Carlos Chagas Institute Fiocruz

Carlos Chagas, Brazil

Carlos Chagas Institute Fiocruz

Carlos Chagas, Brazil

Time filter

Source Type

De Faria T.J.,Federal University of Santa Catarina | Roman M.,Federal University of Santa Catarina | De Souza N.M.,Federal University of Santa Catarina | De Vecchi R.,Federal University of Santa Catarina | And 8 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012

Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits M. tuberculosis growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular M. tuberculosis and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra- and intracellular mycobacteria, which could actively enhance chemotherapy during active TB. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Azeredo C.M.O.,Carlos Chagas Institute Fiocruz | Santos T.G.,Federal University of Paraná | Maia B.H.L.N.S.,Federal University of Paraná | Soares M.J.,Carlos Chagas Institute Fiocruz
BMC Complementary and Alternative Medicine | Year: 2014

Background: Essential oils (EOs) are complex mixtures of secondary metabolites from various plants. It has been shown that several EOs, or their constituents, have inhibitory activity against trypanosomatid protozoa. Thus, we analyzed the biological activity of different EOs on Trypanosoma cruzi, as well as their cytotoxicity on Vero cells. Methods: The following EOs were evaluated on T. cruzi epimastigote forms: Cinnamomum verum, Citrus limon, Cymbopogon nardus, Corymbia citriodora, Eucalyptus globulus, Eugenia uniflora, Myrocarpus frondosus, and Rosmarinus officinalis. Inhibitory activity against T. cruzi (IC50/24 h) and cytotoxicity against Vero cells (CC50/24 h) were evaluated by the MTT assay. The EO of C. verum was selected for further evaluation against trypomastigotes and intracellular amastigotes, as well as on parasite metacyclogenesis. Constituents of C. verum EO were identified by GC-MS. One-way ANOVA statistical analysis was performed with GraphPad version 5.01. Results: Cinnamomum verum EO was the most effective against T. cruzi epimastigotes (IC50/24 h = 24.13 μg/ml), followed by Myrocarpus frondosus (IC50/24 h = 60.87 μg/ml) and Eugenia uniflora (IC50/24 h = 70 μg/ml). The EOs of C. citriodora, E. globulus, and R. officinalis showed no activity at concentrations up to 300 μg/ml. Incubation of T. cruzi metacyclic trypomastigotes and intracellular amastigotes with C. verum EO resulted in IC50/24 h values of 5.05 μg/ml and 20 μg/ml, respectively. Therefore, trypomastigotes are more susceptible than epimastigotes, with selectivity index (SI) about 4.7-fold higher (9.78 and 2.05, respectively). Analysis of C. verum EO by GC-MS showed mainly (E)-cinnamaldehyde (81.52%) and eugenol (16.68%). Conclusions: C. verum essential oil is effective against T. cruzi (epimastigotes, trypomastigotes and amastigotes) and interferes with the parasite differentiation process in vitro. Thus, it represents a strong candidate for further studies to improve its activity on pathogenic trypanosomatids. © 2014 Azeredo et al.; licensee BioMed Central Ltd.


Pinho-Ribeiro F.A.,State University Londrina | Zarpelon A.C.,State University Londrina | Mizokami S.S.,State University Londrina | Borghi S.M.,State University Londrina | And 7 more authors.
Journal of Nutritional Biochemistry | Year: 2016

Lipopolysaccharide (LPS) is the major structural component of Gram-negative bacteria cell wall and a highly pro-inflammatory toxin. Naringenin is found in Citrus fruits and exhibits antioxidant and anti-inflammatory properties through inhibition of NF-κB activation but its effects in LPS-induced inflammatory pain and leukocyte recruitment were not investigated yet. We investigated the effects of naringenin in mechanical hyperalgesia, thermal hyperalgesia and leukocyte recruitment induced by intraplantar injection of LPS in mice. We found that naringenin reduced hyperalgesia to mechanical and thermal stimuli, myeloperoxidase (MPO, a neutrophil and macrophage marker) and N-acetyl-β-D-glucosaminidase (NAG, a macrophage marker) activities, oxidative stress and cytokine (TNF-α, IL-1β, IL-6, and IL-12) production in the paw skin. In the peritoneal cavity, naringenin reduced neutrophil and mononuclear cell recruitment, and abrogated MPO and NAG activity, cytokine and superoxide anion production, and lipid peroxidation. In vitro, pre-treatment with naringenin inhibited superoxide anion and cytokine (TNF-α, IL-1β, IL-6, and IL-12) production by LPS-stimulated RAW 264.7 macrophages. Finally, we demonstrated that naringenin inhibited NF-κB activation in vitro and in vivo. Therefore, naringenin is a promising compound to treat LPS-induced inflammatory pain and leukocyte recruitment. © 2016 Elsevier Inc.


PubMed | Carlos Chagas Institute Fiocruz, University of Sao Paulo and State University Londrina
Type: | Journal: The Journal of nutritional biochemistry | Year: 2016

Lipopolysaccharide (LPS) is the major structural component of Gram-negative bacteria cell wall and a highly pro-inflammatory toxin. Naringenin is found in Citrus fruits and exhibits antioxidant and anti-inflammatory properties through inhibition of NF-B activation but its effects in LPS-induced inflammatory pain and leukocyte recruitment were not investigated yet. We investigated the effects of naringenin in mechanical hyperalgesia, thermal hyperalgesia and leukocyte recruitment induced by intraplantar injection of LPS in mice. We found that naringenin reduced hyperalgesia to mechanical and thermal stimuli, myeloperoxidase (MPO, a neutrophil and macrophage marker) and N-acetyl--D-glucosaminidase (NAG, a macrophage marker) activities, oxidative stress and cytokine (TNF-, IL-1, IL-6, and IL-12) production in the paw skin. In the peritoneal cavity, naringenin reduced neutrophil and mononuclear cell recruitment, and abrogated MPO and NAG activity, cytokine and superoxide anion production, and lipid peroxidation. In vitro, pre-treatment with naringenin inhibited superoxide anion and cytokine (TNF-, IL-1, IL-6, and IL-12) production by LPS-stimulated RAW 264.7 macrophages. Finally, we demonstrated that naringenin inhibited NF-B activation in vitro and in vivo. Therefore, naringenin is a promising compound to treat LPS-induced inflammatory pain and leukocyte recruitment.


Carvalho P.C.,Carlos Chagas Institute Fiocruz | Fischer J.S.G.,Carlos Chagas Institute Fiocruz | Xu T.,Scripps Research Institute | Yates III J.R.,Scripps Research Institute | Barbosa V.C.,Federal University of Rio de Janeiro
Current Protocols in Bioinformatics | Year: 2012

PatternLab for proteomics is a self-contained computational environment for analyzing shotgun proteomic data. Recent improvements incorporate modules to facilitate the computational analysis, such as FastaDBXtractor for sequence database preparation and ProLuCID runner for simplifying and managing the protein identification search engine; modules for pushing the limits on proteomics standards, such as SEPro, which relies on a semi-labeled decoy approach for increasing confidence in filtering and organizing peptide spectrum matches; and modules with novel features, such as SEProQ for enabling labelfree quantitation by extracted ion chromatograms according to a distributed normalized ion abundance factor approach (dNIAF). Existing modules were also improved, such as the TFold module for pinpointing differentially expressed proteins. These new modules are integrated into the previously described arsenal of tools for further data analysis. Here we provide detailed instructions for operating and understanding them. © 2012 by John Wiley & Sons, Inc.


Soares M.J.,Carlos Chagas Institute Fiocruz
BMC complementary and alternative medicine | Year: 2014

Essential oils (EOs) are complex mixtures of secondary metabolites from various plants. It has been shown that several EOs, or their constituents, have inhibitory activity against trypanosomatid protozoa. Thus, we analyzed the biological activity of different EOs on Trypanosoma cruzi, as well as their cytotoxicity on Vero cells. The following EOs were evaluated on T. cruzi epimastigote forms: Cinnamomum verum, Citrus limon, Cymbopogon nardus, Corymbia citriodora, Eucalyptus globulus, Eugenia uniflora, Myrocarpus frondosus, and Rosmarinus officinalis. Inhibitory activity against T. cruzi (IC50/24 h) and cytotoxicity against Vero cells (CC50/24 h) were evaluated by the MTT assay. The EO of C. verum was selected for further evaluation against trypomastigotes and intracellular amastigotes, as well as on parasite metacyclogenesis. Constituents of C. verum EO were identified by GC-MS. One-way ANOVA statistical analysis was performed with GraphPad version 5.01. Cinnamomum verum EO was the most effective against T. cruzi epimastigotes (IC50/24 h = 24.13 μg/ml), followed by Myrocarpus frondosus (IC50/24 h = 60.87 μg/ml) and Eugenia uniflora (IC50/24 h = 70 μg/ml). The EOs of C. citriodora, E. globulus, and R. officinalis showed no activity at concentrations up to 300 μg/ml. Incubation of T. cruzi metacyclic trypomastigotes and intracellular amastigotes with C. verum EO resulted in IC50/24 h values of 5.05 μg/ml and 20 μg/ml, respectively. Therefore, trypomastigotes are more susceptible than epimastigotes, with selectivity index (SI) about 4.7-fold higher (9.78 and 2.05, respectively). Analysis of C. verum EO by GC-MS showed mainly (E)-cinnamaldehyde (81.52%) and eugenol (16.68%). C. verum essential oil is effective against T. cruzi (epimastigotes, trypomastigotes and amastigotes) and interferes with the parasite differentiation process in vitro. Thus, it represents a strong candidate for further studies to improve its activity on pathogenic trypanosomatids.


De Paula Lima C.V.,Carlos Chagas Institute Fiocruz | Batista M.,Carlos Chagas Institute Fiocruz | Kugeratski F.G.,Carlos Chagas Institute Fiocruz | Vincent I.M.,University of Glasgow | And 4 more authors.
BMC Microbiology | Year: 2014

Background: Trypanosoma cruzi, the etiologic agent of Chagas disease, alternates between distinct morphological and functional forms during its life cycle. Axenic multiplication and differentiation processes of this protozoan parasite can be reproduced in vitro, enabling the isolation and study of the different evolutionary forms. Although there are several publications attempting the cultivation of T. cruzi under chemically defined conditions, in our experience none of the published media are capable of maintaining T. cruzi in continuous growth. Results: In this work we modified a known chemically defined medium for Trypanosoma brucei growth. The resulting LM14 and LM14B defined media enabled cultivation of five different strains of T. cruzi for more than forty passages until now. The parasite's biological characteristics such as morphology and differentiation to metacyclic trypomastigotes were maintained when defined media is used. Conclusions: The establishment of a defined medium for T. cruzi cultivation is an important tool for basic biological research allowing several different approaches, providing new perspectives for further studies related to cell biology of this parasite. © 2014 De Paula Lima et al.; licensee BioMed Central Ltd.


PubMed | Carlos Chagas Institute Fiocruz
Type: | Journal: BMC complementary and alternative medicine | Year: 2014

Essential oils (EOs) are complex mixtures of secondary metabolites from various plants. It has been shown that several EOs, or their constituents, have inhibitory activity against trypanosomatid protozoa. Thus, we analyzed the biological activity of different EOs on Trypanosoma cruzi, as well as their cytotoxicity on Vero cells.The following EOs were evaluated on T. cruzi epimastigote forms: Cinnamomum verum, Citrus limon, Cymbopogon nardus, Corymbia citriodora, Eucalyptus globulus, Eugenia uniflora, Myrocarpus frondosus, and Rosmarinus officinalis. Inhibitory activity against T. cruzi (IC50/24 h) and cytotoxicity against Vero cells (CC50/24 h) were evaluated by the MTT assay. The EO of C. verum was selected for further evaluation against trypomastigotes and intracellular amastigotes, as well as on parasite metacyclogenesis. Constituents of C. verum EO were identified by GC-MS. One-way ANOVA statistical analysis was performed with GraphPad version 5.01.Cinnamomum verum EO was the most effective against T. cruzi epimastigotes (IC50/24 h=24.13 g/ml), followed by Myrocarpus frondosus (IC50/24 h=60.87 g/ml) and Eugenia uniflora (IC50/24 h=70 g/ml). The EOs of C. citriodora, E. globulus, and R. officinalis showed no activity at concentrations up to 300 g/ml. Incubation of T. cruzi metacyclic trypomastigotes and intracellular amastigotes with C. verum EO resulted in IC50/24 h values of 5.05 g/ml and 20 g/ml, respectively. Therefore, trypomastigotes are more susceptible than epimastigotes, with selectivity index (SI) about 4.7-fold higher (9.78 and 2.05, respectively). Analysis of C. verum EO by GC-MS showed mainly (E)-cinnamaldehyde (81.52%) and eugenol (16.68%).C. verum essential oil is effective against T. cruzi (epimastigotes, trypomastigotes and amastigotes) and interferes with the parasite differentiation process in vitro. Thus, it represents a strong candidate for further studies to improve its activity on pathogenic trypanosomatids.


PubMed | Carlos Chagas Institute Fiocruz
Type: | Journal: Current protocols in bioinformatics | Year: 2012

PatternLab for proteomics is a self-contained computational environment for analyzing shotgun proteomic data. Recent improvements incorporate modules to facilitate the computational analysis, such as FastaDBXtractor for sequence database preparation and ProLuCID runner for simplifying and managing the protein identification search engine; modules for pushing the limits on proteomics standards, such as SEPro, which relies on a semi-labeled decoy approach for increasing confidence in filtering and organizing peptide spectrum matches; and modules with novel features, such as SEProQ for enabling label-free quantitation by extracted ion chromatograms according to a distributed normalized ion abundance factor approach (dNIAF). Existing modules were also improved, such as the TFold module for pinpointing differentially expressed proteins. These new modules are integrated into the previously described arsenal of tools for further data analysis. Here we provide detailed instructions for operating and understanding them.

Loading Carlos Chagas Institute Fiocruz collaborators
Loading Carlos Chagas Institute Fiocruz collaborators