Navegando por Autor "Alves, Ricardo José"

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An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis.
(2016) Lage, Letícia Martins dos Reis; Barichello, José Mario; Lage, Daniela Pagliara; Mendonça, Débora Vasconcelos Costa; Carvalho, Ana Maria Ravena Severino; Rodrigues, Marcella Rezende; Souza, Daniel Menezes; Roatt, Bruno Mendes; Alves, Ricardo José; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antônio Ferraz; Duarte, Mariana Costa
A clioquinol-containing Pluronic ® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model.
(2020) Tavares, Grasiele de Sousa Vieira; Mendonça, Débora Vasconcelos Costa; Pereira, Isabela Amorim Gonçalves; Silva, João Augusto Oliveira da; Ramos, Fernanda Fonseca; Lage, Daniela Pagliara; Machado, Amanda Sanchez; Carvalho, Lívia Mendes; Reis, Thiago Alves Rosa dos; Melo, Luísa Helena Perin de; Carvalho, Ana Maria Ravena Severino; Ottoni, Flaviano Melo; Ribeiro, Fernanda Ludolf; Freitas, Camila Simões de; Bandeira, Raquel Soares; Silva, Alessandra M.; Chávez Fumagalli, Miguel Angel; Duarte, Mariana Costa; Souza, Daniel Menezes; Alves, Ricardo José; Roatt, Bruno Mendes; Coelho, Eduardo Antônio Ferraz
A clioquinol (ICHQ)-containing Pluronic F127 polymeric micelle system (ICHQ/Mic) was recently shown to be effective against Leishmania amazonensis infection in a murine model. In the present study, ICHQ/ Mic was tested against L. infantum infection. BALB/c mice (n = 12 per group) were infected with L. infantum stationary promastigotes through subcutaneous injection and, 45 days after challenge, received saline or were treated via the subcutaneous route with empty micelles, ICHQ or ICHQ/Mic. In addition, animals were treated with miltefosine by the oral route, as a drug control. Half of the animals were euthanized 1 and 15 days after treatment, aiming to evaluate two endpoints after therapy, when parasitological and immunological parameters were investigated. Results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significantly higher anti-parasite IFN-c, IL-12, GM-CSF, nitrite and IgG2a isotype antibody levels, which were associated with low IL-4 and IL-10 production. In addition, a higher frequency of IFN-c and TNF-a-producing CD4+ and CD8+ T-cells was found in these animals. The parasite load was evaluated in distinct organs, and results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significant reductions in organic parasitism in the treated and infected mice. A comparison between the treatments suggested that ICHQ/Mic was the most effective in inducing a highly polarized Th1-type response, as well as reducing the parasite load in significant levels in the treated and infected animals. Data obtained 15 days after treatment suggested maintenance of the immunological and parasitological responses. In conclusion, ICHQ/Mic could be considered in future studies for the treatment of visceral leishmaniasis.
Flau-A, a naphthoquinone derivative, is a promising therapeutic candidate against visceral leishmaniasis : a preliminary study.
(2022) Mendonça, Débora Vasconcelos Costa; Tavares, Grasiele de Sousa Vieira; Pereira, Isabela Amorim Gonçalves; Silva, João Augusto Oliveira da; Ramos, Fernanda Fonseca; Lage, Daniela Pagliara; Machado, Amanda Sanchez; Carvalho, Lívia Mendes; Reis, Thiago Alves Rosa dos; Carvalho, Ana Maria Ravena Severino; Ottoni, Flaviano Melo; Ribeiro, Fernanda Ludolf; Freitas, Camila Simões de; Martins, Vivian Tamietti; Chávez Fumagalli, Miguel Angel; Duarte, Mariana Costa; Humbertf, Maria V.; Roatt, Bruno Mendes; Souza, Daniel Menezes; Alves, Ricardo José; Coelho, Eduardo Antônio Ferraz
Visceral leishmaniasis (VL) is a neglected tropical disease found in tropical and subtropical regions in the world. The therapeutics used for the treatment against disease presents problems, mainly related to drug toxicity, route of administration, high cost and/or by emergence of resistant strains. In this context, the search for alternative antileishmanial candidates is desirable. Recently, a naphthoquinone derivative namely 2-(2,3,4-tri-O-acetyl-6- deoxy-β-L-galactopyranosyloxy)-1,4-naphthoquinone or Flau-A showed an effective in vitro biological action against Leishmania infantum. In the present study, the efficacy of this naphthoquinone derivative was evaluated in an in vivo infection model. BALB/c mice (n = 12 per group) were infected and later received saline or were treated with empty micelles (B/Mic), free Flau-A or it incorporated in Poloxamer 407-based micelles (Flau-A/ Mic). The products were administered subcutaneously in the infected animals, which were then euthanized one (n = 6 per group) and 15 (n = 6 per group) days post-therapy, when immunological and parasitological eval- uations were performed. Results showed that animals treated with Flau-A or Flau-A/Mic produced significantly higher levels of antileishmanial IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and IgG2a isotype antibody, when compared to data found in the control (saline and B/Mic) groups; which showed significantly higher levels of parasite- specific IL-4, IL-10 and IgG1 antibody. In addition, animals receiving free Flau-A or Flau-A/Mic presented also significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, when compared to the controls. A low hepatic and renal toxicity was also found. Overall, Flau-A/Mic showed better immunological and parasitological results, when compared to the use of free molecule. In conclusion, pre- liminary data suggest that this composition could be considered in future studies as promising therapeutic candidate against VL.
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection.
(2019) Mendonça, Débora Vasconcelos Costa; Tavares, Grasiele de Sousa Vieira; Lage, Daniela Pagliara; Soyer, Tauane Gonçalves; Carvalho, Lívia Mendes; Dias, Daniel Silva; Ribeiro, Patrícia Aparecida Fernandes; Ottoni, Flaviano Melo; Antinarelli, Luciana Maria Ribeiro; Vale, Danniele Luciana; Ribeiro, Fernanda Ludolf; Duarte, Mariana Costa; Coimbra, Elaine Soares; Chávez Fumagalli, Miguel Angel; Roatt, Bruno Mendes; Souza, Daniel Menezes; Barichello, José Mario; Alves, Ricardo José; Coelho, Eduardo Antônio Ferraz
New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome® , Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis.
Para além da oração : uma descrição sistêmico-funcional do sistema de conjunção do português brasileiro.
(2018) Alves, Ricardo José; Figueredo, Giacomo Patrocinio; Figueredo, Giacomo Patrocinio; Mendes, Soélis Teixeira do Prado; Oliveira, Ana Larissa Adorno Marciotto
Nos estudos das gramáticas tradicional (cf. CUNHA; CINTRA, 1983; KURY, 1991; LIMA, 1999) e descritiva (cf. PERINI, 1995; AZEREDO, 1999; BECHARA, 2009), as conjunções são analisadas no nível da oração, em frases isoladas, muitas vezes criadas pelos próprios autores. Devido a isso, outros pesquisadores (CAMACHO, 1999; 2001; NEVES, 2000; ROCHA, 2006; NUNES, 2014; CASTILHO, 2014; ALVES, 2015) propuseram novas análises e ressaltaram a carência dos estudos das conjunções, bem como afirmaram a necessidade de investigá-las. Diante disso, esta dissertação, afiliada aos Estudos Linguísticos, mais especificamente aos estudos de descrição linguística de base sistêmico-funcional (HALLIDAY; MATTHIESSEN, 2014), visa a descrever o sistema de CONJUNÇÃO do português brasileiro. Uma característica fundamental dessa descrição é o seu caráter sistêmico, já que descreve a CONJUNÇÃO do português brasileiro levando-se em consideração a agnação entre as opções desse sistema. Além disso, tendo como ponto de partida a teoria sistêmica, considera-se, neste estudo, a CONJUNÇÃO um sistema semântico que promove a relação conjuntiva entre unidades que vão além da oração (MARTIN, 2007). Para realizar essa descrição, primeiramente extraíram-se os dados do Catálogo da Língua Brasileira (CALIBRA), um corpus monolíngue cujos textos foram coletados com base na tipologia do contexto de cultura. Em seguida, no editor de planilhas Excel, segmentaram-se os textos em figuras, unidade básica do texto responsável por representar a experiência humana na forma de uma configuração: Processo, Participante e Circunstância. Além disso, validaram-se os dados, para que, posteriormente, fosse feita a análise quantitativa deles. Posteriormente, fez-se manualmente a análise qualitativa com base na visão trinocular, adotando-se três perspectivas: “de cima”, identificando similaridades entre padrões de registro realizado pelo mesmo sistema semântico; “de baixo”, examinando similaridades da constituição gramatical; e “ao redor”, descobrindo contrastes entre funções que desempenham o mesmo papel no sistema de CONJUNÇÃO. Assim, descreveu-se o sistema de CONJUNÇÃO do português brasileiro. Foram encontradas quatro CONJUNÇÕES, que geraram suas respectivas opções: REFORMULAÇÃO: reelaborativa e exemplificativa; ADIÇÃO: aditiva positiva, aditiva negativa e alternativa; CONTRAPOSIÇÃO: concessiva, adversativa, comparativa e redirecionativa; TEMPO: sucessiva posterior, sucessiva anterior, sucessiva simultânea e ordenativa; e, por fim, CONSEQUÊNCIA: conclusiva, final, condicional e explicativa.
A Pluronic® F127-based polymeric micelle system containing an antileishmanial molecule is immunotherapeutic and effective in the treatment against Leishmania amazonensis infection.
(2019) Tavares, Grasiele de Sousa Vieira; Mendonça, Débora Vasconcelos Costa; Miyazaki, Carolina Kei; Lage, Daniela Pagliara; Soyer, Tauane Gonçalves; Carvalho, Lívia Mendes; Ottoni, Flaviano Melo; Dias, Daniel Silva; Ribeiro, Patrícia Aparecida Fernandes; Antinarelli, Luciana Maria Ribeiro; Ribeiro, Fernanda Ludolf; Duarte, Mariana Costa; Coimbra, Elaine Soares; Chávez Fumagalli, Miguel Angel; Roatt, Bruno Mendes; Souza, Daniel Menezes; Barichello, José Mario; Alves, Ricardo José; Coelho, Eduardo Antônio Ferraz
Clioquinol (5-chloro-7-iodoquinolin-8-ol or ICHQ) was recently showed to presents an in vitro effective antileishmanial action, causing changes in membrane permeability, mitochondrial functionality, and parasite morphology. In the present study, ICHQ was incorporated into a Poloxamer 407-based polymeric micelles system (ICHQ/M), and its antileishmanial activity was in vivo evaluated in L. amazonensis-infected BALB/c mice. Amphotericin B (AmpB) and its liposomal formulation (Ambisome®) were used as controls. Parasitological and immunological evaluations were performed 30 days after the treatment. Results indicated more significant reductions in the average lesion diameter and parasite burden in ICHQ or ICHQ/M-treated mice, which were associated with the development of a polarized Th1 immune response, based on production of high levels of IFN-γ, IL-12, TNF-α, GM-CSF, and antileishmanial IgG2a antibody. Control groups´ mice produced high levels of IL-4, IL-10, and IgG1 isotype antibody. No organic toxicity was found by using ICHQ or ICHQ/M to treat the animals, although those receiving AmpB and Ambisome® have presented higher levels of renal and hepatic damage markers. In conclusion, results suggested that the ICHQ/M composition can be considered as an antileishmanial candidate to be tested against human leishmaniasis.
Síntese de amidas e sulfonamidas de d-galactopiranosilamina e lactosilamina e avaliação de suas interações com lectinas de erythrina cristagalli e de ricinus communis.
(2007) Butera, Anna Paola; Souza Filho, José Dias de; Carvalho, Diogo Teixeira; Figueiredo, Rute Cunha; Faria, Luiz Carlos Alves de; Nunes, Maria Angélica Antunes; Prado, Maria Auxiliadora Fontes; Alves, Ricardo José; Andrade, Milton Hércules Guerra de; Rúbio, Karina Taciana Santos
We report herein the synthesis of some -D-galactopyranosylamine and -lactosylamine amides and sulfonamides. The interactions of these compounds with lectins from the seeds of Erythrina cristagalli (LEC) and Ricinus communis (RCA120) were evaluated in a hemagglutination inhibitory activity assay. D-Galactose and lactose were used as reference compounds. The -lactosylamine amides and sulfonamides were nearly as active as lactose in inhibiting LEC mediated hemagglutination and were less active against RCA120 agglutinin. The -D-galactopyranosylamine amides and sulfonamides were, with one exception, considerably less active than Dgalactose in the assay with both lectins.
Splenectomy increases mortality in murine Trypanosoma cruzi infection.
(2011) Maioli, Tatiani Uceli; Assis, Frankcinéia Aparecida de; Vieira, Paula Melo de Abreu; Borelli, Primavera; Santiago, Helton da Costa; Alves, Ricardo José; Romanha, Alvaro José; Carneiro, Cláudia Martins; Faria, Ana Maria Caetano de
The spleen is a secondary lymphoid organ that harbours a variety of cells such as T and B lymphocytes and antigen-presenting cells important to immune response development. In this study, we evaluated the impact of spleen removal in the immune response to experimental Trypanosoma cruzi infection. C57BL/6 mice were infected with Y strain of the parasite and infection was followed daily. Mice that underwent splenectomy had fewer parasites in peripheral blood at the peak of infection; however, mortality was increased. Histological analysis of heart and liver tissues revealed an increased number of parasites and inflammatory infiltrates at these sites. Spleen removal was associated with reduction in IFN-γ and TNF-α production during infection as well as with a decrease in specific antibody secretion. Haematological disorders were also detected. Splenectomized mice exhibited severe anaemia and decreased bone marrow cell numbers. Our results indicate that spleen integrity is critical in T. cruzi infection for the immune response against the parasite, as well as for the control of bone marrow haematological function.
Synthesis of novel papulacandin D analogs and evaluation of their antifungal potential.
(2020) Bretas, Ana Carolina Oliveira; Souza, Thiago Belarmino de; Borelli, Beatriz; Johan, Suzana; Alves, Ricardo José
Systemic fungal infections are a growing problem in contemporary medicine and few drugs are licensed for therapy of invasive fungal infections. Differences between fungi and humans, like the presence of a cell wall in fungal cells, can be explored for designing new drugs. (1,3)-β-D-glucan synthase, an enzyme that catalyzes the synthesis of (1,3)-β-D-glucan, a structural and essential component of the fungal cell wall, is absent in mammals and this makes it an excellent target for the development of new antifungal agents. Papulacandins are a family of natural antifungal agents targeting (1,3)-β-D-glucan synthase. In this study we describe the synthesis and biological evaluation of two new Papulacandin analogs as potential (1,3)-β-D-glucan synthase inhibitors.
Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system.
(2016) Duarte, Mariana Costa; Lage, Letícia Martins dos Reis; Lage, Daniela Pagliara; Martins, Vivian Tamietti; Carvalho, Ana Maria Ravena Severino; Roatt, Bruno Mendes; Souza, Daniel Menezes; Tavares, Carlos Alberto Pereira; Alves, Ricardo José; Barichello, José Mario; Coelho, Eduardo Antônio Ferraz
Newtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered, as well as the evaluation of new molecules that have already shown to present biological activity. In this context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline (8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load. The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines, as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1 isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion, 8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined with other drugs, as an alternative treatment for VL.