PROCESS OF CHOLESTEROL CHOLELITHIASIS INDUCED BY DIET IN PRAIRIE DOG - PHYSICOCHEMICAL CHARACTERIZATION

  • 1 January 1976
    • journal article
    • research article
    • Vol. 87  (6) , 987-998
Abstract
Ninety-seven adult male and female prairie dogs were used in the present study. Seventy-two were fed the high cholesterol diet and sacrificed at intervals over a 14-day period; the remaining 25 were used as controls. The primary objective was to determine if there was any relationship between the in vivo events induced in prairie dog bile and observations of cholesterol precipitation phenomena in synthetic bile analogues. Solutions of physiologically relevant composition were constructed, which, when plotted according to convention on a tri-linear graph, fell within the zone of metastable or suspended supersaturation. These solutions revealed a consistent and previously undescribed liquid crystal to solid crystal phase transition during their approach to equilibrium at 37.degree. C. The in vivo studies of prairie dog bile following rapid induction of supersaturation revealed identical changes. At 1st, the supersaturated biles were isotropic followed by a period of turbidity and invariable formation of mesophase. After a few days, the liquid crystals decreased and solid cholesterol crystallites appeared. The in vitro work predicted not only static, but dynamic processes as well, with respect to cholesterol precipitation beginning with the metastably supersaturated state and eventuating in gallstone formation. Ancillary new findings, resulting from the high cholesterol diet, included the induction of human-like hyper-.beta.-lipoproteinemia and rapid hepatocyte degranulation shown by EM.

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