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(V.) braziliensis<\/jats:italic>isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments\" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of<jats:italic>L. (V.) braziliensis<\/jats:italic>to NO and nonresponsiveness to antimony therapy and cytokine production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the<jats:italic>in vitro<\/jats:italic>toxicity of NO against the promastigotes stages of<jats:italic>L. (V.) braziliensis<\/jats:italic>isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from<jats:italic>Leishmania<\/jats:italic>infected macrophage were used to measure TNF-\u03b1 and IL-10 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using NaNO<jats:sub>2<\/jats:sub>(pH 5.0) as the NO source,<jats:italic>L. (V.) braziliensis<\/jats:italic>isolated from refractory patients were more NO resistant (IC50 = 5.8 \u00b1 4.8) than<jats:italic>L. (V.) braziliensis<\/jats:italic>isolated from responsive patients (IC50 = 2.0 \u00b1 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant<jats:italic>L. (V.) braziliensis<\/jats:italic>isolated from responsive and refractory patients. NO-resistant<jats:italic>L. (V.) braziliensis<\/jats:italic>isolated from refractory patients infected more macrophages stimulated with LPS and IFN-\u03b3 at 120 hours than NO-susceptible<jats:italic>L. (V.) braziliensis<\/jats:italic>isolated from refractory patients. Also, lower levels of TNF-\u03b1 were detected in supernatants of macrophages infected with NO-resistant<jats:italic>L. (V.) braziliensis<\/jats:italic>as compared to macrophages infected with NO-susceptible<jats:italic>L. (V.) braziliensis<\/jats:italic>(p &lt; 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2334-10-209","type":"journal-article","created":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T18:14:18Z","timestamp":1279217658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-\u03b1 production"],"prefix":"10.1186","volume":"10","author":[{"given":"Anselmo S","family":"Souza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Giudice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia MB","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds H","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia R","family":"de Jesus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana R","family":"de Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar M","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roque P","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"key":"1189_CR1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.4269\/ajtmh.1989.41.687","volume":"41","author":"G Grimaldi Jr","year":"1989","unstructured":"Grimaldi G, Tesh RB, McMahon-Pratt D: A review of the geographic distribution and epidemiology of leishmaniasis in the New World. 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