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See detail2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes
Carballeira, N. M.; Bwalya, A. G.; Itoe, M. A. et al

in Bioorganic & Medicinal Chemistry Letters (2014), 24(17), 4151-4157

The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study ... [more ▼]

The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study, we investigated a series of 2-alkynoic fatty acids (2-AFAs) with chain lengths between 14 and 18 carbon atoms for dual in vitro activity against both life stages. 2-Octadecynoic acid (2-ODA) was identified as the best inhibitor of Plasmodium berghei parasites with ten times higher potency (IC50 = 0.34 μg/ml) than the control drug. In target determination studies, the same compound inhibited three Plasmodium falciparum FAS-II (PfFAS-II) elongation enzymes PfFabI, PfFabZ, and PfFabG with the lowest IC50 values (0.28-0.80 μg/ml, respectively). Molecular modeling studies provided insights into the molecular aspects underlying the inhibitory activity of this series of 2-AFAs and a likely explanation for the considerably different inhibition potentials. Blood stages of P. falciparum followed a similar trend where 2-ODA emerged as the most active compound, with 20 times less potency. The general toxicity and hepatotoxicity of 2-AFAs were evaluated by in vitro and in vivo methods in mammalian cell lines and zebrafish models, respectively. This study identifies 2-ODA as the most promising antiparasitic 2-AFA, particularly towards P. berghei parasites. © 2014 Elsevier Ltd. All rights reserved. [less ▲]

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See detailThe SAFE FOODS framework for improved risk analysis of foods.
König, Ariane UL; Kuiper, H. A.; Marvin, H. J. P. et al

in Food Control (2010), 21(12), 1566-1587

The SAFEFOODS framework proposes an integrated five-step procedure for the risk analysis. The five steps are: framing, risk assessment, evaluation, risk management, and review. The framework is designed ... [more ▼]

The SAFEFOODS framework proposes an integrated five-step procedure for the risk analysis. The five steps are: framing, risk assessment, evaluation, risk management, and review. The framework is designed to address both risks and benefits. The SAFEFOODS approach introduces a 20-member Interface Committee, headed by a risk manager, to run the procedure. First third of the members is risk managers, second third is independent scientific experts and the last third is stakeholders with economic interests and with consumer interests. The role of the different steps in the procedure and the role of each category of Committee Members during the process are described. The proposal suggests a strict separation of responsibilities between managerial members on one side and scientific members and stakeholder members on the other side. This division of responsibilities in the committee opens up new possibilities for transparency, openness and participation without violation of the delegation-of-power rule. For the communication with the interested parties and the public at large during the process it is foreseen to create an Internet Forum, and use press conferences, press releases and interviews. Overall the SAFEFOODS proposal shall be seen as an invitation for rethinking the current risk assessment/risk management system in EU. [less ▲]

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