川芎嗪致30例不良反应文献分析

目的:探讨川芎嗪致不良反应的一般规律及特点,为临床合理用药提供参考。方法:对国内医药期刊报道的30例川芎嗪不良反应病例进行分类统计分析。结果:川芎嗪致不良反应与性别无关,多发生于>50a年龄组,其出现时间可发生于用药后的各个时间段。不良反应累及机体多个器官系统,临床表现复杂多样,主要表现为变态反应,严重者可出现过敏性休克。结论:临床医师、药师应了解川芎嗪所致不良反应的规律和特点,加强其应用的监测,以减少不良反应的发生。     

Anti-clastogenic effect of magnolol on benzo(a)pyrene-induced clastogenicity in mice.

It was previously reported that magnolol strongly inhibited the mutagenicity induced by the indirect mutagens [benzo(a)pyrene (B(a)P), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-aminoanthracene (2AA), and 7,12-dimethylbenz[a]anthracene (DMBA)] in Salmonella typhimurium TA98 and TA100 in the Ames test, and that the mechanism of this anti-mutagenic effect may involve the inhibition of the metabolic activation of indirect mutagen enzymes. In this study, the in vivo anti-clastogenic effect of magnolol against clastogenicity induced by B(a)P was evaluated using the micronucleus test in mice. Animals were treated with an oral administration of magnolol (1, 10, and 100 mg/kg) at -24, 0, 24, 48, 72, and 96 h before a single intraperitoneal injection of B(a)P. Peripheral blood specimens were prepared 48 h after administration of B(a)P, and analyzed by the acridine orange (AO) technique. The results indicated that magnolol inhibited clastogenicity induced by B(a)P at various administration times. In order to elucidate the mechanism behind this effect, we measured the activity of the detoxifying enzymes [UDP-glucuronosyltransferase (UGT) and glutathione-S-transferase (GST)] and antioxidative enzymes [superoxide dismutase (SOD) and catalase] in the liver when treated with an oral administration of magnolol at various administration times. Its effect on clastogenicity created by exposure to oxidative DNA damage-inducing X-ray irradiation was also evaluated using the micronucleus test in mice. Results showed that magnolol increased the activity of both UGT and SOD enzymes, and also inhibited the clastogenicity induced by X-ray irradiation. Magnolol had an anti-clastogenic effect on B(a)P in the micronucleus test as well as an anti-mutagenic effect on indirect mutagens in the Ames test. The anti-clastogenic effect of magnolol was also suggested by the increases in UGT and SOD enzyme activity, and by the attenuation of oxidative damage induced by X-ray irradiation.     

Assessing 12(S)-lipoxygenase inhibitory activity using colorectal cancer cells overexpressing the enzyme.

12(S)-Lipoxygenase (LOX) is regarded as a pro-tumorigenic enzyme and as a potential target for therapy and prevention of cancer so that the search for specific 12(S)-LOX inhibitors is part of drug development strategies. To facilitate the identification of specific 12(S)-LOX inhibitors we have created an assay cell line by introducing a12(S)-LOX expression vector into SW480 colorectal cancer cells. When arachidonic acid was supplied in the medium both transiently and stably overexpressing cells produced 12(S)-hydroxytetraenic acid (HETE) originating from the transfected gene at 4-5-fold the amount obtained from control transfectants. 12(S)-HETE production was 1913.7+/-17.2pg/ml and reached a steady state level 24h after addition of arachidonic acid. To demonstrate the models suitability of 12(S)-LOX overexpressing SW480 cells they were used to measure the inhibitory activity of the plant phenols baicalein, kaempferol, quercetin, nordihydroguaretic acid and resveratrol which are known for their chemopreventive as well as LOX-inhibitory activity in different tumour models. All 5 compounds inhibited 12(S)-HETE production at concentrations below those necessary for growth inhibition.     

复方氨基酸注射液(3AA)细菌内毒素检查法的建立

为建立复方氨基酸注射液（3AA）细菌内毒素检查法,笔者参照〈中国药典〉2005年版细菌内毒素检查法进行试验,结果该药原液对细菌内毒素和鲎试剂的反应无干扰作用.该药可采用细菌内毒素检查法控制药品质量.     

滴注过程中应注意避光的药品

综述了对光敏感、易光化降解、易氧化的临床常用注射剂的光稳定性研究进展。除硝普钠、对氨基水杨酸钠、两性霉素B等注射液需避光滴注外,吡啶类、噻嗪类、酚类、部分维生素类、喹诺酮类及抗肿瘤化疗药物在临床使用时,也应当采用避光滴注的措施,以保证临床用药的安全性和有效性。     

配伍使用赖氨匹林与庆大霉素对豚鼠的听力影响实验

 目的观察混合给药后的配伍安全以及豚鼠ABR检测和细胞形态学的变化。方法混合2种药物后,进行灯检,pH值、旋光度检测,两种药物均为临床使用剂量,观察两种药物在临床使用剂量下混合给药的安全性和有效性。健康杂色雄性豚鼠随机分为3组,GM组、GM+Aspirin-DL-Lysine组、对照组,采用听性脑干反应(ABR)、耳蜗铺片观察用药前后听阈及耳蜗毛细胞形态学改变,并检测庆大霉素血药浓度。结果混合后药物的pH值、颜色、及澄明度均无变化,混合试液与单纯药物溶液之间的旋光度无明显差异。①GM组不同频率下的ABR阈移分别为:1kHz15～18dB,8kHz17～20dB,GM+Aspirin-DL-Lysine组的阈移分别为:1kHz9～15dB,8kHz10～15dB。两组间差异显著(P<0.05);②耳蜗铺片结果显示:耳蜗铺片GM组底圈毛细胞有损伤,与正常组比较排列不整齐,毛细胞损伤向上逐渐减轻,提示与听阈升高的程度相平行。而GM+As-pirin-DL-Lysine组的毛细胞排列整齐,无损伤。结论赖氨匹林(来比林)与庆大霉素可以安全的配伍使用。单独注射正常量庆大霉素4周使豚鼠的高频ABR升高,混合注射GM+Aspirin-DL-Lysine后对豚鼠的ABR影响不明显。注射正常量庆大霉素使豚鼠耳蜗毛细胞有损伤,底圈比顶圈重,与正常组比较,毛细胞排列紊乱。而配伍使用GM+Aspirin-DL-Lysine可以减轻庆大霉素对毛细胞的损伤。与正常组比较无明显差别。     

Toxicologic evaluation of modified gum acacia: mutagenicity, acute and subchronic toxicity.

Modified gum acacia, produced from acacia gum by a process analogous to the production of modified food starch, was tested for mutagenicity in the microbial reverse mutation assay. The assay employed a wide range of dose levels, both with and without metabolic activation. Test results gave no indication that modified gum acacia possessed any mutagenic potential. The acute oral toxicity of modified gum acacia was determined in two studies employing Sprague-Dawley rats, and the LD50 values were found to be >2000 mg/kg. The primary dermal irritation potential of modified gum acacia was evaluated in rabbits by the Draize method. Test results indicated that modified gum acacia was slightly irritating by the Environmental Protection Agency (EPA) classification but not a primary irritant by Consumer Product Safety Commission (CPSC) guidelines. The subchronic toxicity of modified gum acacia was examined in Sprague-Dawley rats fed diets containing 0%, 1%, 2.5%, and 5% modified gum acacia for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. Results of these studies indicate that modified gum acacia does not possess mutagenic potential and that animals are not adversely affected by acute or subchronic exposure to modified gum acacia.     

乌司他丁在体外循环中肺保护机制的研究

目的:探讨体外循环所引起的肺组织炎性损伤,研究术中应用乌司他丁(UTI)保护作用及可能的机制.方法:25例患者随机分为两组,实验组将乌司他丁2万U/kg于体外循环开始后,直接加入体外循环机中;对照组除用等量生理盐水替代乌司他丁外,其他条件相同.动态检测两组患者左右房中性粒细胞数(polymorphonuclear neutrophils,PMN)、血小板数(et);血清白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平;气道压力、肺泡氧合指数(OI).结果:①对照组主动脉开放心脏复跳后5 min左房PMN、Pt明显低于右房(P＜0.05);②体外循环(cardiopulmonary bypass,CPB)开始后,两组桡动脉血IL-6、TNF-α进行性升高,于主动脉开放心脏复跳后达最高,后逐渐下降,但仍高于CPB前,对照组增高更显著(P＜0.05).③CPB开始后,两组桡动脉血IL-10进行性增高,于主动脉开放心脏复跳后,达到最高,后逐渐下降,但仍高于CPB前,实验组增高更显著(P＜0.05).④两组患者肺泡氧合指数(OI)CPB后比麻醉诱导时增高,对照组升幅明显高于实验组(P＜0.05).⑤两组气道峰压、气道平台压在停CPB和手术结束后均有升高,但对照组升高更显著(P＜0.05),且对照组与实验组有显著差异(P＜0.05).结论:乌司他丁能通过抑制血小板、中性粒细胞的激活、肺内聚集和扣留,抑制炎症因子IL-6、TNF-α的产生,并能促进抗炎因子IL-10的释放,从而减轻体外循环后肺损伤和通气功能障碍,保护并改善术后肺功能.     

川芎嗪对大鼠脑缺血再灌注Bcl-2、c-fos、Caspase-3的影响

目的:探讨川芎嗪干预脑缺血再灌注损伤后对Bd-2蛋白、C-fos蛋白、Caspase-3蛋白的表达影响及其保护大脑损伤的作用机制.方法:将SD大鼠30只,随机分为3组,即假手术组、模型组和治疗组,每组10只.建立脑缺血再灌注模型.治疗组用川芎嗪干预,采用免疫组化法测定川芎嗪干预大鼠脑缺血24 h后对Bd-2蛋白、C-fos蛋白、Caspase-3蛋白表达的变化.结果:在脑缺血再灌注损伤24 h后,治疗组脑组织Bcl-2蛋白阳性神经元数较模型组明显增多,差异有显著性意义(P＜0.01);治疗组C-fos蛋白和Caspase-3蛋白表达阳性神经元数较模型组明显减少,差异有显著性意义(P＜0.01).结论:川芎嗪能上调Bcl-2蛋白和下调C-fos蛋白和Caspase-3蛋白表达,川芎嗪可能通过抑制脑缺血再灌注损伤后细胞凋亡机制,从而对脑脑缺血再灌注损伤有保护作用.     

辛开苦降法治疗肥胖2型糖尿病的临床研究

目的:分析肥胖2型糖尿病临床表现和病机特点,比较辛开苦降法和传统治疗消渴方法滋阴清热法在肥胖2型糖尿病临床治疗中的降糖减肥疗效,评价辛开苦降法治疗肥胖2型糖尿病的临床适用范围和安全性;方法:在常规控制血糖,饮食控制的基础上,采用随机、对照、开放研究,将80例肥胖2型糖尿患者随机分为两组,治疗组—辛开苦降组,对照组—滋阴清热组,观察周期为12周,观察指标为体重指数、腰臀比、空腹和餐后2h血糖。结果:辛开苦降组降糖有效率为72.5%,减肥有效率70%;滋阴清热组降糖有效率为47.5%,减肥32.5%,两组比较,有显著性差异。各组治疗期间均未见明显不良反应。结论:辛开苦降法治疗肥胖2型糖尿病安全有效,减肥降脂疗效明显优于对照组滋阴清热组,组方用药符合肥胖2型糖尿病证治规律,适用于肥胖2型糖尿病。