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The European Federation for Pharmaceutical Sciences (EUFEPS) was founded 25 years ago by more than 20 national pharmaceutical societies and faculty members. As a pan-European organization, it brings together pharmaceutical societies as well as academic, industrial and regulatory scientists engaged in drug research and development, drug regulation and education of professionals working in these fields. EUFEPS represents pharmaceutical sciences in Europe and is recognized as such by both the European Commission and the European Medicines Agency. EUFEPS cooperates with the European Federation of Pharmaceutical Industries and other European organizations and maintains global connections with agencies such as the US Food and Drug Administration and the American Association of Pharmaceutical Scientists. EUFEPS has established specified networks forming the basis of its activities. The creation of a Network on Veterinary Medicines is prompted by the manifold problems resulting from the use of veterinary drugs and its inherent interconnections with human medicine, environmental and public health. A long-term goal of this initiative was to expand the spectrum of available therapeutics for use in animals, including the development of innovative delivery systems.

Veterinary medicines account for a substantial portion of the production, sale, and consumption of medicines in Europe, and probably world-wide. This calls our attention to the fact that only healthy farm animals can ensure safe and sufficient livestock products to meet the growing demand for animal protein. Human and veterinary medicine share many common features - expressed and symbolised by the "One Health Concept". This concept forms the logical basis for the maintenance of healthy livestock by the control of zoonoses and foodborne diseases, the prevention of poor sanitary conditions, and the reduction of microbial and parasitic threats, including resistance to antibiotics and anti-parasitic drugs. Achieving these aims will require international cooperation and interdisciplinary action. A new initiative of the European Federation for Pharmaceutical Sciences (EUFEPS) - the Network on Veterinary Medicines - has the potential to manage and overcome these challenges. A number of EUFEPS expertise networks have already been established, and some will be instrumental in supporting the activities of the Network on Veterinary Medicines, e.g., the European Network on PharmacoGenomics Research and Implementation (EPRIN), as well as the Network on Bioavailability and Biopharmaceutics, and the envisioned Network on Systems Pharmacology. Notably, the EUFEPS Networks on Safety Sciences, on Environment and Pharmaceuticals and on NanoMedicine as well as on Regulatory Science, represent promising partners. New technologies are being introduced to veterinary medicine for the treatment of numerous and frequently species-specific conditions. Scientific input from different areas is required to evaluate the potential benefitrisk profiles of these novel products, drug delivery techniques, and medical attention for animals as a whole. Drug treatment of food-producing animals inevitably affects consumer safety and public health, as any administration of medicines to animals may result i

Amyotrophic lateral sclerosis (ALS) affects anterior horn cells of the spinal cord causing an indolent slow and steady deterioration of muscle strength leading inevitably to death in respiratory failure. ALS is a model condition for neurodegenerative disorders. Exposure to different agents dispersed in the environment has been suggested to cause neurodegeneration but no convincing evidence for such a link has yet been presented. Respiratory exposure to metallic mercury (Hg0) from different sources may be suspected. Body distribution of metallic mercury is fast and depends on solubility properties. Routes of transport, metabolism, excretion and biological half-life determine the overall toxic effects. Inhalation experiments were performed in 1984 where small marmoset monkeys (Callithrix jacchus) were exposed to 203Hg0 vapour mixed into the breathing air (4–5 μg/l). After 1 hr of exposure, they were killed and whole body autoradiograms prepared to study the distribution of mercury within organs. Autoradiograms showed that Hg was deposited inside the spinal cord. Areas of enhanced accumulation anatomically corresponding to motor nuclei could be observed. This study describes a reinvestigation, with new emphasis on the spinal cord, of these classical metal exposure data in a primate, focusing on their relevance for the causation of neurodegenerative disorders. A comparison with more recent rodent experiments with similar findings is included. The hypothesis that long-time low-dose respiratory exposure to metals, for example, Hg, contributes to neurodegenerative disorders is forwarded and discussed.

A major objective of Computational Toxicology is to provide reliable and useful estimates in silico of (potentially) harmful actions of chemicals in humans. Predictive models are commonly based on in vitro and in vivo data, and aims at supporting risk assessment in various areas, including the environmental protection, food, and pharmaceutical sectors. The field is however hampered by the lack of standards, access to high quality data, validated predictive models, as well as means to connect toxicity data to genomics data. We present a framework and roadmap for a novel public infrastructure for predictive computational toxicology and chemical safety assessment, consisting of: (1) a repository capable of aggregating high quality toxicity data with gene expression data, (2) a repository where scientists can share and download predictive models for chemical safety, and (3) a user-friendly platform which makes the services and resources accessible for the scientific community. Databases under the framework will adhere to open standards and use standardized open exchange formats in order to interoperate with emerging international initiatives, such as the FP7-funded OpenTox and ToxBank projects. The infrastructure will strengthen and facilitate already ongoing activities within in silico toxicology, open up new possibilities for incorporating genomics data in chemicals safety modeling (toxicogenomics), as well as deepen the exploitation of signal transduction networks. The initiative will lay the foundation needed to boost decision support in risk assessment in a wide range of fields, including drug discovery, food safety, as well as agricultural and ecological safety assessment.

Microvascular pericytes are of key importance in neoformation of blood vessels, in stabilization of newly formed vessels as well as maintenance of angiostasis in resting tissues. Furthermore, pericytes are capable of differentiating into pro-fibrotic collagen type I producing fibroblasts. The present study investigates the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) on pericyte proliferation, cell viability, migration and differentiation. The results show that HDAC inhibition through exposure of pericytes to VPA in vitro causes the inhibition of pericyte proliferation and migration with no effect on cell viability. Pericyte exposure to the potent HDAC inhibitor Trichostatin A caused similar effects on pericyte proliferation, migration and cell viability. HDAC inhibition also inhibited pericyte differentiation into collagen type I producing fibroblasts. Given the importance of pericytes in blood vessel biology a qPCR array focusing on the expression of mRNAs coding for proteins that regulate angiogenesis was performed. The results showed that HDAC inhibition promoted transcription of genes involved in vessel stabilization/maturation in human microvascular pericytes. The present in vitro study demonstrates that VPA influences several aspects of microvascular pericyte biology and suggests an alternative mechanism by which HDAC inhibition affects blood vessels. The results raise the possibility that HDAC inhibition inhibits angiogenesis partly through promoting a pericyte phenotype associated with stabilization/maturation of blood vessels.

Background: Endogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17), sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon. Results: We identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2 exposure and sex effects were neuropeptide K (downregulated by EE2 in males and females), gastrin-releasing peptide (more highly expressed in control and EE2 exposed males) and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex). We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide. Conclusions: This study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model., ReproSafe

Polybrominated diphenyl ethers (PBDEs) are commonly used flame retardants in various consumer products. Pre- and postnatal exposure to congeners of PBDEs disrupts normal brain development in rodents. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to analyze concentration-dependent differences in protein expression in cultured cortical cells isolated from rat fetuses (GD 21) after 24 h exposure to PBDE-99 (3, 10, or 30 muM). Changes on a post-translational level were studied using a 1 h exposure to 30 muM PBDE-99. The effects of 24 h exposure to 3 and 30 muM PBDE-99 on mRNA levels were measured using oligonucleotide microarrays. A total of 62, 46, and 443 proteins were differentially expressed compared to controls after 24 h of exposure to 3, 10, and 30 muM PDBE-99, respectively. Of these, 48, 43, and 238 proteins were successfully identified, respectively. We propose that the biological effects of low-concentration PBDE-99 exposure are fundamentally different than effects of high-concentration exposure. Low-dose PBDE-99 exposure induced marked effects on cytoskeletal proteins, which was not correlated to cytotoxicity or major morphological effects, suggesting that other more regulatory aspects of cytoskeletal functions may be affected. Interestingly, 0.3 and 3 muM, but not 10 or 30 muM increased the expression of phosphorylated (active) Gap43, perhaps reflecting effects on neurite extension processes.

Replik på Maths Berlins artikel Desinformation om biverkningsriskerna för barn och foster med tiomersal i vaccin

There is an urgent need for new in vitro methods to predict the potential developmental toxicity of candidate drugs in the early lead identification and optimisation process. This would lead to a reduction in the total number of animals required in full-scale developmental toxicology studies, and would improve the efficiency of drug development. However, suitable in vitro systems permitting robust high-throughput screening for this purpose, for the most part, remain to be designed. An understanding of the mechanisms involved in developmental toxicity may be essential for the validation of in vitro tests. Early response biomarkers - even a single one - could contribute to reducing assay time and facilitating automation. The use of toxicogenomics approaches to study in vitro and in vivo models in parallel may be a powerful tool in defining such mechanisms of action and the molecular targets of toxicity, and also for use in finding possible biomarkers of early response. Using valproic acid as a model substance, the use of DNA microarrays to identify teratogen-responsive genes in cell models is discussed. It is concluded that gene expression in P19 mouse embryocarcinoma cells represents a potentially suitable assay system, which could be readily used in a tiered testing system for developmental toxicity testing.

Background: The contrasting dose of sex chromosomes in males and females potentially introduces a large-scale imbalance in levels of gene expression between sexes, and between sex chromosomes and autosomes. In many organisms, dosage compensation has thus evolved to equalize sex-linked gene expression in males and females. In mammals this is achieved by X chromosome inactivation and in flies and worms by up- or down-regulation of X-linked expression, respectively. While otherwise widespread in systems with heteromorphic sex chromosomes, the case of dosage compensation in birds (males ZZ, females ZW) remains an unsolved enigma. Results: Here, we use a microarray approach to show that male chicken embryos generally express higher levels of Z-linked genes than female birds, both in soma and in gonads. The distribution of male-to-female fold-change values for Z chromosome genes is wide and has a mean of 1.4-1.6, which is consistent with absence of dosage compensation and sex-specific feedback regulation of gene expression at individual loci. Intriguingly, without global dosage compensation, the female chicken has significantly lower expression levels of Z-linked compared to autosomal genes, which is not the case in male birds. Conclusion: The pronounced sex difference in gene expression is likely to contribute to sexual dimorphism among birds, and potentially has implication to avian sex determination. Importantly, this report, together with a recent study of sex-biased expression in somatic tissue of chicken, demonstrates the first example of an organism with a lack of global dosage compensation, providing an unexpected case of a viable system with large-scale imbalance in gene expression between sexes.

BACKGROUND: Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms. RESULTS: Using cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head) that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females) were common among the differentially expressed genes, several of which (WPKCI-8, HINT, MHM non-coding RNA) have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7, CCNH and BTF2-P44) encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation. CONCLUSION: In conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.