Actividad física y estrés oxidativo

La práctica regular de actividad física (AF) se asocia con una menor mortalidad y morbilidad cardiovascular. Parte de estos efectos beneficiosos están relacionados con los efectos favorables sobre los factores de riesgo cardiovascular clásicos. Sin embargo estos efectos explican sólo una parte de la protección de la AF sobre este tipo de enfermedades. La oxidación de las partículas de LDL colesterol tiene un papel fundamental en el proceso de la arteriosclerosis que es el mecanismo etiopatogénico de gran parte de las enfermedades cardiovasculares. En esta revisión narrativa se presenta el conocimiento actual sobre la relación entre la práctica de AF y la oxidación lipídica

Physical activity and lipid oxidation

Regular physical activity (PA) is associated with lower cardiovascular mortality and morbidity. Part of these benefits is related to the effects over the classic cardiovascular risk factors. These effects, however, only explain part of the protection of PA from these types of diseases. The oxidation of LDL cholesterol particles, which is the aetiopathogenic mechanism of a great part of cardiovascular diseases, plays an important role in the arteriosclerotic process. This narrative review presents current knowledge on the relationship between carrying out physical activity and lipid oxidation

Interrelationship of serum paraoxonase activity and paraoxonase genetic variants on atherosclerosis risk

La paraoxonasa (PON1) és una esterasa calciodepenent estretament associada a les lipoproteïnes d'alta densitat (HDL) que contenen apolipoproteïna AI, i s'ha descrit que dóna capacitat antioxidant a les HDL, amb la qual cosa disminueix l'acumulació dels lipoperòxids. L'activitat PON1 està sota control genètic i ambiental, i varia àmpliament entre individus i poblacions. L'activitat PON1 del paraoxon com a substrat és modulada per diversos polimorfismes en el locus PON1 dels humans. Un d'aquests polimorfismes és el PON1-192, que conté PON1 Q, una isoforma amb baixa activitat per la hidròlisi de paraoxon que té una glutamina a la posició 192, mentre que la isoforma R d'alta activitat conté una arginina a la posició 192. L'associació de l'activitat PON1 amb l'arteriosclerosi en estudis humans, animals i in vitro és prou consistent. Per tant, cal conèixer els factors que poden influenciar la PON1 sèrica. Els estudis genètics d'associació són menys consistents, probablement perquè els polimorfismes de la PON1 tenen només efecte en el risc de malaltia cardíaca coronària en grups particulars d'individus amb la presència de factors addicionals. És particularment important estudiar les interaccions gen-ambient que poden modular l'expressió fenotípica de la PON1 en diferents poblacions.Paraoxonase (PON1) is a calcium-dependent esterase, closely associated with high-density lipoprotein (HDL)-containing apolipoprotein AI, that has been reported to confer antioxidant properties on HDL by decreasing the accumulation of lipid peroxidation products. PON1 activity is under genetic and environmental regulation and appears to vary widely among individuals and populations. PON1 enzyme activity for paraoxon as a substrate is modulated by a number of polymorphisms at the PON1 locus in humans. One of them is the PON1-192 genetic polymorphism that comprises PON1 Q, an isoform which has a glutamine at position 192, and shows a low activity towards paraoxon hydrolysis, while the high paraoxon-activity PON1 R isoform contains an arginine at position 192. The association of PON1 activity levels with atherosclerosis in human, animal and in vitro studies is consistent and exciting. Therefore, there is an obvious need to know whether environmental factors can influence serum PON1. The genetic association studies for PON1 and atherosclerosis are less consistent, since the PON1 polymorphisms probably only produce an effect on coronary heart disease risk in particular subgroups of subjects in the presence of additional factors. It is particularly important to study gene-environmental interactions that may modulate phenotypic expression of PON1 in different populations

International differences in treatment effect: do they really exist and why?

With the increasing globalization of clinical trials, the opportunity exists to explore potential geographic differences in treatment effect within any major trial. Such geographic differences may arise because of international differences in patient selection, medical practice, or evaluation of outcomes, and such international variations need better documentation in trial reports. Appropriate pre-defined statistical analyses, including statistical tests of interaction regarding geographic heterogeneity in treatment effect, are important. Geographic variations are a particularly tricky form of subgroup analysis: they lack statistical power, are at best hypothesis-generating and can generate more confusion than insight. Referring to key examples, e.g. the PLATO and MERIT-HF, we emphasize the need for caution in interpreting evidence of potential geographic inconsistencies in treatment effect. Although it is appropriate to explore any biological or practical reasons for apparent geographic anomalies in treatment effect, the play of chance is often the most plausible and wise interpretation