Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways

Aliskiren (ALS) is well known for its antihypertensive properties. However, the potential underlying the molecular mechanism and the anti-hypertrophic effect of ALS have not yet been fully elucidated. The aim of the present study was to investigate the role of ALS in mammalian target of rapamycin (mTOR) and apoptosis signaling using in vivo and in vitro models of cardiac hypertrophy. A rat model of cardiac hypertrophy was induced by isoproterenol treatment (5 mg·kg-1·day-1) for 4 weeks, with or without ALS treatment at 20 mg·kg-1·day-1. The expression of hypertrophic, fibrotic, and apoptotic markers was determined by RT-qPCR. The protein expression of apoptotic markers mTOR and p-mTOR was assessed by western blot analysis. The proliferation of H9C2 cells was monitored using the MTS assay. Cell apoptosis was analyzed using flow cytometry. In vivo, isoproterenol-treated rats exhibited worse cardiac function, whereas ALS treatment reversed these dysfunctions, which were associated with changes in p-mTOR, Bcl-2, Bax, and cleaved caspase-3 expression, as well as the number of apoptotic cells. In vitro, H9C2 cardiomyocyte viability was significantly inhibited and cardiac hypertrophy was induced by Ang II administration, but ALS reversed Ang II-induced H9C2 cardiomyocyte hypertrophy and death. Furthermore, Ang II triggered the activation of the mTOR and apoptosis pathways in hypertrophic cardiomyocytes that were inhibited by ALS treatment. These results indicated that ALS alleviated cardiac hypertrophy through inhibition of the mTOR and apoptosis pathways in cardiomyocytes.

Evaluation of growth performance and gastro-intestinal parameters on the response of weaned piglets to dietary organic acids

ABSTRACT Two experiments (E) were carried out to evaluate the effects of fumaric acid and an acidifier blend [composed by calcium formate, calcium lactate and medium-chain fatty acids (capric and caprylic)] in piglet diets containing colistin (40 ppm) or halquinol (120 ppm) on performance, diarrhea incidence (E1), organs relative weight, pH values, intestinal morphometry and microbiota (E2). In E1, 192 and E2, 24 piglets weaned at 21-day-old were randomly assigned to blocks with 2x2 factorial arrangement of treatments [absence or presence of fumaric acid x absence or presence of acidifier blend], six replicates of eight (E1) and one piglet per pen (E2). For E1, the treatments were control (CD): no acidifier product + 40 ppm of colistin, FA: fumaric acid in absence of acidifier blend, AB: acidifier blend in absence of fumaric acid and, AF+AB: presence of fumaric acid and acidifier blend. For E2, the pre-starter I diet were used and the same treatments as E1 evaluated. No treatment effects (P>0.05) were observed on performance, diarrhea incidence (E1), gut pH values and duodenum morphometry of piglets (E2). However, the addition of AB increased (P<0.05) large intestine relative weight and, FA addition decreased (P<0.05) pancreas relative weight, jejunum villi height and, total coliform and E. coli counts in cecum. The inclusion of FA and AB in diets containing colistin or halquinol did not improve performance, although FA exerted an inhibitory effect on cecum microbiota.

Dosis efecto de la administración de fumarato ferroso en personas ancianas con deficiencia de hierro / Dose effect of ferrous fumarate administration in elderly persons with iron deficiency

Antecedentes: la anemia es un problema hematológico prevalente en ancianos, que afecta a 14 por ciento de los hombres y a 6 por ciento de las mujeres de la población mayor de 60 años de edad en México. Objetivo: determinar el efecto de la administración prolongada de fumarato ferroso en ancianos con deficiencia de hierro. Método: se estudió una población de 178 ancianos con edades entre 65 y 100 años, en 51 de estos sujetos (28.65 por ciento) se diagnosticaron niveles séricos anormales de hierro, menores de 80m g/dL para los hombres y 60 m g/dL para las mujeres, únicamente 21 de estos ancianos (11.8 por ciento) aceptaron participar en el estudio, en los cuales se estudió la respuesta a la administración oral de 5 mg/kg de hierro elemental durante seis meses.Los pacientes fueron clasificados según la alteración de los parámetros del metabolismo del hierro en tres grupos. (grupo 1 = 10.9 por ciento anemia; grupo 2 = 28.0 por ciento y grupo 3 = 63.0 por ciento de anemia). Resultados: la eficacia del tratamiento se evaluó por los cambios ocurridos en los parámetros hematológicos, como concentración de hierro sérico, hemoglobina, ferritina e índice de saturación, a los 0, 30, 90 y 180 días. Se observó que el tratamiento con fumarato ferroso durante seis meses produjo mejoría en la población estudiada determinada por el incremento significativo en los valores de los parámetros del metabolismo del hierro.Conclusiones: los resultados de este estudio sugieren la utilidad del tratamiento prolongado con fumarato ferroso en pacientes ancianos con deficiencia de hierro, para evitar fallas terapéuticas como consecuencia del no cumplimiento, el cual es común en ellos