摘要:

Abstract:Papaverine and nitroglycerine relaxed rabbit colon muscle. The relaxation was preceded by an increase of the cyclic AMP content of the muscle. There was a correlation between the degree of relaxation and the increase of cyclic AMP. A reduction of ATP content was obtained with these drugs; this effect was not present in the Ca++‐poor preparation in spite of the fact that the cyclic AMP level was still increased. Papaverine but not nitroglycerine reduced the phosphodiesterase activity of the intact rabbit colon. In a homogenate of colon muscle a marked inhibition of phosphodiesterase activity was obtained. The phosphodiesterase activity from different cell fractions was also studied. Phosphodiesterase from the cytoplasmic fraction was activated by papaverine and nitroglycerine, while that of a Ca++‐binding microsomal fraction like that of mitochondria was inhibited. Diazoxide and hydralazine relaxed bovine mesenteric artery but not rabbit colon. The relaxation was associated and correlated with an increase in the cyclic AMP content. A reduction in the ATP content and an activation of phosphorylaseaactivity was also obtained; the ATP reduction was Ca++‐dependent. A weak inhibitory effect on phosphodiesterase activity was observed in hornogenate of the artery after diazoxide. Hydralazine activated phosphodiesterase in a homogenate of mesenteric artery in a low concentration but inhibited it in a high concentration. It is suggested that cyclic AMP mediates, at least partly, the relaxing action of these four drugs probably by stimulating a Ca++‐binding process in the smooth musc

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01478.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Following oral administration of trimethoprim (TMP) in doses varying from 4.0 to 11.2 mg TMP per kg body weight per 24 hours over a period of 1‐5 days, the concentration was determined in lung tissue (obtained by open biopsy), bronchial secretion or saliva, in a total of 51 cases. A microbiological method was used to determine the concentration, usingB. pumilusas test organism. The concentrations of TMP found in the lung tissue, bronchial secretion and saliva (6‐13 hours after the last administration of TMP) were at a therapeutically active level (≥ MIC × 5) with regard to the majority of those bacteria usually occurring in respiratory tract infections. In 14 out of 17 patients, TMP was found in the lung tissue in concentrations which were 1 1/2 to 3 1/2 times higher than the corresponding serum concentration. In the other 3 patients, the concentrations found were 4 1/2 times, 7 times and 14 times higher in the lung tissue than in the serum. In the case of bronchial secretion, 6 patients showed a TMP concentration which was 1/2 to 4 times the corresponding serum concentration, while in 14 patients, an examination of the saliva showed a TMP concentration which was 1‐8 1/2 times that of the corresponding serum conce

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01479.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The atria and the upper part of the intra‐ventricular septum were removed from rabbit and cat heart, and the ventricular preparations were perfusedin vitrowith Krebs's solution. Preparations from twenty cats and 15 rabbits were studied for their sensitivity to acetylcholine. In the isolated rabbit ventricular preparations, acetylcholine in doses of 0.01‐0.1 pg caused a very weak negative inotropic and a chronotropic effect. Higher doses caused a dose‐dependent standstill. The cat ventricle preparations were rather insensitive to acetylcholine. When studied against noradrenaline induced increases in heart rate and force of contraction, acetylcholine in these preparations, also, caused a negative inotropic and chronotropic effect. In both the cat and rabbit preparations, the effect of acetylcholine was blocked by atropine 0.1 μg/ml in the perfusing solution. After pretreatment with atropine, acetylcholine (50‐100 μg) caused a positive inotropic and chronotropic effect that was blocked with propranolol 0.1‐0.2 μg/ml. This effect of acetylcholine was not obtained in preparations from reserpine treated animals.It was concluded that the cat and rabbit ventricle myocardium contains receptors to acetylcholine, and that stimulation of these cause a negative inotropic and chronotropic effect. Moreover, acetylcholine may release noradrenaline from the adrenergic nerve fibres. The difference in sensitivity to acetylcholine between the two species may indicate a difference in the significance of parasympathetic nerve stimulation to the ventricular myocardium in the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01480.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Two cases of digitalis poisoning are described. Case 1, a man, aged 40 years, swallowed for suicidal purposes about 50 digitalis tablets, each containing 50 mg standardized digitalis leaf, digitalis purpurea (0.5 i.u.). Death occured about 8 hours after the intake. A quantitative determination of digitalis glycoside in the gastric contents, and in the contents of the small intestine, blood and heart was performed with xanthydrol. Case 2, a child, 11 days old, because of a congenital heart disease was treated with digoxin. 1/2‐1 hour before death the child was given 0.7 mg digoxin intravenously. A quantitative determination of digoxin was performed with xanthydrol in the liver, heart and lung and by the fluorometric method in the liver, heart, kidney, urine and bloo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01481.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Whole‐body autoradiography of mice 5, 20, 60, 240 min. and 1 and 4 days after intravenous injection of14C‐thiourea and14C‐thiouracil showed a very similar distribution pattern for both substances. The concentration of radioactivity in the thyroid was higher than the average concentration as early as 5 min. after injection and it remained higher than in any other organ during the 4 days observation period. A high radioactivity was also found in the walls of large blood vessels, adrenal cortex, and the mammary gland as well as in the liver, lungs, and the kidney, where it persisted for as long as 24 hours. In the foetuses a very high uptake of radioactivity was found in the thyroid while the concentration in the other foetal tissues as well as in placenta did not exceed that of the blood of m

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01482.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Isolated superior cervical ganglia from rats pretreated with guanethidine sulphate intraperitoneally in single daily doses of 20‐40 mg/kg for 5‐21 days showed transmitted action potentials of normal form but diminished amplitude following single or repetitive stimulation of the preganglionic nerve. Curves relating the relative reduction in ganglionic action potential height with increasing frequency of stimulation were similar in preparations from control and guanethidine pretreated rats. Ganglia from guanethidine pretreated rats had the same sensitivity to exogenous acetylcholine as those from the controls as judged by doseidepolarization response curves. The absolute values of depolarization were, however, diminished. No impairment of the conduction of impulses in the preganglionic nerve or of the effect of antidromic stimulation was observed. The addition of guanethidine to the bath fluid resulted in an acute reversible ganglion block. A 50 % reduction of the ganglionic action potentials following single stimuli was observed at a concentration of 2 × 10−5M. At guanethidine concentrations of 5 × 10−5M maximum depolarizations obtained with acetylcholine or carbachol were reduced by approximately 50 % but the doselresponse curves were not shifted. Recovery was complete after washing. Retractions of the cat nictitating membrane following repetitive stimulation of the preganglionic nerve after pretreatment with guanethidine 5‐40 mg/kg for 14 days were preferentially decreased at low stimulus frequencies. The nictitating membrane was hypersensitive to intravenous adrenaline or noradrenaline. Contralateral ganglia from both rats and cats exhibited profound structural changes consisting of chromatolysis of the nerve cells and infiltration of small cells. The effects of guanethidine on the neurophysiological parameters are probably the result of a dose dependent inactivation of the majority of the gan

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01483.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The administration of guanethidine sulphate in doses above 10 mg/kg intraperitoneally for more than a week induced a considerable reduction (up to 80 %) of the noradrenaline content in the adult rat superior cervical ganglion. With 5 mg/kg no changes were observed, even after administration for 4 weeks. Single injections of 5 and 20 mg/kg had no effect on the ganglionic noradrenaline. Following administration for 14 days in a dose of 20 mg/kg, normalization of the ganglionic noradrenaline was complete within 8 days. Following 40 mg/kg For 18 days recovery was only partial ‐ probably due to irreversible degeneration of some ganglion cells. The effect of guanethidine on the noradrenaline content in the superior cervical ganglion is different from its noradrenaline depleting effect in sympathetically innervated peripheral organs and is assumed to be secondary to chromatolytic changes in the ganglionic nerve cells induced by guanethidine, some of these changes being irreversible following high doses for long periods of administratio

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01484.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The effects of hyper‐ and hypothermic acting compounds on the rectal and skin temperature, oxygen consumption, and heart rate were studied in the decapitated rat. Noradrenaline infusion (2 μg/kg/min.) caused thermogenesis, increased oxygen consumption, tachycardia, and vasoconstriction. 2,4‐Dinitrophenol (2 × 2.5 mg/kg intraperitoneally) and sodium salicylate (150 mg/kg intra‐peritoneally), which cause an uncoupling of the oxydative phosphorylation, caused thermogenesis and increased oxygen consumption but no significant changes in the skin temperature or heart rate. The effects of noradrenaline but not those of 2,4‐dinitrophenol and sodium salicylate could be blocked or reduced by the administration of propranolol and phentolamine. Thus the thermogenesis caused by noradrenaline could be differentiated from that caused by uncouplers of oxydative phosphorylation. The metabolic poison, iodoacetic acid reduced or prevented the noradrenaline induced thermogenesis when given as a pretreatment (30 mg/kg intraperitoneally) 60‐75 min. before the noradrenaline infusion. Chlorpromazine (10 mg/kg intraperitoneally) did not influence the noradrenaline induced thermogenesis either when given as a pretreatment or when given during the infusion. It is concluded that the decapitated rat is useful for the study of the mechanism of action of hyper‐ and hypothermic act

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01485.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY