Nucleation time and cholesterol saturation index of hepatic and gall-bladder bile were measured in 16 patients with cholesterol gall stones to determine whether a gall bladder or liver defect was responsible for the rapid nucleation time of gall-bladder bile in such patients. Although hepatic bile was consistently more saturated than gall-bladder bile, the in vitro nucleation time of gall-bladder bile was more rapid. Dilution of gall-bladder bile to hepatic bile concentrations did not affect nucleation time. The results indicate that the gall bladder plays an important role in the production of the rapidly nucleating bile which is found in patients with cholesterol gall stones, and that this role is not simply concentration of bile by the gall bladder. Normal and abnormal gall-bladder biles were also compared in a larger group of patients. The view that there is a nucleation defect in cholesterol cholelithiasis which is independent of cholesterol saturation was confirmed. Subgroups of normal and gall-stone population were defined by the nucleation time and saturation index. Results suggested that solitary stones may be produced under different conditions than multiple stones. Some putative nucleating factors were examined but none was found to distinguish between normal and gall-stone bile.

https://gut.bmj.com/content/gutjnl/24/9/836.full.pdf

Nucleation of cholesterol monohydrate crystals from hepatic and gall-bladder bile of patients with cholesterol gall stones.

Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones

https://www.gastrojournal.org/article/0016-5085(90)90297-E/pdf

High protein and total lipid concentration are associated with reduced metastability of bile in an early stage of cholesterol gallstone formation.

Human gall bladder mucus glycoprotein was isolated by Sepharose 4B gel filtration followed by caesium chloride density gradient ultracentrifugation from four groups: patients with cholesterol gall stones, patients with pigmented stones, patients with complete obstruction of the cystic duct and patients with no biliary tract abnormalities (controls). Mucus glycoprotein concentrations in cholesterol gall stone bile (203 micrograms/ml +/- 199 SD, n = 17), pigment gall stone bile (110 micrograms/ml +/- 77 SD, n = 6) and control gall bladder bile (96 micrograms/ml +/- 98 SD, n = 11) were not significantly different. While bile from patients with complete obstruction of the cystic duct contained significantly higher concentrations of mucus glycoprotein (6220 micrograms/ml +/- 4130, n = 4). In vitro cholesterol nucleation time was not correlated to gall bladder mucus glycoprotein concentrations. Qualitative analysis of the carbohydrate and amino acid composition showed a basic structure typical of mucus glycoproteins in general. It is unlikely that either quantitative or qualitative differences in mucus glycoproteins are responsible for the rapid in vitro nucleation time characteristic of cholesterol gall stone patients.

https://gut.bmj.com/content/gutjnl/27/4/374.full.pdf

Quantitative and qualitative comparison of gall bladder mucus glycoprotein from patients with and without gall stones.

Effect of human biliary immunoglobulins on the nucleation of cholesterol.

Bile and serum cholesterol concentrations were analyzed by the same saponification, extraction and gas chromatographic procedure, utilizing stigmasterol as an internal standard and trifluoroacetate derivatization. The method was rapid and highly sensitive, requiring only 20 to 50 mul of sample. Comparable levels of precision were achieved by parallel analysis of a series of bile and serum samples by the present method and the Abell colorimetric method; a high degree of correlation was found between these two methods.

Rapid microanalysis of cholesterol in bile and serum by gas chromatography.

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Rapid microanalysis of cholesterol in bile and serum by gas chromatography.