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Biomedical subjects

C S Song

Publications and source records attributed to C S Song.

At least 73 records · Page 4Linked to original sources
PubMed1972

The influence of pyrogen-induced fever on salicylamide metabolism in man.

Salicylamide is metabolized in man by biotransformation to salicylamide glucuronide, salicylamide sulfate, and gentisamide glucuronide. The metabolites are quantitatively and rapidly excreted in urine. Study of the metabolism of this drug in volunteers during episodes of pyrogen-induced fever shows a significant reduction in the half-life (t(1/2)) of the excretion of the drug metabolites. The proportion of the drug transformed to its major metabolite, salicylamide glucuronide, is significantly reduced by fever, with concomitant increase in the proportion of one or both of the other metabolites. Thus, the pattern of urinary metabolites of salicylamide is altered. The shortened t(1/2) of the metabolite excretion is probably due to increased hepatic and renal blood flow known to accompany pyrogen-induced fever. This concept was supported by the observation that when two subjects were placed in a high-temperature environmental chamber, a condition in which hepatic and renal blood flows are known to diminish, the t(1/2) of salicylamide metabolite excretion actually increased. No simple explanation exists to explain the changed metabolite pattern noted during febrile periods. It is most likely to be due to complex interactions between the direct or indirect effects of the pyrogens and the factors affecting the hepatic biotransformation of drugs.

Adult↗
PubMed1971

The influence of postnatal development on drug-induced hepatic porphyria and the synthesis of cytochrome P-450. A biochemical and morphological study.

The mitochondrial enzyme delta-aminolevulinate synthetase (ALAS) controls the rate-limiting step in the synthesis of porphyrins and heme. An experimental form of hepatic porphyria can be readily elicited in laboratory animals, such as the rat, by drugs and foreign chemicals which are known to enhance the de novo formation of this enzyme in the liver. The present study shows that there is a striking refractoriness to the induction of ALAS during the perinatal period in the rat. Chemicals which have potent porphyria-inducing activity in adult animals have no significant inducing effect on hepatic ALAS in neonates. The ultrastructural changes which accompany the induction of ALAS by drugs and chemicals in adult liver also fail to take place in the livers of neonates. A progressive capacity for responding to the action of chemical inducers of hepatic ALAS does, however, develop in neonatal animals so that by approximately 5-6 wk of age experimental porphyria can be elicited as effectively in them as in adults. The reasons for the refractoriness of hepatic ALAS to induction in the perinatal period are not known; but the findings of this study make it clear that ALAS belongs to that increasingly large group of liver enzymes in mammals whose appearance, increase of activity, or inducibility is developmentally determined. The occurrence of developmental changes in the indicibility of ALAS in the liver of neonates also provided an opportunity to study the relationship of this enzyme activity to the drug-mediated induction of the hepatic hemoprotein cytochrome P-450. This inducible hemoprotein serves as the terminal oxygenase in the microsomal mixed-function oxidase system in the liver. The results of this study indicate that, in contrast to the refractoriness of ALAS to induction, significant drug-induced changes of hepatic P-450 content and of hemeprecursor incorporation into this cytochrome do take place in neonates. The synthesis of P-450 thus appears to be under a regulatory control different from that of ALAS in neonates, and the relation between ALAS activity and P-450 formation is not therefore a direct one.

Acyltransferases↗
PubMed1969

The occurrence of substances in human plasma capable of inducing the enzyme delta-aminolevulinate synthetase in liver cells.

We have demonstrated the presence, in the plasma of several patients with acute intermittent porphyria, of a substance which strongly induced the synthesis of porphyrins in chick embryo liver cells growing in primary culture. The induction response evoked by this humoral agent was in all respects similar to that elicited by drugs and hormones which are known to enhance porphyrin production by inducing the de novo formation of delta-aminolevulinate synthetase, the rate-limiting enzyme in this pathway. Inducing properties were not found in the plasma of normal individuals or in that from porphyric patients in remission. Significant inducing activity was, however, found in the plasma of some normal subjects ingesting drugs or contraceptive steroid mixtures. The occurrence of a potent inducer of delta-aminolevulinate synthetase in the plasma of certain porphyric patients may have clinical significance for these genetically susceptible individuals. It will also permit chemical characterization of those humoral agents which may be related to the episodic exacerbations of this hereditary liver disease.

Animals↗
PubMed1969

Plasma membranes of the rat liver. Isolation and enzymatic characterization of a fraction rich in bile canaliculi.

A method is described for the rapid isolation of a plasma membrane fraction containing a high concentration of intact bile canaliculi from the rat liver. Isolated bile canaliculi retain most of the ultrastructural features exhibited in the intact liver cell. The final fraction contains 5'-nucleotidase activity at approximately the same concentration as that in previous preparations of plasma membranes. In the presence of 0.01 M Mg(++), 5'-nucleotidase exhibits a double pH optimum at pH values of 7.5 and 9.5. The activities of glucose-6-phosphatase and alkaline phosphatase are present in low amounts. Cytochrome P-450 is not detectable. Na(+)-K(+)-activation of ATPase is observed to the extent of 20-36% in about half of the assays. The availability of a method for preparation of intact bile canaliculi should prove useful for studying the biochemical events associated with the transport of bile constituents into canaliculi.

Adenosine Triphosphatases↗