562 research outputs found
Antihypertensive treatment and multifactorial approach for renal protection in diabetes
No full textType 2 diabetes is reaching epidemic proportions throughout the world, representing the most common cause of ESRD. Early identification of renal impairment associated with diabetes and initiation of renoprotective therapy are imperative. High BP, dyslipidemia, long duration of diabetes, and poor glycemic control are important risk factors; their modification, renal function monitoring, and combined therapies are the current integrated approaches to treat patients with diabetic kidney disease. Strong evidence suggests that achieving target BP goals via inhibition of the renin-angiotensin-aldosterone system confers significant renal protection for diabetic patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers lower BP and reduce both the progression of renal damage and adverse cardiovascular events; some important renoprotective actions seem to be independent of the antihypertensive effect. Stringent quality of glycemic control is another key point to prevent onset of nephropathy or slow its progression. Evidence from basic research and clinical trials indicates that hypolipidemic drugs, mainly statins, contribute to modulate the progression of renal damage in diabetes; their use should be considered in any patient with diabetes. Smoking cessation may slow nephropathy progression; given the additional health benefits of stopping smoking, this advice is an important part of the strategy of diabetic nephropathy treatment and prevention. In conclusion, a target-driven, long-term, intensified intervention aimed at multiple risk factors should be recommended in patients with diabetes to preserve their kidney function
Association between glycosuria and albuminuria in patients with type 2 diabetes from the CREDENCE trial: a mechanistic link?
No full textP2 receptors: new potential players in atherosclerosis
No full textAtherosclerosis is a focal inflammatory disease of the arterial wall. It starts with the formation of fatty streaks on the arterial wall that evolve to form a raised plaque made of smooth muscle cells (SMCs), and infiltrating leukocytes surrounding a necrotic core. The pathogenesis of the atherosclerotic lesion is incompletely understood, but it is clear that a dysfunction of the endothelium, recruitment and activation of inflammatory cells and SMC proliferation have a pivotal role. Over recent years receptors for extracellular nucleotides, the P2 receptors, have been recognized as fundamental modulators of leukocytes, platelets, SMCs and endothelial cells. P2 receptors mediate chemotaxis, cytokine secretion, NO generation, platelet aggregation and cell proliferation in response to accumulation of nucleotides into the extracellular milieu. Clinical trials have shown the benefit of antagonists of the ADP platelet receptor(s) in the prevention of vascular accidents in patients with atherosclerosis. Therefore, we anticipate that a deeper understanding of the involvement of P2 receptors in atheroma formation will open new avenues for drug design and therapeutic intervention
C. Ivlii Solini Polyhistor, a Martino Anton. Delrio emendatvs.
No full textDrukkersmerk op het titelbladenMartini [A]ntonii Delrio in C. Ivlii Solini Polyhistoren EmendationesHerkomst: bibliothe. de BaudelooHerkomst: stempel Bibliothèque publique de Douay ; stempel Bibliothèque royale de Belgique, doubleCockx-Indestege, E. Belgica typographica ; 4369Machiels, J. Catalogus van de boeken gedrukt vóór 1600 ; S 414Voet, L. Plantin Press (1555-1589) ; 2220Europeana-GoogleBook
Microalbuminuria e aterosclerosi.
No full textarticolo in italiano rivolto ai medici di medicina general
Human primary fibroblasts express in vitro a purinergic P2X7 receptor coupled to ion fluxes, microvesicule formation and IL-6 release
No full textWe have investigated reponses to extracellular ATP in human fibroblasts obtained by skin biopsies. Our data show that these cells express a P2X7 purinergic receptor, as judged by (1) RT-PCR with specific primers, (2) reactivity with a specific anti-P2X7 antiserum, (3) activation by the selective P2X agonist benzoylbenzoylATP and (4) stimulation of transmembrane ion fluxes. Stimulation with benzoylbenzoylATP, and to a lesser extent with ATP, also caused striking morphological changes and increased formation of cytoplasmic microvesicles. These changes were fully reversible upon nucleotide removal. Two known blockers of P2X receptors, oxidised ATP and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, inhibited the morphological changes fully and the ion fluxes partially. The residual rise in intracellular Ca2+ levels and membrane depolarization observed in the presence of the inhibitors were dependent upon activation of a P2Y-type receptor exhibiting a peculiar pharmacological profile, in that CTP was the preferred agonist. ATP stimulation triggered release of the pro-inflammatory cytokine IL-6 in fibroblasts pre-treated with PMA and bacterial endotoxin. These observations reveal a novel pathway for fibroblast activation and for their recruitment in the inflammatory response
The dark side of extracellular ATP in kidney diseases
No full textIntracellular ATP is the most vital source of cellular energy for biologic systems, whereas extracellular ATP is a multifaceted mediator of several cell functions via its interaction, in an autocrine or paracrine manner, with P2 purinergic receptors expressed on the cell surface. These ionotropic and metabotropic P2 purinergic receptors modulate a variety of physiologic events upon the maintenance of a highly sensitive "set point," the derangement of which may lead to the development of key pathogenic mechanisms during acute and chronic diseases. Growing evidence suggests that extracellular ATP signaling via P2 purinergic receptors may be involved in different renal pathologic conditions. For these reasons, investigators and pharmaceutical companies are actively exploring novel strategies to antagonize or block these receptors with the goal of reducing extracellular ATP production or accelerating extracellular ATP clearance. Targeting extracellular ATP signaling, particularly through the P2X7 receptor, has considerable translational potential, given that novel P2X7-receptor inhibitors are already available for clinical use (e.g., CE224,535, AZD9056, and GSK1482160). This review summarizes the current evidence regarding the involvement of extracellular ATP and its P2 purinergic receptor-mediated signaling in physiologic and pathologic processes in the kidney; potential therapeutic options targeting extracellular ATP purinergic receptors are analyzed as well
The P2x7 receptor: A promising pharmacological target in diabetic retinopathy
No full textDiabetes is a worldwide emergency. Its chronic complications impose a heavy burden on patients, health systems, and on society as a whole. Diabetic retinopathy is one of the most common and serious complications of diabetes, and an established risk factor for blindness in adults. Over 15 years of investigation led to the identification of vascular endothelial growth factor (VEGF) as a main pathogenic factor in diabetic retinopathy and to the introduction of highly effective anti-VEGF-based therapies, such as the monoclonal antibody bevacizumab or its fragment ranibizumab, which helped to prevent diabetes-related blindness in millions of patients. Recently, a pathogenic role for uncontrolled increases in the extracellular ATP concentration (eATP) and for overactivation of the purinergic receptor P2X7 (P2X7R) has been suggested. The P2X7R is an eATP-gated plasma membrane channel expressed in multiple tissues and organs, with a pleiotropic function in inflammation, immunity, cancer, and hormone and growth factor release. P2X7R stimulation or overexpression positively regulate the secretion and buildup of VEGF, thus promoting neo-angiogenesis in a wide variety of disease processes. In this review, we explore current evidence that supports the role of P2X7R receptor signaling in the pathogenesis of diabetic retinopathy, as well as the most appealing current therapeutical options for P2X7R targeting
Blood pressure variability: A new target to slow the progression of vascular damage in type 2 diabetes?
No full textNo abstract availabl
- …
