4 results on '"de Oliveira Cardoso J"'
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2. A specific Leishmania infantum polyepitope vaccine triggers Th1-type immune response and protects against experimental visceral leishmaniasis.
- Author
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Lopes Valentim Di Paschoale Ostolin T, Rodrigues Gusmão M, Augusto Siqueira Mathias F, Mirelle de Oliveira Cardoso J, Mendes Roatt B, Dian de Oliveira Aguiar-Soares R, Conceição Ruiz J, de Melo Resende D, Cristiane Fortes de Brito R, and Barbosa Reis A
- Subjects
- Adjuvants, Immunologic pharmacology, Animals, Antigens, Protozoan, Dogs, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Tumor Necrosis Factor-alpha, Leishmania infantum, Leishmaniasis Vaccines, Leishmaniasis, Visceral prevention & control
- Abstract
The development of an immunogenic, effective, and safe vaccine is essential as an alternative for disease control. The present study aimed to evaluate the immunogenicity and efficacy potential of a polyepitope T-cell antigen candidate against visceral leishmaniasis in a murine model. BALB/c mice were immunized with three doses subcutaneously with Poly-T Leish alone or adjuvanted with Saponin plus Monophosphoryl lipid A, with 15-day intervals between doses, and challenged with 10
7 stationary-phase Leishmania infantum promastigotes via tail vein. Immunogenicity and parasitism in spleen and liver of immunized mice were evaluated 45 days post-challenge. Our results revealed that the immunization with Poly-T Leish and Poly-T Leish/SM increases the percentage of specific T (CD4+ and CD8+ ) lymphocytes proliferation in vitro after antigen-specific stimulation. Also, Poly-T Leish and Poly-T Leish/SM groups showed a high percentage of IFN-γ and TNF-α-producing T cells, meanwhile, the Poly-T Leish/SM group also showed an increased percentage of multifunctional T cells producing double and triple-positive (IFN-γ+ TNF-α+ IL-2+ ) cytokines. The immunization with Poly-T Leish or Poly-T Leish/SM stimulated a decreased IL-4 and IL-10 compared to the Saline and adjuvant group. Poly-T Leish/SM immunized mice exhibit a noteworthy reduction in the parasite burden (spleen and liver) through real-time PCR (96%). Moreover, we observed higher nitrite secretion in 120-hour stimulated-culture supernatant using Griess method. We demonstrated that the Poly-T Leish/SM candidate was potentially immunogenic, providing enhancement of protective immune mechanisms, and conferred protection reducing parasitism. Our candidate was considered potential against visceral leishmaniasis, and eventually, could be tested in phase I and II clinical trials in dogs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
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3. Down regulation of IL-10 and TGF-β1 mRNA expression associated with reduced inflammatory process correlates with control of parasitism in the liver after treatingL. infantuminfected dogs with the LBMPL vaccine therapy.
- Author
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Mendes Roatt B, Mirelle de Oliveira Cardoso J, Cristiane Fortes de Brito R, Eduardo Soares Reis L, José Lucas Moreira G, Melo de Abreu Vieira P, Marques de Souza F, Geraldo de Lima W, Dian de Oliveira Aguiar-Soares R, Cordeiro Giunchetti R, and Barbosa Reis A
- Subjects
- Animals, Dogs, Down-Regulation, Immunotherapy, Active, Inflammation, Interleukin-10 genetics, Liver pathology, RNA, Messenger genetics, Transforming Growth Factor beta1 genetics, Dog Diseases parasitology, Dog Diseases therapy, Leishmania infantum, Leishmaniasis, Visceral, Vaccines
- Abstract
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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
4. Design of experiments applied to stress testing of pharmaceutical products: A case study of Albendazole.
- Author
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Ardila JA, de Alvarenga Junior BR, Durango LC, Soares FLF, Perlatti B, de Oliveira Cardoso J, Oliveira RV, Forim MR, and Carneiro RL
- Subjects
- Albendazole, Chromatography, Liquid, Drug Compounding, Hydrogen Peroxide, Anthelmintics, Pharmaceutical Preparations
- Abstract
Forced degradation tests are studies used to assess the stability of active pharmaceutical ingredients (APIs) and their formulations. These tests are performed submitting the API under extreme conditions in order to know the main degradation products in a short period of time. The results of these studies are used to assess the degradation susceptibility of APIs and to validate chromatographic analytical methods. However, most of degradation studies are performed using one-factor-at-the-time (OFAT) which does not consider the interactions between degradation variables. This work proposes the use of Design of Experiment (DoE) approach in forced degradation of albendazole (ABZ). It was used a central composite design (CCD) to evaluate the forced degradation in a multivariate way. Experiments were performed taking into account the variables pH, temperature, oxidizing agent (H
2 O2 ) and UV radiation. It was verified the influence of the variables and their interactions on the ABZ degradation. The ABZ oxidation showed to be the main degradation route for ABZ, which is strongly influenced by the temperature. The hydrolysis was relevant at alkaline medium and high temperature. LC-IT-MSn was used to identify the degradation products. It was found three known degradation products (albendazole-2-amino, albendazole sulfoxide and albendazole sulfone) and a new derivate of albendazole molecule (albendazole sulfoxide with a chlorine). This last one was isolated and characterized by UPLC-QToF-MS and NMR analyses., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
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