25 research outputs found

    Efecto protector del azul de metileno en la retinopatía del prematuro experimental

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    Introducción: La hipoxia-isquemia por asfixia perinatal (AP) es causa de lesiones en la retina, pudiendo llevar a la ceguera por retinopatía proliferativa isquémica (RPI). En estudios previos hemos demostrado neurodegeneración, gliosis y neovascularización compatibles con la ROP, e identificado que el sistema nitrérgico está involucrado en su fisiopatología. Objetivos: Analizar la aplicación de azul de metileno como potencial estrategia terapéutica, dado que inhibe a la enzima óxido nítrico sintasa. Métodos: Se estudió la actividad enzimática y expresión de nNOS mediante Western blot, histoquímica de NADPHd e inmunohistoquímica contra nNOS, en la retina de animales de 30 días en un modelo de AP. Resultados: Se observó que a los 30 días postnatal, la nNOS aumenta significativamente su actividad y expresión en aquellos animales sometidos a AP al ser comparados con el grupo control (CTL). En el grupo AP tratado con azul de metileno (AZM) no se encontraron diferencias significativas en la actividad de NOS constitutiva con respecto al grupo CTL, mientras que su expresión evaluada por western blot fue menor. Los estudios realizados con histoquímica para NADPHd e inmunohistoquímica contra nNOS refuerzan estos resultados. Conclusiones: El NO es un radical libre que participa como neurotóxico en el desarrollo de la ROP por AP. La aplicación de azul de metileno como estrategia terapéutica, tiene un potente efecto bloqueante en la actividad de la enzima NOS constitutiva, y en la expresión de la misma. Este hallazgo alienta estudios futuros más exhaustivos para evaluar el uso del azul de metileno con el fin de atenuar o evitar el daño retiniano.Introduction: Hipoxia-ischemia by perinatal asphyxia (PA) is cause of retinal lesions, and can produce blindness by ischemic proliferative retinopathy (IPR). Previously, we have demonstrated retinal neurodegeneration, gliosis and neovascularization. Furthermore, we have identified the involvement of the nitregic system in it physiopatology. Objectives: Studying the participation of nitric oxide (NO) through the neuronal isoform of the enzyme nitric oxide sinthase (nNO) as trigger of the structural and molecular alterations previously observed by our group of research, and analyzing the application of methylene blue (MB) a therapeutic strategy. Methods: The studies were performed in retina by using enzymatic activity, NADPHd histochemical method and immunohistochemistry against nNOS. The studies were applied in three diferent groups (control, PA and MB) of 30 postnatal day animals. Results: At 30 postnatal day, we observed a significant increase of nNOS ativity and expression in retinas of those animals subjected to PA, when compared with the control group. In the group treated with methylene blue we did not found significant diferences in constitutive NOS activity, meanwhile it expression evaluated by western blot was lower than controls. The histochemical and immunohistochemical studies support these results. Conclusions: NO, is a free radical that act as a neurotoxic agent, seems to have a crucial role in the development of ROP after PA. The application of methylene blue as a therapeutic strategy showed a strong protective efect inhibiting the constitutive NOS activity and it expression. This founds stimulates future studies with the aim of using MB in order to avoid or decrease retinal damage.Fil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Fernández, J. C.. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Ibarra, Mariano Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Peña, Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Contartese, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Dorfman, Verónica Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Loidl, Cesar Fabian. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Hypothermia prevents gliosis and angiogenesis development in an experimental model of ischemic proliferative retinopathy

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    PURPOSE: To develop a time course study of vascularization and glial response to perinatal asphyxia in hypoxic-ischemic animals, and to evaluate hypothermia as possible protective treatment. METHODS: We used retinas of 7-, 15-, 21-, and 30-day-old male Sprague-Dawley rats that were exposed to perinatal asphyxia at either 37°C (PA) or 15°C (HYP). Born to term animals were used as controls (CTL). We evaluated the thickness of the most inner layers of the retina (IR), including internal limiting membrane, the retinal nerve fiber layer, and the ganglion cell layer; and studied glial development, neovascularization, adrenomedullin (AM), and VEGF by immunohistochemistry, immunofluorescence, and Western blot. RESULTS: A significant increment in IR thickness was observed in the PA group from postnatal day (PND) 15 on. This alteration was concordant with an increased number of new vessels and increased GFAP expression. The immunolocalization of GFAP in the internal limiting membrane and perivascular glia of the IR and in the inner processes of Müller cells was coexpressed with AM, which was also significantly increased from PND7 in PA animals. In addition, VEGF expression was immunolocalized in cells of the ganglion cell layer of the IR and this expression significantly increased in the PA group from PND15 on. The retinas of the HYP group did not show differences when compared with CTL at any age. CONCLUSIONS: This work demonstrates that aberrant angiogenesis and exacerbated gliosis seem to be responsible for the increased thickness of the inner retina as a consequence of perinatal asphyxia, and that hypothermia is able to prevent these alterations.Fil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Dorfman, Verónica Berta. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ibarra, Mariano Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Peña, Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Contartese, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Goldstein Raij, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acosta, Juan Manuel. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larráyoz, Ignacio M.. Centro de Investigación Biomédica de La Rioja; EspañaFil: Martínez Murillo, Ricardo. Consejo Superior de Investigaciones Cientificas; España. Instituto Cajal. Departamento de Neurobiología Molecular, Celular y del Desarrollo; EspañaFil: Martínez, Alfredo. Centro de Investigación Biomédica de La Rioja; España. Consejo Superior de Investigaciones Cientificas; EspañaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentin

    Análisis de los decretos emitidos por el Poder Ejecutivo de la Provincia de Buenos Aires durante el año 2018

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    El presente trabajo es el resultado de un intenso proceso de investigación que tuvo como objeto de estudio el análisis detallado de todos los decretos dictados por el Poder Ejecutivo de la Provincia de Buenos Aires durante el 2018 –año correspondiente al punto intermedio del mandato de María Eugenia Vidal (2015-2019)–. El propósito principal de esta propuesta es aportar una descripción minuciosa sobre una significativa porción de la actividad desarrollada por la Gobernadora durante el año demarcado, cuya importancia reside, en primer lugar, en el volumen de decretos analizados -un total de mil novecientos sesenta y nueve (1969)-; en segundo lugar, en la actualidad de la información que presentan –dado que 2018 es el último año completo de su gestión–; y, por último, en la diversidad de datos que estos documentos presentan.Facultad de Ciencias Jurídicas y Sociale

    Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

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    Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

    The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

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    Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Sstructural and ultrastructural study of an experimental model of retinopathy of prematurity (ROP)

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    La asfixia perinatal (AP) es el problema más serio a nivel mundial en Perinatología. Cada año, cuatro millones de recién nacidos sufren AP. Según numerosas estadísticas clínicas, una tercera parte fallece y otro tercio no padecerá consecuencias, mientras que el tercio restante sufrirá daños neurológicos, entre los cuales se incluyen diferentes grados de retinopatía isquemica (Hill l99l, Younkin l992).Obstetric complications and perinatal asphyxia including (AP) are causes of retinal lesions such as ischemic proliferative retinopathy, included as retinopathy of prematurity (ROP). To date there are no models to study this condition. We present an experimental AP model, with which we were able to study structural and ultrastructural alterations in the retina. We observed signs of neurodegeneration in the development of epiretinal neovascular membranes, newly formed vessels and astroglial reaction. These changes are consistent with the histopathologic descriptions of ROP. In conclusion, the AP model is useful for studying experimentally ROP. The application of hypothermia has a potent protective effect on the changes described. This would allow the development of therapies to prevent or mitigate damage to the retina, providing improved quality of life and reducing medical costs, family and social pathologies of avoidable blindness.Fil: Rey Funes, Manuel. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; ArgentinaFil: Ibarra, Mariano Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Larrea, Pablo. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; ArgentinaFil: Loidl, Cesar Fabian. Universidad Catolica de Cuyo - Sede San Juan; Argentin

    Reingreso hospitalario a 30 días en pacientes pediátricos con enfermedades crónicas complejas

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    Resumen: Introducción: La tasa de reingreso hospitalario a 30 días del alta es una medida de calidad de la atención médica. Los pacientes pediátricos con enfermedades crónicas complejas tienen altas tasas de reingreso. La falla en la transición entre el cuidado hospitalario y domiciliario podría explicar este fenómeno. Objetivos: Estimar la tasa de incidencia de reingreso hospitalario a 30 días en pacientes pediátricos con enfermedades crónicas complejas, estimar cuántos son potencialmente prevenibles y explorar posibles factores asociados a reingreso. Materiales y método: Estudio de cohorte prospectivo incluyendo pacientes hospitalizados con enfermedades crónicas complejas de un mes a 18 años de edad. Se excluyeron pacientes con enfermedad oncológica y cardiopatías congénitas. Se evaluaron el reingreso a 30 días y el reingreso potencialmente prevenible. Se valoraron características sociodemográficas, geográficas, clínicas y de la transición hacia el cuidado domiciliario. Resultados: Se incluyeron 171 hospitalizaciones; dentro de los 30 días reingresaron 28 pacientes (16,4%; IC95% 11,6-22,7). De los 28 reingresos, 23 (82,1%; IC95% 64,4-92,1) fueron potencialmente prevenibles. La enfermedad respiratoria se asoció con mayor probabilidad de reingreso. No se encontró asociación entre el reingreso a 30 días y los factores de la transición al cuidado domiciliario evaluados. Conclusiones: La tasa de reingreso a 30 días en pacientes con enfermedad crónica compleja fue del 16,4%, y el 82,1% fueron potencialmente prevenibles. Únicamente la enfermedad respiratoria se comportó como factor de riesgo para reingreso a 30 días. Abstract: Introduction: The rate of hospital readmission within 30 days of discharge is a quality indicator in health care. Paediatric patients with complex chronic conditions have high readmission rates. Failure in the transition between hospital and home care could explain this phenomenon. Objectives: To estimate the incidence rate of 30-day hospital readmission in paediatric patients with complex chronic conditions, estimate how many are potentially preventable and explore factors associated with readmission. Materials and method: Cohort study including hospitalized patients with complex chronic conditions aged one month to 18 years. Patients with cancer or with congenital heart disease requiring surgical correction were excluded. The outcomes assessed were 30-day readmission rate and potentially preventable readmissions. We analysed sociodemographic, geographic, clinical and transition to home care characteristics as factors potentially associated with readmission. Results: The study included 171 hospitalizations, and 28 patients were readmitted within 30 days (16.4%; 95% CI, 11.6–22.7). Of the 28 readmissions, 23 were potentially preventable (82.1%; 95% CI, 64.4–92.1). Respiratory disease was associated with a higher probability of readmission. There was no association between 30-day readmission and the characteristics of the transition to home care. Conclusions: The 30-day readmission rate in patients with complex chronic disease was 16.4%, and 82.1% of readmissions were potentially preventable. Respiratory disease was the only identified risk factor for 30-day readmission
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