glycoursodeoxycholic-acid and Cholelithiasis

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups).

Topics: Adult; Aged; Bile; Bile Acids and Salts; Bilirubin; Bolivia; Case-Control Studies; Cholelithiasis; Female; Gallbladder Neoplasms; Gallstones; Humans; Lithocholic Acid; Male; Mexico; Middle Aged; Sulfates; Ursodeoxycholic Acid

In order to test whether shock wave fragmentation of human gallstones increases their dissolution rates in a bile acid-lecithin solution, we carried out in vitro experiments. Stones comparable in size, weight and cholesterol content (86%) from the same human gallbladder were disintegrated by shock waves. A glycoursodeoxycholic acid (GUDC)-lecithin solution served as solvent. After 10 days incubation in this solvent, intact stones had lost only 4% of their cholesterol. This value increased to 92% after disintegration of the stones by 300 shock wave discharges. Fragments with a size of less than 2 mm had lost 55% of their cholesterol after day 1 and 99% after day 10. A large stone fragment cleaved off by shock waves lost much more cholesterol (42% after 10 days) than an intact untreated stone (4% after 10 days) comparable in size, weight and cholesterol content. These data show that shock wave lithotripsy of cholesterol gallstones considerably accelerates their dissolution rate in a GUDC-lecithin solvent, the desirable fragment size being 2 mm or less. However, even large fragments may lose much more cholesterol than comparable intact stones as a result of changes in surface structure as documented by scanning electron microscopy. The experiments favor the concept of a combined treatment of gallbladder stones by extracorporeally generated shock waves and bile salt therapy.

Topics: Cholelithiasis; Cholesterol; Humans; Lithotripsy; Microscopy, Electron, Scanning; Phosphatidylcholines; Solubility; Solutions; Ursodeoxycholic Acid

Cheno- and ursodeoxycholic acid feeding are both efficient in conservative gallstone therapy. Urso decreases biliary cholesterol excretion even more than cheno. Glyco-urso becomes dose dependent the predominant bile acid conjugate in bile under urso feeding. We therefore studied the kinetics of cholesterol gallstone dissolution in aqueous solutions of 100 mM glyco-cheno, 100 mM glyco-urso, and mixtures of both consisting of 40 mM glyco-urso plus 60 mM glyco-cheno and 80 mM glyco-urso plus 20 mM glyco-cheno in vitro. The daily dissolution rates of cholesterol achieved by these solutions were for 100 mM glyco-cheno 0.87 +/- 0.1 mg (mean +/- SEM), for 40 mM glyco-urso plus 60 mM glyco-cheno 0.28 +/- 0.003 mg, for 80 mM glyco-urso plus 20 mM glyco-cheno 0.07 +/- 0.002 mg, and for 100 mM glyco-urso 0.07 +/- 0.03 mg. Correspondingly were the weight decreases of the gallstones by 100 mM glyco-cheno 1.2 +/- 0.1 mg/day, by 40 mM glyco-urso plus 60 mM glyco-cheno 0.3 +/- 0.01 mg/day, by 80 mM glyco-urso plus 20 mM glyco-cheno 0.11 +/- 0.02 mg/day, and by 100 mM glyco-urso 0.1 +/- 0.02 mg/day. Complete gallstone dissolution occurred during the observation time of 4 months only by 100 mM glyco-cheno in 12.8 +/- 3.3 weeks. Thus glyco-urso dissolves only little cholesterol and decreases the speed of cholesterol gallstone dissolution. It is concluded that high doses of urso in gallstone therapy which lead to great amounts of glyco-urso in bile may diminish gallstone dissolution rates.

Topics: Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Deoxycholic Acid; Drug Interactions; Glycine; Glycochenodeoxycholic Acid; Humans; Kinetics; Ursodeoxycholic Acid

Topics: Chenodeoxycholic Acid; Cholelithiasis; Cholesterol; Deoxycholic Acid; Diffusion; Glycine; Glycochenodeoxycholic Acid; In Vitro Techniques; Kinetics; Solubility; Taurine; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid; Water; X-Ray Diffraction