摘要:

AbstractIn isolated human crural arteries and veins, digoxin induced slowly developing, long‐lasting contractions. These contractions were not diminished by α‐adrenoceptor blockade or by washing, but were abolished by the calcium antagonist nifedipine. In the presence of digoxin, the maximum contractile responses to noradrenaline (18 μM) and potassium (127 mM) markedly increased, and the glycoside shifted the noradrenaline concentration‐response curve to the left. Immersion of vein preparations in calcium‐free medium for 30 min. abolished the digoxin contraction, whereas responses could still be elicited by potassium and noradrenaline. A change of the extracellular potassium concentration from 4.6 mM in normal Krebs to 1.15 mM always increased tension in vein preparations, whereas a change from 4.6 to 6.9 and 9.2 mM caused relaxation, and a further increase to 13.8 mM contracted the preparations. After pretreatment with digoxin (1μM), a potassium change from 4.6 to 1.15 mM caused relaxation and all concentrations exceeding 4.6 mM produced contraction. It is concluded that digoxin has a direct contractile effect on isolated human crural vessels, and that this effect is dependent on the extracellular calcium concentration. In the presence of the glycoside, the responses to noradrenaline and potassium are potentiated. Vascular responses to changes in extracellular potassium concentration are influenced

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02390.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractEffects of diazepam and alcohol on psychomotor skills were measured in two trials. In the first one, 200 healthy students volunteered for a double‐blind single‐dose study. Three doses of diazepam (5, 10 and 20 mg) and alcohol (0.5, 0.8 and 1.2 g/kg) were used alone and combined to construct dose‐response graphs. All doses of alcohol impaired divided attention while co‐ordinative skills were impaired by the 1.2 g/kg dose. Diazepam alone did not impair reactive or co‐ordinative skills whereas the combinations of diazepam and alcohol did so. To further elucidate the subacute effects, a double‐blind randomized study was conducted administering 2 and 10 mg of diazepam t.i.d. for two weeks to 18 healthy volunteers. The psychomotor tests were performed on the 7th and 14th days of drug administration, and 0.5 g/kg of alcohol was given on either day. Diazepam 2 mg, alone or with alcohol, did not differ from placebo. 10 mg of diazepam slightly increased reaction times but not reaction mistakes, and impaired both co‐ordination and attention. Alcohol did not enhance diazepam effects. We suggest that a development of tolerance to diazepam may compensate the deleterious interaction of the agents found in

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02391.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractIn vivoabsorption of phenytoin from the small intestine was studied by anin vivoclosed segment technique. Phenytoin in concentrations of 1000, 2000, and 4000 μmol/1 was administered in dissolved form. Polythylene glycol 4000 was used as a non‐absorbable marker. The concentrations of phenytoin in the intestinal lumen. in the mucosa, and in cardiac blood were measured both by spectrophotometry and by gas chromatography. Phenytoin was absorbed very rapidly, and the proportion absorbed increased with increasing dose. Thus, during the first 10 min. about 85 per cent of the largest dose but only 25 percent of the smallest dose had been absorbed. The phenytoin concentration in mucosa and serum increased in an analogous way; maximum values were observed within the first ten minutes. The concentrations in mucosa and serum were dose dependent during the first ten minutes. 0.01 mmol/1 and 1 mmol/1 phlorizin significantly reduced the transfer of phenytoin (4000 and 2000 μmol/1) from the gut lumen to the mucosa. No inhibition was observed when the initial phenytoin dose was 1000 μmol/1. The results suggest that an active transport mechanism, sensitive to phlorizin, is involved in the intestinal absorption of phenytoin in the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02392.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe blood pressure response after ethanol administration was studied in relation to blood acetaldehyde levels, aldehyde‐dehydrogenase (ALDH) ‐ and dopamine‐β‐hydroxylase (DBH) activities in rats pretreated with the ethanol‐sensitizing compounds disulfiram, cyanamide and coprine and the DBH‐inhibitor FLA‐57. Disulfiram, cyanamide and coprine, but not FLA‐57, inhibited the low‐KmALDH in the liver and caused an increased acetaldehyde level in blood. Disulfiram and FLA‐57, but not cyanamide and coprine, decreased the DBH‐activity in the heart and the levels of norepinephrine in the heart and the brain. In disulfiram‐treated rats with a low DBH‐activity, a fall in blood pressure was observed at acetaldehyde levels being slightly higher than those found in control rats. In disulfiram‐treated rats with a DBH‐activity close to control activity and in rats pretreated with cyanamide or coprine, a fall in blood pressure was found at acetaldehyde levels being 4‐5 times higher than the control level. No effects on blood pressure were observed in rats pretreated with FLA‐57. In rats pretreated with coprine + FLA‐57, the fall in blood pressure was similar, or even lower, than in rats pretreated with coprine alone. The results suggest that acetaldehyde is the main determinant of the hypotension elicited by ethanol in rats pretreated with ALDH‐inhibitors, and that the role of DBH in the disulfiram‐ethanol reaction has

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02393.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe storage of blood alcohol samples was studied. The samples were analysed and then frozen and kept at — 20° for 6 months before reanalysis. The results from this reanalysis did not deviate to any significant extent from those originally obtained. The process of freezing and thawing the same samples before analysis was repeated three times without any significant difference from the results obtained with the fresh blood sampl

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02394.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe effect of the central depressants nitrous oxide, halothane, pentobarbital and ethanol upon cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2) and cerebral vascular reactivity to carbon dioxide were measured using the rapid and repetitive intraarterial133Xenon injection technique modified for rat studies. The cerebrovascular resistance (CVR) during normocapnia in the pentobarbital group was significantly higher (P<0.01) than in the nitrous oxide group thus indicating a vasoconstrictor effect of pentobarbital that may be clinically important, because the ability of barbiturates to contract vessels in healthy brain regions may partly explain the protective properties of these drugs against cerebral ischemia. The results indicated that pentobarbital and ethanol may act synergistically with carbon dioxide in depressing CMRO2and cerebral vascular reactivity. Finally, it is concluded that nitrous oxide anaesthesia (70% N2O: 30% O2) is suitable as a reference situation in rat studies of the effect of pharmocological agents on CBF, CMRO2and cerebrovascular reactivity.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02395.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe 5‐hydroxytryptamine (5‐HT) antagonism of methysergide was compared with that of the phenylpiperidine 5‐HT uptake inhibitors, paroxetine and femoxetine, using two different models; the isolated cat middle cerebral artery and the common carotid artery of pithed rat perfused with the rat's own blood (autoperfusion). The extracorporeal circulation consisted of about 1.5 ml blood, which was temperature regulated to 36‐38° at the inlet to the carotid vessel by an automatic thermistor coupled heating system. In these experiments systemic blood pressure responses and perfusion pressure responses to 5‐HT were recorded simultaneously. The 5‐HT induced contractile response of the middle cerebral artery was reduced in a non‐competitive way by both uptake inhibitors at concentrations above 0.3 μM which is about 100 times the concentration needed for methysergide. In autoperfusion experiments inhibition was observed only at 5 mg/kg of both drugs. However, methysergide 0.001 mg/kg totally abolished all 5‐HT responses. The uptake inhibitors can therefore be described as weak

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02396.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractDNA synthesis in isolated nuclei from both fluoride sensitive and resistant LS cells was inhibited by fluoride at and above 3 mM. These fluoride concentrations also had an inhibitory effect on DNA synthesis in intact sensitive cells, but not in resistant cells. Due to previous findings that the intracellular fluoride concentration in the sensitive cells is only 30‐40% of the extracellular, it is suggested that inhibition of DNA synthesis in intact cells is secondary to the inhibitory effect on protein synthesi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02397.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractOne and 24 hours after the administration of63NiCl2and63Ni(CO)4to mice63Ni was present in association with both particulate and soluble cellular constituents in the lung, liver and kidney. After disruption of the cellular organells by sonication, a considerable part of the63Ni was still bound to the cellular fragments. Sephadex G‐75 chromatography of the cytosol of the lung showed that the largest proportion of63Ni was eluted in the void volume and a smaller proportion was present in the salt volume. In the kidney, the proportions were reversed. Twentyfour hours after the injection of63NiCl2an intermediate63Ni‐containing peak, with an estimated molecular weight of about 30,000, was found in the lung and the kidney. In the liver of63NiCl2‐injected mice, most of the nickel was recovered in the void volume, a lesser amount in the salt volume. There was no evidence that63Ni was bound to metallothionein (induced by Cd‐pretreatment) or to superoxide dismutase in the studied tissues. Pretreatments with non‐labelled NiCl2did not alter the elution profiles. In serum, most63Ni was present in association with albumin. Gel‐chromatograms of red blood‐cell hemolysates from63Ni(CO)4‐injected mice showed63Ni at an elution volume corresponding to hemoglobin, but63Ni‐binding ligands with higher and lower molecular weights

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02398.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe influence of age, pretreatment with CdCl2and long‐term oral treatment with CdSO4on whole‐body retention, organ distribution and the biological half‐time of109CdCl2(given as a single oral dose) was studied in mice in three separate experiments:I) Male CBA‐mice, 1, 3 and 6 months of age, were given a single oral dose of CdCl2labelled with109Cd. The whole‐body retention of the radiolabelled cadmium was inversely related to age. This was explained by a significantly higher intestinal absorption of109Cd in the younger mice, compared to the older. No influence of age on the biological half‐time of109Cd was observed.II) Three groups of adult of male CBA‐mice were pretreated with 75 mgCd/l (as CdCl2) in the drinking water for 130, 13 or 0 days, respectively, before receiving a single oral dose of CdCl2labelled with109Cd. The two pretreated groups showed higher intestinal absorption of radio‐labelled cadmium and a statistically significant longer biological half‐time of109Cd compared to mice not pretreated with cadmium. The organ retention of radiolabelled cadmium was markedly higher in mice given cadmium in the drinking water compared with those given deionized water.III) Male and female adult CBA‐mice were exposed to a single oral dose of CdCl2labelled with109Cd, via stomachtube. and were thereafter given either deionized water (control group) or 50 mgCd/l (as CdCO4) in the drinking water continuously for 18 months. The organ retention of the radiolabelled cadmium was higher in mice exposed to cadmium in the drinking water compared to those given deionized water. Mice exposed to cadmium via the drinking water had a markedly longer biological half‐time of109Cd compared to non‐Cd‐exposed mice. In all experiments the animals retaining a larger proportion of the cadmium dose showed higher liver: kidney ratios of the radiolabelled cadmium compared to mice retaining less cadmium.The conclusions of the present studies were:Age is of significant importance to the metabolism of cadmium due to the marked raise in intestinal absorption in the youngest age. pretreatment with cadmium caused a higher intestinal absorption of radiolabelled cadmium. A longer biological hall‐time of109Cd was seen both after pretreatment and subseq

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02399.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY