IFEG   20353
INSTITUTO DE FISICA ENRIQUE GAVIOLA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Modelling GM1 treatment in Experimental Chagas´ Disease
Autor/es:
S. COSSY ISASI; M. RODRÍGUEZ; L. MARTÍNEZ; M. CORDERO; S. LOPRESTI; C.A. CONDAT; G.J. SIBONA
Lugar:
Los Cocos, Córdoba
Reunión:
Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2009
Institución organizadora:
Sociedad Argentina de Biofísica
Resumen:
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Being one
of the worlds neglected diseases, Chagas has neither a vaccine nor a
satisfactory
therapy. Treatment of murine models of the acute infection with the ganglioside
GM1 has shown a strikingly nonlinear effect, leading to a strong decrease in
parasite load at low doses but reverting to a load increase at high doses.
Cardiocyte destruction concomitant with the disease is also significantly
reduced by a moderate application of GM1. A mathematical model for the
interaction between the parasite and the immune system is shown to explain
these effects and is used to predict an optimal dosage that maximizes parasite
removal with minimal cardiocyte destruction. In murine models of the chronic
disease, GM1 treatment improved electrocardigraphic records in mice with
prolonged QT interval. Long QT syndrome" (LQTS), is associated with
delayed cardiac repolarization. Acquired LQTS most often results from
administration of structurally diverse drugs that can block cardiac K+
channels, in particular channels carrying the rapid delayed rectifier current,
IKr. When chronic mice (with
arrhythmia and prolonged QT) were given one injection of GM1 and monitored one
month later, approximately 30% contraction of prolonged QT was observed. Since ganglioside GM1 regulates Na+/K+ ATPase
in cultured neurons and muscle cells, and since QT interval reflects potassium
repolarizing current it seems possible that this mechanisms underlie mice
improvement. Since
parasitemia is undetectable in the chronic disease, modeling strategy shifts
from population competition to models of molecular interactions.