Asunto(s)
Antineoplásicos/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Purinas/uso terapéutico , Quinazolinonas/uso terapéutico , Anciano , Linfoma de Burkitt/diagnóstico por imagen , Linfoma de Burkitt/virología , Comorbilidad , Infecciones por VIH/complicaciones , Ensayos Analíticos de Alto Rendimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Mutación , Recurrencia , Proteína p53 Supresora de Tumor/genéticaAsunto(s)
Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Osteólisis Esencial/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Adulto , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Osteólisis Esencial/etiología , Osteólisis Esencial/patología , Piperidinas , Resultado del TratamientoRESUMEN
BACKGROUND: There is evidence that the tea catechin epigallocatechin-3-gallate (EGCG) modulates myocardial contractility. However, the underlying mechanisms remain to be determined. AIMS: To study potential signalling pathways involved in EGCG-induced contractile parameters. METHODS AND RESULTS: EGCG increased fractional shortening in rat cardiac myocytes and enhanced intracellular systolic Ca2+ concentrations. In isolated rat hearts, perfusion with EGCG resulted in significant, dose-dependent increase in peak systolic left ventricular pressure, as well as in contraction and relaxation velocities. Heart rate did not change. Inhibition of the beta1-receptor with metoprolol had no influence on the contractile effects of EGCG. Furthermore, levels of cAMP and phosphorylation of phospholamban did not change with EGCG, indicating that the beta-receptor pathway is not involved. The L-type Ca2+ channel inhibitors, nifedipine and gallopamil, failed to modulate EGCG-induced increase in contractility. However, the myocardial effects and intracellular calcium transients stimulated by EGCG were significantly reduced by the antagonist of the Na+/H+ exchanger (NHE) methyl-N-isobutyl amiloride (MIA), and by blocking of the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R7943. CONCLUSION: These results indicate that Ca2+-dependent positive inotropic and lusitropic effects of EGCG are mediated in part via activation of the Na+/H+ exchanger and the reverse mode of the Na+/Ca2+ exchanger in the rat myocardium.