Prevention Of Gallstones Research Articles

Prevention of cholesterol-induced gallstones by hyodeoxycholic acid in the prairie dog.

Prairie dogs of both sexes were fed a semisynthetic diet containing 0.35% cholesterol for a period of 8 weeks. This lithogenic diet induced cholesterol gallstones in ten "lithogenic control animals", five males and five females. Three animals maintained with a high glucose, fat-free diet did not develop gallstones although the cholesterol saturation of their bile approached unity. The formation of gallstones was prevented in four out of five males and all five females fed the lithogenic diet plus 0.1% hyodeoxycholic acid (30 mg per kg body weight per day). The biles of the prairie dogs receiving hyodeoxycholic acid were abnormally colored, cloudy, and highly saturated with cholesterol but contained neither cholesterol crystals nor gallstones (with the exception of one male). Feeding the relatively hydrophilic bile acid, hyodeoxycholic acid, was associated with an increase in hepatic microsomal HMG-CoA reductase activity. Cholesterol 7 alpha-hydroxylase, on the other hand, was inhibited by the administered bile acid. The dietary hyodeoxycholic acid was transformed, in part, to 3 alpha, 6 beta-dihydroxy-5-beta-cholanoic acid and hyocholic acid. It is concluded that hyodeoxycholic acid and its metabolites did not prevent the induced cholelithiasis by causing a decrease in the concentration of biliary cholesterol. Instead, this hydrophilic bile acid apparently increases the amount of cholesterol in the bile, probably in the form of a liquid crystalline mesophase. Hyodeoxycholic acid apparently prevents gallstones by preventing the nucleation and aggregation of cholesterol crystals. The lithogenic diet induced moderate to marked bile duct proliferation together with portal fibrosis and inflammatory infiltration. The addition of hyodeoxycholic acid to the lithogenic diet reduced all of the portal tract changes.

Assessment of Potential Dietary Methods for Prevention of Cholesterol Gallstones

Assessment of Potential Dietary Methods for Prevention of Cholesterol Gallstones

Interactions Between Ionized Calcium and Sodium Taurocholate: Bile Salts Are Important Buffers for Prevention of Calcium-Containing Gallstones

Abstract Calcium precipitation in bile is a requisite physicochemical event in the pathogenesis of pigment gallstones that, in turn, may serve as a nucleus for precipitation of cholesterol from its supersaturated state to form cholesterol stones. Using the Ca2+-ion electrode, the interactions of calcium with taurocholate anions were studied at 24°C and pH 7.0 over physiologic ranges (0.5–200 mM) of bile salt (BS) and total calcium (0.15–15 mM). All studies were made at a 0.295 M total ionic strength to minimize possible bile salt effects on Ca2+-activity coefficients. It was found that Ca2+ reacts with free taiurocholate anions to form the free acid salt CaBS+, with a formation constant (K'f) of about 794. In micellar solutions, Ca2+ reacted with two taurocholate anions in the micelle to form the neutral salt Ca(BS)20. The K'f for this reaction was low, about 7.6, or roughly 1/100th that of the free acid salt. Upon further addition of calcium to such micellar solutions, Ca(BS)20 appeared to be converted to a micellar acid salt, CaBS+. In any given solution, therefore, three distinct species could be present: (a) free CaBS+, (b) micellar Ca(BS)20, and (c) micellar CaBS+. In the presence of calcium, there was no critical micellar concentration (CMC) for taurocholate, but rather continuous micelle formation along a rectangular hyperbola. Knowledge of overall apparent K'f values, and K'f values for both CABS+ and CA(BS)20 permitted calculation of the relative proportions of free and micellar calcium-taurocholate in any given solution. The term CMC50 is introduced to indicate that at which 50% of calcium is free and 50% is in micellar form. It is concluded that bile acid anions, both free and micellar, constitute an important potential buffer for intraluminal calcium in the biliary tree and intestine. By thus limiting ambient Ca2+ concentration, bile acid anions may protect against calcium precipitation with various anions in bile such as bilirubinate (pigment gallstones), and may also affect the interactions of calcium within the intestinal lumen (absorption of free fatty acids, oxalate, etc.), as well as mucosal absorption of both Ca2+ and bile acid anions.

Interaction of chenodeoxycholic acid and dietary cholesterol in the treatment of cholesterol gallstones

Standard doses of chenodeoxycholic acid (15 mg/kg/day) fail to dissolve gallstones in 30 to 50 percent of patients with radiolucent gallstones in a functioning gallbladder. In humans, increasing dietary cholesterol produces increased biliary secretion of cholesterol. Restriction of dietary cholesterol reduces the minimum effective dose of chenodeoxycholic acid and speeds gallstone dissolution. In this study we investigated the interaction of dietary cholesterol and chenodeoxycholic acid in the prevention of gallstones in the prairie dog gallstone model. In animals fed a moderately lithogenic diet, standard doses of chenodeoxycholic acid failed to prevent gallstones. Reduction of the cholesterol stimulus or doubling the dose of chenodeoxycholic acid prevented the formation of gallstones. These findings support the hypothesis that the formation and dissolution of cholesterol gallstones are an expression of the relative strengths of saturating and desaturating stimuli. Therefore, rational therapy for cholesterol gallstone dissolution and prevention requires both reduction of lithogenic stimuli and optimal titration of chenodeoxycholic acid.

Prevention of Cholesterol Gallstones by Lignin and Lactulose in the Hamster

The effect on prevention of cholesterol gallstones by a nonfermentable type of fiber, lignin, and a fermentable fiber analogue, lactulose, was studied in hamsters fed an essential fatty acid deficient diet. Control animals had a high incidence of cholesterol gallstones (21 of 24) and lithogenic bile (lithogenic index 1.08). Animals fed lignin had significantly fewer gallstones (11 of 25), improved cholesterol saturation of gallbladder bile, and increased fecal bile acid excretion. Lactulose-fed animals had significantly fewer gallstones (12 of 24) but no significant change in cholesterol saturation of gallbladder bile or in fecal bile acid excretion. Serum cholesterol concentration was reduced, however, and fecal neutral steroid excretion was increased. Gallstones were completely prevented in animals fed both lignin and lactulose (0 of 22), but gallbladder bile cholesterol saturation was not significantly different from the lignin-fed group. Gallbladder bile mucopolysaccharide concentrations did not differ among groups. Lignin appears to prevent cholesterol gallstones in this model by improving cholesterol saturation of bile. The mechanism of action of lactulose is not yet clear.

The effect of added bran to the diet on the saturation of bile in people without gallstones

Bran was added to the diet of eleven volunteers without gallstones, and its effect on bile saturation, bile acid profile in bile, and serum cholesterol and triglycerides was determined. Bile cholesterol saturation was decreased after two months of feeding bran to those female subjects who had supersaturated bile. Bran may be effective in decreasing the lithogenic potential of bile in people without gallstones, and further studies on its place in the prevention of gallstones in susceptible individuals are indicated.

Cholelithiasis in mice: Effects of different chemicals upon formation and prevention of gallstones

Prevention of gallstones induced in mice by 1% cholesterol and 0.5% cholic acid (lithogenic diet) for 8 weeks was obtained by simultaneously feeding sulfaguanidine (1.5%) and dodecyl sodium sulfate (0.5–1.0%) along with the lithogenic diet. Citrus pectin (3%), egg lecithin (1%), n-octyl alcohol (1%), neomycin sulfate (0.2–0.5%) and l-ascorbic acid (5%) added to the lithogenic diet did not prevent gallstone formation. The condition of the liver, fatty or normal, in the experiment could not be correlated with the stone formation. Lower serum and liver cholesterol levels and an elevation of lecithin concentrations in serum was noticed in mice fed the sulfaguanidine and dodecyl sodium sulfate diet.

Effect of Regular Emptying of the Gallbladder on Gallstone Formation in the Rabbit

The importance of regular gallbladder evacuation in the prevention of gallstones was tested. Fourteen rabbits were fed dihydrocholesterol which causes gallstones. Seven were injected with cholecystokinin (CCK) twice daily and the other 7 with placebo. Stones formed in all rabbits that received CCK as well as in all of those that did not. The failure of CCK to prevent stone formation may be due to two phenomena that were observed: failure of the gallbladder to empty all of its contents after CCK administration, and the inclusion of concretions in the mucus on the wall of the gallbladder.

Effect of polyunsaturated and saturated fatty acids on the cholesterol holding capacity of human bile.

The key to the prevention of gallstones or to the dissolution of stones already in existence probably lies in rendering hepatic bile unsaturated with respect to cholesterol. Cholesterol comprises 80%-100% of the commonly encountered gallstones. Comparative vertebrate biochemistry has shown that the bile of most animals can carry in solution considerably more cholesterol than is normally present; in man, however, the bile is practically saturated with cholesterol. For example, human bile can normally carry 15 to 25 mg.% additional cholesterol in solution, while the cholesterol-holding capacity (CHC) of dog bile is 120 mg.%. Not only are most animals free of stones, but human stones placed in their gallbladders undergo dissolution.1,2Also, some cases of spontaneous disappearance of gallstones in man have been reported.3,4 In theory, CHC might be increased either by lowering the cholesterol content of bile, while keeping its other constituents unchanged, or by increasing the concentrations

Observations on sciatica and other neuralgic affections, with a consideration of their frequent origin from a disordered state of the stomach; interspersed with some novel views respecting the origin and prevention of gall-stones; both diseases exemplified by the author’s own case; together with an account of the waters of Bagnères de Bigorre and Barége in their treatment

Observations on sciatica and other neuralgic affections, with a consideration of their frequent origin from a disordered state of the stomach; interspersed with some novel views respecting the origin and prevention of gall-stones; both diseases exemplified by the author’s own case; together with an account of the waters of Bagnères de Bigorre and Barége in their treatment