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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Item 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 BarbosaThis 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.Item Evaluation of pulmonary tuberculosis diagnostic tests in children and adolescents at a pediatric reference center.(2022) Rossoni, Andrea Maciel de Oliveira; Lovero, Kathryn L.; Tahan, Tonny T.; Ruffino Netto, Antonio; Rossoni, Marssoni Deconto; Almeida, Isabela Neves de; Lizzi, Elisângela Aparecida da Silva; Kritski, Afranio Lineu; Rodrigues, Cristina O.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.Item Chemical characterization and anti-inflammatory assessment of the hydroethanolic extract of Fridericia chica.(2020) Takenaka, Isabella Kuniko Tavares Magalhães; Amorim, Juliana Mendes; Barros, Patrícia Aparecida Vieira de; Brandão, Geraldo Célio; Contarini, Sara Moreira Lopes; Melo, Éricka Lorenna de Sales Souza e; Leite, Camila Megale Almeida; Martins, Flaviano dos Santos; Cardoso, Valbert Nascimento; Castilho, Rachel Oliveira; Diniz, Simone Odília Antunes FernandesFridericia chica (Bonpl.) L.G. Lohmann, Bignoniaceae, is an Amazonian species known as “pariri” or “crajiru” that is included in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (Renisus). This herbal remedy is traditionally used as an infusion to treat diarrhea, anemia, inflammation, symptoms of mucositis, and frequent complications of chemotherapy. This study aimed to characterize the chemical profile of the hydroethanolic extract of F. chica and to assess its intestinal anti-inflammatory activity. The chemical profile of the leaves was determined by ultra-performance liquid chromatog raphy coupled to mass spectrometry, and its potential anti-inflammatory activity in the gut was evaluated in mucositis induced by 5-fluorouracil. Three novel compounds from this the species were identified 6,7,3′,4′-tetrahydroxy-5-methoxyflavilium-O-glu curonide, scutellarein-O-glucuronide, and 5-methyl-scutellarein-O-glucuronide, as well as flavones and anthocyanidins that have been previously described. Mice received the hydroethanolic extract (300 mg/kg) for 9 days, and no signs of toxicity were observed. After 72 h of 5-fluorouracil administration, intestinal permeability, bacterial translocation, myeloperoxidase activity, eosinophil peroxidase activity, and histological analyses were performed. Treatment with the analyzed extract was beneficial, as it normalized intestinal permeability, bacterial translocation, myeloperoxidase activity/eosinophil peroxidase and preserved intestinal epithelium architecture. This study provides new insights into the chemical composition and biological activity of the polar extracts from “pariri”, an important Amazonian crude medicinal drug.Item Benznidazole, itraconazole and their combination in the treatment of acute experimental chagas disease in dogs.(2019) Cunha, Eleonora Lima Alves; Torchelsen, Fernanda Karoline Vieira da Silva; Cunha, Lucas Maciel; Oliveira, Maykon Tavares de; Fonseca, Kátia da Silva; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Lana, Marta deChagas disease (CD) is a serious public health problem in Latin America and its treatment remains neglected. Benznidazole (BZ), the only drug available in Brazil, presents serious side effects and low therapeutic efficacy, especially at the chronic phase. The last clinical trials demonstrated that the first generation of azole compounds were less successful than BZ in CD chemotherapy, which stimulated studies of these compounds associated to BZ and nifurtimox (NF). This study evaluated the therapeutic efficacy of BZ, itraconazole (ITZ) and their combination (BZ + ITZ) in dogs infected with the VL-10 T. cruzi strain in the acute phase of the disease. Twenty young mongrel dogs were inoculated with 2.0 × 103 blood trypomastigotes/kg and divided into four groups: treated with BZ, ITZ and BZ + ITZ for 60 days, and control group (INT). The parasitemia of the BZ + ITZ and BZ groups were similar and showed significant reduction compared to the INT group. The group treated with ITZ also showed significant parasitemia reduction compared to the INT group. The global analysis of hemoculture (HC), blood PCR, conventional serology (CS-ELISA), heart qPCR and histopathology techniques, used in the post-treatment evaluation, revealed that BZ + ITZ combination lead to a more reduction of parasitemia during the acute phase and heart qPCR positivity, less cardiac damage (inflammation and fibrosis in the left ventricle) and total survival. According to the classical cure criteria one animal treated with BZ + ITZ can be considered cured in its final evaluation and two other dogs, one of this group and one treated with ITZ were in process of cure. At least for BZ-resistant T. cruzi strains such as VL-10, BZ + ITZ was not effective to induce parasitological cure or a profound and sustained reduction of the parasite burden in blood and infected organs.Item Mixed formulation of conventional and pegylated meglumine antimoniate-containing liposomes reduces inflammatory process and parasite burden in Leishmania infantum-infected BALB/c mice.(2017) Reis, Levi Eduardo Soares; Brito, Rory Cristiane Fortes de; Cardoso, Jamille Mirelle de Oliveira; Mathias, Fernando Augusto Siqueira; Soares, Rodrigo Dian de Oliveira Aguiar; Carneiro, Cláudia Martins; Vieira, Paula Melo de Abreu; Ramos, Guilherme Santos; Frezard, Frederic Jean Georges; Roatt, Bruno Mendes; Reis, Alexandre BarbosaPentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.Item Gemcitabine/cisplatin treatment induces concomitant sertad1, cdkn2b and gadd45a modulation and cellular changes in bladder cancer cells regardless of the site of TP53 mutation.(2017) Silva, Glenda Nicioli da; Filoni, Leandro Toshio; Salvadori, Maria Cecília Barbosa da Silveira; Salvadori, Daisy Maria FáveroSimultaneous use of cisplatin (CIS) and gemcitabine (GEN) for treating bladder cancer has increased because of their complementary effects. However, the molecular mechanisms underlying the activities of these two antineoplastic drugs are not fully known. Here, molecular biology techniques and microscopy were used to investigate transcriptomic and morphological changes in low and highgrade urinary bladder transitional carcinoma cell lines [RT4 - wild type TP53; 5637 - two TP53 mutations, one in codon 72 (Arg-Pro) and other in codon 280 (Arg-Thr) and T24 - inframe deletion of tyrosine 126 in the TP53 allele] simultaneously treated with CIS/GEN. Gene expression profile was evaluated by PCR arrays; cell morphology by scanning and transmission electron microscopy, and apoptosis was analyzed using fluorescent dye. Results showed concomitantly upregulation of CDKN2B (G1/S transition), GADD45A (DNA repair and apoptosis) and SERTAD1 (regulation of transcription) gene, increased number of nuclear chamfers and apoptotic cells, and reduced number of microfilaments, organelles and in the size of the nucleus in 5637 and T24 cells after simultaneous treatment with CIS/GEN. In conclusion, independently of the TP53 mutation status and tumor grade, CIS/ GEN induced gene modulation accompanied by changes in cell morphologies, which confirm the antiproliferative activity of the treatment protocol. These findings help to understand the pathways modulated by these antineoplastic agents and may provide insights for anti-cancer chemotherapy.Item Relationship between head and neck cancer therapy and some genetic endpoints.(2014) Minicucci, Eliana Maria; Silva, Glenda Nicioli da; Salvadori, Daisy Maria FáveroHead and neck cancer (HNC) is the sixth most common human malignancy worldwide. The main forms of treatment for HNC are surgery, radiotherapy (RT) and chemotherapy (CT). However, the choice of therapy depends on the tumor staging and approaches, which are aimed at organ preservation. Because of systemic RT and CT genotoxicity, one of the important side effects is a secondary cancer that can result from the activity of radiation and antineoplastic drugs on healthy cells. Ionizing radiation can affect the DNA, causing single and double-strand breaks, DNA-protein crosslinks and oxidative damage. The severity of radiotoxicity can be directly associated with the radiation dosimetry and the dose-volume differences. Regarding CT, cisplatin is still the standard protocol for the treatment of squamous cell carcinoma, the most common cancer located in the oral cavity. However, simultaneous treatment with cisplatin, bleomycin and 5-fluorouracil or treatment with paclitaxel and cisplatin are also used. These drugs can interact with the DNA, causing DNA crosslinks, double and single-strand breaks and changes in gene expression. Currently, the late effects of therapy have become a recurring problem, mainly due to the increased survival of HNC patients. Herein, we present an update of the systemic activity of RT and CT for HNC, with a focus on their toxicogenetic and toxicogenomic effects. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved. Key words: Chemotherapy; Head and neck cancer; Radiotherapy; Toxicogenetic; Toxicogenomic Core tip: The main therapies for head and neck cancer (HNC) are surgery, radiotherapy (RT) and chemotherapy. Considering that both RT and chemotherapeutical drugs can interact with the DNA, one of the important, late-occurring complications is a therapy-related secondary tumor resulting from the genotoxic effects of the therapy on the healthy cells. This review presents an update of the toxicogenetic and toxicogenomic effects of HNC treatments, highlighting the main mechanisms evolved in the secondary damage caused by RT and chemotherapies.Item Variation in susceptibility to benznidazole in isolates derived from Trypanosoma cruzi parental strains.(2001) Veloso, Vanja Maria; Toledo, Max Jean de Ornelas; Lana, Marta de; Chiari, Egler; Tafuri, Washington Luiz; Bahia, Maria TerezinhaIn this work, the susceptibility to benznidazole of two parental Trypanosoma cruzi strains, Colombian and Berenice-78, was compared to isolates obtained from dogs infected with these strains for several years. In order to evaluate the susceptibility to benznidazole two groups of mice were infected with one of five distinct populations isolated from dogs as well as the two parental strains of T. cruzi. The first group was treated with benznidazole during the acute phase and the second remained untreated controls. The animals were considered cured when parasitological and serological tests remained persistently negative. Mice infected with the Colombian strain and its isolates Colombian (A and B) did not cure after treatment. On the other hand, all animals infected with Berenice-78 were cured by benznidazole treatment. However, 100%, 50% and 70% of cure rates were observed in animals infected with the isolates Berenice-78 B, C and D, respectively. No significant differences were observed in serological profile of infected control groups, with all animals presenting high antibody levels. However, the ELISA test showed differences in serological patterns between mice inoculated with the different T. cruzi isolates and treated with benznidazole. This variability was dependent on the T. cruzi population used and seemed to be associated with the level of resistance to benznidazole.Item An alternative in vitro drug screening test using Leishmania amazonensis transfected with red fluorescent protein.(2013) Rocha, Marcele Neves; Corrêa, Célia Maria; Melo, Maria Norma; Beverley, Stephen M.; Martins Filho, Olindo Assis; Madureira, Ana Paula; Soares, Rodrigo Pedro PintoFluorescent and colorimetric reporter genes are valuable tools for drug screening models, since microscopy islabor intensive and subject to observer variation. In this work, we propose afluorimetric method for drugscreening using redfluorescent parasites. FluorescentLeishmania amazonensiswere developed aftertransfection with integration plasmids containing either red (RFP) or greenfluorescent protein (GFP)genes. After transfection, wild-type (LaWT) and transfected (LaGFP and LaRFP) parasites were subjected toflow cytometry, macrophage infection, and tests of susceptibility to current antileishmanial agents andpropranolol derivatives previously shown to be active againstTrypanosoma cruzi. Flow cytometry analysisdiscriminated LaWT from LaRFP and LaGFP parasites, without affecting cell size or granulosity. Withmicroscopy, transfection with antibiotic resistant genes was not shown to affect macrophage infectivity andsusceptibility to amphotericin B and propranolol derivatives. Retention offluorescence remained in theintracellular amastigotes in both LaGFP and LaRFP transfectants. However, detection of intracellular RFPparasites was only achieved in thefluorimeter. Murine BALB/c macrophages were infected with LaRFPparasites, exposed to standard (meglumine antimoniate, amphotericin B, Miltefosine, and allopurinol) andtested molecules. Although it was possible to determine IC50values for 4 propranolol derivatives (1, 2b, 3, and4b), all compounds were considered inactive. This study is thefirst to develop afluorimetric drug screeningtest forL. amazonensisRFP. Thefluorimetric test was comparable to microscopy with the advantage of beingfaster and not requiring manual counting.Item Cell cycle kinetics, apoptosis rates and gene expressions of MDR - 1, TP53, BCL - 2 and BAX in transmissible venereal tumour cells and their association with therapy response.(2016) Flórez, Luis Mauricio Montoya; Fêo, Haline Ballestero; Silva, Glenda Nicioli da; Yamatogi, Ricardo Seiti; Aguiar, Antonio José de Araujo; Araújo Junior, João Pessoa; Rocha, Noeme SousaTransmissible venereal tumour (TVT) generally presents different degrees of aggressiveness, which makes them unresponsive to conventional treatment protocols. This implies a progressive alteration of their biological profile. This study aimed to evaluate the cytotoxicity, cell survival, apoptosis and cell cycle alterations in TVT cell cultures subjected to treatment with vincristine. Similarly, it assessed possible implications of MDR-1, TP53, BCL-2, and BAX gene expressions in eight TVT primary cultures for both resistance to chemotherapy and biological behaviour.When comparing TVT cells receiving vincristine to those untreated, a statistical difference related to increased cytotoxicity and decreased survival rates, and alterations in G1 and S cell cycle phases were found but without detectable differences in apoptosis. Increased MDR-1 gene expression was observed after treatment. The groups did not differ statistically in relation to the TP53, BAX and BCL-2 genes. Although preliminary, the findings suggest that such augmented expression is related to tumour malignancy and chemotherapy resistance.