Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

Introduction: Epidemiological studies suggest a relationship between vitamin D deficiency and cardiovascular and respiratory diseases. However, whether total, bioavailable, and/or free vitamin D levels have a prognostic role in pulmonary arterial hypertension (PAH) is unknown. We aimed to determine total, bioavailable, and free 25-hydroxy-vitamin D (25(OH)vitD) plasma levels and their prognostic value in PAH patients. Methods: In total, 67 samples of plasma from Spanish patients with idiopathic, heritable, or drug-induced PAH were obtained from the Spanish PH Biobank and compared to a cohort of 100 healthy subjects. Clinical parameters were obtained from the Spanish Registry of PAH (REHAP). Results: Seventy percent of PAH patients had severe vitamin D deficiency (total 25(OH)vitD < 10 ng/mL) and secondary hyperparathyroidism. PAH patients with total 25(OH)vitD plasma above the median of this cohort (7.17 ng/mL) had better functional class and higher 6-min walking distance and TAPSE (tricuspid annular plane systolic excursion). The main outcome measure of survival was significantly increased in these patients (age-adjusted hazard ratio: 5.40 (95% confidence interval: 2.88 to 10.12)). Vitamin D-binding protein (DBP) and albumin plasma levels were downregulated in PAH. Bioavailable 25(OH)vitD was decreased in PAH patients compared to the control cohort. Lower levels of bioavailable 25(OH)vitD (<0.91 ng/mL) were associated with more advanced functional class, lower exercise capacity, and higher risk of mortality. Free 25(OH)vitD did not change in PAH; however, lower free 25(OH)vitD (<1.53 pg/mL) values were also associated with high risk of mortality. Conclusions: Vitamin D deficiency is highly prevalent in PAH, and low levels of total 25(OH)vitD were associated with poor prognosis

Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K+ Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency

Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH

Gestión de exámenes online. Base de datos de preguntas y desarrollo de software

Depto. de Farmacología y ToxicologíaFac. de MedicinaFALSEsubmitte

Base de datos de preguntas y actualización del software. Herramientas para la generación de exámenes presenciales u online

Depto. de Farmacología y ToxicologíaFac. de MedicinaFALSEsubmitte

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

Introduction: Epidemiological studies suggest a relationship between vitamin D deficiency and cardiovascular and respiratory diseases. However, whether total, bioavailable, and/or free vitamin D levels have a prognostic role in pulmonary arterial hypertension (PAH) is unknown. We aimed to determine total, bioavailable, and free 25-hydroxy-vitamin D (25(OH)vitD) plasma levels and their prognostic value in PAH patients. Methods: In total, 67 samples of plasma from Spanish patients with idiopathic, heritable, or drug-induced PAH were obtained from the Spanish PH Biobank and compared to a cohort of 100 healthy subjects. Clinical parameters were obtained from the Spanish Registry of PAH (REHAP). Results: Seventy percent of PAH patients had severe vitamin D deficiency (total 25(OH)vitD < 10 ng/mL) and secondary hyperparathyroidism. PAH patients with total 25(OH)vitD plasma above the median of this cohort (7.17 ng/mL) had better functional class and higher 6-min walking distance and TAPSE (tricuspid annular plane systolic excursion). The main outcome measure of survival was significantly increased in these patients (age-adjusted hazard ratio: 5.40 (95% confidence interval: 2.88 to 10.12)). Vitamin D-binding protein (DBP) and albumin plasma levels were downregulated in PAH. Bioavailable 25(OH)vitD was decreased in PAH patients compared to the control cohort. Lower levels of bioavailable 25(OH)vitD (<0.91 ng/mL) were associated with more advanced functional class, lower exercise capacity, and higher risk of mortality. Free 25(OH)vitD did not change in PAH; however, lower free 25(OH)vitD (<1.53 pg/mL) values were also associated with high risk of mortality. Conclusions: Vitamin D deficiency is highly prevalent in PAH, and low levels of total 25(OH)vitD were associated with poor prognosis

Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice

Background and purposeAlcohol abuse has been associated with erectile dysfunction (ED), but the implicated molecular mechanisms are unresolved. This study analyses the role of alterations in soluble guanylyl cyclase (sGC) in ED.Experimental approachED was analysed in adult male C57BL/6J mice subjected to the Chronic Intermittent Ethanol (CIE) paradigm. Erectile function was assessed in anaesthetised mice in vivo by evaluating intracavernosal pressure (ICP) and in vitro in isolated mice corpora cavernosa (CC) mounted in a myograph. Protein expression and reactive oxygen species were analysed by western blot and dihydroethidium staining, respectively.Key resultsIn CIE mice, we observed a significant decrease in the relaxant response of the CC to stimulation of NO release from nitrergic nerves by electrical field stimulation, to NO release from endothelial cells by acetylcholine, to the PDE5 inhibitor sildenafil, and to the sGC stimulator riociguat. Conversely, the response to the sGC activator cinaciguat, whose action is independent of the oxidation state of sGC, was significantly enhanced in these CC. The responses to adenylyl cyclase stimulation with forskolin were unchanged. We found an increase in reactive oxygen species in the CC from CIE mice as well as an increase in CYP2E1 and NOX2 protein expression. In vivo pre‐treatment with tempol prevented alcohol‐induced erectile dysfunction.Conclusions and implicationsOur results demonstrate that alcoholic mice show ED in vitro and in vivo due to an alteration in the redox state of sGC and suggest that sGC activators may be effective in ED associated with alcoholism.Ministerio de Economía y Competitividad (España)Ministerio de Ciencia e Innovación (España)Ministerio deSanidad, Servicios Sociales e Igualdad (España)European CommissionUniversidad Complutense de MadridBanco SantanderDepto. de Farmacología, Farmacognosia y BotánicaFac. de MedicinaTRUEpubAPC financiada por la UC

Imported strongyloidiasis in Spain

The objective of this study was to assess the epidemiological, laboratory, and clinical features of imported strongyloidiasis in a tropical medicine referral unit in Madrid, Spain.This was a retrospective study based on a review of medical records. A patient was diagnosed with strongyloidiasis when the infection could be detected by conventional stool analysis and/or serology against Strongyloides stercoralis, regardless of the presence of symptoms. RESULTS: One hundred and seventy-eight cases of strongyloidiasis were included in the study. Stool tests were performed in all patients, and serology in 160 patients (89.9%). The diagnosis of strongyloidiasis was based on serology only in four patients; 21 patients only had positive stool tests. A third of the total strongyloidiasis cases in this study were travel-related, mainly associated with short trips (<2 months). Only 47.8% of total cases were symptomatic. We found no differences in clinical presentation between immigrants and travelers with strongyloidiasis. CONCLUSIONS: Not only should strongyloidiasis be suspected in symptomatic travelers and immigrants, but it should also be ruled out when elevated IgE levels or eosinophilia are present. Strongyloidiasis can be asymptomatic in HIV patients, but it should be diagnosed and treated before a possible hyperinfection develops.This study was supported by RICET RD06/0021/0003 ISCIII-RETICS. Ethical approval: The study was approved by the institutional ethics committee (GER-STR.201201).S

Ressources paysagères et ressources énergétiques dans les montagnes sud-européennes. Histoire, comparaison, expérimentation

Programme de recherche IGNIS MUTAT RES. Penser l’architecture, la ville et le paysage au prisme de l’énergi

Elaboración de casos clínicos para el aprendizaje basado en casos prácticos: una herramienta pedagógica para la inmersión en la materia de profesores noveles y un recurso didáctico en la metodología de aprendizaje con participación del estudiante

El proyecto propone la elaboración de nuevos casos clínicos que asemejen situaciones reales sobre los que los estudiantes puedan desarrollar un aprendizaje autónomo dirigido por el profesorado en función de los conceptos que sean de interés para cada grupo farmacológico y acercándole a la situación más cercana a su práctica profesional. Los objetivos del proyecto son: 1) Generar una base de nuevos casos clínicos dirigidos a que los estudiantes trabajen sobre grupos de fármacos en un contexto lo más real posible. Los diferentes casos que se elaboren en este proyecto podrán ser utilizados en la docencia de diversas asignaturas impartidas por miembros del departamento de Farmacología y Toxicología. Las sesiones dirigidas al estudio basado en la resolución de casos se plantean como una herramienta docente que tiene como finalidad el desarrollo de competencias transversales como promover la motivación, el trabajo en equipo, la participación de los estudiantes en los debates, así como, fomentar el pensamiento crítico y el conocimiento del método científico. Este tipo de aprendizaje en contexto facilita la integración de los conocimientos y su mayor retención además de la dotar a los estudiantes con las habilidades para fomentar un aprendizaje continuo. 2) Apoyar la formación del profesorado de reciente incorporación, así como del personal investigador que participan como colabores en tareas docentes del departamento y que podrían ser potenciales futuros docentes.Depto. de Farmacología y ToxicologíaFac. de MedicinaFALSEsubmitte