短程小剂量口服激素在婴幼儿喘息急性期联合降阶梯治疗方案中的作用研究

目的：前期研究表明,与目前常用的静脉激素及抗生素治疗方案相比,由泼尼松＋阿奇霉素＋妥洛特罗贴剂＋氯雷他定＋孟鲁司特钠组成的联合降阶梯治疗方案对婴幼儿喘息具有更好的疗效。在此基础上,本研究将进一步探讨作为联合降阶梯治疗方案组分之一的泼尼松在其中的作用。方法：选取2011年10—12月来我院哮喘门诊就诊的婴幼儿喘息患儿,共计100例,随机分为泼尼松组和对照组各50例。泼尼松组用药方案：泼尼松0．5mg／（kg·d）×3d,每天1次晨顿服;阿奇霉素10mg／（kg·d）×3d,每天1次口服;妥洛特罗贴剂0．5mg／d（1贴）×7d;氯雷他定糖浆3mL／d×14d,每天1次口服;孟鲁司特钠4mg／d×14d,每天1次口服。对照组除无泼尼松外,其他药物用法用量同泼尼松组。结果：（1）两组在治疗第3天和第7天咳嗽、喘息、哮呜音症状均较治疗前好转。（2）泼尼松组在治疗第3天咳嗽、哮呜音症状评分以及临床疗效均优于对照组（P〈0．05）。结论：短程小剂量口服激素是婴幼儿喘息急性期联合降阶梯治疗方案的有效组分之一。     

转运体在药物经肝脏清除过程中的作用

肝脏在药物的体内清除过程中具有重要作用,它不仅是药物代谢的主要场所,还控制着药物及其代谢物的胆汁排泄过程。转运体是控制细胞内外物质传输的一类功能性膜蛋白,其在肝脏有广泛表达,并能对药物进入肝细胞以及排泄至胆汁的过程进行调控,因而,对于肝脏清除过程具有重要作用。本文从肝脏中重要转运体的分布、功能以及底物选择性出发,对其在药物的肝脏清除中的作用、由其引起的药物药物相互作用以及重要转运体的基因多态性研究进行了综述。     

Tanshinone IIA triggers p53 responses and apoptosis by RNA polymerase II upon DNA minor groove binding

Our previous work has shown that tanshinone IIA (Tan IIA) is a DNA minor groove binder instead of an intercalator as previously thought. In this study, we have further demonstrated that the molecular antitumor pharmacology of Tan IIA is dependent on its groove-binding capability. First, we investigated the structure damage to duplex DNA upon Tan IIA binding using circular dichroism spectra. Subsequently, we performed western blot, flow cytometry analysis, chromatin immunoprecipitation, and quantitative real-time PCR to illustrate the RNAPII degradation, phosphorylation, and distribution along the transcribed gene in H22 cells exposed to Tan IIA. In addition, p53 activation and apoptosis induction in both cultured H22 cells and in mice bearing the ascitic-type H22 were measured following Tan IIA treatment. It was revealed that Tan IIA decreases the level of RNAPII by altering DNA structure. At the low dose range (0.2-4 μM) of Tan IIA exposure, the DNA structure damage results in the inhibition of RNAPII binding to DNA and the initiation of RNAPII phosphorylation, while higher concentrations of Tan IIA (4-20 μM) cause complete phosphorylation and degradation of RNAPII followed by p53 activation and apoptosis. A similar apoptosis induction by RNAPII was observed in animals. Apoptosis of tumor cells from ascitic fluid was not detected until RNAPII levels were downregulated by Tan IIA, which requires 40 mg/kg body weight of Tan IIA. It was concluded that DNA-conformational-damage-dependent RNAPII response upon groove binding is the molecular basis of the antitumor property of Tan IIA, in vivo and in vitro.     

进行性肌阵挛癫痫患者口服苯妥英钠致非惊厥性癫痫持续状态

1例16岁女性进行性肌阵挛癫痫患者,口服苯妥英钠0.15 g、1次/12 h治疗1周后出现非惊厥性癫痫持续状态,脑电图呈全导持续性棘慢波节律。7周后入我院,立即将苯妥英钠减量至0.05 g,2次/d,2 d后停用,同时给予患者丙戊酸钠0.3 g,1次/8 h;氯硝西泮1 mg,1次/12 h;左乙拉西坦0.25 g,1次/12 h。治疗第3天患者肌阵挛发作消失,治疗第6天脑电图示散在棘慢波、慢波,住院12 d,病情平稳出院。     

雷珠单抗临床应用新进展概述

雷珠单抗(ranibizumab)是第二代人源化抗血管内皮生长因子(VEGF)重组鼠单克隆抗体片段,能与所有活性形式的VEGF-A结合,防止其与VEGFR1及VEGFR2结合,从而减少血管内皮细胞增殖和降低血管通透性,抑制新生血管生成。近年来,其临床应用范围不断扩大,新的观察结果和观点、理念不断涌现。现将近年来雷珠单抗在眼科临床应用的最新进展作一综述。     

l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes

l-Theanine is a unique amino acid in green tea. We here evaluated the protective effects of l-theanine on ethanol-induced liver injury in vitro and in vivo. Our results revealed that l-theanine significantly protected hepatocytes against ethanol-induced cell cytotoxicity which displayed by decrease of viability and increase of LDH and AST. Furthermore, the experiments of DAPI staining, pro-caspase3 level and PARP cleavage determination indicated that l-theanine inhibited ethanol-induced L02 cell apoptosis. Mechanically, l-theanine inhibited loss of mitochondrial membrane potential and prevented cytochrome c release from mitochondria in ethanol-treated L02 cells. l-Theanine also prevented ethanol-triggered ROS and MDA generation in L02 cells. l-Theanine restored the antioxidant capability of hepatocytes including GSH content and SOD activity which were reduced by ethanol. In vivo experiments showed that l-theanine significantly inhibited ethanol-stimulated the increase of ALT, AST, TG and MDA in mice. Histopathological examination demonstrated that l-theanine pretreated to mice apparently diminished ethanol-induced fat droplets. In accordance with the in vitro study, l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.     

Detection of bacterial endotoxin in paclitaxel liposome

Based on current research, there are three technologies during the test of bacterial endotoxin of liposomes: (1) extraction of bacterial endotoxin from liposomes; (2) addition of bacterial endotoxin in the process of recovery test; and (3) elimination of the interference factors from drugs and excipients. In the present study, we pointed out that the key technologies to test bacterial endotoxin from paclitaxel liposome included following steps: extraction of bacterial endotoxins from ethanol-dissolved liposomes; preparation of positive control of recovery solution by adding 0.01 mL standard endotoxins in 1 mL liposome ethanol solution; and the use of 0.5% human albumin to eliminate the interference from detection, and accurate detection of the bacterial endotoxin of liposomes.     

New direction for clinical pharmacy in China: adopting a “form follows function” approach to improve future healthcare outcomes

Clinical pharmacy is an important development in modern pharmacy practice. In China, the recent recognition of clinicalpharmacists by the Ministry of Health is an important step that can lead to a successful change in the functional role of the pharmacists to directly improve the health care outcomes. To optimize this role change, we propose that a “form follows function” structure be implemented. We believe that a “form” consisting of three components is highly desirable and should be established with careful coordination: (1) a formal education/training curriculum; (2) a professional organization to lead the clinical improvements in practice/research; and (3) an accrediting body for quality education/training and practice. By incorporating the clinical pharmacy experiences in USA and other countries as well as adopting this “form follows function” approach, we predict a bright future for the clinical pharmacists in China as valuable members of health care team to positively impact the health care outcomes.     

尼莫地平缓释胶囊相对生物利用度的研究

12例健康志愿者随机交叉口服进口尼莫地平普通片和尼莫地平缓释胶囊60mg后, 利用高效液相色谱法测定血药浓度并对其生物利用度进行了研究.尼莫地平缓释胶囊和进口片的T1/2分别为3.74±0.84 h和1.98 ± 0.59 h;Cmax分别为25.41±9.32mg·L-1和80.08±16.65 mg·L-1; Tmax分别为3.25±0.97 h和0.75±0.21 h; AUC分别为167.4±27.3 mg·h·L-1和 194.7 ± 29.7mg·h·L-1;缓释胶囊的相对生物利用度为87.07%±9. 19%.8 例健康志愿者随机交叉多剂量口服尼莫地平缓释胶囊(60 mg,bid) 和尼莫地平普通片(30 mg,qid),达稳态时测得峰浓度分别为25.81±7.12 mg·L-1 和 41.21±10.04 mg·L-1; 谷浓度分别为7.19±1.84 mg·L-1和5.59 ± 1. 62 mg·L-1;两者血药浓度的波动系数分别为1.12±0.16和1.51±0.17.     

HPLC法测定乳疮丸中绿原酸的含量

目的：建立HPLC法测定乳疮丸中绿原酸含量的方法。方法：色谱柱为YMC-Pack ODS-A（250mm×4.6mm,5μm）;流动相为乙腈-水-磷酸（10∶90∶0.4）;检测波长为327nm;流速为1.0ml/min;柱温为30℃;进样量10μl。结果：绿原酸测定的线性范围为0.0308~0.308μg,回归方程为Y=98466.04X-24944.48,r=0.999961,平均回收率为100.55%,RSD为1.06%（n=6）。结论：该方法结果准确,操作简单,重现性好,可作为乳疮丸质量控制方法。