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      Heat Stress Reduces Intestinal Barrier Integrity and Favors Intestinal Glucose Transport in Growing Pigs

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          Abstract

          Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold ( P<0.05). As expected, HS decreased feed intake by 53% ( P<0.05) and body weight ( P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased ( P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations ( P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase ( P<0.05) and casein kinase II-α ( P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS ( P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS ( P<0.05). This was supported by increased ileum Na +/K + ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression ( P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.

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          Impact of regional climate change on human health.

          The World Health Organisation estimates that the warming and precipitation trends due to anthropogenic climate change of the past 30 years already claim over 150,000 lives annually. Many prevalent human diseases are linked to climate fluctuations, from cardiovascular mortality and respiratory illnesses due to heatwaves, to altered transmission of infectious diseases and malnutrition from crop failures. Uncertainty remains in attributing the expansion or resurgence of diseases to climate change, owing to lack of long-term, high-quality data sets as well as the large influence of socio-economic factors and changes in immunity and drug resistance. Here we review the growing evidence that climate-health relationships pose increasing health risks under future projections of climate change and that the warming trend over recent decades has already contributed to increased morbidity and mortality in many regions of the world. Potentially vulnerable regions include the temperate latitudes, which are projected to warm disproportionately, the regions around the Pacific and Indian oceans that are currently subjected to large rainfall variability due to the El Niño/Southern Oscillation sub-Saharan Africa and sprawling cities where the urban heat island effect could intensify extreme climatic events.
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            Early weaning stress impairs development of mucosal barrier function in the porcine intestine.

            Early life stress is a predisposing factor for the development of chronic intestinal disorders in adult life. Here, we show that stress associated with early weaning in pigs leads to impaired mucosal barrier function. Early weaning (15- to 21-day weaning age) resulted in sustained impairment in intestinal barrier function, as indicated by reductions in jejunal transepithelial electrical resistance and elevations in mucosal-to-serosal flux of paracellular probes [(3)H]mannitol and [(14)C]inulin measured at 5 and 9 wk of age, compared with that shown in late-weaned pigs (23- to 28-day weaning age). Elevated baseline short-circuit current was observed in jejunum from early-weaned pigs and was shown to be mediated via enhanced Cl(-) secretion. Jejunal barrier dysfunction in early-weaned pigs coincided with increased lamina propria immune cell density particularly mucosal mast cells. The mast cell stabilizer drug sodium cromoglycolate ameliorated barrier dysfunction and hypersecretion in early-weaned pigs, demonstrating an important role of mast cells. Furthermore, activation of mast cells ex vivo with c48/80 and corticotrophin-releasing factor (CRF) in pig jejunum mounted in Ussing chambers induced barrier dysfunction and elevations in short-circuit current that were inhibited with mast cell protease inhibitors. Experiments in which selective CRF receptor antagonists were administered to early-weaned pigs revealed that CRF receptor 1 (CRFr1) activation mediates barrier dysfunction and hypersecretion, whereas CRFr2 activation may be responsible for novel protective properties in the porcine intestine in response to early life stress.
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              Molecular basis of epithelial barrier regulation: from basic mechanisms to clinical application.

              The intestinal epithelium is faced with the complex task of providing a barrier while also allowing nutrient and water absorption. The frequency with which these processes are disrupted in disease can be taken as evidence of their importance. It is therefore of interest to define the mechanisms of altered intestinal barrier and transport function and develop means to correct disease-associated defects. Over the past 10 years, some of the molecular events underlying physiological epithelial barrier regulation have been described. Remarkably, recent advances have shown that activation of the same mechanisms is central to barrier dysfunction in both in vitro and in vivo models of disease. Although the contribution of barrier dysfunction to pathogenesis of chronic disease remains incompletely understood, it is now clear that cytoskeletal regulation of barrier function is both an important pathogenic process and that targeted inhibition of myosin light chain kinase, which affects this cytoskeleton-dependent tight junction dysfunction, is an attractive candidate for therapeutic intervention.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                1 August 2013
                : 8
                : 8
                : e70215
                Affiliations
                [1 ]Department of Animal Science, Iowa State University, Ames, Iowa, United States of America
                [2 ]Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
                Universidad Pablo de Olavide, Centro Andaluz de Biología del Desarrollo-CSIC, Spain
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SP RB LB JR NG RR. Performed the experiments: SP RB VM TW JR JJ. Analyzed the data: NG RB SP LB. Contributed reagents/materials/analysis tools: TW NG LB JR. Wrote the paper: SP LB NG.

                Article
                PONE-D-13-01640
                10.1371/journal.pone.0070215
                3731365
                23936392
                5571bb56-2f09-48bf-b896-119ed4fec0bc
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 January 2013
                : 18 June 2013
                Page count
                Pages: 9
                Funding
                This research was partially supported by the Iowa Pork Producers Association and the Agriculture and Food Research Initiative Competitive Grant 2011-67003-30007 from the USDA National Institute of Food and Agriculture. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Agriculture
                Animal Management
                Animal Production
                Biology
                Anatomy and Physiology
                Digestive System
                Biochemistry
                Metabolism
                Immunology
                Immunity
                Inflammation
                Zoology
                Animal Physiology
                Medicine
                Clinical Immunology
                Immunity
                Inflammation
                Veterinary Science
                Animal Types
                Large Animals

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                Uncategorized

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