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Biomedical subjects

A F Hofmann

Publications and source records attributed to A F Hofmann.

At least 325 records · Page 18Linked to original sources
PubMed1973

Effect of oral chenodeoxycholic acid on bile acid kinetics and biliary lipid composition in women with cholelithiasis.

Bile acid kinetics and biliary lipid composition were characterized in six women with gallstones before and after 6 mo of oral therapy with chenodeoxycholic acid, an agent that induces dissolution of cholesterol gallstones in man. Over a dosage range of 1-4 g/day, absorption varied from 0.8 to 2.3 g/day. The chenodeoxycholic acid pool expanded two-to sixfold, and bile became composed predominantly (> 90%) of chenodeoxycholic acid conjugated chiefly with glycine. Cholic acid and deoxycholic acid pools decreased markedly, so that the total bile acid pool expanded much less, about twofold on the average. Cholic acid synthesis decreased in five of the six patients, consistent with negative feedback inhibition of cholic acid synthesis by chenodeoxycholic acid. In four patients whose bile was above or close to saturation with cholesterol, the bile became unsaturated; in two patients, whose bile was unsaturated, it remained so. In five patients with radiolucent gallstones, chenodeoxycholic acid therapy was continued after completion of kinetic and composition measurements; the stones decreased in size or dissolved entirely during the subsequent 6 to 18 mo. Similar measurements of bile acid kinetics and biliary lipid composition were made before and after a 6-mo period without medication in a control group of six healthy women; no changes occurred.

Administration, Oral↗
PubMed1972

Metabolism of steroid and amino acid moieties of conjugated bile acids in man. I. Cholylglycine.

Cholyl-2,4-(3)H-glycine-1-(14)C was administered orally to eight healthy subjects with indwelling nasoduodenal tubes. The distribution of radioactivity among bile acids and the specific activity of cholylglycine were determined in bile collected at intervals for 7 days. (3)H and (14)C were measured in stool. (14)C in breath was calculated from interval (14)CO(2) specific activity determinations. The daily fractional turnover of the glycine moiety (mean +/-SE, 106+/-17%) was three times greater than that of the cholyl moiety (38+/-7%). On the basis of certain assumptions, it was calculated that about 18% of the cholylglycine pool was deconjugated per enterohepatic cycle. The extent of deconjugation appeared to be unrelated to the efficiency of absorption of the cholyl moiety, which averaged 90-95% per enterohepatic cycle. (14)C was recovered predominantly in breath (52+/-5% of administered dose), and 24 hr (14)CO(2) excretion correlated highly (r = 0.95) with daily fractional turnover of the glycine moiety. (3)H excretion occurred predominantly in feces, and the rate correlated highly (r = 0.92) with the daily fractional turnover of the cholyl moiety. Deoxycholylglycine became labeled with (3)H rapidly, indicating the occurrence of bacterial 7-dehydroxylation of the cholyl moiety and absorption of deoxycholic acid. This biotransformation occurred in all eight subjects but varied in degree and was unrelated to the degree of deconjugation. Since ingested glycine-1-(14)C was not incorporated into bile acid glycine, appearance of (14)C in deoxycholylglycine (observed in three of eight subjects) indicated that 7-dehydroxylation of cholylglycine can occur without deconjugation. Dehydroxylation was also observed in vitro when fecal homogenates were incubated with cholylglycine.

Bile↗
PubMed1972

Metabolism of steroid and amino acid moieties of conjugated bile acids in man. II. Glycine-conjugated dihydroxy bile acids.

Chenodeoxycholyl-2,4-(3)H-glycine-1-(14)C and deoxycholyl-2,4-(3)H-glycine-1-(14)C were synthesized and administered orally to 10 healthy subjects. Distribution of radioactivity among bile acids and specific activity of steroid and amino acid moieties were determined in bile samples. (3)H and (14)C were measured in feces. (14)C in breath was calculated from interval (14)CO(2) specific activity determinations. The daily fractional turnover of the glycine moiety of chenodeoxycholyl and deoxycholylglycines was more than three times that of the steroid moiety. Pool size of chenodeoxycholylglycine was about twice that of deoxycholylglycine, but similar fractional turnover rates of steroid and amino acid moieties suggested that intestinal absorption of the two conjugated bile acids was equally efficient (about 95%). The amount of unlabeled deoxycholic acid (newly formed by bacterial 7alpha-dehydroxylation) absorbed from the intestine approximated 30% of the cholic acid that was lost. (3)H radioactivity remained predominantly in administered bile acid implying that, normally, secondary bile acids derived from chenodeoxycholic acid are not appreciably absorbed from the intestine and that deoxycholic acid is not hydroxylated by the liver. Approximately 25% of administered (14)C was recovered in the breath in the first 24 hr and less than 8% in the feces in 8 days; (14)CO(2) excretion correlated highly with fractional turnover of the glycine moiety. (3)H appeared predominantly in feces, and the rate of excretion correlated highly with the fractional turnover of the steroid moiety of bile acids. From the results in this paper plus previous measurements on the metabolism of cholylglycine, we calculated that about 6 mmoles/day of glycine is used for bile acid conjugation in health.

Adult↗