Thesis (M.S.)--Rochester Institute of Technology, 2009. / Typescript. Includes bibliographical references (leaves 37-38).

Nitric oxide (NO) has been shown to be lethal for a variety of intracellular pathogens including Leishmania. In murine models, the inducible nitric oxide synthase gene (iNOS) is expressed in activated macrophages and is involved in the synthesis of NO. Because the role of NO and iNOS in human leishmaniasis was less clear, we examined the expression of the iNOS gene in human macrophages infected with Leishmania in vitro and in biopsy tissue from subjects with cutaneous leishmaniasis. / Pentavalent antimony (Sb5+) in the form of Pentostam(TM) or Glucantime(TM) is still the treatment of choice despite its toxicity. Aldara(TM) (5% imiquimod) is an immune-response modifying agent that has been approved by the Food and Drug Administration in the USA for treating genital warts caused by papillomaviruses. We conducted an open-label, prospective study of combined Glucantime(TM) + Aldara(TM) therapy in subjects with CL who had previously failed a complete course of Glucantime(TM) treatment at regular doses. (Abstract shortened by UMI.)

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Texas at El Paso, 2009. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

De 12 casos de leishmaniose tegumentar (LT) em AIDS, em São Paulo, sete do levantamento retrospectivo (1990 a 2001) e cinco do prospectivo (2001 a 2004), com contato prévio com área endêmica para leishmanioses, 50% eram usuários de drogas injetáveis (1990-2001). Apresentavam média de linfócitos T CD4+ de 77 células/mm3, um era C2 e 11, C3 (classificação de HIV, segundo CDC) e 70% tinha sorologia positiva para leishmanioses. As manifestações de LT em mucosa e pele eram diversificadas: úlcera única ou lesões múltiplas e polimórficas ou disseminadas, incluindo comprometimento genital em 4 casos. Todos receberam tratamento específico para leishmaniose e 50%, HAART. 50% recidivaram e 50% foram a óbito no período, independentemente do uso do HAART / From 12 cases of tegumentary leishmaniasis (TL) in AIDS, from São Paulo, seven from retrospective (1990 a 2001) and five from prospective studies (2001 a 2004), with previous contact with endemic areas for leishmaniasis, 50% were endovenous drug users (1990-2001). Presenting mean 77 CD4+ T cells/mm3, one was C2 and 11 were C3 (HIV classification, according to CDC) and 70% had positive serology for leishmaniasis. Presentation of TL in the skin and mucosa were diversified: single or multiple ulcers and polymorphic or disseminated lesions, including lesions in genital area in 4 cases. All were treated with anti-leishmanial drugs and 50% with HAART. 50% presented relapse and 50% died during follow up period, independently of use of HAART

De 12 casos de leishmaniose tegumentar (LT) em AIDS, em São Paulo, sete do levantamento retrospectivo (1990 a 2001) e cinco do prospectivo (2001 a 2004), com contato prévio com área endêmica para leishmanioses, 50% eram usuários de drogas injetáveis (1990-2001). Apresentavam média de linfócitos T CD4+ de 77 células/mm3, um era C2 e 11, C3 (classificação de HIV, segundo CDC) e 70% tinha sorologia positiva para leishmanioses. As manifestações de LT em mucosa e pele eram diversificadas: úlcera única ou lesões múltiplas e polimórficas ou disseminadas, incluindo comprometimento genital em 4 casos. Todos receberam tratamento específico para leishmaniose e 50%, HAART. 50% recidivaram e 50% foram a óbito no período, independentemente do uso do HAART / From 12 cases of tegumentary leishmaniasis (TL) in AIDS, from São Paulo, seven from retrospective (1990 a 2001) and five from prospective studies (2001 a 2004), with previous contact with endemic areas for leishmaniasis, 50% were endovenous drug users (1990-2001). Presenting mean 77 CD4+ T cells/mm3, one was C2 and 11 were C3 (HIV classification, according to CDC) and 70% had positive serology for leishmaniasis. Presentation of TL in the skin and mucosa were diversified: single or multiple ulcers and polymorphic or disseminated lesions, including lesions in genital area in 4 cases. All were treated with anti-leishmanial drugs and 50% with HAART. 50% presented relapse and 50% died during follow up period, independently of use of HAART

Introdução: Um dos primeiros sistemas de defesa contra os microrganismos é a via dos receptores Toll-like (TLRs). A ativação destes receptores leva à síntese de citocinas, dando início à resposta imune inata. Em modelos animais, o TLR2, TLR4 e TLR9 parecem estar relacionados com o reconhecimento de antígenos de Leishmania. A relação entre TLRs e leishmânia pode ser um mecanismo chave no desenvolvimento da doença ou no controle da mesma. Até o momento não existem estudos de TLRs na leishmaniose cutânea humana. Objetivo: Determinar o padrão de expressão e as células associadas com o TLR2, TLR4 e TLR9 na leishmaniose cutânea. O objetivo secundário é correlacionar a quantidade de TLRs com a quantidade de citocinas e células inflamatórias na pele. Métodos: Cem biópsias de pacientes com leishmaniose cutânea causadas por Leishmania (V.) braziliensis foram selecionadas inicialmente. Apenas os casos confirmados (presença de amastigotas no raspado, teste de Montenegro positivo, imunoistoquímica com presença de antígenos de Leishmania e reação em cadeia da polimerase com DNA de Leishmania (V.) braziliensis foram incluídos. Um grupo controle de pele normal foi incluído para comparação (quatro casos). A expressão de TLR2, TLR4 e TLR9 foi determinada por técnica imunoistoquímica, da mesma forma que os fenótipos celulares (células NK, macrófagos, células dendríticas, células CD4 e CD8) e citocinas (IL-1, IL-6, IL-12, TNF-alfa, IFN-gama). Dupla-marcação foi realizada para identificar as células que expressaram os TLRs analisados. Análise semi-quantitativa foi utilizada para avaliação da expressão de TLRs na epiderme, enquanto na derme foi realizada análise quantitativa. O nível de significância foi estabelecido com p<0,05. Resultados: Doze casos preencheram os critérios de inclusão. Os pacientes eram todos masculinos, com lesões apenas em membros inferiores e mediana de idade de 23 anos [16-47]. A expressão de TLR2, TLR4 e TLR9 na epiderme da pele normal foi alta. Quando comparados com pele normal, tanto TLR4 quanto TLR2 mostraram menor expressão no epitélio dos pacientes com leishmaniose e não houve expressão de TLR9. A média de células expressando TLR2 na derme foi de 136,36±82,46 células/mm2, ao passo que a média de células expressando TLR4 foi de 3,21±4,11 células/mm2. A contagem de TLR9 foi de 86,15±88,36 células/mm2 predominando em áreas de formação de granulomas. A regressão linear não demonstrou relação entre a contagem de células marcadas ou citocinas com TLR2 ou TLR4. O aumento proporcional da expressão de TLR9 relacionou-se com maior expressão de IL-12 e IL-4 (p < 0,05). A dupla marcação demonstrou que os macrófagos expressaram TLR2. A dupla marcação não mostrou expressão de TLR2 nas células dendríticas e nas células NK. Conclusão: A leishmaniose cutânea localizada associa-se com a presença de TLR2, TLR4 e TLR9. No epitélio a expressão de TLR2 e TLR4 em pacientes com leishmaniose está diminuída em relação aos pacientes controles. A expressão do TLR2 na derme é estatisticamente maior que a de TLR4 e TLR9, a qual é expressa pelos macrófagos. A expressão de TLR9 ocorre principalmente nas áreas de granulomas havendo relação com a expressão de IL-12 e IL-4 / Introduction: One of the first systems of defense against microorganisms is the Toll-like receptors (TLRs) pathway. The activation of these receptors promotes the cytokine synthesis, initiating the innate immune response. In animal models, TLR2, TLR4 and TLR9 appear to be related to the recognition of antigens of Leishmania. The relationship between TLRs and Leishmania can be a key mechanism in the development of the disease or it control. Until now, there are not studies about TLRs in human cutaneous leishmaniasis. Objective: To determine the expression pattern and the cells associated with TLR2, TLR4 and TLR9 in cutaneous leishmaniasis. The secondary objective is to correlate the amount of TLRs with the amount of cytokines and inflammatory cells. Methods: One hundred biopsies from patients with cutaneous leishmaniasis caused by Leishmania (V.) braziliensis were initially selected. Only confirmed cases of cutaneous leishmaniasis were included in the analysis (presence of amastigotes in the scraping, positive Montenegro test, immunohistochemistry with the presence of Leishmania antigens and polymerase chain reaction with DNA from Leishmania (V.) braziliensis. A control group (4 cases) of normal skin was included for comparison. The expression of TLR2, TLR4 and TLR9 was determined by immunohistochemistry, as well as cell phenotypes (NK cells, macrophages, dendritic cells, CD4 and CD8) and cytokines (IL-1, IL-6, IL-12, TNF-alpha, IFN-gamma). Double-staining was used to determine the cells expressing TLRs. Semi-quantitative analysis was used for evaluation of the expression of TLRs in the epidermis. Quantitative analysis was performed to evaluate the expression in the dermis. The level of significance was defined as p <0.05. Results: 12 cases fulfilled inclusion criteria. The patients were all male, with lesions in lower limbs and median age of 23 years [16-47]. The expression of TLR2 and TLR4 in the epidermis of normal skin was high. When compared with normal skin, TLR2 and TLR4 showed lower expression in the epidermis. There was no expression of TLR9 in the epidermis in cases of cutaneous leishmaniasis and normal skin. The mean number of cells expressing TLR2 in the dermis was 136.36±82.46 cells/mm2, while the average of cells expressing TLR4 was 3.21±4.11 cells/mm2. The count of TLR9 was 86.15±88.36 cells/mm2, and it was found mainly in the areas of granuloma formation. Linear regression showed no relationship between the number of labeled cells or cytokines with TLR2 or TLR4. There was an association between TLR9 and two cytokines (IL-12 and IL-4). This correlation suggested that the proportional increase in the expression of TLR9 was related to greater expression of IL-12 and IL-4 (p<0.05). The double staining showed that macrophages and endothelial cells expressed TLR2. The double staining showed no expression of TLR2 in dendritic cells and NK cells. Conclusion: The localized cutaneous leishmaniasis associated with the presence of TLR2, TLR4 and TLR9. The expression of TLR2 in the dermis was statistically greater than that of TLR4 and TLR9, which is expressed by macrophages. The expression of TLR9 occurs primarily in the areas of granulomas was associated with the expression of IL-12 and IL-4

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.