Targeted Thrombolytic Therapy

Venous and arterial thrombosis are closely related to many severe diseases, especially to cardiovascular and cerebrovasular disorders. Thrombolytic therapy has been proven to be an effective method to treat such disease, which decreased the mortality and morbidity greatly.     

早期应用纳洛酮治疗急性重症颅脑损伤

目的 观察早期应用纳洛酮对急性重症颅脑损伤的临床疗效及对改善预后的影响.方法 62例急性重症颅脑损伤患者按就诊顺序分为治疗组30例和对照组32例,所有患者均给予脱水剂、镇静类、钙离子拮抗剂等药物,以及吸氧、支持、亚低温冬眠和抗感染治疗.治疗组除采用以上常规处理外,均在入院后6 h内应用纳洛酮,剂量为0.4 ms/(kg·d),生理盐水稀释至500 ml,用输液泵24 h持续静脉输入,3 d后改为0.1 mg/(kg·d),7 d后停药,观察2组患者生命体征、格拉斯哥昏迷量表评分、觉醒时间、呼吸衰竭纠正时间,并进行统计学分析.参考格拉斯哥预后量表判断预后.结果 治疗组恢复良好10例(33.3%),死亡7例(23.3%),觉醒时间为(7.6±4.5)d,呼吸衰竭纠正时间为(6.6±3.7)d;对照组恢复良好7例(21.9%),死亡12例(37.5%),觉醒时间为(10.4±4.72)d,呼吸衰竭纠正时间为(9.9±4.1)d,2组差异均有统计学意义(P<0.05或P<0.01).结论 早期使用纳洛酮可降低急性重型颅脑损伤的致残率、病死率,减轻脑水肿,促使脑神经功能恢复,改善生活质量.     

阿片肽与缺血性脑损伤

阿片肽及其受体系统在缺血性脑损伤的病理生理发展过程中具有非常重要的作用。其在缺血性脑损伤中的作用尚存争议，本文综述了阿片肽及其受体系统在缺血性脑损伤中的作用及其可能机制，有助于探索阿片肽在围术期的合理应用，为缺血性脑损伤防治研究提供新方向。     

Cholera Toxin B-Mediated Targeting of Lipid Vesicles Containing Ganglioside GM1 to Mucosal Epithelial Cells

Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1. Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles. Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [K_d = 7.8 × 10^–4 M lipid (Caco-2) and 7.6 × 10^–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells. Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa.     

Cyclic analogues of Thr6-bradykinin,N8-Lys-bradykinin and endo-Lys8a-vespulakinin 1

Syntheses are described of the endo-Lys^8a-vespulakinin 1 and of cyclo-Thr⁶- and cyclo-N^ε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys^8a-VSK-1 and Thr⁶-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its N^α-Boc-[(Gal β)Thr³, (Gal β)Thr⁴]-analogue, were used to prepare N^α-(1–8 VSK 1)-cyclo-N^ε-kallidin and N^α-[(Gal β)Thr³, (Gal β)Thr⁴, 1–8 VSK 1]-cyclo-N^ε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995.     

Antibody reactivity to a synthetic peptide (P62) of the Epstein-Barr nuclear antigen in sera of patients with X-linked lymphoproliferative syndrome

An enzyme-linked immunosorbent assay (ELISA) was used to measured IgG antiboody titers againt a synthetic peptide whose sequence was derived from the glycine-alanine repeating region of Epstein-Barr virus nuclear associated antigen 1 (EBNA-1). Antibody titers were determined in sera from 15 normal subjects, sera from 21 normal male siblings of X-linked lymphoproliferative syndrome (XLP) patients, from 20 XLP patients comprising a total of 42 samples, and ten samples before and ten samples after gamma-globulin therapy in ten patients with XLP. Data analysis demonstrated that while there are differences between the ELISA and ACIF, they appear to measure a similar response as demonstrated by their correlation coefficient (0.77) and the GMT to EBNA observed by both methods. No cross-reactivity of cytomegalovirus antibodies to the EBNA-1 peptide was observed by immunobv using adsorption against AD-169 infected MRC-5 cells.. However, non-specific binding was observed if samples were not pre-incubated in a 10% goat serum PBS-Tween 20 solution. This pre-treatment removed the non-specific binding that falsely elevated GMT in approximately 15% of both normal and XLP samples in ELISA. The ELISA system appears to be a sensitive, reproducible and objective test that may be useful for assessing the antibody responses of patients to the EBNA-1 protein.     

不同微生物诱导家蝇幼虫表达抗菌肽的特性

研究不同微生物诱导家蝇幼虫表达的抗菌肽特性.用3种不同的病源菌通过针刺感染的方法诱导家蝇幼虫表达抗菌肽,通过Sephadex G25分离,用Hult mark改进法和抑菌圈测定法作抑菌试验,用毛细管电泳（CE）分析不同微生物诱导得到的抗菌肽样品差异,检测抗菌肽的热稳定性和酸碱耐受性.发现不同微生物诱导产生的家蝇抗菌肽具有广谱抑菌性,但不同样品对不同病源菌抑菌活性有差异,不同测定抑菌效果的方法对抑菌结果有影响,各种抗菌肽样品CE蛋白谱具有明显不同.抗菌肽样品都具有热稳定性和酸碱耐受性.说明不同微生物诱导产生的家蝇抗菌肽类型以及抗菌肽含量与诱导源有关,抗菌肽为家蝇幼虫体内固有成分,诱导增加了抗菌肽的表达量同时刺激新抗菌肽的产生.用志贺氏菌、金黄色葡萄球菌、鼠伤寒沙门氏菌诱导家蝇幼虫可产生较多含量高活性好的抗菌肽.     

双特异抗体介导的人单核—巨噬细胞对荷人肝癌裸鼠的抑制作用

观察双特异性单克隆抗体介导的人单核－巨噬细胞在裸鼠体内对肝癌生长的抑制作用。用化学交联法制备双特异性单克隆抗体ＨＡｂ１８－ＭＡｂ７及ＨＡｂ１８Ｆ（ａｂ）２－ＭＡｂ７Ｆ（ａｂ＇＿２，并将其与单核－巨噬细胞－同注入荷人肝癌裸鼠体内，观察肿瘤体积的变化。     

Identifying target segments of male drinkers for health promotion

Data from a 1988 national drinking survey was cluster analysedto identify different types of male drinkers, to assist in thetargeting of health promotion strategies. Of the five segmentsgenerated by the clustering, one labelled Young Heavy DrinkingMales was identified as the most appropriate target segment,because although they were the segment reporting the highestlevel of alcohol-related problems they were also the segmentmost likely to feel they were drinking too much They were thereforethe segment most likely to be responsive to advertising thatsought to support people who wanted to change their drinkinghabits. They were also the most appropriate target for the longer-termgoal of changing the climate of opinion regarding the acceptabilityof more moderate drinking. Comparisons with two previous clusteranalyses showed a high degree of similarity, suggesting thatclustering is a reliable vehicle for identifying drinker types.     

Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.