减肥药物的研究进展及前景

目的寻找有效安全的减肥药物。方法查阅国内外文献,了解不同类减肥药物的进展和作用特点．结果各类药物对临床治疗肥胖具有一定重要的意义。结论研制和开发新型、有效、安全的减肥药物,临床医师可根据不同的作用机制选用合适的药物治疗肥胖,从而达到合理用药的目的。     

减肥药物及相关靶点研究进展

肥胖是体内脂肪过度蓄积导致健康损害的一种机体状态，其根本原因是由于机体能量摄入大于能量消耗而导致的代谢异常。肥胖与多种疾病密切相关，且发病率逐年攀升，已成为全世界面临的严峻问题。然而目前，各国减肥药物在市数量极少，远不能满足市场需求。近年来，随着对肥胖生理病理机制的深入研究，一系列新靶点新药物被发现具有良好的减肥前景。本文旨在总结阐明肥胖的发生机制，更新减肥相关药物及靶点的最新进展，以期为减肥药物研究的未来发展提供方向。     

减肥药物最新研究进展

减肥药物按作用机制可分为3类：抑制食欲药物、抑制肠道消化吸收药物和增加能量消耗药物。现分别介绍上述各类中的代表性药物和正处于临床或临床前研究阶段、有开发前景的药物的最新研究进展。     

减肥药研发:窘境背后的希望

肥胖严重威胁着人们的健康,已经成为全球性的流行病。由于目前能有效治疗肥胖的手段有限,肥胖难以得到有效控制。由于药物的不良反应问题,已上市的减肥药大部分都被淘汰,肥胖正在面临无药可治的窘迫局面。人体中有许多靶点能够起到调节能量代谢,控制体重的作用。作用于这些靶点的减肥药物正在研发中。本文综述了治疗肥胖相关的药物靶点和作用机制以及减肥药物的研发现状。     

北京人的“瘦身”状况

北京美兰德信息公司医药调研部于今年九月初针对北京市区15—54岁居民进行了一次关于肥胖和减肥行为的调查研究。本次调查采用电话调查、网上调查和专家访问相结合的方法进行,共获取有效样本818人。调查结果表明,北京市区15—54岁的肥胖人口约有93万人,曾经或正在减肥的有120万人,58万人采用药物减肥。 5个人中一个胖子 本次调查引入亚太地区标准体重指数[BMI=体重(公斤)/身高(米)2]。     

肥胖症治疗药物的不良反应

肥胖是多种因素共同作用的结果,目前真正被批准可以被长期用于减重的药物主要分为两类:一类是作用于中枢神经系统的食欲抑制剂;另一类是抑制肠道吸收脂肪的药物。在肥胖患病率日益增高的情况下,减肥药物的不良反应尤为关注。可以说减肥药物发展的历史就是其有效性与安全性相博弈的历程,本文就目前临床被批准可以长期使用的减肥药物的心血管系统不良反应、消化系统不良反应、肝脏不良反应、致畸作用等常见不良反应进行简要综述,来指导临床上肥胖治疗药物的合理选择。     

江苏减肥药品市场调查与分析

“肥胖”已成为现代人生活的大敌，目前医学界已将肥胖与爱滋病、吸毒、酗酒并列为世界四大社会医学问题。世界卫生组织（WHO）已确认肥胖是一种疾病，并向全世界宣布：“肥胖症将成为全球首要健康问题”。中国减肥产品市场去年销售额超过６０亿元，且仍以年增长２３％的速度在扩大。目前，社会上减肥产品的宣传铺天盖地，人们对减肥的认识也千差万别。什么是肥胖，什么样的人需要减肥，什么样的人需要药物减肥，生产产品的厂家如何宣传自己的产品，等等这些问题值得我们关注。为了了解减肥市场的基本情况，我们在江苏省南京（宁）、苏州…     

针灸减肥60例临床疗效观察

目的：探讨运用针灸方法减肥对肥胖患者的临床应用和疗效。方法：对60例符合标准的肥胖患者运用中医理论辨证论治分型的方法进行选穴针灸。2个疗程后观察体重、体围（腰围、臀围、大腿围、手臂围）以及脂肪含量、BMI、基础代谢的变化。结果：体重、体重指数、脂肪百分率、基础代谢与治疗前后比较,P〈0.01;腰围、臀围、大腿围与治疗前比较,P〈0.01,上臂围与治疗前比较,P〈0.05,均有显著差异。结论：针灸对肥胖患者具有明显的减肥效果。     

胃左动脉栓塞术在肥胖治疗中的研究进展

近年来,我国肥胖人群的规模急速增长.肥胖是心脑血管疾病、癌症、糖尿病等慢性病的重要诱因,严重影响人类的身心健康.目前外科减肥手术是治疗肥胖较有效的手段之一,但属创伤性治疗.未来减肥手术应朝着更加安全、微创、有效的方向发展,胃左动脉栓塞术因其创伤小、恢复快、疗效好已经引起广泛关注.本文主要回顾肥胖的传统治疗手段,阐述ghrelin激素在能量平衡调节中的作用及胃左动脉栓塞对ghrelin激素的影响,对胃左动脉栓塞术在肥胖治疗方面的研究进展作一综述.     

针刺治疗单纯性肥胖73例临床观察

单纯性肥胖是人体内热量的摄入大于消耗和利用，造成脂肪在体内积聚，导致体重超常的病症。随着我国经济的发展，人民生活习惯的改变及饮食结构的变化，肥胖人口数蛰也呈急剧上升趋势。肥胖不仅影响人们外观形体的审美，更严重的是它危害人体的健康，是脂质代谢紊乱、冠心病、2型糖尿病、心脑血管病的危险因素。目前肥胖已成为严重威胁人类身心健康的全球性疾病，减肥已成为热门课题．减肥方法较多。针灸作为一种非药物疗法且效果显著．在临床已得到广泛运用。笔者收集了112例肥胖病人．其中73例用针刺治疗．取得较好的效果。     

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.