1,437 research outputs found

    Antimicrobial consumption at the hospital level in latin america. Similarities and differences according to each country

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    One of the main problems for health service around the world is the antimicrobial resistance (AMR). Objective: to describe the antimicrobial consumption (AMC) at hospital level in Latin American countries and compare the amount and type of antibiotics usage among them in order to guide local public health actions towards AMR prevention.Design: A descriptive study of antimicrobial consumption at hospital level among six health institution in Latin America with an analytical comparative stage. Antimicrobials included corresponded to the WHO Anatomical Therapeutic Chemical (ATC) classification system subgroups: J01, A07A and P01AB. Methods: WHO GLASS methodology was applied for surveillance of AMC, using the ATC classification based on Defined Daily Dose (DDD) and DDD/100 hospital discharges as standard unit of measurement. Antimicrobials consumed were also classified according to the WHO AccessWatch-Reserve (AWaRe) classification. Results: The quantitative data, measured in DDD/100 hospital discharges, showed a wide range of consumption (182.48 - 2260.95). Qualitative analysis according to the AWaRe classification also showed a wide range in terms of consumption of Access (38.14% - 73.64%), Watch (24.93% - 60 .53%) and Reserve (0.31% - 3.55%) groups expressed as a percentage of the total consumption.Conclusion: Great heterogeneity and arbitrariness exist in the selection of antimicrobials for hospital use. Although this situation might be explained on local antimicrobial resistance, the history of prescription, local pharmaceutical promotion, and pharmacological education of health professional in each country, particular habits and distinctive culture may justify the differential consumption patterns observed in each institution in this study.Fil: Marin, Gustavo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Giangreco, Luis. Universidad Nacional de La Plata; ArgentinaFil: Hernández, Yago. Universidad Nacional de La Plata; ArgentinaFil: Dorati, Cristian. Universidad Nacional de La Plata; ArgentinaFil: Mordujovich Buschiazzo, Perla. Universidad Nacional de La Plata; ArgentinaFil: Bay, María Rosa. Hospital Interzonal General de Agudos San Roque - Mb Gonnet ; Gobierno de la Provincia de Buenos Aires;Fil: Gonzalez, Gladys María Adriana. Hospital Interzonal General de Agudos San Roque - Mb Gonnet ; Gobierno de la Provincia de Buenos Aires;Fil: Aldunate, Francisca. Pontificia Universidad Católica de Chile; ChileFil: López Peña, Mónica. Ministerio de Salud y Protección Social; ColombiaFil: Martínez Parra, Adriana. Ministerio de Salud y Protección Social; ColombiaFil: Ching Fung, Shing Mi. Costa Rican social security; Costa RicaFil: Alfonso Arvez, María José. Ministry of Public Health and Social Welfare; ParaguayFil: Mantilla Ponte, Hilda. General Directorate of Medicines, Supplies and Drugs; PerúFil: Marin, Danini. General Directorate of Medicines, Supplies and Drugs; PerúFil: Rojas, Robin. General Directorate of Medicines, Supplies and Drugs; PerúFil: Castro, José Luis. Pan-American Health Organization; Estados Unido

    The use of caspase inhibitors in pulsed-field gel electrophoresis may improve the estimation of radiation-induced DNA repair and apoptosis

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    <p>Abstract</p> <p>Background</p> <p>Radiation-induced DNA double-strand break (DSB) repair can be tested by using pulsed-field gel electrophoresis (PFGE) in agarose-encapsulated cells. However, previous studies have reported that this assay is impaired by the spontaneous DNA breakage in this medium. We investigated the mechanisms of this fragmentation with the principal aim of eliminating it in order to improve the estimation of radiation-induced DNA repair.</p> <p>Methods</p> <p>Samples from cancer cell cultures or xenografted tumours were encapsulated in agarose plugs. The cell plugs were then irradiated, incubated to allow them to repair, and evaluated by PFGE, caspase-3, and histone H2AX activation (γH2AX). In addition, apoptosis inhibition was evaluated through chemical caspase inhibitors.</p> <p>Results</p> <p>We confirmed that spontaneous DNA fragmentation was associated with the process of encapsulation, regardless of whether cells were irradiated or not. This DNA fragmentation was also correlated to apoptosis activation in a fraction of the cells encapsulated in agarose, while non-apoptotic cell fraction could rejoin DNA fragments as was measured by γH2AX decrease and PFGE data. We were able to eliminate interference of apoptosis by applying specific caspase inhibitors, and improve the estimation of DNA repair, and apoptosis itself.</p> <p>Conclusions</p> <p>The estimation of radiation-induced DNA repair by PFGE may be improved by the use of apoptosis inhibitors. The ability to simultaneously determine DNA repair and apoptosis, which are involved in cell fate, provides new insights for using the PFGE methodology as functional assay.</p

    Microarray Screening for Genes Involved in Oligodendrocyte Differentiation in the Zebrafish CNS

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    Within the vertebrate nervous system, myelination is required for the normal function of neurons by facilitating the rapid conduction of action potentials along axons. Oligodendrocytes are glial cells which myelinate axons in the central nervous system. Disruption of myelination and remyelination failure can cause human diseases such as multiple sclerosis. Despite the importance of myelination, the molecular basis of oligodendrocyte differentiation and myelination are still poorly understood. To understand the molecular mechanisms which regulate oligodendrocyte differentiation and myelination, novel genes were identified using a microarray analysis. The analysis used oligodendrocyte lineage cells isolated from transgenic zebrafish expressing fluorescent proteins in the oligodendrocyte lineage cells. Seven genes not previously known to be involved in oligodendrocyte differentiation were identified, and their expression during oligodendrocyte development was validated

    Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

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    &lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

    The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

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    Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence. © 2024, The Author(s)

    Observation of trapped light within the radiation continuum

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    The ability to confine light is important both scientifically and technologically. Many light confinement methods exist, but they all achieve confinement with materials or systems that forbid outgoing waves. These systems can be implemented by metallic mirrors, by photonic band-gap materials, by highly disordered media (Anderson localization) and, for a subset of outgoing waves, by translational symmetry (total internal reflection) or by rotational or reflection symmetry. Exceptions to these examples exist only in theoretical proposals. Here we predict and show experimentally that light can be perfectly confined in a patterned dielectric slab, even though outgoing waves are allowed in the surrounding medium. Technically, this is an observation of an ‘embedded eigenvalue’—namely, a bound state in a continuum of radiation modes—that is not due to symmetry incompatibility. Such a bound state can exist stably in a general class of geometries in which all of its radiation amplitudes vanish simultaneously as a result of destructive interference. This method to trap electromagnetic waves is also applicable to electronic and mechanical waves.United States. Army Research Office (Institute for Soldier Nanotechnologies under contract no. W911NF-07-D0004)United States. Department of Energy (grant no. DE-SC0001299)National Science Foundation (U.S.) (NSF grant no. DMR-0819762
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