摘要:

AbstractThe passage of digoxin into the cerebrospinal fluid (CSF) was studied in 8 infants on maintenance therapy with digoxin, 11 adult patients on long‐term digoxin therapy, and 15 patients, previously non‐digitalized, who were given 0.5 mg digoxin orally 1 hr to 12 hrs prior to lumbar puncture. Digoxin in the serum and CSF was determined by radioimmunoassay. In the infants a mean serum concentration of 1.5 ng/ml (range 0.7‐2.3 ng/ml) was found, and a simultaneous mean CSF concentration of 0.5 ng/ml (range 0.3‐1.1 ng/ml). In the adults on long‐term therapy, the corresponding figures were 1.1 ng/ml (range 0.5‐2.2 ng/ml) and 0.3 ng/ml (range 0‐0.6 ng/ml). Among the 15 patients given a single oral dose of digoxin, detectable CSF concentrations (0.2‐0.3 ng/ml) were found in five, 1‐12 hrs after the administration of the drug. In three paediatric patients with hydrocephalus (3 months ‐ 5 years) digoxin therapy was started as an attempt to decrease CSF production. In these patients, the production of CSF was reduced by 17, 25 and

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02139.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractGuanethidine sulphate 5 and 40 mg/kg was administered intraperitoneally to adult rats for 4, 8, 14, and 28 days followed by discontinuation for 1 day, after administration for 28 days and additionally for 8, 14, 29, and 60 days. Under chloralose‐urethane anaesthesia the mean arterial blood pressure and the mean heart rate were determined and the response of these parameters to intravenous noradrenaline 3‐1600 ng was recorded. The blood pressure was not significantly changed after guanethidine 5 mg/kg, but lowered by 40 mg/kg, the decrease being reversible on discontinuation. The response of both parameters to noradrenaline was increased by guanethidine depending on the dose. The hypersensitivity was partly reversible on discontinuation, but a significantly increased sensitivity of the heart rate to noradrenaline was observed 60 days after discontinuation of guanethidine 40 mg/kg for 28 days. Histologically a profound loss of nerve cells of the superior cervical ganglion was observed following guanethidine 40 mg/kg, whereas no change was observed after 5 mg/kg. The present investigation has demonstrated that guanethidine 5 mg/kg does not induce histological or permanent haemodynamic changes, whereas 40 mg/kg for 28 days result in an incomplete sympathectomy accompanied by a partially irreversible hypersensitivity to noradrenaline. There is no simple relation between the loss of ganglion cells and the haemodynamic changes, and hence the hypersensitivity to noradrenaline is only in part due to the destruction of the postganglionic sympathetic neurone obtained by long term administration of large doses of guanethid

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02140.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractGuanethidine sulphate in doses of 5 and 40 mg/kg was administered intraperitoneally to adult rats daily for three months followed by discontinuation of administration for one day or three months. Following guanethidine 40 mg/kg a loss of approximately 95 % of the nerve cells of the superior cervical ganglion was observed. No changes were observed after 5 mg/kg. The average mean arterial blood pressure (measured under chloralose‐urethane anaesthesia) was lowered by 33 and 54 mmHg by guanethidine 40 mg/kg for three months followed by discontinuation for one day and three months respectively. The heart rate was unchanged. Guanethidine 5 mg/kg did not change any of these parameters. The increase in blood pressure and heart rate caused by intravenously administered noradrenaline was greatly enhanced following guanethidine 40 mg/kg, whereas only small changes were observed following 5 mg/kg. Following discontinuation for one day of 40 mg/kg for three months the potency ratios for the mean arterial blood pressure and the mean heart rate were 31 and 21 respectively, after discontinuation for three months 44 and 17 respectively. The potency ratios following guanethidine 5 mg/kg were 1.5 to 2.0. No changes were observed in the weight of the suprarenal glands following guanethidine. The present investigation has demonstrated an almost total chemical sympathectomy by guanethidine 40 mg/kg for three months and a persistent hypersensitivity to noradrenaline even after discontinuation of medication for three month

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02141.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe effect on 5‐hydroxytryptamine release from rabbit platelets to plasma of ten known sympathomimetic or anorectic phenethylamines and eight N‐ or O‐acetyl derivatives of these substances were studied in order to find possible structure‐action relationships and a possible correlation to the pulmonary hypertension inducing ability of some anorexigens. Among the mainly indirectly acting sympathomimetics amphetamine and ephedrine showed a similar high 5HT‐releasing effect. Tyramine was slightly weaker, while the direct acting phenylephrine (metaoxedrine) and orciprenaline were much weaker. Acetylation increased the 5HT releasing effect of amphetamine, ephedrine and tyramine but decreased this effect of phenylephrine and orciprenaline. Among the anorectic phenethylamines the 5HT‐releasing effect decreased in the following order, aminorex, amphetamine, clophorex, chlorphentermine, diethylpropion (amphe‐pramon), phentermine. With regard to aminorex, which is a releaser of platelet 5HT and an inhibitor of both MAO activity and 5HT uptake in pulmonary tissue, it seems possible that the pulmonary hypertension can be caused by high concentratio

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02142.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractSuspensions of liver cells isolated from perfused rat livers were incubated with antipyrine‐N‐methyl‐14C. Antipyrine was eliminated by first‐order kinetics during incubations for 3 hours with primary suspensions (parenchymal cells + non‐parenchymal cells) and suspensions of purified parenchymal cells. Antipyrine concentrations were unchanged when incubated with suspensions of non‐parenchymal cells, dead cells or medium only. At the end of incubation period, 4‐OH‐antipyrine and 3‐CH2OH‐antipyrine were detected mainly as the glucuronide or sulphate conjugates, and evidence for the N‐demethylation of antipyrine was also obtained. Half‐lives for elimination of antipyrine in primary cell suspensions were not significantly different from the half‐lives measured in parenchymal cell suspensions. This finding together with the lack of metabolism of antipyrine found in non‐parenchymal cell suspensions suggest that oxidation and conjugation of antipyrine is mainly confined to the parenchymal cells. There was significant inhibition of antipyrine metabolism in primary suspensions by phenylbutazone (1.6 × 10‐3M), dexamethasone (2 × 10‐4M) and ethanol (1.3 × 10‐2M, 0.75 %0). We suggest that the use of primary suspensions of isolated rat liver cells provide a rapid and simple method for the study of factors infl

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02143.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe tissue distribution of14C‐labelledN,N‐diethyl‐m‐toluamide (DEET), a widely used mosquito repellent, was studied by means of whole‐body auto‐radiography after cutaneous application to mice. The early picture was very similar to that previously observed after intravenous injection of the substance, with high concentration of radioactivity mainly in the lacrimal gland, liver, bile, intestinal contents, kidney, urine, and nasal mucosa. Urinary excretion in mice was highest early after application whereas in a human volunteer maximal excretion appeared only after several hours. In mice a low but significant excretion persisted throughout the observation time of one month, probably emanating from the considerable amount of radioactivity remaining in the smeared skin area, as observed both autoradiographically and by means of quantitative m

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02144.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of carbamazepine were studied during pregnancy and early childhood by investigating the extent of its placental penetration and its distribution in the foetal and neonatal tissues at autopsy. In foetuses the liver and kidney contained high levels of carbamazepine, whereas brain and lungs had low values. Carbamazepine‐10,11‐epoxide was also detected in the foetal circulation. At autopsy material, carbamazepine was localized mostly in the cerebral cortex, heart, liver and kidney. The concentration of carbamazepine in the milk was found to be 60 per cent of the respective plasma va

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02145.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractBy the means of thin‐layer chromatography (TLC) prior to fluorometry it was possible to determine furosemide (F) in plasma and urine with improved specificity. Antranilic acid (A) and 4‐chlor‐5‐sulphamoyl‐antranilic acid (CSA) could be determined simultaneously with F in plasma. In urine, only F and A could be determined quantitatively by this method. The sensitivity is 0.1 μg/ml for F and 0.15‐0.20 μg/ml for A and CSA. By means of TLC prior to fluorometry the blank value for F was reduced in normal subjects and in different groups of patients, and its diurnal variation was eliminated. The average values of the plasma concentrations of F after the intravenous injection of 40 mg into 12 normal subjects were at all times found to be lower by the TLC method than by the fluorometric method without TLC. A higher plasma clearance and a lower volume of distribution were found for F when the values obtained by the TLC method were used for th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02146.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractRats of the Wistar/Af/Han/Mol/(Han 67) strain have previously been shown to respond in a variable way to phenobarbital treatment, as far as the induction of aldehyde dehydrogenase activity is concerned (Marselos1976). This biochemical property is genetically determined and concerns the high‐Km aldehyde dehydrogenase of the hepatic cytosol. In this study, administration of phenobarbital (1 mg/ml of drinking water, for 1 week) produces a uniform induction of aldehyde dehydrogenase in all rats, when measured with micromolar substrate concentration. The inducible low‐Km enzyme of the cytosol is not genetically determined like the high‐Km enzyme, and shows a wide specificity for aliphatic as well as for aromatic aldehydes. Despite the inducibility of the cytosolic enzymes, no alterations are found in the mitochondrial aldehyde dehydrogenase activities after phenobarbital treatment. The oxidation of D‐glucuronolactone takes place only in the cytosol, and seems to be dependent on the low‐Km aldehyde dehydrogenase. This is consistent with NMR studies, which showed that a very minimal amount of D‐glucuronolactone is in aldehyde form under the measurement conditions usually applied. Further, the oxidation of D‐glucuronolactone is also enhanced by phenobarbital in all rats without a genetic predisposition, and its dose‐response curve is very similar to that of the low‐Km aldeh

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02147.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractA sensitive gas chromatographic method for the simultaneous determination of codeine and morphine in plasma and brain samples is described. The method involves solvent extraction of the compounds from plasma, derivatization with pentafluoropropionic anhydride and subsequent separation on a 3 % OV‐17 column. The quantification is performed with electron capture detection. The sensitivity of the method (0.75 ng of morphine and 7.5 ng of codeine in a sample) makes it especially useful for pharmacokinetic investigations. The method was successfully applied to determine the time course of codeine and its metabolite morphine after intravenous administration of codeine to the ra

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02148.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY