ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb03232.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb03233.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb03234.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractDifferent routes of elimination of emepronium have been quantitated in conscious and anaesthetized dogs. Smoothed plasma concentration time curves and urinary excretion data obtained following intravenous bolus injection of 5 mg/kg indicate at least four different phases with the following half‐lives: 5 min., I hour, 10 hours and 9 days. The initial dilution space, 0.2‐0.6 l/kg, is rather similar to the extracellular volume (0.20‐0.35 l/kg). From infusion experiments plasma clearance of emepronium have been found to be 33±2 ml. min‐1.kg‐1(meani ± S.E.M., n = 14). The drug is secreted by the renal tubules at a maximum rate of 20 μg/min. at a plasma concentration of about 200 μg/l. Compared with other quaternary ammonium compounds, this is an easily saturated mechanism with a low capacity. The renal clearance constitutes about 30 % of the plasma clearance at a plasma concentration of 200 μg/l. The biliary excretion rate increases proportionally to a plasma concentration up to 100 μg/l and then reaches a maximal rate which is dependent on the bile flow. The biliary clearance decreases from 7 to 2 ml.min.‐1.kg‐1when the bile flow changes from 7 to 4 g/ hour and the plasma concentration is 200 μg/l. Experiments with bile diversion and saline perfusion of isolated intestinal segments reveal an intestinal route of elimination of both emepronium and metabolites. The bile diversion experiments indicate that about 5‐15% of an intravenous dose is excreted through the gastrointestinal epithelium. Perfusion of isolated intestinal loops indicates an apparent clearance of 4‐5 ml. min‐1.m‐1over a wide range of steady state plasma concentrations (20‐1200 μ/l). An apparent total intestinal clearance could be calculated to about 7 ml. min.‐1.kg‐1. The remaining part of the plasma clearance (about 8 ml. min.‐1. kg‐1in an anaesthetized dog) is accounted for by metabolism. The degree of protein binding has been shown to be low, about 20 per cent, and the red blood cell penetrationin vitrois only 1‐10% o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02293.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb03235.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb03236.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractCarbon disulphide (CS2) exposure has been shown to activate the UDPglucuronosyltransferase of liver microsomes in rats pretreated with phenobarbitone. Now the nature of CS2induced activation of the enzymes has been studied further. Phenobarbitone pretreated rats were exposed to 0.15% CS2for 2 hrs on two successive days. The activity of UDPglucuronosyltransferase was measured from the liver microsomes after the enzymes was activated by incubation of the microsomes with various concentrations of the detergents Triton X‐100, digitonin and cetylpyridinium chloride. The exposed animals showed an increased enzyme activity at all applied concentrations of the detergents; therefore in addition to membrane destruction by CS2exposure, some other mechanism must also be involved in the CS2induced activation of liver microsomal UDPglucuronosyltransferase. The changes in membrane lipid‐protein interactions with 1‐anilino‐8‐naphthalene sulphonate (ANS) were also probed. The CS2exposed animals had more high‐affinity binding sites for ANS in their liver microsomal membranes, and in addition the quantum yield of ANS fluorescence was enhanced by CS2. The changes differed from those found after carbon tetrachloride exposure and suggest that, even if the two drugs have some common effects on microsomes, e.g. UDPglucuronosyltransferase activation, P‐450 destruction and lipid peroxidation induction, the changes they cause in the microsomal micro‐env

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02294.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb03237.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe ciliotoxicity of trichloroethylene was studied in terms of the time required for ciliostasis in specimens of trachea from 35 male rabbits following exposure of the specimens to different vapour concentrations. The highest vapour concentration was linked with the most rapid ciliostasis but even in the lowest concentration tested, 5.000 p.p.m. (26g/m3), hastened ciliostasis. Specimens from the upper region of the trachea underwent ciliostasis more slowly than did those from the lower region. The absolute uptake of trichloroethylene was lower in the former than in the latter specimen. The difference in uptake could not be explained by a difference in weight or in lipid content. That ciliostasis occurred at different times depending upon the region of the trachea, favours the theory of a critical tissue concentration for trichloroethylene.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02295.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractArrhythmias were induced in isolated rat atrial muscle preparations by increasing the calcium concentration of the Ringer solution, while the potassium concentration was kept low. A rise in the resting tension occurred simultaneously. The release of aspartate aminotransferase (ASAT) from the fibrillating atria was not higher than the release from non‐fibrillating atria pretreated with a calcium‐antagonistic drug, nifedipine 100 μg/l. It is suggested that calcium‐induced rat atrial arrhythmias in the present experiments are caused by a direct effect on calcium influx through the excitable membrane and not as a result of myocardial lesion caused by calcium ov

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02296.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY