摘要:

Abstract:The performance of eight healthy young males was tested by means of 8 psychological and psychomotor tests 13/4and 41/2hrs after the administration of either ethanol, diazepam 10 or 20 mg, or placebo. The mean plasma concentrations of diazepam were estimated to be 230 (10 mg dose) and 495 ng/ml (20 mg) respectively after 13/4hr and 145 (10 mg), and 310 ng/ml (20 mg) after 41/2hrs; ethanol was estimated to be 0.091% after 13/4hr and 0.049% after 41/2hrs. Diazepam produced stronger subjective sensations of relaxation and reduced concentration than ethanol, whereas the test subjects experienced a similar depressing effect on motivation and effectivity after ethanol and after the largest dose of diazepam (20 mg). Both diazepam and ethanol reduced the scores in the following tests: Memorizing, Sorting (of coloured tablets), Complex Coordination and Critical Flicker Fusion Frequency. The scores in Letter‐Cancellation and Mirror Tracing tests were also reduced by both drugs, but in different ways; ethanol made the test subjects attempt more but increased their number of errors, while diazepam on the other hand slowed the subjects, so that they made fewer mistakes, but attempted less. Diazepam (20 mg) also reduced their time evaluation ability, while ethanol did not affect it significantly. Judged by clinical examination diazepam had a less marked effect on proprioception, speech and balance than ethanol. The effect of diazepam on the Flicker Fusion and Mirror Tracing tests could still be recognized 41/2hr after administration of the dru

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01461.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The anti‐inflammatory effects of adrenaline, isoprenaline, noradrenaline, tyramine, reserpine, guanethidine and fibrinolysin®were tested against carrageenin‐induced rat paw oedema. All the substances significantly inhibited the oedema. The inhibition by tyramine enhanced the effect of reserpine. The MAO‐inhibitor iproniazid potentiated the effect of noradrenaline and reduced the effect of reserpine. Thein vivoeffects of adrenaline, noradrenaline, reserpine and fibrinolysin on parameters of the plasma kinin system were investigated. Neither kininogen nor prekallikrein was influenced by any of the substances tested. The effect of noradrenaline, reserpine and guanethidine on the blood serotonin level was also investigated. Noradrenaline and guanethidine did not influence the serotonin level under experimental conditions which cause a significant reduction in the carrageenin‐induced rat paw oedema. The depletion by reserpine of the serotonin stores did not correlate with the rat paw oedema inhibition values. Nevertheless, a slight reduction in the blood concentration of serotonin after pedal injection of carrageenin might indicate a local release of the amine. Finally, plasminogen was estimated by a caseinolytic procedure in the plasma of rats injected with noradrenaline. Noradrenaline inhibited the rat paw oedema, but no reduction of the plasminogen level was observed. It was concluded that normal catecholamine stores rather than normal serotonin stores, and the application to the blood platelet serotonin, seemed essential for the development of carrageenin‐induced rat paw oedema. The fact that pretreatment with catecholamines inhibited the development of oedema might suggest that the same pathway of biochemical events is involved in the inflammatory process and in the preventive mechanism, the inhibition then reflecting an acute activation and depletion of a factor later in th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01462.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Indirect evidence has been provided of the presence of 3 kininogen fractions: The average amounts of kinin released by human plasma kallikrein (1.2 μg/ml plasma) and by human urine kininogenase (2.4 μg/ml plasma) when added up exceeded the amount of kinin released by combined use of the two enzyme preparations (3.0 μg/ml plasma). Methods were as described by BRISEIDet al. (1968). It is suggested that plasma kallikrein released kinin from 2 kininogen fractions, SI′ and SI″, and that urine kallikrein released kinin from 2 kininogen fractions, S1″ and S2. Repeated incubation with each of the kininogenase preparations did not increase the yield of kinin. Soybean trypsin inhibitor did not reduce the amount of kinin released by urine kallikrein. In control experiments a leucine aminopeptidase preparation transformed kallidin to bradykinin, but did not increase the kinin activity of the urine kallikrein incubates. Experiments carried out . with plasma kallikrein and padutin in 60°‐heated plasma supported the assumption of the 3 kininoge

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01463.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Prekallikrein in human citrated plasma was activated by incubation with acetone, 17 or 25% (v/v). EDTA‐2Na was added before or after the evaporation of acetone. Determinations of the relative activities of the enzyme preparations were based on the release of kinin from the 3 functional states of kininogen in human citrated EDTA‐plasma as described by BRISEIDet al. (1973). Incubations were carried out at 37° or at 0°. The kininogen 1/kininogen 2 activityratios were the same at 37° and 0°, indicating that the kininogenase activities tested were the same. The relative activities of the different kallikrein preparations varied with the type of kininogen used, possibly reflecting the presence of more than one kininogenase. Purification of the kallikrein combined with determinations of kininogen 1/kininogen 2 activity‐ratios must be carried out to solve th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01464.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The effect of phenoxybenzamine, an α‐adrenergic receptor blocking agent belonging to the β‐haloalkylamine group of drugs, has been tested on isolated rat atria. Phenoxybenzamine in concentrations ranging from 5 × 10−6M to 5 × 10−5M had positive chronotropic, but negative inotropic effects. At higher dose levels (10−4M and 5 × 10−4M), the rate decreased, whereas the depressing effect on contractile force was almost unchanged. The threshold for electrical stimulation and the effective refractory period were not affected. Phenoxybenzamine 2.5 × 10−5M protected against the changes in the rate and force of atrial contractions caused by acetylcholine 5 × 10−6M. In addition, the changes in the rat electrogram induced by acetylcholine were prevented by the drug. Atrial flutter and fibrillation produced by a standardized combination of electrical stimulation and acetylcholine were converted into sinus rhythm after the addition of phenox

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01465.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Sciatic nerves of the frog were soaked with equimolar solutions of the3H‐enantiomers of compound RAC 109, a spirosuccinimide with local anaesthetic action. The enantiomers were taken up equally by. (1) sheathed nerves during 2 hrs soaking with 2.5 mM solutions, (2) sheathed nerves and 10 min. soaking with 1.25‐40.0 mM solutions and (3) desheathed nerves during 1 hr soaking with 0.25 mM solutions. The washout curves for the two forms after application (2.5 mM) to sheathed nerves for 1 hr were identical. Recording of the block of the action potential with simultaneous determination of the concentration of the compound in sheathed nerve revealed a difference in the rate of block (5.0 mM) and the depth of block at equilibrium (2.5 mM) between the enantiomers, but the same uptake and retention in nerve. The epineural sheath was not a stereo‐selective barrier to penetration. Series of equilibrium blocks with 0.01‐0.4 mM3H‐enantiomers showed an approximately four‐fold difference in concentration in de‐sheathed nerve with a 50 per cent block of nervous conduction. The enantiomer RAC 109 I was consistently more potent than RAC 109 II. The findings suggest that the difference in the nerve blocking potency of the enantiomers can hardly be ascribed to a difference in the uptake of the compo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01466.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The absorption, accumulation and elimination of PCB (Clophen A50) in goldfish was studied. To ensure well‐defined and reproducible PCB concentrations in the water phase (0.01, 0.05, 0.10 and 0.50 p.p.m.) the experiments were made in aluminium foil containers. A rapid uptake and accumulation was observed but only slight changes in the relative composition of the absorbed PCB's were found. In the elimination experiment it was found that the content of PCB in the fish was halved during the first three weeks of the experimental period but that the half‐life for PCB rose during the experim

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01467.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:A prolonged toxicity study was performed in Beagle dogs. The adenine was dissolved by heating in the presence of an equimolar amount of lactic acid, diluted with saline to a 2.5 or 0.5% solution and given intravenously. The dose levels were 10, 20, 35, 85 and 135 mg/kg body weight. The substance was given during three weeks (five or six days a week) and the rate of infusion was either 0.6, 7.5 or 15 g adenine/hour. At dose levels above 10 mg/kg signs of renal impairment of varying degree appeared. All three dogs on 135 mg/kg, two out of three on 85 mg/kg and one out of four on 35 mg/kg died after four infusions. Another dog on 35 mg/kg died after eleven infusions. The values for serum creatinine and blood urea nitrogen were increased. The dogs also showed impairment of urine concentrating ability. In all cases autopsy re vealed evidence of uraemia. Crystals of 2,8‐dihydroxyadenine were found in the kidneys and nephrotic tubular changes were marked. The reversibility of the renal impairment was tested in one surviving dog on 85 mg/kg. The dog recovered clinically but the histological renal alterations seemed to be irreversible. The highest dose which could be considered safe in dogs was 10 mg/kg body weigh

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01468.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:The diaminophenols DAOC and DABP have been investigated for their methaemoglobin‐forming effect. Both substances were found to be active methaemoglobin inducersin vitroas well asin vivoon goats and pigs. After intra‐peritoneal administration of 33 mg/kg (DAOC), and 43 mg/kg (DABP) of the diaminophenols, the animals died within one hour. Administered in this way DAOC produced a lethal methaemoglobinemia within 15‐20 minutes, while after intraruminal administration the methaemoglobinemia developed less dramatically. At corresponding doses DABP produced almost the same level of methaemoglobinemia in the animals. In a more prolonged experiment haemolysis and acute nephrosis were observed, and haemoconcentration occurred in all the animals. It is concluded that the diaminophenol metabolites are responsible for the methaemoglobin formation following dinitrophenol poisonings in rumi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01469.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

Abstract:Median threshold concentrations for the riot control agento‐chlorobenzylidene malononitrile (CS) to produce blepharospasm were found to be 5.9 × 10−5M for the rabbit, 2.2 × 10−5M for the guinea pig and 3.2 × 10−6M for man. The threshold concentration to produce sensation on the human cornea was 7.3 × 10−7M. A dose‐response relationship was demonstrated. Extrapolation of log‐probit plots for sensation on the human eye suggest that 2.7 × 10−5M would be incapacitating. The median threshold concentration of CS required to produce sensation on the human tongue was 6.8 × 10−6M; a concentration 9.4 times that required to produce eye sensations. A dose‐response relationship on the tongue was demonstrated. The use of irritant tests, species variations in response, and the effects of solvents on t

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1973.tb01470.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY