05). Patients with positive upper esophageal pH test (n = 67) also had significantly higher prevalence of acid regurgitation symptoms (43/67 vs 74/152, P < 0.05). Prevalence of other upper gastrointestinal and respiratory symptoms were similar between patients with positive and negative upper and lower pH test. Patients with abnormal EM were significantly older (49 ± 14 vs 45 ± 13 years, P < 0.05) and had higher prevalence of chronic cough than patients with normal EM(30/93 vs 26/143,
P < 0.05). In patients with positive pH tests, the prevalence of dysphagia, chronic cough, and hoarseness of voice were significantly higher in patients with abnormal than those selleck products with normal EM (18/31 vs 18/56, P < 0.05; 12/31 vs 6/56, P < 0.005 and 19/31 vs 18/56, P < 0.01,
respectively). Whereas in patients with negative lower pH tests, only the prevalence of heartburn was significantly lower in patients with normal than those with abnormal EM (26/87 vs 30/62, P < 0.05). Acid regurgitation but not heartburn was associated with GER. Esophageal dysmotility had no significant effect on acid regurgitation symptom but associated with chronic cough, hoarseness of voice, and dysphagia only in patients with abnormal esophageal acid exposure. "
“Hepatic ischemia and reperfusion (IR) injury is a major clinical problem that leads to frequent extrahepatic complications including intestinal dysfunction Luminespib solubility dmso and acute kidney injury (AKI). In this study we aimed to determine the mechanisms of hepatic IR-induced extrahepatic organ dysfunction. Mice subjected to 60 minutes of hepatic IR not only developed severe hepatic injury but also developed significant AKI and small intestinal injury. Hepatic IR induced small intestinal Paneth cell degranulation and increased interleukin-17A (IL-17A) levels in portal vein plasma and small intestine. We also detected increased levels of IL-17A messenger RNA (mRNA) and protein in Paneth cells after hepatic IR with laser capture dissection. IL-17A-neutralizing DOCK10 antibody treatment or genetic deletion of either IL-17A or IL-17A receptors significantly protected
against hepatic IR-induced acute liver, kidney, and intestinal injury. Leukocyte IL-17A does not contribute to organ injury, as infusion of wildtype splenocytes failed to exacerbate liver and kidney injury in IL-17A-deficient mice after hepatic IR. Depletion of Paneth cell numbers by pharmacological (with dithizone) or genetic intervention (SOX9 flox/flox Villin cre+/− mice) significantly attenuated intestinal, hepatic, and renal injury following liver IR. Finally, depletion of Paneth cell numbers significantly decreased small intestinal IL-17A release and plasma IL-17A levels after liver IR. Conclusion: Taken together, the results show that Paneth cell-derived IL-17A plays a critical role in hepatic IR injury and extrahepatic organ dysfunction.