ABSTRACT
Two unrelated infants were diagnosed with and initially treated for hemophagocytic lymphohistiocytosis (HLH), but progressed to cholestasis and liver failure. Early onset lysosomal acid lipase deficiency (EO-LAL-D) was suspected due to lymphocytes with cytoplasmic vacuolation and/or adrenal calcifications and confirmed by enzymatic and genetic analysis. Enzyme replacement therapy with sebelipase alfa was implemented, but both children died, despite initial improvement. Since this inborn error of metabolism progresses rapidly in infants, early diagnosis is crucial, and appropriate treatment should be started as soon as possible. The authors suggest that the diagnosis of EO-LAL-D should be considered in infants with symptoms of HLH.
Subject(s)
Sterol Esterase/therapeutic use , Wolman Disease/drug therapy , Age of Onset , Female , Humans , Infant, Newborn , Lymphohistiocytosis, Hemophagocytic/etiology , Male , Wolman Disease/complications , Wolman DiseaseABSTRACT
Cardiac hypertrophy is a chronic complex disease that occurs in response to hemodynamic load and is accompanied by oxidative stress and mitochondrial dysfunction. Mitochondrial ATP-sensitive K channels (mitoKATPs) have previously been shown to prevent oxidative cardiac damage under conditions of ischemia/reperfusion. However, the effect of these channels on cardiac hypertrophy has not been tested to date. In this study, we show that treatment of Swiss mice with isoproterenol (30 mg·kg·d) induces cardiac hypertrophy while significantly decreasing the levels of reduced protein thiols, glutathione, catalase, and superoxide dismutase activity, indicative of a condition of oxidative imbalance. Treatment with diazoxide (a mitoKATP opener, 5 mg·kg·d) normalized the levels of protein thiols and reduced glutathione, rescued superoxide dismutase activity, and significantly prevented cardiac hypertrophy. The protective effects of diazoxide were mitigated by the mitoKATP blockers 5-hydroxydecanoate (5 mg·kg·d) and glibenclamide (3 mg·kg·d), demonstrating that they were related to activation of the channel. Taken together, our results establish that mitoKATP activation promotes very robust prevention of cardiac hypertrophy and associated oxidative imbalance and suggest that these channels can be important drug targets for the pharmacological control of cardiac hypertrophy.
Subject(s)
Cardiomegaly , Diazoxide/pharmacology , Oxidative Stress/drug effects , Potassium Channels/metabolism , Animals , Antioxidants/pharmacology , Cardiomegaly/drug therapy , Cardiomegaly/metabolism , Cardiotonic Agents/pharmacology , Disease Models, Animal , Mice , Mitochondria, Heart/metabolism , Treatment Outcome , Vasodilator Agents/pharmacologyABSTRACT
La meningitis bacteriana producida por haemophilus influenzae tipo b (HIB) es una enfermedad grave por la presentacion del cuadro clinico propiamente dicho, como por las secuelas que resultan de esta enfermedad. El fenomeno patogenico critico en el caso de las enfermedades mas graves causadas por microorganismos del tipo b es la invacion por parte de este, de las mucosas respiratorias y su supervivencia en la sangre. La relacion del estado de portador, o no, del HIB en las vias respiratorias altas, con el desarrollo de un cuadro meningeo, es aun una incognita. En los diferentes estudios realizados esta implicado el Haemophilus influenzae del serogrupo b, dek biotipo I y del subtipo 3L. Se observa mayor incidencia de menningitis por HIB en niños menores de 5 años, siendo la causa mas frecuente en esta edad...
