Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

《农业环境科学学报》2022年刊出论文简评

本文简要地介绍了2022年《农业环境科学学报》刊出论文的总体情况和农业环境领域当前的研究热点,重点评述了土壤环境、环境健康与农产品安全、废弃物处理及资源化利用、农业与全球变化领域刊出的论文,总结了当前这些领域重点关注的科学问题及取得的主要进展。     

饲料原料与成品的仓储监管

饲料安全即畜产品安全、食品安全和生态安全。在饲料的整个生产加工、储运与使用过程中,往往由于管理不善及不可克服的客观因素的影响,容易使其原料或成品出现"三害"——霉变毒害、虫害和鼠害。仅以仓储监管中常出现这些问题的危害性与克制的具体方法做一综述,并着重提出了"狠抓仓储环境,营造一个良好的生态氛围,乃是实现饲料安全的根本性措施"的观点,以引起相关单位与生产者关注。     

高县茶叶生产存在的质量安全问题及对策

介绍了高县茶叶发展现状,分析其生产中存在的质量安全问题,并提出对策,以期为该县茶叶优质安全发展提供参考。     

维生素E的生物学功能和安全性评价研究进展

维生素E是机体重要的脂溶性维生素,具有抗氧化、维持生育和调节免疫系统等诸多生物学功能.多数研究表明维生素E毒性较低,但高剂量的维生素E可引起机体内其他脂溶性维生素的缺乏,同时对免疫效果产生不利影响.本文对维生素E的生物学功能、吸收代谢特点和安全性评价进行了综述,旨在为在动物上制订维生素E的安全限量提供理论参考.     

基于叶绿素评价氟啶胺对几种农作物的生态安全性

对大田栽培作物玉米、棉花、红薯和花生,用喷雾器喷施不同浓度杀菌剂氟啶胺,24 h后测定四种作物叶绿素和类胡萝卜素的含量。结果表明：2 000至3 000倍氟啶胺对花生、3 000倍氟啶胺对红薯和棉花是安全的,而氟啶胺对玉米则几乎是不利的。     

非调质钢分类的研究

目前非调质钢应用中存在钢种较多、钢号繁杂的问题，因此，有必要对共进行分类。本文提出可以分别根据非调质钢的发展阶段、显微组织、碳含量、合金元素含量的不同来进行分类，这些新的分类方法可用于指导非调质钢的生产管理。     

Assessing hygiene proficiency on organic and conventional pig farms regarding pork safety: A pilot study in Finland

A key element in the EU Common Agricultural Policy (CAP) will be a single farm payment system that is linked to compliance with rules on, for instance hygiene standards. However, there are no recommended methods for assessing the hygiene proficiency of pig production farms. The present study was undertaken to develop a method for this purpose. A first implementation was done on pilot scale; with a set of both conventional and organic pig farms (N = 15). Fifty hygiene-related factors were selected, especially with reference to the possible proliferation of enteric pathogens Listeria monocytogenes, Yersinia enterocolitica and Yersinia pseudotuberculosis. The factors were allocated into 8 evaluation categories: (1) general production management, (2) animal density, (3) the outdoor area for pigs, (4) pest and pet animals, (5) general hygiene in the piggery, (6) pen hygiene, (7) feed production hygiene, and (8) feeding hygiene. A farm questionnaire and a supplementary on-site observation form were devised, and one arbitrary scale of hygiene points assigned for each factor. In addition to the mailed questionnaires, one person subsequently visited all the farms, perused the questionnaire with the owners and completed the observation form. The hygiene scores of the farms in each evaluation category were compared both without weighting and with weighting based on expert opinions. The method proved to be feasible and applicable to different types of production.     

Enjoyment and fear in urban woodlands – Does age make a difference?

Urban dwellers experience conflicting thoughts and feelings about urban woodlands; valued for their natural qualities, the relief they provide from the stress of modern urban living and the opportunities they afford for children's play and exploration. At the same time the seclusion inherent in this type of urban greenspace seems fraught with risk from crime, vandalism and abuse. Whilst many of these characteristics are well-researched, less is known about the differing perceptions of particular social groups. This study aimed to explore the ways in which age affects urban dwellers’ aspirations, values and fears concerning the woods, and woodland accessibility, focusing on the views of elderly people (aged over 65). This pilot study was based in Norfolk Heritage Park, an urban park containing a variety of woodland settings located in Sheffield, UK. The questionnaire survey (participantsn=97) revealed that although walking is the most popular leisure activity, most respondents did not visit urban parks as often as they would like, regardless of age. Whilst many of the meanings associated with urban woodland (“relaxation”, “peacefulness”, “seasonal change”, “scenery” and “education”) were shared amongst age groups, it seemed that the elderly respondents particularly valued the woods for their links with the past, and opportunities for immersion in the natural world. Some respondents from all age groups had fears about their personal security in the woodland, and the concerns of the elderly were heightened by their perceived frailty, reduced mobility and sense of vulnerability; this age group had a corresponding need for particular measures to alleviate these problems. The study provides preliminary evidence for the idea that adults of different ages have differing perceptions and requirements in relation to urban woodlands. Due to the small sample size and other methodological issues, further research is needed to confirm and develop the findings.     

转基因植物对蜜蜂的安全性（下）

转基因植物已在全球范围内大面积推广应用 ,全球 5大转基因植物中的油菜、棉花、玉米均是主要的蜜粉源植物 ,对养蜂生产有重要意义 ,其对蜜蜂的安全性问题值得关注。 2种主要的抗虫 (Bt毒蛋白、蛋白酶抑制剂 )基因或抗真菌基因的产物只有在高浓度时才可能对工蜂的寿命、消化酶活性、行为等有不良影响。从目前的研究来看 ,转基因植物对蜜蜂是安全的