塞来昔布在类风湿性关节炎中对甲氨喋呤的药代动力学影响

目的：确定塞来昔布对于经常服用稳定剂量甲氨喋呤（ＭＴＸ）治疗类风湿性关节炎（ＲＡ）患者的肾脏清除率和血浆药代动力学方面的影响。方法：选取１４例至少已服用ＭＴＸ３个月,且每个星期的剂量稳定在５－１５ｍｇ,有类风湿关节炎的成年妇女,随机给予塞来昔布（２００ｍｇ．ｂｉｄ）或安慰剂单盲治疗,每一阶段７,分二阶段交叉试验,研究ＭＴＸ的药代动力学和肾脏平均清除率。结果：当ＭＴＸ和塞来昔布或安慰剂合用时,ＭＴＸ     

Prevention of transfusion-associated graft-versus-host disease: selection of an adequate dose of gamma radiation

To determine the optimal dose of gamma radiation necessary to inhibit T- lymphocyte function and prevent transfusion-acquired graft-versus-host disease (TA-GVHD), a donor plateletpheresis component was initially divided into ten 20-mL samples. One sample was not irradiated, while the other nine samples were treated with gamma radiation at doses ranging from 500 to 4500 cGy. T-lymphocyte function was subsequently measured by mixed lymphocyte cultures and mitogen stimulation assays. The results were assessed in each test by calculating the percentage of inhibition of each irradiated sample as compared to that of the unirradiated sample. The accuracy of the delivered dose of gamma radiation was measured with thermoluminescent dosimeters. It was concluded that a nominal dose of 3000 cGy (actual dose delivered, 2898 cGy) is the appropriate amount of gamma radiation needed to eliminate T- lymphocyte-mediated graft-versus-host disease.     

长期运动对十二指肠黏膜一氧化氮合成和铁贮存的调控效应

目的:观察长期运动对十二指肠黏膜一氧化氮合成和铁贮存的影响及一氧化氮对铁贮存的调节作用。方法:实验于2004-04/09在江苏大学医学院铁代谢研究室完成。①健康雌性SD大鼠40只,随机分为静息组、静息并应用一氧化氮抑制剂组、运动组、运动并应用一氧化氮抑制剂组,每组10只。②静息并应用一氧化氮抑制剂组和运动并应用一氧化氮抑制剂组饮用水中含有一氧化氮抑制剂(1g/L),运动组和运动并应用一氧化氮抑制剂组的大鼠游泳3个月。③3个月后分析各组大鼠血浆铁饱和度,一氧化氮浓度以及十二指肠黏膜一氧化氮含量和非血红素铁含量。结果:实验过程中死亡11只,进入结果分析29只(静息组8只、静息并应用一氧化氮抑制剂组5只、运动组8只、运动并应用一氧化氮抑制剂组8只)。①运动及一氧化氮抑制剂对大鼠血浆铁饱和度和一氧化氮浓度的影响:运动组的血浆铁饱和度低于静息组(P<0.01);运动并应用一氧化氮抑制剂组的血浆铁饱和度低于静息并应用一氧化氮抑制剂组(P<0.05),并且高于运动组(P<0.05)。运动组血浆一氧化氮浓度显著高于静息组(P<0.01);运动并应用一氧化氮抑制剂组的血浆一氧化氮浓度低于运动组(P<0.01),与静息并应用一氧化氮抑制剂组差别不显著(P>0.05)。②运动及一氧化氮抑制剂对大鼠十二指肠黏膜一氧化氮和非血红素铁含量的影响:运动组的十二指肠一氧化氮含量高于静息组(P<0.01);静息并应用一氧化氮抑制剂组的一氧化氮含量低于静息组(P<0.01);运动并应用一氧化氮抑制剂组的一氧化氮含量低于运动组(P<0.01),但高于静息并应用一氧化氮抑制剂组(P<0.01),与静息组差别不显著。与静息组比较,运动组和静息并应用一氧化氮抑制剂组的十二指肠黏膜非血红素铁含量均降低(P<0.05)。结论:静息状态下十二指肠黏膜细胞一氧化氮合成具有较高的紧张性,可能参与维持非血红素铁含量。长期运动可刺激十二指肠黏膜一氧化氮合成,降低铁贮存。但其机制是否涉及运动诱导的一氧化氮的直接作用以及是否参与铁吸收的调节有待于进一步研究。     

Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

变价态唐松草新碱—PVC膜离子选择电极的研制及解离常数的测定

本文研制了以四苯硼—唐松草新碱缔合物为电活性物质的变价态唐松草新碱—PVC膜电极。电极膜按电活性物质:PVC:DBP为1:8:8组成。该电极在pH 5.0～6.0,Ⅰ=0.05的NaCl—HCl溶液中Nernst响应范围为1×10^-3～1×10^-5mol/L。电极斜率为58.2 mV/logc。检测限为2.5×10^-6mol/L。用直接电位法考察了TDH⁺,TDH₂CF⁺⁺共存时溶液pH和电极斜率S的关系。用S—pH关系,测定了25℃,Ⅰ=0.05时的Ka₁值为(2.5±0.2)×10^-4,用E—pH关系,测定了25℃,Ⅰ=0.05时的Ka₂值为(8.1±0.9)×10^-8。     

柱前荧光标记高效液相色谱法对血浆中l-麻黄碱和d-伪麻黄碱的定量分析

l-麻黄碱和d-伪麻黄碱是生药麻黄中早为人知而至今仍被广泛用于临床的一对手性异构生物碱。由于二者为生药麻黄中的主要成分但药理活性不同,为便于临床监控及有效用药,高分辨高灵敏度的检测方法的开发迫在眉睫。本文以易于得到的dansylchloride为柱前荧光标识试剂,在确定了最佳衍生化及分离条件的基础上,建立了理想的色谱分析系统(线性检测范围1～800ng·ml^-1)。同时运用此方法,完成了对静注l-麻黄碱和d-伪麻黄碱后豚鼠血浆内该对手性异构体水平的考查,并且定量检测了服用中成药小青龙合剂后人血浆中的该对手性异构体。