PubMed · 4875455
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D M Small. 1968-09-12. Gallstones.. https://doi.org/10.1056/nejm196809122791106
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Human bile and cholesterol gallstones contain sterols including methylated (lanosterol and other dimethyl and monomethyl sterols), and demethylated cholesterol precursor sterols (delta 8-lathosterol, lathosterol, and desmosterol), plant sterols (campesterol and sitosterol), and cholestanol. The aim of the study was to analyze the noncholesterol sterols in gallbladder bile and stones from female and male patients with cholesterol stones (CS) and pigment stones (PS) to ascertain whether any sterol fraction contributes to the gallstone formation. Classification of gallstones to CS and PS was performed on the basis of the stone cholesterol content. The study group consisted of 165 consecutive cholecystectomized patients, 150 with CS and 15 with PS. Bile acids and sterols were quantitated using gas-liquid chromatography (GLC). The biliary lipid and noncholesterol sterol/cholesterol proportions were similar in the CS and PS patients. The proportions of methylated and plant sterols were significantly lower in the CS than in bile, whereas those of delta 8-lathosterol, lathosterol, and cholestanol were significantly higher. The PS, in contrast to the CS, were neither sex nor weight related. The bile acid and phospholipid concentrations and the proportions of lanosterol, delta 8,24-dimethylsterol, and sitosterol were up to 50 times higher and those of delta 8-lathosterol and lathosterol twice lower in the PS than in the CS. The results suggest that, in general, the stones with low cholesterol content are proportionately richer in nonpolar precursor and plant sterols and lower in demethylated precursors, the situation being opposite for the CS. The stone/bile ratios suggest that in both stone groups, but especially in the CS, levels of the polar precursor sterols and cholestanol were enriched in the stone, whereas levels of the nonpolar precursor sterols, and to a lesser extent plant sterols, were not enriched in the stone despite their high biliary proportions.
To accurately determine the cholesterol (Ch) distribution between mixed micelles and vesicles in lithogenic bile, both ultracentrifugation and gel chromatography with the correct intermixed micellar/vesicular bile salt concentration (IMC) have been proposed. We have systematically compared both separation techniques with physiological model biles to ascertain their quantitative separation ability. After determination of optimal ultra-centrifugation conditions in systems containing only micelles or vesicles, Ch-supersaturated model biles [3-10 g/dL, 10 mol percent Ch, taurocholate (TC)]/([TC + egg yolk phosphatidylcholine (EYPC)] = 0.6 and 0.7) were adjusted to a density of 1.03 g/mL, and ultracentrifuged at 42,000 rpm and 37 degrees C for 13 hours. Identical model biles were subjected to gel chromatography with the correct IMC, either directly or after remixing and incubation at 37 degrees C after ultracentrifugation. By ultracentrifugation, 31 percent +/- 2 percent (TC/(TC + EYPC) = 0.6) and 40 percent +/- 5 percent (TC/(TC + EYPC) = 0.7) of total Ch were found in vesicles (Ch/EYPC molar ratios = 1.0 and 1.3, respectively). However, by gel chromatography, only 19 percent +/- 2 percent (Ch/EYPC = 1.0) and 22 percent +/- 2 percent (Ch/EYPC = 1.5) of total Ch were found in the corresponding biles. Gel chromatography of biles (TC/(TC + EYPC) = 0.7) ultracentrifuged for various durations showed a progressive increase in vesicular Ch to 41 percent after 13 hours. On incubation for 11.5 hours after ultracentrifugation, vesicular Ch decreased to 31 percent, thus approaching the initial (gel chromatography) value. Quasielastic light scattering also demonstrated formation of vesicles in ultracentrifuged Ch-unsaturated model bile (cholesterol saturation index (CSI) approximately 0.97). As compared with gel chromatography, ultracentrifugation systematically elevates vesicular Ch, possibly because of induced shifts in lipids between lipid aggregates caused by variation in local bile salt concentration. Because ultracentrifugation can alter the phases present in bile, gel chromatography with the correct IMC more accurately represents the distribution of Ch in biliary lipid aggregates.
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