摘要:

AbstractThe levels of dopamine, noradrenaline and 5‐hydroxytryptamine were estimated in the hypothalamus and limbic areas, corpus striatum, cerebellum and the brain‐stem of rats administered thallous acetate (5 mg/kg i.p.) daily for 7 days. Significant decreases in the concentration of dopamine occurred in the hypothalamus, limbic areas and corpus striatum. Noradrenaline did not reveal significant alteration in any of the regions of the brain examined. The concentration of 5‐hydroxytryptamine was significantly lowered in the corpus striatum, cerebellum and the brain

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02251.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractA model for examination of the effect of hypoalbuminaemia on drug pharmacokinetics in laboratory animal is described. The model has been used to investigate the effect of protein binding on the kinetics of sulphadimethoxine in rabbits. A greater volume of distribution of sulphadimethoxine is shown in the dextran induced hypoalbuminaemic rabbits in comparison with control animals. It is concluded that the suggested model is convenient for investigation of the influences of protein binding on drug pharmacokinetics.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02252.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe systemic availability of clomethiazole was assessed by comparing blood levels after intravenous and oral administration. Clomethiazole was rapidly absorbed after oral administration to volunteers, particularly when administered as syrup. The fraction of the given dose that reached the systemic circulation after 1 capsule of clomethiazole (192 mg clomethiazole) was 0.25±0.18, after 2 capsules (384 mg clomethiazole) 0.38±0.18, and after 15 ml syrup (480 mg clomethiazole) 0.42±0.20. The time‐blood concentration profiles were consistent with a two‐compartment open model and the mean elimination half‐lives of 3.6‐5.0 hrs. were found for the different formulations and administration routes. Elimination half‐lives showed little variation and a mean systemic clearance of 49 ml/min./kg was found for clomethiazole after intravenous administration. Clomethiazole is bound to human plasma proteins (63.4±1.6%, 37°), a binding which is not affected by Vacutainer® sample tubes. The blood/plasma distribution of clomethiazole was 0.76±0.02 at 37°. A sensitive mass fragmentographic assay for the determination of clomethiazole in blood/plasma down to levels of 1 ng/ml (6.2 nmo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02253.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractRegional blood flow responses to 1‐deamino‐6‐carba‐(8‐arginine)‐vasopressin (dCAVP) were investigated in pregnant guinea pigs by the radioactive microsphere technique. Intravenous injection of 0.1 μg/kg body weight caused a moderate rise in mean arterial blood pressure from 6.8 to 7.9 kPa, a significant reduction in tissue perfusion of the stomach, mammary gland, urinary bladder and vagina, and a significant increase in renal and cerebral blood flow. In a small number of animals given 1.0 μg/kg of dCAVP, which evoked a strong pressor response, it was also possible to demonstrate a reduction in cutaneous and pancreatic blood flow and an augmentation of adrenal blood flow. Uterine and maternal placental blood flow did not alter significantly following administration of this vasopre

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02254.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe concentrations of total mercury and methyl mercury were determined in organs from several species of birds of prey. The organ distributions were calculated for each species. For total and non‐methyl mercury, significant differences were found between the species. For methyl mercury no such differences were found. The liver: kidney ratios in White‐tailed Eagle were 1:2.4 and 1:0.9 for total and methyl mercury, respectively. The corresponding figures for the Eagle Owl were 1:0.7 and 1:0.8. The distribution pattern and the degree of methylation were mainly dependent on the mercury levels, and there seemed to be an inverse relationship between the total mercury levels and the percentages of methyl mercury in the organs, especially in the kidney. There were good correlations between the methyl mercury concentrations in the liver, kidney, and muscle. The demethylation of methyl mercury seems to be a significant detoxication route for methyl mercury in birds of p

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02255.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractCopper‐64 was injected intravenously into three sheep. The total excretion of copper in sheep was low since only 1.4‐1.7% of the dose injected was excreted during a period of 60 hrs. following the injection. It was found that the biliary system was not a main excretory pathway for copper; other routes of excretion into the gastrointestinal tract seemed to be more important. The urinary and the biliary excretion were of comparable magnitude. The activity in the bile was found to be lower than in the plasma throughout the sampling period. It is assumed that a low excretion capacity of copper in the bile of sheep may be a possible factor of importance for the high susceptibility of this species to excess of cop

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02256.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe hepatotoxic effects of carbon tetrachloride (0.01 ml/kg i.p.), thioacetamide (50 mg/kg intraperitoneally), paracetamol (0.5 g/kg intraperitoneally), and allyl alcohol (0.05 ml/kg intraperitoneally) as estimated by determination of serum enzyme activities (GOT, GPT, SDH) were enhanced in mice treated with one oral dose of 4.8 g/kg ethanol 16 hrs. previously. Pretreatment of mice with ethanol did not increase the hepatotoxic actions of bromobenzene (0.25 ml/kg intraperitoneally), phalloidin (1.5 mg/kg intraperitoneally), α‐amanitin (0.75 mg/kg intraperitoneally), and praseodymium (12 mg/kg intravenously) though there was a trend to higher enzyme activities in the case of bromobenzene. In guinea‐pigs ethanol also aggravated CCl4‐induced liver damage, but only strengthened the hepatotoxic activity of D‐galactosamine (150 mg/kg intraperitoneally). Treatment with 4.8 g/kg ethanol did not influence liver glutathione levels in mice but increased aniline hydroxylation in the 9000 × g liver homogenate supernatant of mice and guinea‐pigs. A dose of 2.4 g/kg ethanol, on the other hand, neither increased aniline hydroxylase activity nor enhanced carbon tetrachloride‐induced hepatotoxicity in mice. It is assumed that the enhanced sensitivity to hepatotoxic agents after treatment with ethanol may be due to an enhanced microsomal activation of the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02257.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract1‐aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH)in vivoandin vitro.Like cyanamide it has a rapid onset of actionin vivowith the highest inhibition occurring after 2‐24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low‐KmALDH stronglyin vivo, however, in markedly different doses. Cyanamide inhibited the high‐KmALDH onlyin vivo, whereasin vitro, the high‐KmALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low‐Kmenzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram‐ethanol reaction

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02258.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractIn conscious dogs chlorazanil (2.5 mg/kg intravenously) markedly enhanced (5‐10 fold) urinary excretion of prostaglandins E2and F2α. The effect came to a peak at 15‐30 min. following the administration. Chlorazanil did not modify renal blood flow or inulin clearance in non‐pretreated or indomethacin pretreated dogs and the plasma renin activity remained unchanged. A marginal natriuretic and antikaliuretic activity by chlorazanil was similarly observed in non‐pretreated dogs and dogs pretreated with indomethacin. The possible effects of the prostaglandins released by chlorazanil remained obscure.In vitrochlorazanil (10‐4M) exhibited a moderate inhibition of 15‐OH‐prostaglandin dehydrogenase but an enhanced excretion of 15‐keto‐13, 14‐dihydro PGF2αin vivosuggested that chlorazanil increased renal prostaglandin activity by increased prostaglandin synthesis, probably due to increased precursor availability. This was presumably mediated by some as yet unknown factor since chlorazanil (4 × 10‐5M) failed to affect the release of precursor and prostaglandins from isolated Krebs‐Hensele

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02259.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractLong‐term (several years) exposure to fluoride induced decreased production of lactate in cultured, fluoride resistant LS cells. In intact, sensitive cells, 6 mM NaF had no effect on glycolysis, whereas in homogenates, from both resistant and sensitive cells, lactate production was blocked by 6 mM NaF, indicating the cell membrane to be a barrier to fluoride. A lower intracellular rather than extracellular fluoride concentration was found in the sensitive cell with a ratio of 0.4, whereas fluoride resistant cells excluded fluoride from their intracellular milie

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02260.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY