摘要:

AbstractSignificant reductions were registered in the plasma levels of prekallikrein proactivator (pro‐PKA), prekallikrein (PK), and high molecular weight kininogen (HMWK) 3‐5 min. after the intravenous injection into rats of serotonin (0.02‐0.20 mg/kg) or noradrenaline (0.02 mg/kg), whereas adrenaline (0.02 mg/kg) showed no effect, and tyramine (3.0 mg/kg) only slightly lowered the parameters mentioned. Pretreatment with reserpine (1.5 mg/kg) injected intraperitoneally 24 hours before dextran (10 mg/100 g) inhibited the dextran‐induced lowering of pro‐PKA and PK, but not the lowering of HMWK, while the effects of serotonin (0.13 mg/kg) were not influenced. After pretreatment of the rats with guanethidine (150 mg and 150 mg/kg respectively 48 hours and 24 hours before dextran) the dextran‐induced reductions in the levels of pro‐PKA and PK took place to the same extent as in control rats. while the lowering of HMWK was abolished. Pretreatment with reserpine protected against dextran‐induced oedemas, whereas pretreatment with guanethidine did not. It is concluded that catecholamines are probably not important in the initial phase of the dextran reaction in the rat, whereas serotonin seems to be an essential factor at this stage, as it is known to be during the fully developed dextran reaction. The results indicate that HMWK is not essential in connection with the early events of the dextran reaction, whereas the parameters pro‐PKA and PK seem to be of primary importance

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02378.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractActivation of plasminogen‐free rat citrated plasma (RCPL‐P) with acetone/kaolin yielded BAEe‐esterase activities of 0.6‐0.8 U/ml. Gel filtration demonstrated one single peak of BAEe‐esterase activity (mol. wt. approximately 135000) with a kininogenase‐esterase ratio (3.3) close to that known for human plasma kallikrein (2.7). Similarly activated rat citrated plasma (RCPL) revealed on gel filtration an additional esterase peak (mol. wt. approximately 47,000) with a low kininogenase‐esterase ratio (0.3), and should accordingly not be used for a BAEe‐esterase assay of rat plasma kallikrein. Acetone activation of RCPL‐P and of RCPL yielded prekallikrein activator (PKA) activities which were about doubled by treatment with kaolin to 1.9‐2.1 and 3.5‐4.2 PKA‐U/ml respectively. Gel filtration of acetone‐activated RCPL‐P or RCPL revealed two peaks of PKA activity, mol. wt. approximately 110,000 corresponding to activated factor XII (XIIa), and mol. wt. approximately 33,000 corresponding to XII fragments (XIIf). Kaolin‐treatment of acetone‐activated RCPL‐P, but not of RCPL, caused an extensive fragmentation of XII, to the 4‐6 times more active XIIf. The lower yield of PKA‐activity in acetone/kaolin‐activated RCPL‐P, as compared with activated RCPL, seems to be due to the absence of a factor of significance for the activation of factor XII, which is not plasmin, plasma kalli

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02379.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe latex ofEuphorbia poissoniiwas found to contain irritant aromatic diterpene esters based upon resiniferonol, 12‐deoxy‐16‐hydroxy‐phorbol and 12‐deoxyphorbol. Four resiniferonol esters, 9,13,14‐ortho‐phenylacetyl‐resiniferonol‐20‐0‐[p‐hydroxy‐phenylacetate]; 9,13,14‐orthophenylacetyl‐resiniferonol‐20‐0‐[m‐methoxy‐m′‐hydroxy‐phenylacetate]; 9,13,14‐orthophenylacetyl‐resiniferonol‐20‐0‐acetate and resiniferonol‐14‐0‐phenylacetate‐20‐0‐[m‐methoxy‐m′‐hydroxy‐phenylacetate], were identified. Two further esters were identified as 12‐deoxy‐164‐[2‐methylbutyroyl]‐phorbol‐13‐0‐phenylacetate‐204‐acetate and 12‐deoxy‐16‐0‐[2‐methylbutyroyl]‐phorbol‐13‐0‐phenylacetate. These compounds represent the first aromatic esters of this parent diterpene to be obtained from natural sources. The third group of compounds were identified as 12‐deoxyphorbol‐l 3‐0‐[p‐hydroxy‐phenylacetate]‐204‐acetate; 12‐deoxyphorbol‐l 3‐0‐[p‐acetoxyphenylacetate‐20‐0‐acetate; 12‐deoxyphorbol‐13‐0‐phenylacetate‐20‐0‐acetate and

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02380.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractAnaesthetized Beagle dogs were given increasing intravenous doses of imipramine, chlorimipramine or zimelidine. At each dose interval the interference of the drug administered with the effects on blood pressure and heart rate of vagal stimulation, NA injection and tyramine injection was investigated. Also, thein vitrouptake of 5‐HT into platelets afterin vivoadministration to unanaesthetized dogs of 5 mg chlorimipramine or 5 mg zimelidine was studied. Chlorimipramine and zimelidine were found to be about equipotent as regards 5 HT‐uptake into platelets afterin vivoadministration. Imipramine and chlorimipramine potentiated the effects of NA after the 2 mg/kg dose. Imipramine but not chlorimipramine interfered with the effects of tyramine after the 4 mg/kg dose. Zimelidine did not interfere with either NA or tyramine at any dose level studied (maximal cumulative dose 62 mg/kg). The effect of vagal stimulation was significantly inhibited after 8 mg/kg (cumulative dose 14 mg/kg) of imipramine and 16 mg/kg (cumulative dose 30 mg/kg) of chlorimipramine and zimelidine, respectively. It is concluded that zimelidine in comparison with imipramine and chlorimipramine has no or at most a slight effect on peripheral adrenergic neurones. It has less pronounced anticholinergic properties than imipramine but is about equipotent to chlorimipramine in this resp

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02381.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe bicyclic compound zimelidine has a pronounced inhibitory effect on neuronal 5‐hydroxytryptamine (5‐HT) uptake in animals. Healthy male volunteers were, in randomized order, given 100 mg zimelidine, 25 mg imipramine and 50 mg chlorimipramine. Before and 90 min after drug intake, increasing doses of noradrenaline was infused (0.006 μg × kg‐1× min‐1, 0.02 μg × kg‐1× min.‐1and 0.06 pg × kg‐1× min‐1, respectively), and the effect on heart rate and blood pressure was monitored. In some additional experiments N A was infused 4 and 6 hours after oral intake of imipramine and chlorimipramine, respectively. Imipramine in contrast to chlorimipramine and zimelidine potentiated the effects of noradrenaline on the diastolic blood pressure when infused 90 min. after drug intake. When infused 6 hours after oral intake of 50 mg chlorimipramine the effects of noradrenaline were potentiated in two out of three subjects. No anticholinergic effects, measured as blockade of salivary secretion, were observed after any of the three drugs at the doses used. The peak plasma concentration of zimelidine was obtained 2 hours after oral administration and the half‐life of elimination was estimated to about 7 hours. The bioavailability of orally given zimelidine at the studied dose was about 20 per cent. The metabolite desmethylzimelidine was present in the plasma in a similar concentration to that of the parent drug up to 8 hours after oral administration and thereafter in significantly higher concentration indicating a slower rate of elimination for the metabolite. The absorption of imipramine and chlorimipramine from the gastrointestinal tract was rather slow with a peak plasma concentration obtained as late as 6 hours after the drugs were given. The rate of elimination was about the same for imipramine and chlorimipramine and compared to zimelidine these two compounds we

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02382.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractByin vitroexperiments with equilibrium dialysis and 5 μg PPC per ml an average of 99.7±0.2% was bound to serum proteins. The binding in a solution with the albumin concentration which was present in the Serum samples did not differ from this binding or from the binding in plasma where coagulation was prevented with either heparin or citrate. The binding constant in albumin solutions at 37° was 4.5±0.3 1/molX 10‐5and an average of 1.16±0.04 primary binding sites was found. The association constant for the PPC albumin interaction was temperature dependent and the results of thermodynamic calculations suggested a combined ionic and non‐polar type of binding as the change in enthalpy contributed with 40% of change in free energy. A large positive entropy change was found (15.79 Kcal/mol/°K). The addition of phytomenadione to albumin solutions and of menadione to plasma caused a considerable decrease in the protein bound fraction of PPC, indicating the relevance of a study concerning the possible clinical consequences of these int

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02383.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractColisa fasciatius, a freshwater teleost, were exposed for 90 hrs to 45 p.p.m. nickel sulphate under static test conditions. The treatment resulted in leucopenia due to reduction in the number of small lymphocytes and polycythemia with concomitant increases in the haematocrit and haemoglobin values, and in retardation of the erythrocyte sedimentation rate of the moribund fish. No differences in total thrombocyte count, clotting time, and hepatosomatic index were found between the control and the treated fish. Lymphopenia and erythrocytosis may be used in presumptive monitoring nickel toxicity in fish.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02384.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractSix anaesthetized Swedish land‐race pigs were intoxicated by an intravenous infusion of nortriptyline‐HCl (NT) up to a concentration of 4.58±0.58 (X±S.E.M.) μM in arterial whole blood. A rapid injection of 2 mg/kg b.wt. lidocaine‐HCl in the right atrium was followed by a rise in arterial whole blood concentration of NT up to a maximum of 7.32± 0.28μM NT. Amount displaced NT from the cardio‐pulmonary circulation after the14C‐lidocaine bolus, was calculated to be 0.66 ± 0.03 μmol. Lung uptake of14C‐lidocaine during first‐pass through the lung was not influenced to any statistically significant degree compared to a control group. Thus, first‐pass uptake (FPU) was 30±8 (X̄±S.E.M.)% and 39±5% respectively. The duration of the QRS‐complex of the ECG was increased (P<0.01) during the infusion of NT from 0.07±0.01 (X±S.E.M.) sec. to 0.14±0.02 sec. when 250 mg NT‐HCl had been administered. The QRS‐duration was decreased (P<0.01) after the injection of the14C‐lidocaine bolus to 0.09±0.01 sec. Mean arterial blood pressure and heartrate decreased slightly during the infusion of NT, but did not change im

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02385.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe interaction of salicylates and other non‐steroidal anti‐inflammatory drugs was studied in rats. Concurrent oral administration of sodium salicylate (SS) or salicylic acid (SA) and indomethacin (IND) significantly reduced the gastro‐ulcerogenicity and the plasma concentrations of IND. Acetylsalicylic acid (ASA) failed to do so. IND had no significant influence on plasma concentrations of SA. Simultaneous administration of SS and IND intraperitoneally or subcutaneously showed the same pattern of interaction as for oral administration. Concurrent oral administration of SS and IND exerted similar anti‐inflammatory activity as the single drugs. SS significantly antagonized the ulcerogenicity of ibuprofen and tended to antagonize the ulcerogenic activity of ASA, phenylbutazone, tolfenamic acid and naproxen. The results suggest that in rats SS and SA (but not ASA) interact with IND concerning both gastro‐ulcerogenicity and plasma concentrations of IND (but not of SA) and that the interaction is systemic in nature. We propose that the ulcerogenic interaction might be explained partly by the reduced IND plasma concentrations and partly by a weaker inhibition by SS of the prostaglandin system in the ra

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02386.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe mechanism of the anti‐inflammatory activity and ulcerogenicity of (2‐dimethylamino‐1(2)‐methyl) ethyl ester of the 1‐(2‐carboxyethyl)‐2‐(p‐chlorophenyl)‐4,5‐bis‐(p‐methoxyphenyl)‐imidazole (A‐162‐ester) was compared with that of indomethacin in rats and enzymatic preparations derived from other species. A‐162‐ester was found to be deesterified in plasma to A‐162. A‐162‐ester was about 3 times less anti‐inflammatory and about 17 times less ulcerogenic than indomethacin. A‐162‐ester, when given orally, decreased prostaglandin I2(PGI2) biosynthesis by gastric mucosa. The IC50 was close to the ulcerogenic ED50. Indomethacin ‐ in the same test ‐ was 37 times more potent than A‐162‐ester and the PGI2inhibition and ulcerogenic dose‐response curves for indomethacin were parallel. In otherin vitrosystems of prostaglandin (PG) biosynthesis, the inhibitory activity of A‐162 was comparable to that of indomethacin. It is concluded that the ulcerogenicity of indomethacin results from a high affinity of this drug to gastric mucosal wall PG‐synthetase which leads to decreased PGI2formation at this site. The relatively low ulcerogenicity of A‐162‐ester most pro

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02387.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY