A RELIGIÃO PARA OS GRUPOS SOCIAIS «ÀS MARGENS DA HISTÓRIA»

Entre os pensadores marxistas, Gramsci é um dos autores que mais aprofundou as questões ligadas à religião e às dinâmicas a ela subjacentes. Sem preâmbulos, tentarei ir ao cerne do assunto, partindo de uma pergunta: que tipo de religião encontramos na análise política de Gramsci e quanto do pensamento de Gramsci existe e existiu em certas maneiras de viver a religião que ocorreram nas periferias do mundo na época contemporânea

Boi de piranha, Encher o bucho, Rodar a Baiana. Gli idiomatismi nella storia del Brasile

The article relates the idioms in use in contemporary Brazil with the history of the country, starting with a look at some of the most peculiar aspects of this South American nation

A QUESTÃO MORAL EM TEMPOS DE CRISE

A leitura combinada das notas 16 e 17 do Caderno 13 fornece uma síntese de conceitos cruciais do arcabouço filosófico gramsciano e, ao mesmo tempo, caracterizase como uma das páginas mais nobres sobre a ideia de fazer política e do dever ser da “grande política”. Recebido em 18 de setembro de 2016Aceito em 24 de outubro de 2016Editado em 15 de dezembro de 201

The T2238C human atrial natriuretic peptide molecular variant and the risk of cardiovascular diseases

Atrial natriuretic peptide (ANP) is a cardiac hormone which plays important functions to maintain cardio-renal homeostasis. The peptide structure is highly conserved among species. However, a few gene variants are known to fall within the human ANP gene. The variant rs5065 (T2238C) exerts the most substantial effects. The T to C transition at the 2238 position of the gene (13-23% allele frequency in the general population) leads to the production of a 30-, instead of 28-, amino-acid-long α-carboxy-terminal peptide. In vitro, CC2238/αANP increases the levels of reactive oxygen species and causes endothelial damage, vascular smooth muscle cells contraction, and increased platelet aggregation. These effects are achieved through the deregulated activation of type C natriuretic peptide receptor, the consequent inhibition of adenylate cyclase activity, and the activation of Giα proteins. In vivo, endothelial dysfunction and increased platelet aggregation are present in human subjects carrying the C2238/αANP allele variant. Several studies documented an increased risk of stroke and of myocardial infarction in C2238/αANP carriers. Recently, an incomplete response to antiplatelet therapy in ischemic heart disease patients carrying the C2238/αANP variant and undergoing percutaneous coronary revascularization has been reported. In summary, the overall evidence supports the concept that T2238C/ANP is a cardiovascular genetic risk factor that needs to be taken into account in daily clinical practice

Multivariate risk assessment and risk score cards in hypertension

Cardiovascular disease represents the leading cause of morbidity and mortality in Western countries, and hypertension-related cardiovascular events affect about 37 million people per year, worldwide. In this perspective, hypertensive patients are at increased risk to experience cardiovascular events during life-long period, and treatment of high blood pressure represents one of the most effective strategies to reduce global cardiovascular risk. However, due to its multifactorial pathophysiology and its frequent association with other relevant risk factors and clinical conditions, treatment of hypertension requires an integrated approach, including lifestyle measures, antihypertensive drugs and other therapies. Yet, worldwide general practitioners continue to focus their attention on the management of a single risk factor, eg, blood pressure, rather than to global cardiovascular risk profile. In this view, modern strategies of cardiovascular prevention in hypertensive patients should move from a single risk factor based approach toward a more comprehensive risk evaluation in the individual patient. In other words, it is important to define the global cardiovascular risk to manage hypertensive patients at high-risk, rather than to focus on the high level of a single risk factor, for reducing cardiovascular morbidity and mortality in the general population, as well as in hypertensive population

Angiotensin II receptor blockers and myocardial infarction: an updated analysis of randomized clinical trials

OBJECTIVE: To evaluate the effects of treatments based on angiotensin II receptor blockers (ARBs) on the risk of myocardial infarction (MI), cardiovascular and all-cause death, as compared with conventional treatment or placebo. METHODS: We performed a meta-analysis of all available major international, randomized clinical trials (20 trials, n = 108 909 patients, mean age 66.5 +/- 4.1 years), published by 31 August 2008, comparing ARBs with other drugs or conventional therapies (placebo) and reporting MI incidence. RESULTS: During a mean follow-up of 3.3 +/- 1.1 years, a total of 2374/53 208 and 2354/53 153 cases of MI were recorded in ARB-based groups and in comparator arms, respectively [odds ratio (OR) 95% confidence interval (CI) 1.008 (0.950-1.069)]. Risks of MI were not different when tested in different clinical conditions, including hypertension, high cardiovascular risk, stroke, coronary disease, renal disease and heart failure. No significant differences in the risk of MI between treatment with ARBs versus placebo [OR 95% CI 0.944 (0.841-1.060)], beta-blockers and diuretics [OR 95% CI 0.970 (0.804-1.170)], calcium channel blockers [OR 95% CI 1.112 (0.971-1.272)], or angiotensin-converting enzyme (ACE) inhibitors [OR 95% CI 1.008 (0.926-1.099)] were observed. Analysis of trials comparing combination therapy based on ARBs plus ACE inhibitors versus active treatments or placebo showed equivalent MI risk [OR 95% CI 0.996 (0.896-1.107)]. CONCLUSION: The present meta-analysis indicates that the risk of MI is comparable with use of ARBs and other antihypertensive drugs in a wide range of clinical conditions

C2238/αANP modulates apolipoprotein E through Egr-1/miR199a in vascular smooth muscle cells in vitro

Subjects carrying the T2238C ANP gene variant have a higher risk to suffer a stroke or myocardial infarction. The mechanisms through which T2238C/αANP exerts detrimental vascular effects need to be fully clarified. In the present work we aimed at exploring the impact of C2238/αANP (mutant form) on atherosclerosis-related pathways. As a first step, an atherosclerosis gene expression macroarray analysis was performed in vascular smooth muscle cells (VSMCs) exposed to either T2238/αANP (wild type) or C2238/αANP. The major finding was that apolipoprotein E (ApoE) gene expression was significantly downregulated by C2238/αANP and it was upregulated by T2238/αANP. We subsequently found that C2238/αANP induces ApoE downregulation through type C natriuretic peptide receptor (NPR-C)-dependent mechanisms involving the upregulation of miR199a-3p and miR199a-5p and the downregulation of DNAJA4. In fact, NPR-C knockdown rescued ApoE level. Upregulation of miR199a by NPR-C was mediated by a reactive oxygen species-dependent increase of the early growth response protein-1 (Egr-1) transcription factor. In fact, Egr-1 knockdown abolished the impact of C2238/αANP on ApoE and miR199a. Of note, downregulation of ApoE by C2238/αANP was associated with a significant increase in inflammation, apoptosis and necrosis that was completely rescued by the exogenous administration of recombinant ApoE. In conclusion, our study dissected a novel mechanism of vascular damage exerted by C2238/αANP that is mediated by ApoE downregulation. We provide the first demonstration that C2238/αANP downregulates ApoE in VSMCs through NPR-C-dependent activation of Egr-1 and the consequent upregulation of miR199a. Restoring ApoE levels could represent a potential therapeutic strategy to counteract the harmful effects of C2238/αANP

Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat

UCP2 maps nearby the lod score peak of STR1-stroke QTL in the SHRSP rat strain. We explored the potential contribution of UCP2 to the high-salt diet (JD)-dependent increased stroke susceptibility of SHRSP. Male SHRSP, SHRSR, two reciprocal SHRSR/SHRSP-STR1/QTL stroke congenic lines received JD for 4 weeks to detect brain UCP2 gene/protein modulation as compared with regular diet (RD). Brains were also analyzed for NF-κB protein expression, oxidative stress level and UCP2-targeted microRNAs expression level. Next, based on knowledge that fenofibrate and Brassica Oleracea (BO) stimulate UCP2 expression through PPARα activation, we monitored stroke occurrence in SHRSP receiving JD plus fenofibrate versus vehicle, JD plus BO juice versus BO juice plus PPARα inhibitor. Brain UCP2 expression was markedly reduced by JD in SHRSP and in the (SHRsr.SHRsp-(D1Rat134-Mt1pa)) congenic line, whereas NF-κB expression and oxidative stress level increased. The opposite phenomenon was observed in the SHRSR and in the (SHRsp.SHRsr-(D1Rat134-Mt1pa)) reciprocal congenic line. Interestingly, the UCP2-targeted rno-microRNA-503 was significantly upregulated in SHRSP and decreased in SHRSR upon JD, with consistent changes in the two reciprocal congenic lines. Both fenofibrate and BO significantly decreased brain microRNA-503 level, upregulated UCP2 expression and protected SHRSP from stroke occurrence. In vitro overexpression of microRNA-503 in endothelial cells suppressed UCP2 expression and led to a significant increase of cell mortality with decreased cell viability. Brain UCP2 downregulation is a determinant of increased stroke predisposition in high-salt-fed SHRSP. In this context, UCP2 can be modulated by both pharmacological and nutraceutical agents. The microRNA-503 significantly contributes to mediate brain UCP2 downregulation in JD-fed SHRSP

In vitro characterization of mitochondrial function and structure in rat and human cells with a deficiency of the NADH:ubiquinone oxidoreductase Ndufc2 subunit

Ndufc2, a subunit of the NADH:ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage. The latter was associated with increased oxidative stress and significant ultrastructural impairment of mitochondrial morphology with a loss of internal cristae. In both models the exposure to stress stimuli, such as high-NaCl concentration or LPS, exacerbated the mitochondrial damage and dysfunction. Resveratrol significantly counteracted the ROS generation. These findings provide additional insights on the role of an altered pattern of mitochondrial structure-function as a cause of human diseases. In particular, they contribute to underscore a potential genetic risk factor for cardiovascular diseases, including stroke

Atrial natriuretic peptide stimulates autophagy/mitophagy and improves mitochondrial function in chronic heart failure

Mitochondrial dysfunction, causing increased reactive oxygen species (ROS) production, is a molecular feature of heart failure (HF). A defective antioxidant response and mitophagic flux were reported in circulating leucocytes of patients with chronic HF and reduced ejection fraction (HFrEF). Atrial natriuretic peptide (ANP) exerts many cardiac beneficial effects, including the ability to protect cardiomyocytes by promoting autophagy. We tested the impact of ANP on autophagy/mitophagy, altered mitochondrial structure and function and increased oxidative stress in HFrEF patients by both ex vivo and in vivo approaches. The ex vivo study included thirteen HFrEF patients whose peripheral blood mononuclear cells (PBMCs) were isolated and treated with αANP (10-11 M) for 4 h. The in vivo study included six HFrEF patients who received sacubitril/valsartan for two months. PBMCs were characterized before and after treatment. Both approaches analyzed mitochondrial structure and functionality. We found that levels of αANP increased upon sacubitril/valsartan, whereas levels of NT-proBNP decreased. Both the ex vivo direct exposure to αANP and the higher αANP level upon in vivo treatment with sacubitril/valsartan caused: (i) improvement of mitochondrial membrane potential; (ii) stimulation of the autophagic process; (iii) significant reduction of mitochondrial mass-index of mitophagy stimulation-and upregulation of mitophagy-related genes; (iv) reduction of mitochondrial damage with increased inner mitochondrial membrane (IMM)/outer mitochondrial membrane (OMM) index and reduced ROS generation. Herein we demonstrate that αANP stimulates both autophagy and mitophagy responses, counteracts mitochondrial dysfunction, and damages ultimately reducing mitochondrial oxidative stress generation in PBMCs from chronic HF patients. These properties were confirmed upon sacubitril/valsartan administration, a pivotal drug in HFrEF treatment