摘要:

AbstractVariousin vitro‐inhibitors were added with3H‐benzo(a)pyrene (BP) into the perfusion fluids in isolated rat lung perfusions to see whether their effects are dependent on the integrity of tissue.3H‐BP and its metabolites were measured by thin‐layer chromatography and radiometry from both samples of perfusion medium and homogenates of lung tissue. The total covalent binding to lung tissue was used as a measure of the formation of reactive metabolites. In methylcholanthrene‐induced rat lung, the metabolism of BP was inhibited by α‐naphthoflavone, an inhibitor of monooxygenase, and less with diethylmaleate, a depletor of glutathione, with salicylamide, an inhibitor of conjugases, and, astonishingly, with D‐saccharo‐1,4‐lactone, an inhibitor of β‐glucuronidase. With trichloropropene oxide, which inhibits epoxide hydratase, the metabolism was either decreased or unchanged. Nicotine had no effect on BP‐metabolism. Nicotine and diethylmaleate increased statistically significantly and α‐naphthoflavone and salicylamide decreased the covalent binding of radioactivity to lung tissue. In most cases, the changes in BP metabolism observed during perfusion can be explained on the basis of effects of modif

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02351.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractToxogonin (80 mg/kg intraperitoneally) given 15 min. prior to the administration of organophosphorus insecticides dimethoate, malathion, parathion and azinphos‐methyl, organophosphorus warfare agents soman and tabun, or carbamates physostigmine, pyridostigmine and aldicarb, reduced the toxicity in mice of these agents by increasing their LD50 dose 1.5‐3 fold. The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin. Similar results were obtained for P2S (150 mg/kg intraperitoneally) with respect to the toxicity of dimethoate, soman and pyridostigmine, whereas no effect could be detected on the toxicity of tabun. Only a slight reduction in the toxicity of physostigmine was observed. The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated anim

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02352.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractNitrazepam and its main metabolites, 7‐aminonitrazepam and 7‐acetamidonitrazepam, free and conjugated, were determined in the human urine after a single oral dose of 5 mg. The determinations were performed by GLC method using63Ni‐EC‐detector for unchanged nitrazepam and nitrogen selective detector for the metabolites. Unchanged nitrazepam was poorly eliminated through the kidneys (about 1 per cent of the dose). The interindividual variation of total excreted urinary metabolites was large ranging between 848‐4933 pg (17‐99 per cent of the dose during 7 days). Of this amount conjugated metabolites made up 57 per cent. The urinary half‐lives of free and conjugated 7‐aminonitrazepam were (mean and ranges) 44 (23‐65) and 46 (25‐69) hrs, and of 7‐acetamidonitrazepam 12 (5‐31) and 18 (5‐46) hrs, respectively. The half‐lives of the excreted amounts of the metabolites did not correlate with any pharmacokinetic parameter of un

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02353.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of nitrazepam in saliva and serum was studied in 12 healthy volunteers after a single administration of a 5 mg nitrazepam tablet. The binding of nitrazepam to plasma proteins was determined 4 hours after the administration by ultracentrifugation. The analysis of nitrazepam concentrations was performed by63Ni‐EC‐GLC. The pharmacokinetic parameters were evaluated manually or by AUTOAN‐program in serum, and manually in saliva. The concentrations of nitrazepam in serum and saliva correlated significantly (r=0.472, P<0.001, n=97). The ratio saliva: serum was, however, time dependent. The protein free fraction in serum was significantly higher (P<0.01) than the salivary concentration at the same time (4 hours after administration). The peak concentrations in serum and saliva were 40.7 and 1.9 ng/ml (P<0.001) and the times to reach the peak maximum 2.4 and 2.5 hours, respectively (difference not significant). The mean half‐life of nitrazepam in serum was 30.5 hrs and in saliva 39.9 hrs, the difference being significant at P<0.05. The distribution phase parameters, poorly described before, were calculated. The clinical value of nitrazepam analysis in saliva seems to be neg

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02354.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractDigoxin had contractant effects on isolated, human mesenteric arteries and veins. Veins were more sensitive to this action of the glycoside than arteries. The contractions were not affected by phentolamine or by washing with a digoxin‐free solution. However, they were abolished by the calcium antagonist nifedipine, and by washing with a calcium‐free medium. In the presence of digoxin, the maximum response to noradrenaline (1.8 × 10‐5M) increased markedly in both arteries and veins, and the concentration‐response curve for the amine was displaced to the left. Immersion of vein preparations in calcium‐free solution for 30 min. abolished the digoxin contracture; an increase in extracellular calcium restored the response. Changes in extracellular potassium concentration caused changes in tension of the mesenteric veins similar to those previously demonstrated in peripheral veins ‐ both in the presence and in the absence of digoxin. It is concluded that digoxin contracts mesenteric vessels by a direct action on the muscle cells, and potentiates the contractant effects of noradrenaline. These effects are dependent on the availability of extracellular calcium. Mesenteric vascular reactions caused by changes in extracellular potassium are influence

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02355.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe activity of ornithine decarboxylase (ODC) in suspension cultures of mouse fibroblasts. LS cells, varied in a characteristic cyclic pattern after dilution of the cultures. Two strains of fluoride resistant LS cells, FR6 and LSFR6 cells, exhibited the same cyclic pattern, but with markedly higher ODC activities. These fluoride resistant cells, however, contained less putrescine, the product of the ODC reaction. Possible reasons for this finding are discussed.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02356.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractIn order to confirm our previous findings of increased sulphafurazole (sulfisoxazole, SF) inactivation by intestinal occlusion, SF was given intravenously 20 mg/kg to rats with a low small intestinal occlusion and to sham‐operated controls 40‐45 hours after the operation. Occlusion did not cause major changes in the distribution of SF to various tissues, but there were some indications of increased SF acetylation after occlusion. The occlusion rats produced ascitic fluid into the abdominal cavity and the total SF levels in the ascitic fluid were almost identical to those in blood, also after oral administration of SF, 50 mg/kg. After intraperitoneal administration of 2 ml of SF (60 μg/ml) more SF accumulated into the small intestinal wall in occlusion rats than in controls, and the acetyl SF levels were increased in the small and large intestine. So, our previous suggestion of an increased excretory function of the large intestine in occlusion states may not be the only explanation for increased drug levels in the large intestine found after oral administration of SF. Part of the SF in the intestinal wall can also result from ascitic fluid SF, and ascites must be taken into account when considering drug pharmakokine

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02357.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractMice given64CuCl2and65ZnCl2(10 μmol/kg) were treated with sodium diethyldithiocarbamate (0.5 mmol/kg). The treatment increased the brain level of radioactive copper five‐fold and that of radioactive zinc three‐fold. Such redistribution of metal ions may be explained from the formation of lipophilic metal chelates. The increased brain levels may involve neurotoxic eff

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02358.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe effects of glutathione depletion in isolated hepatocytes have been studied. A list of compounds which depleted glutathione and induced lipid peroxidation and cell lysis is given. The effects of halogenated acetamides were studied in more detail and results of studies on the interaction of iodoacetamide with cellular constituents are presented. A single metabolite of iodoacetamide, tentatively identified as the glutathione conjugate, was excreted from the cells while less than one percent of the “parent compound” was retained, tightly bound to macromolecules. This bound component could not be associated with the cellular damage. Methionine, cysteine and α‐tocopherol, as well as paracetamol and ethylmorphine, were found to prevent lipid peroxidation and lysis. It is concluded that GSH deficiencyper secan lead to lipid peroxidation and that this reaction caused the observed hepatocellular

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02359.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractTwo adult patients ingested an overdose of 2.4 g and 8.0 g of sotalol hydrochloride, respectively, i.e. 7‐25 times the mean daily dose. Certain signs as bradycardia and hypotension were similar to those described for other beta‐blocking agents. In addition to these, however, both patients had severe cardiac tachyarrhythmias and a considerably prolonged QT‐interval in their electrocardiogram. The decline of serum sotalol concentrations followed first‐order kinetics with the elimination half‐life of 13‐15 hours. There was a good correlation between the serum sotalol concentration and the prolongation of the QT‐interval. Sotalol differs from other beta‐blocking agents in its effects on the action potential of the ventricular muscle and Purkinje fibers of the heart. This is likely to explain the different symptoms and findings of sotalol intoxication compared to those seen in connection with other beta

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02360.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY