RESUMO
BACKGROUND: Malaria is a parasitic disease that compromises the human host. Currently, control of the Plasmodium falciparum burden is centered on artemisinin-based combination therapies. However, decreased sensitivity to artemisinin and derivatives has been reported, therefore it is important to identify new therapeutic strategies. METHOD: We used human erythrocytes infected with P. falciparum and experimental cerebral malaria (ECM) animal model to assess the potential antimalarial effect of eugenol, a component of clove bud essential oil. RESULTS: Plasmodium falciparum cultures treated with increasing concentrations of eugenol reduced parasitemia in a dose-dependent manner, with IC50 of 532.42 ± 29.55 µM. This effect seems to be irreversible and maintained even in the presence of high parasitemia. The prominent effect of eugenol was detected in the evolution from schizont to ring forms, inducing important morphological changes, indicating a disruption in the development of the erythrocytic cycle. Aberrant structural modification was observed by electron microscopy, showing the separation of the two nuclear membrane leaflets as well as other subcellular membranes, such as from the digestive vacuole. Importantly, in vivo studies using ECM revealed a reduction in blood parasitemia and cerebral edema when mice were treated for 6 consecutive days upon infection. CONCLUSIONS: These data suggest a potential effect of eugenol against Plasmodium sp. with an impact on cerebral malaria. GENERAL SIGNIFICANCE: Our results provide a rational basis for the use of eugenol in therapeutic strategies to the treatment of malaria.
Assuntos
Antimaláricos/farmacologia , Edema Encefálico/tratamento farmacológico , Eugenol/farmacologia , Estágios do Ciclo de Vida/efeitos dos fármacos , Malária Cerebral/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/parasitologia , Edema Encefálico/parasitologia , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Humanos , Concentração Inibidora 50 , Estágios do Ciclo de Vida/fisiologia , Malária Cerebral/parasitologia , Malária Falciparum/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium berghei/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/patogenicidadeRESUMO
OBJECTIVE: To determine the efficacy of albendazole plus dexamethasone in children with 1 or 2 ring-enhancing lesions (by computed tomography scan) on resolution of lesions and recurrence of seizure. STUDY DESIGN: Randomized controlled open trial. METHODS: Children of either sex, 1 to 14 years of age, with seizures and 1 or 2 ring-enhancing lesions <20 mm in diameter on computed tomography scan, likely to have neurocysticercosis, were assigned to treatment l groups. Children assigned to the treatment group (n=61) were given 0.15 mg/kg per day dexamethasone for 5 days plus 15 mg/kg per day albendazole for 28 days, starting on the third day of dexamethasone. Control group (n=62) children were given neither dexamethasone or albendazole. Anti-epileptic therapy was given to both the study groups. RESULTS: The lesions resolved completely or partially in more children in the treated group compared with the control group (79% versus 57%; P=.02). The proportion of children who had seizures was significantly lower in the treated group compared with the control group at 3 months (10% versus 32%; P=.006) and 6 months (13% versus 33%; P=.03). CONCLUSIONS: Albendazole plus dexamethasone increased complete or partial resolution of lesions and reduced the risk of subsequent recurrence of seizures among children with neurocysticercosis who had with seizures and 1 or 2 ring-enhancing lesions on computed tomography.
Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema Encefálico/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Dexametasona/uso terapêutico , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/tratamento farmacológico , Adolescente , Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Anticonvulsivantes/uso terapêutico , Encéfalo/parasitologia , Edema Encefálico/parasitologia , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neurocisticercose/parasitologia , Fenitoína/uso terapêutico , Recidiva , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Tomografia Computadorizada por Raios XRESUMO
We describe eight cases of pediatric patients whose neuroimages performed after seizures revealed abnormalities that were compatible with edema surrounding calcified lesions and which disappeared in subsequent examinations.