B Acad Nat Med Paris
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B Acad Nat Med Paris · Mar 2016
Review[Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs): Fears of widespread drug resistance].
Malaria treatment with ACTs (Artemisinin-based Combination Therapies), combining a chemical derivative of artemisinin, and a partner drug has, for more than 15 years, produced a notable decrease in the mortality in tropical and subtropical areas. However, since 2008, a serious threat has emerged in western Cambodia, where the clinical efficacy of artemisinins has significantly declined, with a delayed parasite clearance rate and high recrudescence rates in the following weeks. ⋯ ACTs remain effective as long as the partner drug retains its activity but more and more clinical failures related to parasite resistance to both resistant parasites in sub-Saharan Africa, the continent most affected by malaria, as was the case in the past with other antimalarial treatments. It is therefore essential to better understand, from phenotypic and genotypic points of view, the mechanisms of resistance developed by the parasite Plasmodium falciparum face artemisinin and its derivatives in order to offer new therapeutic tools.
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Artemisinin resistance in P. falciparum is spreading in South East Asia and threatens the recent progresses made in the fight against malaria. A race against time has started to eliminate P.falciparum in this region before it becomes resistant to all available treatments. ⋯ The slowly eliminated dihydro-artemisinin and piperaquine is the drug of choice in mass drug administration in the foci of high prevalence of sub-microscopic and asymptomatic infections. Initial results after 18 months of activities are promising: the participation of the population was excellent and there was a sharp reduction of P.falciparum incidence without evidence of worsening resistance.
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Due to major advances in the understanding of iron metabolism as well as in the bioche- iuical, imaging, and genetic domains: i) The nosologicalframework of hemochromatosis (HC) encompasses not only HFE-HC, by far the most frequent HC form, but also non-HFE HC diseases which comprise essentially juvenile HC and the ferroportin disease. ii) The diagnostic approach has become totally non invasive, based on clinical, imaging and biological data. iii) The treatment remains, for most forms, based on venesections, but the innovative emerging therapeutic approach is represented by hepcidin supplementation.
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B Acad Nat Med Paris · Jun 2015
Strategy of translational research on Alzheimer's disease: targets, animal models and biomarkers.
Alzheimer's disease causes severe cognitive alterations in humans and is associated with two main pathologic processes: the β-amyloid and tau pathologies. Imaging biomarkers can reveal the natural history of the disease and show an alteration of glucose metabolism and an evolving cerebral atrophy process. The discovery of new therapies against this disease relies on early stages of drug development that can be evaluated precisely only in animals. ⋯ Animal models can also help to validate new hypotheses on disease mechanisms. We focus here on the protein misfolding hypothesis of Alzheimer as it will probably modulate our vision of the disease in forthcoming years. This hypothesis suggests that native Aβ peptides become toxic when their conformation in alpha helices evolves into a beta-sheet conformation and also suggests that misfolded proteins can transmit their misfolded conformation to normal proteins.
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Pain is a real issue of public health, quality and evolution of a system of health test: this is a major social problem. Pain management meets a humanistic, ethical purpose and dignity of man because of the physical and psychological implications. It induces a disability which excludes the patient of society gradually or suddenly. ⋯ The progress of medicine has helped the healing of certain serious diseases, but also favoured acute diseases to turn to chronic diseases. The result is an increase in of lifetime sometimes without disease, but this survival may be also accompanied by disease or disability. Progress, pain and suffering, the end of life, ethics will be the core of the basic thoughts of tomorrow.