RESUMEN
BACKGROUND: Leprosy is complicated by immunological reactions which can occur before, during and after successful completion of multidrug therapy. Genetic studies have suggested that polymorphisms in toll-like receptors (TLRs) may affect the susceptibility of an individual with leprosy to developing Type 1 reactions. OBJECTIVES: To examine the gene and protein expression of TLRs in the cutaneous lesions of leprosy Type 1 reactions at the onset of reaction and during systemic corticosteroid therapy. METHODS: Patients who were being treated for leprosy type 1 reactions with corticosteroids as part of a randomized controlled trial of corticosteroid treatment had skin biopsies performed before, during and at the end of treatment. The gene and protein expression of TLR2 and TLR4 were measured. RESULTS: We have demonstrated that the gene hARP-P0 is a suitable control gene for TLR gene expression studies in this population. The gene and protein expression of TLR2 and TLR4 were both reduced significantly during corticosteroid treatment. CONCLUSIONS: This is the first study to examine the expression of TLR2 and TLR4 in vivo in individuals experiencing leprosy Type 1 reactions. The data support the possibility of an important role for TLR2 and TLR4 in the pathogenesis of this important complication of leprosy.
Asunto(s)
Glucocorticoides/uso terapéutico , Lepra/tratamiento farmacológico , Receptor Toll-Like 2/fisiología , Receptor Toll-Like 4/fisiología , Adolescente , Adulto , Análisis de Varianza , Antibióticos Antituberculosos/uso terapéutico , ADN Complementario/biosíntesis , Quimioterapia Combinada , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Lepra/genética , Lepra/mortalidad , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Prednisolona/uso terapéutico , Receptor Toll-Like 2/efectos de los fármacos , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/efectos de los fármacos , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Adulto JovenRESUMEN
Left Ventricular Noncompaction (LVNC) is a genetic cardiac disease of emerging importance with a distinct clinical and pathophysiological presentation. The most common clinical manifestations include heart failure, arrhythmias and embolic events, and in children it may be associated with facial dysmorphisms and Wolff-Parkinson-White syndrome. The diagnosis of LVNC, however, is often missed, most often as a consequence of ignorance of the condition. Echocardiography is considered the reference standard for the diagnosis of LVNC. Prognosis remains poor for patients with impaired systolic left ventricular function, as treatment options are very limited. Because of the familial association of LVNC, first-degree relatives should be screened by Echocardiography.