胍丁胺对兔窦房结起搏细胞的电生理效应(英文)

目的:研究胍丁胺(Agm)对兔窦房结起搏细胞的电生理效应及其作用机制。方法:应用玻璃微电极方法。结果:Agm不仅能剂量依赖地抑制兔窦房结起搏细胞的V_(max),APA和VDD,RPF;而且能延长APD_(90);idazoxan能明显抑制Agm的电生理效应;而L-NAME不能影响Agm的电生理效应;提高灌流液中的Ca~(2 )浓度可对抗Agm的作用;ATP-敏感性钾通道开放剂(lemakalim)可部分拮抗Agm延长APD_(90)的作用。结论:Agm对窦房结的电生理效应由肾上腺素能α-受体和咪唑啉受体介导,并与Ca~(2 )内流和K~ 外流减少有关。     

In vitro antifungal activities of new imidazole salts towards dermatophytes

The in vitro activities of two new miconazole and econazole salts with the sulphosalicylic acid against 71 clinical isolates of dermatophytes were evaluated in comparison with those of miconazole, miconazole nitrate, econazole and econazole nitrate. Miconazole sulphosalicylate and econazole sulphosalicylate were equally effective in inhibiting the fungal growth compared with miconazole, econazole, and their nitrates.     

Synthesis, antitumor, and antibacterial activity of bis[4,5-diarylimidazol-2-ylidene]methane derivatives

Cationic [bis(1,3-diethyl-4,5-diarylimidazol-2-ylidene)]Au(I) bromide complexes have demonstrated considerable potential as new antitumor agents. In order to investigate whether the gold is crucial for the antitumor activity, the imidazole ligands were connected by a methylene bridge. Biological evaluation revealed that bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]methane compounds exhibited growth inhibition effects against mammary (MCF-7 and MDA-MB 231) and colon (HT-29) carcinoma cell lines. In comparison with gold complexes, the methylene derivatives showed drastically reduced cell growth inhibitory properties. However, the growth of bacteria was significantly inhibited by bis[1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]methane dibromide (4) and opens a new application of this compound type.     

Current Trends in the Pharmacological Treatment of Alcohol-related Problems

Abstract: Since alcohol-related problems affect almost 20% of the adult population, effective therapies are needed. Newly developed pharmacological strategies have been tested experimentally in animals and humans and progress is apparent. For example, an imidazobenzodiazepine (Ro15–4513) has recently been found to antagonize ethanol intoxication in rats selectively. However, testing in humans may be prevented by toxicity and ethical concerns. Abrupt discontinuation of ethanol intake in dependent subjects results in a withdrawal syndrome (AWS). With the recently developed benzodiazepine loading dose technique, practically all patients can be effectively treated with oral diazepam. Recent studies in rats suggest that non-sedative calcium channel blockers (e.g. nitrendipine, nifendipine) may also attenuate the AWS. New pharmacological strategies for decreasing alcohol consumption have also been developed. In three randomized, double-blind, controlled studies, serotonin uptake inhibitors (zimelidine, citalopram and viqualine) have consistently attenuated alcohol consumption in early stage problem drinkers. Effects on ethanol intake are distinct from the antidepressant properties of these drugs and they are most likely explained by a facilitation of satiety signals. Recently, new pharmacological approaches for attenuating neurological and hepatic alcohol-related problems have been described. Examples illustrate how the integration of basic and clinical pharmacological strategies may lead to improved pharmacotherapy for alcoholism within the foreseeable future.     

Fungistatic Activity of Miconazole against Candida albicans in Relation to pH and Concentration of Nonprotonated Drug

At less than 10(-5) M, miconazole (MCZ) exerts a fungistatic effect on Candida albicans, presumably by interfering with ergosterol biosynthesis. The imidazole moiety of MCZ is subject to protonation (pKa approximately 6.5). Based on pKa and greater water solubility of protonated (MCZH+) versus nonprotonated (MCZo) drug, fungistatic action ought to be markedly affected by environmental pH, but apparently it is not. In this report growth phase, pH, and concentrations of MCZ and MCZo have been studied in relation to fungistasis. Yeasts were grown in a synthetic liquid medium and MCZ effects were monitored by viability determinations. Results showed that fungistatic activity is little affected by growth phase and is largely independent of drug concentration and pH. Antagonism of fungistasis by low pH was demonstrated only at less than 10(-7) M MCZ. Data supported earlier proposals that MCZo is required for biological activity and suggested that target sites are saturated at very low levels of drug.