米格列奈片人体药动学研究

 目的 考察米格列奈在中国健康人体内的药动学特征， 估算主要药动学参数，为本品的临床应用提供参考。 方法 12 名健康受试者，按平行三周期设计方法进行 3 个剂量组（分别为 5 ， 10 ， 20 mg ）的单次 po 给药。给药后按预定时间点抽取静脉血 3.5 mL ，用液相色谱 - 质谱联用法测定血浆中米格列奈的浓度，估算药动学参数。 结果 12 名受试者单次口服米格列奈片 5 ， 10 和 20 mg 后， <> ρ _max 分别为（ 742.86 ± 272.60 ），（ 1 447.42 ± 590.64 ）和（ 2 614.43 ± 721.09 ） μg·L^-1 ； t _max 分别为 （ 0.32 ± 0.12 ），（ 0.34 ± 0.11 ）和（ 0.35 ± 0.11 ） h ； t _1/2 分别为（ 1.61 ± 0.39 ），（ 1.91 ± 0.66 ）和（ 1.70 ± 0.38 ） h ； AUC_0-12 分别为（ 1 006.27 ± 218.09 ），（ 1 928.35 ± 596.17 ）和 (3 677.82 ± 901.27) μg·h·L^-1 。 结论 米格列奈 在人体内的吸收、分布、代谢和排泄均为一级动力学过程，吸收、消除速率呈现剂量非依赖性。     

顶空—气相色谱法测定盐酸洛美利嗪中乙腈残留量

目的：建立盐酸洛美利嗪原料药中乙腈残留量的测定方法。方法：采用顶空进样法，80％DMF水溶液为溶剂，平衡温度70℃，平衡时间40min，气相色谱条件：采用不锈钢填充色谱柱：柱长2m，内径3mm，粒径为0.25-0.32mm的二乙烯苯与乙基乙烯苯共聚物有机担体为填料，柱温130℃，FID检测器，检测器温度250℃，氮气为载气，流速50mL.min^-1。结果：乙腈在23．46－234．6μg.mL^-1的浓度范围内呈良好的线性关系（r=0.9978)，回收率为96．7％（RSD＝3．8％），检出限小于40μg.g^-1。结论：本方法简单，快捷且灵敏度高，可以用于盐酸洛洛美利嗪中乙腈残留量的控制。     

Effects of exercise on muscle activation and metabolism in multiple sclerosis

We investigated the role of metabolism in muscle fatigue during voluntary exercise in persons with mild multiple sclerosis (MS). Six MS and 8 healthy control subjects performed intermittent, progressive, isometric contractions of the ankle dorsiflexors, during which we measured maximum voluntary force (MVC), inorganic phosphate (Pi), phosphocreatine (PCr), and pH. During exercise. MVC fell sooner in MS, but by the end of exercise the relative decrease in MVC was similar in both groups. In contrast, at the end of exercise Pi/PCr increased to 1.86 ± 0.22 in controls but to only 0.66 ± 0.04 in MS (P < 0.01); likewise, pH was 6.75±0.04 in controls and unchanged (7.06 ± 0.04) in MS (P <0.01). The smaller metabolic change at the same relative exercise intensity suggests a failure of muscle activation that is present even in mild MS. Neurophsyiologic measures of activation indicated some central activation failure and no neuromuscular junction impairment in MS, and suggested that activation failure beyond the muscle membrane(excitation–contraction coupling) may be important in MS. We conclude that metabolic factors do not play a significant role in the development of muscle fatigue during voluntary exercise in mild MS. © 1994 John Wiley & Sons, Inc.     

白桦树皮挥发油成分的研究

采用气相色谱－质谱联用方法，对白桦树皮挥发油进行了研究，共鉴定出２９种化合物，主要成分为２－氧代丙酸（５３．５４％）。     

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

健康志愿者１０名，随机交叉口服硫酸吗啡控释片（ＣＲＭＳ）３０ｍｇ（３０ｍｇ×１）和硫酸吗啡普通片（ＩＲＭＳ）２０ｍｇ（１０ｍｇ×２），分别于服药前后各时点取静脉血，用ＧＣＭＳ测定血浆中吗啡含量。以药代软件程序处理，分别求得ＣＲＭＳ和ＩＲＭＳ的Ｃｍａｘ为１９．３８±３．８０和２１．２７±６．２１ｎｇ／ｍｌ；ｔｍａｘ为２．３６±０．３７ｈ和０．５５±０．１６ｈ；ｔ１／２β为３．５３±０．８７ｈ和３．０３±０．７４ｈ，曲线下面积ＡＵＣ为１４５．１５±１７．６５和９３．０８±１６．６５ｎｇ·ｈ／ｍｌ。癌症病人多次口服硫酸吗啡至稳态，ＣＲＭＳ和ＩＲＭＳ的峰浓度分别为２７．４３±０．３３ｎｇ／ｍｌ，２２．６８±０．１６ｎｇ／ｍｌ；谷浓度分别为１９．４５±１．４４ｎｇ／ｍｌ；１８．１４±０．４９ｎｇ／ｍｌ。     

Transjugular intrahepatic cavoportal shunt for Budd–Chiari syndrome

Budd–Chiari syndrome (BCS) is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for BCS are limited. We report a case of a 21-year-old woman with protein S and C deficiency with gross ascites. Treatment with transjugular intrahepatic portosystemic shunt (TIPS) was attempted, which revealed occluded hepatic veins, so transcaval TIPS was performed. No serious procedure-related complication occurred. After successful shunt creation, the patient's symptoms subsided and she was discharged and followed up for 6 months.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

6－甲氧基正丁苯酞在大鼠肝微粒体中的代谢研究

报道了用ＧＣ／ＭＳ方法及衍生化技术研究６甲氧基正丁苯酞（ＭＢＰ）在大鼠肝微粒体中的代谢转化结果。６甲氧基正丁苯酞在苯巴比妥（ＰＢ）诱导的大鼠肝微粒体中主要转化为３羟基、γ羟基取代物，６羟基正丁苯酞与一个环氧化代谢产物     

Identification of GRASP-1 as a novel 97 kDa autoantigen localized to endosomes

We have identified an autoantigen that is recognized by antibodies from an 18-year-old female with a history of recurrent infections who later in her clinical course developed Raynaud's phenomenon and telangiectasias. By indirect immunofluorescence (IIF), the index serum produced a unique cytoplasmic discrete speckled (CDS) staining pattern that partially colocalized with early endosome antigen 1 (EEA1) but not Golgi complex or other cytoplasmic organelles in HEp-2 cells. When HEp-2 cells were treated with 0.1 N HCl, the cytoplasmic speckled staining of the index serum was markedly decreased, suggesting that the reactive antigen was soluble. Western blot analysis showed a reactive approximately 97 kDa protein in a saline soluble protein preparation from HeLa cells. Mass spectrometric analysis of the excised 97 kDa band that was immunoprecipitated from HeLa cell extracts identified GRASP-1 as a possible target. The index serum and anti-GRASP-1 antibodies colocalized to structures in the cytoplasm of HEp-2 cells. Synthetic peptides representing the full-length GRASP-1 protein were used to identify reactive epitopes. Like many other cytoplasmic autoantigens, GRASP-1 has numerous coiled-coil domains throughout the protein with the exception of short segments at the amino and carboxyl terminus.     

Thermal gradients in microtitration plates. Effects on enzyme-linked immunoassay

Temperature studies of microtitration plates demonstrate that the use of a common bacteriology incubator for heating the plates can cause a phase lag of over 30 min for the fluid in the wells to reach 37°C from ambient temperature, and that a temperature gradient of as much as 1.6°C can exist between the peripheral and center wells. This gradient is a cause of the ‘rim’ or edge effect noted in enzyme immunoassay using microtitration plates. The problem is corrected by the use of a specially designed forced air microtitration plate incubator.