1,721,152 research outputs found
Correction to :β adrenergic receptor kinase C-terminal peptide gene-therapy improves ß2-adrenergic receptor-dependent neoangiogenesis after hindlimb ischemia (Journal of Pharmacology and Experimental Therapeutics (2016) 356:2 (503–513) DOI: 10.1124/jpet.115.228411)
No full textIn the above article [Cannavo A, Liccardo D, Lymperopoulos A, Gambino G, D’Amico ML, Rengo F, Koch WJ, Leosco D, Ferrara N, and Rengo G (2016) J Pharmacol Exp Ther 356(2): 503–513; DOI: 10.1124/jpet.115.228411], the following funding information was omitted: This work was funded by the National Institutes of Health [Grant R37 HL061690]. The authors regret this error and any inconvenience it may have caused
The adrenergic system in cardiovascular pathophysiology: a translational science point of view.
No full textAging and aging theories
No full textSeveral theories have sought to explain aging, here precisely defined as “increasing mortality with increasing chronological age in populations in the wild”. They all fall within one of two opposite and incompatible paradigms. For the first (“old paradigm”), aging is the result of degenerative phenomena that natural selection cannot counteract completely, due to insufficient strength or opposing selective pressures. For the second (“new paradigm”), aging is favoured by natural selection in terms of supra-individual selection: it belongs to a broader category of phenomena, on the whole defined as “phenoptosis”, which are explicable only in terms of supra-individual selection. For the new paradigm, aging is a specific function that is genetically determined and regulated, with its own physiology, pathology and phylogeny. This paper describes the theoretical arguments and the empirical evidence that support or are in contrast with each of the two paradigms. Subsequently, on the basis of an imposing and authoritative amount of research, aging mechanisms at the cellular and organismal levels are described. The clear existence of such mechanisms is indispensable proof to support the new paradigm and is in complete and unsolvable contrast with the old paradigm
Elderly at time of COronaVIrus disease 2019 (COVID-19): possible role of immunosenescence and malnutrition
No full textThe unprecedented COVID-19 pandemic is rapidly and unpredictably evolving and the majority of deaths are occurring in older people. A partial description of the magnitude of the scenario is provided by numbers and statistics, which probably underestimate the ongoing tragedy. In the present opinion paper, we have focused our attention on the evidence of the relationship among malnutrition, immunosenescence, and the higher morbidity and mortality in elderly patients. In particular, we propose the intriguing hypothesis that correction of nutritional deficits may attenuate the age-dependent alterations of the innate and adaptive immune system which participate in the increased susceptibility and worse outcome observed in the elderly COVID-19 patients
Adrenal adrenoceptors in heart failure: fine-tuning cardiac stimulation
No full textChronic heart failure (HF) is characterized by sympathetic hyperactivity reflected by increased circulating catecholamines (CAs), which contributes significantly to its morbidity and mortality. Therefore, sympatholytic treatments, that is, treatments that reduce sympathetic hyperactivity, are being pursued currently for the treatment of HF. Secretion of CAs from the adrenal gland, which is a major source of CAs, is regulated by alpha(2)-adrenoceptors (alpha(2)ARs), which inhibit, and by beta-adrenoceptors (betaARs), which enhance CA secretion. All ARs are G-protein-coupled receptors (GPCRs), whose signaling and function are regulated tightly by the family of GPCR kinases (GRKs). Despite the enormous potential of adrenal ARs for the regulation of sympathetic outflow, elucidation of their properties has only begun recently. Here, recent advances regarding the roles of adrenal ARs in the regulation of sympathetic outflow in HF and the regulatory properties of ARs are discussed, along with the potential benefits and challenges of harnessing their function for HF therapy
Adrenergic nervous system in heart failure: Pathophysiology and therapy
No full textHeart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that become activated in the syndrome to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to push the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF, along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart
Future G protein-coupled receptor targets for treatment of heart failure
No full textHeart failure (HF) still poses an enormous clinical challenge, as its incidence, morbidity, and mortality rates are continuously rising. G protein-coupled receptors (GPCRs) constitute the most ubiquitous superfamily of plasma membrane receptors and represent the single most important type of therapeutic drug target. Because there is overstimulation of the failing heart by various endogenous ligands, such as catecholamines and angiotensin II - which by activating their cognate GPCRs in cardiac muscle induce detrimental effects - therapeutic targeting of these receptors has been pursued. This research has led to the development of successful and useful drug classes, such as angiotensin-converting enzyme inhibitors and α-adrenergic receptor blockers. However, there still is a need to develop innovative treatments that might be more effective at reversing compromised myocyte function. Over the past several years, much evidence has accumulated indicating that a single GPCR, activated by the same endogenous ligand, can elicit several different signaling pathways with quite different, and often opposite, cellular effects. Because the aforementioned ligands, currently used for HF, target these receptors on their extracellular interface, thus merely preventing the endogenous agonists from binding the receptor, they inhibit all the signaling pathways elicited by the receptor indiscriminately. Importantly, several of these pathways emanating from the same GPCR can actually be beneficial for therapy, so their enhancement rather than their blockade is desirable for HF therapy. This highlights the need for selective targeting of GPCR-induced signaling pathways on the intracellular interface of the receptor, which might produce new and innovative therapies for cardiovascular disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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