American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jan 2008
Decline in intestinal mucosal IL-10 expression and decreased intestinal barrier function in a mouse model of total parenteral nutrition.
Loss of intestinal epithelial barrier function (EBF) is a major problem associated with total parenteral nutrition (TPN) administration. We have previously identified intestinal intraepithelial lymphocyte (IEL)-derived interferon-gamma (IFN-gamma) as a contributing factor to this barrier loss. The objective was to determine whether other IEL-derived cytokines may also contribute to intestinal epithelial barrier breakdown. ⋯ TPN administration led to a marked decline in IEL-derived IL-10 expression. This decline was coincident with a loss of intestinal EBF. As the decline was partially attenuated with the administration of exogenous IL-10, our findings suggest that loss of IL-10 may be a contributing mechanism to TPN-associated epithelial barrier loss.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Dec 2007
Excitatory effects of synchronized intestinal electrical stimulation on small intestinal motility in dogs.
The aim of this study was to investigate effects of synchronized intestinal electrical stimulation (SIES) on small intestinal motility in dogs. Seventeen dogs were equipped with a duodenal cannula for the measurement of small bowel motility using manometry; an additional cannula was equipped in six of the dogs with 1.5 m distal to the first one for the measurement of small intestinal transit. Two pairs of bipolar electrodes were implanted on the small intestinal serosa with an interval of 5 cm; glucagon was used to induce postprandial intestinal hypomotility. ⋯ The other six dogs were used for the measurement of small intestinal transit. We found that 1) SIES induced small intestinal contractions during phase I of the migrating motor complex (MMC) (contractile index or CI: 5.2 +/- 0.6 vs. 10.3 +/- 0.7, P = 0.003); 2) in the fed state, SIES significantly improved glucagon-induced small intestinal postprandial hypomotility (CI: 3.4 +/- 0.5 vs. 6.0 +/- 0.3, P = 0.03); 3) SIES significantly accelerated small intestinal transit delayed by glucagon (70.4 +/- 3.1 vs. 44.5 +/- 3.1 min, P < 0.01); 4) there was a negative correlation between the CI and transit time (r = -0.427, P = 0.048); and 5) the excitatory effect of SIES was blocked by atropine. SIES may have a therapeutic potential for treating patients with small intestinal disorders.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Oct 2007
Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis.
Emerging evidence has implicated reactive oxygen species (ROS) in the pathogenesis of inflammatory bowel disease (IBD). Although intestinal epithelial cells produce the ROS-neutralizing enzyme superoxide dismutase (SOD), the protein and activity levels of copper/zinc (Cu/Zn) and manganese (Mn) SOD are perturbed in inflamed tissues of IBD patients. Thus we investigated the ability of MnSOD from Streptococcus thermophilus to reduce colitis symptoms in interleukin (IL) 10-deficient mice using Lactobacillus gasseri as a delivery vehicle. ⋯ The anti-inflammatory effects of L. gasseri were associated with a reduction in the infiltration of neutrophils and macrophages. Transcripts of antioxidant genes were equivalent in colonic tissues obtained from control and probiotic-treated IL-10-deficient mice. This study demonstrates that L. gasseri producing MnSOD has significant anti-inflammatory activity that reduces the severity of colitis in the IL-10-deficient mouse.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Sep 2007
2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake.
Ischemia-reperfusion (I/R) injury is a commonly encountered clinical problem in liver surgery and transplantation. The pathogenesis of I/R injury is multifactorial, but mitochondrial Ca(2+) overload plays a central role. We have previously defined a novel pathway for mitochondrial Ca(2+) handling and now further characterize this pathway and investigate a novel Ca(2+)-channel inhibitor, 2-aminoethoxydiphenyl borate (2-APB), for preventing hepatic I/R injury. ⋯ In vivo I/R increased liver enzymes 10-fold, and 2-APB prevented this when administered pre- or postischemia. 2-APB significantly reduced cellular damage determined by hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of liver tissue. In vitro I/R caused a dissociation between cytochrome c and mitochondria in Hep G2 cells that was prevented by administration of 2-APB. These data further establish the role of cellular Ca(2+) uptake and subsequent mitochondrial Ca(2+) overload in I/R injury and identify 2-APB as a novel pharmacological inhibitor of liver I/R injury even when administered following a prolonged ischemic insult.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jun 2007
Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice.
Dysfunctional cross talk between adipose tissue and liver tissue results in metabolic and inflammatory disorders. As an insulin sensitizer, rosiglitazone (Rosi) improves insulin resistance yet causes increased adipose mass and weight gain in mice and humans. Conjugated linoleic acid (CLA) reduces adipose mass and body weight gain but induces hepatic steatosis in mice. ⋯ The combined administration of CLA and Rosi reduced hepatic liver triglyceride content as well as lipogenic gene expression compared with CLA alone. In summary, dietary CLA prevented weight gain in Rosi-treated mice without attenuating the beneficial effects of Rosi on insulin sensitivity. Rosi ameliorated CLA-induced lipodystrophic disorders that occurred in parallel with rescued expression of adipocytokine and adipocytes-abundant genes.