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Biomedical subjects

G W Hepner

Publications and source records attributed to G W Hepner.

At least 55 records · Page 3Linked to original sources
PubMed1975

Kinetics of cholesterol and bile acids in patients with cholesterol cholelithiasis.

The kinetics of cholesterol and bile acid was determined from a 10-week analysis of the biliary lipids after a single injection of labeled cholesterol in parallel with a conventional 1-week study of primary bile acid kinetics. Six healthy controls and 6 patients with cholesterol cholelithiasis were studied. Two of the 6 cholesterol cholelithiasis subjects had kinetic values that were very similar to the controls and the other 4 were significantly different. These 4 patients had significantly smaller primary bile acid pools and significantly lower fractional conversions of cholesterol to both primary bile acids, with concomitantly lower bile acid flux. No significant differences were obtained for the size of the rapidly miscible cholesterol pool, the fractional rate of loss and flux of biliary neutral sterol, and the fractional turnover of the primary bile acid pools. These kinetic data support the hypothesis that in some patients with cholesterol cholelithiasis there is defective conversion of cholesterol to bile acids.

Adult↗
PubMed1973

Metabolism of steroid and amino acid moieties of conjugated bile acids in man. 3. Cholyltaurine (taurocholic acid).

After oral administration of [2,4-(3)H]-cholyl[(35)S]taurine to eight healthy subjects with indwelling nasoduodenal tubes, the specific activity of the cholyl and taurine moieties and the distribution of radioactivity in biliary bile acid and urinary metabolites, as well as total urinary and fecal (35)S and (3)H, were measured at intervals for 4-8 days. Similar measurements were made after [(35)S]taurine was given orally or intravenously or instilled into the distal intestine. The daily fractional turnover rate of the taurine moiety of cholyltaurine was low and similar to that of the cholyl moiety, indicating that deconjugation occurring during enterohepatic cycling was less than half that previously observed for glycine-conjugated bile acids. Some of the cholyl moiety was absorbed but, since reconjugation occurred predominantly with glycine, little reincorporation into the cholyltaurine pool was observed. Some of the taurine moiety was also absorbed intact but entered large taurine pools, and little reincorporation into the cholyltaurine pool was seen. Oral administration of taurine expanded the cholyltaurine pool and induced a decrease in the fractional turnover rate of the cholyl moiety of cholyltaurine, interpreted to indicate a greater reincorporation of the cholyl moiety because of increased reconjugation with taurine. Taurine moiety not absorbed as taurine appeared to be absorbed largely as sulfate which, like taurine, entered large endogenous pools. Little fecal excretion of (35)S occurred. (35)S was excreted in urine as taurine and sulfate, and excretion in the first 24 h (as percentage of administered dose) correlated highly (r = 0.93) with the daily fractional turnover rate of the taurine moiety. When taurine was instilled into the distal intestine, it appeared as such in plasma, but the more distal the site of instillation, the greater the fraction of urinary (35)S present as sulfate. The [(35)S]sulfate appeared to have come from bacterial degradation of [(35)S]taurine because, when [(35)S]taurine was given intravenously, (35)S was excreted in urine chiefly as [(35)S]taurine with little SO(4)=(-)[(35)S] being present.

Bile↗
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↗
PubMed1970

Alterations in human intestinal microflora during experimental diarrhoea.

Large quantities of fluid administered through an intestinal tube caused alterations in small bowel bacteriology in four of seven subjects. In two normal individuals, colonic bacteria were found after fluid infusion in areas of the small bowel which previously had none. The faecal microflora was also altered by the fluid purge: anaerobes were reduced in some subjects and large numbers of Enterobacter species emerged in others. In a patient with pancreatic insufficiency and diarrhoea, the concentration of Enterobacter in the faeces was directly related to the number of bowel motions per day. Treatment with pancreatic enzymes curtailed the diarrhoea and markedly reduced these organisms. Intubation showed that Enterobacter were harboured in the small intestine and suppressed in the large bowel during periods of normal bowel action. Diarrhoea caused by pancreatic enzyme withdrawal or fluid purgation removed the colonic inhibition and allowed these organisms to appear in the faeces. Acidic diarrhoea induced by lactose feeding to three hypolactasic patients caused reductions in the numbers of E. coli in the stool but increases in Enterobacter species. Bacteroides also declined in one subject. Certain alterations in small and large bowel bacteriology observed in these forms of experimental diarrhoea have also been described in naturally occurring diarrhoea of diverse aetiologies.

Adolescent↗