Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: Effect of angiotensin II and role of insulinlike growth factor-1 receptor transactivation

We investigated whether angiotensin II (Ang II)-induced reactive oxygen species (ROS) generation is altered in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) during the phases of prehypertension, developing hypertension, and established hypertension and assessed the putative role of insulinlike growth factor-1 receptor (IGF-1R) in Ang II-mediated actions. The VSMCs from SHR and Wistar-Kyoto rats (WKY) aged 4 (prehypertensive), 9 (developing hypertension), and 16 (established hypertension) weeks were studied. The ROS production and NAD(P)H oxidase activation were determined by fluorescence and chemiluminescence, respectively. The role of IGF-1R was assessed with the selective inhibitor AG1024. The ROS bioavailability was manipulated with Tiron (10-5 mol/L) and diphenylene iodonium (DPI) (10-6 mol/L). Angiotensin II dose dependently increased ROS production in WKY and SHR at all ages. The Ang II-induced responses were greater in SHR versus WKY at 9 and 16 weeks (P < .05). The Ang II-stimulated ROS increase was greater in 9- and 16-week-old SHR versus 4-week SHR (P < .05). These effects were reduced by AG 1024. Basal NAD(P)H oxidase activity was higher in VSMCs from 9-week-old SHR versus 4-week-old rats (P < .05). Angiotensin II induced a significant increase in oxidase activity in VSMCs from 9- and 16-week-old SHR (P < .001), without influencing responses in cells from 4-week-old SHR. Pretreatment of 9- and 16-week-old SHR cells with AG1024 reduced Ang II-mediated NAD(P)H oxidase activation (P < .05). Basal and Ang II-induced NAD(P)H-driven ROS generation are enhanced in VSMCs from SHR during development of hypertension, but not in cells from prehypertensive rats. Transactivation of IGF-1R by Ang II may be important in vascular oxidative excess in the development of hypertension in SHR.Fil: Cruzado, Montserrat Cecilia. Universidad Nacional de Cuyo; Argentina. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Risler, Norma Raquel. Universidad Nacional de Cuyo; ArgentinaFil: Miatello, Roberto Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Yao, Guoying. Institut de Recherches Cliniques de Montréal; CanadáFil: Schiffrin, Ernesto L.. Institut de Recherches Cliniques de Montréal; CanadáFil: Touyz, Rhian M.. Institut de Recherches Cliniques de Montréal; Canad

Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy

Background. The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods. Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE 50% reduction in glomerular filtrate rate or end-stage renal disease. Results. Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P 1⁄4 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with 50% had poorer renal function compared with the other groups. Conclusions. We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research

Fundamental Parameters of He-Weak and He-Strong Stars

We carried out low resolution spectroscopic observations in the wavelength range 3400-4700 A of 20 He-weak and 8 He-strong stars to determine their fundamental parameters by means of the Divan-Chalonge-Barbier (BCD) spectrophotometric system. For a few He-weak stars we also estimate the effective temperatures and the angular diameters by integrating absolute fluxes observed over a wide spectral range. Non-LTE model calculations are carried out to study the influence of the He/H abundance ratio on the emergent radiation of He-strong stars and on their Teff determination. We find that the effective temperatures, surface gravities and bolometric absolute magnitudes of He-weak stars estimated with the BCD system and the integrated flux method are in good agreement between each other, and they also agree with previous determinations based on several different methods. The mean discrepancy between the visual absolute magnitudes derived using the Hipparcos parallaxes and the BCD values is on average 0.3 mag for He-weak stars, while it is 0.5 mag for He-strong stars. For He-strong stars, we note that the BCD calibration, based on stars in the solar environment, leads to overestimated values of Teff. By means of model atmosphere calculations with enhanced He/H abundance ratios we show that larger He/H ratios produce smaller BD which naturally explains the Teff overestimation. We take advantage of these calculations to introduce a method to estimate the He/H abundance ratio in He-strong stars. The BD of HD 37479 suggests that the Teff of this star remains fairly constant as the star spectrum undergoes changes in the intensity of H and He absorption lines. Data for the He-strong star HD 66765 are reported for the first time.Comment: Accepted for publication in A&

Effect of Finerenone on chronic kidney disease outcomes in type 2 diabetes

Background: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown. Methods: In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively). Conclusions: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.)

Novel utility-scale photovoltaic plant electroluminescence maintenance technique by means of bidirectional power inverter controller

Nowadays, photovoltaic (PV) silicon plants dominate the growth in renewable energies generation. Utility-scale photovoltaic plants (USPVPs) have increased exponentially in size and power in the last decade and, therefore, it is crucial to develop optimum maintenance techniques. One of the most promising maintenance techniques is the study of electroluminescence (EL) images as a complement of infrared thermography (IRT) analysis. However, its high cost has prevented its use regularly up to date. This paper proposes a maintenance methodology to perform on-site EL inspections as efficiently as possible. First, current USPVP characteristics and the requirements to apply EL on them are studied. Next, an increase over the automation level by means of adding automatic elements in the current PV plant design is studied. The new elements and their configuration are explained, and a control strategy for applying this technique on large photovoltaic plants is developed. With the aim of getting on-site EL images on a real plant, a PV inverter has been developed to validate the proposed methodology on a small-scale solar plant. Both the electrical parameters measured during the tests and the images taken have been analysed. Finally, the implementation cost of the solution has been calculated and optimised. The results conclude the technical viability to perform on-site EL inspections on PV plants without the need to measure and analyse the panel defects out of the PV installation

Galectin-3 shapes toxic alpha-synuclein strains in Parkinson's disease.

Parkinson's Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. Galectin-3 (GAL3) is known to have a detrimental function in neurodegenerative diseases. It is a galactose-binding protein without known catalytic activity and is expressed mainly by activated microglial cells in the central nervous system (CNS). GAL3 has been previously found in the outer layer of the LB in post-mortem brains. However, the role of GAL3 in PD is yet to be elucidated. In post-mortem samples, we identified an association between GAL3 and LB in all the PD subjects studied. GAL3 was linked to less αSYN in the LB outer layer and other αSYN deposits, including pale bodies. GAL3 was also associated with disrupted lysosomes. In vitro studies demonstrate that exogenous recombinant Gal3 is internalised by neuronal cell lines and primary neurons where it interacts with endogenous αSyn fibrils. In addition, aggregation experiments show that Gal3 affects spatial propagation and the stability of pre-formed αSyn fibrils resulting in short, amorphous toxic strains. To further investigate these observations in vivo, we take advantage of WT and Gal3KO mice subjected to intranigral injection of adenovirus overexpressing human αSyn as a PD model. In line with our in vitro studies, under these conditions, genetic deletion of GAL3 leads to increased intracellular αSyn accumulation within dopaminergic neurons and remarkably preserved dopaminergic integrity and motor function. Overall, our data suggest a prominent role for GAL3 in the aggregation process of αSYN and LB formation, leading to the production of short species to the detriment of larger strains which triggers neuronal degeneration in a mouse model of PD

Cellular Immunity to Predict the Risk of Cytomegalovirus Infection in Kidney Transplantation: A Prospective, Interventional, Multicenter Clinical Trial

Background: Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. Methods: This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γrelease assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. Results: Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30-9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31-59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89-237.96]). Conclusions: Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. Clinical Trials Registration: NCT02550639

Capacitando comunidades marginales a través de un medio masivo de comunicación

Se toma como muestra al partido de La Matanza situado en la provincia de Buenos Aires, el cual cuenta con más de 1.500.000 habitantes. Esta población que supera en número a la de 19 provincias tomadas separadamente, es solo inferior a la Ciudad Autónoma de la Provincia de Buenos Aires y las provincias de Buenos Aires, Córdoba, Santa Fe y Mendoza. Dentro de este Partido conviven comunidades residenciales junto a marginales, por ello se hace un estudio a fin de cuantificar la brecha tecnológica y luego aplicar una metodología que permita acercar el conocimiento a las zonas más marginales a fin de disminuir dicha brecha e incluir a las mismas en la sociedad del conocimiento.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

Implementación de una estrategia para reducir la brecha tecnológica

En el presente artículo se muestra la existencia de la brecha tecnológica entre las comunidades que utilizan las TICs (Tecnologías de la Información y Comunicación) como parte de su vida cotidiana y aquellas que no poseen ningún tipo de conocimiento al respecto. Es posible a través de los resultados arrojados por un relevamiento realizado en comunidades con características socio-culturales distintas evidenciar la distancia en materia de tecnología que separa a las comunidades. Tomando conciencia de la existencia de la brecha tecnológica, en este trabajo se presentan los resultados de implementar una estrategia que les permita a los ciudadanos con escasos recursos, que residen en las zonas más marginales, acceder al conocimiento.Presentado en el VIII Workshop Tecnología Informática aplicada en Educación (WTIAE)Red de Universidades con Carreras en Informática (RedUNCI

Implementación de una estrategia para reducir la brecha tecnológica

En el presente artículo se muestra la existencia de la brecha tecnológica entre las comunidades que utilizan las TICs (Tecnologías de la Información y Comunicación) como parte de su vida cotidiana y aquellas que no poseen ningún tipo de conocimiento al respecto. Es posible a través de los resultados arrojados por un relevamiento realizado en comunidades con características socio-culturales distintas evidenciar la distancia en materia de tecnología que separa a las comunidades. Tomando conciencia de la existencia de la brecha tecnológica, en este trabajo se presentan los resultados de implementar una estrategia que les permita a los ciudadanos con escasos recursos, que residen en las zonas más marginales, acceder al conocimiento.Presentado en el VIII Workshop Tecnología Informática aplicada en Educación (WTIAE)Red de Universidades con Carreras en Informática (RedUNCI