Studies on the effect of tetrandrine on microtubules. I. Biochemical observation and electron microscopy

Microtubules were purified by using two cycles of assembly and disassembly processes on fresh brain homogenates from 30 guinea pigs. The yield was about 60 mg. The effect of tetrandrine on tubulin was determined by spectrophotometric analysis and electron microscopy. In addition, we used the indirect immunofluorescent method including tubulin antibody to locate the presence of microtubules in 3T3 cells by fluorescence microscopy. The effects of colchicine and P204 were studied for comparison at the same time. The results showed that colchicine can effectively depolymerize microtubules, while tetrandrine showed aggregation, and in a different manner. The shape and structure of microtubules were definitely destroyed by colchicine, but were not affected by P204 which protected against the destructive effect of tetrandrine. This result indicated the safety of using a combination of P204 and tetrandrine in the treatment of silicosis.     

糖基化终末产物对大鼠肾系膜细胞纤溶酶原激活物抑制物-1表达韵影响

目的：观察糖基化终末产物（AGEs）对大鼠肾系膜细胞纤溶酶原激活物抑制物-1（PAI-1）表达的影响及其与细胞外基质（ECM）成分含量的关系。方法：体外培养正常大鼠肾系膜细胞，分别用糖化牛血清白蛋白（AGEs）及未经糖化的牛血清白蛋白（BSA）处理，以常规培养的肾系膜细胞作为对照，检测不同时间、不同浓度AGEs对纤维连接蛋白（FN）、Ⅳ型胶原、PAI-1表达的影响。MTT法检测AGEs对系膜细胞增殖的作用，ELISA测定条件培养基中FN、Ⅳ型胶原及PAI-1蛋白含量，逆转录聚合酶链式反应（RT—PCR）检测系膜细胞PAI-1 mRNA的表达。结果：与相应浓度的BSA比较，AGEs（0—200mg／L）对系膜细胞增殖无明显影响，但可不同程度地刺激系膜细胞FN、Ⅳ型胶原、PAI-1蛋白的产生。RT—PCR检测显示，给予AGEs（100mg／L）的系膜细胞PAI-1 mRNA的表达明显增加（P〈0．01）。结论：AGEs促进系膜细胞PAI—1的表达，提示AGEs通过上调PAI-1的表达而减少细胞外基质降解，可能是糖尿病肾病细胞外基质积聚的原因之一。     

阿尔茨海默病中肿瘤坏死因子-α基因多态性及表达

目的探讨肿瘤坏死因子-α(TNF-α)基因多态性与广东地区汉族人群散发性阿尔茨海默病(SAD)发病易感性的关系。方法采用聚合酶链反应-序列特异性引物(PCR-SSP)方法,检测44例SAD病人(AD组)及45例正常老年人(对照组)TNF-α基因的TNF-α1及TNF-α2等位基因频率。按比值比(OR)作疾病关联分析。用放免法检测两组的血清TNF-α含量。结果AD组的TNF-α2基因频率为0．182,明显高于对照组的0．078(OR=2．635,P=0．039)；AD组血清TNF-α含量为(567．85±102．43) ng/L,明显高于对照组的(389．73±56．68)ng/L(P＜0．05)。结论广东地区汉族人群中,TNF-α基因多态性与SAD有关联．TNF-α2等位基因与SAD的易感性有关。     

Rural-urban differentials of premature mortality burden in south-west China

Background  

Yunnan province is located in south western China and is one of the poorest provinces of the country. This study examines the premature mortality burden from common causes of deaths among an urban region, suburban region and rural region of Kunming, the capital of Yunnan.     

Roles of DNA polymerase β on repair of DNA damaged by γ－rays irradiation

ＲｏｌｅｓｏｆＤＮＡｐｏｌｙｍｅｒａｓｅβｏｎｒｅｐａｉｒｏｆＤＮＡｄａｍａｇｅｄｂｙγ－ｒａｙｓｉｒｒａｄｉａｔｉｏｎＣａｉＪｉａｎｍｉｎｇ（蔡建明）；ＺｈｅｎｇＸｉｕｌｏｎｇ（郑秀龙）；ＬｕｏＣｈｅｎｇｊｉ（罗成基）；ＧａｏＪｉａｎｇｕｏ（高建国...     

丙型肝炎患者外周血单核细胞中丙型肝炎病毒复制的研究

９例临床诊断为丙型肝炎患者，研究其外周血单核细胞中ＨＣＶＲＮＡ的存在及复制。９例患者血清标本抗－ＨＣＶ及ＨＣＶＲＮＡ均为阳性，采用高敏感的逆转录一套式ＰＣＲ法测定其外周血单核细胞中ＨＣＶ正、负链ＲＮＡ，结果９例患者外周血单核细胞中７例ＨＣＶ正链ＲＮＡ阳性，３例ＨＣＶ负链ＲＮＡ阳性，证实部分丙肝患者外周血单核细胞中存在ＨＣＶ的复制，表明肝细胞并非为ＨＣＶ感染与复制的唯一场所。     

医院内感染病原菌及其对抗生素的耐药状况

调查1988年3月～5月我院591例住院病例,发生96例次院内感染,总发病率16.2％。院内感染病原菌中,革蓝氏阴性杆菌占72.9％,革蓝氏阳性球菌占12.9％,念珠菌属占14.1％。院内感染病原菌的耐药性明显高于院外菌株。绿脓杆菌对庆大霉素和羧苄青霉素的耐药率分别为63.6％和54.5％。其它革蓝氏阴性杆菌院内株对常用抗生素如氨苄青霉素、羧苄青霉素、庆大霉素和妥布拉霉素的耐药率分别为82.5％、 67.5％、47.5％和45％。革蓝氏阳性球菌院内株的耐药性也很严重,表葡菌对多种半合成青霉素类、红霉素、复方新诺明甚至万古霉素的耐药率达60％以上。同时分离出耐甲氧西林金葡菌。     

In vitro metabolic study of temsirolimus: preparation, isolation, and identification of the metabolites.

The in vitro metabolism of temsirolimus, (rapamycin-42-[2,2-bis-(hydroxymethyl)]-propionate), an antineoplastic agent, was studied using human liver microsomes as well as recombinant human cytochrome P450s, namely CYP3A4, 1A2, 2A6, 2C8, 2C9, 2C19, and 2E1. Fifteen metabolites were detected by liquid chromatography (LC)-tandem mass spectrometry (MS/MS or MS/MS/MS). CYP3A4 was identified as the main enzyme responsible for the metabolism of the compound. Incubation of temsirolimus with recombinant CYP3A4 produced most of the metabolites detected from incubation with human liver microsomes, which was used for large-scale preparation of the metabolites. By silica gel chromatography followed by semipreparative reverse-phase high-performance liquid chromatography, individual metabolites were separated and purified for structural elucidation and bioactivity studies. The minor metabolites (peaks 1-7) were identified as hydroxylated or desmethylated macrolide ring-opened temsirolimus derivatives by both positive and negative mass spectrometry (MS) and MS/MS spectroscopic methods. Because these compounds were unstable and only present in trace amounts, no further investigations were conducted. Six major metabolites were identified as 36-hydroxyl temsirolimus (M8), 35-hydroxyl temsirolimus (M9), 11-hydroxyl temsirolimus with an opened hemiketal ring (M10 and M11), N- oxide temsirolimus (M12), and 32-O-desmethyl temsirolimus (M13) using combined LC-MS, MS/MS, MS/MS/MS, and NMR techniques. Compared with the parent compound, these metabolites showed dramatically decreased activity against LNCaP cellular proliferation.     

Reconstruction of the thumb and radial side of palm--a report of 6 cases

Since 1985, on the basis of anatomic study of dorsal pedal artery, thumb and radial side of palm reconstruction have been successfully performed in one stage by using opposite composite dorsal pedal flap including the second toe, the second metatarsal and the first toe web. Because they were all distributed by dorsal pedal artery and great saphenous vein, dissecting these tissues was not difficult. Good function and cosmetic appearance were achieved following reconstruction.