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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.

Da Costa C.F.,Institute Tecnologia em Farmacos Farmanguinhos | Da Costa C.F.,Federal University of Juiz de fora | Pinheiro A.C.,Institute Tecnologia em Farmacos Farmanguinhos | De Almeida M.V.,Federal University of Juiz de fora | And 2 more authors.
Chemical Biology and Drug Design | Year: 2012

In this work, 17 new N-acylhydrazone derivatives of amino acids have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. The compounds 8b, 8e, 8f, 9a-d, and 10c exhibited an important minimum inhibitory concentration activity between 12.5 and 50μg/mL, which can be compared with that of the tuberculostatic drug d-cycloserine (20μg/mL). In this work 17 new N-acylhydrazone derivatives of amino acids have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Eight compounds were non-cytotoxic and exhibited an important MIC activity between 12.5 and 50μg/mL, which can be compared with that of the tuberculostatic drug d-cycloserine (20μg/mL). © 2011 John Wiley & Sons A/S.

Gibson G.,Escola Nacional de Saude Publica Sergio Arouca | Souza-Santos R.,Escola Nacional de Saude Publica Sergio Arouca | Brasil P.,Institute Pesquisas Clinicas Evandro Chagas | Pacheco A.G.,Escola Nacional de Saude Publica Sergio Arouca | And 4 more authors.
Cadernos de Saude Publica | Year: 2013

We analyzed factors associated with severe cases of dengue in children and adolescents hospitalized during the 2007/2008 epidemic in Rio de Janeiro, Brazil. This is a retrospective case-control study that covers 88 cases of severe dengue in patients admitted to four tertiary care children's hospitals. Controls consisted of 22 children with non-severe dengue living in the same neighborhood as the patients with severe dengue. Differences in prevalence of the clinical signs - abdominal pain, breathing difficulty, drowsiness or irritability - emerged on the third day after the onset of symptoms, in the febrile stage. Cases and controls received first medical care at the same clinical stage of disease. However, hospital admission of severe cases occurred later, on average between the third and fourth day after the onset of the disease. Early discharge of patients with fever whose condition could have progressed to severe dengue may have been a consequence of the type of medical assistance provided by primary care units, suggesting deficiencies both in the use of the risk classification protocol and patient triage.

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.

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.

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