大籽獐牙菜的抗内毒素作用

目的:研究大籽獐牙菜对内毒素的拮抗作用。方法:通过观察大籽獐牙菜提取物对内毒素攻击小鼠的死亡率的影响及体外抗内毒素作用。结果:大籽獐牙菜提取物能提高内毒素攻击小鼠的生存率,延长平均存活时间。大籽獐牙菜溶液的浓度对抗内毒素作用强度的影响较大,当大籽獐牙菜浓度大于0.062 5g.mL-1(稀释度在1∶16)时对内毒素有明显的破坏作用,但当浓度稀释至0.031 2 g.mL-1(稀释度在1∶32)时,抗内毒素的作用明显减弱或消失。结论:大籽獐牙菜具有很好的抗内毒素作用。     

板蓝根中4(3H)-喹唑酮的抗内毒素作用

目的 研究板蓝根中4(3H)-喹唑酮(QZO)的抗内毒素作用.方法 鲎试验法测定抗内毒素;内毒素致家兔发热实验检测其体内抗内毒素作用;脂多糖致小鼠死亡实验测定QZO的保护作用及其对脂多糖致小鼠过度释放肿瘤坏死因子(TNFα)和一氧化氮(NO)的影响,研究QZO的抗内毒素作用.结果 0.832 mg·ml-1QZO可使4 EU内毒素降解为1.19 EU,破坏率71.31%;0.5%QZO溶液可使内毒素引起的家兔体温升高显著降低,使同剂量脂多糖引起的小鼠死亡率从70%降为30%;板蓝根中的QZO可抑制脂多糖致小鼠血清中TNFα和NO的过度释放,抑制率呈剂量依赖性.结论 从板蓝根中提取分离出的QZO有抗内毒素作用.     

板蓝根中水杨酸的抗内毒素作用

目的:研究板蓝根中水杨酸的抗内毒素作用。方法:将水杨酸配成0.25%水溶液,鲎试验法进行抗内毒素定量测定;内毒素致家兔发热实验检测水杨酸体内抗内毒素作用;脂多糖致小鼠死亡实验测定水杨酸保护作用及水杨酸对脂多糖致小鼠过度释放肿瘤坏死因子(TNFα)和一氧化氮(NO)的影响实验,研究水杨酸的抗内毒素作用。结果:0.416g.L-1水杨酸可使4EU内毒素降解为1.08EU,破坏率为74.07%;0.25%水杨酸溶液可使内毒素引起的家兔体温升高显著降低、使同等剂量脂多糖引起的小鼠死亡率从70%降为25%;板蓝根中的水杨酸可抑制脂多糖致小鼠血清中TNFα和NO的过度释放,其抑制率呈剂量依赖性。结论:从板蓝根中提取分离出的水杨酸有抗内毒素作用。     

板蓝根中苯甲酸的抗内毒素作用

目的研究板蓝根中苯甲酸的抗内毒素作用。方法将苯甲酸配成0.25%水溶液,鲎试验法进行抗内毒素定量测定;内毒素致家兔发热实验检测苯甲酸体内抗内毒素作用;脂多糖致小鼠死亡实验测定苯甲酸保护作用及苯甲酸对脂多糖致小鼠过度释放肿瘤坏死因子（TNF-α）和一氧化氮（NO）的影响研究苯甲酸的抗内毒素作用。结果0.416 mg.mL^-1苯甲酸可使4 EU内毒素降解为0.926 EU,破坏率为78%;0.25%苯甲酸溶液可使内毒素引起的家兔体温升高显著降低,使同等剂量脂多糖引起的小鼠死亡率从70%降为20%;板蓝根中的苯甲酸可抑制脂多糖致小鼠血清中TNF-α和NO的过度释放,其抑制率呈剂量依赖性。结论从板蓝根中提取分离出的苯甲酸有抗内毒素作用。     

板蓝根中邻氨基苯甲酸的抗内毒素作用

目的研究板蓝根中邻氨基苯甲酸(o-aminobenzoic acid,OABA)的抗内毒素作用.方法将邻氨基苯甲酸配成0.5%水溶液,鲎试验法进行抗内毒素定量测定;内毒素致家兔发热实验检测邻氨基苯甲酸体内抗内毒素作用;脂多糖(LPS)致小鼠死亡试验测定邻氨基苯甲酸保护作用及邻氨基苯甲酸对脂多糖致小鼠过度释放肿瘤坏死因子-α(TNF-α)和一氧化氮(NO)的影响试验,研究邻氨基苯甲酸的抗内毒素作用.结果 0.833 mg·mL-1邻氨基苯甲酸可使4 EU内毒素降解为0.668 EU,破坏率为84.4%;0.5%邻氨基苯甲酸溶液可使内毒素引起的家兔体温升高显著降低,使同等剂量脂多糖引起的小鼠死亡率从70%降为20%;板蓝根中的邻氨基苯甲酸可抑制脂多糖致小鼠血清中TNF-α和NO的过度释放,其抑制率呈剂量依赖性.结论从板蓝根中分离出的邻氨基苯甲酸有抗内毒素作用.     

消炎退热颗粒清热解毒作用研究

目的：观察中成药消炎退热颗粒（DPZG）对家兔发热模型、小鼠急性耳廓肿胀模型、小鼠内毒素血症模型的作用,探讨其清热解毒的作用和机理。方法：采用脂多糖（lipopolysaccharides,LPS）耳缘静脉注射建立家兔发热模型,评价其解热作用;采用二甲苯致小鼠急性耳廓肿胀模型评价其抗炎作用;建立小鼠内毒素血症模型,观察DPZG对于D-氨基半乳糖（ACTD）敏化小鼠LPS致死攻击的影响,评价其抗内毒素的作用;以Elisa法检测DPZG对内毒素血症模型小鼠血清中TNF-α、IL-1β等炎症因子水平的影响,Western blot法检测小鼠肝、脾、肾组织中膜突蛋白（moesin）以及磷酸化P38 MAPK表达。结果：与模型组比较,DPZG对家兔体温升高有显著抑制作用,与阿司匹林趋同;可显著降低二甲苯致小鼠急性耳廓肿胀程度;可显著升高内毒素血症模型小鼠存活率;显著降低小鼠血清中TNF-α、IL-1β水平和小鼠肝脾肾组织内p-P38MAPK和膜突蛋白（moesin）的表达,效果明显优于中成药对照药蒲地蓝消炎口服液（PBKH）。结论：消炎退热颗粒有显著清热解毒作用,主要作用方式是解热、抗炎、抗内毒素,且效果明显优于PBKH。其作用机制可能与抑制IL-1β、TNF-α、Moesin以及p-P38 MAPK的表达有关。     

黄芩中黄芩苷的抗内毒素作用

目的 探讨黄芩中黄芩苷的抗内毒素作用。方法将黄芩苷配成0.5%水溶液，鲎实验法进行抗内毒素定量测定；内毒素致家兔发热实验检测黄芩苷体内抗内毒素作用；脂多糖致小鼠死亡实验测定黄芩苷保护作用及黄芩苷对脂多糖致小鼠过度释放肿瘤坏死因子（TNF）和一氧化氮（NO）的影响实验，研究黄芩苷的抗内毒素作用。结果0.833 g· mL 1黄芩苷可使4 EU内毒素降解为0.546 EU，破坏率为87.45%；0.5%黄芩苷溶液可显著降低内毒素引起的家兔体温升高，同等剂量脂多糖引起的小鼠死亡率从70.0%降为10.0%；黄芩中的黄芩苷可抑制脂多糖致小鼠血清中TNF和NO的过度释放，其抑制率呈剂量依赖性。结论 从黄芩中提取分离出的黄芩苷有抗内毒素作用。     

斑马鱼内毒素炎症模型建立及中药抗内毒素炎症研究

革兰阴性菌外膜结构成分脂多糖(LPS)即内毒素,是其主要致病因子,具有广泛而复杂的生物学效应,可直接或间接引起机体发热、代谢改变、免疫功能紊乱,多器官功能损害、休克乃至死亡等许多病理生理过程。这些效应主要是通过LPS与细胞表面的受体结合,激活细胞内信号转导系统,促进细胞因子及炎症介质的大量合成与释放,导致机体失控性炎症反应。在现代医学对由内毒素触发全身炎症反应综合征的治疗仍然一筹莫展的今天,不断有中药、复方或其所含成分被证明对受内毒素攻击的动物有保护作用,我们先期的研究结果亦证明中医经典复方凉膈散具有良好的抗内毒素炎症活性,从中药寻找抗内毒素治疗措施呈现良好的前景,抗内毒素中药活性筛选成为关注的热点。然而,对于中药或复方来说,由于成分复杂,影响因素众多,限制了细胞筛选体系和分子筛选体系的应用,特别是在以有效部位、提取物甚至水煎剂为研究对象时则更加困难。若用哺乳动物模型进行大规模筛选,则费时、费力、费物资,代价难以承受。利用斑马鱼模型来筛选药物已成为发现候选药物的主要技术。近年来,转基因、诱导突变和反义morpholino knockdown等技术的使用,结合活体成像技术,使斑马鱼成为研究人类炎症免疫疾病相关的病理生理学及在活体内进行高通量药物筛选的良好模式生物。近年在国家自然科学基金资助下,开展了斑马鱼内毒素炎症模型构建及基于该模型的中药抗内毒素炎症活性筛选研究。采用LPS卵黄囊注射诱导成功建立斑马鱼内毒素炎症模型。以LPS诱导的中性粒细胞及巨噬细胞的迁移聚集、斑马鱼死亡率和生存时间可作为评价抗内毒素炎症活性参考指标。利用斑马鱼内毒素炎症模型开展了凉膈散方提取物(不同极性提取部位)抗内毒素活性筛选,凉膈散方中单味中药提取物(不同极性提取部位)抗内毒素活性筛选及凉膈散方所含活性单体抗内毒素活性筛选。研究证明该模型用于中药抗内毒素活性评价是可行的。鉴于有效成分组方是创新中药研发的新形式、新方法,我们利用斑马鱼内毒素炎症模型开展了抗内毒素中药有效成分组方的配伍与配比研究,获得优化配方并申请专利保护。利用LPS诱导的马鱼内毒素炎症模型,建立适宜于不同层次(中药单体成分、单味中药及复方不同提取部位或组分)中药形式抗内毒素活性筛选方法,为抗内毒素中药筛选提供一个介于体外初筛与哺乳动物验证之间的快速、低成本和活体筛选新方法,具有良好的应用前景。     

布渣叶抗内毒素和急性毒性实验研究

目的:研究布渣叶的抗内毒素作用和急性毒性。方法:采用内毒素致小鼠休克死亡法观察布渣叶的抗内毒素作用。通过对小鼠空腹ig给药,观察小鼠出现的毒性反应,测定半数致死剂量(LD50)。结果:23.4、11.7g.kg-1剂量下布渣叶能显著提高内毒素血症小鼠生存率(P<0.05),LD50=91.76g(生药).kg-1,相当于成人日用量的214倍。结论:布渣叶具有较好的抗内毒素作用,在临床常规剂量下使用是安全、毒性极小的。     

几种中药化学成分抗内毒素研究现状

目的：探讨粉防已碱等中药化学成分抗内毒素研究现状。方法：用文献检索法检索中文期刊中已报道有抗内毒素作用的中药化学成分，并对其抗内毒素作用的研究方法，研究成果作介绍。结果；粉防已碱等中药化学成分通过抑制内毒素刺激机体释放炎性因子TNFα、IL－8、NO、PAF，抑制TXA2合成，保护内皮细胞，减少内毒素致小鼠死亡率，降低内毒素致兔发热反应温度，缓解休克期肺血管收缩、改善肺循环灌注状态，破坏内毒素化学结构等多种途径拮抗内毒素。结论：粉防已碱等中药化学成分有抗内毒素作用，可作为含该类化学成分抗内毒素中药的质控制指标成分。     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.