硫酸乙酰肝素蛋白聚糖与病毒感染

目的综述硫酸乙酰肝素蛋白聚糖（heparan sulfate proteoglycan,HSPG）与病毒感染的关系。方法查阅近年文献,进行整理和归纳。结果细胞表面HSPG可作为病毒感染的初始结合受体,并对病毒有储存和保护作用,另外HSPG也参与病毒的侵入过程并与病毒转录反式激活有关。结论细胞表面HSPG与病毒感染有着密切的关系。通过对HSPG在病毒感染过程的机制研究,一方面为开发抗病毒药物提供新的思路,另一方面可以通过提高病毒载体的靶向性和感染率,从而提高基因治疗的效果。     

Epitope-Dependent Selective Targeting of Thrombomodulin Monoclonal Antibodies to Either Surface or Intracellular Compartment of Endothelial Cells

Abstract

Internalization of antibodies to thrombomodulin (TM) may provide a mechanism for intraendothelial targeting of drugs or genes. This study characterized three monoclonal antibodies against human TM (mAb 1009,1029, and 1045) and examined their internalization by human umbilical vein endothelial cells (HUVEC). It assessed binding of antibodies to recombinant human TM containing chondroitin sulfate (complete, cTM) and TM lacking chondroitin sulfate (incomplete, iTM). Direct RIA, indirect RIA, and ELISA and competitive ELISA show that (1) mAb 1009 binds to both cTM and iTM independently of divalent cations; (2) binding of mAb 1029 to iTM requires divalent cations, while binding to cTM is cation-independent; (3) mAb 1045 binds selectively to cTM independently of divalent cations. Binding of all three antibodies to the surface TM in HUVEC at 4°C was similar by indirect immunostaining. In permeabilized HUVEC, however, mAb 1009 and 1029 provide brighter intracellular staining than mAb 1045. Uptake of ¹²⁵I-mAb 1009 by HUVEC at 37°C was significantly higher than that of ¹²⁵I-mAb 1045. Low temperature markedly suppresses binding of ¹²⁵I-mAb 1009 to HUVEC, but has no effect on ¹²⁵I-mAb 1045 binding. About 80% of radiolabeled mAb 1045 bound to HUVEC at 37°C could be eluted by acidic buffer from the cell surface, but only 40% of mAb 1009 and 1029 was elutable at these conditions. About 70-80 % of ¹²⁵I in cell lysates was TCA-soluble after HUVEC incubation with either mAb 1009 and 1029, but only 10 and 2.5% of ¹²⁵I was TCA-soluble in cell lysates and medium after 90 min incubation with ¹²⁵I-mAb 1045 at 37°C. Therefore, HUVEC internalize and degrade an mAb that reacts with iTM, yet do not internalize an mAb that reacts selectively with cTM (mAb 1045). This result implies that either HUVEC do not internalize cTM constitutively or mAb 1045 suppresses TM internalization. Therefore, antibodies recognizing different TM epitopes might provide targeting of drugs to different cellular compartments.     

硫酸锌对大鼠毒性的某些生物化学和病理学研究

硫酸锌对大鼠的急性毒性属低毒物质,对小鼠属中等毒性物质。大鼠90天喂养试验硫酸锌摄入量为68.5mg/kg及其以上时,血清铜蓝蛋白活性明显降低,血清铁和高密度脂蛋白胆固醇降低,肾脏和睾丸出现多种病变,如肾小球肿胀和蛋白管型等,睾丸基膜增厚和间质细胞增生等。摄入量在19.5mg/kg及其以下时,不产生任何毒性作用。提示硫酸锌的最大无作用剂量为19.5mg/kg。     

车间空气中硫酸二甲酯卫生标准研究

本标准是根据毒理学实验，劳动卫生学调查，职业人群流行病学调查并参考国外标准，结合我国国情，提出车间空气中硫酸二甲酯最高容许浓度为０．５ｍｇ／ｍ＾３（皮）。     

DX-120型离子色谱法测定水中硫酸盐的不确定度评定

目的对DX-120型离子色谱法测定水中硫酸盐含量进行不确定度评估。方法采用离子色谱法测定水样(A、B)中硫酸盐含量,分析不确定度的来源。结果不确定度分量有重复性、标准曲线、标准溶液和样品溶液定容。综合不确定分量值水样A为0.158 mg/L,水样B为1.66 mg/L。水样测定结果及不确定度表达(k=2):A水样中SO24-含量为(12.0±0.4)mg/L,B水样中SO42-含量为(148±4)mg/L。结论该方法对水中硫酸盐含量进行的不确定度评估合理,可靠。     

Évaluation de l’utilisation du sulfate de magnésium dans la prévention secondaire de l’éclampsie : étude rétrospective sur 39 cas

Introduction

The use of magnesium sulfate (MgSO₄) has been advocated since 2000 in France in the management of eclampsia. The aim of this study was to determine the frequency of use of this treatment for eclampsia in a French department.

Patients and methods

All patients obstetrical patients admitted to Critical Care Units of Seine-Maritime for eclampsia over a period of 7 years (2002–2008) were included. Obstetric data, the treatment used for eclampsia and pre-eclampsia and maternofetal complications were collected. The primary outcome parameter was the use of MgSO₄ in the secondary prevention of eclampsia.

Results

Thirty-nine patients were included. Nineteen patients (48%) had eclampsia in prepartum, three (8%) in per-partum and 17 (44%) in post-partum periods. The use of MgSO₄ in the secondary prevention of eclampsia was observed in 92% of cases (36/39). Primary prevention was seen in 8% of cases. The duration of treatment was 2 days (1–7 days). The maternal and perinatal mortality was respectively 2.5 and 11%.

Conclusion

In this study, the use of MgSO₄ in the secondary prevention is frequent. This result emphasizes the importance of the recommendations of learned societies in the homogenization of the management of rare but serious conditions such as eclampsia.     

IUGR胎鼠脑组织线粒体酶活性改变及硫酸镁的保护作用

目的 :探讨胎儿宫内生长迟缓 (IUGR)胎鼠脑组织线粒体ATP酶活性、线粒体Ca2 ,Mg2 含量改变及硫酸镁对其影响。方法 :采用被动吸烟方法建立孕鼠IUGR模型 ,部分孕鼠 (实验A组 )尾静脉注射硫酸镁 ,测定各组胎鼠脑组织线粒体Na -K -ATP酶 ,Ca2 -ATP酶 ,Mg2 -ATP酶活性及线粒体Ca2 ,Mg2 含量。结果 :IUGR胎鼠脑组织线粒体三种酶的活性均下降 ,线粒体Ca2 含量增高 ,Mg2 离子含量降低 ,应用硫酸镁对上述指标具有明显的改善作用 (P <0 .0 5 )。结论 :硫酸镁可以改善IUGR胎鼠脑线粒体酶活性 ,对脑组织具有保护作用。     

非小细胞性肺癌患者血清硫酸粘多糖片段的检测及其临床意义

目的 :探讨血清硫酸粘多糖片段的检测对非小细胞性肺癌诊断的临床应用价值 ,为肺癌的早期诊断提供依据。方法 :应用乳胶凝集法检测非小细胞性肺癌患者血清硫酸粘多糖片段 ,同时应用化学发光法检测CEA。结果 :非小细胞性肺癌患者血清硫酸粘多糖阳性率为 86 2 0 % ,显著高于血清CEA阳性率 5 2 87% (P <0 0 5 )。在肺癌早期血清硫酸粘多糖阳性率即可达78 2 6 %。其检测敏感性为 86 2 0 % ,特异性为 94 83% ,两者联合检测阳性率可达 91 95 %。结论 :血清硫酸粘多糖是诊断及早期诊断非小细胞性肺癌的可靠指标 ,敏感性、特异性高 ,和CEA联合检测 ,可提高阳性率。     

离子色谱法同时测定葡萄糖酸钙及其杂质(Cl-,SO42-)的含量

本文采用Waters ILC-1离子液相色谱仪,IC-PAK A50×4.6mm色谱柱,pH6.61×10^-3mol/L邻苯二甲酸溶液为流动相,430型电导检测器检测,由外标法和外标单点校正法同时测定了葡萄糖酸钙及其杂质(Cl^-,SO₄^2-)的含量。方法简便、快速,测定结果与中国药典法一致。外标法和外标单点校正法测定Cl^-,SO₄^2-的平均回收率为100.8%和100.2%,相关系数分别为0.9951(n=8)和0.9961(n=8)。     

Development and validation of a novel LC non-derivatization method for the determination of amikacin in pharmaceuticals based on evaporative light scattering detection

A novel method for the direct determination of the aminoglycoside antibiotic amikacin and its precursor component kanamycin was developed and validated, based on reversed phase LC with evaporative light scattering detector (ELSD). ELSD response to amikacin was found to be enhanced by: (a) use of ion-pairing acidic reagents of increased molecular mass, (b) increase of mobile phase volatility and (c) decrease of peak width and asymmetry (obtained by controlling the mobile phase acidity and/or ratio of organic solvent to water). Utilizing a Thermo Hypersil BetaBasic C₁₈ column, the selected optimized mobile phase was water–methanol (60:40, v/v), containing 3.0 ml l⁻¹ nonafluoropentanoic acid (18.2 mM) (isocratic elution with flow rate of 1.0 ml min⁻¹). ELSD experimental parameters were: nitrogen pressure 3.5 bar, evaporation temperature 50 °C, and gain 11. Amikacin was eluted at 8.6 min and kanamycin at 10.4 min with a resolution of 1.5. Logarithmic calibration curves were obtained from 7 to 77 μg ml⁻¹ (r > 0.9995) for amikacin and 8 to 105 μg ml⁻¹ (r > 0.998) for kanamycin, with a LOD equal to 2.2 and 2.5 μg ml⁻¹, respectively.

In amikacin sulfate pharmaceutical raw materials, the simultaneous determination of sulfate (t_R = 2.3 min, LOD = 1.8 μg ml⁻¹, range 5–40 μg ml⁻¹, %R.S.D. = 1.1, r > 0.9997), kanamycin and amikacin was feasible. No significant difference was found between the results of the developed LC–ELSD method and those of reference methods, while the mean recovery of kanamycin from spiked samples (0.5%, w/w) was 97.3% (%R.S.D. ≤ 2.0, n = 6). Further, the developed method was applied for the determination of amikacin in pharmaceutical formulations (injection solutions) without any interference from the matrix (recovery from spiked samples ranged from 95.6 to 103.8%).