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R Lester

Publications and source records attributed to R Lester.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1968

Renal excretion of urobilinogen in the dog.

The renal excretion of urobilinogen was studied in dogs by standard clearance techniques. The use of radiochemically pure tritiated mesobilirubinogen as a representative urobilinogen afforded much greater analytical precision than can be obtained with the usual colorimetric and fluorimetric techniques which are only semiquantitative. With constant plasma levels of urobilinogen, raising urinary pH from 5 to 8 increased urobilinogen excretion from about 30% to up to 200% of the filtered load. When urinary pH was kept constant, changes in blood pH had no effect on urobilinogen excretion. Increases in urinary flow had no effect on urobilinogen excretion when the urine was alkaline but increased excretion markedly during aciduria. Probenecid did not influence urobilinogen excretion by the kidney. It is concluded that urobilinogen is excreted by a three-component system of glomerular filtration, active secretion, and pH-dependent nonionic diffusion in the distal nephron. Urobilinogen is a weak acid, and this mode of excretion is similar to that of other weak, organic acids, such as salicylates. These results indicate that urinary pH and flow must be considered in the clinical interpretation of measurements of urinary urobilinogen.

Acidosis↗
PubMedDate not supplied

Bile acid metabolism in the fetus and newborn.

The development of bile acid synthesis, secretion and absorption was studied in laboratory animals and humans. Although there is species variation, a developmental pattern emerges. Bile acid pool size and synthesis rates increase during the final third of gestation and the perinatal period. Similarly, bile acid secretion is a developing function during the final third of gestation and is incompletely developed at birth. The ileal mechanism for active bile acid transport is absent at birth and only develops during the first 2--5 weeks or more of life. It is therefore possible that the intestinal conservation of bile acid is ineffective in the newborn. The combination of immaturity of bile acid synthesis, secretion and absorption probably contributes to the fat malabsorption especially evident in low birth weight infants. Finally, synthesis, secretion and absorption can be induced to develop early by the administration of adrenocortical steroid. The induction of mechanisms for bile acid metabolism raises the possibility of therapeutic intervention in severe cases of neonatal malabsorption of lipid.

Aging↗
PubMedDate not supplied

Metabolism of 24-norlithocholic acid in the rat: formation of hydroxyl- and carboxyl-linked glucuronides and effect on bile flow.

24-Norlithocholic (3 alpha-hydroxy-24-nor-5 beta-cholan-23-oic) acid is the lower homologue of lithocholic acid, a potent cholestatic agent. In order to characterize its cholestatic potential and metabolic fate, 3 beta-tritiated 24-norlithocholate was infused intravenously into adult male Sprague-Dawley rats prepared with an external biliary fistula. The results demonstrate that 24-norlithocholate does not induce cholestasis in rats when administered in doses in excess of those necessary for lithocholate to produce cholestasis. Hydroxyl- and carboxyl-linked glucuronides were identified as major metabolites secreted in the bile. Especially noteworthy is the identification of carboxyl-linked glucuronides of mono-, di- and trihydroxylated C23 bile acids. Their total amount (25% of recovered radioactive products) is comparable to that of the hydroxyl-linked glucuronide of 24-norlithocholic acid (41%). In this study, for the first time, a bile acid diglucuronide, substituted both at 3-hydroxyl and carboxyl groups, was detected (11%).

Animals↗