deoxycholic-acid and Bile-Duct-Diseases

Topics: Bile Duct Diseases; Cholelithiasis; Deoxycholic Acid; Humans; Lithotripsy

Topics: Bile Duct Diseases; Caprylates; Chenodeoxycholic Acid; Cholelithiasis; Deoxycholic Acid; Ethers; Glycerides; Humans; Lithotripsy; Methyl Ethers; Solvents; Ursodeoxycholic Acid

Topics: Anticholesteremic Agents; Bile; Bile Duct Diseases; Cholelithiasis; Cholesterol; Deoxycholic Acid; Drug Evaluation; Humans; Ursodeoxycholic Acid

Twenty-eight patients with radiolucent biliary duct stones without cholangitis and jaundice were randomly allocated into two treatment groups receiving ursodeoxycholic acid 12 mg/kg (group A) or placebo (group B) in three daily doses for 24 months. In group A stones disappeared completely in seven patients and partially in one; placebo administration had no effect on stone size and three patients of group B (only one of group A) went to surgery for complications. Ursodeoxycholic acid treatment did not adversely affect liver function tests, and alkaline phosphatase decreased. Abdominal and biliary colics also became less frequent in the first six months of therapy in group A, but not in the placebo group. The bile was supersaturated with cholesterol in both groups, but decreased significantly only in patients receiving ursodeoxycholic acid even though the lithogenic index remained high. Cholesterol saturation of bile does not seem to be the only factor determining the dissolution of biliary duct stones which sometimes contain cholesterol as the main component.

Topics: Adolescent; Adult; Aged; Bile; Bile Acids and Salts; Bile Duct Diseases; Cholelithiasis; Cholesterol; Clinical Trials as Topic; Deoxycholic Acid; Double-Blind Method; Female; Humans; Male; Middle Aged; Random Allocation; Ursodeoxycholic Acid

We investigated the roles of hydrophobic deoxycholic acid (DCA) and hydrophilic ursocholic acid (UCA) in the regulation of the orphan nuclear farnesoid X receptor (FXR) in vivo. Rabbits with bile fistula drainage (removal of the endogenous bile acid pool), rabbits with bile fistula drainage and replacement with either DCA or UCA, and intact rabbits fed 0.5% cholic acid (CA) (enlarged endogenous bile acid pool) were studied. After bile fistula drainage, cholesterol 7alpha-hydroxylase (CYP7A1) mRNA and activity levels increased, FXR-mediated transcription was decreased, and FXR mRNA and nuclear protein levels declined. Replacing the enterohepatic bile acid pool with DCA restored FXR mRNA and nuclear protein levels and activated FXR-mediated transcription as evidenced by the increased expression of its target genes, SHP and BSEP, and decreased CYP7A1 mRNA level and activity. Replacing the bile acid pool with UCA also restored FXR mRNA and nuclear protein levels but did not activate FXR-mediated transcription, because the SHP mRNA level and CYP7A1 mRNA level and activity were unchanged. Feeding CA to intact rabbits expanded the bile acid pool enriched with the FXR high affinity ligand, DCA. FXR-mediated transcription became activated as shown by increased SHP and BSEP mRNA levels and decreased CYP7A1 mRNA level and activity but did not change FXR mRNA or nuclear protein levels. Thus, both hydrophobic and hydrophilic bile acids are effective in maintaining FXR mRNA and nuclear protein levels. However, the activating ligand (DCA) in the enterohepatic flux is necessary for FXR-mediated transcriptional regulation, which leads to down-regulation of CYP7A1.

Topics: Animals; Bile Acids and Salts; Bile Duct Diseases; Bile Ducts; Cholesterol 7-alpha-Hydroxylase; Cholic Acids; Cyclophilins; Deoxycholic Acid; DNA-Binding Proteins; Fistula; Homeostasis; Male; Rabbits; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Transcription Factors; Transcription, Genetic

Topics: Bile Duct Diseases; Chenodeoxycholic Acid; Cholelithiasis; Deoxycholic Acid; Humans; Ursodeoxycholic Acid

Topics: Animals; Bile; Bile Acids and Salts; Bile Duct Diseases; Bile Ducts; Biliary Fistula; Cholagogues and Choleretics; Dehydrocholic Acid; Deoxycholic Acid; Dogs