dinoprost and Cholelithiasis

Topics: Animals; Arachidonic Acids; Bile; Chemical and Drug Induced Liver Injury; Cholelithiasis; Dinoprost; Dinoprostone; Gallbladder; Humans; Leukotrienes; Liver; Prostaglandins; Thromboxane A2

Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Cholecystokinin; Cholelithiasis; Dinoprost; Epoprostenol; Female; Gallbladder; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Prostaglandins; Thromboxane A2

To assess parameters of lipid peroxidation in bile of patients with hepatobiliary and pancreatic diseases.. F2-isoprostanes (F2-IPs) and 4-hydroxynonenal (4-HNE) were measured in bile collected during 31 ERCP procedures using gas chromatography/mass spectrometry.. In 11 subjects with normal ERCP (controls), bile contained significant amounts of F2-IPs (188 +/- 27 pg/ml) and 4-HNE (37.5 +/- 8.0 ng/ml). In 10 individuals with bile duct stones, there was a 3-fold increase of F2-IPs (523 +/- 129 pg/ml; p < 0.05) and a 2.5-fold increase of 4-HNE (89.6 +/- 18.0 ng/ml; p < 0.05). In 10 patients with various pancreatic diseases, bile F2-IPs were also enhanced (545 +/- 112 pg/ml; p < 0.01). There was no significant change in alpha-tocopherol, whereas beta-carotene was decreased in biliary tract and pancreatic diseases (p < 0.05). Results of serum liver tests were normal with the exception of bilirubin, which was increased together with alkaline phosphatase. Concentrations of total lipids, phospholipids, and cholesterol did not differ significantly between the three groups.. These data provide the first evidence in humans supporting the role of oxidative stress in the pathogenesis of biliary and pancreatic disease.

Topics: Aged; Aldehydes; Analysis of Variance; beta Carotene; Bile; Bile Duct Diseases; Cholangiopancreatography, Endoscopic Retrograde; Cholelithiasis; Chromatography, High Pressure Liquid; Dinoprost; Gas Chromatography-Mass Spectrometry; Humans; Middle Aged; Pancreatic Diseases; Vitamin E

Bile was obtained from 82 patients with various biliary tract diseases and concentrations of prostagloandins, leukotriens, mucin, and a number of lithogenic components were measured in order to evaluate the role of these substances in the pathogenesis of gallstone formation. The characteristics of bile in cases of cholesterol gallstones included high concentrations of prostaglandins and hexosamine and a high cholesterol saturation index. Prostaglandin E2 and prostaglandin F2 alpha concentrations in bile were correlated with hexosamine concentration, and prostaglandins and hexosamine were found to be actively synthesized and secreted in the gallbladder. Prostaglandins E2 and F2 alpha may therefore stimulate mucin secretion in the gallbladder with supersaturated bile. The characteristics of bile in cases of calcium bilirubinate gallstones included a high detection rate for bacteria, high beta-glucuronidase activity, a high percentage of unconjugated bilirubin, a low cholesterol saturation index and high concentrations of prostaglandins and hexosamine. Moreover, the synthesis and secretion of prostaglandins in the biliary tract were accelerated in cases of infected bile. Thus, hypersecretion of mucin, stimulated by prostaglandins, my participate in the onset and development of biliary tract infection or in the formation of calcium bilirubinate gallstones. Regarding the role of prostaglandins and mucin, the hypotheses for gallstone formation previously reported by many authors are supported by the clinical data obtained in the current study.

Topics: Bile; Cholelithiasis; Dinoprost; Dinoprostone; Humans; Mucins; Prostaglandins

The bile content of trace elements, prostaglandins and cyclic nucleotides was measured in 66 patients in the early times (from 2 to 3 weeks) after cholecystectomy. In 60 patients, the content of trace elements was measured in blood serum. The above characteristics were found to correlate with the clinical features of the patients. The relationship was also established between blood serum and bile trace elements, between prostaglandins and cyclic nucleotides.

Topics: Adolescent; Adult; Age Factors; Bile; Cholecystectomy; Cholecystitis; Cholelithiasis; Dinoprost; Female; Humans; Male; Middle Aged; Nucleotides, Cyclic; Prostaglandins; Prostaglandins E; Sex Factors; Time Factors; Trace Elements