急性中毒并多器官功能失常综合征61例临床分析

目的调查急性中毒并多器官功能失常综合征(MODS)的发病情况和转归。方法回顾性分析300例急性中毒患者,其中61例并发MODS。结果61例并发MODS中,死亡14例,病死率22.9％。发生2、3、4、5或5个以上器官功能失常病死率分别为4.7％、15.7％、37.5％、80％。受累器官个数在死亡组和存活组的比较差异显著。结论 不同中毒致MODS的病死率不同,随器官功能失常数目的增加而升高。     

香菇多糖对巨噬细胞一氧化氮和一氧化氮合酶活性的影响

目的研究香菇多糖(LTN)诱导巨噬细胞的一氧化氮(NO)生成和一氧化氮合酶(iNOS)的活性,探讨LTN的免疫调节作用机理.方法采用Griess反应和荧光法测定不同剂量的LTN作用小鼠腹腔巨噬细胞后NO的生成量和iNOS活性.观察mRNA转录抑制剂、蛋白质合成抑制剂和iNOS抑制剂对巨噬细胞NO的生成和iNOS活性的影响.结果LTN能使小鼠腹腔巨噬细胞NO生成增加,iNOS活性增高,并呈作用剂量依赖关系.3种抑制剂均能抑制LTN诱导的小鼠腹腔巨噬细胞N0的生成和iNOS活性.结论LTN能刺激小鼠腹腔巨噬细胞提高iNOS活性和NO的生成.提示LTN的免疫调节作用机制可能与LTN刺激巨噬细胞NO生成有关.     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

《医话选粹》自序

医话是医业的小品文,不拘形式,不拘框架,与文学小品文唯一不同的是专谈医生的事务。因此,它自然是医生写的、讲的,是医生读的、听的。其中大至民族民生的卫生大事,小至日常卫生的琐事,只要是健康卫生范围内的事,都可秉笔而书。但有一点是主要的,那就是必须使读者在业务方面有所收获,此有别于茶余饭后的闲话聊天,读过、阅过、听过之后,读(听)者脑子里一无所得。是古人所谓“开卷有益”。     

实验性偏头痛动物模型c-fos、c-jun基因表达

目的　复制实验性偏头痛动物模型并探讨其c -fos、c -jun基因表达。方法　采用CristinaTassorelli硝酸甘油法复制大鼠实验性偏头痛模型。免疫组化ABC法研究偏头痛大鼠脑组织即刻早期基因c -fos、c -jun的表达。结果　硝酸甘油型实验性偏头痛大鼠出现双耳发红、甩头、前肢频繁搔头 ,活动增加等外在表现 ,脑组织c -fos、c -jun基因表达阳性细胞数增加 ,基因表达阳性细胞的面积扩大、灰度降低或变化不大。结论　硝酸甘油型实验偏头痛大鼠模型复制方法简单、重复性较好、脑组织c -fos和c -jun基因异常表达明显 ,可以作为偏头痛治疗药物筛选、药效评价和发病机理研究的动物模型。     

大肠癌病人血清胃泌素水平变化的临床研究

（目的）探讨血清胃泌素与大肠癌的关系及其临床意义。（方法）用放免法测定39例行根治术的大肠癌病人空腹血清胃泌素水平。（结果）大肠癌病人血清胃泌素水平明显高于对照组（P＜0.05）；高分化腺癌组术前血清胃泌素水平显著高于对照组及中、低分化腺癌组（P＜0.05），术后其鲁沙素水平明显下降（P＜0．05）；Dukes’A、B期术前血清胃泌素水平明显高于对照组及Dukes’C期组（P＜0．05），Dukes’A期病人根治术后其胃沙素水平较术前明显下降（P＜0．05）。（结论）血清胃泌素可能对大肠癌细胞有内分泌促生长作用；血清胃泌素水平测定可作为大肠癌诊断及预后判断的辅助指标，并可为选择大肠癌病人行激素治疗提供参考依据。     

芩栀胶囊的一般药理作用研究

目的：观察芩栀胶囊对小鼠、大鼠精神神经系统和麻醉犬心血管系统、呼吸系统的影响，探讨其用药安全性。方法：芩栀胶囊灌胃给药，观察给药后小鼠和大鼠的一般行为表现及平衡爬杆实验，考察其对精神神经系统的影响；芩栀胶囊十二指肠给药，在八道生理记录仪上记录给药前后相关指标的变化，考察其对心血管系统及呼吸系统的影响。结果：芩栀胶囊不影响小鼠和大鼠的一般行为表现，姿势、步态正常，无肌颤、流涎、瞳孔异常等变化，在平衡爬杆时间点，大鼠30min内跌落次数〈3次；对麻醉犬呼吸频率、血压、心率等未见影响。结论：一般药理作用研究表明，芩栀胶囊对动物精神神经系统、心血管系统及呼吸系统无明显影响，提示其不良反应小。     

中药复方治疗糖尿病肾病的临床研究

目的研究中药复方治疗糖尿病肾病的疗效及作用机理.方法选非胰岛素依赖型糖尿病(NIDDM),尿蛋白排泄率(UAER):20～200μg/min123例,分3组进行治疗,疗程8周.观察治疗前后空腹血糖、UAER、血压、内皮素含量等.结果治疗后中药组空腹血糖、血压、UAER、血浆TXB2及内皮素含量显著下降,与西药对照组比较无显著差别.结论该中药复方能保护早期糖尿病肾病患者肾功能,其作用可能与改善血管内皮功能有关.     

银杏叶提取物EGb761通过caspase-3抑制TNF-α诱导HeLa细胞凋亡

目的探讨caspase-3的活化在银杏叶提取物EGb761对肿瘤坏死因子-α(TNF-α)诱导HeLa细胞凋亡中的影响.方法采用流式细胞术检测细胞凋亡,Western blot检测caspase-3 p20活性片段,Caspase-3 Colorimetric Assay试剂盒测定caspase-3活性.结果流式细胞术分析结果显示,EGb761在10～40 mg/L终浓度范围内对重组人肿瘤坏死因子-α(rhTNF-α)诱导的HeLa细胞凋亡均有显著的抑制作用(P＜0.01),呈剂量依赖关系;Western blot检测显示,rhTNF-α诱导的HeLa细胞caspase-3 p20活性片段水平增高,能被不同剂量EGb761(10～40 mg/L)明显抑制,且随EGb761浓度增加抑制效果增强;caspase-3活性测定结果显示,EGb761对rhTNF-α诱导的caspase-3活化有显著的抑制作用,且随剂量增加抑制作用增强.结论结果提示,EGb761抑制TNF-α诱导的HeLa细胞凋亡可能与其抑制caspase-3活化有关.     

Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites.

Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore.