摘要:

The responsiveness of the hepatic microsomal aryl hydrocarbon hydroxylase (AHH) to testosterone enanthate (TE; 2.5 μmol/kg/day for 9 days) was sex-dependent in adult rats, the enzyme being very resistant to TE in normal adult or ovariectomized females. Administration of testosterone propionate or diethylstilbestrol (1.45 μmol) to neonatal female rats at 1 and 3 days of age did not increase the responsivity to TE in adulthood. However, exposure of female rats to TE (5.0 μmol/kg/day) during the peripubertal period (35–50 days old) resulted in increased sensitivity to TE (+55.2%) when tested in adulthood. The responsivity was further potentiated (+109.3 %) if the animals were ovariectomized at 28 days of age. Prepubescent ovariectomized females which received corn oil or estradiol benzoate (1.5 μmol/kg on alternate days) during puberty were not able to respond to TE significantly. These results suggest that the refractoriness of the hepatic AHH to testosterone in adult female rats is determined by the absence of testosterone, as well as the presence of estrogens, during pu

ISSN:0031-7012    

DOI:10.1159/000138002

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The possibility that oral cholestyramine treatment might indirectly increase hepatic drug oxidations was investigated in rats using pentobarbital, antipyrine, zoxazol-amine, and aminopyrine as probes of the hepatic mixed function oxidase system and in humans using amobarbital and antipyrine as probes. Cholestyramine pretreatment of rats for 5 days (87.5 mg/kg twice daily by stomach tube) shortened pentobarbital sleep times, decreased antipyrine-induced hypothermia, but did not influence either zoxazolamine paralysis times or the in vitro N-demethylation of aminopyrine. Neither pentobarbital nor antipyrine pharmacokinetics in rats were affected by the cholestyramine pretreatment. Similarly, in two-way crossover studies with human subjects, a 5-day oral cholestyramine pretreatment (4 g 3 times daily) had no demonstrable effect on the pharmacokinetics of single doses of amobarbital (200 mg i.v.) or antipyrine (500 mg per os). After cholestyramine pretreatment, a trend toward diminished CNS depression produced by amobarbital was observed, but the effect was not statistically significant. The results suggest that hepatic mixed function oxidases in rats for which aminopyrine, antipyrine, pentobarbital, and zoxazolamine are substrates and that hepatic mixed function oxidases in humans for which amobarbital and antipyrine are substrates are not significantly affected by cholestyramine pretreatment.

ISSN:0031-7012    

DOI:10.1159/000138003

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Feeding a thiamin-deficient diet to male and female rats for 3 weeks alters the mixed function oxidases responsible for metabolizing benzo(a)pyrene and enhances the response of these enzymes to induction by phenobarbital or 3-methylcholanthrene. The caloric restriction observed in thiamin deprivation may be partially responsible for the enhanced metabolism in this condition but, as established in pair-feeding studies, was not responsible for the enhanced response to enzyme inducers seen in these animals. The degree of altered response was also seen to depend on the sex of the rat and on the substrate concentration of the incubation mixture.

ISSN:0031-7012    

DOI:10.1159/000138004

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00–18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00–06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male m

ISSN:0031-7012    

DOI:10.1159/000138005

出版商:S. Karger AG    

年代:1984

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138006

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The imidazobenzodiazepine midazolam (MDZ), along with its 1 -hydroxy and 4-hydroxy metabolites (1-OH-MDZ, 4-OH-MDZ) can be simultaneously quantitated by electron capture gas-liquid chromatography. After addition of diazepam as internal standard, alkalinized plasma samples are extracted into benzene-isoamyl alcohol. The organic extract is separated, evaporated to dryness, reconstituted, and chromatographed using 3% SP-2250 as the liquid phase. The indentity of 4-OH-MDZ, not previously detected in human plasma in unconjugated form, was verified by negative-ion chemical ionization mass spectroscopy. After single oral doses of MDZ administered to humans, concentrations of MDZ and 1-OH-MDZ (alternatively named 1-hydroxymethyl midazolam) were similar, and both compounds were eliminated from plasma in parallel. Concentrations of 4-OH-MDZ were considerably lower, but this metabolite was also eliminated in parallel with the parent compound.

ISSN:0031-7012    

DOI:10.1159/000138007

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Hoe 263 inhibited the contraction of the potassium-depolarized pulmonary artery of the guinea pig. In this experiment it was slightly more active than verapamil. The calcium uptake of the potassium-depolarized pulmonary artery was inhibited by Hoe 263 more effectively than by prenylamine. The upstroke velocity of the potassium-depolarized papillary muscle of the guinea pig was depressed with similar concentrations of Hoe 263 and verapamil. In the (3H)-nitrendipine binding test, Hoe 263 was effective at similar concentrations as prenylamine and verapamil. The positive inotropic effect of K-strophanthin was depressed by Hoe 263 at concentrations which were comparable with those necessary for verapamil.

ISSN:0031-7012    

DOI:10.1159/000138008

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Rats treated with desoxycorticosterone acetate and sodium chloride (DOCA/ NaCl) developed a time-dependent increase in blood pressure which was associated with a reduced in vitro β- and an elevated α-adrenergic responsiveness. Isoproterenol-induced relaxation of aortic smooth muscle from the DOCA-NaCl-treated rats was similar to controls 1 week after treatment, was significantly attenuated as the blood pressure began to rise (week 4) and was completely abolished when the blood pressure exceeded 150 mm Hg (week 12). The aortic smooth muscle sensitivity to norepinephrine was significantly increased prior to (week 1), during the rise (week 4) and during the maintenance of an elevated systolic blood pressure (>150 mm Hg; week 12). No significant differences were observed between the two groups in either the contractile response of the aortic ring preparations to potassium chloride or in the relaxation properties in response to sodium nitrite. These results demonstrate that alterations in both the α- and β-adrenergic responsiveness occur in the DOCA/NaCl-treated animal. The enhancement of the α-adrenergic responsiveness occurs prior to any change in blood pressure, while the attenuated β-adrenergic responsiveness parallels the elevation in blood pressure, suggesting that these reciprocal alterations of adrenergic responsiveness may be responsible for the eventual development of hypertension induced with DOCA/NaCl treatment in

ISSN:0031-7012    

DOI:10.1159/000138009

出版商:S. Karger AG    

年代:1984

数据来源: Karger