PubMed Health⌕ Search

Biomedical subjects

R Lester

Publications and source records attributed to R Lester.

At least 109 records · Page 6Linked to original sources
PubMed1975

Bile salt metabolism in the human premature infant. Preliminary observations of pool size and synthesis rate following prenatal administration of dexamethasone and phenobarbital.

Bile salt synthesis and bile salt pool size were determined by isotope dilution in two groups of healthy premature infants, utilizing nonradioactive deuterium-labeled bile salts. All 9 infants were between 32 and 36 weeks of gestation; however, in one group (4 infants), the mothers had received either dexamethasone or phenobarbital prior to delivery. The total bile salt pool averaged 20 mg for the infants of untreated mothers and 79 mg for the infants of treated mothers; similarly, the bile salt synthesis of 8 mg per day in the untreated group was increased to 27 mg per day for the treated group. Expressed per sq m of body surface, the cholic acid pool for the treated group was 321 mg per sq m, and the cholic acid synthesis rate equaled 98 mg per sq m per day; values equal to those for full term infants and nearly 4 times those for the untreated prematures. The intraduodenal bile salt concentrations obtained during meals were also low in the untreated group, equaling 1.2 mM as compared to 5.3 mM for the treated group. The reductions of bile salt pool size, synthesis, and intestinal concentration establish that the functional maturity of the liver, and possibly the gastrointestinal tract, is reduced in premature infants. The results further suggest that this maturity may be dramatically influenced by medications administered to the mother prior to delivery.

Bile Acids and Salts↗
PubMed1975

Alcohol-induced testicular atrophy. An experimental model for hypogonadism occurring in chronic alcoholic men.

Elucidation of mechanisms involved in the hypogonadism and feminization observed in chronic alcoholic men requires the development of an experimental animals model system. Such an animal system should be inducible with ethanol feeding and should duplicate endocrine changes known to occur in chronic alcoholic men. We report such an animal model system. Animals fed a diet with ethanol accounting for 36% of total calories develop significant testicular, prostatic, and seminal vesicle atrophy (P less than 0.01) and greatly reduced plasma testosterone levels (P less than 0.01). Animals fed a similar diet with sucrose isocalorically substituted for ethanol do not. Testicular, prostatic, and seminal vesicular mass relative to body mass and plasma testosterone levels in these isocaloric control animals do not vary significantly from those obtained for age-matched control animals fed an ad libitum rat chow diet. These findings indicate that the caloric deprivation associated with chronic ethanol ingestion is not responsible for gonadal injury and atrophy of the sex steroid-sensitive tissues in the alcohol-fed animals. This animal model provides a useful means of directly examining perturbation in gonadal function that occurs in man as a consequence of chronic ethanol ingestion and confirms our previous data which suggest that ethanol is a primary testicular toxin.

Alcoholism↗
PubMed1975

Bile-salt metabolism in the primate fetus.

Fetal bile salt metabolism was assessed by the intravenous infusion of e114C]cholate into 6 monkey fetuses. The placental transfer, fetal plasma clearance, and fetal hepatic excretion of the administered radiolabeled bile salt were measured. Placental transfer averaged 30% of the injected dose, while biliary excretion averaged 36%. Of the amount excreted by the fetal liver, 78% was in the form of [14C]taurocholate. The findings suggest that bile salt metabolic and excretory mechanisms are undergoing developmental maturation at birth.

Animals↗
PubMed1974

Ethanol inhibition of vitamin A metabolism in the testes: possible mechanism for sterility in alcoholics.

Vitanin A (retinol) is essential for spermatogenesis. Alcohol dehydrogenase, the enzyme responsible for ethanol metabolism, is also required for the conversion of retinol to bioactive retinal at the end organ site. Ethanol inhibits the oxidation of retinol by testicular homogenates containing alcohol dehydrogenase. Thus, a possible biochemnical mechanism for the sterility of chronic alcoholics is identified.

Alcohol Oxidoreductases↗
PubMed1973

Foetal bile pigment handling after administration of (14C)haemin.

1. Advanced techniques for intra-uterine surgery were used to study haem degradation in foetal sheep prepared in utero with indwelling jugular, carotid and biliary cannulas. [(14)C]haemin was administered I.V. to the foetus, and plasma disappearance, biliary excretion, placental transfer and tissue distribution of radioactivity were measured over a 5-8 hr period.2. 8-30% of the (14)C-label was recovered in foetal bile, about 40% of this as bilirubin and the rest as unidentified [(14)C]haemin derivatives. 4-21% was transferred across the placenta, appearing in maternal bile almost exclusively as [(14)C]bilirubin. Excretion of (14)C-label totalled 18-33%.3. Six adult sheep infused with [(14)C]haemin excreted 19-49% of the dose in the bile over 8 hr, one third as bilirubin.4. The amount of endogenous bilirubin excreted per unit time/unit wt. of foetal liver increased with increasing foetal wt.5. It is concluded that near-term foetal sheep have a maturing mechanism for haem catabolism. Haem is partially excreted in foetal bile as bilirubin. Another fraction is transferred across the placenta, probably after prior conversion to bilirubin. The remainder is converted to un-identifiable end-products. Total excretion is approximately as effective as that in adults.

Animals↗
PubMed1972

Fetal bile salt metabolism. II. Hepatic excretion of endogenous bile salt and of a taurocholate load.

Bile salt metabolism was studied in fetal dogs 1 wk before term. The size and distribution of the fetal bile salt pool were measured, and individual bile salts were identified. The hepatic excretion of endogenous bile salts was studied in bile fistula fetuses, and the capacity of this excretory mechanism was investigated by the i.v. infusion of a load of sodium taurocholate-(14)C up to 20 times the endogenous pool size. The total fetal bile salt pool was 30.9+/-2.7 mumoles, of which two-thirds was in the fetal gallbladder. Expressed on a body weight basis, this was equal to approximately one-half the estimated pool size in the adult dog (119.2+/-11.3 vs. 247.5+/-33.1 mumoles/kg body wt). Measurable quantities of bile salt were found in small bowel (6.0+/-1.8 mumoles), large bowel (1.1+/-0.3 mumoles), liver (1.2+/-0.5 mumoles), and plasma (0.1+/-0.03 mumoles). Plasma bile salt levels were significantly greater in fetal than in maternal plasma (1.01+/-0.24 mug/ml vs. 0.36+/-0.06 mug/ml; P < 0.05). Fetal hepatic bile salt excretion showed a fall over the period of study from 2.04+/-0.34 to 0.30+/-0.07 mumoles/hr. The maximal endogenous bile salt concentration in fetal hepatic bile was 18.7+/-1.5 mumoles/ml. The concentration in fetal gallbladder bile was 73.9+/-8.6 mumoles/ml; and, in those studies in which hepatic and gallbladder bile could be compared directly, the gallbladder appeared to concentrate bile four- to fivefold.Taurocholate, taurochenodeoxycholate, and taurodeoxycholate were present in fetal bile, but no free bile salts were identified. The presence of deoxycholate was confirmed by thin-layer chromatography and gas liquid chromatography, and the absence of microorganisms in fetal gut suggests that it was probably transferred from the maternal circulation. After infusion of a taurocholate load, fetal hepatic bile salt excretion increased 30-fold, so that 85-95% of the dose was excreted by the fetal liver during the period of observation. Placental transfer accounted for less than 5% of the dose. Fetal bile volume increased 15-fold on average, while bile salt concentrations increased two- to threefold. It is concluded that bile salt is taken up, conjugated, and excreted by the fetal liver with remarkable efficiency. The excreted material is either stored and concentrated in the fetal gallbladder or released into the intestine and reabsorbed to be reexcreted in bile.

Animals↗
PubMed1971

Fetal bile salt metabolism. I. The metabolism of sodium cholate-14C in the fetal dog.

Cholate metabolism was studied in fetal dogs 1 wk before term and was compared with cholate metabolism in adult dogs. Tracer amounts of sodium cholate-(14)C were administered to the fetus in utero by intravenous infusion over 6 hr. Fetal plasma disappearance, biliary excretion, tissue distribution, and placental transfer of cholate were measured over 10 hr. Infused cholate-(14)C was cleared rapidly from fetal plasma principally by the fetal liver and to a minor extent by placental transfer to the mother. The taurine conjugate was formed in the fetal liver and was excreted into the proximal small intestine via the biliary tree. Indirect evidence for the functioning enterohepatic circulation of bile salt in the fetus was obtained. Comparison with the results of similar experiments in adult dogs showed that the fetal liver was almost as efficient as the adult liver in the uptake, conjugation, and excretion of tracer amounts of cholate-(14)C. The maximal rate of excretion of radiolabel attained by the fetus was somewhat slower than in the adult (82.8 +/-1.4% and 96.1 +/-4.0% [mean +/-SE] of the infusion rate, respectively), and the proportion of the total dose excreted by the fetal liver during 10 hr was smaller (81.4 +/-1.3% vs. 96.6 +/-4.4%). This difference could be only partly accounted for by placental transfer (2.8 +/-0.6% of the fetal dose). Labeled cholate and taurocholate were excreted by the fetus at similar rates, which suggests that, under the conditions of study, conjugation had little influence on the rate of transfer of cholate across the liver cell. It is concluded that the fetal dog, 1 wk before birth, has a remarkably mature and efficient mechanism for the uptake and excretion of cholate.

Animals↗