Paraoxonase: its multiple functions and pharmacological regulation

La homocisteína, aminoácido no-proteico, es un importante factor de riesgo de aterosclerosis y trombosis, afecta la vasodilatación y la función normal del endotelio vascular, es pro-inflamatoria e induce estrés de retículo endoplásmico. Su conformación más reactiva, la homocisteína tiolactona, producto de la acción no específica de la metionil-t RNA sintetasa, se incorpora a proteínas mediante puentes disulfuro (S-homocisteinilación) o uniones amida (Nhomocisteinilación) produciendo graves efectos sobre la estructura y función proteica conduciendo a toxicidad celular, respuestas autoinmunes y aterogénesis. La enzima paraoxonasa-1, integrante de la lipoproteína de alta densidad, fue inicialmente considerada por su capacidad de hidrolizar derivados organofosfato, pero luego se le atribuyó un importante papel protector contra la aterosclerosis por prevenir la oxidación de lipoproteínas e hidrolizar homocisteína tiolactona. Existen evidencias acerca del papel de paraoxonasa-1 en la enfermedad vascular. Los factores genéticos (polimorfismos de la paraoxonasa-1), ambientales y el estilo de vida influyen sobre su concentración y actividad biológica, pero distintos fármacos como hipolipemiantes o cardioprotectores y otros, como antibióticos y esteroides, son también importantes moduladores. En la presente revisión se actualiza la más destacada información sobre los estudios clínicos y experimentales que permiten entender el papel que cumple esta enzima en la protección ante el desarrollo de la aterosclerosis.Homocysteine, a non-protein amino acid, important risk factor for atherosclerosis and thrombosis, causes dysfunction of vascular endothelial cells traduced in inadequate vasodilatation mechanism, is pro-inflammatory and induces endoplasmic reticulum stress. The more reactive conformation is the homocysteine thiolactone (HcyT), product to the nonspecific action of methionyl-tRNA synthetase, which is incorporated into proteins by disulfide bonds (S-homocysteinilation) or amide bonds (N-homocysteinilation) affecting protein structure and function leading to cell toxicity, autoimmune responses and atherogenesis. The enzyme paraoxonase-1 (PON1), part of high density lipoprotein (HDL), had been studied only for its ability to hydrolyze organophosphate derivatives. But, more recently it has been attributed other important role. The enzyme activities are involving in protecting against the development of atherosclerosis, by preventing oxidation of lipoproteins and hydrolyze HcyT. There is growing evidence about the protective role of PON1 in vascular disease. Genetic factors (polymorphisms of the PON1), environmental and lifestyle influence their concentration and biological activity, but drugs used as cardioprotectives and lipid-lowering or others, such as antibiotics and steroids, are also important modulators. This review is an updated of the most prominent information on clinical and experimental studies for understanding the role of the PON-1 in the protection against development of atherosclerosis.Fil: Fridman, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana; ArgentinaFil: Porcile, Rafael. Universidad Abierta Interamericana; ArgentinaFil: Morales, Analía Verónica. Universidad Abierta Interamericana; ArgentinaFil: Gariglio, Luis Osvaldo. Universidad Abierta Interamericana; Argentin

Unusual case of a myxoma atrial left presenting with recurrent monoparesis

Usually, embolism is described from cardiac or large artery disease. Atrial fibrillation is the most common cause of cardiogenic emboli in stroke. Myxoma is responsible in only a few cases. We describe here a case of a patient who presented with recurrent pure left brachial monoparesis as a manifestation of a cardiac myxoma

Economic development, technical change and income distribution: A conversation between Keynesians, Schumpeterians and Structuralists. Introduction to the Special Issue

The original “manifesto” that gave rise to the Structuralist development theory was written for the Economic Commission of Latin America (ECLA, subsequently ECLAC, after incorporating the Caribbean States in 1984) by Raul Prebisch (1949). This work had a strong impact on both the theoretical and policy debates and served as a rationale for the efforts at structural change and industrialization that many developing countries adopted in the following decades. By and large, the Latin American Structuralist tradition focuses on how the external constraint disproportionately affects output growth and domestic policies in less developed economies. The existence of bottlenecks in the productive system and labor market dualism characterizing peripheral economies opens space for state intervention and industrial policies as a way to promote structural transformation and economic development