566 research outputs found

    Visual decline in aged mice is delayed by proinsulin

    Get PDF
    1 p.Visual decline is normally associated to the aging process.We search for cellular and molecular processes associated to normal aging. In addition, we have previously shown that human proinsulin (hPi) delays vision loss, as determined by electroretinography (ERG),and retinal degeneration, as determined by photoreceptor counting,in the rd10 mouse and the P23H rat models of Retinitis Pigmentosa.Our aim is to reveal additional potential benets of a hPi-based treatment in the aged retina.CONSOLIDER CSD2010-00045 SpainPeer reviewe

    Adalimumab reduces photoreceptor cell death in a mouse model of retinal degeneration

    Get PDF
    Growing evidence suggests that inflammation is involved in the progression of retinitis pigmentosa (RP) both in patients and in animal models. The aim of this study was to investigate the effect of Adalimumab, a monoclonal anti-TNFα antibody, on retinal degeneration in a murine model of human autosomal recessive RP, the rd10 mice at postnatal day (P) 18. In our housing conditions, rd10 retinas were seriously damaged at P18. Adalimumab reduced photoreceptor cell death, as determined by scoring the number of TUNEL-positive cells. In addition, nuclear poly (ADP) ribose (PAR) content, an indirect measure of PAR polymerase (PARP) activity, was also reduced after treatment. The blockade of TNFα ameliorated reactive gliosis, as visualized by decreased GFAP and IBA1 immunolabelling (Müller cell and microglial markers, respectively) and decreased up-regulation of TNFα gene expression. Adalimumab also improved antioxidant response by restoring total antioxidant capacity and superoxide dismutase activity. Finally, we observed that Adalimumab normalized energetic and metabolic pattern in rd10 mouse retinas. Our study suggests that the TNFα blockade could be a successful therapeutic approach to increase photoreceptor survival during the progression of RP. Further studies are needed to characterize its effect along the progression of the diseaseThis work was supported by the European Regional Development Fund, Institute of Health Carlos III, PI12/0481, SAF2013-41059-R and SAF2013-41945 from the Spanish Ministry of Economy and Competitiveness (MEC). CIBERER is an initiative of the Institute of Health Carlos III from the MEC. Regina Rodrigo has a research-contract SNS Miguel Servet (CP09/118) from Institute of Health Carlos II

    Behavioral modeling of SAR ADCs in Simulink

    Get PDF
    This paper presents a toolbox for the behavioral simulation of SAR ADCs in Simulink®. The models include the most limiting circuit effects such as sampled thermal noise, capacitor mismatch, finite settling, comparator noise and offset. A user friendly interface is also included to allow study and high-level design of SAR ADCs, which is illustrated by means of a design example. It is also shown that the proposed toolbox is several orders of magnitude faster than electrical simulators, while keeping a high accuracy

    p75NTR antagonists attenuate photoreceptor cell loss in murine models of retinitis pigmentosa

    Get PDF
    ProNGF signaling through p75NTR has been associated with neurodegenerative disorders. Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies that causes progressive photoreceptor cell degeneration and death, at a rate dependent on the genetic mutation. There are more than 300 mutations causing RP, and this is a challenge to therapy. Our study was designed to explore a common mechanism for p75NTR in the progression of RP, and assess its potential value as a therapeutic target. The proNGF/p75NTR system is present in the dystrophic retina of the rd10 RP mouse model. Compared with wild-type (WT) retina, the levels of unprocessed proNGF were increased in the rd10 retina at early degenerative stages, before the peak of photoreceptor cell death. Conversely, processed NGF levels were similar in rd10 and WT retinas. ProNGF remained elevated throughout the period of photoreceptor cell loss, correlating with increased expression of α2-macroglobulin, an inhibitor of proNGF processing. The neuroprotective effect of blocking p75NTR was assessed in organotypic retinal cultures from rd10 and RhoP mouse models. Retinal explants treated with p75NTR antagonists showed significantly reduced photoreceptor cell death, as determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and by preservation of the thickness of the outer nuclear layer (ONL), where photoreceptor nuclei are located. This effect was accompanied by decreased retinal-reactive gliosis and reduced TNFα secretion. Use of p75NTR antagonist THX-B (1,3-diisopropyl-1-[2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-acetyl]-urea) in vivo in the rd10 and RhoP mouse models, by a single intravitreal or subconjunctival injection, afforded neuroprotection to photoreceptor cells, with preservation of the ONL. This study demonstrates a role of the p75NTR/proNGF axis in the progression of RP, and validates these proteins as therapeutic targets in two different RP models, suggesting utility irrespective of etiology.Fil: Platón-Corchado, María. Consejo Superior de Investigaciones Científicas; EspañaFil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Jmaeff, Sean. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Marchena, Miguel. Consejo Superior de Investigaciones Científicas; EspañaFil: Hernández-Pinto, Alberto M.. Consejo Superior de Investigaciones Científicas; EspañaFil: Hernández-Sánchez, Catalina. Consejo Superior de Investigaciones Científicas; EspañaFil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; CanadáFil: de la Rosa, Enrique J. Centro de Investigaciones Biológicas; Españ

    La expresión de proinsulina atenúa los trastornos de la retina asociados a la edad en distintos modelos de envejecimiento fisiopatológico

    Get PDF
    Póster presentado en el XXXVI Congreso de la Sociedad Española de Bioquímica y Biología Molecular SEBBM, celebrada del 3 al 6 de septiembre de 2013 en Madrid (España)Peer Reviewe

    Suspended planar-array chips for molecular multiplexing at the microscale

    Get PDF
    A novel suspended planar‐array chips technology is described, which effectively allows molecular multiplexing using a single suspended chip to analyze extraordinarily small volumes. The suspended chips are fabricated by combining silicon‐based technology and polymer‐pen lithography, obtaining increased molecular pattern flexibility, and improving miniaturization and parallel production. The chip miniaturization is so dramatic that it permits the intracellular analysis of living cells

    Raltegravir in second-line antiretroviral therapy in resource-limited settings (SELECT): a randomised, phase 3, non-inferiority study

    Get PDF
    For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings
    corecore