EFAR - Escola de Farmácia

URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/451

Notícias

O curso de Farmácia em Ouro Preto foi criado em 1839, sendo a mais antiga Escola de Farmácia da América Latina.

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2004 - 200922010 - 201912020 - 20223

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Assunto: search.filters.subject.Immunotherapy

Resultados da Pesquisa

Agora exibindo 1 - 6 de 6
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    LBMPL vaccine therapy induces progressive organization of the spleen microarchitecture, improved Th1 adaptative immune response and control of parasitism in Leishmania infantum naturally infected dogs.
    (2022) Roatt, Bruno Mendes; Cardoso, Jamille Mirelle de Oliveira; Reis, Levi Eduardo Soares; Moreira, Gabriel José Lucas; Gonçalves, Letícia Captein; Marques, Flávia de Souza; Moreira, Nádia das Dores; Vieira, Paula Melo de Abreu; Soares, Rodrigo Dian de Oliveira Aguiar; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa
    The spleen plays a central role in human and canine visceral leishmaniasis, where the activation of the immune response occurs in one of the tissues where Leishmania infantum reproduces. Therefore, this organ is both a target to understand the mechanisms involved in the parasite control and a parameter for assessing the therapeutic response. In this sense, this study aimed to evaluate the main histological, immunological and parasitological aspects in the spleen of symptomatic dogs naturally infected by L. infantum treated with the therapeutic vaccine LBMPL. For this, dogs were divided into four groups: dogs uninfected and untreated (NI group); L. infantum-infected dogs that were not treated (INT group); L. infantum-infected dogs that received treatment only with monophosphoryl lipid A adjuvant (MPL group); and L. infantum-infected dogs that received treatment with the vaccine composed by L. braziliensis promastigote proteins associated with MPL adjuvant (LBMPL group). Ninety days after the therapeutics protocol, the dogs were euthanized and the spleen was collected for the proposed evaluations. Our results demonstrated a reduction of hyperplasia of red pulp and follicular area of white pulp, increased mRNA expression of IFN-γ, TNF-α, IL-12 and iNOS, and decreased IL-10 and TGF-β1, and intense reduction of splenic parasitism in dogs treated with the LBMPL vaccine. These results possibly suggest that the pro-inflammatory environment promoted the progressive organization of the splenic architecture favoring the cellular activation, with consequent parasite control. Along with previously obtained data, our results propose the LBMPL vaccine as a possible treatment strategy for canine visceral leishmaniasis (CVL).
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    Down regulation of IL-10 and TGF-β1 mRNA expression associated with reduced inflammatory process correlates with control of parasitism in the liver after treating L. infantum infected dogs with the LBMPL vaccine therapy.
    (2022) Roatt, Bruno Mendes; Cardoso, Jamille Mirelle de Oliveira; Brito, Rory Cristiane Fortes de; Reis, Levi Eduardo Soares; Moreira, Gabriel José Lucas; Vieira, Paula Melo de Abreu; Souza, Flávia Marques de; Lima, Wanderson Geraldo de; Soares, Rodrigo Dian de Oliveira Aguiar; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa
    The liver plays an important role in human and canine visceral leishmaniasis, then it is considered as target to understand the mechanisms involved in the parasite control and a parameter to assess therapeutic responses. In this sense, our study focuses on evaluating the major alterations in the liver by histological (morphometric parenchyma inflammation/semi-quantitative portal inflammation), immunohistochemical assays (parasitism), and qPCR (parasitism and cytokine gene expression) in Leishmania infantum naturally infected dogs and treated with LBMPL vaccine. Animals were divided in four groups: NI group (n = 5): uninfected and untreated dogs; INT group (n = 7): L. infantum-infected dogs and not treated; MPL group (n = 6): L. infantum-infected dogs that received only monophosphoryl lipid A adjuvant, and LBMPL group (n = 10): L. infantum-infected dogs that received treatment with the vaccine composed by L. braziliensis disrupted promastigotes associated with MPL adjuvant. Ninety days after the end of treatments, the dogs were euthanized, and the liver was collected for the proposed evaluations. Significantly lower portal inflammatory reactions, and lower parenchyma inflammation were observed in the LBMPL group compared to INT and MPL groups. iNOS mRNA expression was higher in LBMPL group and in contrast, IL-10 and TGF-β1 mRNA expression was lower in this group when compared to INT group. Immunohistochemical and qPCR analysis showed significant parasite load reduction in LBMPL group compared to INT and MPL animals. Our data suggest that in naturally Leishmania-infected dogs, LBMPL vaccine reduces the damage in the hepatic tissue, being able to attenuate the type 2 immune response. It could be associated with a marked reduction in the parasitism decreasing liver inflammation in treated dogs. Along with previously obtained data, our results suggest that LBMPL vaccine can significantly contribute to the therapy strategy for L. infantum infected dogs.
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    IL-10 receptor blockade controls the in vitro infectivity of Leishmania infantum and promotes a Th1 activation in PBMC of dogs with visceral leishmaniasis.
    (2021) Cardoso, Jamille Mirelle de Oliveira; Brito, Rory Cristiane Fortes de; Costa, Ana Flávia Pereira; Mathias, Fernando Augusto Siqueira; Reis, Levi Eduardo Soares; Vieira, João Filipe Pereira; Soares, Rodrigo Dian de Oliveira Aguiar; Reis, Alexandre Barbosa; Roatt, Bruno Mendes
    An important strategy to reduce the risk of visceral leishmaniasis (VL) in humans is to control the infection and disease progression in dogs, the domestic reservoir of Leishmania infantum parasites. Certain therapeutic strategies that modulate the host immune response show great potential for the treatment of experimental VL, restoring the impaired effector functions or decreasing host excessive responses. It is known that the overproduction of interleukin-10 (IL-10) promotes parasite replication and disease progression in human VL as well as in canine visceral leishmaniasis (CVL). Thus, in the present study we investigated the potential of the anticanine IL-10 receptor-blocking monoclonal antibody (Bloq IL-10R) to control and reduce in vitro infectivity of L. infantum and improve the ability of PBMC isolated from VL dogs to alter the lymphoproliferative response and intracytoplasmic cytokines. Overall, GFP+ Leishmania showed lower capacity of in vitro infectivity in the presence of Bloq IL-10R. Moreover, addition of Bloq IL-10R in cultured PBMC enhanced T-CD4 and CD8 proliferative response and altered the intracytoplasmic cytokine synthesis, reducing CD4+IL-4+ cells and increasing CD8+IFNγ+ cells after specific antigen stimulation in PBMC of dogs. Furthermore, we observed an increase of TNF-α levels in supernatant of cultured PBMC under IL-10R neutralizing conditions. Together, our findings are encouraging and reaffirm an important factor that could influence the effectiveness of immune modulation in dogs with VL and suggest that blocking IL-10R activity has the potential to be a useful approach to CVL treatment.
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    A vaccine therapy for canine visceral leishmaniasis promoted significant improvement of clinical and immune status with reduction in parasite burden.
    (2017) Roatt, Bruno Mendes; Soares, Rodrigo Dian de Oliveira Aguiar; Reis, Levi Eduardo Soares; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; Brito, Rory Cristiane Fortes de; Silva, Sydnei Magno da; Gontijo, Nelder de Figueiredo; Ferreira, Sidney de Almeida; Valenzuela, Jesus G.; Oliveira, Rodrigo Corrêa de; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa
    Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series. The animals were evaluated before (T0) and 90 days after treatment (T90) for their biochemical/hematological, immunological, clinical, and parasitological variables. Our major results showed that the vaccine therapy with LBMPL was able to restore and normalize main biochemical (urea, AST, ALP, and bilirubin) and hematological (erythrocytes, hemoglobin, hematocrit, and platelets) parameters. In addition, in an ex vivo analysis using flow cytometry, dogs treated with LBMPL vaccine showed increased CD3+ T lymphocytes and their subpopulations (TCD4+ and TCD8+), reduction of CD21+ B lymphocytes, increased NK cells (CD5−CD16+) and CD14+ monocytes. Under in vitro conditions, the animals developed a strong antigen- specific lymphoproliferation mainly by TCD4+ and TCD8+ cells; increasing in both TCD4+IFN-γ+ and TCD8+IFN-γ+ as well as reduction of TCD4+IL-4+ and TCD8+IL-4+ lymphocytes with an increased production of TNF-α and reduced levels of IL-10. Concerning the clinical signs of canine visceral leishmaniasis, the animals showed an important reduction in the number and intensity of the disease signs; increase body weight as well as reduction of splenomegaly. In addition, the LBMPL immunotherapy also promoted a reduction in parasite burden assessed by real-time PCR. In the bone marrow, we observed seven times less parasites in LBMPL animals compared with MPL group. The skin tissue showed a reduction in parasite burden in LBMPL dogs 127.5 times higher than MPL. As expected, with skin parasite reduction promoted by immunotherapy, we observed a blocking transmission to sand flies in LBMPL dogs with only three positive dogs after xenodiagnosis. The results obtained in this study highlighted the strong potential for the use of this heterologous vaccine therapy as an important strategy for VL treatment.
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    Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine.
    (2004) Borja Cabrera, Gulnara Patricia; Mendes, Amanda Cruz; Souza, Edilma Paraguai de; Okada, Lilian Y. Hashimoto; Trivellato, Fernando Antonio de Assis; Kawasaki, Jarbas Kiyoshi Alves; Costa, Andreia Cerqueira; Reis, Alexandre Barbosa; Genaro, Odair; Batista, Leopoldina Maria Melo; Palatnik, Marcos; Souza, Clarisa Beatriz Palatnik de
    The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally infected withLeishmania donovani and on 21 Leishmania chagasi naturally infected dogs when seropositive to FML but completely asymptomatic. The clinical signs of the experimentally infected, symptomatic dogs only disappeared after the complete vaccination. Protection was obtained in 3/5 animals that remained asymptomatic, IDR positive and parasite free, 1 year after infection. Furthermore, the asymptomatic, FML-vaccine treated dogs showed stable anti-FML IgG1 levels, increasing IgG2 levels and 79–95% of positive DTH response, during the whole experiment. Twenty-two months after complete vaccination, no obits due to visceral leishmaniasis were recorded and 90% of these dogs were still asymptomatic, healthy and parasite free. On the other hand, 37% (17/46 dogs) kala-azar obits were recorded in a control group that received no treatment during the same period, and that was FML-seropositive and asymtpomatic at the beginning of the assay. Our results indicate that the FML-vaccine was effective in the immunotherapy against visceral leishmaniasis of asymptomatic infected dogs. Normal proportions of CD4 and CD21 lymphocytes were detected in PBMC by FACS analysis, in dogs submitted to immunotherapy, suggesting their non-infectious condition. All animals showed as well significantly increased percents of CD8 lymphocytes as expected for Quillajasaponin (QuilA) vaccine treatments.
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    Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched-Leishmune ® vaccine.
    (2007) Santos, Fernanda Nunes; Borja Cabrera, Gulnara Patricia; Myashiro, L. M.; Grechi, Juliana; Reis, Alexandre Barbosa; Moreira, Márcio Antônio Batistela; Martins Filho, Olindo Assis; Luvizotto, Maria Cecília Rui; Menz, Ingrid; Pessôa, L. M.; Gonçalves, Pablo Rodrigues; Palatnik, Marcos; Souza, Clarisa Beatriz Palatnik de
    In order to assess the immunotherapeutic potential on canine visceral leishmaniasis of the Leishmune ® vaccine, formulated with an increased adjuvant concentration (1 mg of saponin rather than 0.5 mg), 24 mongrel dogs were infected with Leishmania (L.) chagasi . The enriched-Leishmune ® vaccine was injected on month 6, 7 and 8 after infection, when animals were seropositive and symptomatic. The control group were injected with a saline solution. Leishmune ® -treated dogs showed significantly higher levels of anti-FML IgG antibodies (ANOVA; p < 0.0001), a higher and stable IgG2 and a decreasing IgG1 response, pointing to a TH1 T cell mediated response. The vaccine had the following effects: it led to more positive delayed type hypersensitivity reactions against Leishmania lysate in vaccinated dogs (75%) than in controls (50%), to a decreased average of CD4+ Leishmania -specific lymphocytes in saline controls (32.13%) that fell outside the 95% confidence interval of the vaccinees (41.62%, CI95% 43.93–49.80) and an increased average of the clinical scores from the saline controls (17.83) that falls outside the 95% confidence interval for the Leishmune ® immunotherapy-treated dogs (15.75, CI95% 13.97–17.53). All dogs that received the vaccine were clustered, and showed lower clinical scores and normal CD4+ counts, whereas 42% of the untreated dogs showed very diminished CD4+ and higher clinical score. The increase in clinical signs of the saline treated group was correlated with an increase in anti-FML antibodies (p < 0.0001), the parasitological evidence ( p = 0.038) and a decrease inLeishmania -specific CD4+ lymphocyte proportions (p = 0.035). These results confirm the immunotherapeutic potential of the enriched-Leishmune ® vaccine. The vaccine reduced the clinical symptoms and evidence of parasite, modulating the outcome of the infection and the dog’s potential infectiosity to phlebotomines. The enriched-Leishmune ® vaccine was subjected to a safety analysis and found to be well tolerated and safe