Subject(s)
Antineoplastic Agents/therapeutic use , Burkitt Lymphoma/drug therapy , Burkitt Lymphoma/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , Purines/therapeutic use , Quinazolinones/therapeutic use , Aged , Burkitt Lymphoma/diagnostic imaging , Burkitt Lymphoma/virology , Comorbidity , HIV Infections/complications , High-Throughput Screening Assays , Humans , Magnetic Resonance Imaging , Male , Mutation , Recurrence , Tumor Suppressor Protein p53/geneticsSubject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Osteolysis, Essential/drug therapy , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adenine/analogs & derivatives , Adult , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Male , Osteolysis, Essential/etiology , Osteolysis, Essential/pathology , Piperidines , Treatment OutcomeABSTRACT
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.