Tolerance and autoimmunity: novel therapeutic approaches

La función primaria del sistema inmune es resguardar al individuo de los patógenos potencialmente dañinos que invaden el medio ambiente en el cual nos desarrollamos. Este cuenta con dos grandes ramas, la inmunidad innata y la adaptativa, ambas con la propiedad de diferenciar lo peligroso de aquello inofensivo. Estos procesos se hallan regulados por mecanismos homeostáticos que constituyen la tolerancia inmunológica, a los fines de limitar aquellos procesos prolongados y silenciar los potencialmente autoagresivos. Ante la falla de estos mecanismos de control, surgen las enfermedades autoinmunes. Avances en el conocimiento de la fisiopatología de estas entidades, han abierto un nuevo capítulo en el terreno de la inmunofarmacología. Su prometedor potencial actualmente nos ofrece novedosas herramientas terapéuticas para controlar y atenuar el daño causado por este tipo de respuestas. No obstante, debe continuarse la investigación en el campo de los agentes biológicos, ya que ninguno de ellos se encuentra libre de inconvenientes. Seguramente, futuros hallazgos se concretarán en futuros aciertos. Y los aciertos, en Medicina, equivalen a esperanza.The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the “magic bullet”.Fil: Ciliberti, Esteban. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Carambia, Leandro. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cavallin, Sebastian. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cerda, Osvaldo L.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Poderoso, Juan J.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Musique et processus identitaire : les églises nationale de Rome (16e - début 17e siècle)

This themed session relates to a research project devoted to analysis of the musical model of the national churches in Rome, jointly funded by the European Union (Marie Curie Programme) and the University of Liège. This research aims to contribute towards the study of music in the national churches in Rome during the 16th and 17th centuries by examining the fundamental issue of cultural exchanges between these institutions and the nations they represented in the pontifical city. Michela Berti and Emilie Corswarem will present an overview of the results obtained by the project to date, focussing on one of its main aspects: analysis of how the liturgical and paraliturgical traditions, as an expression of ‘nationhood’, may constitute one of the axes around which communities strengthened their identity in a foreign country. In the second part of the session, Galliano Ciliberti and Esteban Hernandez, collaborators on the project, will focus on concrete examples relating to the churches of S. Luigi dei Francesi and S. Giacomo degli Spagnoli. Galiano Ciliberti: From a liturgical perspective, the French national church in Rome, S. Luigi dei Francesi, held a particular position among the chapels of the 17th century in Rome. The discovery of three signed volumes by Vincezo Ugolini, dating from the years of his magisterium at S. Luigi (1616-1620 and 1631-1638) opens up new avenues for research. The repertoires contained in these books of vespers for the feast of the titular Saint of the national churches, do not follow the Roman liturgical Rite but the earlier Parisian Rite. Some pieces (such as the Prière du Roy and the Salvuum fac) anticipate the liturgical practice established by Louis XIV at Versailles. Esteban Hernández Castelló: As numerous publications have already shown, the national churches played an active role in Rome. The increasing 'Spanish' presence and its rise in power and influence in the Urbs in the 16th century was visible in many ways and undoubtedly justify, at least in part, its ambition to establish traditions which were particular to Spanish churches in the town, and which, in some cases, sought to 'contaminate' Roman traditions. The first exhaustive catalogue of the musical archives of Santa Maria in Monserrato degli Spagnoli (as well as some items belonging to San Giacomo) has revealed - among other things - a musical manuscript, which shows entirely Spanish customs and habits being exported to Rome. In particular, this is true for the subject of this communication: polyphonic song of the Passion for the Dominica in Ramis.Le modèle musical des églises nationales à Rome à l’époque baroque (BeIPD-COFUND-IPD APPEL 2013

Ezetimibe added to statin therapy after acute coronary syndromes

BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization ( 6530 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit