COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Acción de la brandicinina y de los inhibidores de la fosfodiesterasa 4 en la fisiología de la micción

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Fisiología Animal, leída el 14-10-2014Sección Deptal. de Fisiología (Farmacia)Fac. de FarmaciaTRUEunpu

Cardiac System during the Aging Process

The aging process is accompanied by a continuous decline of the cardiac system, disrupting the homeostatic regulation of cells, organs, and systems. Aging increases the prevalence of cardiovascular diseases, thus heart failure and mortality. Understanding the cardiac aging process is of pivotal importance once it allows us to design strategies to prevent age-related cardiac events and increasing the quality of live in the elderly. In this review we provide an overview of the cardiac aging process focus on the following topics: cardiac structural and functional modifications; cellular mechanisms of cardiac dysfunction in the aging; genetics and epigenetics in the development of cardiac diseases; and aging heart and response to the exercise.Sección Deptal. de Fisiología (Farmacia)Depto. de EnfermeríaFac. de FarmaciaFac. de Enfermería, Fisioterapia y PodologíaTRUEpu

Repercusión de las heridas crónicas en las unidades de rehabilitación funcional

Introducción y objetivos: el cuidado de heridas crónicas viene siendo objeto de especial discusión por parte de enfermería, donde se buscan nuevos conocimientos para fundamentar su práctica. Los objetivos principales de este estudio son determinar la incidencia y la prevalencia de las HC y su repercusión en la rehabilitación de los pacientes ingresados en las unidades de rehabilitación funcional (URF). Metodología: se ha diseñado un estudio cuantitativo observacional analítico longitudinal de cohortes, utilizando como población accesible los pacientes que ingresaron en las URF de un centro sociosanitario de media/larga estancia de Madrid durante el año 2011. Resultados: durante el año 2011 ingresaron en las URF 261 pacientes con una media de edad de 77,41 ± 12,5 años; el 69% de la muestra, mujeres. El 33,7% de los pacientes ingresaron con HC y la incidencia acumulada fue del 4,6% de pacientes por año. Respecto a la estancia en las URF, existe una diferencia de 22 días entre la media de estancia de pacientes con HC y sin dichas lesiones. Según los datos obtenidos, observamos que un paciente con HC tiene menor tendencia a conseguir la independencia y mayor riesgo de desarrollar úlceras por presión. Conclusión: con este estudio remarcamos la alta prevalencia de HC que existe en las URF y su repercusión en la rehabilitación del paciente debido al aumento de estancia en días, lo que puede conllevar un incremento de la carga económica y asistencial

Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries

Benign prostatic hypertrophy has been known to be related with glandular ischemia processes, and nitric oxide (NO) is a potent vasodilator agent. Therefore, the current study investigates the mechanisms underlying the NO-induced vasorelaxation in pig prostatic small arteries. In microvascular myographs, relaxation to electrical field stimulation (EFS), or to exogenous (S)-nitroso-N-acetylpenicillamine (SNAP) and acetylcholine (ACh), was observed on noradrenaline-precontracted prostatic small arterial rings under non-adrenergic and non-cholinergic (NANC) conditions. EFS (1-16 Hz) and exogenous SNAP (0.1-30 μM) evoked frequency- and concentration-dependent relaxation, respectively. Tetrodotoxin, a neuronal voltage-gated Na(+) channel blocker, abolished the EFS-evoked relaxation. ACh (1 nM-10 μM) induced concentration-dependent relaxation, which was reduced by the NO synthase inhibitor N(G)-nitro-L: -arginine (L: -NOARG). L: -NOARG also reduced the EFS-elicited relaxation but failed to modify the response to SNAP. 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin (IbTX), blockers of soluble guanylyl cyclase and large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, respectively, reduced EFS-, SNAP-, and ACh-induced relaxation. The combination of ODQ with IbTX did not produce further inhibition of the responses to either SNAP or ACh, compared with ODQ alone. Blockade of cyclooxygenases and intermediate and small conductance Ca(2+)-activated, ATP-dependent, and voltage-gated K(+) channels did not change the EFS and SNAP responses. In conclusion, our results suggest that NO and non-NO non-prostanoid factor(s) derived from NANC nerves are involved in the vasodilatation of pig prostatic small arteries. NO produces relaxation through soluble guanylyl cyclase activation-dependent BK(Ca) channel opening and through guanylyl cyclase-independent mechanisms. The vasodilatation elicited by NO could be useful to prevent prostatic ischemia.Depto. de EnfermeríaFac. de Enfermería, Fisioterapia y PodologíaTRUEunpu

Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries

Benign prostatic hypertrophy has been known to be related with glandular ischemia processes, and nitric oxide (NO) is a potent vasodilator agent. Therefore, the current study investigates the mechanisms underlying the NO-induced vasorelaxation in pig prostatic small arteries. In microvascular myographs, relaxation to electrical field stimulation (EFS), or to exogenous (S)-nitroso-N-acetylpenicillamine (SNAP) and acetylcholine (ACh), was observed on noradrenaline-precontracted prostatic small arterial rings under non-adrenergic and non-cholinergic (NANC) conditions. EFS (1-16 Hz) and exogenous SNAP (0.1-30 μM) evoked frequency- and concentration-dependent relaxation, respectively. Tetrodotoxin, a neuronal voltage-gated Na(+) channel blocker, abolished the EFS-evoked relaxation. ACh (1 nM-10 μM) induced concentration-dependent relaxation, which was reduced by the NO synthase inhibitor N(G)-nitro-L: -arginine (L: -NOARG). L: -NOARG also reduced the EFS-elicited relaxation but failed to modify the response to SNAP. 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin (IbTX), blockers of soluble guanylyl cyclase and large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, respectively, reduced EFS-, SNAP-, and ACh-induced relaxation. The combination of ODQ with IbTX did not produce further inhibition of the responses to either SNAP or ACh, compared with ODQ alone. Blockade of cyclooxygenases and intermediate and small conductance Ca(2+)-activated, ATP-dependent, and voltage-gated K(+) channels did not change the EFS and SNAP responses. In conclusion, our results suggest that NO and non-NO non-prostanoid factor(s) derived from NANC nerves are involved in the vasodilatation of pig prostatic small arteries. NO produces relaxation through soluble guanylyl cyclase activation-dependent BK(Ca) channel opening and through guanylyl cyclase-independent mechanisms. The vasodilatation elicited by NO could be useful to prevent prostatic ischemia.Depto. de EnfermeríaFac. de Enfermería, Fisioterapia y PodologíaTRUEpu

Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling.

Purpose: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck. Materials and methods: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension. Results: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+). Conclusions: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation. Keywords: 4-AP; 4-aminopyridine; AM; ATP; ATP dependent K(+); CGRP; COX; CSE; CSPA; Ca(2+) activated K(+); Emax; K(ATP); K(Ca); K(V); KPSS; L-NOARG; MLCP; N(G)-nitro-L-arginine; NO; PACAP; PKA; PSS; TRPA(1); TRPV(1); VOC; VPAC; [Ca(2+)](i); acetoxymethyl ester; adenosine 5′-triphosphate; calcitonin gene-related peptide; capsaicin sensitive primary afferent; cyclooxygenase; cystathionine γ-lyase; hydrogen sulfide; intracellular Ca(2+); maximum response; muscle, smooth; myosin light chain phosphatase; nitric oxide; physiological saline solution; pituitary adenylyl cyclase activating polypeptide; potassium channels; potassium rich PSS; protein kinase A; synaptic transmission; transient receptor potential A1; transient receptor potential vanilloid 1; urinary bladder; vasoactive intestinal peptide receptor; voltage gated Ca(2+); voltage gated K(+).Depto. de EnfermeríaFac. de Enfermería, Fisioterapia y PodologíaTRUEunpu

Mechanisms involved in the adenosine-induced vasorelaxation to the pig prostatic small arteries

Benign prostatic hypertrophy has been related with glandular ischemia processes and adenosine is a potent vasodilator agent. This study investigates the mechanisms underlying the adenosine-induced vasorelaxation in pig prostatic small arteries. Adenosine receptors expression was determined by Western blot and immunohistochemistry, and rings were mounted in myographs for isometric force recording. A(2A) and A(3) receptor expression was observed in the arterial wall and A(2A)-immunoreactivity was identified in the adventitia-media junction and endothelium. A(1) and A(2B) receptor expression was not obtained. On noradrenaline-precontracted rings, P1 receptor agonists produced concentration-dependent relaxations with the following order of potency: 5'-N-ethylcarboxamidoadenosine (NECA) = CGS21680 > 2-Cl-IB-MECA = 2-Cl-cyclopentyladenosine = adenosine. Adenosine reuptake inhibition potentiated both NECA and adenosine relaxations. Endothelium removal and ZM241385, an A(2A) antagonist, reduced NECA relaxations that were not modified by A(1), A(2B), and A(3) receptor antagonists. Neuronal voltage-gated Ca(2+) channels and nitric oxide (NO) synthase blockade, and adenylyl cyclase activation enhanced these responses, which were reduced by protein kinase A inhibition and by blockade of the intermediate (IK(Ca))- and small (SK(Ca))-conductance Ca(2+)-activated K(+) channels. Inhibition of cyclooxygenase (COX), large-conductance Ca(2+)-activated-, ATP-dependent-, and voltage-gated-K(+) channel failed to modify these responses. These results suggest that adenosine induces endothelium-dependent relaxations in the pig prostatic arteries via A(2A) purinoceptors. The adenosine vasorelaxation, which is prejunctionally modulated, is produced via NO- and COX-independent mechanisms that involve activation of IK(Ca) and SK(Ca) channels and stimulation of adenylyl cyclase. Endothelium-derived NO playing a regulatory role under conditions in which EDHF is non-functional is also suggested. Adenosine-induced vasodilatation could be useful to prevent prostatic ischemia.Depto. de EnfermeríaFac. de Enfermería, Fisioterapia y PodologíaTRUEpu

Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle

Aims: The current study investigates the role played by bradykinin (BK) receptors in the contractility to the pig bladder neck smooth muscle. Methods: Bladder neck strips were mounted in myographs for isometric force recordings and BK receptors expression was also determined by immunohistochemistry. Results: B2 receptor expression was observed in the muscular layer and urothelium whereas B1 expression was consistent detected in urothelium. A strong B2 immunoreactivity was also observed within nerve fibers among smooth muscle bundles. On urothelium-denuded preparations basal tone, BK induced concentration-dependent contractions which were reduced in urothelium-intact samples, by extracellular Ca(2+) removal and by blockade of B2 receptors and voltage-gated Ca(2+) (VOC) and non-VOC channels, and increased by cyclooxygenase (COX) inhibition. On phenylephrine-precontracted denuded strips, under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. In urothelium-intact samples, the B1 receptor agonist kallidin promoted concentration-dependent relaxations which were reduced by blockade of B1 receptors, COX, COX-1 and large-conductance Ca(2+) -activated K(+) (BKCa ) channels and abolished in urothelium-denuded samples and in K(+) -enriched physiological saline solution-precontracted strips. Conclusions: These results suggest that BK produces contraction of pig bladder neck via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry via VOC and non-VOC channels with a minor role for intracellular Ca(2+) mobilization. Facilitatory neuronal B2 receptors modulating NANC inhibitory neurotransmission and urothelial B1 receptors producing relaxation via the COX-1 pathway and BKCa channel opening are also demonstrated.Ministerio de Ciencia e Innovación (España)Fundação para a Ciência e Tecnologia, Ministério da Educação e Ciência (Portugal)Depto. de FisiologíaFac. de FarmaciaTRUEpu

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

Introduction: Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. Aim: To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. Methods: Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i ) and tension for rolipram in bladder neck samples were used. Main outcome measures: PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. Results: PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa ) and intermediate (IKCa ) conductance Ca2+ -activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2 S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. Conclusions: PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]i desensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.Depto. de EnfermeríaFac. de Enfermería, Fisioterapia y PodologíaTRUEpu