微生物来源的纤溶酶类溶栓剂研究开发状况

溶栓疗法是血栓性疾病安全且有效的手段。目前临床使用的溶栓药物主要是纤溶酶原激活剂类。通过国内外对微生物中提取纤溶酶的研究和开发状况作出了分析和总结,从而对寻找新型的、相对廉价有效的溶栓剂提供了依据。     

国内溶栓药物的临床应用综述

溶栓药物是指作用于血栓形成过程中的某些环节,使血栓溶解,达到开通血管作用的药物。血栓性疾病是严重危害人类健康的疾病之一,其致残率和致死率均较高。常见的血栓性疾病有急性心肌梗死、脑梗死、肺静脉栓塞等。自从1959年Fletcher等首次静脉应用链激酶（Streptokinase,SK）治疗急性心肌梗死获得成功,溶栓药物成为治疗血栓性疾病的里程碑。随着临床应用研究的发展,溶栓药物已广泛应用于各种血栓性疾病的治疗,本文通过CHKD检索,参阅了1994～2009年国内相关文献,综述溶栓药物的临床应用,现综述如下。     

延长溶栓药物半衰期的策略研究

血栓性疾病是近年来人类健康的头号杀手,其临床治疗一直备受关注。以溶栓药物为基础的溶栓疗法虽可以有效治疗血栓性疾病,但存在药物半衰期短和给药频繁等问题。延长药物半衰期对将来溶栓药物的发展尤为重要。本文系统分析现有溶栓药物半衰期的影响因素和相应的解决策略,为将来的药物改造提供一定的理论指导。     

溶血栓药物研究进展

血栓性疾病如心肌梗死、动脉血栓和脑梗死等严重危害人类的身体健康,溶栓被认为是治疗血栓性疾病的重要方法之一。近年来溶栓药物的研发主要集中在两方面,一方面为通过基因工程和单克隆抗体技术改造的新型纤溶酶原激活剂药物,另一方面为新来源的溶栓药。本文将先概述溶栓机理,并对近年来溶栓药物的研究进展及发展方向进行综述。     

纤溶活性的药学测定方法研究

目前血栓性疾病是世界上最严重的影响人类健康的疾病,目前还缺乏很好的治疗药物。动物,植物和微生物等为开发抗血栓药物提供广阔的资源。在自然界的抗血栓药物中像尿激酶、纳豆激酶、水蛭素及蚓激酶已经被开发成新药物并在临床上起到一定作用。纤溶酶和激酶能直接降解血纤维蛋白,从而使血栓得到溶解,因此研究和开发新型的纤溶酶是目前最有效的治疗手段,建立简单快速的抗血栓活性检测方法是这项研究的基础。本文就目前国内外纤溶酶检测方法作一综述,希望为改进溶栓活性体外检测方法提供参考。     

抗血栓药物研究进展

由血栓引起的疾病是人类的常见多发病,溶栓疗法是治疗血栓性疾病的重要方法之一。因此通过血栓形成机制来研究新的抗血栓药物显得极为重要,临床上用于血栓治疗的药物主要分为3类：抗凝血药物、溶血栓药和抗血小板类药物。     

溶栓药物的临床应用及其进展

血栓性疾病是严重危害人类健康的疾病之一,其发病率、致残率和致死率均较高。常见的有急性心肌梗死、脑血栓、肺静脉栓塞、动脉血栓和缺血性休克等。其中急性心肌梗死的病死率高达30%。据世界卫生组织统计,世界每年死于血栓性疾病的人数约2600万,我国每年心血管疾病死亡者占因病死亡总人数的40.7%,其比例远高于癌症,居各类死因之首[1]。溶栓治疗被认为是治疗血栓性疾病最为有效的方法,寻找和研制溶栓成功率高、不良反应小的药物对治疗血栓性疾病有重要     

哺乳动物代谢的微生物模型

由于哺乳动物产生的药物代谢产物往往仅有痕量,故难以测定其化学结构和生物活性。本文综述应用微生物模拟哺乳类代谢过程,使产生足量的药物代谢产物,以供用于药理研究。微生物转化微生物转化即指微生物系统对各种化学物     

抗血栓药物研究进展

由血栓引起的疾病是人类的常见多发病,溶栓疗法是治疗血栓性疾病的重要方法之一.因此通过血栓形成机制来研究新的抗血栓药物显得极为重要,临床上用于血栓治疗的药物主要分为3类:抗凝血药物、溶血栓药和抗血小板类药物.     

溶栓药物的临床应用及其进展

血栓性疾病是严重危害人类健康的疾病之一,其发病率、致残率和致死率均较高.常见的有急性心肌梗死、脑血栓、肺静脉栓塞、动脉血栓和缺血性休克等.其中急性心肌梗死的病死率高达30%.据世界卫生组织统计,世界每年死于血栓性疾病的人数约2600万,我国每年心血管疾病死亡者占因病死亡总人数的40.7%,其比例远高于癌症,居各类死因之首[1].溶栓治疗被认为是治疗血栓性疾病最为有效的方法 ,寻找和研制溶栓成功率高、不良反应小的药物对治疗血栓性疾病有重要的意义.     

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.