Mosaab A. Omar

Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites

A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine Babesia parasites and 5% for equine Babesia and Theileria parasites. The IC50 values of diminazene aceturate obtained by fluorescence and microscopy did not differ significantly. Likewise, the IC50 values of luteolin, pyronaridine tetraphosphate, nimbolide, gedunin, and enoxacin did not differ between the two methods. In conclusion, our fluorescence-based assay uses low HCT and does not require daily replacement of culture medium, making it highly suitable for in vitro large-scale drug screening against Babesia and Theileria parasites that infect cattle and horses.

Gebel-criteria for risk assessment in nanotoxicology

Risk assessment of nanomaterials represents one of the cutting-edge topics in toxicology (Zhao et al., 2014; Lucafo et al., 2013; Fadeel et al., 2013; Kroll et al., 2012; Kim et al., 2012; Hadrup et al., 2012; Lange and Obendorf, 2012; Xu et al., 2013). Numerous nanomaterial containing consumer products have already been introduced on the market, including textiles, sunscreens, paints, car tyres and electronics (Bolt et al., 2012; Kumar and Dhawan, 2013; Schluesener and Schluesener, 2013; Marchan, 2012). The number of manuscripts published in this field is high, with more 500 publications focusing on nanosafety-associated topics per year (Bolt et al., 2012; Schäfer et al., 2013; Horie et al., 2013; Klein et al., 2012; Hoelting et al., 2013; Silva et al., 2014). It has become clear that a detailed physical and chemical characterization of nanomaterials is required for risk evaluation (Park et al., 2013; Xiong et al., 2013; Zhao et al., 2013; Couto et al., 2014). Among the current challenges are the methodological requirements in exposure monitoring (Babič et al., 2014; Lainé et al., 2014; Su et al., 2014; Bruchet et al., 2013). Because of the enormous variability and the rapid development of novel materials it has become difficult for regulators to keep pace and maintain overview. In this complex situation the Advisory Board of the German Society of Toxicology introduced the Gebelcriteria, a novel concept of risk assessment in nanotoxicology (Gebel et al., 2014). According to this concept, a first step in evaluating novel nanomaterials should be to check whether they belong to one of the three following categories: Category 1: Nanoparticles for which toxicity is mediated by the specific chemical properties of its components, such as relaxed ions. Nanomaterials belonging to this category must be evaluated on a case-bycase basis. Category 2 are rigid biopersistent respirable fibrous nanomaterials. They may cause lung cancer and mesotheliomas, if they show a high aspect ratio. In this case they will act similarly as carcinogenic asbestos fibres. Category 3 are respirable granular biodurable particles. After inhalation they may cause inflammation and finally lung cancer. It should be considered that nanomaterials of categories 2 and 3 are of relevance only after inhalation (Gebel et al., 2014). Considering the complex situation in current nanotoxicology the introduction of the three ‘Gebel-criteria’ will facilitate risk assessment in future.

Perspectives of tissues in silico

1 Department of Forensic Medicine and Veterinary Toxicology, Faculty of Veterinary Medicine, South Valley University, 83523 Qena-Egypt 2 Department of Medical Laboratories, Collage of Applied Medical Sciences, Majmaah University-Kingdom of Saudi Arabia 3 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Sıhyyie/Ankara-Türkiye 4 Division of Cerebral Circuitry, National Institute for Physiological Sciences, OkazakiJapan

Recent developments in animal sciences.

1 Department of Forensic Medicine and Veterinary Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena-Egypt 2 Department of Environmental Toxicology, Faculty of Biology, University Essen-Duisburg, Essen-Germany 3 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Sıhyyie/Ankara-Türkiye 4 Animal Nutrition Group, Institute of Animal Science, University of Bonn, Germany 5 Department of Medical Laboratories, College of Science, Majmaah University, AlZulfi-KSA

Quantification of three-dimensional structures in liver tissue

Unpredicted hepatotoxicity represents the most frequent reason for withdrawal of drugs from the market (Godoy et al., 2013). Therefore, large efforts are currently undertaken to establish improved techniques to predict hepatotoxicity (Shimizu et al. One of the concepts of this type of in vitro research is that stress responses to chemicals are similar in vitro and in vivo. Therefore, activation of stress response pathways in vitro may indicate a potential hazard it has also become clear that a full replacement of animal experiments for toxicity testing will not be possible within the next one or two decades (Adler et al., 2011; Hammad, 2013). Reasons are difficulties to include xenobiotic metabolism into in vitro tests, to model interactions between cell types, to extrapolate from in vivo doses to in vitro concentrations and to simulate the consequences of long term exposure in vitro (Tice et al., 2013; Ghallab, 2013). However, one additional aspect may currently be underestimated: we still know too little about mechanisms of in vivo toxicity to establish in vitro systems in a way that the most critical in vivo processes are recapitulated. Although this may seem paradoxical, progress in replacement of animal experiments currently depends on progress in understanding the mechanisms of toxicity in vivo. Histological alterations often constitute a fingerprint of toxic mechanisms (Hammad et al., 2014). Particularly, liver toxicity often leads to altered tissue microarchitecture (Höhme et al. studies on liver histology largely rely on image analysis of two-dimensional pictures. However, many aspects of liver tissue architecture such as the complex bile canalicular and sinusoidal networks can be much better quantified using three-dimensional reconstructions. In this context, it represents an important step forward that Dr. Hammad and his team have