RESUMEN
We report here the case of a child with a known muscular abnormality and susceptibility to malignant hyperthermia who abruptly died after receiving a therapeutic dose of ondansetron. Also, we discuss the pharmacodynamic relationship of ondansetron to malignant hyperthermia in a susceptible host.
Asunto(s)
Antieméticos/efectos adversos , Predisposición Genética a la Enfermedad , Hipertermia Maligna/etiología , Miopatías Estructurales Congénitas/genética , Ondansetrón/efectos adversos , Canal Liberador de Calcio Receptor de Rianodina/genética , Antieméticos/farmacología , Antieméticos/uso terapéutico , Preescolar , Enfermedades en Gemelos/genética , Resultado Fatal , Humanos , Masculino , Hipertermia Maligna/genética , Ondansetrón/farmacología , Ondansetrón/uso terapéutico , Trillizos , Gemelos Monocigóticos , Vómitos/tratamiento farmacológicoRESUMEN
To probe the stability of the seven-iron ferredoxin from Thermus thermophilus (FdTt), we investigated its chemical and thermal denaturation processes in solution. As predicted from the crystal structure, FdTt is extremely resistant to perturbation. The guanidine hydrochloride-induced unfolding transition shows a midpoint at 6.5 m (pH 7, 20 degrees C), and the thermal midpoint is above boiling, at 114 degrees C. The stability of FdTt is much lower at acidic pH, suggesting that electrostatic interactions are important for the high stability at higher pH. On FdTt unfolding at alkaline pH, new absorption bands at 520 nm and 610 nm appear transiently, resulting from rearrangement of the cubic clusters into linear three-iron species. A range of iron-sulfur proteins has been found to accommodate these novel clusters in vitro, although no biological function has yet been assigned.