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Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation.

ABSTRACT: Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O-positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate-induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction.

SUBMITTER: Durgampudi C

PROVIDER: S-EPMC4044711 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation.

Durgampudi Chandra C Noel Pawan P Patel Krutika K Cline Rachel R Trivedi Ram N RN DeLany James P JP Yadav Dhiraj D Papachristou Georgios I GI Lee Kenneth K Acharya Chathur C Jaligama Deepthi D Navina Sarah S Murad Faris F Singh Vijay P VP

The American journal of pathology 20140601 6

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables ...[more]

PMID: 24854864

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Project description:To investigate the clinical usefulness of early endoscopic ultrasonography (EUS) in the management of acute biliary pancreatitis (ABP).All consecutive patients entering the emergency department between January 2010 and December 2012 due to acute abdominal pain and showing biochemical and/or radiological findings consistent with possible ABP were prospectively enrolled. Patients were classi?ed as having a low, moderate, or high probability of common bile duct (CBD) stones, according to the established risk strati?cation. Exclusion criteria were: gastrectomy or patient in whom the cause of biliary obstruction was already identified by ultrasonography. All enrolled patients underwent EUS within 48 h of their admission. Endoscopic retrograde cholangiopancreatography was performed immediately after EUS only in those cases with proven CBD stones or sludge. The following parameters were investigated: (1) clinical: age, sex, fever; (2) radiological: dilated CBD; and (3) biochemical: bilirubin, AST, ALT, gGT, ALP, amylase, lipasis, PCR. Association between presence of CBD stone at EUS and the individual predictors were assessed by univariate logistic regression. Predictors significantly associated with CBD stones (P < 0.05) were entered in a multivariate logistic regression model.A total of 181 patients with pancreatitis were admitted to the emergency department between January 2010 and December 2012. After exclusion criteria a total of 71 patients (38 females, 53.5%, mean age 58 ± 20.12 years, range 27-89 years; 33 males, 46.5%, mean age 65 ± 11.86 years, range 41-91 years) were included in the present study. The probability of CBD stones was considered low in 21 cases (29%), moderate in 26 (37%), and high in the remaining 24 (34%). The 71 patients included in the study underwent EUS, which allowed for a complete evaluation of the target sites in all the cases. The procedure was completed in a mean time of 14.7 min (range 9-34 min), without any notable complications.The overall CBD stone frequency was 44% (31 of 71), with a significant increase from the group at low pretest probability to that at moderate (OR = 5.79, P = 0.01) and high (OR = 4.25, P = 0.03) pretest probability.Early EUS in ABP allows, if appropriate, immediate endoscopic treatment and significant spare of unnecessary operative procedures thus reducing possible related complications.

Dataset Information

Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation.

Publications

Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation.

Similar Datasets

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