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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2020 - 202326

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Autor: search.filters.author.Soares, Rodrigo Dian de Oliveira AguiarData inicial: 2020

Resultados da Pesquisa

Agora exibindo 1 - 10 de 26
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    A systematic review of drug-carrying nanosystems used in the treatment of leishmaniasis.
    (2023) Registre, Charmante; Soares, Rodrigo Dian de Oliveira Aguiar; Rúbio, Karina Taciana Santos; Santos, Orlando David Henrique dos; Carneiro, Simone Pinto
    Leishmaniasis is an infectious disease responsible for a huge rate of morbidity and mortality in humans. Chemotherapy consists of the use of pentavalent antimonial, amphotericin B, pentamidine, miltefosine, and paromomycin. However, these drugs are associated with some drawbacks such as high toxicity, administration by parenteral route, and most seriously the resistance of some strains of the parasite to them. Several strategies have been used to increase the therapeutic index and reduce the toxic effects of these drugs. Among them, the use of nanosystems that have great potential as a site-specific drug delivery system stands out. This review aims to compile results from studies that were carried out using first- and second-line antileishmanial drug- carrying nanosystems. The articles referred to here were published between 2011 and 2021. This study shows the promise of effective applicability of drug-carrying nanosystems in the field of antileishmanial therapeutics, with the perspective of providing better patient adherence to treatment, increased therapeutic efficacy, reduced toxicity of conventional drugs, as well as the potential to efficiently improve the treatment of leishmaniasis.
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    The use of an adjuvant system improves innate and adaptive immune response when associated with a Leishmania (Viannia) braziliensis antigen in a vaccine candidate against L. (Leishmania) infantum infection.
    (2023) Mathias, Fernando Augusto Siqueira; Ostolin, Thais Lopes Valentim Di Paschoale; Reis, Levi Eduardo Soares; Cardoso, Jamille Mirelle de Oliveira; Brito, Rory Cristiane Fortes de; Soares, Rodrigo Dian de Oliveira Aguiar; Roatt, Bruno Mendes; Vieira, Paula Melo de Abreu; Reis, Alexandre Barbosa
    Background: The adjuvants’ optimal dose and the administration route can directly influence the epitope recognition patterns and profiles of innate response. We aimed to establish the effect and the optimal dose of adjuvant systems for proposing a vaccine candidate to be employed with Leishmania (Viannia) braziliensis. Methods: We evaluated the adjuvants saponin (SAP), monophosphoryl lipid A (MPL) and resiquimod (R-848) isolated and combined as adjuvant systems in a lower dose corresponding to 25%, 33%, and 50% of each adjuvant total dose. Male outbred BALB/c mice were divided into 13 groups, SAP, MPL, and R-848 isolated, and the adjuvant systems SAP plus MPL (SM), SAP plus R-848 (SR), and MPL plus R-848 (MR). Results: SM50 increased levels of all chemokines analyzed and TNF production, while it presented an increased inflammatory cell infiltrate in the skin with macrophage recruitment. Thus, we proposed a vaccine candidate employing L. (V.) braziliensis antigen associated with the SM adjuvant system against experimental L. (Leishmania) infantum challenge. We observed a significant increase in the frequency of cells expressing the central and effector memory CD4+ T cells phenotype in immunized mice with the LBSM50. In the liver, there was a decreased parasite load when mice received LBSM50. Conclusions: When combined with L. (V.) braziliensis antigen, SM50 increases TNF and IFN-γ, which generates central and effector memory CD4+ T cells. Therefore, using an adjuvant system can promote an effective innate immune response with the potential to compose future vaccines.
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    ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of chagas’ disease.
    (2023) Castro, Júlia Teixeira de; Brito, Rory Cristiane Fortes de; Souza, Natália Satchiko Hojo de; Azevedo, Bárbara Ribeiro Batista Vaz de; Castro, Natália Salazar de; Ferreira, Camila Pontes; Giusta, Caroline Junqueira; Fernandes, Ana Paula Salles Moura; Vasconcellos, José Ronnie Carvalho de; Cardoso, Jamille Mirelle de Oliveira; Soares, Rodrigo Dian de Oliveira Aguiar; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Valiate, Bruno Vinícius Santos; Toledo, Cristiane; Salazar, Andres M.; Caballero, Otávia; Vieira, Joseli Lannes; Teixeira, Santuza Maria Ribeiro; Reis, Alexandre Barbosa; Gazzinelli, Ricardo Tostes
    Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzispecific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.
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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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    CD4+ T-lymphocytes from asymptomatic dogs infected with Leishmania infantum are able to activate macrophages for higher leishmanicidal ability in an in vitro co-culture experiment.
    (2022) Vieira, João Filipe Pereira; Cardoso, Jamille Mirelle de Oliveira; Brito, Rory Cristiane Fortes de; Roatt, Bruno Mendes; Carneiro, Cláudia Martins; Valadares, Diogo Garcia; Soares, Rodrigo Dian de Oliveira Aguiar; Reis, Alexandre Barbosa
    Dogs are the most common domestic reservoir of Leishmania infantum, making canine visceral leishmaniasis (CVL) a serious public health issue. Identifying new methodologies that can mimic lymphoid and myeloid competence in naturally infected dogs could lower costs and save time in preliminary screenings of potential immunotherapeutic agents and vaccines against CVL. For that, we established a cell-to-cell communication approach between lymphocytes and myeloid cells from healthy, asymptomatic (infected, without apparent clinical signs) and symptomatic (infected with apparent clinical signs) dogs. Peripheral blood mononuclear cells (PBMC) from these dogs were used as source of CD4+, CD8+ T lymphocytes and macrophages, that were posteriorly infected with L. infantum GFP+ promastigotes (green fluorescent protein). Macrophages co-cultured with purified lymphocytes were tested for the ability to control cellular parasitism, and their microbicidal function by producing nitric oxide (NO) and reactive oxygen species (ROS). The kind of T cell response within the co-culture was also evaluated, by assessing their ability to produce interferon-gamma (IFN-γ) and interleukin 4 (IL-4). The data suggests that T lymphocytes from symptomatic dogs are more prone to produce IL-4 than the ones from asymptomatic dogs. Macrophages from asymptomatic dogs also demonstrated a higher microbicidal potential, with increased levels of NO and ROS production, compared to symptomatic dogs, mainly in highly parasitized cells. Together, our results identify the ratio of IL-4/IFN-γ produced by CD4+ and CD8+ T cells, as well as, the ratio between parasite GFP signal/NO and ROS signal in macrophages as potential immunological biomarkers of failure and success of the screened agents. Our findings also propose a reliable methodology that can be used to follow the immune response in trials of potential drugs or vaccines targeting CVL.
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    A specific Leishmania infantum polyepitope vaccine triggers Th1-type immune response and protects against experimental visceral leishmaniasis.
    (2022) Ostolin, Thais Lopes Valentim Di Paschoale; Gusmão, Miriã Rodrigues; Mathias, Fernando Augusto Siqueira; Cardoso, Jamille Mirelle de Oliveira; Roatt, Bruno Mendes; Soares, Rodrigo Dian de Oliveira Aguiar; Ruiz, Jeronimo Conceição; Resende, Daniela de Melo; Brito, Rory Cristiane Fortes de; Reis, Alexandre Barbosa
    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 107 stationary-phase Leishmania infantum promastigotes via tail vein. Immunogenicity and parasitism in spleen and liver of immunized mice were evaluated 45 days postchallenge. 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.
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    Immunoprophylaxis using polypeptide chimera vaccines plus adjuvant system promote Th1 response controlling the spleen parasitism in hamster model of visceral leishmaniasis.
    (2022) Gusmão, Miriã Rodrigues; Ostolin, Thais Lopes Valentim Di Paschoale; Carvalho, Lívia Mendes; Costa, Ana Flávia Pereira; Moreira, Gabriel José Lucas; Cardoso, Jamille Mirelle de Oliveira; Soares, Rodrigo Dian de Oliveira Aguiar; Reis, Alexandre Barbosa; Brito, Rory Cristiane Fortes de; Roatt, Bruno Mendes
    In recent years, several advances have been observed in vaccinology especially for neglected tropical diseases (NTDs). One of the tools employed is epitope prediction by immunoinformatic approaches that reduce the time and cost to develop a vaccine. In this scenario, immunoinformatics is being more often used to develop vaccines for NTDs, in particular visceral leishmaniasis (VL) which is proven not to have an effective vaccine yet. Based on that, in a previous study, two predicted T-cell multi-epitope chimera vaccines were experimentally validated in BALB/c mice to evaluate the immunogenicity, central and effector memory and protection against VL. Considering the results obtained in the mouse model, we assessed the immune response of these chimeras in Mesocricetus auratus hamster, which displays, experimentally, similar pathological status to human and dog VL disease. Our findings indicate that both chimeras lead to a dominant Th1 response profile, inducing a strong cellular response by increasing the production of IFN-c and TNF-a cytokines associated with a decrease in IL-10. Also, the chimeras reduced the spleen parasite load and the weight a correlation between protector immunological mechanisms and consistent reduction of the parasitic load was observed. Our results demonstrate that both chimeras were immunogenic and corroborate with findings in the mouse model. Therefore, we reinforce the use of the hamster as a pre-clinical model in vaccination trials for canine and human VL and the importance of immunoinformatic to identify epitopes to design vaccines for this important neglected disease.
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    Performance of the Wondfo 2019-nCoV antigen test using self-collected nasal versus professional-collected nasopharyngeal swabs in symptomatic SARS-CoV-2 infection.
    (2022) Cardoso, Jamille Mirelle de Oliveira; Roatt, Bruno Mendes; Vieira, Paula Melo de Abreu; Paiva, Nívia Carolina Nogueira de; Souza, Breno Bernardes; Lisboa, Oscar Campos; Soares, Rodrigo Dian de Oliveira Aguiar; Reis, Alexandre Barbosa; Vital, Wendel Coura; Carneiro, Cláudia Martins
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    Coffea arabica extracts and their chemical constituents in a murine model of gouty arthritis : how they modulate pain and inflammation.
    (2022) Matosinhos, Rafaela Cunha; Bezerra, Juliana Pantaleão; Barros, Camila Helena; Bernardes, Ana Catharina Fernandes Pereira Ferreira; Araújo, Marcela Carolina de Paula Michel; Coelho, Grazielle Brandão; Soares, Rodrigo Dian de Oliveira Aguiar; Sachs, Daniela; Guimarães, Dênia Antunes Saúde
    Ethnopharmacological relevance: Coffea arabica is commonly known for its cardiotonic and neurotonic activities, but in some places’ folk medicine, like in Arabia and Africa, C. arabica is used to treat headache, migraine, the flu, anemia, oedema, asthenia, asthma, inflammation and wounds. Aims of the study: The aims were to evaluate if the aqueous extracts of Coffea arabica, prepared from beans with different degrees of roasting, and their main chemical constituents could exert an in vivo anti-gouty effect. Materials and methods: Coffea extracts were obtained from the beans of not roasted, light, medium and dark roasted coffee and from decaffeinated and traditional coffees and were prepared with water at 25◦C and at 98◦C. C57BL/6 mice were induced to gout by an injection of monosodium urate crystals and treated with coffee extracts at doses of 25, 75 and 225 mg/kg and their chemical constituents at a dose of 10 mg/kg. The antinociceptive and anti-inflammatory effects were evaluated. Results: Treatments with Coffea extracts prepared with water at 98◦C were more effective to exert antinociceptive and anti-inflammatory activities than the ones prepared with water at 25◦C. Caffeic and chlorogenic acids reduced hypernociception in animals when compared with negative control group (7.79 and 5.69 vs 18.53; P < 0.05 and P < 0.001, respectively), inhibited neutrophil migration (1.59 × 104 and 0.38 × 104 vs 9.47 × 104; P < 0.0001 both) and decreased pro-inflammatory cytokines concentration (IL-1β, IL-6 and TNF-α). Conclusions: We have demonstrated that our treatments attenuated gout, and this effect could be attributed to a reducement in hypernociception, neutrophil migration and cytokines concentration. These results suggest coffee as a potential candidate for studies in acute gout therapy.
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    Comparative evaluation of meglumine antimoniate encapsulated in a mixture of conventional and PEGylated liposomes and immunotherapy using an anti-canine IL-10 receptor-blocking monoclonal antibody on canine visceral leishmaniasis.
    (2022) Cardoso, Jamille Mirelle de Oliveira; Brito, Rory Cristiane Fortes de; Mathias, Fernando Augusto Siqueira; Reis, Levi Eduardo Soares; Vieira, João Filipe Pereira; Ostolin, Thais Lopes Valentim Di Paschoale; Andrade, Hélida Monteiro de; Ramos, Guilherme Santos; Frezard, Frederic; Soares, Rodrigo Dian de Oliveira Aguiar; Roatt, Bruno Mendes; Reis, Alexandre Barbosa
    This study compared the therapeutic potential of the chemotherapy using meglumine antimoniate encapsulated in a mixture of conventional and PEGylated liposomes (Nano Sbv ) and immunotherapy with anti-canine IL-10 receptor-blocking monoclonal antibody (Anti IL-10R) on canine visceral leishmaniasis (CVL). Twenty mongrel dogs naturally infected by L. infantum, displaying clinical signs of visceral leishmaniasis were randomly divided in two groups. In the first one, nine dogs received six intravenous doses of a mixture of conventional and PEGylated liposomes containing meglumine antimoniate at 6.5 mg Sb/kg/dose. In the second one, eleven dogs received two intramuscular doses of 4 mg of anti-canine IL-10 receptor-blocking monoclonal antibody. The animals were evaluated before (T0) and 30, 90, and 180 days after treatments. Our major results demonstrated that both treatments were able to maintain hematological and biochemical parameters, increase circulating T lymphocytes subpopulations, increase the IFN-γ producing T-CD4 lymphocytes, restore the lymphoproliferative capacity and improve the clinical status. However, although these improvements were observed in the initial post-treatment times, they did not maintain until the end of the experimental follow-up. We believe that the use of booster doses or the association of chemotherapy and immunotherapy (immunochemotherapy) is promising to improve the effectiveness of treating CVL for improving the clinical signs and possibly reducing the parasite burden in dogs infected with Leishmania infantum.