2007
DOI: 10.1590/s0365-05962007000200002
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Tratamento da Leishmaniose Tegumentar Americana

Abstract: A leishmaniose tegumentar americana é doença infecciosa da pele e mucosa, cujo agente etiológico é um protozoário do gênero Leishmania. Seu tratamento é desafio porque as drogas disponíveis apresentam elevada toxicidade, e nenhuma delas é bastante eficaz. A recidiva, a falha terapêutica em pacientes imunodeprimidos e a resistência ao tratamento são fatores que motivam a busca de uma droga ideal.

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Cited by 52 publications
(40 citation statements)
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References 102 publications
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“…Another hypothesis suggests that Sb V acts as a prodrug that is transformed into the more toxic trivalent form (Sb III ) to exert its antileishmanial activity (6)(7)(8)(9). In fact, some studies indicate that Sb III production in vivo is responsible for both therapeutic activity and antimony toxicity (10)(11)(12). Furthermore, we have confirmed this hypothesis by showing that meglumine antimoniate causes DNA damage in vivo but not in vitro.…”
supporting
confidence: 59%
“…Another hypothesis suggests that Sb V acts as a prodrug that is transformed into the more toxic trivalent form (Sb III ) to exert its antileishmanial activity (6)(7)(8)(9). In fact, some studies indicate that Sb III production in vivo is responsible for both therapeutic activity and antimony toxicity (10)(11)(12). Furthermore, we have confirmed this hypothesis by showing that meglumine antimoniate causes DNA damage in vivo but not in vitro.…”
supporting
confidence: 59%
“…As leishmanioses são um conjunto de doenças causadas por protozoários do gênero Leishmania, que podem ocorrer na pele, nas membranas mucosas ou nas  vísceras. Embora o antimoniato de N-metilglucamina tenha sido introduzido em 1945 e ainda seja a droga de primeira escolha para o tratamento das leishmanioses (Frézard e Demicheli, 2010), o índice de sucesso terapêutico, usando o esquema preconizado pelo Ministério da Saúde, varia de 26% a 91,4% (Lima et al, 2007). Além disso, o uso de antimoniato de N-metilglucamina está associado a efeitos adversos, como, artralgia, cefaleia, reações cutâneas, mialgias, dores abdominais, alterações hepáticas, cardiológicas e renais (Rodrigues et al, 2007).…”
unclassified
“…Unfortunately, therapies for treating Leishmania infection remain limited, and pentavalent antimonials have remained the drugs of choice for over 60 years. All fi rst and second drug choices, including miltefosine, have high toxicity, require parenteral use, have high rates of relapse and drug resistance, and ultimately lead to treatment failure, especially in immunocompromised patients who desperately require new therapies 3 . Miltefosine (hexadecylphosphocholine) is an alkylphosphocholine, originally developed for the treatment of cancer, which was discovered to possess antifungal, antiamoebic, and leishmanicidal activity 4,5 .…”
mentioning
confidence: 99%
“…Miltefosine (hexadecylphosphocholine) is an alkylphosphocholine, originally developed for the treatment of cancer, which was discovered to possess antifungal, antiamoebic, and leishmanicidal activity 4,5 . The drug exerts its cytotoxic effect by interfering with the metabolism of membrane phospholipids, altering the composition, permeability, stability, and fluidity of the cell membrane, subsequently inducing apoptos is 3,6 . Miltefosine's mechanism of action also indirectly induces immunomodulatory antileishmanial mechanisms by increasing production of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 12 (IL-12), thereby increasing phagocytosis and inducing an immune response biased towards a Th1 profi le 7,8 .…”
mentioning
confidence: 99%