Successful drug development despite adverse preclinical findings part 2: examples

To illustrate the process of addressing adverse preclinical findings (APFs) as outlined in the first part of this review, a number of cases with unexpected APF in toxicity studies with drug candidates is discussed in this second part. The emphasis is on risk characterization, especially regarding the mode of action (MoA), and risk evaluation regarding relevance for man. While severe APFs such as retinal toxicity may turn out to be of little human relevance, minor findings particularly in early toxicity studies, such as vasculitis, may later pose a real problem. Rodents are imperfect models for endocrine APFs, non-rodents for human cardiac effects. Liver and kidney toxicities are frequent, but they can often be monitored in man and do not necessarily result in early termination of drug candidates. Novel findings such as the unusual lesions in the gastrointestinal tract and the bones presented in this review can be difficult to explain. It will be shown that well known issues such as phospholipidosis and carcinogenicity by agonists of peroxisome proliferator-activated receptors (PPAR) need to be evaluated on a case-by-case basis. The latter is of particular interest because the new PPAR α and dual α/γ agonists resulted in a change of the safety paradigm established with the older PPAR α agonists. General toxicologists and pathologists need some understanding of the principles of genotoxicity and reproductive toxicity testing. Both types of preclinical toxicities are major APF and clinical monitoring is difficult, generally leading to permanent use restrictions.     

不同细胞培养基细胞培养动力学比较试验

应用宜兴赛尔生物化工厂产１９９、Ｆ－１０、１６４０和ＤＭＥＭ细胞培养基与美国Ｓｉｇｍａ公司产１９９、Ｆ－１０、１６４０和ＤＭＥＭ细胞培养基分别配制细胞培养液，培养ＳＰ２／０和Ｖｅｒｏ细胞系及原代鸡胚成纤维细胞（ＣＥＦ），做细胞培养动力学比较试验。比较这两种来源的细胞培养基对细胞生长的形态、分裂速度及鸡马立克氏病毒（Ｍａｒｅｋ＇ｓｄｉｓｅａｓｅｖｉｒｕｓ．ＭＤＶ）疫苗毒株ＨＶＴ－ＦＣ１２６和ＲｉｓｐｅｎｓＣＶＩ９８８在ＣＥＦ单层上增殖量的差异。研究结果表明，四种国产细胞培养基与对应的四种进口培养基对细胞生长及病毒增殖的影响无显著差异     

棉花早熟性研究进展及其应用

早熟棉适于麦(油)后直播,实现粮棉一年两熟,对棉花产业稳定发展具有重要意义。本文对早熟性的遗传特性、早熟相关QTL定位、早熟相关基因挖掘的进展进行了阐述;总结了早熟棉的发展与育种现状以及早熟棉种质资源的创新利用;介绍了早熟棉在我国黄河流域、长江流域、西北内陆棉区的生产示范应用情况;提出了我国早熟棉育种的研究展望,为我国早熟棉育种提供参考。     

Prevalence of fecal contamination in sandpits in public parks in Sapporo City, Japan

A total of 107 sandpits in public parks in Sapporo City were examined, 9 and 73 were contaminated with helminth eggs and fecal coliforms, respectively. Of the nine in which eggs were detected, eight were contaminated with Toxocara spp. and one with Capillaria spp. eggs. The contamination rate of sandpits of more than 30 m2 ranged from 43 to 50%, while in those 30 m2 or less it was between 73 and 92%. Although helminth eggs were evenly distributed throughout all layers of the sandpits, fecal coliforms were localized on the sandpit surfaces. Recovered Toxocara eggs were identified according to their size and surface structures, and almost all eggs were T. cati. Based on these results, and given the inherent habits of cats, measures to prevent their defecation in sandpits are needed, especially ones of smaller size.     

农业政策性金融服务乡村振兴的可行性分析

探讨了新时代数字农业政策性金融服务体系的建设和推进,以促进经济高质量发展。研究指出,建设该体系对于将发展红利通过金融手段普及给广大人民群众至关重要。此外,本文还探讨了数字农业政策性金融服务与乡村振兴、城镇化建设之间的关联,强调了提高服务质量和效率的策略。在保障服务质量方面,本文提出了建立透明严格的监管制度的必要性,以应对金融风险。最后,为推进地区间数字农业政策性金融服务的融合交流,促进金融服务与经济发展的协调,呼吁加强区域合作和支持中西部地区的发展,为新时代数字农业政策性金融服务体系的发展提供参考。     

高产杂交棉棉铃发育特点的研究

在新疆生态条件下,选用不同叶形杂交棉品种,分析比较不同品种棉铃直径、长度、体积、重量以及纤维品质的变化。结果表明,铃龄20d之前品种间棉铃最大直径、长度、体积及棉铃干重无明显差异;铃龄20d以后,棉铃最大直径、长度、体积及干重迅速增加,品种间均表现为石杂2号新陆早43号新陆早33号。对产量及纤维品质的分析表明,新陆早43号和石杂2号单株结铃数、铃重及产量均高于新陆早33号,但棉纤维平均长度、马克隆值和断裂比强度等纤维指标均低于新陆早33号。