斑蝥素脂质体凝胶剂的研制与质量评价

目的 :研究斑蝥素脂质体凝胶的制备工艺 ,并初步评价其质量。方法 :用均匀设计法优选斑蝥素脂质体 (LC)的最佳处方及制备工艺 ,借助数字显微镜及病理图像分析系统 (MoticB5 professionalseries)观测其外观、大小及分布 ;用离心法结合GC法测定其包封率及渗漏率 ;并进一步将其制成凝胶剂 ,初步观察其稳定性 ,并以家兔为试验对象与对照品 (较膏剂 )比较其皮肤刺激性 ,用大鼠离体皮肤的扩散实验与对照品比较斑蝥素的透皮扩散情况。结果 :所得脂质体外观圆整 ,粒径分布均匀 ,平均包封率为 (79.7± 1 .2 ) %(n =5 ) ,稳定性良好 ;所得凝胶剂为半透明粘稠状胶体 ,与对照品相比皮肤刺激性显著减小 ,2 4h后皮肤内斑蝥素的滞留量显著增加 (为对照组的 2 .6倍 ) ,而透皮扩散的量极微。结论 :该脂质体凝胶制备工艺可行 ,质量稳定 ,检测方法可靠 ,高效、低毒 ,可望成为临床治疗斑秃的新制剂。     

Integral pharmacokinetics of multiple lignan components in normal, CCl4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers

Although pharmacokinetic alternations by hepatic injury have been extensively studied, little is known about the potential influence of hepatoprotective agent's treatment. This study was aimed to investigate the holistic pharmacokinetics of multiple lignans, CYP3A regulations, and their correlations with hepatic injury biomarkers, in hepatic injured rats pretreated with or without schisandra lignan extract (SLE) and dimethyl-diphenyl-bicarboxylate (DDB). Integral pharmacokinetics of multiple lignans based on an AUC-weighting approach was determined in normal, CCl4 induced hepatic injury rats pretreated with or without SLE and DDB. Protein expression and activities of CYP3A were determined. Pharmacokinetic parameters and CYP3A activities were correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. CCl4 induced acute hepatic injury resulted in a nearly 8-fold enhancement of integral plasma exposures of multiple lignans, which was caused by the significant down-regulation of CYP3A. SLE and DDB pretreatment exhibited potent hepatoprotective effects, accompanied with the restored expression and activity of CYP3A, and the recovery of the respective and integral pharmacokinetics of lignans components. The integral AUC_0-tn and CYP3A activities correlated well with ALT and AST. This study suggested that the pharmacokinetic regulating effects of hepatoprotective agent's on themselves and co-prescribed drugs should be of concern, and hepatic injury biomarkers may serve as good predictors.     

颅脑损伤患者医院获得性肺炎常见病原菌及其耐药性 FREE

目的了解颅脑损伤合并医院获得性肺炎（hospital acquired pneumonia,HAP）患者常见病原菌及其耐药性。方法回顾性分析某院神经外科2004年1月-2009年6月收治的161例颅脑损伤合并HAP患者痰标本分离的病原菌及其药敏资料。结果161例患者分离病原菌274株,其中革兰阴性杆菌221株（80.66%),以肺炎克雷伯菌（25.18%）、铜绿假单胞菌（14.23%）、大肠埃希菌（13.50%）为主;革兰阳性球菌42株(15.33%),以金黄色葡萄球菌（5.11%）、凝固酶阴性葡萄球菌（4.38%）为主;真菌11株（4.01%)。产超广谱β 内酰胺酶（ESBLs）株68株,其中大肠埃希菌产ESBLs株检出率为78.38%(29/37),肺炎克雷伯菌为43.48%(30/69),阴沟肠杆菌为56.25%(9/16);检出耐高浓度庆大霉素肠球菌4株（66.67%）。病原菌耐药率均较高, 革兰阴性杆菌普遍呈现多药耐药性。结论颅脑损伤合并HAP病原菌仍以革兰阴性菌为主,耐药率高,应加强监控。     

循环内皮祖细胞及其应用

内皮祖细胞(endothelial progenitor cells,EPCs)是一类能增殖、迁移并分化为成熟血管内皮细胞,但尚未表达成熟血管内皮细胞表型,也未形成血管的前体细胞。对于存在于人体外周血循环中的内皮祖细胞,称为循环内皮祖细胞(circulating endothelial progenitor cells,CEPCs),其参与出生后血管新生和内皮损伤后的修复过程。CEPCs已成为心血管疾病等存在内皮损伤相关研究的热点。本文综述了循环内皮祖细胞的生物学特性,影响循环内皮祖细胞数量和功能的因素,以及循环内皮祖细胞在实际中应用的最新研究进展,为心血管疾病诊断和治疗提供新思路、新手段。     

2型糖尿病治疗新药坎格列净的研究进展

坎格列净是一种钠-葡萄糖共转运蛋白2抑制药,抑制葡萄糖的肾重吸收,增加葡萄糖的尿排泄.美国FDA于2013年3月批准其上市,用于治疗2型糖尿病.坎格列净可有效降低2型糖尿病患者的血糖水平,还可降低患者体质量和收缩压,且低血糖风险较小.不良反应是增加泌尿生殖道感染.本文就其作用机制、药动学、临床疗效及安全性等作一综述.     

当归多糖对AD模型小鼠抗衰老作用研究

目的观察当归多糖对AD模型小鼠学习记忆功能,测定脑组织中NO含量、p16蛋白含量、NOS及AchE活性,探讨当归多糖治疗衰老的作用机制。方法 KM小鼠72只,采用Y型迷宫实验测定小鼠的学习记忆能力,应用生化法测定脑组织NO含量、NOS及AchE活性,ELISA法测定p16蛋白含量。结果当归多糖各剂量组小鼠学习记忆能力明显得到改善,脑组织中NO浓度、NOS活性、AchE活性和p16蛋白含量与对照组比较显著降低。结论当归多糖具有延缓衰老的作用,可能机制是通过抗氧化作用和调控细胞周期实现的。     

Chitosan-Based Hybrid Nanocomplex for siRNA Delivery and Its Application for Cancer Therapy

Purpose

Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.

Methods

Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.

Results

Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.

Conclusions

A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum.     

关节镜手术围手术期抗菌药物应用的干预效果

目的了解某院关节镜手术干预前后围手术期预防性抗菌药物使用情况,评价干预效果,为规范临床合理使用抗菌药物提供依据。方法2012年8月起采取措施干预围手术期抗菌药物应用,对2011年9月—2013年8月该院312例关节镜手术患者围手术期抗菌药物的使用及手术切口感染情况进行回顾性调查。结果共调查患者312例,干预前150例,干预后162例,干预前后切口感染发病率均为0。干预后抗菌药物使用率为26.54%,低于干预前的100.00%,差异有统计学意义(χ2=1.781,P＜0.001)。不合理预防性使用抗菌药物的现象明显改善,平均抗菌药物费用比较,差异有统计学意义（t=3.330,P＜0.001）,由干预前的（1 165.69±756.33）元,下降至干预后的（32.71±119.29）元。结论干预后该院关节镜手术围手术期抗菌药物使用率明显下降,用药合理性提高,仍保持切口零感染。     

医院药物不良反应127例分析

目的 总结医院药物不良反应（ADR）发生情况,为临床合理用药提供依据.方法 应用Excel软件对解放军第二六四医院2012年上报的127例ADR报告,分别从患者性别、年龄、引起ADR的药品种类、涉及器官或系统以及临床表现等进行分类统计、分析.结果 ADR报告涉及的127例患者中,男61例（48.0％）,女66例（52.0％）,男女比例为1∶1.08;60岁以上患者占比最高（49例,38.6％）.ADR的临床表现以皮疹、瘙痒等皮肤及其附件损害为主（61例,48.0％）,其次为消化系统（24例,18.9％）和免疫系统（20例,15.7％）.损害涉及的药品有56种,抗感染药占首位（19种,52例,40.9％）,其次为中成药（17种,31例,24.4％）;头孢菌素类是引发ADR的主要抗感染药（25例,48.1％）,以头孢西丁为首.结论 本院ADR主要累及皮肤及附件,抗感染药引发ADR最多,以头孢菌素类多见.