EMA采取措施减小含钆造影剂的使用风险

欧洲药品管理局（EMA）采取了一组旨在最大限度减小含钆造影剂引起肾源性系统纤维化（NSF）风险的建议。含钆造影剂用于磁共振成像造影。管理局的人用药品委员会（CHMP）评估了这些药品,     

欧盟评估抗抑郁药引起PPHN风险

欧洲药品管理局（EMA）人用药品委员会药物警戒工作组对5-羟色胺能抗抑郁药引起的新生儿持续性肺动脉高压（PPHN）风险进行了评估,并建议修订药品说明书。     

EMEA评估认为促红细胞生成素效益大于风险

2007年10月29日，欧洲药品管理局（EMEA）公布了对促红细胞生成素类药品的安全性评估结果。     

西安杨森制药有限公司被要求对“楷莱”“万珂”采取措旋控制风险

根据欧洲药品管理局最新公告,英国、法国药品监管机构和美国食品药品管理局于2011年11月7～11日对Ben Venus Laboratories公司（简称“BVL公司”）在美国的生产场地进行联合药品生产质量管理规范（GMP）现场检查,发现其无菌灌装过程质量管理存在缺陷。     

他莫昔芬在某些患者中出现治疗应答降低的风险

欧洲药品管理局（EMA）人用药品委员会药物警戒工作组（PhVWP）在2010年9月份召开的全体会议中讨论了他莫昔芬在某些患者中出现治疗应答降低的风险。     

英国警告舒尼替尼合并双膦酸盐治疗的颌骨坏死风险

英国药品和健康产品管理局（MHRA）和辉瑞公司联合发布了有关舒尼替尼（商品名Sutent,索坦）的最新安全性信息。     

欧盟修改抗抑郁药说明书警告成年患者自杀风险

2008年2月4日，英国药品和健康产品管理局（MHRA）发布关于修改抗抑郁药说明书的信息，警告25岁以下成年患者使用抗抑郁药导致自杀风险升高。 欧洲药品管理局人用医药产品委员会药物警戒工作组对美国食品药品监督管理局（FDA）近期完成的关于选择性5-羟色胺再摄取抑制剂（SS-RIs）和其他抗抑郁药的成人临床试验数据汇总分析结果进行了评估。     

英国警告雾化纤维蛋白黏合剂引起的风险

英国药品和健康产品管理局（MHRA）在2010年9月发布的（（DrugSafetyUpdate））中指出，雾化纤维蛋白黏合剂可能导致致命的气泡栓塞，用药时必须提高警惕。     

双氯芬酸增加动脉血栓事件风险

澳大利亚药品管理局（ TGA）于1014年8月1日发布药品安全信息［1］,指出处方药双氯芬酸增加动脉血栓事件风险。     

新西兰警告奥美拉唑的低镁血症风险

新西兰药品和医疗器械安全管理局（Medsafe）在其发布的2010年第2期（（Prescriber Update））中提醒医疗专业人员,已经发现使用奥美拉唑和低镁血症之间有关联。含奥美拉唑的药品信息正在更新过程中。     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

Hsp90 inhibitor BILBO21 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53- MDM2 balance

Aim： To investigate the effects of BILBO21, an inhibitor of heat shock protein 90 （Hsp90） alone or in combination with triptolide （TPL） on T-cell acute lymphoblastic leukemia （T-ALL） and the mechanisms of action. Methods： Human T-ALL cells line Molt-4 was examined. The cell viability was measured using M]-I- assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. Results： Treatment of Molt-4 cells with BILBO21 （50-800 nmol/L） inhibited the cell growth in a dose-dependent manner （the IC~ovalue was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h）. BILBO21 dose-dependently induced Go/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BILBO21 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BILBO21 （50-400 nmol/L） dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL （5-40 nmol/L） dose- dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BILBO21 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. Conclusion： The combination of BILBO21 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.     

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats,dogs and humans in vitro

Aim： （＋）Doxazosin is a long-lasting inhibitor of a1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. Methods： Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. Results： Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [（-）doxazosin： 89.4%-94.3%; （＋）doxazosin： 90.9%-95.4%]. （＋）Doxazosin exhibited significantly higher protein binding capacities than （-）doxazosin in all the three species, and the difference in the bound concentration （Cb） between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog〉human〉rat. Conclusion： （-）Doxazosin and （＋）doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.     

人参北芪片的质量控制研究

目的建立人参北芪片的质量标准,控制制剂的质量。方法采用薄层色谱法对制剂中组成药味人参进行鉴别,采用HPLC-蒸发光散射检测法测定制剂中的黄芪甲苷,并进行方法学考察。结果人参的薄层鉴别中,斑点清晰,阴性无干扰。黄芪甲苷在0.9976～14.9640μg与峰面积呈良好的线性关系,平均回收率为98.06%,RSD为1.60%。结论建立的薄层色谱和高效液相色谱定性、定量方法可以用来控制人参北芪片的质量,方法简便可行。     

Molecular modeling,quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT~ and ETA receptor antagonists

Aim： Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods： Molecular modeling approach combining quantum-polarized ligand docking （QPLD）, MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results： 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship： substitution of methoxymethyl and cyclooctanone might increase the activity against AT~ receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT~ receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion： This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are found to be the best dual antagonists against AT1R and ETA receptors.     

树突状细胞的肿瘤个体化治疗

肿瘤免疫治疗这一概念是基于机体的免疫系统在对抗肿瘤时的调节与反应。有效的免疫治疗的最主要的优点在于相对较少的副作用,针对肿瘤细胞的靶向特异性,并且能产生对抗肿瘤特异性抗原的长期记忆[1]。     

新生儿缺氧缺血性脑病并发热个案报道

1 病案介绍 患儿,男,新生儿(30 min),因颜面及全身皮肤青紫30 min于2011年1月11日转入儿科.患儿系第一胎,第一产,足月,因"胎儿宫内窘迫,脐绕颈2圈,羊水Ⅱ度污染"于入院前30 min在我院妇产科剖宫产分娩,胎头取出顺利,胎盘完整,无羊水呛入,生后无自主呼吸及心跳,颜面及全身皮肤青紫,肌张力差,插鼻管尚有反应,经心肺复苏,约3 min后心跳恢复,10 min后建立自主呼吸,但呼吸不规则,继续气囊加压给氧辅助呼吸至30 min,自主呼吸明显好转,皮肤青紫有所缓解,拔除气管插管后,患儿未出现呼吸暂停,急转入儿科治疗.其母孕期健康,无特殊服药史,父亲体健,非近亲婚配,无传染病史,无家族性遗传及代谢病史.     

奥氮平联用舍曲林致皮肤色素沉着及幻觉症状再现1例

1 临床资料 患者,男,32岁.既往体健,否认食物药物过敏史.个人史无特殊,家族史:患者二叔为自杀死亡. 患者于31岁时无诱因慢性起病,表现为认为被议论、被害,凭空听见有人骂自己,于2010年第1次住院,诊断精神分裂症,予奥氮平(最高用至 20 mg/d)系统治疗,3个月后好转出院,坚持服用奥氮平20 mg/d治疗,病情稳定.后因病失去工作,患者开始病情加重,语乱,生活懒散,情绪差,有自杀念头.2011年第2次送入院.