大承气汤颗粒剂对正常小鼠肠道运动的影响

目的：观察大承气汤颗粒剂对正常小鼠肠道运动的影响,方法：测量给小鼠炭末灌胃后一定时间内炭末在小肠推进距离,计算给药后５小时内排出湿粪的数目及炭末排出时间,结果：大承气汤颗粒剂使正常小鼠炭末推进率,湿粪计数明显增加（Ｐ〈０．０５／Ｐ〈０．０１）。炭末排出时间明显缩短（Ｐ〈０．０５／Ｐ〈０．０１）。结论：大承气汤颗粒剂使正常小鼠肠道动力功能增强。     

激光散斑衬比成像技术观察补阳还五汤对大鼠脑缺血再灌注后脑微血流的影响

目的：建立脑缺血再灌注大鼠模型,观察补阳还五汤对大鼠脑缺血再灌注后脑微血流的影响。方法：将动物分为对照组、模型组、补阳还五汤组、重组人血管内皮抑制素组、补阳还五汤+重组人血管内皮抑制素组,应用激光散斑衬比成像技术观察大鼠梗死区域脑血流状态,测定脑组织的含水量,并检测血管内皮生长因子（vascular endothelial growth factor,VEGF）蛋白及基因表达水平。结果：与对照组相比,脑缺血再灌注大鼠模型大鼠脑血流速度明显降低（P<0.01）,脑组织含水量增高（P<0.01）,VEGF蛋白和基因的表达减少（P<0.01）;与模型组相比,补阳还五汤组能明显提高脑缺血再灌注大鼠模型大鼠脑血流速度（P<0.01）,降低脑组织含水量（P<0.01）,提高VEGF蛋白和基因的表达（P<0.01）。结论：补阳还五汤具有改善缺血再灌注后脑血流的作用,而调节VEGF蛋白及基因的表达水平是其参与改善脑血流的主要途径之一。     

国产洛伐他汀（Lovastatin）调血脂作用的实验观察

通过观察重庆制药五厂研制生产的洛伐他汀对由ＴｒｉｔｏｎＷＲ－１３３９所致的大鼠高脂血症的影响。灌服１０ｍｇ／ｋｇ的作用最为明显，可使因Ｔｒｉｔｏｎ升高的血清总胆固醇，低密度脂蛋白的含量显著降低（Ｐ〈０．０１）而使高密度脂蛋白含量显著升高（Ｐ〈０．０１），但对甘油三脂的含量无显著影响。     

^ωN—硝基左旋精氨酸对大鼠脑缺血后脑区一氧化氮生成的影响

用荧光法研究＾ωＮ－硝基左旋精氨酸（Ｌ－ＮＮＡ）对大鼠脑缺血后大脑皮层、海马、纹状体和小脑中一氧化氮（ＮＯ）的变化，结果显示Ｌ－ＮＮＡ可明显减少缺血１０ｍｉｎ不同脑区ＮＯ的含量（Ｐ〈０．０５或Ｐ〈０．０１）；左旋精氨酸可部分逆转Ｌ－ＮＡＡ的使用，使ＮＯ的含量增加（Ｐ〈０．０５或Ｐ〈０．０１）。提示Ｌ－ＮＡＡ可减少脑缺血时ＮＯ的过量生成而具有潜在的治疗作用。     

组氨酸改善大鼠血栓形成性局部脑缺血时脑水肿及心功能障碍

观察组氨酸对脑血栓形成后脑水肿及功能障碍的影响。方法：用光化学法诱导大鼠血栓形成性局部脑缺血。结果：大鼠脑血栓形成后脑水份明显增加（Ｐ＜０．０１），左室收缩压（ＬＶＳＰ）峰值及左室内压变化速率明显降低（Ｐ＜０．０５）。结论：ｉｖ组氨酸５ｍｇ．ｋｇ＾－１可明显改善脑缺血所致脑水肿及心功能障碍而具有保护脑功能效应。     

MN 9202抗角叉菜胶引起的大鼠血栓形成作用及其对血液流变学的影响

目的：观察新的二氢吡啶类钙通道阻滞剂２，６－二甲基－４－（３－硝基苯基）－１，４－二氢－３，５－吡啶二羧酸－３－甲酯－５－正戊酯（ＭＮ９２０２）对角叉菜胶引起的大鼠血栓形成的影响，探讨其抗血栓形成作用的血液流变学机制。方法：大鼠ｓｃ角叉菜胶５ｍｇ·ｋｇ－１复制血栓模型。给药后观察大鼠尾部血栓形成状况，进行血液流变学分析。结果：ＭＮ９２０２０．１、１、１０μｍｏｌ·ｋｇ－１能对抗角叉菜胶引起的大鼠血栓黑尾的形成（Ｐ＜０．０５，Ｐ＜０．０１），呈现出明显的剂量依赖关系（ｒ＝０．９９９５）；０．０１，０．１，１，１０μｍｏｌ·ｋｇ－１能降低ＲＢＣ聚集指数（Ｐ＜０．０５，Ｐ＜０．０１），增强ＲＢＣ变形性（Ｐ＜０．０５，Ｐ＜０．０１），但不改变ＲＢＣ电泳迁移率；大剂量的ＭＮ９２０２１，１０μｍｏｌ·ｋｇ－１能降低切变率为１５０·ｓ－１、５０·ｓ－１、１·ｓ－１时全血粘度。结论：ＭＮ９２０２具有对抗角叉菜胶引起的大鼠血栓形成作用。其作用可能与其改善血液流变性特征有关。     

蚯蚓提取物治疗原发性肾小球疾病高凝状态

目的：探讨蚯蚓提取物对原发性肾小球疾病中凝血、抗凝、纤溶功能及血液流变学的影响。方法：对３６例原发性肾病综合征和３０例慢性肾小球肾炎给予ｐｏ蚯蚓提取物１５０ｍｇ／次,ｔｉｄ,连用１４ｄ在用药前后采血测定凝血、抗凝纤溶及血液流变学指标。结果：治疗后血ＫＰＴＴ、ＰＴ、ＴＴ较治疗前明显延长（Ｐ〈０．０１、Ｐ〈０．０５）,ＡＴ－Ⅲ及ｔ－ＰＡ活性在治疗后较治疗前明显升高（Ｐ〈０．００１,Ｐ〈０．０１）,ＦＤ     

尼莫地平对大鼠急性脑缺血再灌注损伤的作用

目的：研究尼莫地平（Ｎｉｍ）对脑缺血损伤的作用，方法：大鼠脑缺血模型采用四血管结扎法（４－ＶＯ），单胺递质测定采用荧光光分光度法，结果：腹腔注射尼莫地平０．７５ｍｇ．ｋｇ＾－１和１．５ｍｇ．ｋｇ＾－１能显改善缺血再灌注损伤的脑电活动，脑电恢复时间可恢复到１９±３ｍｉｎ和１７±４ｍｉｎ（Ｐ〈０．０１），尼莫地平还能明显减轻缺血３０ｍｉｎ后再灌注１ｈ的单胺递质的降低；结论：Ｎｉｍ对缺血引起损伤的神经     

补阳还五汤对自发性脑出血的作用

目的：观察补阳还五汤对自发性脑出血的影响。方法：选择脑半球出血旦在１１ ｍＬ～５０ ｍＬ之间的６８例患者,除脱水降颅压等一般治疗外,每日服用补阳还五汤中药二剂,疗程２１ｄ,另设６６例同样患者仅给一般治疗作为对照。结果：疗程结束后经功能缺损程度积分评估试验组明显优于对照组（Ｐ＜０．０５）,复查ＣＴ结果示血肿吸收体积＞５０％者亦以试验组为多（Ｐ＜０．０５）。结论：补田还五汤能够加速自发性脑出血的吸收,改善病情预后。     

脂必妥对大鼠高脂血症模型血脂水平的影响

目的：研究脂必妥的降脂疗效，方法：通过对大鼠腹腔注射脂酶抑制剂－１０％泰洛沙泊溶液（３ｍＬ／ｋｇ）后７ｍｉｎ，分别用脂必妥２．５９，１．２９，０．６５ｇ／ｋｇ，及洛伐他汀１０ｍｇ／ｋｇ灌胃药给，结果；脂必妥２．５９ｇ／ｋｇ，组及洛伐他汀组（１０ｍｇ／ｋｇ）的胆固醇（ＴＣ）值分别降低３３％（Ｐ〈０．０１）及３１％（Ｐ〈０．０１），组间比较Ｐ〉０．０５，低密度脂蛋白胆固醇（ＬＤＬ－ｃｈ）值分别降低５０     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Glycofection: The Ubiquitous Roles of Sugar Bound on Glycoplexes

Glycofection (transfection by using sugar-substituted polylysine) was assessed in order to provide an alternative to viral vectors for the transfer of genes into vascular smooth muscle cells. A rabbit vascular smooth muscle cell line (Rb-1 cells) was selectively transfected by using glycoplexes (glycosylated polylysine/pSV2LUC complexes) in the presence of 10 mu M of the fusogenic peptide GALA. A sugar-specific transfection was obtained when the glycofection was conducted for 1 h with glycoplexes containing either alpha Gal, alpha -Glc, alpha -GalNAc, beta -GlcNAc, or beta -GalNAc residues. The gene expression was high after transfection, with glycoplexes bearing alpha Gal, alpha -GalNAc, or beta -GalNAc residues that were weakly internalized, and low with glycoplexes carrying Lact or Rha residues that were well taken up by cells. These results suggest that 1) glycofection can be a good approach for a selective transfer of genes intovascular smooth muscle cells, 2) an efficient uptake of the glycoplexes is not the unique limiting step for an efficient transfection, and 3) the sugar-dependent trafficking of the glycoplexes inside the cells may account for the transfection efficiency.     

直肠癌下切缘病理组织学分析

目的探讨直肠癌逆向浸润与下切缘的安全距离的关系。方法对36例直肠癌Miles手术和Dixon手术后标本的肿瘤下缘1.0cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查,观察直肠癌逆向浸润或转移的距离。结果36例直肠癌标本距癌肿下缘1.0 cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查均为阴性,结论直肠癌远恻逆向浸润或转移未见超过1.0cm,因此认为保肛手术时切除肿瘤远侧肠管(包括系膜)2.0cm是安全的。