@article{hassel_spier_aldridge_watnick_argenzio_snyder_2009, title={Influence of diet and water supply on mineral content and pH within the large intestine of horses with enterolithiasis}, volume={182}, ISSN={["1090-0233"]}, DOI={10.1016/j.tvjl.2008.05.016}, abstractNote={To determine the effects of two diets and water supplies on intestinal pH and mineral concentrations in the colon of horses, and to identify whether differences in these parameters exist in horses with and without enterolithiasis, surgical fistulation of the right dorsal colon was performed in six adult horses, three with and three without enterolithiasis. Each horse underwent four feeding trials: grass hay and untreated water, alfalfa hay and untreated water, grass hay with filtered/softened water, and alfalfa hay with filtered/softened water. Samples of colonic contents were analyzed for pH, dry matter, and mineral concentrations. Horses with enterolithiasis had higher calcium, magnesium, phosphorus and sulfur concentrations and higher pH in colonic contents than controls. Horses fed alfalfa had lower colonic sodium and potassium, higher calcium, magnesium, phosphorus and sulfur concentrations, and a more alkaline pH than those fed grass. Grass hay consumption leads to reduced concentrations of select minerals and a more acidic colonic environment compared with alfalfa, probably beneficial in the prevention of enterolithiasis. Under controlled dietary and management conditions, horses with enterolithiasis have differences in colonic mineral and pH parameters that may be consistent with physiological differences between horses with and without the disease.}, number={1}, journal={VETERINARY JOURNAL}, author={Hassel, Diana M. and Spier, Sharon J. and Aldridge, Brian M. and Watnick, Mitchell and Argenzio, Robert A. and Snyder, Jack R.}, year={2009}, month={Oct}, pages={44–49} }
 @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={Background: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. Aims: To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. Methods: 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. Results: 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. Conclusions: 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{gookin_duckett_armstrong_stauffer_finnegan_murtaugh_argenzio_2004, title={Nitric oxide synthase stimulates prostaglandin synthesis and barrier function in C-parvum-infected porcine ileum}, volume={287}, ISSN={["0193-1857"]}, DOI={10.1152/ajpgi.00413.2003}, abstractNote={Cell culture models implicate increased nitric oxide (NO) synthesis as a cause of mucosal hyperpermeability in intestinal epithelial infection. NO may also mediate a multitude of subepithelial events, including activation of cyclooxygenases. We examined whether NO promotes barrier function via prostaglandin synthesis using Cryptosporidium parvum-infected ileal epithelium in residence with an intact submucosa. Expression of NO synthase (NOS) isoforms was examined by real-time RT-PCR of ileal mucosa from control and C. parvum-infected piglets. The isoforms mediating and mechanism of NO action on barrier function were assessed by measuring transepithelial resistance (TER) and eicosanoid synthesis by ileal mucosa mounted in Ussing chambers in the presence of selective and nonselective NOS inhibitors and after rescue with exogenous prostaglandins. C. parvum infection results in induction of mucosal inducible NOS (iNOS), increased synthesis of NO and PGE2, and increased mucosal permeability. Nonselective inhibition of NOS ( NG-nitro-l-arginine methyl ester) inhibited prostaglandin synthesis, resulting in further increases in paracellular permeability. Baseline permeability was restored in the absence of NO by exogenous PGE2. Selective inhibition of iNOS [l- N6-(1-iminoethyl)-l-lysine] accounted for ∼50% of NOS-dependent PGE2synthesis and TER. Using an entire intestinal mucosa, we have demonstrated for the first time that NO serves as a proximal mediator of PGE2synthesis and barrier function in C. parvum infection. Expression of iNOS by infected mucosa was without detriment to overall barrier function and may serve to promote clearance of infected enterocytes.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, JL and Duckett, LL and Armstrong, MU and Stauffer, SH and Finnegan, CP and Murtaugh, MP and Argenzio, RA}, year={2004}, month={Sep}, pages={G571–G581} }
 @article{cole_argenzio_eisemann_2004, title={Physiological responses in swine treated with water containing sodium bicarbonate as a prophylactic for gastric ulcers}, volume={82}, DOI={10.2527/2004.8292757x}, abstractNote={Maintenance of gastric pH above 4.0 aids the prevention of bile acid-mediated ulcerative damage to the pars esophageal tissue in pigs. One means of doing so is the addition of buffering compounds, such as sodium bicarbonate, to the water supply; however, any potential physiological effect of buffer consumption has yet to be determined. Experiment 1 tested the acute effects of buffer addition to the water supply on systemic acid-base and electrolyte balance in swine (BW 40.7 +/- 3.0 kg). Consumption of water calculated to a 200 mOsm solution with sodium bicarbonate for 24 h increased (P < 0.05) blood Na+, HCO3(-), and pCO2, although these effects were all within physiologically tolerable levels. Urine pH and Na+ excretion increased (P < 0.001) following the consumption of NaHCO3, with Na+ concentration almost threefold higher in treated pigs compared with controls. Experiment 2 determined the chronic systemic effects of buffer consumption by measuring blood and urine variables, with pigs consuming NaHCO3-treated water throughout. Water consumption increased (P < 0.001) during buffer consumption, although intake levels remained within normal ranges. Blood pH levels were not affected by long-term consumption of dietary buffer; however, blood HCO3(-) (P < 0.05), Na+, and pCO2 (P < 0.01) increased. Urine pH and urine Na+ concentration increased (P < 0.01) in buffer-treated compared with control animals. Results indicate that sodium bicarbonate can safely be added to the water supply for pigs, with no clinically relevant alterations in acid-base balance because the animals readily compensate for buffer intake.}, number={9}, journal={Journal of Animal Science}, author={Cole, J. T. and Argenzio, R. A. and Eisemann, J. H.}, year={2004}, pages={2757–2763} }
 @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} }
 @article{nadeau_andrews_patton_argenzio_mathew_saxton_2003, title={Effects of hvdrochloric, valeric, and other volatile fatty acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses}, volume={64}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2003.64.413}, abstractNote={AbstractObjective—To identify in vitro effects of hydrochloric acid, valeric acid, and other volatile fatty acids (VFAs) on the pathogenesis of ulcers in the nonglandular portion of the equine stomach.Sample Population—Gastric tissues from 13 adult horses.Procedure—Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance and conductance calculated after tissues were bathed in normal Ringer's solution (NRS) or NRS and hydrochloric, valeric, acetic, propionic, and butyric acids. Treated tissues were examined histologically.Results—Incubation in 60mM valeric acid at pH ≤ 7.0 abruptly and irreversibly abolished Isc, which was followed by a slower decrease in resistance and an increase in conductance. Incubation in 60mM acetic, propionic, and butyric acids and, to a lesser extent, hydrochloric acid at pH ≤ 7.0 significantly decreased Isc, which was followed by an increase in resistance and a decrease in conductance.Conclusions and Clinical Relevance—Incubation in valeric acid at pH ≤ 7.0 caused a dramatic decrease in mucosal barrier function in the nonglandular portion of the stomach. Changes in barrier function attributable to exposure to valeric acid were associated with histopathologic evidence of cellular swelling in all layers of the nonglandular mucosa. Because of its high lipid solubility, valeric acid penetrates the nonglandular gastric mucosa, resulting in inhibition of sodium transport and cellular swelling. Valeric acid and other VFAs in gastric contents may contribute to the pathogenesis of ulcers in the nonglandular portion of the stomach of horses. (Am J Vet Res2003;64:413–417)}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Nadeau, JA and Andrews, FM and Patton, CS and Argenzio, RA and Mathew, AG and Saxton, AM}, year={2003}, month={Apr}, pages={413–417} }
 @article{nadeau_andrews_patton_argenzio_mathew_saxton_2003, title={Effects of hydrochloric, acetic, butyric, and propionic acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses}, volume={64}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2003.64.404}, abstractNote={AbstractObjective—To identify the pathogenesis of gastric ulcers by comparing injury to the nonglandular gastric mucosa of horses caused by hydrochloric acid (HCl) or volatile fatty acids (VFAs).Sample Population—Gastric tissues from 30 horses.Procedure—Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance calculated for tissues after addition of HCl and VFAs to normal Ringer's solution (NRS). Tissues were examined histologically.Results—Mucosa exposed to HCl in NRS (pH, 1.5) had a significant decrease in Isc, compared with Isc for mucosa exposed to NRS at pH 4.0 or 7.0. Also, exposure to 60mM acetic, propionic, and butyric acids (pH, 4.0 or 1.5) caused an immediate significant decrease in Isc. Recovery of sodium transport was detected only in samples exposed to acetic acid at pH 4.0. Recovery of sodium transport was not seen in other mucosal samples exposed to VFAs at pH ≤ 4.0.Conclusions and Clinical Relevance—Acetic, butyric, and propionic acids and, to a lesser extent, HCl caused decreases in mucosal barrier function of the nonglandular portion of the equine stomach. Because of their lipid solubility at pH ≤ 4.0, undissociated VFAs penetrate cells in the nonglandular gastric mucosa, which causes acidification of cellular contents, inhibition of sodium transport, and cellular swelling. Results indicate that HCl alone or in combination with VFAs at gastric pH ≤ 4.0 may be important in the pathogenesis of gastric ulcers in the nonglandular portion of the stomach of horses. (Am J Vet Res2003;64:404–412)}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Nadeau, JA and Andrews, FM and Patton, CS and Argenzio, RA and Mathew, AG and Saxton, AM}, year={2003}, month={Apr}, pages={404–412} }
 @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 Ω·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{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"]}, DOI={10.2460/ajvr.2002.63.1076}, abstractNote={AbstractObjective—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.Animals—6 pigs weighing between 60 and 70 kg.Procedure—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.Results—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.Conclusions and Clinical Relevance—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. (Am J Vet Res2002;63:1076–1082)}, 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} }
 @misc{gookin_nordone_argenzio_2002, title={Host responses to Cryptosporidium infection}, volume={16}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2002)016<0012:HRTCI>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 16, Issue 1 p. 12-21 Open Access Host Responses to Cryptosporidium Infection Jody L. Gookin, Corresponding Author Jody L. Gookin Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC. Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; e-mail: [email protected]Search for more papers by this authorShila K. Nordone, Shila K. Nordone Departments of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this authorRobert A. Argenzio, Robert A. Argenzio Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this author Jody L. Gookin, Corresponding Author Jody L. Gookin Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC. Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; e-mail: [email protected]Search for more papers by this authorShila K. Nordone, Shila K. Nordone Departments of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this authorRobert A. Argenzio, Robert A. Argenzio Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2002.tb01602.xCitations: 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 Abstract Cryptosporidium is a clinically and economically important infection whose pathogenic effect begins with colonization of the intestinal epithelium. Despite intensive efforts, a consistently effective therapy for the infection has yet to be identified. Morbidity and mortality results from ongoing loss of absorptive epithelium, which leads to villous atrophy and malabsorption and release of inflammatory mediators that stimulate electrolyte secretion and diarrhea. With further clarification of the mechanisms underlying enterocyte malfunction in Cryptosporidium infection, it should be possible to design rational nutritional and pharmacologic therapies to enhance nutrient and water absorption, promote the clearance of infected enterocytes, and restore normal villus architecture and mucosal barrier function. References 1 Current WL. Cryptosporidiosis. J Am Vet Med Assoc 1985; 187: 1334– 1338. 2 Guerrant RL. Cryptosporidiosis: An emerging, highly infectious threat. Emerg Infect Dis 1997; 3: 51– 57. 3 Division of Child Health and Development. Improving Child Health. IMCI: The Integrated Approach. Geneva , Switzerland : World Health Organization; 1997. 4 MacKenzie WR, Hoxie NJ, Proctor ME. 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Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism. Hepatology 1998; 28: 906– 913. 22 Marcial MA, Madara JL. Cryptosporidium: Cellular localization, structural analysis of absorptive cell-parasite membrane-membrane interactions in guinea pigs, and suggestion of protozoan transport by M cells. Gastroenterology 1986; 90: 583– 594. 23 Tzipori S, Widmer G. The biology of Cryptosporidium. Contrib Microbiol 2000; 6: 1– 32. 24 Elliott DA, Clark DP. Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infect Immun 2000; 68: 2315– 2322. 25 Bonnin A, Lapillonne A, Petrella T, et al. Immunodetection of the microvillus cytoskeleton molecules villin and ezrin in the parasi-tophorous vacuole wall of Cryptosporidium parvum. Eur J Cell Biol 1999; 78: 794– 801. 26 Forney JR, DeWald DB, Yang S, et al. A role for host phos-phoinositide 3-kinase and cytoskeletal remodeling during Cryptosporidium parvum infection. Infect Immun 1999; 67: 844– 852. 27 Perkins ME, Riojas YA, Wu TW, et al. CpABC, a Cryptosporidium parvum ATP-binding cassette protein at the host-parasite boundary in intracellular stages. Proc Natl Acad Sci USA 1999; 96: 5734– 5739. 28 Argenzio RA, Liacos JA, Levy ML, et al. Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose-Na absorption in enteric cryptosporidiosis of pigs. Gastroenterology 1990; 98: 1129– 1140. 29 Griffiths JK, Moore R, Dooley S, et al. Cryptosporidium parvum infection of Caco-2 cell monolayers induces an apical monolayer defect, selectively increases transmonolayer permeability, and causes epithelial cell death. Infect Immun 1994; 62: 4506– 4514. 30 Planchon SM, Martins CAP, Guerrant RL, et al. Regulation of intestinal epithelial barrier function by TGF-β1. Evidence for its role in abrogating the effect of a T cell cytokine. J Immunol 1994; 153: 5730– 5739. 31 Goodgame RW, Kimball K, Ou CN, et al. Intestinal function and injury in acquired immunodeficiency syndrome-related cryptosporidiosis. Gastroenterology 1995; 108: 1075– 1082. 32 Moore R, Tzipori S, Griffiths JK, et al. Temporal changes in permeability and structure of piglet ileum after site-specific infection by Cryptosporidium parvum. Gastroenterology 1995; 108: 1030– 1039. 33 Capet C, Kapel N, Huneau JF, et al. Cryptosporidium parvum infection in suckling rats: Impairment of mucosal permeability and Na+-glucose cotransport. Exp Parasitol 1999; 91: 119– 125. 34 Chen XM, Gores GJ, Paya CV, et al. Cryptosporidium parvum induces apoptosis in biliary epithelia by a Fas/Fas ligand-dependent mechanism. Am J Physiol 1999; 277: G599– G608. 35 McCole DF, Eckmann L, Laurent F, et al. Intestinal epithelial cell apoptosis following Cryptosporidium parvum infection. Infect Immun 2000; 68: 1710– 1713. 36 Seydel KB, Zhang T, Champion GA, et al. Cryptosporidium parvum infection of human intestinal xenografts in SCID mice induces production of human tumor necrosis factor alpha and interleukin-8. Infect Immun 1998; 66: 2379– 2382. 37 Kandil HM, Berschneider HM, Argenzio RA. Tumor necrosis factor-α changes porcine intestinal ion transport through a paracrine mechanism involving prostaglandins. Gut 1994; 35: 934– 940. 38 Argenzio RA, Rhoads JM. Reactive oxygen metabolites in piglet cryptosporidiosis. Pediatr Res 1997; 41: 521– 526. 39 Guarino A, Canani RB, Casola A, et al. Human intestinal cryptosporidiosis: Secretory diarrhea and enterotoxic activity in Caco-2 cells. J Infect Dis 1995; 171: 976– 983. 40 Kapel N, Huneau JF, Magne D, et al. Cryptosporidiosis-induced impairment of ion transport and Na+-glucose absorption in adult im-munocompromised mice. J Infect Dis 1997; 176: 834– 837. 41 Argenzio RA, Lecce J, Powell DW. Prostanoids inhibit intestinal NaCl absorption in experimental porcine cryptosporidiosis. Gastroenterology 1993; 104: 440– 447. 42 Argenzio RA, Rhoads JM, Armstrong M, et al. Glutamine stimulates prostaglandin-sensitive Na+-H+ exchange in experimental porcine cryptosporidiosis. Gastroenterology 1994; 106: 1418– 1428. 43 Argenzio RA, Armstrong M, Rhoads JM. Role of the enteric nervous system in piglet cryptosporidiosis. J Pharm Exp Ther 1996; 279: 1109– 1115. 44 Bern MJ, Sturbaum CW, Karayalcin SS, et al. Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and the enteric nervous system. J Clin Invest 1989; 83: 1810– 1820. 45 Laurent F, Kagnoff MF, Savidge TC, et al. Human intestinal epithelial cells respond to Cryptosporidium parvum infection with increased prostaglandin H synthase 2 expression and prostaglandin E2 and F2α production. Infect Immun 1998; 66: 1787– 1790. 46 Moon HW, Kohler EM, Whipp SC. Vacuolation: A function of cell age in porcine ileal absorptive cells. Lab Invest 1973; 28: 23– 28. 47 Cho JH, Musch MW, DePaoli AM, et al. Glucocorticoids regulate Na/H exchange expression and activity in region and tissue-specific manner. Am J Physiol 1994; 267: C796– C803. 48 Kandil HM, Gray M, Armstrong M, et al. Interaction between PGE2 and tumor necrosis factor in porcine intestinal inflammation and damage. Gastroenterology 1994; 106: A798. 49 Mead JR, Arrowood MJ, Sidwell RW, et al. Chronic Cryptosporidium parvum infection in congenitally immunodeficient SCID and nude mice. J Infect Dis 1991; 163: 1297– 1304. 50 McDonald V, Deer R, Uni S, et al. Immune responses to Cryptosporidium muris and Cryptosporidium parvum in adult immunocom-petent or immunocompromised (nude and SCID) mice. Infect Immun 1992; 60: 3325– 3331. 51 Kuhls TL, Greenfield RA, Mosier DA, et al. Cryptosporidiosis in adult and neonatal mice with severe combined immunodeficiency. J Comp Pathol 1992; 106: 399– 410. 52 Rohlman VC, Kuhis TL, Mosier DA, et al. Cryptosporidium parvum infection after abrogation of natural killer cell activity in normal and severe combined immunodeficient mice. J Parasitol 1993; 79: 295– 297. 53 Chai J-Y, Guk S-M, Han H-K, et al. Role of intraepithelial lymphocytes in mucosal immune responses of mice experimentally infected with Cryptosporidium parvum. J Parasitol 1999; 85: 234– 239. 54 Culshaw RJ, Bancroft GJ, McDonald V. Gut intraepithelial lymphocytes induce immunity against Cryptosporidium infection through a mechanism involving gamma interferon production. Infect Immun 1997; 65: 3074– 3079. 55 Taghi-Kilani R, Sekla L, Hayglass KT. The role of humoral immunity in Cryptosporidium spp. infection. Studies with B cell-depleted mice. J Immunol 1990; 145: 1571– 1576. 56 Perryman LE, Mason PH, Chrisp CE. Effect of spleen cell populations on resolution of Cryptosporidium parvum infection in SCID mice. Infect Immun 1994; 62: 1474– 1477. 57 Waters WR, Harp JA. Cryptosporidium parvum in T-cell receptor (TCR)-α- and TCR-δ-deficient mice. Infect Immun 1996; 64: 1854– 1857. 58 Aguirre SA, Mason PH, Perryman LE. Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection. Infect Immun 1994; 62: 697– 699. 59 McDonald V, Robinson HA, Kelly JP, et al. Immunity to Cryptosporidium muris infection in mice is expressed through gut CD4+ intraepithelial lymphocytes. Infect Immun 1996; 64: 2556– 2562. 60 Wyatt CR, Brackett EJ, Perryman LE, et al. Activation of intestinal intraepithelial T lymphocytes in calves infected with Cryptosporidium parvum. Infect Immun 1997; 65: 185– 190. 61 Wyatt CR, Brackett EJ, Barrett WJ. Accumulation of mucosal T lymphocytes around epithelial cells after in vitro infection with Cryptosporidium parvum. J Parasitol 1999; 85: 765– 768. 62 Adjei AA, Curran BC, Castro M, et al. γδ+ T cells and 65-kDa heat shock protein expression following Cryptosporidium parvum challenge in athymic C57BL/6J nude mice. Immunol Lett 2000; 72: 35– 38. 63 Waters WR, Harp JA, Nonnecke BJ. Phenotypic analysis of peripheral blood lymphocytes and intestinal intra-epithelial lymphocytes in calves. Vet Immunol Immunopathol 1995; 48: 249– 259. 64 Ungar BLP, Kao TC, Burris AA, et al. Cryptosporidium infection in an adult mouse model: Independent roles for IFNγ and CD4+ T lymphocytes in protective immunity. J Immunol 1991; 147: 1014– 1022. 65 Chen W, Harp JA, Harmsen AG. Requirements for CD4+ cells and gamma interferon in resolution of established Cryptosporidium parvum infection in mice. Infect Immun 1993; 61: 3928– 3932. 66 Chen W, Harp JA, Harmsen AG, et al. Gamma interferon functions in resistance to Cryptosporidium parvum infection in severe combined immunodeficient mice. Infect Immun 1993; 61: 3548– 3551. 67 Enriquez FJ, Sterling CR. Role of CD4+ Thl- and Th2-cell secreted cytokines in cryptosporidiosis. Fol Parasitol 1993; 40: 307– 311. 68 Urban JF, Fayer R, Chen SJ, et al. IL-12 protects immunocom-petent and immunodeficient neonatal mice against infection with Cryptosporidium parvum. J Immunol 1996; 156: 263– 268. 69 Aguirre SA, Perryman LE, Davis WC, et al. IL-4 protects adult C57BL/6 mice from prolonged Cryptosporidium parvum infection: Analysis of CD4+αβ+IFN–γ+ and CD4+αβ+IL-4+ lymphocytes in gut-associated lymphoid tissue during resolution of infection. J Immunol 1998; 161: 1891– 1900. 70 Lukin K, Cosyns M, Mitchell T, et al. Eradication of Cryptosporidium parvum infection by mice with ovalbumin-specific T cells. Infect Immun 2000; 68: 2663– 2670. 71 Griffiths JK, Theodos C, Paris M, et al. The gamma interferon gene knockout mouse: A highly sensitive model for evaluation of therapeutic agents against Cryptosporidium parvum. J Clin Microbiol 1998; 36: 2503– 2508. 72 You X, Mead JR. Characterization of experimental Cryptosporidium parvum infection in IFN-γ knockout mice. Parasitology 1998; 117: 525– 531. 73 Colgan SP, Parkos CA, Matthews JB, et al. Interferon-γ induces a cell surface phenotype switch on T84 intestinal epithelial cells. Am J Physiol 1994; 267: C402– C410. 74 Müerköster S, Laman JD, Rocha M, et al. Functional and in situ evidence for nitric oxide production driven by CD40-CD40L interactions in graft-versus-leukemia reactivity. Clin Cancer Res 2000; 6: 1988– 1996. 75 Pollok RC, Farthing MJ, Bajaj-Elliott M, et al. Cellular mechanisms of interferon γ mediated inhibition of Cryptosporidium parvum infection. Gastroenterology 2000; 118: A817. 76 Dignass AU, Podolsky DK, Rachmilewitz D. NOX generation by cultured small intestinal epithelial cells. Dig Dis Sci 1995; 40: 1859– 1865. 77 Foy TM, Aruffo A, Bajorath J, et al. Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 1996; 14: 591– 617. 78 Leitch GJ, He Q. Reactive nitrogen and oxygen species ameliorate experimental cryptosporidiosis in the neonatal BALB/c mouse model. Infect Immun 1999; 67: 5885– 5891. 79 Leitch GJ, He Q. Arginine-derived nitric oxide reduces fecal oocyst shedding in nude mice infected with Cryptosporidium parvum. Infect Immun 1994; 62: 5173– 5176. 80 Hayward AR, Chmura K, Cosyns M. Interferon-γ is required for innate immunity to Cryptosporidium parvum in mice. J Infect Dis 2000; 182: 1001– 1004. 81 Kuhls TL, Mosier DA, Abrams VL, et al. Inability of interfer-on-gamma and aminoguanidine to alter Cryptosporidium parvum infection in mice with severe combined immunodeficiency. J Parasitol 1994; 80: 480– 485. 82 James SL. Role of nitric oxide in parasitic infections. Microbiol Rev 1995; 59: 533– 547. 83 Eckmann L, Laurent F, Langford TD, et al. Nitric oxide production by human intestinal epithelial cells and competition for argi-nine as potential determinants of host defense against the lumen-dwelling pathogen Giardia lamblia. J Immunol 2000; 164: 1478– 1487. 84 Brune B, von Knethen A, Sandau KB. Nitric oxide and its role in apoptosis. Eur J Pharmacol 1998; 351: 261– 272. 85 Miller MJS, Thompson JH, Zhang X-J, et al. Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 1995; 109: 1475– 1483. 86 Theodos CM, Sullivan KL, Griffiths JK, et al. Profiles of healing and nonhealing Cryptosporidium parvum infection in C57BL/6 mice with functional B and T lymphocytes: The extent of gamma interferon modulation determines the outcome of infection. Infect Immun 1997; 65: 4761– 4769. 87 Smith LM, Bonafonte MT, Mead JR. Cytokine expression and specific lymphocyte proliferation in two strains of Cryptosporidium parvwm-infected gamma-interferon knockout mice. J Parasitol 2000; 86: 300– 307. 88 Bellamy R. The natural resistance-associated macrophage protein and susceptibility to intracellular pathogens. Microbes Infect 1999; 1: 23– 27. 89 Feng J, Li Y, Hashad M, et al. Bovine natural resistance associated macrophage protein 1 (Nrampl) gene. Genome Res 1996; 6: 956– 964. Citing Literature Volume16, Issue1January 2002Pages 12-21 ReferencesRelatedInformation}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, JL and Nordone, SK and Argenzio, RA}, year={2002}, pages={12–21} }
 @article{gookin_rhoads_argenzio_2002, title={Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum}, volume={283}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00005.2001}, abstractNote={ Reports conflict regarding the effect of nitric oxide (NO) on intestinal epithelium. In chronic injury, NO appears detrimental by combining with reactive oxygen to form potent-free radicals. In contrast, inhibition of NO synthesis after acute injury exacerbates damage and inflammation. Recent studies have disclosed constitutive expression of inducible NO synthase (iNOS) by normal intestinal epithelia, yet little attention has been given to the role of iNOS in acute epithelial repair. We studied the local effects of iNOS on early epithelial repair of porcine ileal mucosa injured by deoxycholate within Ussing chambers. iNOS was constitutively expressed by the villous epithelium, and after deoxycholate injury, iNOS was expressed by injured and detaching enterocytes. Selective inhibition of iNOS abolished increases in NO synthesis and villous reepithelialization after injury. Exogenous l-arginine rescued baseline reepithelialization from NOS inhibitors but was only capable of stimulating additional repair in the presence of serum. These results demonstrate that iNOS-derived NO is a key mediator of early villous reepithelialization following acute mucosal injury. }, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, JL and Rhoads, JM and Argenzio, RA}, year={2002}, month={Jul}, pages={G157–G168} }
 @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.}, 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{hunt_fu_armstrong_rennix_webster_galanko_chen_weaver_argenzio_rhoads_2002, title={Oral bovine serum concentrate improves cryptosporidial enteritis in calves}, volume={51}, ISSN={["0031-3998"]}, DOI={10.1203/00006450-200203000-00017}, abstractNote={Cryptosporidium parvum produces a prolonged watery diarrhea unresponsive to conventional antimicrobials. Because of reported efficacy of antibody-based immunotherapy, we studied the effect of inexpensive, commercially available oral bovine serum concentrate (BSC) in experimental cryptosporidiosis. Twenty-four calves were treated with 57 g/d BSC (n = 12) or soy protein (n = 12) added to their standard whey protein-based milk replacer (227 g/2 L twice daily). Of the 24, 9 were also treated with l-glutamine (GLN), 8 g/L (50 mM) in the milk (5 calves in the BSC group and 4 in the soy group). Animals were inoculated with 108 cryptosporidium oocysts per os on d 8 of life and received oral rehydration on d 12–14. Eight uninfected controls were treated with BSC or soy protein. Fecal and urine volume and urinary Cr-EDTA excretion were measured. Animals were killed on d 18 of life. Cryptosporidiosis induced severe watery diarrhea lasting >9 d and produced a 25% increase in intestinal permeability, a 33% decrease in villous surface area, and a 40% reduction in mucosal lactase specific activity. Glutamine treatment had no effect on the diarrhea or any of the intestinal tests; and therefore pooled data were used to compare the 12 calves treated with BSC with the 12 treated with soy. In animals receiving BSC, peak diarrheal volume and intestinal permeability were reduced 33%, fewer oocysts were shed, intestinal crypts were significantly deeper, and villous surface area returned to normal by 9 d after infection (all p ≤ 0.05). BSC should be studied as a treatment for human cryptosporidiosis.}, number={3}, journal={PEDIATRIC RESEARCH}, author={Hunt, E and Fu, Q and Armstrong, MU and Rennix, DK and Webster, DW and Galanko, JA and Chen, WN and Weaver, EM and Argenzio, RA and Rhoads, JM}, year={2002}, month={Mar}, pages={370–376} }
 @article{mcconnico_argenzio_roberts_2002, title={Prostaglandin E-2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis}, volume={66}, number={1}, journal={Canadian Journal of Veterinary Research}, author={McConnico, R. S. and Argenzio, R. A. and Roberts, M. C.}, year={2002}, pages={50–54} }
 @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={Background: 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. Aims: 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. Methods: 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-PGF1α (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. Results: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5×10−6 M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5×10−6 M) or the COX-2 inhibitor NS-398 (5×10−6 M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1α 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. Conclusions: 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} }
 @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} }
 @inbook{monteiro-riviere_argenzio_2001, title={The excretory system}, volume={13}, booktitle={Biology of the domestic pig}, publisher={Ithaca, NY: Comstock Pub. Associates/Cornell University Press}, author={Monteiro-Riviere, N. A. and Argenzio, R. A.}, editor={W. G. Pond, H. J. MersmannEditor}, year={2001}, pages={585–624} }
 @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{nadeau_andrews_mathew_argenzio_blackford_sohtell_saxton_2000, title={Evaluation of diet as a cause of gastric ulcers in horses}, volume={61}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2000.61.784}, abstractNote={AbstractObjective—To measure pH, volatile fatty acid (VFA) concentrations, and lactate concentrations in stomach contents and determine number and severity of gastric lesions in horses fed bromegrass hay and alfalfa hay-grain diets.Animals—Six 7-year-old horses.Procedure—A gastric cannula was inserted in each horse. Horses were fed each diet, using a randomized crossover design. Stomach contents were collected immediately after feeding and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after feeding on day 14. The pH and VFA and lactate concentrations were measured in gastric juice. Number and severity of gastric lesions were scored during endoscopic examinations.Results—The alfalfa hay-grain diet caused significantly higher pH in gastric juice during the first 5 hours after feeding, compared with that for bromegrass hay. Concentrations of acetic, propionic, and isovaleric acid were significantly higher in gastric juice, and number and severity of nonglandular squamous gastric lesions were significantly lower in horses fed alfalfa hay-grain. Valeric acid, butyric acid, and propionic acid concentrations and pH were useful in predicting severity of nonglandular squamous gastric lesions in horses fed alfalfa hay-grain, whereas valeric acid concentrations and butyric acid were useful in predicting severity of those lesions in horses fed bromegrass hay.Conclusions and Clinical Relevance—An alfalfa haygrain diet induced significantly higher pH and VFA concentrations in gastric juice than did bromegrass hay. However, number and severity of nonglandular squamous gastric lesions were significantly lower in horses fed alfalfa hay-grain. An alfalfa hay-grain diet may buffer stomach acid in horses. (Am J Vet Res2000;61: 784–790)}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Nadeau, JA and Andrews, FM and Mathew, AG and Argenzio, RA and Blackford, JT and Sohtell, M and Saxton, AM}, year={2000}, month={Jul}, pages={784–790} }
 @article{vaden_sellon_melgarejo_williams_trogdon_vancamp_argenzio_2000, title={Evaluation of intestinal permeability and gluten sensitivity in Soft-Coated Wheaten Terriers with familial protein-losing enteropathy, protein-losing nephropathy, or both}, volume={61}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2000.61.518}, abstractNote={AbstractObjective—To evaluate intestinal permeability and gluten sensitivity in a family of Soft-Coated Wheaten Terriers (SCWT) affected with protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both.Animals—6 affected adult dogs.Procedure—Intestinal biopsy specimens, urine protein- to-creatinine ratio, serum concentrations of albumin and globulin, and concentration of α1-protease inhibitor in feces were evaluated before, during, and 13 weeks after daily administration of 10 g of gluten for 7 weeks. Eosinophils and lymphocytes-plasmacytes were enumerated in intestinal biopsy specimens. Intestinal permeability was evaluated before and during the sixth week of gluten administration via cellobiose-mannitol and chromium-EDTA absorption tests.Results—Serum globulin concentration decreased significantly after prolonged administration of gluten. Although not significant, there was an increase in lymphocytes- plasmacytes and a decrease in eosinophils in intestinal biopsy specimens. Furthermore, these counts were greater than those reported for clinically normal dogs. Gluten administration did not increase intestinal permeability.Conclusions and Clinical Relevance—Daily administration of gluten was associated with a significant decrease in serum globulin concentration in SCWT affected with PLE or PLN, but other variables remained unchanged. Although enhanced wheatgluten sensitivity may be one factor involved in the pathogenesis of PLE or PLN in SCWT, this syndrome does not appear to be the result of a specific sensitivity to gluten. (Am J Vet Res2000;61:518–524)}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Vaden, SL and Sellon, RK and Melgarejo, LT and Williams, DA and Trogdon, MM and VanCamp, SD and Argenzio, RA}, year={2000}, month={May}, pages={518–524} }
 @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 PGE2enhances 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 PGE2-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 [3H] N-formyl-methionyl-leucyl phenylalanine (FMLP) and [3H]mannitol were monitored as indicators of recovery of barrier function. Treatment with genistein (10−4M) and PGE2(10−6M) resulted in synergistic elevations in R and additive reductions in mucosal-to-serosal fluxes of [3H]FMLP and [3H]mannitol, whereas treatment with genistein alone had no effect. Treatment of injured tissues with genistein and either 8-bromo-cAMP (10−4M) or cGMP (10−4M) resulted in synergistic increases in R. However, treatment of tissues with genistein and the protein kinase C (PKC) agonist phorbol myristate acetate (10−5–10−6M) had no effect on R. Genistein augments recovery of Rin 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"]}, DOI={10.1016/S0016-5085(00)70417-3}, abstractNote={<h2>Abstract</h2> <b>Background & Aims:</b> 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. <b>Methods:</b> 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). <b>Results:</b> In glutamine-starved cells, 10 mmol/L glutamine in the absence of serum stimulated [<sup>3</sup>H]thymidine incorporation 8-fold. This effect was inhibited by 60% with 8-(4-chlorophenylthio) (8-CPT)-cAMP (100 μmol/L) + isobutyl methylxanthine (100 μmol/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. <b>Conclusions:</b> Increased levels of intracellular cAMP inhibit ERKs but only partially reduce glutamine-stimulated proliferation in enterocytes adapted to low glutamine. GASTROENTEROLOGY 2000;118:90-100}, 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{kandil_argenzio_sartor_2000, title={Low endogenous prostaglandin E-2 predisposes to relapsing inflammation in experimental rat enterocolitis}, volume={45}, ISSN={["1573-2568"]}, DOI={10.1023/A:1026675005554}, abstractNote={Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2/IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day of indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. Imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.}, number={11}, journal={DIGESTIVE DISEASES AND SCIENCES}, author={Kandil, HM and Argenzio, RA and Sartor, RB}, year={2000}, month={Nov}, pages={2091–2099} }
 @article{regina_eisemann_lang_argenzio_1999, title={Changes in gastric contents in pigs fed a finely ground and pelleted or coarsely ground meal diet}, volume={77}, DOI={10.2527/1999.77102721x}, abstractNote={The objective was to characterize the change in stomach contents in relation to time after feeding between pigs consuming a restricted amount of a finely ground and pelleted (FGP) or coarsely ground meal (CGM) diet. Particular interest was placed on the concentration of organic acids and ammonia, the products of microbial fermentation. Thirty barrows were ranked by weight and assigned to a postfeeding time of 2, 4, 6, 8, or 12 h and either the FGP or CGM diet. Initiation and termination of the experiment were staggered over a 2-wk period. The treatment period was 42 d. Percentage of dry matter was higher (P<.01) in the stomach contents of pigs on the CGM diet. Concentrations of pepsin and protein were higher (P<.05) and ammonia tended to be higher (P = .10) in the proximal stomach of pigs fed the FGP diet. In contrast, concentrations of acetate and L-lactate were higher (P<.05) in the proximal stomach of pigs fed the CGM diet. All pigs on the CGM diet had stomachs that graded as normal on visual inspection. There was variable damage to the stomachs of pigs on the FGP diet. Measurement of chromium concentration in the stomach after an oral dose of Cr-EDTA clearly demonstrated the mixing that occurs between the proximal and distal stomach by 2 h after feeding in pigs consuming the FGP diet, whereas a gradient was maintained in pigs consuming the CGM diet. Thus, components normally secreted in the distal stomach return to the proximal stomach. These data show that components secreted in the distal region, such as acid and pepsin, may play a role in initiating damage to the stratified squamous mucosa. High concentrations of organic acids in the stomach of pigs on the CGM diet were not associated with damage to the stratified squamous mucosa in the esophageal region.}, number={10}, journal={Journal of Animal Science}, author={Regina, D. C. and Eisemann, J. H. and Lang, J. A. and Argenzio, R. A.}, year={1999}, pages={2721–2729} }
 @article{argenzio_1999, title={Comparative pathophysiology of nonglandular ulcer disease: A review of experimental studies}, DOI={10.1111/j.2042-3306.1999.tb05163.x}, abstractNote={SummaryUlceration of the nonglandular, stratified squamous mucosa of the equine and porcine stomach is a common event in both species, although in pigs the fatality rate is significant and it is an economically important disease. Because the barrier function of this mucosa in horses and pigs appears similar, it is probable that similar pathophysiological mechanisms may be responsible for the initiating lesions and reparative events. Recent studies of ulcer pathogenesis in the pig have shown that feed preparation or prolonged fasting can result in disruption of the normal stratification of gastric contents, thereby allowing high concentrations of HCl, pepsin and refluxed bile to mix in the proximal stomach. Conditions simulating those foundin vivohave been shown to damage this mucosain vitroand indicate that luminal products, such as short chain fatty acids and bile salts, which act in synergy with HCl, probably are necessary to induce significant damage to this mucosa. Studies of the equine stomach have shown a similar proximal to distal pH gradient in the fed stomach, a significant duodenal‐gastric reflux, and induction of squamous ulcers with fasting, thereby illustrating that similar conditions may be responsible for damage to the equine nonglandular mucosa.}, journal={Equine Veterinary Journal}, author={Argenzio, R. A.}, year={1999}, pages={19} }
 @inbook{argenzio_1999, title={Comparative pathophysiology of nonglandular ulcer disease: A review of experimental studies}, booktitle={Equine gastric ulceration  (Equine veterinary journal supplement)}, publisher={Suffolk, UK: British Equine Veterinary Association}, author={Argenzio, R. A.}, editor={T. S. Mair, P. D. Rossdale and Merritt, A. M.Editors}, year={1999}, pages={19–23} }
 @article{eisemann_argenzio_1999, title={Effects of diet and housing density on growth and stomach morphology in pigs}, volume={77}, DOI={10.2527/1999.77102709x}, abstractNote={Two experiments were conducted to evaluate the impact of housing density on the stomach morphology of growing pigs and determine whether there was an interaction between housing density and diet. All diets were corn-soybean meal based. In Exp. 1, 42 barrows (41.0+/-.95 kg BW) were allotted either individually or three pigs per pen to evaluate the effects of crowding on stomach lesions. Pen space per pig was 1.54 and .51 m2, respectively. All pigs were fed a finely ground and pelleted diet (610 microm) for 6 wk. The ADG decreased (P<.05) for the pigs housed three per pen during wk 4 to 6 only. There was no effect of housing density on feed intake or gain/feed ratio. Neither visual nor histological ulcer score differed between the two treatment groups. No stomachs were graded as normal. In Exp. 2, 80 barrows (39.8+/-.9 kg BW) were allotted either two or four pigs per pen. Pen space per pig was .77 and .39 m2, respectively. Half of the pigs in each housing situation were fed a coarse meal diet (1,050 microm), and half of the pigs were fed a finely ground and pelleted diet (577 microm) throughout the 49-d experimental period. Throughout the trial, pigs housed two per pen gained at a greater rate (P<.05) than pigs housed four per pen. From d 14 to the end of the trial, pigs consuming the finely ground and pelleted diet gained at a greater rate (P<.05) than pigs fed the coarse meal diet. The differences in ADG were reflected in final body weight. Stomach weight as a percentage of body weight was higher for animals on the coarse meal diet. Visual and histological ulcer scores were similar, and both were higher (P<.001) on the finely ground and pelleted diet, indicating greater damage. There was no effect of space restriction on stomach morphology. These data show the major effect of diet type on stomach lesions with no interaction with space restriction.}, number={10}, journal={Journal of Animal Science}, author={Eisemann, J. H. and Argenzio, R. A.}, year={1999}, pages={2709–2714} }
 @article{eisemann_argenzio_1999, title={Effects of diets differing in propensity to promote gastric lesions on defense systems in gastric mucosae}, volume={77}, DOI={10.2527/1999.77102715x}, abstractNote={The objectives were to characterize biochemical changes, focusing on the antioxidant defense system, in stratified squamous and oxyntic mucosae in pigs fed diets with differing propensity to promote gastric lesions. Barrows (n = 24; 48.7+/-1.0 kg BW) housed in individual pens were used in the experiment. Barrows were fed a corn-soybean meal diet. Half of the animals were fed the diet as a coarsely ground meal (CGM; average particle size = 886 microm), and half were fed the diet as a finely ground pelleted (FGP; average particle size = 528 microm) feed. Initiation and termination of the experiment were staggered over a 3-wk period. Diets were fed for 6 wk. Visual evaluation of the stratified squamous mucosa of the proximal stomach showed increased (P<.001) damage in animals fed the FGP diet. These results were supported by histological evaluation. Thiobarbituric acid-reacting substances (TBARS), indicative of peroxide generation, relative to amount of protein were higher (P<.001) in stratified squamous than in oxyntic mucosa, and, per unit of tissue, TBARS were highest in stratified squamous mucosa of animals fed the FGP diet. Glutathione peroxidase activity followed a pattern similar to that of peroxides. Prostaglandin E2 was higher (P<.004) in stratified squamous than in oxyntic mucosa. In contrast, the activity of catalase was higher (P<.001) in oxyntic mucosa and was not affected by diet. The data show differences in the production of peroxides, the antioxidant defense system, and PGE2 between stratified squamous and oxyntic mucosae. Generation of prooxidants and the antioxidant defense system may play a role in the predilection of ulcers for the stratified squamous mucosal region of the pig stomach.}, number={10}, journal={Journal of Animal Science}, author={Eisemann, J. H. and Argenzio, R. A.}, year={1999}, pages={2715–2720} }
 @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={<h2>Abstract</h2> <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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} }
 @article{kandil_argenzio_sartor_1999, title={Low endogenous prostaglandin E-2 predisposes to relapsing inflammation in experimental rat enterocolitis}, volume={44}, number={10}, journal={Digestive Diseases and Sciences}, author={Kandil, H. M. and Argenzio, R. A. and Sartor, R. B.}, year={1999}, pages={2110–2118} }
 @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} }
 @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 PGI2 and PGE2 have a synergistic role in restoring electrical transepithelial resistance ( R) in ischemia-injured porcine ileum via the second messengers Ca2+ and cAMP. Because Ca2+ 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/cm2). 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} }
 @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={SummaryRecent 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} }
 @misc{sneddon_argenzio_1998, title={Feeding strategy and water homeostasis in equids: the role of the hind gut}, volume={38}, ISSN={["1095-922X"]}, DOI={10.1006/jare.1997.0354}, abstractNote={Abstract Ungulates are the most abundant and diverse group of mammals in arid areas. Non-ruminants, or hind gut fermenters, constitute only three extant families (horses, rhinos and tapirs); ruminants are far more dominant and form the remainder. Much of perissodactyl evolution occurred during the Eocene, Oligocene and Miocene eras when arid savannah-type conditions prevailed. Adoption of hind gut fermentation as a digestive strategy early on in their evolution confined equids to feeding on coarse grassland, characterized by high fibre and low protein content. Hind gut fermentation of such vegetation, combined with high rates of voluntary food intake and passage of digesta, gave equids an advantage over ruminants of similar body size in digestive efficiency on high fibre grasses. This digestive strategy explains the present day ecological niche of wild equids. The large volume of water required for microbial fermentation of fibrous vegetation constitutes a fluid reservoir which could act as a potential source of fluid for the remaining body fluid pools during periods of dehydration. Evidence for such a role of the gastrointestinal tract in water homeostasis has recently been reviewed for ruminants. In this review, feeding and digestive strategies of ruminants and hind gut fermenters are compared with respect to body size. Evidence for the existence of a gastrointestinal fluid reservoir in equids is then provided. Finally, an overview of the physiological mechanisms associated with the movement of fluid across the hind gut epithelium in equids is given.}, number={3}, journal={JOURNAL OF ARID ENVIRONMENTS}, author={Sneddon, JC and Argenzio, RA}, year={1998}, month={Mar}, pages={493–509} }
 @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-α (TGF-α), 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-α. 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-α 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-α 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-α. 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{krakowka_eaton_rings_argenzio_1998, title={Production of gastroesophageal erosions and ulcers (GEU) in gnotobiotic swine monoinfected with fermentative commensal bacteria and fed high-carbohydrate diet}, volume={35}, ISSN={["0300-9858"]}, DOI={10.1177/030098589803500406}, abstractNote={Erosions and gastroesophageal ulcers (GEU) were produced in the pars esophagea of young gnotobiotic swine fed a carbohydrate-enriched liquid diet and monoinfected with two different fermentative commensal bacteria, Lactobacillus and Bacillus sp. In contrast, piglets, fed a similar diet and inoculated with Gastrospirillum sp. ( Helicobacter heilmannii), a helicobacter species that colonizes the gastric mucosa, did not develop GEU. Experimental GEU likely develops secondary to epithelial damage mediated by microbial-origin acids whose production is potentiated by high dietary carbohydrate and parietal cell-origin hydrochloric acid.}, number={4}, journal={VETERINARY PATHOLOGY}, author={Krakowka, S and Eaton, KA and Rings, DM and Argenzio, RA}, year={1998}, month={Jul}, pages={274–282} }
 @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}, 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} }
 @article{blikslager_roberts_gerard_argenzio_1997, title={How important is intestinal reperfusion injury in horses?}, volume={211}, 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"]}, DOI={10.1016/S0039-6060(97)90107-0}, abstractNote={<h2>Abstract</h2> <b>Background.</b> 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. <b>Methods.</b> 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. <b>Results.</b> 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% O<sub>2</sub>, 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). <b>Conclusions.</b> 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{rhoads_argenzio_chen_rippe_westwick_cox_berschneider_brenner_1997, title={L-glutamine stimulates intestinal cell proliferation and activates mitogen-activated protein kinases}, volume={272}, ISSN={["0193-1857"]}, DOI={10.1152/ajpgi.1997.272.5.g943}, abstractNote={ We studied the mechanisms by which L-glutamine (Gln), a major fuel for enterocytes, signals proliferation in intestinal epithelial cell lines. Gln was additive to epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) in stimulating DNA synthesis, as assessed by [3H]thymidine incorporation. Extracellular signal-regulated kinases (ERKs) p42mapk and p44mapk and Jun nuclear kinases (JNKs) phosphorylate and activate nuclear transcription factors. Proteins of the c-Jun, ATF-2, and c-Fos families aggregate to form DNA-binding homodimers or heterodimers called activating protein 1 (AP-1). In vitro assays and functional assays of phosphorylation demonstrated that Gln activates both ERKs and JNKs, resulting in a fourfold increase in AP-1-dependent gene transcription. Gln was required for EGF signaling through ERKs. Maximal stimulation of proliferation required approximately 2.5 mM Gln. c-Jun mRNA levels responded to Gln in "Gln-starved" porcine IPEC-J2 cells and in rat IEC-6 cells. Although Gln metabolism is required for the proliferative response, several Gln by-products did not stimulate [3H]thymidine incorporation, with the exception of arginine. Gln may be a unique nutrient for enterocytes, capable of dual signaling and augmenting the effects of growth factors that govern cellular proliferation and repair. }, number={5}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Rhoads, JM and Argenzio, RA and Chen, WN and Rippe, RA and Westwick, JK and Cox, AD and Berschneider, HM and Brenner, DA}, year={1997}, month={May}, pages={G943–G953} }
 @inbook{argenzio_1997, title={Neuro-immune pathobiology of infectious enteric disease}, volume={412}, DOI={10.1007/978-1-4899-1828-4_2}, abstractNote={Recent knowledge of neuro-endocrine-immune communication in the intestinal mucosa has provided a new paradigm for the pathophysiology of diarrheal disease that will significantly alter and advance therapeutic strategies. Mast cells, enteroendocrine cells and phagocytes are the proximate mediators of signalling cascades activated by parasitic nematodes and food allergens, enterotoxigenic bacteria, and at least some of the invasive pathogens, respectively. These proximate, trigger cells give rise to products that affect epithelial function directly, or indirectly through stimulation of prostaglandin production by mesenchymal cells, and enteric nerve stimulation, which can markedly amplify the initial stimulus. The enteric nervous system in fact may mediate the majority of the secretory response induced by enterotoxins or phagocytes. The signalling network mediated by cells in the lamina propria provides new points of control for pharmacological therapy.}, booktitle={Mechanisms in the pathogenesis of enteric diseases (Advances in experimental medicine and biology ;  v. 412)}, publisher={New York: Plenum Press}, author={Argenzio, R. A.}, editor={P. S. Paul, D. H. Francis and Benfield, D. A.Editors}, year={1997}, pages={21–29} }
 @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}, number={2}, journal={Journal of Pharmacology and Experimental Therapeutics}, author={Argenzio, R. A. and Armstrong, M. U. 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{argenzio_rhoads_1997, title={Reactive oxygen metabolites in piglet cryptosporidiosis}, volume={41}, ISSN={["1530-0447"]}, DOI={10.1203/00006450-199704000-00011}, abstractNote={Piglet cryptosporidiosis is characterized by intestinal villous damage and malabsorption, and by reduced NaCl absorption in response to prostaglandins(PGs), which act directly on the epithelium and indirectly through enteric nerves. We hypothesized that phagocyte-derived reactive oxygen metabolite(ROM) production contributed to PG synthesis and altered transport in inflamed ileum. Ileal mucosa from control and infected piglets was analyzed for villous height, PGE2, catalase (an endogenous antioxidant), and malondialdehyde(MDA, a by-product of lipid peroxidation) from d 2-8 after infection. The response of control ileal mucosa to exogenous ROM and infected mucosa to antioxidant treatment was also studied in tissues mounted in Ussing chambers. Increased levels of MDA on d 2 preceded increased PGE2 on d 3-4, which correlated with the acute diarrheal phase; however the most severe villous atrophy (d 8) correlated with the highest levels of catalase and MDA but low levels of PGE2. Control mucosa responded to H2O2 with indomethacin- and tetrodotoxin-sensitive transient increases in short circuit current (Isc), which were accompanied by increased tissue production of 6-keto-PGF1a, the stable metabolite of PGI2; however, no increased PGE2 production was detectable. A stable analog of PGI2, carbacyclin, mimicked the transient Isc response to H2O2; however, several antioxidants failed to alter the abnormal Isc of infected tissue. These results suggest that there is evidence of increased ROM production in cryptosporidial infection and that intestinal PG synthesis and inhibited NaCl absorption may be mediated partially by ROM in this model. Additional, cooperative factors, such as PGE2 production, however, are likely needed to induce the alterations in ion transport seen in this infection.}, number={4}, journal={PEDIATRIC RESEARCH}, author={Argenzio, RA and Rhoads, JM}, year={1997}, month={Apr}, pages={521–526} }
 @article{argenzio_eisemann_1996, title={Mechanisms of acid injury in porcine gastroesophageal mucosa}, volume={57}, number={4}, journal={American Journal of Veterinary Research}, author={Argenzio, R. A. and Eisemann, J.}, year={1996}, pages={564} }
 @article{argenzio_lecce_powell_1993, title={PROSTANOIDS INHIBIT INTESTINAL NACL ABSORPTION IN EXPERIMENTAL PORCINE CRYPTOSPORIDIOSIS}, volume={104}, ISSN={["0016-5085"]}, DOI={10.1016/0016-5085(93)90412-6}, abstractNote={Recent studies of piglet cryptosporidiosis have shown that impaired Na(+)-coupled glucose absorption is associated with a loss of two thirds of the villous absorptive surface and an inflammatory infiltration of the lamina propria. Because inflammatory cells release eicosanoids that may alter electrolyte transport, the present study examined the role of prostanoids on NaCl transport.Ileal mucosa was stripped of its muscle layers and mounted in Ussing chambers in the presence or absence of indomethacin. Adjacent tissue was also frozen for subsequent extraction and radioimmunoassay of prostaglandin E2 (PGE2).Results showed that net Na+ absorption is inhibited and net Cl- secretion is induced in infected piglets. Indomethacin restored net Na+ and Cl- absorption to control levels and exogenous PGE reversed this effect. Radioimmunoassay of tissue extracts showed that PGE2 increased from 56.7 +/- 9.6 ng/cm2 in control to 134 +/- 16.8 ng/cm2 in infected ileum (P < 0.01).These data indicate that in addition to the Na-glucose malabsorption arising from structural damage, part of the diarrhea of these infected animals must be attributed to local prostanoid production.}, number={2}, journal={GASTROENTEROLOGY}, author={ARGENZIO, RA and LECCE, J and POWELL, DW}, year={1993}, month={Feb}, pages={440–447} }
 @article{argenzio_meuten_1991, title={SHORT-CHAIN FATTY-ACIDS INDUCE REVERSIBLE INJURY OF PORCINE COLON}, volume={36}, ISSN={["0163-2116"]}, DOI={10.1007/BF01296816}, abstractNote={Carbohydrate malabsorption frequently results in an increased net production of organic acids by colonic microorganisms and an acidification of colonic contents. Colonic structure and function during and following mucosal exposure to acetate at various H ion concentrations was examined under both in vivo and in vitro conditions. An acetic acid dose and time-dependent injury of the surface epithelium sequentially resulted in (1) degeneration and extrusion of enterocytes and increased ion permeability (pH 5.0); (2) formation of subepithelial blisters and increased mucosal permeability to mannitol (pH 4.0), and (3) sloughing of surface epithelium and the abolition of active NaCl absorption (pH 3.0). Both acetate and lactate at pH 4.0 produced significantly greater injury than similarly acidified NaCl. Crypt cell structure and Cl secretory function were preserved, however, and migration of viable cells from adjacent crypts rapidly covered the denuded surface within 30-60 min of recovery. Normal structure and function were nearly restored in 2 hr. These results suggest that colonic mucosal injury is possible under conditions that may be present during carbohydrate malabsorption syndromes. They also provide evidence that the process of surface reepithelialization may be of central importance in the defense and repair of the colonic mucosa during such acid-induced injury.}, number={10}, journal={DIGESTIVE DISEASES AND SCIENCES}, author={ARGENZIO, RA and MEUTEN, DJ}, year={1991}, month={Oct}, pages={1459–1468} }
 @article{argenzio_clarke_1989, title={Electrolyte and water absorption in the hind gut of herbivores}, journal={Acta Veterinaria Scandinavica}, author={Argenzio, R. A. and Clarke, L. L.}, year={1989}, pages={159} }