Angiotensin II stimulates superoxide production by nitric oxide synthase in thick ascending limbs

Angiotensin II (Ang II) causes nitric oxide synthase (NOS) to become a source of superoxide (O2 (-)) via a protein kinase C (PKC)-dependent process in endothelial cells. Ang II stimulates both NO and O2 (-) production in thick ascending limbs. We hypothesized that Ang II causes O2 (-) production by NOS in thick ascending limbs via a PKC-dependent mechanism. NO production was measured in isolated rat thick ascending limbs using DAF-FM, whereas O2 (-) was measured in thick ascending limb suspensions using the lucigenin assay. Consistent stimulation of NO was observed with 1 nmol/L Ang II (P \u3c 0.001; n = 9). This concentration of Ang II-stimulated O2 (-) production by 50% (1.77 ± 0.26 vs. 2.62 ± 0.36 relative lights units (RLU)/s/μg protein; P \u3c 0.04; n = 5). In the presence of the NOS inhibitor L-NAME, Ang II-stimulated O2 (-) decreased from 2.02 ± 0.29 to 1.10 ± 0.11 RLU/s/μg protein (P \u3c 0.01; n = 8). L-arginine alone did not change Ang II-stimulated O2 (-) (2.34 ± 0.22 vs. 2.29 ± 0.29 RLU/s/μg protein; n = 5). In the presence of Ang II plus the PKC α/β1 inhibitor Gö 6976, L-NAME had no effect on O2 (-) production (0.78 ± 0.23 vs. 0.62 ± 0.11 RLU/s/μg protein; n = 7). In the presence of Ang II plus apocynin, a NADPH oxidase inhibitor, L-NAME did not change O2 (-) (0.59 ± 0.04 vs. 0.61 ± ×0.08 RLU/s/μg protein; n = 5). We conclude that: (1) Ang II causes NOS to produce O2 (-) in thick ascending limbs via a PKC- and NADPH oxidase-dependent process; and (2) the effect of Ang II is not due to limited substrate

Efeitos da disrupção endócrina na gestação: uma revisão sistemática

Endocrine disruptors are ubiquitous natural and synthetic environmental pollutants that can mimic, block or disturb normal hormonal function. Environmental exposure to these pollutants is almost impossible to prevent due to their presence in the air, water, soil, food and in many other materials with which we come in contact daily, such as plastics. Foetuses are vulnerable during pregnancy because their organism is in a developmental stage, and any disruption may affect their health in the short and/or long term. There is some evidence that these substances disrupt tissue differentiation and growth processes, cause birth defects and affect the length of pregnancy. In this review we will focus on environmental epidemiology and related literature in order to update current knowledge based on the actual evidence of the effects of these substances on the aetiology of preterm delivery, miscarriages, low birth weight, malformations, cryptorchidism, hypospadias and micropenis. The difficulty in studying this topic is due to the high number of involved factors, which makes the available results inconclusive or even contradictory. Consequently, further research is necessary.Los alteradores endocrinos son contaminantes ambientales, naturales y sintéticos, ubicuos, que pueden mimetizar, bloquear o alterar funciones hormonales. La exposición ambiental a estos contaminantes es prácticamente imposible de evitar debido a que están presentes en el aire, en el agua, en los suelos, en los alimentos, y en muchos de los materiales con los que estamos en contacto diariamente, como los plásticos. La gestación supone una etapa de vulnerabilidad para el feto porque su organismo está en proceso de desarrollo y cualquier alteración puede afectar su salud a corto o largo plazo. Hay cierta evidencia de que estas sustancias alteran procesos de crecimiento y diferenciación de tejidos, producen malformaciones y afectan la duración del embarazo. Hasta el momento se conoce algo de sus efectos en la etiología de la criptorquidia, hipospadias y micropene, abortos espontáneos, partos prematuros y el bajo peso al nacimiento, efectos que serán revisados en este documento que quiere aportar una actualización del conocimiento, concentrándose en la epidemiología ambiental y la literatura relacionada. La dificultad para estudiar este tema por la cantidad de factores que intervienen hace que los resultados existentes no sean concluyentes o incluso contradictorios, por lo que es necesario que se siga investigando.Os disruptores endócrinos são contaminantes ambientais ubíquos, naturais e sintéticos, que podem mimetizar, bloquear ou alterar funções hormonais. A exposição ambiental a estes contaminantes é quase impossível de evitar porque estão presentes no ar, na água, no solo, nos alimentos e em muitos materiais de uso cotidiano como os plásticos. A gestação é uma etapa de vulnerabilidade para o feto porque o organismo está em processo de desenvolvimento e qualquer alteração pode afetar gravemente a sua saúde a curto ou longo prazo. Existe alguma evidência de que estas sustâncias alteram processos de crescimento e diferenciação de tecidos, produzem malformações e afetam a duração da gravidez. Neste momento já existe algum conhecimento sobre os seus efeitos na etiologia da criptorquidia, hipospadia, micropénis, aborto espontâneo, parto prematuro e baixo peso à nascença. Efeitos esses que serão revisados neste documento visando uma atualização do conhecimento, concentrando-se na epidemiologia ambiental e na literatura relacionada. A dificuldade para estudar este tema pela quantidade de fatores intervenientes faz com que os resultados existentes não sejam conclusivos ou até que sejam contraditórios, pelo que, será necessário que se continue investigando

Brain health in diverse settings : How age, demographics and cognition shape brain function

Peer reviewe

Brain clocks capture diversity and disparities in aging and dementia

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.</p

Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

Peer reviewe

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

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

Características clínico-epidemiológicas de pacientes hipertensos en un Consultorio Médico de Santa Clara

High blood pressure is a chronic non-transmittable disease, which is also a risk factor for the development of other clinical conditions. The incidence of arterial hypertension in the Cuban population is high.Aim: to characterize the evolution of arterial hypertension in a Family Doctor's Office.Methods: an observational, descriptive and cross-sectional study was carried out at the Family Doctor's Office 17-19 in the municipality of Santa Clara. The study covered the months of January to March 2020. Of the 256 hypertensive patients, a sample of 52 was selected by a simple random method.Results: Males predominated (53.84 %), together with the age group between 40 and 49 years (28.84 %). A total of 63.46 % of the patients were white-skinned. 51.61% presented risk factors. The risk factors with the highest incidence were smoking, followed by obesity and sedentary lifestyle.Conclusions: the most affected hypertensive patients are male. Most patients have a family history of high blood pressure. Smoking is a high incidence risk factor in the hypertensive population.Introducción: la hipertensión arterial es una enfermedad crónica no transmisible, que a la vez constituye un factor de riesgo para el desarrollo de otras enfermedades. La incidencia de la hipertensión arterial en la población de Cuba es alta.Objetivo: caracterizar el comportamiento de la hipertensión arterial en un Consultorio Médico de Familia.Métodos: se realizó un estudio observacional, descriptivo y transversal en el Consultorio Médico de Familia 17-19 del municipio Santa Clara. El período de estudio comprendió los meses de enero a marzo del 2020. La población fue de 256 hipertensos y se escogió una muestra de 52 hipertensos por muestreo aleatorio simple.Resultados: predominó el sexo masculino (53,84 %), y el grupo de edad entre 40 y 49 años (28,84 %). El 63,46 % de los pacientes fueron de color de la piel blanca. El 51,61 % presentaron factores de riesgo. Los factores de riesgo de mayor incidencia fueron el tabaquismo, seguido por la obesidad y el sedentarismo.Conclusiones: los pacientes hipertensos más afectados son los del sexo masculino. La mayor parte de los pacientes tienen antecedentes familiares de hipertensión arterial. El tabaquismo es un factor de riesgo de alta incidencia en la población hipertensa

Effects of Reactive Oxygen Species on Tubular Transport along the Nephron

Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA. In fact, ROS are used by immune systems to kill virus and bacteria, causing inflammation and local tissue damage. Today, we know that the functions of ROS are not so limited, and that they also act as signaling molecules mediating processes as diverse as gene expression, mechanosensation, and epithelial transport. In the kidney, ROS such as nitric oxide (NO), superoxide (O2−), and their derivative molecules hydrogen peroxide (H2O2) and peroxynitrite (ONO2−) regulate solute and water reabsorption, which is vital to maintain electrolyte homeostasis and extracellular fluid volume. This article reviews the effects of NO, O2−, ONO2−, and H2O2 on water and electrolyte reabsorption in proximal tubules, thick ascending limbs, and collecting ducts, and the effects of NO and O2− in the macula densa on tubuloglomerular feedback