Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells

Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxigenase (COX)1, dimethylarginine dimethylaminohydrolase (DDAH)2, phospholipase A2 group IV (PLA2G4) B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes

La biopsia embrionaria con láser permite el diagnóstico genético preimplantacional ovino sin reducir la supervivencia a término

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Rendimiento del MOET aplicado al programa de selección de la Rasa Aragonesa de UPRA-Grupo Pastores

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The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Status of seismic response control techniques in Colombia

En este artículo se presenta un análisis del estado actual del uso de las técnicas de control de respuesta sísmica en edificaciones colombianas. Se identifican las principales tecnologías utilizadas en el mundo, se muestra el resultado de una encuesta realizada a ingenieros diseñadores de estructuras, con el fin de detectar el grado de aceptación de estas técnicas en Colombia, y se exponen las principales razones por las cuales no han tenido aplicación significativa en el país. Los resultados de la encuesta revelan que Colombia todavía está lejos de la vanguardia en el uso de técnicas de control de respuesta sísmica y que las entidades y profesionales involucrados en el proyecto de edificaciones desconocen estas técnicas o desconfían de sus ventajas tanto económicas como estructurales. Finalmente, se invita, por medio de experiencias en otros países, a considerar estas técnicas en el diseño estructural de edificaciones colombianas.This paper presents general aspects of the present situation of the use of seismic response-control techniques in Colombian buildings. The most prevalent techniques used worldwide are identified, and the results of a survey conducted among Colombian structural design engineers aimed at detecting some of the reasons why these techniques have not had a significant applicability in the country are presented. The results of the survey reveal that Colombia is still far from being a leading country in the application of seismic response control techniques, and that most entities and practitioners involved in building planning either do not know these techniques or are not well aware of economical benefits as well as improved structural performance. Finally, based on experiences gained in other countries, the use of these techniques in structural design for Colombia buildings is encouraged

Metallic hysteretic dampers as a seismic response control technique in Colombian buildings

En este artículo se presenta un análisis cualitativo de la posibilidad de implementar técnicas de control de respuesta sísmica en edificaciones en Colombia. Teniendo en cuenta las condiciones locales actuales de la ingeniería y de las prácticas de construcción en el país, se presentan las principales razones por las que se considera que la técnica de protección pasiva de estructuras sería la más apta para ser implementada en Colombia. Se plantean aspectos deseables para la fabricación y aplicación de disipadores de energía metálicos, y se presentan los disipadores tipo riostras metálicas con pandeo restringido como una opción viable para la protección y control del daño estructural en edificaciones en el país.This paper presents a qualitative analysis of the possibility of implementing seismic response control techniques in buildings in Colombia. Given the current local conditions in engineering and construction in the country, herein are presented the main reasons why it is considered that the passive control of structures would be the most suitable technique to be implemented in Colombia. Desirable features on the fabrication and application of metallic energy dissipators are exposed, and metallic buckling-restrained braces (BRB) dissipators are presented as one viable option for the protection and control for structural damage of buildings in the country

Sistemas de control de respuesta sísmica en edificaciones

En este artículo se presenta un compendio del tema de los sistemas de control de respuesta sísmica en edificaciones. Se realiza una presentación general del concepto físico de balance de energía en un sistema estructural, se identifican los diferentes tipos de energía y se relacionan los sistemas para el control de respuesta sísmica con el tipo de energía que disipan. Se presentan algunos ejemplos de los tipos de dispositivos comerciales más usados en el mundo para el control de respuesta sísmica de edificaciones.This paper corresponds to a summary of the common aspects of the state-of-the-art seismic response control techniques to buildings. It is presented an overview of the energy balance concept in a structural system; it is also discussed the types of energy and its role into the total energy dissipation. Besides, some examples of the most widely used devices for seismic response control techniques are presented