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Campo DC | Valor | Idioma |
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dc.contributor.author | Moens, Britta | - |
dc.contributor.author | Decanine, Daniele | - |
dc.contributor.author | Menezes, Soraya Maria | - |
dc.contributor.author | Cunha, Antônio Ricardo Khouri | - |
dc.contributor.author | Santos, Gilvanéia Silva | - |
dc.contributor.author | Lopez, Giovanni | - |
dc.contributor.author | Alvarez, Carolina | - |
dc.contributor.author | Talledo, Michael | - |
dc.contributor.author | Gotuzzo, Eduardo | - |
dc.contributor.author | Kruschewsky, Ramon de Almeida | - |
dc.contributor.author | Castro, Bernardo Galvão | - |
dc.contributor.author | Vandamme, Anne Mieke | - |
dc.contributor.author | Weyenbergh, Johan Van | - |
dc.creator | Moens, Britta | - |
dc.creator | Decanine, Daniele | - |
dc.creator | Menezes, Soraya Maria | - |
dc.creator | Cunha, Antônio Ricardo Khouri | - |
dc.creator | Santos, Gilvanéia Silva | - |
dc.creator | Lopez, Giovanni | - |
dc.creator | Alvarez, Carolina | - |
dc.creator | Talledo, Michael | - |
dc.creator | Gotuzzo, Eduardo | - |
dc.creator | Kruschewsky, Ramon de Almeida | - |
dc.creator | Castro, Bernardo Galvão | - |
dc.creator | Vandamme, Anne Mieke | - |
dc.creator | Weyenbergh, Johan Van | - |
dc.date.accessioned | 2014-08-22T14:38:43Z | - |
dc.date.available | 2014-08-22T14:38:43Z | - |
dc.date.issued | 2012-07 | - |
dc.identifier.issn | 1549-1277 | - |
dc.identifier.uri | http://repositorio.ufba.br/ri/handle/ri/15680 | - |
dc.description | p. 1-15 | pt_BR |
dc.description.abstract | Background Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA) monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. Principal Findings Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. Conclusions In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets. | pt_BR |
dc.language.iso | en | pt_BR |
dc.rights | Acesso Aberto | pt_BR |
dc.source | http://dx.doi.org/10.1371/journal.pntd.0001729 | pt_BR |
dc.title | Ascorbic Acid Has Superior Ex Vivo Antiproliferative, Cell Death-Inducing and Immunomodulatory Effects over IFN-α in HTLV-1-Associated Myelopathy | pt_BR |
dc.title.alternative | PLoS Medicine | pt_BR |
dc.type | Artigo de Periódico | pt_BR |
dc.identifier.number | v. 6, n. 7 | pt_BR |
Aparece nas coleções: | Artigo Publicado em Periódico (Faculdade de Medicina) |
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Arquivo | Descrição | Tamanho | Formato | |
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Ricardo Khouri.pdf | 712,94 kB | Adobe PDF | Visualizar/Abrir |
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