Antimalarials in the treatment of schistosomiasis

With just one drug used for individual patient management and community-based morbidity control, the treatment, control, and eventual elimination of schistosomiasis is vulnerable should resistance to praziquantel emerge and spread. The discovery and development of novel chemical entities that exhibit antischistosomal properties, and the repurposing of existing drugs for schistosomiasis is thus of central importance as long as praziquantel remains effective. Here, we discuss the public health relevance of schistosomiasis, which is currently considered a neglected tropical disease. We recapitulate the past and current drug armamentarium against schistosomiasis, including shortcomings and a target product profile of an antischistosomal drug. The central piece of our review is the discovery of the antischistosomal properties of various antimalarial drugs, notably the artemisinins, synthetic trioxolanes, and mefloquine. We summarize findings from preclinical investigations and experiences made thus far from clinical studies. We conclude that a closer collaboration between the malaria and schistosomiasis communities might facilitate the discovery and development of novel antischistosomal drugs, and will foster monitoring and evaluation of the ancillary benefits of antimalarial prophylaxis and treatment against schistosomiasis.     

Artemisinin drugs: novel antimalarial agents

Artemisinin and its derivatives, artesunate and artemether, represent a new class of antimicrobial drug with potent activity against Plasmodium falciparum. Although they show excellent efficacy in both severe and uncomplicated malaria, dosage regimens still need to be optimised and pharmacokinetic profiles defined. In the treatment of uncomplicated malaria, the artemisinin drugs should be used in combination with a long acting antimalarial to protect both drugs against the emergence of resistance. In the treatment of severe malaria, parenteral artemether is at least as effective as quinine and is simpler to use. The use of rectal preparations of artesunate and artemisinin at the rural health level will facilitate early initiation of the treatment of falciparum malaria and this may reduce the proportion of patients progressing to severe disease. All of the artemisinin drugs have comparable efficacy; the choice of derivative should be based upon availability, cost and quality of the preparation. Artemisinin, artesunate and artemether are well-tolerated in both adults and children, with no evidence to date of serious clinical toxicity.     

Artemisinin drugs: novel antimalarial agents

Artemisinin and its derivatives, artesunate and artemether, represent a new class of antimicrobial drug with potent activity against Plasmodium falciparum. Although they show excellent efficacy in both severe and uncomplicated malaria, dosage regimens still need to be optimised and pharmacokinetic profiles defined. In the treatment of uncomplicated malaria, the artemisinin drugs should be used in combination with a long acting antimalarial to protect both drugs against the emergence of resistance. In the treatment of severe malaria, parenteral artemether is at least as effective as quinine and is simpler to use. The use of rectal preparations of artesunate and artemisinin at the rural health level will facilitate early initiation of the treatment of falciparum malaria and this may reduce the proportion of patients progressing to severe disease. All of the artemisinin drugs have comparable efficacy; the choice of derivative should be based upon availability, cost and quality of the preparation. Artemisinin, artesunate and artemether are well-tolerated in both adults and children, with no evidence to date of serious clinical toxicity.     

青蒿素类药物的主要研究进展述评

青蒿素是从我国中草药成分里通过化学提炼开发出的有价值药物成分,在治疗疟疾方面取得世界瞩目的成绩。鉴于世界卫生组织已开始重视疟原虫耐药性的严重性,青蒿素类药物在其他领域的临床应用开发显得尤为重要：包括抗寄生虫、抗肿瘤、抗孕等方面的预防和治疗进展,将为其今后的发展前景带来新思路。     

抗疟药物的应用与发展

［摘 要］人类在抗疟药物的应用过程中,先后经历了蚊帐、纱窗、巫术、中草药等传统办法,由金鸡纳树皮的疗效促使了奎宁、氯喹的产生,以及DDT杀虫剂和青蒿素类药物的使用,上述治疗手段和方法都对控制疟疾的传播扩散发挥了重要作用。本文通过回顾这些抗疟药物应用历程的同时,以期展望该领域的发展前景和未来趋势。     

青蒿素类药物作用机制的探讨

具有过氧基团结构的青蒿素类化合物主要用于耐药性疟原虫感染治疗，但其作用机制尚未明确。本文根据有关文献的报道，对青蒿素类化合物体内作用的机制进行了探讨，并介绍了一些新的研究结果和研究热点。     

Patent Evaluation: Artemisinin Analogues as Potential Antimalarial Agents

Summary

Novelty: A process for synthesizing polyoxa heterocyles and, in particular, the antimalarial agent artemisinin and its analogues is disclosed. A new family of artemisinin analogues is disclosed.

Biology: In vitro IC₅₀ data for selected tricyclic artemisinin analogues in drug-resistant strains of P. falciparum are presented. For example, t-butylteperether has IC₅₀ values of 0.41 and 0.53 mg/ml against W-2 and D-6 clones, respectively.

Chemistry: The total synthesis by diastereo-selective silyation is described.     

Assessment of early acute lung injury in rats exposed to aerosols of consumer products: attempt to disentangle the "Magic Nano" conundrum

In Germany in 2006 a series of rapidly developing and sometimes severe cases of pulmonary health impairment were observed after normal use of the "Magic Nano Glass & Ceramic" spray and "Magic Nano Bath" spray. In contrast, the previously marketed "Magic Nano" pump spray product (handheld trigger device without propellants) was unobtrusive. Analysis of particles discharged from these products did not reveal stable (solid) nano-sized particles. The precipitous increase of pulmonary health impairment in humans caused by "Magic Nano Sprays" triggered a comparative assessment of the acute inhalation toxicity of "Magic Nano Glass & Ceramic" spray, "Magic Nano Bath" spray, and "Magic Nano" pump spray in rats. The first two test specimens were examined as spray-can aerosols using an intermittent generation principle, whereas the undiluted liquid content of the pump spray was continuously aerosolized. Groups of Wistar rats were nose-only exposed for 4 h. However, due to mortality occurring already during exposure following exposure to Glass & Ceramic spray, the exposure duration was reduced to approximately 2 h in some groups. In addition to endpoints called for by contemporary testing guidelines, respiratory tract injury was also probed by respiratory function measurements during exposure supplemented by analyses in bronchoalveolar lavage (BAL) fluid on the first postexposure day, including lung histopathology in rats exposed to Glass & Ceramic spray. The Glass & Ceramic spray caused mortality at 2269 mg/m(3) and above, the pump spray was in the beginning lethal range at 81222 mg/m(3), while the bath spray was tolerated without mortality up to the maximum tested nominal concentrations of 28100 mg/m(3). The time-adjusted 4-h LC(50) of Glass & Ceramic spray was 5098 mg/m(3). The analysis of respiratory patterns revealed changes indicative of both upper and lower respiratory tract sensory irritation. In addition to clinical signs suggestive of marked lung irritation, especially in the rats exposed to the Glass & Ceramic spray, histopathology revealed lung inflammation, hemorrhages, edema, and focal septal thickening. Lung weights and BAL endpoints (lactate dehydrogenase [LDH], protein, gamma-glutamyltransaminase, and neutrophilic granulocytes) were markedly increased. In summary, this comparative study demonstrates that the conventional OECD 403 protocol is suitable to comparatively assess the potential and potency of these types of consumer products in their end-use configuration. Measurements in BAL were most suitable for the identification of acute lung injury. By contrast, lung function measurements during exposure did not demonstrate any conclusive association with lung injury. It does not appear that the particle size per se is a key determinant in the toxicity of "Magic Nano Glass & Ceramic" spray (approximately 100% mortality occurred at a MMAD of approximately 7 microm; GSD approximately 3). This might suggest that more volatile substances or substances contained in the test articles that co-evaporate with solvents or water may be causative for the findings observed. Hence, the findings of this study support the notion that the assessment of the acute inhalation toxicity of complex end-use products is methodologically challenging and cannot be readily anticipated based on compositional or physical (particle size) data. Accordingly, in the absence of predictive and validated in vitro assays, in vivo inhalation testing of potentially toxic commercialized spray products appears to be indispensable for consumer safety. In order to prevent indiscriminant testing of such products in bioassays, the development of standardized in vitro alternatives should be considered with high priority.     

青蒿素市场中的逆淘汰分析

目的:解决青蒿素市场中的逆淘汰。方法:具体分析青蒿素市场中逆淘汰出现的原因、表现、后果,提出解决的措施。结果与结论:青蒿素生产企业应从建立品牌、提高产品质量、解决代理关系中信息不对称问题等三方面入手避免逆淘汰的发生。     

青蒿素芳香醚类衍生物的合成

设计合成了十个新的青蒿素芳香醚类衍生物，进行了抗疟与抗肿瘤活属恬的药理筛选，结果显示这些衍生物除有抗疟活性外还具有明显的抗肿瘤活性。