白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。     

Asymptomatic autoimmune chronic active hepatitis in a male adolescent

We report a 12-year-old boy presenting with smooth muscle antibody-positive auto-immune chronic active hepatitis. Suspicion of the diagnosis arose after a routine blood test which revealed abnormal liver function tests. In spite of the presence of cirrhosis and patchy necrosis on liver biopsy, our patient never showed any clinical feature of impaired liver function. This observation demonstrates that auto-immune hepatitis may exist for a long time before clinical symptoms appear and probably explains why some cases of auto-immune hepatitis finally present as fulminant liver failure.     

The AmRo study: pregnancy outcome in HIV-1-infected women under effective highly active antiretroviral therapy and a policy of vaginal delivery

OBJECTIVE: To explore pregnancy outcome in HIV-1-positive and HIV-negative women, and mother-to-child transmission (MTCT) according to mode of delivery under effective highly active antiretroviral therapy (HAART). DESIGN: Cohort of 143 pregnant HIV-1-infected women including a matched case-control study in a 2:1 ratio of controls to cases (n=98). SETTING: Academic Medical Center in Amsterdam and Erasmus Medical Center in Rotterdam, the Netherlands. POPULATION: Consecutive referred HIV-1 infected pregnant women treated with HAART and matched control not infected pregnant women. MAIN OUTCOME MEASURES: MTCT, preterm delivery, low birthweight, pre-eclampsia. RESULTS: MTCT was 0% (95% CI 0-2.1%). Seventy-eight percent of HIV-1-infected women commenced and 62% completed vaginal delivery. The calculated number of caesarean sections needed to prevent a single MTCT was 131 or more. Preterm delivery rates were 18% (95% CI 11-27) in women infected with HIV-1 and 9% (95% CI 5-13) in controls (P=0.03). HAART used at <13 weeks of gestation was associated with a 44% preterm delivery rate compared with 21% when HAART was started at or after 13 weeks and 14% in controls. (Very) low birthweight and incidence of pre-eclampsia were not different between HIV-1 and controls. CONCLUSIONS: We have not demonstrated any MTCT after vaginal delivery in women effectively treated by HAART. The HAART-associated increase in preterm delivery rate is mainly seen after first trimester HAART use.     

The evidence for physiologic management of the active phase of the first stage of labor

The active phase of first stage labor is generally defined as the period between 3 cm to 4 cm to complete cervical dilatation, in the presence of regular uterine contractions. Most women will experience this portion of labor within hospital obstetric units, where care commonly features restriction to bed, electronic fetal monitoring, early treatment of "slow" labors, and few pain management options beyond epidurals and narcotics. However, the available evidence on appropriate care for healthy childbearing women favors activity in labor, intermittent auscultation, patience from caregivers, and nonpharmacologic methods of pain relief. This article reviews the evidence for care practices that support physiologic labor. Modifying intrapartum care to reflect current evidence will improve women's health, and will require a multilevel approach and consistent midwifery demonstration of the model.     

三氧化二砷脂质体的制备及其对鼠脑胶质瘤的影响

目的研究三氧化二砷（As2o3）脂质体注射液对大鼠体内C6胶质瘤细胞凋亡的影响。方法采用超声薄膜分散法制备As籼脂质体，将126只成瘤大鼠分为As2O3脂质体组、As2O3组、生理盐水组。原子荧光法检测注射As2O3脂质体和As2O3后大鼠脑组织中As2O3浓度。从电镜、TUNNEL和大鼠生存时间等方面研究As2O3脂质体对C6胶质瘤的影响。结果As203，脂质体提高了As2O3的血-脑屏障通过。电镜和TUNEL检测显示：As203脂质体组细胞凋亡率给药后3d为（13．53±1．68）％，7d为（20．03±0．79）％，多于As2O3组和盐水组。动物生存时间亦优于其他两组。结论超声薄膜分散法是制备As2O3脂质体的较好方法。As203脂质体可较As203更明显地诱导鼠脑胶质瘤细胞凋亡，延长载瘤鼠的生存期。     

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.     

慢性活动性肝炎中单核性细胞超微形态研究

经电镜观察,慢活肝中主要为淋巴细胞及单核巨噬细胞浸润。淋巴细胞分3型,通过4种方式与肝细胞接触,可能代表杀伤肝细胞的动态过程。与肝细胞接触的主要为起细胞毒作用的T_8~+Ⅱ型淋巴细胞及单核巨噬细胞。多数T_4~+淋巴细胞为Ⅰ型淋巴细胞,可能为T辅助细胞。在肝细胞损伤中,淋巴细胞及单核巨噬细胞均起重要作用。     

固尔苏治疗NRDS前后血管内皮分泌功能的改变

目的 :研究肺表面活性物质 (PS)治疗新生儿呼吸窘迫综合征 (NRDS)前后血管内皮分泌功能变化及可能的治疗机理。方法 :用PS制剂固尔苏治疗 18例NRDS患儿 ,于治疗前 3 0min ,治疗后 1、 6、 12、 2 4h ,用硝酸还原酶法测定NO (一氧化氮 )、放射免疫法测定ET (内皮素 )、 6 K PGF1α (6 酮前列环素 )。结果 :固尔苏治疗后患儿NO、 6 K PGF1α明显升高 ,ET明显下降 ,与治疗前比较有显著性差异 (P <0 0 1)。治疗后 1、 6、 12、 2 4hNO、6 k PGF1α、ET各组间两两比较无明显差异 (P >0 0 5 )。结论 :PS治疗NRDS的机理可能是通过改善血管内皮功能发挥作用 ,为用外源性NO吸入和静注前列环素辅助治疗NRDS提供可能的实验依据。