Digoxin and ouabain increase the synthesis of cholesterol in human liver cells

Digoxin and ouabain are steroid drugs that inhibit the Na⁺/K⁺-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver HepG2 cells, enhancing the activity and the expression of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver cells. Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009     

硝苯地平对兔体内地高辛药代动力学的影响

目的研究家兔服用硝苯地平后对地高辛血药浓度及药代动力学的影响,为临床合理用药提供参考。方法选取8只新西兰兔,雌雄各半,进行自身交叉对照实验。一组口服硝苯地平5天后口服地高辛,另一组仅口服地高辛,均于给药后于耳缘静脉采血0．7ml,洗净2周后,两组交叉给药,采血后血样经离心处理后取血清用荧光偏振免疫分析法测定血药浓度;使用DAS2．0程序计算药代动力学参数,SPSS统计处理软件进行统计学处理。结果合用硝苯地平后,地高辛达峰浓度升高33％（P〈0．05）;药一时曲线下面积增加40％（P〈0．05）;半衰期延长72％（P〈0．05）;总清除率减少40％。结论服用硝苯地平后可以使地高辛在兔体内的药动学过程发生明显改变,表明地高辛与硝苯地平合用时,应谨慎地观测地高辛的生理效应,并且注意监测地高辛血药浓度。     

小剂量卡普托利治疗老年人早期左心衰竭36例

本文采用小剂量卡普托利治疗老年人早期左心衰竭36例(治疗组),男30例,女6例,年龄60—84(平均68.2)岁。卡普托利剂量:12.5mg,3次/天,3天—2周为一个疗程。结果:总有效率88.8％(32/36),其中75％(24/32)的病例在用药1周内获效。除2例发生皮疹且在停药后自行消失外,余无副作用。而用Digoxin(0.25mg/天,疗程同上)治疗的36例(对照组)结果:总有效率72.2％,其副作用高达27.2％(10/36)。     

Pichia酵母宿主细胞DNA残留量检测方法的建立

为检测重组人血白蛋白中外源性DNA残留量,以宿主酵母工程菌基因组DNA为模板,使用地高辛标记探针进行点杂交.结果证明:该方法检测灵敏度较好,特异性较强,操作安全简便,可用于重组人血白蛋白的检测.     

洋地黄中毒24例临床分析

目的观察洋地黄中毒的临床特点,规范洋地黄的临床应用.方法对24例洋地黄中毒患者的临床表现、心电图改变、离子及肾功能等情况进行动态学观察.结果洋地黄的应用应规范化,剂量不宜过大,特别是合并低钾血症及肾功能不全者更要减少用量.结论洋地黄中毒引发的恶性心律失常可导致死亡,临床医生要早发现、早停药、早干预.