A 14 años de la desaparición forzada de Iván Torres Millacura : ¿qué ha cambiado?

A 14 años de la desaparición de Iván Torres Millacura, pese a la condena de la Corte Interamericana de Derechos Humanos y las condenas penales de dos de los autores, más la sanción del delito autónomo de desaparición forzada de personas en 2011, ésta práctica aberrante, sumada a las facultades policiales de detención por averiguación de antecedentes o identidad, sin control judicial, constituyen fuente permanente de hostigamiento por parte de funcionarios públicos a sectores vulnerables de la sociedad, principalmente jóvenes pobres. El funcionamiento violento de instituciones públicas es un fenómeno violatorio de derechos humanos que no sólo tienen como consecuencia la vulneración y violación de derechos fundamentales de las personas, sino que además son permeables a derivar rápidamente en la responsabilidad internacional del Estado, sino se piensa en medidas de prevención y fundamentalmente en sanciones adecuadas que impidan la impunidad de los casos y con ello la repetición de los mismos.Fil: Lecour, Lucas Jorge. Universidad Nacional de Cuyo. Facultad de Derech

Studies of symbiotically important Rhizobium meliloti exopolysaccharides EPSII and succinoglycan

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biology, 1999.Includes bibliographical references.by Louis LeCour, Jr.S.M

When are pro-inflammatory cytokines SAFE in heart failure?

The cytokine hypothesis presently suggests that an excessive production of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF) and interleukin 6 (IL6), contributes to the pathogenesis of heart failure. The concept, successfully proved in genetically modified animal models, failed to translate to humans. Recently, accumulation of apparently paradoxical experimental data demonstrates that, under certain conditions, production of pro-inflammatory cytokines can initiate the activation of a pro-survival cardioprotective signalling pathway. This novel path that involves the activation of a transcription factor, signal transducer and activator of transcription 3 (STAT3), has been termed the survival activating factor enhancement (SAFE) pathway. In this review, we will discuss whether targeting the SAFE pathway may be considered as a preventive and/or therapeutic measure for the treatment of heart failur

Cardioprotective strategies are not “one size fi ts all”. Is it time to consider personalised medicine?

Since the discovery of the conditioning phenomenon in 1986 (whereby brief episodes of ischaemia reperfusion protect against a sustained ischaemic insult), thousands of preclinical studies have explored the benefits and signaling mechanisms of this cardioprotective strategy which aims to protect patients undergoing percutaneous coronary interventions (PCI), or cardiopulmonary bypass (CPB) surgery, against ischaemia reperfusion injury. A large number of proof of concept clinical trials have highlighted the benefits ofconditioning to protect patients against ischaemia reperfusion injury, but none have yet translated to the clinical routine. The outcomes of the multicenter studies ERICCA,(1) RIPHeart(2) and CIRCUS(3) which involved larger number of patients (1 612, 1 385 and 970 respectively) were eagerly awaited, hoping that pharmacological conditioning with cyclosporine A, or remote ischaemic preconditioning, could soon become part of the clinical routine

Influence of Tumour Necrosis Factor Alpha on the Outcome of Ischaemic Postconditioning in the Presence of Obesity and Diabetes

Obesity and diabetes contribute to cardiovascular disease and alter cytokine profile. The cytokine, tumour necrosis factor alpha (TNFα), activates a protective signalling cascade during ischaemic postconditioning (IPostC). However, most successful clinical studies with IPostC have not included obese and/or diabetic patients. We aimed to investigate the influence of TNFα on the outcome of IPostC in obese or diabetic mice. TNF knockout or wildtype mice were fed for 11 weeks with a high carbohydrate diet (HCD) to induce modest obesity. Diabetes was induced in a separate group by administration of a single intraperitoneal injection of streptozotocin. Hearts were then isolated and subjected to ischaemia (35 min of global ischaemia) followed by 45 min of reperfusion. HCD increased body weight, plasma insulin and leptin levels while the glucose level was unchanged. In streptozotocin-treated mice, blood glucose, plasma leptin and insulin were altered. Control, obese or diabetic mice were protected with IPostC in wiltype animals. In TNF knockout mice, IPostC failed to protect control and diabetic hearts while a slight protection was observed in obese hearts. Our data confirm a bidirectional role for TNFα associated with the severity of concomitant comorbidities and suggest that diabetic and/or modestly obese patients may still benefit from IPostC

P652The cardioprotective effect of exogenous sphingosine-1-phosphate requires the activation of endogenous sphingosine-1-phosphate via the sphingosine kinase 1

Purpose: Exogenous administration of sphingosine-1-phosphate (S1P) alone, or as part of high density lipoprotein, protects against myocardial infarction. S1P-induced cardioprotection targets the inhibition of the mitochondrial permeability transition pore via mechanisms that remain unclear. In the cell, the endogenous production of S1P from sphingosine is dependent on the activation of sphingosine kinases (SphK) 1 and 2. These two kinases play a role in cardioprotection against ischemia-reperfusion (IR) injury. Therefore, we hypothesised that the cardioprotective effect of exogenous S1P requires the activation of endogenous S1P via SphK. Methods: Isolated cardiomyocytes from adult wildtype mice were exposed to 2 hours of simulated ischemia (SI) in the presence of S1P (10nM) with/without N,N-dimethylsphingosine (DMS, a SphK1 and 2 inhibitor, 10μM) or SKI (a specific SphK1 inhibitor, 15μM). Cell viability was assessed using trypan blue staining and normalised to the normoxic control. Isolated perfused hearts from adult wildtype mice were exposed to 35 minutes of global ischemia followed by 45 minutes of reperfusion (IR) in the presence of S1P (10nM) with/without SKI (10μM). Infarct size (IS) was assessed using tripheyltetrazolium chloride staining and SphK1 activity using a specific biochemical fluorescence based assay kit. Both parameters were normalised to the IR control. Results: In isolated cardiomyocytes, viability under normoxic conditions was 76±1%. SI reduced viability to 52±1% (p< 0.001 vs. normoxia). Pre-treatment with S1P restored the viability to 75±1% (p<0.001 vs. SI). The beneficial effect of S1P was partially inhibited in the presence of DMS (67±4%) (ns vs. S1P) and totally abrogated with SKI pre-treatment (54±2%). Similarly, pre-treatment with S1P in isolated hearts reduced IS following IR from 50±1% (IR control) to 31±2% (S1P) (p<0.001 vs. control). Pre-treatment with SKI abrogated the cardioprotective effect of S1P (56±8%) (p<0.05 vs. S1P) as well as the S1P-induced increase in SphK1 activity (from S1P: 196±79 arbitrary units (AU) to SKI+S1P: 53±27 AU, p<0.05 vs. S1P). Conclusions: Our data, performed in both isolated cardiomyocytes and isolated hearts subjected to an ischemia/reperfusion insult, strongly suggest that exogenous sphingosine-1-phosphate-induced cardioprotection is dependent on the activation of endogenous sphingosine-1-phosphate via sphingosine kinase

Wine and heart health: learning from the French paradox

Wine with good food (albeit fatty) is an integral part of the French dietary pattern which is often called the French paradox. We note that among the inherent compounds in wine, especially red, that could confer cardioprotection, are resveratrol and melatonin. However, we do not think that drinking red wine is the sole explanation for the French paradox, whereby a rich high fat diet is associated with a lower than expected incidence of coronary heart disease. Rather, we note differences in French social behaviour – French eating is for refined pleasure and conviviality. ''Food is bought, cooked, and celebrated.'' Gardening with the availability and love of fresh vegetables is common. This lifestyle may be the key to the French paradox which, however, seems to be a passing phenomenon as dietary patterns and passion for gardening change even in France. Recent data suggest that, after all, the French are susceptible to the same rules as are other nations. The true Mediterranean diet pattern, found only in the relatively small geographic part of the South of France, is by contrast low in fat, with little red meat and rich in fish and olive oil. Like the French diet, it emphasises fresh fruit and vegetables and includes modest wine with the meals