16 research outputs found

    The Arguments for Euthanasia and Physician-Assisted Suicide: Ethical Reflections

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    Aplicacion del modelo HBV a la cuenca del Río Cauto en Cuba

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    The work deseribed in this report, was done in eollaboration between the Swedish Meteorological and Hydrologieal Institute (SMID) and the Instituto Nacional de Reeursos Hidraulieos de Cuba (INRH), with financial support from the Swedish Ageney for Teehnieal and Eeonomie Cooperation (BITS). The projeet also reeeived aetive assistanee from the Cuban State Committee for Economie Collaboration (CECE). The main objetive of the projeet was the applieation of the HBV model to the Cauto river basin in eastem Cuba, in order to - foreeast the inflow volwne to the reservoirs located in the basin and - eontribute to the rational use of water in the reservoirs

    A rapid molecular diagnosis of cutaneous leishmaniasis bycolorimetric malachite green-loop-mediated isothermal amplification(LAMP) combined with an FTA card as a direct sampling tool

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    Leishmaniasis remains one of the world’s most neglected diseases, and early detection of the infectiousagent, especially in developing countries, will require a simple and rapid test. In this study, we establisheda quick, one-step, single-tube, highly sensitive loop-mediated isothermal amplification (LAMP) assay forrapid detection of Leishmania DNA from tissue materials spotted on an FTA card. An FTA-LAMP withpre-added malachite green was performed at 64?C for 60 min using a heating block and/or water bathand DNA amplification was detected immediately after incubation. The LAMP assay had high detectionsensitivity down to a level of 0.01 parasites per l. The field- and clinic-applicability of the colorimetricFTA-LAMP assay was demonstrated with 122 clinical samples collected from patients suspected of havingcutaneous leishmaniasis in Peru, from which 71 positives were detected. The LAMP assay in combinationwith an FTA card described here is rapid and sensitive, as well as simple to perform, and has great potentialusefulness for diagnosis and surveillance of leishmaniasis in endemic areas

    Benzodiazepine scaffold as drug-like molecular simplification of FR235222: A chemical tool for exploring HDAC inhibition

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    Synthesis, computational study and biological evaluation of peptidomimetic analogues of FR235222 (3), a natural immunosuppressant and HDAC inhibitor, have been reported. These new compounds, bearing α-hydroxyketone moiety, as more stable zinc binding group (ZBG), were evaluated in vitro as HDAC inhibitors against the human HDACs isoforms 1-9 and in cellular antiproliferative assays on U937 human leukemia cell line. The 1,4-benzodiazepin-2,5- dione (BDZ), capping group and the natural ZBG, (S,R)-2-amino-9-hydroxy-8- oxodecanoic acid (Ahoda), were evaluated in order to probe HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed an interesting activity against a number of HDAC isozymes. The observed activity profile was rationalized by a computational assisted SAR study, in order to understand how the BDZ classes interact with the enzyme into the catalytic pocket. Despite its poor solubility, compound 17b showed significant antiproliferative profile and HDAC inhibition activity. In order to assess how the solubility issue could have affected the biological outcome, bioassay conditions were reproduced and quantification of precipitated particulate material was evaluated by turbidimetric and NMR studies together with physicochemical descriptors prediction. Thus, BDZ 17b has been chosen to be promising lead compounds for further optimization, in order to elucidate molecule-enzyme surface recognition
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