Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19–21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work

An Integrated Approach for a Structural and Functional Evaluation of Biosimilars: Implications for Erythropoietin

BACKGROUND: Authorization to market a biosimilar product by the appropriate institutions is expected based on biosimilarity with its originator product. The analogy between the originator and its biosimilar(s) is assessed through safety, purity, and potency analyses. OBJECTIVE: In this study, we proposed a useful quality control system for rapid and economic primary screening of potential biosimilar drugs. For this purpose, chemical and functional characterization of the originator rhEPO alfa and two of its biosimilars was discussed. METHODS: Qualitative and quantitative analyses of the originator rhEPO alfa and its biosimilars were performed using reversed-phase high-performance liquid chromatography (RP-HPLC). The identification of proteins and the separation of isoforms were studied using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF–MS) and two-dimensional gel electrophoresis (2D-PAGE), respectively. Furthermore, the biological activity of these drugs was measured both in vitro, evaluating the TF-1 cell proliferation rate, and in vivo, using the innovative experimental animal model of the zebrafish embryos. RESULTS: Chemical analyses showed that the quantitative concentrations of rhEPO alfa were in agreement with the labeled claims by the corresponding manufacturers. The qualitative analyses performed demonstrated that the three drugs were pure and that they had the same amino acid sequence. Chemical differences were found only at the level of isoforms containing N-glycosylation; however, functional in vitro and in vivo studies did not show any significant differences from a biosimilar point of view. CONCLUSION: These rapid and economic structural and functional analyses were effective in the evaluation of the biosimilarity between the originator rhEPO alfa and the biosimilars analyzed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40259-015-0136-3) contains supplementary material, which is available to authorized users

Data from: Effects of abiotic environmental factors and land use on the diversity of carrion-visiting silphid beetles (Coleoptera: Silphidae): a large scale carrion study

No description availabl

Clicker Training Mice for Improved Compliance in the Catwalk Test

The CatWalk test relies on the run of mice across the platform to measure a constant speed with low variation. Mice usually require a stimulus to walk to the end of the catwalk. However, such stimuli are usually aversive and can impair welfare. Positive reinforcement training of laboratory animals is a thriving tool for refinement and contributes to meeting the demands instituted by Directive 2010/63/EU. We have already demonstrated the positive effects of clicker training. In this study, we trained male and female mice to complete the CatWalk protocol while assessing the effects of training on their well-being (Open Filed and Elevated Plus Maze). In the CatWalk test, we observed that clicker training improved the running speed of the mice. In addition, clicker training reduced the number of runs required by mice, which was more pronounced in males. Clicker training lowered anxiety-like behaviors in our mice, especially in females, where a significant difference was observed between trained and untrained ones. Based on our findings, we hypothesize that clicker training is an effective tool to motivate mice and increase performance on the CatWalk test without potentially impairing their welfare (e.g., by puffing them)

Effects of abiotic environmental factors and land use on the diversity of carrion-visiting silphid beetles (Coleoptera: Silphidae) : a large scale carrion study

Anthropogenic land use causes global declines in biodiversity. Despite the knowledge that animal carrion is the most nutrient-rich form of dead organic matter, studies on landscape and local scales determining whether and the means by which land use intensity influences the diversity of the carrion-associated insect fauna are globally scarce. We investigated the effects of land use intensity and abiotic and biotic environmental factors on the abundance, species richness, and diversity of the important ecosystem-service-providing silphid beetle taxon (carrion beetles) in three regions of Germany. In 61 forest stands distributed over three geographically distinct regions in Central Europe, we trapped silphid beetles on exposed piglet cadavers during late summer. In all three regions, higher ambient temperatures and higher fine sand contents were associated with the abundance of the silphid beetle taxa. The carrion community silphid diversity was negatively affected by an increase in mean ambient temperature in all three regions. Although management intensity in forests did not affect the overall abundance of Silphidae, the abundance of Nicrophorus humator decreased significantly with higher forest management intensity across all three regions. Unmanaged and age-class forests showed a higher abundance of N. humator compared with extensively managed forest stands. These findings indicate that N. humator has potential as an indicator species for anthropogenic disturbances in forests. Overall, the direct responses of the silphid beetle community to diverse soil characteristics underline soil as an important factor determining the abundance and diversity of necrophagous carrion beetles in Central Europe. To protect these valuable ecosystem-service providers, forest-management-induced soil modifications need to be paid close attention

Effects of abiotic environmental factors and land use on the diversity of carrion-visiting silphid beetles (Coleoptera: Silphidae): A large scale carrion study

<div><p>Anthropogenic land use causes global declines in biodiversity. Despite the knowledge that animal carrion is the most nutrient-rich form of dead organic matter, studies on landscape and local scales determining whether and the means by which land use intensity influences the diversity of the carrion-associated insect fauna are globally scarce. We investigated the effects of land use intensity and abiotic and biotic environmental factors on the abundance, species richness, and diversity of the important ecosystem-service-providing silphid beetle taxon (carrion beetles) in three regions of Germany. In 61 forest stands distributed over three geographically distinct regions in Central Europe, we trapped silphid beetles on exposed piglet cadavers during late summer. In all three regions, higher ambient temperatures and higher fine sand contents were associated with the abundance of the silphid beetle taxa. The carrion community silphid diversity was negatively affected by an increase in mean ambient temperature in all three regions. Although management intensity in forests did not affect the overall abundance of Silphidae, the abundance of <i>Nicrophorus humator</i> decreased significantly with higher forest management intensity across all three regions. Unmanaged and age-class forests showed a higher abundance of <i>N</i>. <i>humator</i> compared with extensively managed forest stands. These findings indicate that <i>N</i>. <i>humator</i> has potential as an indicator species for anthropogenic disturbances in forests. Overall, the direct responses of the silphid beetle community to diverse soil characteristics underline soil as an important factor determining the abundance and diversity of necrophagous carrion beetles in Central Europe. To protect these valuable ecosystem-service providers, forest-management-induced soil modifications need to be paid close attention.</p></div