摘要:

AbstractIf β‐ and α‐adrenergic inotropic effects are cyclic AMP dependent and cyclic AMP independent, respectively, they may be qualitatively different. The inotropic effects of β‐receptor stimulation (isoprenaline) and α‐receptor stimulation (phenylephrine combined with propranolol) were characterized in isolated perfused rat hearts, rat atria and rat papillary muscles. The β‐effect reached its maximum before the α‐effect. The α‐effect followed a three‐phasic time‐course indicating both stimulatory and inhibitory components. The aortic pressure wave (perfused heart) indicated a shorter contraction phase after β‐stimulation than after α‐stimulation. The time to peak tension (atrium, papillary muscle) was relatively shorter after isoprenaline than after α‐stimulation, which tended to prolong it. The contraction‐relaxation cycles (atrium, papillary muscle) were examined by recording the isometric tension (T), its first (T′) and second (T″) derivatives, α‐ and β‐stimulation both increased Tmax, T′max(maximal rate of tension rise), T′min, (maximal rate of tension decline) and T″min(maximal rate of transition from rise to decline of tension). Isoprenaline increased Tmin, (papillary muscle) and T″min(atrium, papillary muscle) relatively more than did α‐stimulation, i.e. the relaxing processes were activated relatively more by β‐stimulation. The results indicate different mechanisms for the two adrenergic inotropic effects. The relatively larger activation of relaxa

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02195.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractTreatment with 2,3‐dimercaptosuccinic acid was more effective than N‐acetyl‐DL‐penicillamine and monomercaptosuccinic acid in mobilizing mercury from mice after the injection of methyl mercuric chloride. Dimercaptosuccinic acid treatment started 4 days after the mercury injection and given for 8 days at a dose of 1 mmol SH/kg per day removed more than 2/3 of the mercury in the brain, while acetylpenicillamine and mercaptosuccinate correspondingly removed less than 1/2 of the brain deposits. Neither treatment with 2,3‐dimercaptopropano‐1‐sulphonate nor with a new thiolated resin, mercaptostarch, mobilized significant amounts of mercury from the brain. Since the toxicity of dimercaptosuccinate seems to be almost as low as that of D‐penicillamine this dithiol may provide a potentially useful agent in clinical poisoning due to

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02196.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractOsmotically balanced solutions of glucose (0.5–300 mM) and sodium chloride, containing surfactants, were instilled into the small or large intestine of anaesthetized rats. Net absorption or secretion of glucose, sodium and potassium was studied. The surfactants tested were dodecylsulphate (3.4–17 mM), dioctyl‐sulphosuccinate (1.8–11 m/M), Lubrol WX (0.1–0.5%), Triton × 100 (0.25%) and desoxycholate (2.5 mM). Qualitatively, the results were similar to those obtained previously with cationic compounds, suggesting a common mode of action for all surfactants studied. 17 mM dodecylsulphate seemed to abolish completely physiological glucose transport in the jejunum and ileum. At a lower concentration, and with the other surfactants, normal glucose transport was affected to an intermedi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02197.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractSevere neurotoxicity has been reported in patients receiving combinations of lithium and butyrophenones and halogenated phenothiazines and the suggestion has been made that lithium is preferentially concentrated in dopamine systems in brain. Conventional flame atomic absorption spectrophotometry does not allow analysis of sufficiently small samples of brain tissue to allow accurate association with specific transmitter systems, although previous reports have suggested that lithium is concentrated in the striatum. A method has been developed using flameless atomic absorption spectrophotometry to allow accurate measurement of lithium concentrations in 10–100 ng amounts in less than 10–100 mg fresh weight of brain tissue. Using this technique in experiments where rats were fed lithium over a period of three weeks, we could not confirm a direct association of lithium with an area predominently served by dopamine transmitt

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02198.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractA new gas chromatographic method, employing a nitrogenphorphorus sensitive detector, for the measurement of chlorpromazine and N‐monodesmethylchlorpromazine is described. The application of the method to the measurement of the drugs in clinical plasma and erythrocyte samples is demonstrated. It was found that the chlorpromazine concentration in the erythrocytes is positively and linearly correlated with the drug level in the plasma. However, a 4‐fold inter‐individual variation in the erythrocyte/plasma concentration ratios was evident. The concentration of the metabolite in the erythrocytes was found to be up to 27% of that of the parent compound. Chlorpromazine was unstable in plasma but stable in erythrocytes during a week's storage in the dark at ‐20°. The possible clinical implications of our findings are d

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02199.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractIsolated hepatocytes lost about half their content of GSH when treatedin vitrowith 90 nmol of diethylmaleate per 106cells. Within one hour GSH started to accumulate in the cells, and the rate of accumulation was taken as a measure of the GSH synthesis rate. The rate was affected by additions of amino acids and horse serum to the incubation medium. The methionine and cysteine uptake rates were much lower than the rate of GSH synthesis and not affected by variations in the GSH synthesis rate. The methionine and cysteine uptake rates were not affected by horse serum. It is concluded that even though exogenous sulphur‐containing amino acids facilitate GSH synthesis, the hepatic cysteine pool is to a large extent replenished by endogenous amino acids derived from protein degradation. In particular, this is the case when the turnover rate of the cysteine pool is increased by drug metabolis

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02200.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe post‐natal growth rate of young mice, pre‐ and post‐natally exposed to either 2,4′,5‐trichlorobiphenyl or 2,2′,4,4′,5,5′‐hexachlorobiphenyl has been studied. The results show that both the chlorobiphenyls have the ability to increase the post‐natal growth rate in mice and they indicate that this ability of 2,4′,5‐trichlorobiphenyl is most pronounced in females whereas that of 2,2′,4,4′,5,5′‐hexachlorobiphe

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02201.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe electrophysiological effects of procainamide and its major metabolite N‐acetylprocainamide were tested and compared on the heart of the anaesthetized dog by means of His bundle electrography and programmed electrical stimulation. Both drugs exerted a negative chronotropic effect. They also increased intra‐atrial and intraventricular conduction times; procainamide was, however, the more potent of the two drugs. In contrast to procainamide, N‐acetylprocainamide did not increase His‐Purkinje and atrioventricular nodal conduction times, and at the lowest dose employed, atrioventricular nodal conduction times were decreased during atrial pacing. Both drugs increased the functional and effective refractory period of the right atrium and ventricle. N‐acetylprocainamide increased the functional refractory period of the atrioventricular node, but to a lesser extent than pro

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02202.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractThe effect of nifedipine (BAY 1040), a calcium‐antagonistic inhibitor of the electromechanical coupling process was tested on atrioventricular conduction and refractoriness of the dog heartin situby means of His‐bundle electrography and programmed electrical stimulation. The animals were anaesthetized with sodium pentobarbital. As the basic effects of the compound can be altered by release of catecholamines from sympathetic nerves of heart and vessels, the dogs were pretreated with acebutolol, a β‐adrenergic receptor blocking agent, which decreased heart rate and prolonged atrioventricular conduction and refractoriness. Nifedipine 1,6 and particularly 30 μg/kg body weight increased the heart rate and decreased atrioventricular conduction time during atrial pacing, whereas atrioventricular conduction time during sinus rhythm and atrioventricular refractoriness were only affected by nifedipine 30 μg/kg. In this respect, nifedipine differs distinctly from another calcium antagonistic compound, v

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02203.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractCoprine or disulfiram was given to rats in various doses at various time intervals before the administration of 2 g/kg ethanol. The ratio acetaldehyde/ethanol in the alveolar air was measured by gas chromatography and was taken as an index of the aldehyde dehydrogenase (ALDH) activity. The activity of dopamine β‐hydroxylase (DBH) was estimated in the same animals by measuring the amount of14C‐octopamine formed from14C‐tyramine in the heart. Coprine and disulfiram both caused an increase in the acetylaldehyde/ethanol ratio, coprine being more potent than disulfiram. Disulfiram, but not coprine, reduced the net yield of14C‐octopamine. In rats pretreated with either coprine or disulfiram, blood‐pressure and heart‐rate were recorded before and after intraperitoneal injections of 0.4 g/kg ethanol. In both cases ethanol caused a marked and rapid fall in blood‐pressure. However, this effect was accompanied by tachycardia only in animals treated with coprine. It is concluded that coprine like disulfiram inhibits ALDH, but only disulfiram causes an additional inhibition of DBH. This difference may account for differences in the cardiovascular resp

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02204.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY