2020年全球新药研发报告(Ⅳ)

2020年因一场突如其来的疫情注定被载入史册,这场百年以来最严重的疫情以惊人的速度在全球迅速蔓延,影响了生活的方方面面。几乎2020年发生的所有事件或新闻报道在某种程度上均受到了新型冠状病毒肺炎（COVID-19）的影响。从这个角度看,2020年也在第一批新冠疫苗和COVID-19治疗药物获得紧急授权使用中高调地结束。尽管新冠疫情大流行占据了2020年的新闻头条,但从年度报告中产品数量来看,各治疗领域推出的新药均创下历史新高,较上一年增加了约50%。值得关注的成果包括：首款丁型肝炎治疗药物上市;预防和治疗埃博拉病毒病的生物制剂获得监管机构批准,该制剂在抗击2016—2018年刚果爆发的埃博拉病毒病方面发挥了作用;首款Hutchinson-Gilford早衰综合征（一种罕见的导致早熟型老化的遗传性疾病）治疗药物获批;首款专门治疗甲状腺眼病（又称Graves眼病）的药物获批;首款非激素、按需用药、可调节阴道pH的避孕药获批;首款针对花生过敏的口服过敏原免疫疗法获批。     

2020年全球新药研发报告(Ⅲ)

2020年因一场突如其来的疫情注定被载入史册,这场百年以来最严重的疫情以惊人的速度在全球迅速蔓延,影响了生活的方方面面。几乎2020年发生的所有事件或新闻报道在某种程度上均受到了新型冠状病毒肺炎（COVID-19）的影响。从这个角度看,2020年也在第一批新冠疫苗和COVID-19治疗药物获得紧急授权使用中高调地结束。尽管新冠疫情大流行占据了2020年的新闻头条,但从年度报告中产品数量来看,各治疗领域推出的新药均创下历史新高,较上一年增加了约50%。值得关注的成果包括：首款丁型肝炎治疗药物上市;预防和治疗埃博拉病毒病的生物制剂获得监管机构批准,该制剂在抗击2016—2018年刚果爆发的埃博拉病毒病方面发挥了作用;首款Hutchinson-Gilford早衰综合征（一种罕见的导致早熟型老化的遗传性疾病）治疗药物获批;首款专门治疗甲状腺眼病（又称Graves眼病）的药物获批;首款非激素、按需用药、可调节阴道pH的避孕药获批;首款针对花生过敏的口服过敏原免疫疗法获批。     

2020年全球新药研发报告（Ⅱ）

2020年因一场突如其来的疫情注定被载入史册,这场百年以来最严重的疫情以惊人的速度在全球迅速蔓延,影响了生活的方方面面。几乎2020年发生的所有事件或新闻报道在某种程度上均受到了新型冠状病毒肺炎（COVID-19）的影响。从这个角度看,2020年也在第一批新冠疫苗和COVID-19治疗药物获得紧急授权使用中高调地结束。尽管新冠疫情大流行占据了2020年的新闻头条,但从年度报告中产品数量来看,各治疗领域推出的新药均创下历史新高,较上一年增加了约50%。值得关注的成果包括：首款丁型肝炎治疗药物上市;预防和治疗埃博拉病毒病的生物制剂获得监管机构批准,该制剂在抗击2016—2018年刚果爆发的埃博拉病毒病方面发挥了作用;首款Hutchinson-Gilford早衰综合征（一种罕见的导致早熟型老化的遗传性疾病）治疗药物获批;首款专门治疗甲状腺眼病（又称Graves眼病）的药物获批;首款非激素、按需用药、可调节阴道pH的避孕药获批;首款针对花生过敏的口服过敏原免疫疗法获批。     

重大传染性疾病的流行病学回顾

摘要：近20年来,多种新型病毒引起的疫情向世界医疗卫生体系提出了严峻的挑战,包括2003年暴发的严重急性呼吸系统 综合征(SARS)、2009年暴发的甲型H1N1流感、2014年暴发的中东呼吸综合征(MERS)和埃博拉病毒病(EVD)、2015年暴发的寨卡 病毒病以及2019年底暴发的新型冠状病毒肺炎(COVID-19)。本文重点综述了SARS、甲型H1N1流感、MERS、EVD、寨卡病毒病 和COVID-19的流行病学特征,并探讨了COVID-19疫情防控带来的启示,以期为今后多种传染性疾病的防控提供理论支持。     

中医辨证埃博拉

2014年,埃博拉病毒肆虐西非数国,甚至使远离非洲大陆的美欧亚各国也深感危机。其实早在几千年前,“埃博拉”就已经存在,但直至1976年才真正发现埃博拉具有强致病性,虽然此前也曾几度流行,但疫情尚不严重。此次埃博拉疫情规模及严重程度为历史罕见。世界各国纷纷积极应对疫情,但西医的治疗手段及成效并不尽如人意。就在众人对埃博拉几乎束手无策之时,有人提出,也许中医将会为对抗埃博拉带来新的希望。而中医对埃博拉会有何看法？他们能否拿出治疗良方？本刊采访国内部分名医大家和首批赴几内亚埃博拉疫区的支援专家,并对他们的观点进行整理、总结,以期为探索最终的治疗埃博拉有效方案提供方法和手段。     

新发传染病及疫苗新技术

自20世纪初,先后暴发了多次威胁人类健康和社会稳定的传染病疫情,如埃博拉出血热、冠状病毒感染引起的严重急性呼吸综合征、中东呼吸综合征和新型冠状病毒肺炎以及寨卡病毒病等。对于尚未表征的新发病原体,尤其是变异速度快、宿主范围广、传播能力强的病毒病原体导致的相关疫情暴发尚无法进行有效预测。目前没有针对上述病毒感染的特效抗病毒药物,接种疫苗是防控疫情最为经济有效的策略。本文对埃博拉病毒、冠状病毒、寨卡病毒的病毒特征以及与之相关的核酸疫苗和病毒载体疫苗技术研究进展做一综述。     

中医谈埃博拉

编者按:2014年,埃博拉病毒肆虐西非数国,甚至使远离非洲大陆的美欧亚各国也深感危机。其实早在几千年前,"埃博拉"就已经存在,但直至1976年才真正发现埃博拉具有强致病性,虽然此前也曾几度流行,但疫情尚不严重。此次埃博拉疫情规模及严重程度为历史罕见。世界各国纷纷积极应对疫情,但西医的治疗手段及成效并不尽如人意。就在众人对埃博拉几乎束手无策之时,有人提出,     

埃博拉病毒病国际学术研讨会在京召开

为共同探讨埃博拉出血热的重点防控问题,进一步加强全球公共卫生安全及应对的合作交流和信息共享,在国家卫计委和世界卫生组织的支持下,中国疾病预防控制中心联合法国巴斯德研究院和梅里埃基金会于2015年3月23日-24日在北京举办埃博拉病毒病国际学术研讨会。国家卫计委副主任崔丽出席会议开幕式并致辞。她指出,2014年西非暴发的埃博拉出血热疫情引起国际社     

国家卫生计生委主任李斌会见世界卫生组织总干事、世界银行行长和联合国人口基金执行主任

<正>本刊讯2014年9月22日,在出席第69届联大关于国际人口与发展会议《行动纲领》特别会议期间,国家卫生计生委主任李斌会见了世界卫生组织总干事陈冯富珍、世界银行行长金墉,以及联合国人口基金执行主任巴巴图德·奥索提迈辛,分别就西非埃博拉疫情防控、医改联合研究,以及人口与发展领域的合作交换了意见。李斌与陈冯富珍会谈时表示,中国政府高度重视西非埃博拉疫情防控。习近平主席、李克强总理多次作出重要指示,刘延东副总理主持专题会议进行部署,要求做好疫情防控准     

冷静对待埃博拉病毒病

埃博拉病毒病（过去称“埃博拉出血热”）是一种烈性传染病,这次爆发迄今已有5500余人受感染,超过2500人死亡。也就是说一旦感染这种病毒,有半数以上的患者不能被救活。据此,民众对这种疾病的恐惧和不安也是可以理解的。今年发生埃博拉病毒病大流行的国家主要是西非四国,即几内亚、利比里亚、塞拉利昂和尼日利亚。到目前为止,英国、瑞士报道过输入病例,输入病例均到流行区旅行过。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.