General pharmacology最新文献

1. This study was designed to determine the antiulcerogenicity of esculine in various types of experimentally induced gastric ulcers in which the appearance of lesions is due to an ischemic process: cold-restraint stress and pylorus-ligated induced ulcers. 2. In the first experimental model, esculine (50 mg/kg) produced a significant diminution not only in the number of haemorrhagic stomachs (21.5% by 37.5% of the controls) but also in the ulcer index, U.I. (1.00 +/- 0.63, P less than 0.05). 3. When the mucosal damage was induced as a consequence of the pylorus-ligated gastric secretion, pretreatment of esculine (25 and 50 mg/kg) prevented the formation of gastric lesions (12.4 +/- 2.8, P less than 0.05 and 12.2 +/- 1.20, P less than 0.005), although it was less effective than ranitidine (2.8 +/- 1.8, P less than 0.025). However a significant reduction on the acidity with a dose of 25 mg/kg was observed (31.69 +/- 6.42, P less than 0.025). For the rest of the studied parameters: pepsin, histamine and Na and K electrolytes no differences with regard to the control groups were produced. 4. The effects of esculine on mucosal lesions produced by intragastric instillation of 1 ml of absolute ethanol, were also studied. In this model esculine did not show any protective effect and high U.I. values were obtained.

1. The effect of steroidal-cyproterone acetate (CPA, 10(-7)-10(-5) M), clormadinone acetate (CMA, 10(-7)-10(-5) M), medroxyprogesterone acetate (MPA, 10(-7)-10(-5) M) and spironolactone (SPI, 10(-7)10(-5)M) and non-steroidal-flutamide (F, 10(-7)-6 x 10(-5) M) and cimetidine (C, 10(-7)-10(-4)M) antiandrogens on contractile force of electrically stimulated left atria of the rat have been assayed. 2. CPA, CMA, MPA and F inhibit, in a dose-dependent way, the contractile force of left atria. SPI enhanced (P less than 0.01 at 10(-6) M), and cimetidine did not modify the contractile force. 3. F, but not CPA, CMA, MPA or SPI, inhibit the contractile force induced by CaCl2 (0.9-7.2 mM) on electrically stimulated left atria. 4. The inhibitory effect of CPA (10(-7)-10(-5) M) was significantly increased by atropine (10(-6) M) and diltiazen (10(-5) M), and significantly reduced by yohimbine (10(-7) M) and in reserpinized (2.5 mg/kg, 48 and 24 hr before experiments) rats. 5. Our results suggest that the negative inotropism of steroidal antiandrogens could be related to inhibition of noradrenaline release, presumably through an alpha 2 adrenergic effect. The negative inotropism produced by F is related to inhibition of calcium dependent process on left atria contraction.

1. Steroidal and non-steroidal anti-inflammatory agents were evaluated for effectiveness for treatment of acute T-2 toxicosis in mice. 2. Non-steroidal agents, indomethacin, phenylbutazone, and acetylsalicylic acid, either were ineffective, or potentiated the lethality of T-2 toxin. 3. Of the anti-inflammatory steroids tested, dexamethasone was the most effective. 4. Dexamethasone was administered before, at the same time as, or after injection of T-2 toxin. 5. As the time between toxin exposure and treatment was increased, there was a corresponding increase in lethality. 6. In conclusion, steroidal, but not non-steroidal, anti-inflammatory agents were effective in decreasing T-2 toxin-induced lethality.

1. A gastric mucosal laminin receptor has been isolated from the epithelial cell membrane by affinity chromatography on Sepharose-bound laminin, and following radioiodination was incorporated into liposomes which displayed specific affinity towards the laminin-coated surface. 2. The binding of liposomal receptor to the laminin-coated surface was inhibited by Helicobacter pylori lipopolysaccharide and reached a maximum value of 96% at 50 micrograms/ml. 3. The inhibitory effect of H. pylori lipopolysaccharide on the receptor-laminin binding was prevented by an antiulcer agent, nitecapone. The effect was concentration dependent and produced a maximum response of 83% at 30 micrograms/ml of drug concentration. 4. The results demonstrate that H. pylori is capable of disrupting gastric mucosal integrity by interfering with epithelial cell-laminin binding, and that an antiucler agent, nitecapone, counteracts this effect.

1. The effect of beta-endorphin (beta-EP) and morphine sulfate (MS), in presence and absence of naloxone (NX), on chicken chorioallantoic membrane was studied as a function of blood vessel proliferation. 2. A 50% reduction in blood vessel proliferation occurred by 10 micrograms of beta-EP or by 5 micrograms of MS per egg compared to controls. 3. An individual dose, i.e. 5 micrograms of beta-EP, did not significantly inhibit blood vessel counts after initial 24 hr period of the drug application when given alone compared to inhibition occurring with combined use of NX. 4. NX (1 microgram) did not significantly reverse the angiostatic effects of MS (10 micrograms) or of beta-EP (5 micrograms). 5. The observed modulation of angiogenesis by opioids suggests involvement of beta-EP and MS in the proliferation of vascular endothelial cells. 6. This may be due to an effect of beta-EP and MS on cell-mediated immunity factors such as interferons, interleukins and prostaglandin E2.

1. The modulatory action of histaminergic drugs: histamine; 2-(2-aminoethyl)thiazole (H1-agonist); dimaprit (H2-agonist); diphenhydramine (H1-receptor antagonist); and cimetidine (H2-receptor antagonist) on rat vas deferens contractions induced by electrical field stimulation (0.1 Hz, 1 pulse, 1 msec duration, supramaximal voltage) was studied either at different calcium concentrations in the nutrient fluid or after verapamil. 2. Histamine and 2-(2-aminoethyl)thiazole inhibited the electrically-evoked contractions (EEC). This effect was unchanged after verapamil. 3. Diphenhydramine potentiated the EEC. Verapamil added before the H1-receptor antagonist inhibited this action. 4. The effects of agonists and antagonists of H-receptors decreased with the increasing of calcium concentration. 5. The results obtained suggested the existence of heterogeneity of prejunctional H-receptors. The function of histaminergic drugs on adrenergic neurotransmission in field stimulated rat vas deferens is Ca(2+)-dependent.

1. Parameters of isolated hearts from rats which were actively sensitized to ovalbumin were found to be impaired on ovalbumin challenge: the heart rate increased whereas the contractility force and coronary flow decreased significantly. 2. Treatment in vivo or in vitro with histamine receptor antagonists (promethacine and cimetidine), the leukotriene antagonist FPL 55712, the PAF antagonist BN 52021, the combined prostaglandin endoperoxide receptor antagonist/thromboxane A2 synthesis inhibitor R 68070, the thromboxane synthetase inhibitor HOE 944, the lipoxygenase inhibitor ZIMET 47/79, the antioxidant sodium hyposulfite or with dexamethasone caused a different improvement of the parameters to a different degree. 3. Consequently, histamine, leukotrienes, PAF, activated oxygen, thomboxane A2 and possibly further autacoids might be involved in mediating the described anaphylactic reaction.

1. Regional activity of histamine was studied in various rabbit arteries, including segments of the aorta, aortic branches, branchout regions and arteries to fore and hind limbs by dose-response experiments. 2. Local histaminergic potencies were found to be heterogenceous. Circular and longitudinal smooth muscle responsivity in the aorta increased in the distal direction; aortic branches have their own histaminergic response characteristics beginning from their branchouts. Paired arteries (right and left subclavia, renal and iliac) possess matching histaminergic activities. 3. The observed characteristics of the responses suggest predetermined distribution of histaminergic activities along systemic circulation which may be regulatory in the distribution of blood.

1. Intravenous venom (0.0625 mg/kg) in the dog caused an immediate increase in coronary blood flow due to a fall in coronary vascular resistance (CVR). 2. Subsequently, total peripheral resistance (TPR) fell causing a significant reduction in aortic blood pressure (ABP). 3. CVR and TPR returned to normal after 20 min but ABP did not recover completely. 4. The failure of ABP to recover was due to decreased stroke volume and cardiac output (CO). 5. Animals died after four doubling doses of venom following irreversible reductions in CO, ABP and coronary flow.

1. In vitro studies were undertaken to investigate the effects of external potassium [K+]0 2.4-7.1 mM and magnesium [Mg2+]0 0-4.8 mM concentration on human chorionic veins basal tone and on serotonin (5-HT)-induced contractions. 2. The higher the [Mg2+]0, the less the basal tension developed in isolated chorionic veins, irrespective of the [K+]0. 3. The EC50 value to 5-HT was enhanced by increases in [Mg2+]0, whereas the ability of 5-HT to induce a maximal contraction was attenuated. 4. The rightward shift of the concentration-response curves and reduced Emax response, observed when the concentration of [Mg2+]0 was raised, indicate a non-competitive antagonism of [Mg2+]0 with 5-HT. 5. The lack of an effect of [K+]0 on the EC50 and Emax values for 5-HT suggest that in this tissue the affinity of 5-HT for 5-HT receptors does not involve potassium. 6. These results suggest that basal tone and 5-HT-induced contractions of human chorionic vascular smooth muscle cells appear to be highly sensitive to alterations in extracellular Mg2+.