摘要:

AbstractThe distribution and excretion of mercury was studied in mice given a single intravenous dose of 5 umol/kg of methyl mercuric chloride. Oral treatment with N–acetyl–DL–penicillamine (3 mmol/kg per day) removed more mercury from the brain and from the whole body than the corresponding treatment with other complexing agents, and it was also effective on delayed treatment. Even more mercury was removed into the faeces and the urine, by higher doses of N–acetyl–DL–penicillamine, and 4 days of treatment with 27 mmol/kg per day of this compound did not give rise to any significant toxic symptoms in the mice.In vitroexperiments showed that the chemical affinity of N–acetyl–DL–penicillamine for methyl mercury was higher than that of the other thiols tested, except D–penicillamine. In contrast to the latter, N–acetyl–DL–penicillamine easily penetrated the cellular membranes, and therefore rapidly removed a substantial fraction of methyl mercury from the blood cells. It is assumed that N–acetyl–DL–penicillamine can reduce the mercury concentration in brain cells by converting the intracellularly non–diffusible methyl mercury

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03180.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe distribution and excretion of mercury was studied in pregnant rats, given a single intravenous dose of 2 μmol/kg of CH3203HgCl on the 13th day of pregnancy. Oral treatment for one week with N–acetyl–DL–penicillamine (4 mmol/kg per day) increased the mercury excretion in faeces (from 45 to 120 nmol) and urine (from 9 to 160 nmol). Such treatment mobilized mercury from all the organs tested, and the foetal and maternal brain levels of mercury were decreased to 1/5 and 1/3 of the controls, respectively. A four–day period of treatment with N–acetyl–DL–penicillamine started three days after the injection of methyl mercury reduced the foetal and maternal brain levels to 1/2 and 2/3 of the controls, respectively. The rapid removal of metal deposits following treatment with N–acetyl–DL–penicillamine is attributed to a free penetration of the complexing thiol into the tissue cells in question. No signs of toxicity were detected in monkeys given an effective daily dose of the agent (4 mmol/kg) for 6 days. In contrast N–acetyl–DL–homocysteine thiolactone was found to be toxic in the monkeys. In addition, the latter agent was ineffective in increasing the mercury elimination from the brains of monk

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03181.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractA modification of a fluorometric assay for phenprocoumon is described. The sensitivity of the method has been increased so that the lower limit is 5 ng/ml. By an ultrafiltration technique, phenprocoumon (PPC), in therapeutic concentrations, was bound to the extent of 99.9%,both in undiluted plasma and in Krebs–Henseleit (K–H) solutions containing 4 g human serum albumin (HSA)/100 ml. An increase in the pH from 6.05 to 8.02 in phosphate buffers containing 0.2 g HSA/100 ml yielded an increase in the apparent association constant for PPC binding to HSA from 0.562–1061/mol to 1.195–1061/mol, while the number of PPC mol bound per mol albumin remain unchainged (1.05 and 1.03 respectively). A reduced binding of PPC in undiluted plasma containing increasing concentrations of furosemide have been observed. Scatchard plots based on binding studies in K–H solutions containing 0.2 g HSA/100 ml indicate a competitive nature of the albumin binding of PPC and f

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03182.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effect of treatment with triparanol (25 mg/kg by gavage every 24 hours for three weeks) on the absorption of phenobarbitone, sulphafurazole, isoniazid, mecamylamine and quinidine from the rat small intestine was studiedin situby measuring their disappearance from the intestinal lumen. The appearance of sulphafurazole and mecamylamine in the intestinal lumen was also studied after their intravenous administration, and the partitioning of mecamylamine between the buffer solution and the intestinal tissue was measuredin vitro.Treatment with triparanol retarded the absorption of sulphafurazole, whereas the absorption of mecamylamine was accelerated. The amount of sulphafurazole and mecamylamine in the intestinal lumen after their intravenous administration was relatively slight. Thein vitropartitioning of mecamylamine into the intestinal tissue was higher in triparanol–treated than in control intestines. Triparanol did not change the absorption of phenobarbitone, isoniazid or quinidine. Phenobarbitone in the whole blood at the end of the experiment was increased after triparanol, but the levels of other drugs were unchanged. Triparanol did not modify drug concentrations in the intestinal wall at the end of the experiment. The relatively slight changes in drug absorption induced by triparanol are probably due to changes in the morphology and composition of the intestinal wal

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03183.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe inhibition of the acetaldehyde dehydrogenase activity in rat liver by an unknown dietary factor, present in a commercial standard diet for rats, was studied. The inhibitory factor was located in the calcinated bonemeal fraction of the diet and was identified by infrared spectrophotometry and thin–layer and paper chromatography as cyanamide or a cyanamide derivative. The occurrence and formation of cyanamide in calcinated bonemeal, its effects on the acetaldehyde dehydrogenases and the metabolism of acetaldehyde in rat liver, are discusse

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03184.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe bull retractor penis muscle was used to compare the α–adrenergic effect of adrenaline, noradrenaline, methoxamine, phenylephrine, metaraminol, tyramine, amphetamine, ephedrine and orciprenaline with that of some of their O– and N–acetyl derivatives. The effect of cocaine on the responses to the drugs was also examined. Methoxamine exhibited the strongest stimulant potency on this smooth muscle. The ED50of the other parent compounds decreased in the following order: adrenaline, noradrenaline, phenylephrine, ephedrine, metaraminol, amphetamine, tyramine. N–acetylation decreased very clearly or even abolished the effect of the drugs. O–acetylation also decreased the effect but not as much as N–acetylation. The effects of the O–acetyl derivatives were probably at least partly due to the corresponding parent compounds released after deacetylation. The very weak effects of the N–acetyl derivatives suggest that little if any N–deacetylation occurred duri

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03185.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effect of calcium and a calcium–antagonistic drug, nifedipine, on the effective refractory period (E. R. P.) of electrically stimulated, isolated rat left atria was studied and compared with the effect on the duration of the intracellularly recorded action potential. To determine E. R. P., two different methods were used. When E. R. P. was determined from the maximum following frequency (m. f. f.), neither varying concentrations of calcium in the Ringer solution, [Ca++]o, nor nifedipine 100 μg/1 influenced E. R. P. significantly. However, when E. R. P. was measured by using programmed electrical stimulation, E. R. P. was shorter than when determined from m. f. f., increasing [Ca++]odecreased E. R. P. and nifedipine 100 μg/1 shortened E. R. P. at low [Ca++]o(2.0 meq./l). Increasing atrial rates also produced a decrease in E. R. P., and the shortening effect of nifedipine was enhanced by increasing the stimulus frequency. The electrical threshold for stimulation increased both with increasing [Ca++]oand increasing stimulus frequencies. However, nifedipine 100 μg/1 had no significant effect on the excitability. It is concluded that programmed electrical stimulation is a more accurate method than m. f. f. for determining E. R. P., and also that a correlation exists between the effect of calcium on E. R. P. and on the action potential dura

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03186.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractRats receiving clofibrate (ethyl–α–p–chlorophenoxyisobutyrate) were given ethanol by stomach–tube, 6–9 g per kg body weight per day, for 3 weeks. The toxicity of ethanol was not greater in these animals than in the controls. No signs of ketoacidosis appeared and, in contrast to the controls, the clofibratetreated animals did not give a hyperglycaemic response after a single large dose of ethanol. Neither Mallory bodies nor signs of inflammation or fatty infiltration were ever seen in livers of clofibrate–treated rats; however, but both histochemical and biochemical techniques revealed a slight although insignificant increase in liver total lipid content in the ethanol–treated controls. The possibility of preventing adverse effects of alcohol in man by clofibrate treatmen

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03187.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractFenitrothion, the indirect cholinesterase inhibitor organophosphorus insecticide, caused alteration in the conditioned avoidance reflex of rats. In trained rats (treated with 10 and 100 mg/kg fenitrothion) the number of conditioned responses diminished the latency period leghtened, and the tendency towards extinction was slower. The whole blood cholinesterase activity showed marked inhibition during the toxic effects. In rabbits, treated with 10 and 25 mg/kg fenitrothion daily, the conduction velocity of the sciatic nerve became slower. At the same time rabbits, poisoned with the higher dose, had marked signs of intoxication while others showed no signs at all. The histological findings showed destruction of the myelinated fibres of the sciatic nerve. Our results indicate that fenitrothion has a neurotoxic effect but the type and the mechanism of action is still obscure.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03188.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractIn unanesthetized rats, theophylline or caffeine in a dose of 150 mg/kg intraperitoneally caused a long–lasting tachycardia, hypermetabolism and hypotension. After 48 hours myocardial necroses were found in all the animals. Propranolol diminished the cardiotoxic as well as the chronotropic, calorigenic and hypotensive effects of theophylline. The calcium antagonists verapamil and D 600 were ineffective in this respect but augmented the acute toxicity of theophylline. Furthermore, the cardiotoxic activity of theophylline was intensified by pretreatment with thyroxine. Total myocardial calcium increased within one hour after the injection of a cardiotoxic dose of isoprenaline (10 mg/kg intraperitoneally) but not after theophylline (150 mg/kg intraperitoneally). Only 24 hours after the theophylline treatment were the myocardial calcium levels elevated. In conclusion, cardiac necroses may be a consequence of hypoxia resulting from the cardiovascular and metabolic actions of theophylline or caffeine. Myocardial calcium overloading does not seem to be an essential factor in the pathogenesis of these necrose

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03189.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY