植物蜕皮素的资源、提取分离与药理作用

从多种陆生植物中分离到对无脊椎动物有生物活性的蜕皮素，其中苋科、马鞭草科、蓼科、唇形科、菊科、天南星科和罗汉松科植物中的含量较高。综述了蜕皮素的植物来源、提取分离方法及药理活性。     

牡荆属植物化学成分及生物活性

对牡荆属植物所含的蜕皮甾酮类、萜类、黄酮类及木脂素类等主要化学成分及其生物活性进行了较全面的综述，为开发利用该属植物提供文献支持。     

蜕皮甾酮对大鼠肺再灌注损伤的影响

目的探索蜕皮激素是否能够减轻肺再灌注损伤。方法应用肺再灌注损伤模型，大鼠颈静脉滴注蜕皮甾酮（３０ｍｇ·ｋｇ－１），并与氢化可的松（１０ｍｇ·ｋｇ－１）相比较，检测动脉血气，测定肺组织血管紧张素转化酶（ＡＣＥ）、丙二醛（ＭＤＡ）及超氧化物岐化酶（ＳＯＤ）的含量，光镜观察肺组织及微血管变化。结果蜕皮甾酮组ＰａＯ２、ｐＨ及ＨＣＯ－３均较损伤对照组明显增高。ＡＣＥ及ＭＤＡ在蜕皮甾酮组明显低于损伤对照组，亦低于氢化可的松对照组。ＳＯＤ则蜕皮甾酮组较损伤对照组明显增高，亦较氢化可的松对照组为高。光镜显示，蜕皮甾酮组的肺组织水肿、微血管腔变窄、内皮肿胀等较损伤对照组明显减轻，而与氢化可的松对照组相似。结论蜕皮甾酮可减轻再灌注时肺血管内皮细胞损伤，对肺再灌注损伤有一定的防治作用，效果不亚于氢化可的松，其机制有待进一步研究。     

β-蜕皮素对心脏移植再灌注损伤的保护作用

目的 :研究植物单体成分 β-蜕皮素 (β- ecdysone,EDS)是否能减轻心脏移植中的脂质过氧化损伤。方法 :SD大鼠 45只分为 3组 :(1)假手术组 :仅开腹 ,不行心脏移植 ;(2 )对照组 :采用改良心脏移植模型 ,行大鼠同种异体异位心脏移植 ;(3) EDS组 :大鼠心脏移植术后应用蜕皮甾酮 (ig,2 0 mg· kg- 1 ,1/日 ,用 7d) ,测定血清心肌酶谱 L DH、GOT、CPK及 MDA、SOD,观察心肌组织的病理变化。结果 :EDS组心肌线粒体等结构损伤明显减轻 ,血清心肌酶谱明显改善 (P<0 .0 1) ,血清脂质过氧化的终产物 MDA明显减少 (P<0 .0 1) ,自由基清除剂 SOD明显增加 (P<0 .0 1)。结论 :在 EDS的作用下 ,心脏移植大鼠脂质过氧化反应明显减弱 ,表现出心肌酶谱改善 ,心肌结构特别是线粒体损伤减轻的效应 ,提示 EDS对心脏移植再灌注损伤有一定保护作用     

β-蜕皮甾酮化学结构修饰研究进展

β-蜕皮甾酮是一种重要的植物甾酮,它参与控制昆虫等无脊椎动物的蜕皮和繁殖过程。药理实验表明β-蜕皮甾酮具有促进蛋白质合成、降低血糖血脂以及改善学习和记忆等多种功效。多年来人们对其化学结构修饰及蜕皮活性的研究取得了一定的进展和成果,该文对历年来β-蜕皮甾酮的化学结构修饰和蜕皮活性研究成果进行概述。     

蜕皮甾酮对东莨菪碱致记忆障碍的改善作用

采用一次性被动迥避式反应方法(跳台法、避暗法)、水迷宫法及穿梭箱法研究了蜕皮甾酮对东莨菪碱造成的小鼠记忆障碍的改善作用.结果表明,蜕皮甾酮36、72mg/kg能明显改善东莨菪碱造成的记忆获得障碍,蜕皮甾酮18、36、72mg/kg能拮抗东莨菪碱引起的小鼠空间辨别障碍,蜕皮甾酮25、50mg/kg能改善东莨菪碱引起的大鼠主动迥避反应障碍,提示蜕皮甾酮能改善东莨菪碱造成的记忆损害.     

蜕皮甾酮对东莨菪碱记忆障碍的改善作用

采用一次性被动迥避式反应方法，水迷宫法及穿梭箱法研究了蜕皮甾酮对东莨菪碱造成的小鼠记忆障碍的改善作用。结果表明，蜕皮甾酮３．６、７．２ｍｇ／ｋｇ能明显改善东莨菪碱造成的记忆获得的障碍，蜕皮甾酮１．８、３．６、７．２ｍｇ／ｋｇ能拮抗东莨菪碱引起的小鼠空间辨别障碍。     

β-蜕皮甾酮的分离及结构修饰

目的从露水草总甾酮中分离β蜕皮甾酮并对其进行结构修饰。方法采用硅胶柱色谱分离β蜕皮甾酮,并以其为原料通过化学合成的各种手段合成结构类似物,利用光谱分析方法对所得化合物进行结构确证。结果与结论从露水草总甾酮中分离了β蜕皮甾酮(20 hydroxyecdysone)及另一含量较大的筋骨草甾酮C(ajugasterone C)。以分离的β蜕皮甾酮为原料化学合成了5种植物甾酮。分别是2,3,20,22双异丙叉基β蜕皮甾酮(20 hydroxyecdysone 2,3,20,22 diacetonideⅠ)、20,22异丙叉基β蜕皮甾酮(20 hydroxyecdysone 20,22 acetonideⅡ)、2,3,20,22双异丙叉基25乙酰基β蜕皮甾酮(viticosterone E 2,3,20,22 diacetonideⅢ)、2,3异丙叉基β蜕皮甾酮(20 hy-droxyecdysone 2,3 acetonideⅣ)、2,3异丙叉基22羰基β蜕皮甾酮(22 oxo 20 hydroxyecdysone2,3 acetonideⅤ)。     

蜕皮甾酮对缺血性脑损伤的影响

研究了蜕皮甾酮对抗急性脑缺血作用及对脑缺血再灌注引起的记忆障碍的影响．结果发现：蜕皮甾酮１４４ｍｇ／ｋｇ能对抗小鼠急性脑缺血造成的损伤和由于脑缺血引起的体温下降并改善由于脑缺血再灌注引起的学习记忆障碍．蜕皮甾酮１０ｍｇ／ｋｇ还能改善大鼠脑缺血引起的脑水肿并显著降低脑缺血大鼠脑组织钙含量．表明蜕皮甾酮对缺血性脑损伤具有保护作用     

蜕皮甾酮对小鼠学习记忆的促进作用

采用一次性训练被动回避性条件反应方法———跳台法,观察了蜕皮甾酮（Ｅｃｄｙｓｔｅｒｏｎｅ）对小鼠学习记忆功能的影响．结果表明,蜕皮甾酮可拮抗东莨菪碱造成的记忆获得障碍,改善环己酰亚胺造成的记忆巩固不良和３０％乙醇造成的记忆再现缺失．蜕皮甾酮还具有抗急性脑缺氧作用,提示蜕皮甾酮可改善记忆障碍,具有较高的药用价值．     

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.     

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.     

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.