Institute Pesquisas Clinicas Evandro Chagas

Rio de Janeiro, Brazil

Institute Pesquisas Clinicas Evandro Chagas

Rio de Janeiro, Brazil
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Pedrosa A.A.S.,Federal University of Alagoas | Camacho L.A.B.,Escola Nacional de Saude Publica Sergio Arouca | Passos S.R.L.,Institute Pesquisas Clinicas Evandro Chagas | de Oliveira R.V.C.,Institute Pesquisas Clinicas Evandro Chagas
Cadernos de Saude Publica | Year: 2011

Consumption of alcoholic beverages is widely encouraged by the mass media, despite the related health risks. Today's students in the health fields are the professionals of tomorrow who will be providing advice and serving as role models for patients. The aim of this study was to analyze alcohol consumption and related factors among these students. A total of 608 male and female university students from Maceió, the capital of Alagoas State, Brazil, completed a self-administered questionnaire. Data analysis included Poisson regression and multinomial logistic models. Prevalence of lifetime use of alcohol was 90.4%. Prevalence of alcohol abuse was 18.3% in men and 6.1% in women. Heavier alcohol consumption and alcohol abuse were observed in males, older students, non-natives of Maceió, smokers, and those exposed to alcohol advertising. The results emphasized the vulnerability of these young people to risky health behaviors. Their future social role highlights distinct needs in their university education to enable them to act professionally in this area.

Cunico W.,Institute Tecnologia em Farmacos Farmanguinhos | Cunico W.,Federal University of Bahia | Gomes C.R.B.,Institute Tecnologia em Farmacos Farmanguinhos | Ferreira M.L.G.,Institute Tecnologia em Farmacos Farmanguinhos | And 4 more authors.
European Journal of Medicinal Chemistry | Year: 2011

Thirteen new hydroxyethylamines have been synthesized from reactions of (2S,3S)Boc-phenylalanine epoxide, piperonylamine and arenesulfonyl chlorides in good yields. These compounds were evaluated as antibacterial agents against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and their activity expressed as the minimum inhibitory concentration (MIC) in μM. Two amino alcohols displayed significant activity when compared with first line drug ethambutol (EMB). Therefore this class of compounds could be a good starting point to develop new lead compounds in the treatment of tuberculosis. © 2010 Elsevier Masson SAS. All rights reserved.

Maretti-Mira A.C.,University of California at Los Angeles | Maretti-Mira A.C.,Instituto Oswaldo Cruz | Bittner J.,University of California at Los Angeles | Oliveira-Neto M.P.,Institute Pesquisas Clinicas Evandro Chagas | And 8 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Introduction: Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not. Methods: Using RNA-seq, we analyzed both the human and Leishmania transcriptomes in primary cutaneous lesions. Results: Limited number of reads mapping to Leishmania transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome. Conclusions: We were able to simultaneously sequence both human and Leishmania mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of L. braziliensis infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity. © 2012 Maretti-Mira et al.

Gomes C.R.B.,Institute Tecnologia em Farmacos Farmanguinhos | Moreth M.,Institute Tecnologia em Farmacos Farmanguinhos | Cardinot D.,Institute Tecnologia em Farmacos Farmanguinhos | Kopke V.,Institute Tecnologia em Farmacos Farmanguinhos | And 4 more authors.
Chemical Biology and Drug Design | Year: 2011

Eleven new amino alcohol derivatives have been synthesized from reactions of lopinavir intermediate and heteroaromatic aldehyde in good yields. These compounds, the antiretrovirals (lopinavir and ritonavir) and lopinavir key intermediate were evaluated as antibacterial agents against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and their activity expressed as the minimum inhibitory concentration (MIC) in μm. Ten amino alcohols evaluated displayed significant activity (MIC between 6.15 and 108.4μm) when compared to first-line drug ethambutol (MIC=15.9μm). Three of them showed more activity than ethambutol (MIC=6.15; 6.21 and 13.4μm). The appreciable activity of these compounds can be considered an important finding for the rational design of new leads for anti-TB compounds. © 2011 John Wiley & Sons A/S.

PubMed | State University of Ponta Grossa, Federal University of Itajubá, Institute Pesquisas Clinicas Evandro Chagas and Federal University of Juiz de fora
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016

We report the synthesis of a series of diaminated terpenoids containing, as side-chain of the diamine core, the head-to-tail prenyl derivatives, with amino amino spacers of variable length. In vitro biological activity of these compounds was evaluated against Mycobacterium tuberculosis and Leishmania amazonensis, and the structure-activity relationships are discussed. Different biological results were observed depending on the terpenic side-chain length. The best results were obtained for trans,trans-farnesol derivatives. Moreover, these results demonstrated that the stereochemistry of the double bond could play an important role in determining antitubercular and antileishmanial activities of these compounds.

Orjuela-Sanchez P.,La Jolla Bioengineering Institute | Ong P.K.,La Jolla Bioengineering Institute | Zanini G.M.,La Jolla Bioengineering Institute | Zanini G.M.,Institute Pesquisas Clinicas Evandro Chagas | And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

Cerebral malaria (CM) is associated with low nitric oxide (NO) bioavailability, cerebrovascular constriction, occlusion, and hypoperfusion. Administration of exogenous NO partially prevents the neurological syndrome and associated vascular pathology in an experimental CM (ECM) mouse model. In this study, we evaluated the effects of transdermal glyceryl trinitrate in preventing ECM and, in combination with artemether, rescuing late-stage ECM mice from mortality. The glyceryl trinitrate and/or artemether effect on survival and clinical recovery was evaluated in C57BL/6 mice infected with P. berghei ANKA. NO synthase (NOS) expression in mouse brain was determined by Western blots. Mean arterial pressure (MAP) and pial arteriolar diameter were monitored using a tail-cuff blood pressure system and a cranial window preparation, respectively. Preventative administration of glyceryl trinitrate at 0.025 mg/h decreased ECM mortality from 67 to 11% and downregulated inducible NOS expression in the brain. When administered as adjunctive rescue therapy with artemether, glyceryl trinitrate increased survival from 47 to 79%. The adjunctive therapy caused a sustained reversal of pial arteriolar vasoconstriction in ECM mice, an effect not observed with artemether alone. Glyceryl trinitrate induced a 13% decrease in MAP in uninfected mice but did not further affect MAP in hypotensive ECM mice. Glyceryl trinitrate, when combined with artemether, was an effective adjunctive rescue treatment for ECM. This treatment ameliorated pial arteriolar vasospasm and did not significantly affect MAP. These results indicate that transdermal glyceryl trinitrate has potential to be considered as a candidate for adjunctive therapy for CM. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

PubMed | Laboratorio Of Virus Respiratorios E Do Sarampo, Instituto Octavio Magalhaes, Estado do Parana, Fundacao Estadual de Producao e Pesquisa em Saude and 2 more.
Type: Journal Article | Journal: Memorias do Instituto Oswaldo Cruz | Year: 2015

The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future.

Cabrales P.,La Jolla Bioengineering Institute | Cabrales P.,University of California at San Diego | Zanini G.M.,La Jolla Bioengineering Institute | Zanini G.M.,Institute Pesquisas Clinicas Evandro Chagas | And 3 more authors.
Journal of Infectious Diseases | Year: 2011

Cerebral malaria (CM) is a leading cause of death in Plasmodium falciparum infections. In the Plasmodium berghei ANKA (PbA) murine model, CM pathogenesis is associated with low nitric oxide (NO) bioavailability and brain microcirculatory complications, with a marked decrease in cerebral blood flow, vasoconstriction, vascular plugging by adherent cells, and hemorrhages. Using intravital microscopy through a closed cranial window, here we show that NO supplementation in the form of a NO donor (dipropylenetriamine NONOate [DPTA-NO]) prevented vasoconstriction and improved blood flow in pial vessels of PbA-infected mice. Arterioles and venules of smaller diameters (20-35.5 μm) showed better response to treatment than vessels of larger diameters (36-63 mu;m). Exogenous NO provided protection against brain hemorrhages (mean, 1.4 vs 24.5 hemorrhagic foci per section) and inflammation (mean, 2.5 vs 10.9 adherent leukocytes per 100 lm vessel length) compared with saline treatment. In conclusion, NO protection against CM is associated with improved brain microcirculatory hemodynamics and decreased vascular pathology. © The Author 2011.

PubMed | Institute Pesquisas Clinicas Evandro Chagas, Instituto Oswaldo Cruz and Escola Nacional de Saude Publica
Type: Clinical Trial, Phase II | Journal: Journal of medical virology | Year: 2016

HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination.

Da-Cruz A.M.,Instituto Oswaldo Cruz | Oliveira-Neto M.P.,Institute Pesquisas Clinicas Evandro Chagas | Bertho A.L.,Instituto Oswaldo Cruz | Mendes-Aguiar C.O.,Instituto Oswaldo Cruz | Coutinho S.G.,Instituto Oswaldo Cruz
Journal of Investigative Dermatology | Year: 2010

Immunopathological studies have contributed to the characterization of in situ inflammatory infiltrates in cutaneous leishmaniasis (CL). However, little is known about the T-cell antigen reactivity of these lesions. Our objective was to analyze the responsiveness of lymphocytes from CL lesions to leishmanial and nonrelated antigens in terms of proliferation and the production of cytokines. Mononuclear cells were extracted from lesions, and blood from CL patients infected with Leishmania (Viannia) braziliensis. Activated cells accounted for 35-45% of lesions T-cell subsets. Elevated levels of C1.7/CD244 + CD8 + T cells suggest in situ cytotoxic effector function. Lymphocytes isolated from the leishmaniasis lesions proliferated and produced IFN-γ in response to leishmanial antigens as well as to irrelevant antigens such as Toxoplasma gondii (Tg). Patients presenting with larger lesions had the highest lymphocyte proliferation indexes. A high frequency of Tg-specific cells was detected in the lesions by limiting dilution assay, similar to the frequency of Leishmania-specific cells. Importantly, Tg-reactive cells were not found in lesions of patients without a history of toxoplasmosis. The proportion of Leishmania-reactive CD4 + and CD8 + T cells in the lesions was quite variable. Overall, these data suggest that T cells reactive to nonrelevant antigens can migrate to leishmanial lesions and possibly influence the pathogenesis of the disease. © 2010 The Society for Investigative Dermatology.

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