Navegando por Palavras-chave "visceral leishmaniasis"
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- ItemSomente MetadadadosAnálise da citotoxicidade renal e hepática de uma droga leishmanicida experimental (rf07) com potencial para a quimioterapia de cães com leishmaniose visceral em uma área endêmica, teresina - pi(Universidade Federal de São Paulo (UNIFESP), 2014-01-31) Pinheiro, Adriana Maria Viana Nunes [UNIFESP]; Schenkman, Sergio Schenkman [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)In Brazil, visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania (L.) chagasi and transmitted by the insect vector Lutzomyia longipalpis. Both humans and dogs are infected by this parasite; however, the treatment administered to humans is not effective in dogs. Since dogs are the principal domestic reservoir host of this parasite, the standardization of a canine treatment can be used as an alternative method to control parasitosis. The objective of this experimental, longitudinal, and quantitative study was to analyze renal and hepatic cytotoxicity in dogs with canine VL (CVL) after treatment with organotellurium compound RF07. Sixteen dogs were divided into four groups composed of four animals each, who received a daily dose of 0.5 mL/kg of the chosen treatment for 3 weeks. The first two groups comprised of CVL animals; the animals in the first group were administered phosphate-buffered saline solution (PBS), whereas the second group received organotellurium compound RF07 at a concentration of 10 ?g/mL. The other two groups were composed of healthy animals, who received the same treatment. Biochemical analysis was conducted to determine the levels of urea, creatinine, alkaline phosphatase, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT). In addition, hematological as well as renal and hepatic histopathological examinations were conducted. Reversal of liver damage was observed in dogs with CVL after drug administration, with a 53% reduction in mean GPT values, which enabled normal activity by the end of the treatment. However, in comparison with the reference values, a significant reduction (80%) was observed in the number of leukocytes at the end of the treatment. In the healthy dogs, drug administration decreased the mean GOT and GPT values by 35% by the end of the third week and 33% by the end of the second week, respectively. In this group, drug administration did not have a significant effect on the hematologic data, whereas the liver showed mild fatty metamorphosis, which was significantly different from that in the liver of CVL animals who received PBS. The kidneys of animals treated with organotellurium compound RF07 showed mild focal inflammatory infiltration with preserved glomerular integrity, which was significantly different compared with the kidneys of CVL animals treated with PBS. Based on these results, we conclude that this experimental drug had the ability to normalize hepatic and hematologic indices. Abstract Additionally, it did not cause hepatocellular damage or adversely affect renal filtration in both healthy dogs as well as those with VL.
- ItemSomente MetadadadosCirculating levels of sTNFR and discrepancy between cytotoxicity and immunoreactivity of TNF-alpha in patients with visceral leishmaniasis(Blackwell Science Ltd, 2000-01-01) Medeiros, Iara Marques de [UNIFESP]; Reed, S.; Castelo Filho, Adauto [UNIFESP]; Salomão, Reinaldo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Rio Grande Norte; Infect Dis Res InstObjective To study the influence of soluble tumour necrosis factor (TNF) receptors (sTNFR) on bioactivity; and immunoreactivity of TNF-alpha in patients with visceral leishmaniasis (Kala-azar) and to examine the association between circulating levels of sTNFR type I and type IT with clinical manifestations of the disease.Methods Ten patients with Kala-azar were enrolled. Plasma samples for TNF-alpha and sTNFR were obtained on days 0, 7 and 21-28 of antimonial therapy. Bioactivity of TNF-alpha was measured by cytotoxicity to L-929 cells and immunoreactivity by enzyme-linked immunosorbent assay (ELISA). sTNFR-I and sTNFR-II were measured by ELISA.Results Measured by ELISA, TNF-alpha was detected at baseline in all patients (range from 22.3 to 163 pg/mL) and showed a linear decline over time on therapy (r = -0.49, P = 0.007). in contrast, when measured by cytotoxicity assay, TNF-alpha was detected in only one patient at baseline (193 pg/mL) and in four patients at the end of therapy (38.7, 95, 133 and 232 pg/mL) and there was no linear association between TNF-alpha. and duration of therapy (r = -0.18, P = 0.45). sTNFR-I and sTNFR-II were detected in all patients before therapy. There was a strong positive correlation between plasma concentrations of sTNFR-I and sTNFR-II (r = 0.8, P = 0.006). Levels of sTNFR-I and sTNFR-II declined exponentially with time on therapyConclusions We concluded that sTNFR-I and sTNFR-II are related to disease activity in patients with Kala-azar and that these circulating receptors may interfere with the biological activity of TNF-alpha in patients with Kala-azar.
- ItemAcesso aberto (Open Access)Cross-protective immunity to Leishmania amazonensis is mediated by CD4+and CD8+epitopes of Leishmania donovani nucleoside hydrolase terminal domains(Frontiers Research Foundation, 2014-05-01) Nico, Dirlei; Gomes, Daniele Crespo; Alves-Silva, Marcus Vinicius; Freitas, Elisangela Oliveira; Morrot, Alexandre; Bahia, Diana [UNIFESP]; Palatnik, Marcos; Rodrigues, Mauricio Martins [UNIFESP]; Palatnik-de-Sousa, Clarisa B.; Universidade Federal do Rio de Janeiro (UFRJ); Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Minas Gerais (UFMG)The nucleoside hydrolase (NH) of Leishmania donovani (NH36) is a phylogenetic marker of high homology among Leishmania parasites. in mice and dog vaccination, NH36 induces a CD4+ T cell-driven protective response against Leishmania chagasi infection directed against its C-terminal domain (F3). the C-terminal and N-terminal domain vaccines also decreased the footpad lesion caused by Leishmania amazonensis. We studied the basis of the crossed immune response using recombinant generated peptides covering the whole NH36 sequence and saponin for mice prophylaxis against L. amazonensis. the F1 (amino acids 1-103) and F3 peptide (amino acids 199-314) vaccines enhanced the IgG and IgG2a anti-NH36 antibodies to similar levels. the F3 vaccine induced the strongest DTH response, the highest proportions of NH36-specific CD4+ and CD8+ T cells after challenge and the highest expression of IFN-gamma and TNF-alpha. the F1 vaccine, on the other hand, induced a weaker but significant DTH response and a mild enhancement of IFN-gamma and TNF-alpha levels. the in vivo depletion with anti-CD4 or CD8 monoclonal antibodies disclosed that cross-protection against L. amazonensis infection was mediated by a CD4+ T cell response directed against the C-terminal domain (75% of reduction of the size of footpad lesion) followed by a CD8+T cell response against the N-terminal domain of NH36 (57% of reduction of footpad lesions). Both vaccines were capable of inducing long-term cross-immunity. the amino acid sequence of NH36 showed 93% identity to the sequence of the NH A34480 of L amazonensis, which also showed the presence of completely conserved predicted epitopes for CD4+ and CD8+ T cells in F1 domain, and of CD4+ epitopes differing by a single amino acid, in F1 and F3 domains. the identification of the C-terminal and N-terminal domains as the targets of the immune response to NH36 in the model of L. amazonensis infection represents a basis for the rationale development of a bivalent vaccine against leishmaniasis.
- ItemSomente MetadadadosImmunization with the cysteine proteinase Ldccys1 gene from Leishmania (Leishmania) chagasi and the recombinant Ldccys1 protein elicits protective immune responses in a murine model of visceral leishmaniasis(Elsevier B.V., 2008-01-30) Ferreira, Josie Haydee L. [UNIFESP]; Gentil, Luciana Girotto [UNIFESP]; Dias, Suzana Souza [UNIFESP]; Fedeli, Carlos Eduardo C. [UNIFESP]; Katz, Simone [UNIFESP]; Barbiéri, Clara Lúcia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fac NOVAFAPIThe gene Ldccys1 enconding a cysteine proteinase of 30kDa from Leishmania (Leishmania) chagasi, as welt as the recombinant cysteine proteinase rLdccys1, obtained by cloning and expression of the Ldccys1 gene in the pHIS vector, were used to evaluate their ability to induce immune protective responses in BALB/c mice against L. (L.) chagasi infection. Mice were immunized subcutaneously with rLdccys1 plus Bacille Calmette Guerin (BCG) or Propionibacterium acnes as adjuvants or intramuscularly with a plasmid carrying the Ldccys1 gene (Ldccys1/pcDNA3) and CpG ODN as the adjuvant, followed by a booster with rLdccys1 plus CpG ODN. Two weeks after immunization the animals were challenged with 1 x 10(7) amastigotes of L. (L.) chagasi. Both immunization protocols induced significant protection against L. (L.) chagosi infection as shown by a very low parasite Load in the spleen of immunized mice compared to the non-immunized controls. However, DNA immunization was 10-fold more protective than immunization with the recombinant protein. Whereas rLdccys1 induced a significant secretion of IFN-gamma and nitric oxide (NO), animals immunized with the Ldccys1 gene increased the production of IgG2a antibodies, IFN-gamma and NO. These results indicated that protection triggered by the two immunization protocols was correlated to a predominant Th1 response. (c) 2007 Elsevier B.V. All rights reserved.