@article{mackey_moeser_2022, title={Sex Differences in Mast Cell-Associated Disorders: A Life Span Perspective}, volume={14}, ISSN={["1943-0264"]}, DOI={10.1101/cshperspect.a039172}, abstractNote={Mast cells are critical innate immune effectors located throughout the body that are crucial for host defense mechanisms via orchestrating immune responses to a variety of host and environmental stimuli necessary for survival. The role of mast cells in brain development and behavior, meningeal function, and stress-related disorders has also been increasingly recognized. While critical for survival and development, excessive mast cell activation has been linked with an increasing number of inflammatory, stress-associated, and neuroimmune disorders including allergy/anaphylaxis, autoimmune diseases, migraine headache, and chronic pain disorders. Further, a strong sex bias exists for mast cell-associated diseases with females often at increased risk. Here we review sex differences in human mast cell-associated diseases and animal models, and the underlying biological mechanisms driving these sex differences, which include adult gonadal sex hormones as well the emerging organizational role of perinatal gonadal hormones on mast cell activity and development.}, number={10}, journal={COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY}, author={Mackey, Emily and Moeser, Adam J. J.}, year={2022}, month={Oct} }
 @article{mackey_thelen_bali_fardisi_trowbridge_jordan_moeser_2020, title={Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood}, volume={117}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1915075117}, abstractNote={Significance}, number={38}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Mackey, Emily and Thelen, Kyan M. and Bali, Vedrana and Fardisi, Mahsa and Trowbridge, Madalyn and Jordan, Cynthia L. and Moeser, Adam J.}, year={2020}, month={Sep}, pages={23751–23761} }
 @article{d'costa_ayyadurai_gibson_mackey_rajput_sommerville_wilson_li_kubat_kumar_et al._2019, title={Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability}, volume={143}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2018.08.053}, abstractNote={Psychological stress and heightened mast cell (MC) activation are linked with important immunologic disorders, including allergy, anaphylaxis, asthma, and functional bowel diseases, but the mechanisms remain poorly defined. We have previously demonstrated that activation of the corticotropin-releasing factor (CRF) system potentiates MC degranulation responses during IgE-mediated anaphylaxis and psychological stress through corticotropin-releasing factor receptor subtype 1 (CRF1) expressed on MCs.In this study we investigated the role of corticotropin-releasing factor receptor subtype 2 (CRF2) as a modulator of stress-induced MC degranulation and associated disease pathophysiology.In vitro MC degranulation assays were performed with bone marrow-derived mast cells (BMMCs) derived from wild-type (WT) and CRF2-deficient (CRF2-/-) mice and RBL-2H3 MCs transfected with CRF2-overexpressing plasmid or CRF2 small interfering RNA. In vivo MC responses and associated pathophysiology in IgE-mediated passive systemic anaphylaxis and acute psychological restraint stress were measured in WT, CRF2-/-, and MC-deficient KitW-sh/W-sh knock-in mice.Compared with WT mice, CRF2-/- mice exhibited greater serum histamine levels and exacerbated IgE-mediated anaphylaxis and colonic permeability. In addition, CRF2-/- mice exhibited increased serum histamine levels and colonic permeability after acute restraint stress. Experiments with BMMCs and RBL-2H3 MCs demonstrated that CRF2 expressed on MCs suppresses store-operated Ca2+ entry signaling and MC degranulation induced by diverse MC stimuli. Experiments with MC-deficient KitW-sh/W-sh mice systemically engrafted with WT and CRF2-/- BMMCs demonstrated the functional importance of MC CRF2 in modulating stress-induced pathophysiology.MC CRF2 is a negative global modulator of stimuli-induced MC degranulation and limits the severity of IgE-mediated anaphylaxis and stress-related disease pathogenesis.}, number={5}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={D'Costa, Susan and Ayyadurai, Saravanan and Gibson, Amelia J. and Mackey, Emily and Rajput, Mrigendra and Sommerville, Laura J. and Wilson, Neco and Li, Yihang and Kubat, Eric and Kumar, Ananth and et al.}, year={2019}, month={May}, pages={1865-+} }
 @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{grilli_tugnoli_passey_stahl_piva_moeser_2015, title={Impact of dietary organic acids and botanicals on intestinal integrity and inflammation in weaned pigs}, volume={11}, ISSN={["1746-6148"]}, DOI={10.1186/s12917-015-0410-0}, abstractNote={Organic acids, such as citric and sorbic acid, and pure plant-derived constituents, like monoterpens and aldehydes, have a long history of use in pig feeding as alternatives to antibiotic growth promoters. However, their effects on the intestinal barrier function and inflammation have never been investigated. Therefore, aim of this study was to assess the impact of a microencapsulated mixture of citric acid and sorbic acid (OA) and pure botanicals, namely thymol and vanillin, (PB) on the intestinal integrity and functionality of weaned pigs and in vitro on Caco-2 cells. In the first study 20 piglets were divided in 2 groups and received either a basal diet or the basal diet supplemented with OA + PB (5 g/kg) for 2 weeks post-weaning at the end of which ileum and jejunum samples were collected for Ussing chambers analysis of trans-epithelial electrical resistance (TER), intermittent short-circuit current (I SC), and dextran flux. Scrapings of ileum mucosa were also collected for cytokine analysis (n = 6). In the second study we measured the effect of these compounds directly on TER and permeability of Caco-2 monolayers treated with either 0.2 or 1 g/l of OA + PB. Pigs fed with OA + PB tended to have reduced I SC in the ileum (P = 0.07) and the ileal gene expression of IL-12, TGF-β, and IL-6 was down regulated. In the in vitro study on Caco-2 cells, TER was increased by the supplementation of 0.2 g/l at 4, 6, and 14 days of the experiment, whereas 1 g/l increased TER at 10 and 12 days of treatment (P < 0.05). Dextran flux was not significantly affected though a decrease was observed at 7 and 14 days (P = 0.10 and P = 0.09, respectively). Overall, considering the results from both experiments, OA + PB improved the maturation of the intestinal mucosa by modulating the local and systemic inflammatory pressure ultimately resulting in a less permeable intestine, and eventually improving the growth of piglets prematurely weaned.}, journal={BMC VETERINARY RESEARCH}, author={Grilli, Ester and Tugnoli, Benedetta and Passey, Jade L. and Stahl, Chad H. and Piva, Andrea and Moeser, Adam J.}, year={2015}, month={Apr} }
 @article{muthusamy_sommerville_moeser_stumpo_sannes_adler_blackshear_weimer_ghashghaei_2015, title={MARCKS-dependent mucin clearance and lipid metabolism in ependymal cells are required for maintenance of forebrain homeostasis during aging}, volume={14}, ISSN={["1474-9726"]}, DOI={10.1111/acel.12354}, abstractNote={Summary}, number={5}, journal={AGING CELL}, author={Muthusamy, Nagendran and Sommerville, Laura J. and Moeser, Adam J. and Stumpo, Deborah J. and Sannes, Philip and Adler, Kenneth and Blackshear, Perry J. and Weimer, Jill M. and Ghashghaei, H. Troy}, year={2015}, month={Oct}, pages={764–773} }
 @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={AIM
To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.


METHODS
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.


RESULTS
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.


CONCLUSION
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{onyiah_sheikh_maharshak_steinbach_russo_kobayashi_mackey_hansen_moeser_rawls_et al._2013, title={Carbon Monoxide and Heme Oxygenase-1 Prevent Intestinal Inflammation in Mice by Promoting Bacterial Clearance}, volume={144}, ISSN={["1528-0012"]}, DOI={10.1053/j.gastro.2012.12.025}, abstractNote={BACKGROUND & AIMS
Heme oxygenase-1 (HO-1) and its metabolic by-product, carbon monoxide (CO), protect against intestinal inflammation in experimental models of colitis, but little is known about their intestinal immune mechanisms. We investigated the interactions among CO, HO-1, and the enteric microbiota in mice and zebrafish.


METHODS
Germ-free, wild-type, and interleukin (Il)10(-/-) mice and germ-free zebrafish embryos were colonized with specific pathogen-free (SPF) microbiota. Germ-free or SPF-raised wild-type and Il10(-/-) mice were given intraperitoneal injections of cobalt(III) protoporphyrin IX chloride (CoPP), which up-regulates HO-1, the CO-releasing molecule Alfama-186, or saline (control). Colitis was induced in wild-type mice housed in SPF conditions by infection with Salmonella typhimurium.


RESULTS
In colons of germ-free, wild-type mice, SPF microbiota induced production of HO-1 via activation of nuclear factor erythroid 2-related factor 2-, IL-10-, and Toll-like receptor-dependent pathways; similar observations were made in zebrafish. SPF microbiota did not induce HO-1 in colons of germ-free Il10(-/-) mice. Administration of CoPP to Il10(-/-) mice before transition from germ-free to SPF conditions reduced their development of colitis. In Il10(-/-) mice, CO and CoPP reduced levels of enteric bacterial genomic DNA in mesenteric lymph nodes. In mice with S typhimurium-induced enterocolitis, CoPP reduced the numbers of live S typhimurium recovered from the lamina propria, mesenteric lymph nodes, spleen, and liver. Knockdown of HO-1 in mouse macrophages impaired their bactericidal activity against E coli, E faecalis, and S typhimurium, whereas exposure to CO or overexpression of HO-1 increased their bactericidal activity. HO-1 induction and CO increased acidification of phagolysosomes.


CONCLUSIONS
Colonic HO-1 prevents colonic inflammation in mice. HO-1 is induced by the enteric microbiota and its homeostatic function is mediated, in part, by promoting bactericidal activities of macrophages.}, number={4}, journal={GASTROENTEROLOGY}, author={Onyiah, Joseph C. and Sheikh, Shehzad Z. and Maharshak, Nitsan and Steinbach, Erin C. and Russo, Steven M. and Kobayashi, Taku and Mackey, Lantz C. and Hansen, Jonathan J. and Moeser, Adam J. and Rawls, John F. and et al.}, year={2013}, month={Apr}, pages={789–798} }
 @article{lennon_maharshak_elloumi_borst_plevy_moeser_2013, title={Early Life Stress Triggers Persistent Colonic Barrier Dysfunction and Exacerbates Colitis in Adult IL-10(-/-) Mice}, volume={19}, ISSN={["1078-0998"]}, DOI={10.1097/mib.0b013e3182802a4e}, abstractNote={Background:It has become increasingly evident that disease flares in the human inflammatory bowel diseases are influenced by life stress. It is known that life stress can trigger disturbances in intestinal barrier function and activate proinflammatory signaling pathways, which are important contributors to intestinal inflammation and clinical disease; however, the exact mechanisms of stress-induced inflammatory bowel disease exacerbations remain to be elucidated. Here, we presented a model of early life stress–induced exacerbation of colitis in interleukin (IL)-10−/− mice. Methods:C57Bl/6 wild-type and IL-10−/− mice were exposed to neonatal maternal separation (NMS) stress on postnatal days 1 to 18 and reared under normal conditions until 10 to 12 weeks of age. At this time, histopathology, colitis scores, intestinal barrier function, proinflammatory cytokine expression, and mast cell activity were evaluated. Results:NMS increased the severity of colitis IL-10−/− mice indicated by greater colitis scores and colonic proinflammatory cytokine concentrations. NMS and IL-10−/− increased colonic permeability; however, NMS alone did not induce colitis. Increased mast cell activation and colonic tryptase release were observed in IL-10−/− mice exposed to NMS, indicating mast cell activation. Conclusions:This study demonstrates that colitis in IL-10−/− mice can be exacerbated by NMS stress. The precise mechanisms of enhanced colitis severity in NMS IL10−/− mice are unclear but persistent defects in intestinal barrier function likely play a contributing role. NMS serves as a novel model to investigate the mechanisms by which early life stress influences the development and course of inflammatory bowel disease in adulthood.}, number={4}, journal={INFLAMMATORY BOWEL DISEASES}, author={Lennon, E. M. and Maharshak, Nitsan and Elloumi, H. and Borst, L. and Plevy, S. E. and Moeser, Adam J.}, year={2013}, pages={712–719} }
 @article{mclamb_gibson_overman_stahl_moeser_2013, title={Early Weaning Stress in Pigs Impairs Innate Mucosal Immune Responses to Enterotoxigenic E. coli Challenge and Exacerbates Intestinal Injury and Clinical Disease}, volume={8}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0059838}, abstractNote={Background and Aims The clinical onset and severity of intestinal disorders in humans and animals can be profoundly impacted by early life stress. Here we investigated the impact of early weaning stress in pigs on intestinal physiology, clinical disease, and immune response to subsequent challenge with enterotoxigenic F18 E. coli (ETEC). Methodology Pigs weaned from their dam at 16 d, 18 d, and 20 d of age were given a direct oral challenge of F18 ETEC at 26 d of age. Pigs were monitored from days 0 to 4 post-infection for clinical signs of disease. On Day 4 post-ETEC challenge, ileal barrier function, histopathologic and inflammatory cytokine analysis were performed on ileal mucosa. Results Early weaned pigs (16 d and 18 d weaning age) exhibited a more rapid onset and severity of diarrhea and reductions in weight gain in response to ETEC challenge compared with late weaned pigs (20 d weaning age). ETEC challenge induced intestinal barrier injury in early weaned pigs, indicated by reductions in ileal transepithelial electrical resistance (TER) and elevated FD4 flux rates, in early weaned pig ileum but not in late weaned pigs. ETEC-induced marked elevations in IL-6 and IL-8, neutrophil recruitment, and mast cell activation in late-weaned pigs; these responses were attenuated in early weaned pigs. TNF levels elevated in ETEC challenged ileal mucosa from early weaned pigs but not in other weaning age groups. Conclusions These data demonstrate the early weaning stress can profoundly alter subsequent immune and physiology responses and clinical outcomes to subsequent infectious pathogen challenge. Given the link between early life stress and gastrointestinal diseases of animals and humans, a more fundamental understanding of the mechanisms by which early life stress impacts subsequent pathophysiologic intestinal responses has implications for the prevention and management of important GI disorders in humans and animals.}, number={4}, journal={PLOS ONE}, author={McLamb, Brittney L. and Gibson, Amelia J. and Overman, Elizabeth L. and Stahl, Chad and Moeser, Adam J.}, year={2013}, month={Apr} }
 @article{cabrera_usry_arrellano_nogueira_kutschenko_moeser_odle_2013, title={Effects of creep feeding and supplemental glutamine or glutamine plus glutamate (Aminogut) on pre- and post-weaning growth performance and intestinal health of piglets}, volume={4}, ISSN={["2049-1891"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84894465013&partnerID=MN8TOARS}, DOI={10.1186/2049-1891-4-29}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY}, author={Cabrera, Rafael A. and Usry, James L. and Arrellano, Consuelo and Nogueira, Eduardo T. and Kutschenko, Marianne and Moeser, Adam J. and Odle, Jack}, year={2013}, month={Aug} }
 @article{robbins_artuso-ponte_moeser_morrow_spears_gebreyes_2013, title={Effects of quaternary benzo(c)phenanthridine alkaloids on growth performance, shedding of organisms, and gastrointestinal tract integrity in pigs inoculated with multidrug-resistant Salmonella spp}, volume={74}, DOI={10.2460/ajvr.74.12.1530}, abstractNote={Abstract}, number={12}, journal={American Journal of Veterinary Research}, author={Robbins, R. C. and Artuso-Ponte, V. C. and Moeser, A. J. and Morrow, W. E. M. and Spears, J. W. and Gebreyes, W. A.}, year={2013}, pages={1530–1535} }
 @article{stoeker_overman_nordone_moeser_simoes_dean_2013, title={Infection with feline immunodeficiency Virus alters intestinal epithelial transport and mucosal immune responses to probiotics}, volume={153}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2013.01.017}, abstractNote={HIV infection is associated with intestinal mucosal dysfunction and probiotics offer the therapeutic potential to enhance the mucosal barrier in HIV+ patients. To evaluate the response of immunocompromised hosts to probiotics, we orally administered Lactobacillus acidophilus to cats with chronic feline immunodeficiency virus (FIV) infection. FIV infection significantly affected transcellular, but not paracellular, transport of small molecules across the intestinal epithelium. Additionally, probiotic treatment of FIV+ cats resulted in changes in cytokine release and mucosal leukocyte percentages that were not paralleled in FIV- cats. These results suggest a novel role for FIV in upregulating transcellular transport across the gastrointestinal epithelial barrier and demonstrate the potential therapeutic use of probiotic bacteria to restore intestinal homeostasis.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Stoeker, Laura L. and Overman, Elizabeth L. and Nordone, Shila K. and Moeser, Adam J. and Simoes, Rita D. and Dean, Gregg A.}, year={2013}, month={May}, pages={146–152} }
 @article{overman_rivier_moeser_2012, title={CRF Induces Intestinal Epithelial Barrier Injury via the Release of Mast Cell Proteases and TNF-alpha}, volume={7}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0039935}, abstractNote={Background and Aims Psychological stress is a predisposing factor in the onset and exacerbation of important gastrointestinal diseases including irritable bowel syndrome (IBS) and the inflammatory bowel diseases (IBD). The pathophysiology of stress-induced intestinal disturbances is known to be mediated by corticotropin releasing factor (CRF) but the precise signaling pathways remain poorly understood. Utilizing a porcine ex vivo intestinal model, the aim of this study was to investigate the mechanisms by which CRF mediates intestinal epithelial barrier disturbances. Methodology Ileum was harvested from 6–8 week-old pigs, mounted on Ussing Chambers, and exposed to CRF in the presence or absence of various pharmacologic inhibitors of CRF-mediated signaling pathways. Mucosal-to-serosal flux of 4 kDa-FITC dextran (FD4) and transepithelial electrical resistance (TER) were recorded as indices of intestinal epithelial barrier function. Results Exposure of porcine ileum to 0.05–0.5 µM CRF increased (p<0.05) paracellular flux compared with vehicle controls. CRF treatment had no deleterious effects on ileal TER. The effects of CRF on FD4 flux were inhibited with pre-treatment of tissue with the non-selective CRF1/2 receptor antagonist Astressin B and the mast cell stabilizer sodium cromolyn (10−4 M). Furthermore, anti-TNF-α neutralizing antibody (p<0.01), protease inhibitors (p<0.01) and the neural blocker tetrodotoxin (TTX) inhibited CRF-mediated intestinal barrier dysfunction. Conclusion These data demonstrate that CRF triggers increases in intestinal paracellular permeability via mast cell dependent release of TNF-α and proteases. Furthermore, CRF-mast cell signaling pathways and increases in intestinal permeability require critical input from the enteric nervous system. Therefore, blocking the deleterious effects of CRF may address the enteric signaling of mast cell degranulation, TNFα release, and protease secretion, hallmarks of IBS and IBD.}, number={6}, journal={PLOS ONE}, author={Overman, Elizabeth L. and Rivier, Jean E. and Moeser, Adam J.}, year={2012}, month={Jun} }
 @article{moeser_borst_overman_pittman_2012, title={Defects in small intestinal epithelial barrier function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine}, volume={93}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2012.01.003}, abstractNote={The objective of this study was to investigate intestinal function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine. Jejunum and distal ileum from control and pigs exhibiting PFTS was harvested at weaning, 4 and 11 days post-weaning (PW) for intestinal barrier function studies and histological analyses (n = 6 pigs per group). Marked disturbances in intestinal barrier function was observed in PFTS pigs, compared with controls, indicated by lower (p < 0.05) TER and increased (p < 0.01) permeability to FITC dextran (4 kDa). Intestines from weaned pigs, subjected to a 4-day fast, exhibited minor disturbances in intestinal barrier function. Villus atrophy and crypt hyperplasia were observed in the PFTS intestine compared with control and fasted pigs. These data demonstrate that PFTS is associated with profound disturbances in intestinal epithelial barrier function and alterations in mucosal and epithelial morphology in which anorexia is not the sole factor.}, number={2}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Moeser, Adam J. and Borst, Luke B. and Overman, Beth L. and Pittman, Jeremy S.}, year={2012}, month={Oct}, pages={975–982} }
 @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={Abstract 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{peace_campbell_polo_crenshaw_russell_moeser_2011, title={Spray-Dried Porcine Plasma Influences Intestinal Barrier Function, Inflammation, and Diarrhea in Weaned Pigs}, volume={141}, ISSN={["1541-6100"]}, DOI={10.3945/jn.110.136796}, abstractNote={The objective of this study was to evaluate the effects of dietary inclusion levels of spray-dried porcine plasma (SDPP) on postweaning (PW) intestinal barrier function, mucosal inflammation, and clinical indices of gut health in pigs. Ex vivo Ussing chamber studies were conducted to measure Ileal and colonic barrier function in terms of transepithelial electrical resistance and paracellular flux of (3)H-mannitol and (14)C-inulin. Intestinal inflammation was assessed by histological analysis and mucosal levels of proinflammatory cytokines. Dietary inclusion of 2.5 and 5% SDPP reduced colonic paracellular permeability of (14)C-inulin compared with controls (0% SDPP) on d 7 PW. Both 2.5 and 5% dietary SDPP reduced ileal (3)H-mannitol and (14)C-inulin permeability on d 14 PW. The 5% SDPP diet reduced colonic short-circuit current, an index of net electrogenic ion transport, and fecal scores when measured on d 7 and 14 PW compared with the control and 2.5% SDPP groups (P < 0.05). Histological analysis revealed fewer lamina propria cells in ileum and colon from pigs fed diets containing 2.5 and 5% SDPP on d 7 and 14 PW. Levels of the proinflammatory cytokine TNFα were reduced in the colon but not ileum from pigs fed the 5% SDPP on d 7 and 14 PW compared with controls (P < 0.05). IFNγ levels were lower than in controls in both of the SDPP-fed groups in the ileum and colon on d 7 but not on d 14 PW. Overall, this study demonstrated that dietary inclusion of SDPP had beneficial effects on intestinal barrier function, inflammation, and diarrhea in weaned pigs.}, number={7}, journal={JOURNAL OF NUTRITION}, author={Peace, Ralph Michael and Campbell, Joy and Polo, Javier and Crenshaw, Joe and Russell, Louis and Moeser, Adam}, year={2011}, month={Jul}, pages={1312–1317} }
 @article{shan_li_simmonds_wang_moeser_delwart_2011, title={The Fecal Virome of Pigs on a High-Density Farm}, volume={85}, ISSN={["1098-5514"]}, DOI={10.1128/jvi.05217-11}, abstractNote={ABSTRACT}, number={22}, journal={JOURNAL OF VIROLOGY}, author={Shan, Tongling and Li, Linlin and Simmonds, Peter and Wang, Chunlin and Moeser, Adam and Delwart, Eric}, year={2011}, month={Nov}, pages={11697–11708} }
 @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{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 [3H]mannitol and [14C]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{hansen_ashwell_moeser_fry_knutson_spears_2010, title={High dietary iron reduces transporters involved in iron and manganese metabolism and increases intestinal permeability in calves}, volume={93}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2009-2341}, abstractNote={A 56-d experiment was designed to examine the effect of high dietary Fe on metal transporters involved in Fe and Mn metabolism. Fourteen weaned Holstein calves were stratified by weight and randomly assigned to 1 of 2 treatments: 1) no supplemental Fe (normal Fe) or 2) 750mg of supplemental Fe/kg of dry matter (high Fe). Jugular blood was collected on d 0, 35, and 56. At the end of the trial, 6 calves per treatment were humanely killed and duodenal scrapings, liver, and heart were collected for analysis. Additionally, proximal duodenum was mounted on Ussing chambers to assess intestinal barrier integrity. Calves receiving high dietary Fe displayed decreased transepithelial resistance and increased apical-to-basolateral flux of radiolabeled mannitol, suggesting that high Fe created increased intestinal permeability. Feeding calves a diet high in Fe decreased average daily gain, dry matter intake, and feed efficiency. Hemoglobin and serum Fe concentrations did not differ due to dietary treatment. High dietary Fe increased concentrations of Fe in the liver, but did not affect heart or duodenal Fe concentrations. Duodenal Mn concentrations were lowered by feeding a high Fe diet, but liver and heart Mn concentrations were not affected. As determined by real-time reverse transcription PCR, relative hepatic expression of the gene that encodes the Fe regulatory hormone hepcidin was 5-fold greater in calves fed high dietary Fe. Hepcidin is released in response to increased Fe status and binds to the Fe export protein ferroportin causing ferroportin to be degraded, thereby reducing dietary Fe absorption. Confirmation of this result was achieved through Western blotting of duodenal protein, which revealed that ferroportin was decreased in calves fed high dietary Fe. Duodenal protein expression of divalent metal transporter 1 (DMT1), a Fe import protein that can also transport Mn, tended to be reduced by high dietary Fe. Transcript levels of several genes involved in Fe metabolism in liver and duodenum were unchanged by treatment. In summary, feeding calves a diet high in Fe induced a signal cascade (hepcidin) designed to reduce absorption of Fe (via reduced protein expression of ferroportin and DMT1) in a manner similar to that reported in rodents. Additionally, reduced levels of DMT1 protein appeared to decrease duodenal Mn, suggesting that Mn may also be a substrate for DMT1 in cattle.}, number={2}, journal={JOURNAL OF DAIRY SCIENCE}, author={Hansen, S. L. and Ashwell, M. S. and Moeser, A. J. and Fry, R. S. and Knutson, M. D. and Spears, J. W.}, year={2010}, month={Feb}, pages={656–665} }
 @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 (3)H-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{hansen_trakooljul_liu_moeser_spears_2009, title={Iron Transporters Are Differentially Regulated by Dietary Iron, and Modifications Are Associated with Changes in Manganese Metabolism in Young Pigs}, volume={139}, ISSN={["1541-6100"]}, DOI={10.3945/jn.109.105866}, abstractNote={To investigate the effects of dietary iron (Fe) on manganese (Mn) metabolism, 24 weaned pigs (21 d old) were blocked by litter and weight and randomly assigned to the following treatments: 1) no supplemental Fe [low Fe (L-Fe)]; 2) 100 mg supplemental Fe/kg [adequate Fe (A-Fe)]; and 3) 500 mg supplemental Fe/kg [high Fe (H-Fe)]. The basal diet was analyzed to contain 20 mg Fe/kg. Tissues were harvested after 32 d of feeding. Daily gain (least square means +/- SEM) was greater in A-Fe pigs (328.3 +/- 29.9 g/d) than in L-Fe pigs (224.0 +/- 11.2 g/d). Hemoglobin concentrations on d 32 were lower in L-Fe pigs (62 +/- 3.5 g/L) than in A-Fe pigs (128 +/- 5.6 g/L) and did not differ between pigs fed A-Fe and H-Fe (133 +/- 12.0 g/L). Liver Fe increased with increasing dietary Fe. Relative hepatic hepcidin expression was greater in pigs fed A-Fe and H-Fe than in those fed L-Fe. Relative expressions of duodenal divalent metal transporter 1 (DMT1) and solute carrier family 39 member 14 (ZIP14) were increased in L-Fe pigs compared with H-Fe pigs. Liver copper (Cu) was higher in L-Fe (0.56 +/- 0.04 mmol/kg) and H-Fe (0.58 +/- 0.04 mmol/kg) pigs than in A-Fe pigs (0.40 +/- 0.04 mmol/kg). Liver Mn was lower in H-Fe pigs (0.15 +/- 0.01 mmol/kg) than in A-Fe (0.23 +/- 0.02 mmol/kg) or L-Fe pigs (0.20 +/- 0.02 mmol/kg). Duodenal Mn concentrations were greater in L-Fe pigs than in A-Fe or H-Fe pigs. Fe deficiency in pigs increased gene expression of duodenal metal transporters (DMT1 and ZIP14) and supplementation with H-Fe reduced expression of DMT1 and ZIP14, which may have decreased absorption of Mn.}, number={8}, journal={JOURNAL OF NUTRITION}, author={Hansen, Stephanie L. and Trakooljul, Nares and Liu, Hsiao-Ching and Moeser, Adam J. and Spears, Jerry W.}, year={2009}, month={Aug}, pages={1474–1479} }
 @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{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={AIM
To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine.


METHODS
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.


RESULTS
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.


CONCLUSION
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{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{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{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={Abstract}, 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{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 [3H]mannitol fluxes. Early weaning resulted in reductions in transepithelial electrical resistance and increases in mucosal permeability to [3H]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 (p70S6K). 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 p70S6Kactivation. 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 p70S6K; [3H]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 p70S6Kphosphorylation (4-fold) and an increased p70S6Klevel (3-fold, P < 0.05). Malnutrition did not alter the magnitude of p70S6Kactivation. Immunolocalization revealed that infection produced a major induction of cytoplasmic p70S6Kand nuclear phospho-p70S6K, mainly in the crypt. A downregulation of semitendinosus muscle p70S6Kphosphorylation was seen at days 1–3 postinoculation. In conclusion, intestinal activation of p70S6Kwas 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{muley_heugten_moeser_rausch_kempen_2007, title={Nutritional value for swine of extruded corn and corn fractions obtained after dry milling}, volume={85}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2006-127}, abstractNote={The experiment was designed to assess whether corn fractions or extrusion of corn can result in feed ingredients with a greater nutritional value than corn. Corn grain (8.0% CP, 0.21% P, 9.8% NDF) was processed by extrusion (82.8 degrees C, 345 kPa steam pressure for 12 s) or by dry milling to derive fractions rich in germ (13.1% CP, 1.19% P, 17.2% NDF), hulls (8.1% CP, 0.27% P, 32.6% NDF), and endosperm, namely tails (6.6% CP, 0.07% P, 3.6% NDF) and throughs (7.4% CP, 0.15% P, 4.5% NDF). Relative recovery in each fraction was 16, 20, 44, and 20%, respectively. Ileal digestibility of DM, P, and amino acids was determined using diets containing 7.0% CP from soybean meal and 5.3% CP from one of the test products. To allow for determination of standardized ingredient, ileal digestibility, basal endogenous AA losses were determined using a protein-free diet (74.6% cornstarch and 18.7% sucrose). Soybean meal ileal digestibility was determined using a diet (12.3% CP) based on soybean meal (23.3%). Eight barrows (27 +/- 2 kg) fitted with T-cannulas were fed 8 experimental diets (5-d adaptation and 2-d collection period) such that each diet was evaluated in at least 5 barrows. Relative to corn (77.9 +/- 1.2%), ileal digestibility of DM was greater for extruded corn (82.5%; P = 0.02), tails (85.9%; P < 0.01), and throughs (85.0%; P < 0.01), but it was lower for hulls (62.2%; P < 0.01) and germ (51.1%; P < 0.01). For P, corn (41.6 +/- 9.5%), throughs (47.2%), and hulls (57.3%) had similar ileal digestibility, but germ (7.9%) had lower ileal digestibility (P = 0.02) than corn; tails (27.6%) and extruded corn (23.5%) were not different from corn or germ but were lower than throughs and hulls. For total AA, corn (84.7 +/- 2.4%), throughs (84.3%), and hulls (85.8%) had similar ileal digestibility, but germ (76.6%) had lower ileal digestibility (P < 0.01) than corn; tails (82.0%) and extruded corn (81.7%) were intermediate. In conclusion, germ and hulls have a low ileal DM digestibility; germ also has low AA and P digestibility. Extrusion improved the ileal DM digestibility of corn. To maximize the ileal digestibility, removal of germ and hull from corn or extrusion of corn may thus be of interest.}, number={7}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Muley, N. S. and Heugten, E. and Moeser, A. J. and Rausch, K. D. and Kempen, T. A. T. G.}, year={2007}, month={Jul}, pages={1695–1701} }
 @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)E2stimulates repair of mucosal barrier function via a mechanism involving Cl−secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE2-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 ( Isc) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01–1 μM lubiprostone to ischemia-injured mucosa induced concentration-dependent increases in TER, with 1 μM lubiprostone stimulating a twofold increase in TER (ΔTER = 26 Ω·cm2; P < 0.01). However, lubiprostone (1 μM) stimulated higher elevations in TER despite lower Iscresponses compared with the nonselective secretory agonist PGE2(1 μM). Furthermore, lubiprostone significantly ( P < 0.05) reduced mucosal-to-serosal fluxes of3H-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 PGE2.}, 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{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 [3H]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{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 ( Isc), transepithelial electrical resistance (TER), and isotopic fluxes of22Na were measured in response to PGE2and 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 Iscand 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 of22Na+(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{kempen_heugten_moeser_muley_sewalt_2006, title={Selecting soybean meal characteristics preferred for swine nutrition}, volume={84}, ISSN={["1525-3163"]}, DOI={10.2527/2006.8461387x}, abstractNote={As environmental constraints become more important issues for the animal industry, selecting feed ingredients that yield good animal performance but also minimize environmental impact of animal production becomes critical. The objective of this research was to identify which compositional features would be desirable for soybean meal to maximize nutritional value and minimize animal waste. Eight soybean samples were selected from a database of 72, such that maximal variability for CP, NDF, and ADF content was obtained. Samples were subsequently processed into meal using standardized procedures. In Experiment 1, 8 cannulated pigs were used to determine ileal digestibility following a Latin square design. In Experiment 2, 5 of the samples were used in complete feeds and 10 pigs were used in a crossover Latin square design to determine the total tract digestibility, odorants in fresh and 5-d-old manure, and ammonia emission from manure. Differences up to 6% in ileal DM digestibility and 8% in ileal CP digestibility were observed. This difference was reduced to 1.1% for total tract DM digestibility and 4% for total tract CP digestibility. Differences in odorant concentration were 3-fold and for in vitro ammonia emission were 42%. The only compositional variable with a significant effect on digestibility was stachyose, which negatively affected ileal digestibility of DM (r = -0.80, P = 0.02) and energy (r = -0.73, P = 0.04). None of the compositional variables measured affected ileal CP digestibility. Ileal CP digestibility, however, was correlated with estimated CP fermentation in the large intestine (r = -0.86, P = 0.06) and with in vitro ammonia emission after 48 h (r = -0.81, P = 0.09). In conclusion, nutritionally relevant variability exists in soy varieties. Low stachyose content is important for maximizing ileal energy digestibility of soybean meal. Although no compositional variable was identified that explained differences in ileal CP digestibility, maximizing ileal CP digestibility is of interest for maximizing the nutritional value of soybean meal and possibly for reducing ammonia and odor emissions.}, number={6}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Kempen, T. A. T. G. and Heugten, E. and Moeser, A. J. and Muley, N. S. and Sewalt, V. J. H.}, year={2006}, month={Jun}, pages={1387–1395} }
 @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={BACKGROUND & AIMS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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{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 NH2-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 E2(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-1β, which is released by PMNs, we postulated that PMNs enhance recovery of ischemia-injured mucosa by a pathway involving IL-1β and COX-2. Application of 5 × 106PMNs 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 μM) and by an IL-1β receptor antagonist (0.1 mg/ml). Addition of 10 ng/ml IL-1β 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-1β or peritoneal PMNs, and the latter was inhibited by an IL-1β receptor antagonist. Real-time PCR revealed that increased mRNA COX-2 expression preceded increased COX-2 protein expression in response to IL-1β. We concluded that PMNs augment recovery of TER in ischemia-injured ileal mucosa via IL-1β-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} }
 @article{moeser_see_heugten_morrow_kempen_2003, title={Diet and evaluators affect perception of swine waste odor: An educational demonstration}, volume={81}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-2142759654&partnerID=MN8TOARS}, DOI={10.2527/2003.81123211x}, abstractNote={An educational program was developed for extension agents, faculty, and graduate students to illustrate the effect of diet composition on odor from swine manure. Participants in this program first received a 2-h detailed review on odorous compounds in manure and the effect of diet on odor. For the second portion of the training, nine manure samples were used from pigs fed diets formulated with feed ingredients predicted to have different effects on odor emission or a nutritionally adequate corn-soybean meal diet. Participants were instructed to rate the odor from these samples for pleasantness, irritation, and intensity on a scale of 0 (best) to 8 (worst), using manure from the corn-soybean meal fed pig as the reference with a score defined as 4 for each variable. Results obtained were summarized and discussed before concluding the program. Participants were Cooperative Extension Agents (n = 13) with swine responsibilities and graduate students and faculty (n = 8). The manure from the diet with the worst odor scores (1% garlic) was rated at 70% more odorous across the three odor variables (P < 0.05) than the diet with the least odorous manure (purified diet). Even though a reference sample was used, individual participants differed in their perception of irritation across samples (P < 0.05), ranging in average score across diets from 2.4 (moderately better than reference) to 5.0 (slightly worse than reference). With extension agents, a 1 to 7 scale (very interesting to not at all interesting) was used for evaluation of the training session. Participants found the material to be interesting (mean = 1.7, SD = 0.7) and the training exercise to be well organized and coherent in its presentation (mean = 1.8, SD = 0.7). Participants enjoyed this training and learned that differences in odor are achievable through altering diet composition, and that the response to swine odor depends on individual odor perception.}, number={12}, journal={Journal of Animal Science}, author={Moeser, A. J. and See, M. T. and Heugten, Eric and Morrow, W. E. M. and Kempen, T. Van}, year={2003}, pages={3211–3215} }
 @article{moeser_kempen_2002, title={Dietary fibre level and enzyme inclusion affect nutrient digestibility and excreta characteristics in grower pigs}, volume={82}, ISSN={["0022-5142"]}, DOI={10.1002/jsfa.1234}, abstractNote={Abstract}, number={14}, journal={JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE}, author={Moeser, AJ and Kempen, TATG}, year={2002}, month={Nov}, pages={1606–1613} }
 @article{moeser_kim_heugten_kempen_2002, title={The nutritional value of degermed, dehulled corn for pigs and its impact on the gastrointestinal tract and nutrient excretion}, volume={80}, DOI={10.2527/2002.80102629x}, abstractNote={Three experiments were designed to assess the feeding value and potential environmental benefits of feeding degermed, dehulled corn, a low fiber by-product originating from the corn dry milling process, to pigs. Twelve 27-kg (SE = 0.8) barrows were used in Exp. 1 to measure the apparent fecal digestibility of DM, GE and N of degermed, dehulled corn compared with corn grain. Two diets were formulated to contain either 96.4% of degermed, dehulled corn or corn grain plus supplemental vitamins and minerals. Digestibilities of DM, GE, and N were greater in degermed, dehulled corn (96.2, 96.0, and 93.6%, respectively) compared with corn grain (89.0, 89.0, and 78.4%, respectively) (P < 0.01). Overall, a 67 and 29% reduction in DM and N excretion, respectively, was observed. In Exp. 2, eight 70-kg (SE =1.8) barrows were surgically fitted with ileal cannulae and fed the same diets as in Exp. 1, to measure the ileal digestibility of nutrients in degermed, dehulled corn. Ileal digestibility of DM, energy, and N was 13, 15, and 7% greater in degermed, dehulled corn (P < 0.05). Apparent ileal digestibility coefficients of leucine, methionine, and phenylalanine were greater in degermed, dehulled corn compared with corn grain (P < 0.05) while a trend for a lower tryptophan digestibility in degermed, dehulled corn was observed (P = 0.067). In Experiment 3, 96 nursery pigs with an initial average BW of 8.8 kg (SE = 0.08), fed a starter diet formulated with degermed, dehulled corn or corn grain as the major grain source, were used in a 28-d growth performance study. At the end of the study, 24 pigs (1 pig per pen) were sacrificed and gastrointestinal tract measurements were taken. Daily growth rates of pigs were the same between diets (0.64 kg/d). A trend for reduced feed intake (P = 0.073) in pigs fed degermed, dehulled corn led to a 4% improvement in gain to feed (P < 0.05). Feeding degermed, dehulled corn had no effect on gut fill, gastrointestinal tract weight, or liver weight (P > 0.05). Ileal villus lengths and crypt depths were not affected by feeding degermed, dehulled corn although ileal villus widths were greater in pigs fed corn grain. Results from these trials suggest that corn processed to remove poorly digestible fiber fractions provides more digestible nutrients than corn grain. As a result, degermed, dehulled corn reduces fecal and N excretion, thus providing a means to reduce nutrient excretion.}, number={10}, journal={Journal of Animal Science}, author={Moeser, A. J. and Kim, I. B. and Heugten, Eric and Kempen, T. Van}, year={2002}, pages={2629–2638} }
 @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} }