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Santa Maria do Suaçuí, Brazil

De Lima D.S.,Federal University of Amazonas | Ogusku M.M.,National Institute of Amazonian Research | Dos Santos M.P.,National Institute of Amazonian Research | De Melo Silva C.M.,Programa de Pos Graduacao em Ciencias Farmaceuticas | And 6 more authors.
PLoS ONE | Year: 2016

Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1∗04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon. The HLA-DRB1∗04 was prevalent in patients with pulmonary TB (p<0.0001; OR = 2.94; 95% CI = 2.12 to 4.08). Direct nucleotide sequencing of DRB1 exon 2 identified nine subtypes of HLA-DRB1∗04. The subtype HLA-DRB1∗04:11:01 (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70) was associated with susceptibility to pulmonary TB while DRB1∗04:07:01 (p<0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) to protection. Notably, the interaction between alcohol and HLA-DRB1∗04:11:01 increased the risk for developing pulmonary TB (p = 0.0001; OR = 51.3; 95% CI = 6.81 to 386). Multibacillary pulmonary TB, the clinical presentation of disease transmission, was strongly associated with interaction to alcohol (p = 0.0026; OR = 11.1; 95% CI = 3.99 to 30.9), HLA-DRB1∗04:11:01 (p = 0.0442; OR =2.01; 95% CI = 1.03 to 3.93) and DRB1∗04:92 (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results show that HLA-DRB1∗04 are associated with pulmonary TB. Interestingly, three subtypes, DRB1∗04:07:01, DRB1∗04:11:01 and DRB1∗04:92 of the HLA-DRB1∗04 could be potential immunogenetic markers that may help to explain mechanisms involved in disease development. © 2016 Souza de Lima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Wayhs C.A.Y.,Programa de Pos Graduacao em Ciencias Farmaceuticas | Tortato C.,Federal University of Rio Grande do Sul | Mescka C.P.,Federal University of Rio Grande do Sul | Pasquali M.A.,Federal University of Rio Grande do Sul | And 6 more authors.
Pharmaceutical Biology | Year: 2013

Context: It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model. Objective: This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST). Materials and methods: Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60mg/kg in male Wistar rats. Insulin (4IU/kg) plus CNZ acute i.p. treatment (0.25mg/kg) was administered 24, 5 and 1h before the FST. Nondiabetic control rats received i.p. injections of saline (1mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined. Results: Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04±0.55), while the activity of catalase (51.83±19.02) and SOD (2.30±1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15±0.02) in the liver of the animals was decreased. Discussion and conclusion: Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST. © 2013 Informa Healthcare USA, Inc.


Goncalves R.M.,State University of Maringa | Lemos C.O.T.,State University of Maringa | Leal I.C.R.,Federal University of Rio de Janeiro | Nakamura C.V.,Programa de Pos Graduacao em Ciencias Farmaceuticas | And 4 more authors.
Molecules | Year: 2013

Calophyllum brasiliense is a rich source of bioactive coumarins, xanthones and biflavonoids. The aim of the study was to compare the phenol contents and the antioxidant activity of C. brasiliense extracts obtained by conventional and supercritical fluid extraction (SFE) methods, as well as the quantification of crude extracts and (-)-mammea A/BB yields. Dichloromethane and hexane were used as solvents for the conventional extractions and SFE was developed using supercritical CO2; the kinetic curves were modeled using a second-order empirical model. The dichloromethane extract presented the best total yield, although it showed the lowest content of (-)-mammea A/BB. The concentration of the coumarin was considerably higher in extracts obtained by the supercritical fluid method and a higher antioxidant activity was assigned to extracts obtained by this technique. Concerning the total phenolic contents, both the dichloro-methane and the supercritical extractions produced satisfactory amounts. The SFE method proved to be more promising than conventional methods. © 2013 by the authors.


Wayhs C.A.Y.,Programa de Pos Graduacao em Ciencias Farmaceuticas | Manfredini V.,Programa de Pos Graduacao em Ciencias Farmaceuticas | Sitta A.,Servico de Genetica Medica | Sitta A.,Federal University of Rio Grande do Sul | And 9 more authors.
Metabolic Brain Disease | Year: 2010

Diabetes may modify central nervous system functions and is associated with moderate cognitive deficits and changes in the brain, a condition that may be referred to as diabetic encephalopathy. The prevalence of depression in diabetic patients is higher than in the general population, and clonazepam is being used to treat this complication. Oxidative stress may play a role in the development of diabetes complications. We investigated oxidative stress parameters in streptozotocin-induced diabetic rats submitted to forced swimming test (STZ) and evaluated the effect of insulin (STZ-INS) and/or clonazepam (STZ-CNZ and STZ-INS-CNZ) acute treatment on these animal model. Oxidative damage to proteins measured as carbonyl content in plasma was significantly increased in STZ group compared to STZ treated groups. Malondialdehyde plasma levels were significantly reduced in STZ-INS and STZ-INS-CNZ groups when compared to STZ rats, being significantly reduced in STZ-INS-CNZ than STZ-INS rats. The activities of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase showed no significant differences among all groups of animals. These findings showed that protein and lipid damage occurs in this diabetes/depression animal model and that the associated treatment of insulin and clonazepam is capable to protect against oxidative damage in this experimental model. © 2010 Springer Science+Business Media, LLC.


Bittencourt L.S.,Federal University of Santa Maria | Machado D.C.,Grande Rio University | Machado M.M.,Federal University of Pampa | Dos Santos G.F.F.,Federal University of Santa Maria | And 7 more authors.
Food and Chemical Toxicology | Year: 2013

The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine = 12.240. mg/g, theobromine = 6.733. mg/g and total catechins = 4.336. mg/g. Cells were exposed to 10 μM SNP during a 6. h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20. mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5. mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels. © 2012 Elsevier Ltd.

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