RESUMO
Current treatments for different clinical forms of leishmaniasis are unsatisfactory, highly toxic and associated with increasing failure rates resulting from the emergence of resistant parasites. Leishmania (Viannia) braziliensis is the main aetiological agent of different clinical forms of American tegumentary leishmaniasis, including the mucosal form for which treatment has high failure rates. The aim of this work was to investigate the activity of the Morita-Baylis-Hillman adduct, methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate in vitro against isolates of L. (V.) braziliensis obtained from patients with different clinical manifestations of tegumentary leishmaniasis: localized cutaneous leishmaniasis, mucosal leishmaniasis and disseminated cutaneous leishmaniasis. The adduct effectively inhibited the growth of promastigotes of the different isolates of L. (V.) braziliensis (IC(50) ≤ 7·77 µg/ml), as well as reduced the infection rate of macrophages infected with these parasites (EC(50) ≤ 1·37 µg/ml). It is remarkable to state that the adduct was more effective against intracellular amastigotes (P ≤ 0·0045). The anti-amastigote activity correlated with an immunomodulatory effect, since the adduct was able to decrease the production of IL-6 and IL-10 by the infected macrophages. However, its effect was independent of nitric oxide production. This work demonstrates the anti-leishmanial activity of methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate and suggests its potential in the treatment of human infections caused by L. (V.) braziliensis.
Assuntos
Antiprotozoários/farmacologia , Benzoatos/farmacologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Leishmania braziliensis/efeitos dos fármacos , Óxido Nítrico/metabolismo , Animais , Benzoatos/toxicidade , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Orofacial granulomatosis is a generic term applied to manifestations of several diseases including sarcoidosis, Crohn's disease, Melkersson-Rosenthal syndrome, cheilitis granulomatosa of Miescher, tuberculosis and foreign-body reactions. What bonds these diseases together is the presence of noncaseating granulomas. A typical clinical manifestation of orofacial granulomatosis is recurrent labial swellings that eventually persist. This article describes 2 cases of OG diagnosed with the aid of immunohistochemical analysis and successfully treated with intralesional steroids.