes the value of diagnostic imaging techniques in the antemortem diagnosis of ectopic ureter.}, number={1}, journal={Veterinary Radiology <html_ent glyph="@amp;" ascii="&"/> Ultrasound}, publisher={Wiley}, author={Blikslager, Anthony T. and Green, Eleanor M. and MacFadden, Karen E. and Fagin, Bennett and Johnson, Gayle C.}, year={1992}, month={Jan}, pages={41–47} }
 @article{blikslager_green_1992, title={Ectopic ureter in horses}, volume={14}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Blikslager, A.T. and Green, E.M.}, year={1992}, pages={802–807} }
 @article{blikslager_baines_bowman_1992, title={Excision of the distal sesamoid bone for treatment of infection of the digit in a heifer}, volume={201}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0027097511&partnerID=MN8TOARS}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Baines, S.J. and Bowman, K.F.}, year={1992}, pages={1905–1906} }
 @article{blikslager_anderson_1992, title={Mycoplasma mycoides subspecies mycoides as the cause of a subauricular abscess and mastitis in a goat}, volume={201}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0027056779&partnerID=MN8TOARS}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Anderson, K.L.}, year={1992}, pages={1404–1406} }
 @article{pedunculated lipomas as a cause of intestinal obstruction in horses: 17 cases (1983-1990)._1992, volume={201}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0027121071&partnerID=MN8TOARS}, number={8}, journal={Journal of the American Veterinary Medical Association}, year={1992}, pages={1249–1252} }
 @article{atlantoaxial malformation in a half-arabian colt._1991, volume={81}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0025929097&partnerID=MN8TOARS}, number={1}, journal={The Cornell veterinarian}, year={1991}, pages={67–75} }
 @article{blikslager_wilson_taylor_macfadden_fischer_fales_1991, title={Salmonella typhimurium abscess as a postoperative complication in a horse with colic}, volume={199}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0026323796&partnerID=MN8TOARS}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Wilson, D.A. and Taylor, D.S. and MacFadden, K.E. and Fischer, J.R. and Fales, W.H.}, year={1991}, month={Dec}, pages={1757–1759} }
 @article{blikslager_sweeney_1991, title={What is your diagnosis? Collapsed trachea from the level of C5 to C7.}, volume={199}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0026217406&partnerID=MN8TOARS}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A.T. and Sweeney, C.L.}, year={1991}, pages={629–630} }
 @article{blikslager_bristol_hunt, title={Abomasal impaction in cattle}, volume={15}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Blikslager, A. T. and Bristol, D. G. and Hunt, E. L.}, pages={1571–1576} }
 @article{blikslager_roberts, title={Accuracy of clinicians in predicting site and type of lesion as well as outcome in horses with colic}, volume={207}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Roberts, M. C.}, pages={1444} }
 @article{blikslager_bristol, title={Avulsion of the origin of the peroneus tertius in a foal}, volume={204}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Bristol, D. G.}, pages={1483–1485} }
 @misc{petschow_blikslager_weaver_campbell_polo_shaw_burnett_klein_rhoads, title={Bovine immunoglobulin protein isolates for the nutritional management of enteropathy}, volume={20}, number={33}, journal={World Journal of Gastroenterology}, author={Petschow, B. W. and Blikslager, A. T. and Weaver, E. M. and Campbell, J. M. and Polo, J. and Shaw, A. L. and Burnett, B. P. and Klein, G. L. and Rhoads, J. M.}, pages={11713–11726} }
 @article{blikslager_roberts_mansmanr, title={Critical steps in managing equine rectal tears}, volume={18}, number={10}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Blikslager, A. T. and Roberts, M. C. and Mansmanr, R. A.}, pages={1140} }
 @inbook{blikslager_jones, title={Disorders of the esophagus}, booktitle={Large animal internal medicine  (3rd Ed.)}, publisher={St. Louis: Mosby}, author={Blikslager, A. T. and Jones, S. L.}, pages={607–617} }
 @article{blikslager, title={Equine colic}, volume={19}, number={3}, journal={Ippologia}, author={Blikslager, A. T.}, pages={21–33} }
 @inbook{jones_blikslager, title={Esophageal diseases}, ISBN={0721697771}, booktitle={Equine internal medicine}, publisher={Philadelphia: W. B. Saunders}, author={Jones, S. L. and Blikslager, A. T.}, editor={S. M. Reed, W. M. Bayly and Sellon, D. C.Editors}, pages={855–863} }
 @article{nighot_moeser_ueno_blikslager, title={Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa}, volume={18}, number={34}, journal={World Journal of Gastroenterology}, author={Nighot, M. and Moeser, A. and Ueno, R. and Blikslager, A.}, pages={4684–4692} }
 @article{blikslager_bowman_abrams_seaboch_hunt, title={Holding power of orthopedic screws in the large metacarpal and metatarsal bones of calves}, volume={55}, number={3}, journal={American Journal of Veterinary Research}, author={Blikslager, A. T. and Bowman, K. F. and Abrams, C. F., Jr. and Seaboch, T. R. and Hunt, E. L.}, pages={415} }
 @inbook{blikslager_jones, title={Ischemic disorders of the intestinal tract}, ISBN={0721697771}, booktitle={Equine internal medicine}, publisher={Philadelphia: W. B. Saunders}, author={Blikslager, A. T. and Jones, S. L.}, editor={S. M. Reed, W. M. Bayly and Sellon, D. C.Editors}, pages={913–922} }
 @article{gerard_bowman_blikslager_tate_bristol, title={Jejunocolostomy or ileocolostomy for treatment of cecal impaction in horses: Nine cases (1985-1995)}, volume={209}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Gerard, M. P. and Bowman, K. F. and Blikslager, A. T. and Tate, L. P., Jr. and Bristol, D. G.}, pages={1287–1289} }
 @article{blikslager_bristol_bowman_engelbert, title={Loop colostomy for treatment of grade-3 rectal tear in horses: Seven cases (1983-1994)}, volume={207}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Bristol, D. G. and Bowman, K. F. and Engelbert, T. A.}, pages={1201–1205} }
 @article{blikslager, title={Management of pain in horses with colic}, volume={1}, journal={Compendium's Standards of Care. Emergency and critical care medicine}, author={Blikslager, A. T.}, pages={7–12} }
 @article{blikslager_anderson, title={Mycoplasma mycoides subspecies mycoides as the cause of a subauricular abscess and mastitis in a goat}, volume={201}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Anderson, K. L.}, pages={1404} }
 @inbook{blikslager_jones, title={Obstructive disorders of the intestinal tract}, ISBN={0721697771}, booktitle={Equine internal medicine}, publisher={Philadelphia: W. B. Saunders}, author={Blikslager, A. T. and Jones, S. L.}, editor={S. M. Reed, W. M. Bayly and Sellon, D. C.Editors}, pages={922–936} }
 @inbook{blikslager, title={Pathophysiology of mucosal injury and repair}, ISBN={0721697771}, booktitle={Equine internal medicine}, publisher={Philadelphia: W. B. Saunders}, author={Blikslager, A. T.}, editor={S. M. Reed, W. M. Bayly and Sellon, D. C.Editors}, pages={802–815} }
 @inbook{blikslager_jones_grondhal_merritt_malbert, title={Pathophysiology of the gastronintestinal tract}, ISBN={0813828260}, booktitle={Veterinary pathophysiology}, publisher={Ames, IA: Blackwell Pub.}, author={Blikslager, A. T. and Jones, S. L. and Grondhal, M. L. and Merritt, A. M. and Malbert, C. H.}, editor={R. H. Dunlop and Malbert, C. H.Editors}, pages={111–142} }
 @article{blikslager_bowman_haven_tate_bristol, title={Pedunculated lipomas as a cause of intestinal obstruction in horses 17 cases (1983-1990)}, volume={201}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Bowman, K. F. and Haven, M. L. and Tate, L. P., Jr. and Bristol, D. G.}, pages={1249–1252} }
 @article{blikslager_bristol, title={Recurrence of avulsion fractures}, volume={205}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Bristol, D. G.}, pages={534} }
 @article{blikslager_anderson_bristol_fubini_anderson, title={Repeat laparotomy for gastrointestinal disorders in cattle: 57 cases (1968-1992)}, volume={207}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Blikslager, A. T. and Anderson, K. L. and Bristol, D. G. and Fubini, S. and Anderson, D. E.}, pages={939–943} }
 @article{blikslager, title={Treatment of ischemic intestinal disease}, journal={Veterinary Clinics of North America. Equine Practice}, author={Blikslager, A. T.}, pages={715–728} }
 @misc{pease_cook_jones_blikslager_scrivani_erb, title={Views conclusions in ultrasound study as unsupported}, volume={228}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Pease, A. and Cook, V. and Jones, S. and Blikslager, A. and Scrivani, P. and Erb, H.}, pages={1011} }
 @article{blikslager, title={What COX-1 and COX-2 do and how they differ}, journal={Veterinary Forum}, author={Blikslager, A. T.}, pages={23–28} }
 @article{schramme_hunter_campbell_blikslager_smith, title={surgical tendonitis model in horses: Techinque, clinical, ultrasonographic and histological characterisation}, volume={23}, number={4}, journal={Veterinary and Comparative Orthopaedics and Traumatology}, author={Schramme, M. and Hunter, S. and Campbell, N. and Blikslager, A. and Smith, R.}, pages={231–239} }