Effect of atorvastatin on lipoxygenase pathway-related gene expression in an in vitro model of lipid accumulation in hepatocytes.

Lipid accumulation in hepatocytes can result from an imbalance between lipid acquisition and lipid catabolism. In recent years, it has been discovered that eicosanoids derived from arachidonic acid (AA) have the potential to create specialized pro-resolving lipid mediators to actively resolve inflammation, but it is not clear whether AA and lipoxygenases exert effects on hepatic inflammation. Here, the effects of atorvastatin on the expression of cytoplasmic phospholipase A2 (cPLA2) and lipoxygenase pathway genes (ALOX5, ALOX12, ALOX15, and ALOX15B) were evaluated in an in vitro model of palmitic acid (PA)-induced hepatocyte lipid accumulation in McA-RH7777 (McA) cells. Palmitic acid increased cPLA2 expression, intracellular AA levels, and ALOX12 expression (P < 0.05). Atorvastatin at various concentrations had no significant effects on AA levels or on cPLA2, ALOX15, and ALOX15B expressions. ALOX5 was not detected, despite multiple measurements. Pro-inflammatory IL-1ß expression levels were upregulated by PA (P < 0.01) and attenuated by atorvastatin (P < 0.001). TNFα did not differ among groups. The expression levels of anti-inflammatory IL-10 decreased in response to PA (P < 0.05), but were not affected by atorvastatin. In conclusion, in an in vitro model of lipid accumulation in McA cells, atorvastatin reduced IL-1ß; however, its effect was not mediated by AA and the lipoxygenase pathway at the established doses and treatment duration. Further research is required to investigate time-response data, as well as other drugs and integrated cell systems that could influence the lipoxygenase pathway and modulate inflammation in liver diseases.

Relación entre prehipertensión arterial y trastornos neurocognitivos / Relationship between prehypertension and neurocognitive disorders

Determinar el desempeño de normotensos y pacientes prehipertensos en estudios neurocognitivos. Método: Se seleccionaron pacientes con monitoreo ambulatorio de presión arterial de los Servicios de Medicina Interna y Cardiología del Hospital Militar "Dr. Carlos Arvelo" entre julio 2016 y julio 2017. Se clasificaron, de acuerdo al JNC 7, en normotensos y prehipertensos (29 normotensos (26.1%) y 29 prehipertensos (64.4%). Se les realizaron pruebas neurocognitivas (atención, funciones ejecutivas, memoria), para determinar el desempeño cognitivo. Resultados: Los pacientes con prehipertensión tuvieron peor ejecución en las mayoría de las pruebas, siendo la alteración más destacada, la función ejecutiva: clases funcionales (p<0,001) errores totales (p 0,005); así como, en pruebas de atención en las cuales todas las modalidades estuvieron comprometidas: atención espacial (p<0,01), digito símbolo (p 0.018), ejecución continua: (p<0.05). También se demostró que a mayor edad mayor compromiso neurocognitivo, y que el estado nutricional parece influir en el desempeño de las funciones ejecutivas siendo el grupo de los obesos el de peor actuación (p 0.04). Discusión: La función frontal fue la singularidad más alterada en los prehipertensos por su labilidad y propensión a apoptosis (filogenéticamente más nueva), motivado por hipoperfusión sostenida. Igualmente, la obesidad promueve citoquinas proinflamatorias, ausencia o disminución del receptor de la leptina, presencia de oxiesteroles, y acúmulo de beta amiloide. Conclusión: los pacientes prehipertensos presentan alteraciones neurocognitivas, surgiendo la interrogante sobre si se deben replantear nuevas metas para el tratamiento de la tensión arterial e inicio precoz en estados preclínicos(AU)

To ascertain the neurocognitive performance in prehypertensive vs normotensive patients. Method: ambulatory blood pressure monitorization in patients attending the Internal Medicine and Cardiology consultations of the Military Hospital "Dr. Carlos Arvelo", Cara-cas,Venezuela between July 2016-2017. They were classified according to the JNC 7 in normotensive and prehypertensive. Neurocognitive studies where performed (attention, memory, and executive function). Results: prehypertensive patients had the worst executive response in most tests; the most altered functional classes (p<0,001), total errors (p 0,005): likewise, all attention tests were compromised: spacial attention (p<0,01), digitsymbol (p 0.018) and continuous execution (p<0.05). We also found that in older age, cognitive function declines and the nutritional state, specially obesity, deteriorates executive function performance (p 0.04). Discussion: executive function corresponds to correct frontal lobe execution, nevertheless it was the most altered singularity in prehypertensive patients, probably due to its liability and propensity to apoptosis (phylogenetically morerecent), and because of sustained hypoperfusion in frontal regions. Likewise, obesity promotes proinflammatory cytokines, absence or down regulation of leptin receptors, presence of oxosteroids and betaamilode cumulus. Conclusion: prehypertensive patients had altered neurocognitive tests, thus arising the question if new guidelines for treatment and optimal management of hypertension should be raised in preclinical conditions(AU)