Faculty Bibliography

To further studies of the metabolism of 26-hydroxycholesterol in fetal and neonatal life, a deuterated compound was prepared from kryptogenin by Clemmensen reduction. The spectra of the deuterated 26-hydroxycholesterol showed that five to nine deuterium atoms were incorporated per 26-hydroxycholesterol molecule, with the maximum incorporation of eight deuterium atoms. The deuterated compound was recovered unchanged from the feces of a child following oral administration. Comparison of the ratio of deuterated to protium compound indicated the presence of an endogenous pool of 26-hydroxycholesterol. Parenteral administration of the compound to a hamster indicated metabolism to deuterated chenodeoxycholic acid. The compound is useful as an isotope tracer for studies of the endogenous metabolism of 26-hydroxycholesterol

Using isotope dilution mass spectrometry, 26-hydroxycholesterol was identified in the serum of normal adults. Total values ranged from 9.2 to 25.6 micrograms/100 ml of which 31-35% was free sterol. Density gradient ultracentrifugation indicates that the steroid is distributed among the low and high density lipoproteins

Synthesis of 3 beta-hydroxy-5-[1,2-3H]cholenoic acid has permitted a study of its metabolism in bile-fistula hamsters that received the compound by intravenous infusion. Metabolites in bile were identified by reverse isotope dilution after their complete resolution by high pressure liquid chromatography using muPorasil. Recovery of administered radioactivity ranged from 21-60% in three animals. In each study, lithocholic acid (0.8-4.4%) and chenodeoxycholic acid (7.8-11.3%) were identified as metabolites of 3 beta-hydroxy-5-cholenoate and can be considered primary bile acids in the side-chain pathway of bile acid synthesis beginning with the oxidation of cholesterol to 26-hydroxycholesterol

Chemical solvolysis of chenodeoxycholic acid sulfates was studied using 4 published methods. Quantitative recovery of chenodeoxycholic acid from the 3-sulfate was obtained with each method. However, only 2 methods yielded chenodeoxycholic acid after solvolysis of the 7-sulfate. In each instance a compound resembling lithocholic acid by GLC but identifiable as a derivative of chenodeoxycholic acid by mass spectrometry was obtained and represents a product formed during solvolysis. Failure to obtain adequate solvolysis of chenodeoxycholic acid 7-sulfate can lead to false identification of monohydroxy bile acids and apparent absence of th 7-sulfate and disulfate esters

The occurrence of transient leukopenia with relative neutropenia in a patient treated with a short course of high-dose mebendazole therapy for inoperable hydatid disease is reported. The toxicology of mebendazole is reviewed