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Biomedical subjects

R Lester

Publications and source records attributed to R Lester.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1970

Bile pigment formation in plants.

The unicellular alga Cyanidium caldarium evolves carbon monoxide during the syntheis of the bile pigment, phycocyanobilin. Carbon monoxide and phycocyanobilin were produced in stoichiometric amounts at comparable rates. Therefore, the mechanism of bile pigment formation in this plant parallels that in mammals.

Bile Pigments↗
PubMed1969

Bilirubin metabolism in the fetus.

Bilirubin metabolism was studied in dog and monkey fetuses. Bilirubin-(3)H was administered to fetal animals in utero by prolonged intravenous infusion. Fetal plasma disappearance, hepatic uptake, biliary excretion, and placental transfer of bilirubin-(3)H were measured.Bilirubin metabolism and excretion in the fetus was much less efficient than in the adult. Fetal plasma levels of tritium were elevated for prolonged periods, and the combined rate of placental and fetal hepatic excretion was lower than normal values for adult hepatic excretion. Species differences were noted. Hepatic conjugation and excretion appeared to be the primary mechanism of fetal metabolism in the dog. In contrast, the amounts of conjugated bilirubin-(3)H excreted in fetal monkey bile were negligible. Small amounts of (3)H-labeled bilirubin derivatives were excreted in fetal bile, but 10 times as much of the administered material was transferred intact across the placenta and excreted by the maternal liver. The relationship of this functional difference to known anatomic and biochemical species differences is discussed. Preliminary observations on alternate routes of fetal bilirubin metabolism were obtained.

Animals↗