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.     

氧化亚氮联合利多卡因行无痛人工流产术280例临床分析

目的: 探讨吸入 50%氧化亚氮 (N2O) 与 50%氧气 (O2 ) 的混合气体联合宫颈注射 2%利多卡因进行无痛人工流产术 (人流术) 的有效性和安全性。方法: 将人流术 580例分为A、B两组。其中A组 280例吸入 50%氧化亚氮 (N2O)与 50%氧气的混合气体联合宫颈注射 2%利多卡因进行无痛人流术, 称为联合组; B组 300例, 不用任何药物, 为对照组, 分析比较两组手术中镇痛效果, 宫口松弛情况, 手术出血量, 人流综合反应。结果: 联合组镇痛完全, 有效率达 97 5%。宫口完全松弛率 97 9%。两组比较有显著性差异 (P<0 05)。结论: 吸入氧化亚氮联合宫颈注射利多卡因进行无痛人流术, 镇痛效果确定, 人流时受术者意识处于朦胧状态, 安静, 无痛苦, 不良反应少, 苏醒快等。     

VITROS 250全自动干化学分析仪的评价

目的评价美国强生VITROS250全自动干化学分析仪器。方法运用相关统计学方法对VITROS250全自动干化学分析仪的精密度、相关性、抗胆红素干扰方面进行分析。结果VITROS250全自动干化学分析仪精密度高,回收率高,相关性好,抗干扰能力强。结论VITROS250全自动干化学分析仪适用于临床实验诊断中心(检验科)急诊化验室生化项目的检测。     

Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (beta 121----Gln) in a Batak Indonesian family

A Batak Indonesian from North Sumatra with hemoglobin (Hb) D Punjab (alpha 2 beta 2 121----Gln) and hemoglobin Constant Spring (Hb CoSp) is described. The 24-year-old man did not have clinical symptoms, and his hematological indices were normal. However, he had a persistent slight elevation of fetal hemoglobin level. His mother and his brother were heterozygous for Hb D Punjab; his father had Hb CoSp trait. A sister did not have any abnormal hemoglobin. To show the exact molecular defect leading to the synthesis of Hb CoSp in this family, genomic DNA from the father was analyzed by hybridization with synthetic oligonucleotides. Genomic DNA was digested with Sst I and Hind III producing a 1.05-kb fragment from the 3' end segment of the alpha 2-globin gene, including the termination codon. Two nonadecamers were synthesized to serve as probes: one, entirely homologous to the normal 3' end of alpha 2A-globin gene sequence, including the termination codon TAA, the other different from it by a replacement of the T in the termination codon TAA with C, changing it to CAA, the codon for the amino acid glutamine. DNA from normal controls gave a positive signal with the normal alpha 2TAA oligonucleotide probe but negative with the alpha 2 CAA probe. The father of propositus who had Hb CoSp trait gave a positive signal with the normal alpha 2TAA oligonucleotide probe as well as with the alpha 2CAA oligonucleotide probe, showing him to be heterozygous for the alpha 2CAA-globin gene. This result shows that the Hb CoSp in the Batak family is indeed due to a replacement of T by C in the TAA termination codon of the alpha 2-globin gene changing it to CAA the condon for glutamine. This explains the resulting readthrough of the untranslated sequence of the mRNA.     

Effect of Cycloheximide on the Adaptive Response Induced by Low Dose Radiation

Human lymphocytes pre-exposed to 10 mGy or 50mGy of X-rays become less sensitive to subsequent large dose irradiation,exhibited lower rate of chromosome aberration than expected.This adaptive response could be inhibited by cycloheximide,a protein synthesis inhibitor for successive 2h period ranging from 0.5h before to 4h after the low dose exposure,indicating that the adaptive response was directly related with the protein synthesis.     

实验性糖尿病大鼠肾脏损害和脂质过氧化物水平的动态研究

动态观察实验性糖尿病大鼠于发病后２、４、６、１２、和１６周肾脏损害指标和肾脏脂质过氧化物（ＬＰＯ）水平的变化。结果表明，发病后各观察时间．或糖尿病大鼠２４ｈ尿Ａｌｂ、β２──ＭＧ排泄量和尿ＮＡＧ活性均明显增高，而２４ｈ尿ＴＨＰ排泄量显著降低，肾脏ＬＰＯ水平明显升高。其中尿ＮＡＧ活性、ＴＨＰ排泄量和肾脏ＬＰＯ水平均随病程延长而更趋明显。这些结果提示，在糖尿病早期除有肾小球功能损害外，肾小管也明显受损，过氧化损伤在糖尿病肾病发病中可能是重要因素之一。尿Ａｌｂ、β２──ＭＧ、ＴＨＰ含量和ＮＡＧ活性可作为糖尿病肾病早期肾损害的敏感指标。     

Graves病的发病与社会心理因素

对１０７例甲状腺机能亢进症患者和９１名正常人采用艾森克个性问卷及自编社会环境的调查显示：４６．９４％的患者起病前有负性生活事件发生，个性特征甲亢组神经不稳定型及掩饰性评分显著高于正常组，有显著性差异，此结果提示甲亢患者存在明显个性缺陷和负性生活事件，这些因素可作为甲亢发病的一种诱因。     

B超和彩色多普勒超声对原发性甲状旁腺功能亢进的诊断价值

报道应用Ｂ型超声及彩色多普勒超声对７６例原发性甲状旁腺功能亢进症进行系统研究的结果。总的诊断效率：敏感性７２％，特异性９２％，正确率８７％，阳性预测值６９％，阴性预测值９２％，以正常位置腺瘤的诊断效率最高，Ｂ型超声及彩色多普勒超声的诊断效率进行比较，敏感性有显著差异（Ｐ＜０．０５），正确率有非常显著差异（Ｐ＜０．０１），说明彩色多普勒超声的诊断正确率较高。本文还讨论了Ｂ型超声对甲状旁腺病变的定位价值、各类甲状旁腺病变的鉴别；同时对异位甲状旁腺病变、原发性甲旁亢危象、各种影像诊断的比较等也进行了讨论。     

精神分裂症患者外周血淋巴细胞姊妹染色单体交换的初步观察

检测了18例精神分裂症患者和25例健康人的SCE频率,结果提示患者组SCE频率显著高于对照组,与年龄、性别、病程、临床类型、有无遗传家族史无明显相关。研究提示SCE频率增高似与疾病本身有关。