Atpasa Na-K dependiente y reactividad vascular en las arterias cerebrales y femorales aisladas del gato

Tesis doctoral original inédita leída en la Universidad de Autónoma de Madrid. Facultad de Medicina, Departamento de Farmacología y Terapéutica. Fecha de lectura: 27-09-198

IL-1β inhibition in cardiovascular complications associated to diabetes mellitus

Diabetes mellitus (DM) is a chronic disease that affects nowadays millions of people worldwide. In adults, type 2 diabetes mellitus (T2DM) accounts for the majority of all diagnosed cases of diabetes. The course of the T2DM is characterized by insulin resistance and a progressive loss of β-cell mass. DM is associated with a number of related complications, among which cardiovascular complications and atherosclerosis are the main cause of morbidity and mortality in patients suffering from the disease. DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications. In this context, the pharmacological approaches to treat diabetes should not only correct hyperglycaemia, but also attenuate inflammation and prevent the development of metabolic and cardiovascular complications. Over the last years, novel biological drugs have been developed to antagonize the pathophysiological actions of IL-1β. The drugs currently used in clinical practice are anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, the soluble decoy receptor rilonacept and the monoclonal antibodies canakinumab and gevokizumab. This review will summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in the context of the cardiovascular complications of DM, and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients.This work was supported by grants from Ministerio de Economía y Competitividad (SAF2014-52762-R) and Banco de Santander-Universidad Autónoma de Madrid (CEAL-AL/2015-17

Reputation drives cooperative behaviour and network formation in human groups

Cooperativeness is a defining feature of human nature. Theoreticians have suggested several mechanisms to explain this ubiquitous phenomenon, including reciprocity, reputation, and punishment, but the problem is still unsolved. Here we show, through experiments conducted with groups of people playing an iterated Prisoner's Dilemma on a dynamic network, that it is reputation what really fosters cooperation. While this mechanism has already been observed in unstructured populations, we find that it acts equally when interactions are given by a network that players can reconfigure dynamically. Furthermore, our observations reveal that memory also drives the network formation process, and cooperators assort more, with longer link lifetimes, the longer the past actions record. Our analysis demonstrates, for the first time, that reputation can be very well quantified as a weighted mean of the fractions of past cooperative acts and the last action performed. This finding has potential applications in collaborative systems and e-commerce.This work was supported in part by MINECO (Spain) through grants PRODIEVO, FIS2011-25167, and FIS2009-09689, by Comunidad de Madrid (Spain) through grant MODELICO-CM, by Comunidad de Aragón (Spain) through a grant to the group FENOL, and by the EU FET Proactive project MULTIPLEX (contract no. 317532)

Evolución de los usos del suelo y las precipitaciones en la cuenca el río Sosa: incidencia en la evolución hidromorfológica el cauce y en el riesgo de crecidas.

El presente estudio trata de un análisis de las características naturales y del medio de la cuenca del río Sosa, el análisis de los usos del suelo que se han dado a lo largo de los años, los cambios sucedidos en el cauce y la relación de todo ello con el riesgo de inundaciones y crecidas especialmente centrado ene l término municipal de Monzón

La evolución del proceso monitorio y el tratamiento de las cláusulas abusivas

El trabajo versa sobre las importantes reformas introducidas por el Legislativo en el proceso monitorio y el nuevo papel asumido por el letrado de la administración de justicia a raíz de la implantación de la nueva oficina judicial. Intentaré arrojar una mirada crítica de estas reformas haciendo hincapié en el debate que ha generado esta atribución de competencias por el letrado de la administración de justicia y los problemas constitucionales que haya podido causar. Hablaré sobre la necesaria reforma acometida por la ley 42/2015 en el proceso monitorio para adecuarlo por fin a las exigencias de la directiva europea 93/13 en materia de protección al consumidor en contratos celebrados con empresarios o profesionales, a raíz de la sentencia Finanmadrid, en cuyo fallo el Tribunal de Justicia de la Unión Europea declara que la normativa española relativa a la aplicación del principio de cosa juzgada en el proceso monitorio no se ajusta al principio de efectividad, dificultando de esta forma la aplicación de la defensa que la directiva 93/13 confiere al consumidor

Visfatin/PBEF/Nampt: A New Cardiovascular Target?

In the last years, a growing interest has emerged toward understanding the role of adipocytokines in the development of cardio-metabolic complications. Five years ago, visfatin/PBEF/Nampt was identified as a novel adipocytokine. In the context of metabolic disorders, extracellular visfatin/PBEF/Nampt was initially claimed as a potentially beneficial molecule due to its insulin-mimetic and glucose-lowering properties. Nevertheless, growing evidence has since then unveiled that visfatin/PBEF/Nampt may rather be a biomarker of inflammation and endothelial damage, and also a direct regulator of the cardiovascular system that modulates cell proliferation and survival, extracellular matrix, vascular reactivity, and inflammation. On one side, the blockade of the deleterious cardiovascular actions of visfatin/PBEF/Nampt is being regarded as a potential approach to prevent and treat, not only cardio-metabolic complications, but also other pathologies implying excessive angiogenesis. Conversely, the administration of visfatin/PBEF/Nampt has shown beneficial effects in different ischemic conditions. Further research is required to evaluate the real value of visfatin/PBEF/Nampt as a pharmacological target

El hidrógeno como vector energético: Mucho hecho pero casi todo por hacer

Los autores desarrollan, muy brevemente, los aspectos esenciales de lo que globalmente se denomina “Sistema Energético Solar-Hidrógeno” o a veces “Economía del hidrógeno”. El hidrógeno, obtenido por descomposición del agua mediante energías primarias renovables (solar, eólica…) se convierte en transportador de energía (vector energético) y en combustible limpio. Se discute la conveniencia del uso del hidrógeno en el contexto energético actual, así como los tres pilares fundamentales del uso del hidrógeno como vector energético: su producción usando fuentes renovables, su acumulación mediante diferentes métodos y, finalmente, su combustió

DPP4 and ACE2 in diabetes and COVID-19: Therapeutic targets for cardiovascular complications?

COVID-19 outbreak, caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus has become an urgent health and economic challenge. Diabetes is a risk factor for severity and mortality of COVID-19. Recent studies support that COVID-19 has effects beyond the respiratory tract, with vascular complications arising as relevant factors worsening its prognosis, then making patients with previous vascular disease more prone to severity or fatal outcome. Angiotensin-II converting enzime-2 (ACE2) has been proposed as preferred receptor for SARS-CoV-2 host infection, yet specific proteins participating in the virus entry are not fully known. SARS-CoV-2 might use other co-receptor or auxiliary proteins allowing virus infection. In silico experiments proposed that SARS-CoV-2 might bind dipeptidyl peptidase 4 (DPP4/CD26), which was established previously as receptor for MERS-CoV. The renin–angiotensin–aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. Imbalance of the RAAS and direct effect of soluble DPP4 exert deleterious vascular effects. We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications. Diabetes affects more than 400 million people worldwide, thus better understanding of how they are affected by COVID-19 holds an important benefit to fight against this disease with pandemic proportionsIV is the recipient of a FPU fellowship (FPU16/02612). TR and JE are supported by KomIT-Center of Competence for Innovative Diabetes Therapy- funded by EFRE-NRW. CP and CS-F are supported by a grant from Plan Nacional de I+D (SAF2017-84776-R

Mechanisms involved in the aging-induced vascular dysfunction

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionVascular aging is a key process determining health status of aged population. Aging is an independent cardiovascular risk factor associated to an impairment of endothelial function, which is a very early and important event leading to cardiovascular disease. Vascular aging, formerly being considered an immutable and inexorable risk factor, is now viewed as a target process for intervention in order to achieve a healthier old age. A further knowledge of the mechanisms underlying the age-related vascular dysfunction is required to design an adequate therapeutic strategy to prevent or restore this impairment of vascular functionality. Among the proposed mechanisms that contribute to age-dependent endothelial dysfunction, this review is focused on the following aspects occurring into the vascular wall: (1) the reduction of nitric oxide (NO) bioavailability, caused by diminished NO synthesis and/or by augmented NO scavenging due to oxidative stress, leading to peroxynitrite formation (ONOO -); (2) the possible sources involved in the enhancement of oxidative stress; (3) the increased activity of vasoconstrictor factors; and (4) the development of a low-grade pro-inflammatory environment. Synergisms and interactions between all these pathways are also analyzed. Finally, a brief summary of some cellular mechanisms related to endothelial cell senescence (including telomere and telomerase, stress-induced senescence, as well as sirtuins) are implemented, as they are likely involved in the age-dependent endothelial dysfunction, as well as in the lower vascular repairing capacity observed in the elderly. Prevention or reversion of those mechanisms leading to endothelial dysfunction through life style modifications or pharmacological interventions could markedly improve cardiovascular health in older peopleThis study is supported by grants from Ministerio de Ciencia e Innovación (Instituto de Salud Carlos III, RETICEF RD06/0013; PI08/1649; SAF2011-28011; SAF2011-24684, Spanish Government, and Sociedad Española de Farmacología/Almirall Prodesfarm