To elucidate the mechanism whereby corticosteroids decrease the serum bilirubin concentration, changes in bilirubin metabolism were studied in patients with Gilbert's syndrome using a bilirubin load test and/or nicotinic acid test before and after corticosteroid treatment. Steroid administration increased hepatic clearance and uptake of bilirubin; the transfer rate for biliary excretion was unaffected. These results suggest that the main effect was enhancement of hepatic uptake or storage of bilirubin, which may be an important mechanism whereby corticosteroids reduce serum bilirubin concentrations in various liver disorders.

Adolescent↗

PubMedDate not supplied

A constitutional unconjugated hyperbilirubinemia combined with indocyanine green intolerance: a new functional disorder?

The kinetics of plasma clearance of indocyanine green and bromosulfophthalein were studied in 49 consecutive patients with chronic unconjugated hyperbilirubinemia. Forty-four patients had Gilbert's syndrome whereas five patients had impaired hepatic uptake of indocyanine green and virtually normal hepatic bromosulfophthalein uptake. There was no difference in bilirubin metabolism between the two groups. A family study of the patients with impaired indocyanine green uptake revealed that the defect appears to be transmitted as an autosomal dominant trait associated with inheritance of impaired bilirubin metabolism. These patients manifest a noval disorder of organic anion transport which, like Gilbert's syndrome, is also characterized by chronic milk unconjugated hyperbilirubinemia.

Adult↗

PubMedDate not supplied

Respective roles of hypoxia and halothane metabolism in halothane-induced liver injury in rats.

To evaluate the respective roles of halothane metabolism and hypoxia in rats with halothane hepatotoxicity, experiments were designed with special reference to blood gas. After pretreatment with phenobarbital (80 mg per kg., i.p.) for four consecutive days, rats were exposed to 1.0% halothane under a mildly hypoxic condition (FiO2 = 14%) for 2 hr. Since halothane anesthesia caused significant decrease in PaO2 levels, rats exposed to a highly hypoxic atmosphere (FiO2 = 10%) in which PaO2 levels were comparable to those in the halothane group, served as the control. In the halothane group, marked centrilobular necrosis and elevation of SGPT activity were observed; neither significant histological lesions nor elevation of transaminase activity occurred in the highly hypoxic group. Although phenobarbital treatment did not decrease PaO2 levels during halothane anesthesia, the serum fluoride level, which appears to reflect quantitatively the reductive pathway of halothane metabolism, increased. These results strongly indicate that halothane metabolism rather than hypoxia, per se, plays a major role in development of halothane-induced liver injury in rats.

Alanine Transaminase↗

PubMedDate not supplied

Effects of hypoxia and phenobarbital treatment on the metabolism of mitomycin C in experimental animals.

To evaluate the effects of anaerobic conditions and inducers for the mixed-function oxidase system on the metabolism of mitomycin C, a bioreductive alkylating agent widely used for the treatment of hepatocellular carcinoma, experiments so designed were performed in rats and mice. Metabolism of mitomycin C by microsomes from normal rat liver and diethyl-nitrosamine-induced mouse hepatocellular carcinoma tissue was assessed from the disappearance of the quinone portion of mitomycin C and by measurement of alkylating metabolites using 4-(p-nitrobenzyl)pyridine as a trapping agent. The metabolism of mitomycin C measured by the two independent methods was strikingly increased under anaerobic conditions in both intact and tumor tissues. Since involvement of cytochrome P-450 in the metabolic activation of mitomycin C was shown recently, effects of representative inducers for the mixed-function oxidase system on the metabolism of mitomycin C were also studied. Phenobarbital treatment resulted in a significant increase in the metabolism of mitomycin C in both intact and tumor tissues under anaerobic conditions. The markedly enhanced formation of active metabolites of mitomycin C under anaerobic conditions may explain on a metabolic basis, at least in part, our recent clinical observations that chemoembolizations with microcapsular forms of mitomycin C is more effective than conventional bolus administration of this agent in the treatment of hepatocellular carcinoma. Combination of anaerobic conditions and induction of the mixed-function oxidase system may be applicable to chemotherapy of hepatic malignancy.

Anaerobiosis↗

PubMedDate not supplied

Correlation of CT values, iodine concentration, and histological changes in the thyroid.

PURPOSE: We have reported that in the thyroid, there is a linear correlation between iodine concentrations and CT values. However, the slope of the regression line was about three times as large as that in KI solutions. We investigated the factor(s) contributing to the increment of the slope of the regression line in the thyroid. METHOD: Solutions of NH4I and thyroid hormones were used to investigate the regression line. Thirty-six thyroids were evaluated to investigate the correlation between the iodine concentrations and the area ratio of thyroid follicles, which were measured by preoperative CT and from tissue slices, respectively. RESULTS: The slopes of the regression lines in the solutions were almost identical to those in KI solutions. In the thyroid, iodine concentrations were logarithmically correlated with the area ratio of follicles. CONCLUSION: The decrease in CT values not only revealed a decrease of iodine concentration in the thyroid but also represented an increase of follicular cells and/or interstitial structures in the volume ratio secondary to it.

Humans↗