尼莫地平片剂生物利用度和健康人药代动力学研究

用高效液相色谱法测定了6名健康志愿者口服二种尼莫地平片剂的相对生物利用度和药代动力学参数。结果表明:尼莫地平在人体内的浓度—时间数据可用一室开放模型拟合,主要动力学参数与国外文献报道一致。新片剂和普通片的人体相对生物利用度分别为82.39%和16.01%。     

Expression of TAL-1 proteins in human tissues

Rearrangement of the tal-1 gene (also known as SCL or TCL-5) occurs in at least 25% of T-cell acute lymphoblastic leukemias (T-ALLs) and results in the aberrant expression of tal-1 mRNA in the neoplastic cells. Also, tal-1 mRNA is constitutively expressed in erythroid precursors and megakaryocytes. This report describes a direct immunocytochemical study of the distribution and localization of TAL-1 protein in normal human tissues and cell lines using four monoclonal antibodies raised against recombinant TAL-1 proteins. One of these reagents recognizes a protein of 41 kD molecular weight in in vitro- translated TAL-1 proteins, two others recognize proteins of 39 and 41 kD molecular weight, and the fourth antibody also recognizes a TAL-1 protein of 22 kD in addition to the 39- and 41-kD proteins. These anti- TAL-1 antibodies label the nuclei of erythroid precursor cells and megakaryocytes in fetal liver and adult bone marrow. The punctate pattern of nuclear labeling suggests that TAL-1 may comprise part of a novel nuclear structure, similar to that recently found for the PML protein. The nuclei of T cell lines known to express mRNA encoding the full-length TAL-1 protein (eg, CCRF-CEM, RPMI 8402, and Jurkat) are also labeled. A study of normal human tissues (including thymus) showed labeling of smooth muscle, some tissue macrophages, and endothelial cells. TAL-1 protein is undetectable in other cell types. These reagents may play an important role in the diagnosis of T-ALL and could also be used in the context of lymphoma diagnosis on routinely fixed material.     

高效液相色谱法测定尿中美芬妥英及代谢产物4'-羟基美芬妥英

A simple, sensitive and reproducible HPLC assay is described for the determination of mephenytoin and 4'-hydroxymephenytoin in human urine. Phenobarbital was used as an internal standard.The compounds were separated on a U-Bondapack RP-C₁₈ column using a mobile phase of and the UV detectou was set at 210 nm. Calibration curves in the range 0.05～1.00ug/ml for mephenytoin and 0.5～100.0ug/ml for 4'-hydroxymephenytoin were linear (r=0.9998and r=0.9992,respectivesy). The average recovery was 95.10±2。95%,and the relative standard devia- tion within day and day to day was less than 10%。The detection limit for mephenytoin was 25mg/ml and 4‘-hydroxymephenytoin was 50mg。ml。The method was used to study the metabolism of S-mephenytoin 4'-hydroxylatoin in 10healthy volunteers.The 12 h urinary metabolic ratio (MR)and hydroxylation index(HI)were calculated to express interindividual variation in metabolism. Two of them exhibited defective 4'-hydroxylation of S-mephenytoin as poor metabllizers (HI:1349.18 and 409.57;MR:105.29 and 8.25).In the remaining 8 subjects, the ranged from 1.68 to 6.71 and the MR ranged from 0.002 to 0.014,as extensive metabolizers of S-mephenytoin.     

粉防己碱对离体大鼠心脏钙反常的保护作用

粉防己碱(Tet)能明显抑制离体大鼠心脏钙反常时心肌组织LDH和蛋白的释出,减少无钙灌流时心肌组织Ca~(2+)丢失和Na~+堆积以及复钙灌流时心肌组织Ca~(2+),Na~+堆积和Mg~(2+),K~+丢失,并呈浓度依赖性。此外,钙反常时心肌组织中微量元素Fe,Zn含量下降,Cu含量增加,而Tet可抑制Fe及Zn含量的下降。维拉帕米(Ver)也有类似作用,电镜下,Tet可部分减轻钙反常时心肌组织超微结构的破坏。     

Lack of evidence of neurotoxicity following 8 weeks of treatment with tripotassium dicitrato bismuthate

Objective: To search for evidence of subclinical neurotoxicity in patients treated with tripotassium dicitrato bismuthate. Design: Prospective, controlled, triplicate study using urinary bismuth concentration, magnetic resonance imaging (MRI), nerve conduction studies, visual evoked response and a battery of 10 neuropsychological screening tests. Setting: Out-patient clinics, Walsgrave Hospital, Coventry, UK. Subjects: Fourteen dyspeptic patients; 8 (treatment group) treated with tripotassium dicitrato bismuthate one tablet q.d.s and 6 (control group) treated with ranitidine 150 mg b.d. for 8 weeks. Main outcome measures: Changes in urinary bismuth, MRI, nerve conduction studies, visual evoked response, and neuropsychological tests performed before, immediately after and 8 weeks after the cessation of treatment. Results: In the treatment group the median (range) urinary bismuth concentration was 1 (1–12) ng/ml before treatment, increased to 560 (140–1300) immediately after treatment (P < 0.01, Wilcoxon Rank Sum test) and was still significantly elevated (23 (7–53) ng/ml) 8 weeks after the cessation of treatment. In the patient who recorded the highest urinary bismuth, a high intensity signal appeared in the globus pallidus immediately after treatment and was still present (though diminished in intensity) 8 weeks after the cessation of treatment. This isolated MRI finding was not associated with evidence of subclinical neurotoxicity. No changes in the MRI, nerve conduction studies, visual evoked response and neuropsychological tests were observed among the other patients studied. Conclusions: Bismuth accumulation occurs in patients receiving a conventional course of treatment with tripotassium dicitrato bismuthate but this is not associated with significant changes in the nervous system.     

幽门螺杆菌感染的药物治疗新进展

0引言幽门螺杆菌(Helicobacter pyiori,H pylori)的发现已有20 a的历史.近20 a来,在胃肠病工作者全面而深入的研究下,H pylori已被确认是慢性胃炎和大部分消化性溃疡的重要病因,与胃黏膜相关性淋巴样组织(MALT)恶性淋巴瘤密切相关,与胃痛的关系也越来越受到人们的重视,世界卫生组织已经将H pylori列为第一类致癌因子,并明确为胃癌的危险因素.正是由于H pylori与胃十二指肠疾病的关系如此密切,H pylori感染的治疗一直是胃肠病工作者所关注的热门课题,根除H pylori能有效治愈溃疡,甚至可作为预防胃癌的工具之一.本文就H pylori感染的治疗现状及药物治疗过程中应注意的几个问题作一综述.     

(赤)-苯丙二醇胺类化合物的合成及抗心律失常活性

为探索关附甲素药效基团,进行结构改造,设计合成了13个(赤)-苯丙二醇胺类化合物(I_1～7,II_1～6)。用乌头碱诱发大鼠心律失常试验表明,多数化合物有一定的抗心律失常活性,其中I₂的抗VT活性及I₃的抗VP活性与关附甲素相近,苯环对位引入吸电性NO₂基(I_1～6)对活性不利。产物制备中发现,烯丙位N原子对Prevost反应的立体选择性有较大影响,将胺基乙酰化后可排除干扰顺利进行反应。