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ABSTRACT: Endothelial rupture of coronary plaque can represent the pathomorphological substratum of acute coronary syndrome (ACS). Polymorphisms in the NOS3 gene (eNOS) -786T>C, 894G>T and intron 4 a/b VNTR can be associated with a higher susceptibility for ACS. The present study is focused on the investigation of the interaction of these polymorphisms and cardiovascular risk factors in 135 patients with ACS and 115 control subjects.
Case-control study where the allele and genotype frequencies of the polymorphisms -786T> C, 894G> T and intron 4 VNTR of the gene encoding eNOS were determined by PCR-RFLP associated with cardiovascular risk factors.
An association of the 894TT genotype and 894GT+GG (OR 1.4; 95% CI 1.0-1.8) in ACS has been observed. Subjects without dyslipidemia and intron 4 a/b genotype present a lower chance for ACS development, whereas subjects without diabetes and 894TT genotype show a higher risk for ACS (OR 1.7; 95% CI 1.2-2.3). In patients without dyslipidemia, the 894GG genotype presented a tendency to behave as a protector factor against ACS. Also, the 894GG genotype has been a protective factor for ACS in females (OR 0.5; CI 95% 0.2-0.9).
Our results suggest that eNOS polymorphisms may be an additional risk factor in development of ACS.
Archives of medical research 04/2012; 43(3):205-11. · 1.88 Impact Factor
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Timothy J Wilson,
Mariana Jobim,
Luiz Fernando Jobim,
Pamela Portela,
Patrícia H Salim,
Mário A Rosito,
Daniel C Damin,
Cristina Flores, Alessandra Peres,
Marta Brenner Machado,
José Artur Bogo Chies,
Gilberto Schwartsmann,
Rafael Roesler
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ABSTRACT: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel, of unknown origin. Exposure to specific environmental factors by genetically susceptible individuals, leading to an inadequate response of the immune system, is one of the potential explanations for the occurrence of these diseases. Natural killer cells are part of the innate immune system recognizing class I HLA (human leukocyte antigen) molecules on target cells through their membrane receptors. The main receptors of the natural killer cells are the killer immunoglobulinlike receptors (KIRs). Our study aimed to evaluate the association between the KIR genes in patients with inflammatory bowel diseases and healthy controls. We typed 15 KIR genes and HLA class I ligands in 248 unrelated Brazilian Caucasians, of which 111 had UC and 137 had CD, and 250 healthy controls by polymerase chain reaction using sequence-specific oligonucleotides and sequence-specific primers. We found an increase in KIR2DL2 in controls (inflammatory bowel disease [IBD]: p < 0.001; UC: p = 0.01; CD: p = not significant [NS]). The genotype 2DL2+/HLA-C lys(80)+ was also more common in controls (IBD: p = 0.005; UC: p = 0.01; CD: p = NS); as well as 2DL1+/HLA-C Asn(80)+ (IBD: p = 0.026; UC: p = NS;CD: p = NS). The imbalance between activating and inhibitory KIR and HLA ligands may explain, at least in part, the pathogenesis of these inflammatory bowel diseases.
Human immunology 03/2010; 71(3):293-7. · 2.55 Impact Factor
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Alessandra Peres,
Aline Grimaldi Lerias,
Ana Karine Kramer de Aguiar,
Andrew Oliveira Silva,
Caroline Borges Costa,
Claudia Bemfica,
Daiani Machado de Vargas,
Dieime de Souza Andrade,
Douglas Senna Engelke,
Elisa Nicoloso Simões Pires,
Gabriel Vasat Furtado,
Gustavo Luiz Erpen,
Janaína De Nardin,
Letícia Muner Otton,
Lucas Silva Tortorelli,
Priscila Machado da Rosa,
José Artur Bogo Chies
Medical Hypotheses 09/2009; 74(1):208-9. · 1.39 Impact Factor
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ABSTRACT: Metabolic syndrome (MS) is a cluster of cardiovascular risk factors such as hypertension, dyslipidemia, obesity and type II diabetes. Here, we performed a case-control study analyzing the association between 894G>T endothelial nitric oxide synthase gene polymorphism (NOS3) and MS in 616 subjects. Genotype frequencies were TT= 9.3%, GG= 37.2 and TG= 53.6% and the allelic frequencies were T=0.36 and G= 0.64. We observed a higher TT genotype frequency in the male MS group than control subjects (p=0.02), independent of other variables. We found an association between hypertension and TT genotype in females. Our data suggests that 894G>T plays a significant role in the mechanistic interaction between metabolic risk such as hypertension and MS, although sex-related differences may exist.
Arquivos brasileiros de endocrinologia e metabologia 11/2008; 52(8):1367-73. · 0.68 Impact Factor
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ABSTRACT: Oxidative stress has been related to aging. Recent evidences suggest that a genetic dimorphism that encodes for either alanine or valine in superoxide dismutase (SOD2) is involved with oxidative stress. However, the current literature is still controversial, and the potential role of the Ala16Val polymorphism in human aging needs to be established. Here we investigated the role of the SOD2 polymorphism in: a) age-related mortality, b) morbidity (breast and prostate cancer), c) immunological markers, and d) DNA damage in peripheral blood cells. We did not find an association between SOD2 polymorphisms and mortality. However, the AA genotype was associated with increased risk for prostate and breast cancer, immunosenescence profile, as well as DNA damage. These data suggest that SOD2 presents characteristics that support the free radical theory of aging.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 05/2005; 60(4):432-8. · 4.60 Impact Factor
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ABSTRACT: Sepsis remains an important and life-threatening problem, and is the most common cause of death in the intensive care unit. One promising therapeutic candidate for protection against injury in sepsis is fructose-1,6-bisphosphate (FBP), a high-energy glycolytic pathway intermediate. The objective of the study was to establish a role for FBP on the immune system, especially in lymphocyte proliferation. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy humans by gradient centrifugation. T-lymphocytes were stimulated for 96 h with phytohemagglutinin (PHA) and varying concentration of FBP. Fructose-1,6-bisphosphate at concentrations between 1.2 and 10 mM decreased proliferation of T-lymphocytes and reduced the viability only at concentrations 5.0 and 10 mM. The levels of soluble IL-2 receptor were reduced at FBP concentrations between 1.2 and 10 mM. In conclusion, this study demonstrates that FBP has important effect on immunomodulatory and this result can be correlated with the protection against injury in sepsis.
International Immunopharmacology 03/2003; 3(2):267-72. · 2.38 Impact Factor
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ABSTRACT: The age-related decline of immunological functions is well established but it remains largely unknown which specific changes are related to disease. We analyzed peripheral blood lymphocytes of 42 healthy elderly as well as 24 healthy young subjects from southern Brazil. No differences in phytohemagglutinin-induced proliferation and CD4:CD8 ratio were found between the subjects. However, CD4 expression (considering mean fluorescence intensity) was found upregulated in elderly subjects. No changes in activation molecules CD25, CD28, CD69 and CD95 were observed. A reduced proportion of naive (CD45RA+) T cells was found in the elderly compared to young subjects. No changes in adhesion molecule expression (CD11c and CD31) were observed. However, the frequencies of CD49d-positive cells, as well as expression of CD62L, were increased in the eldery subjects. We further described two subgroups of eldery subjects with an immunological risk profile defined by lower CD4:CD8 ratio and reduced proliferative response to mitogens. These data suggest that healthy aging is associated with intact T-cell proliferation and some compensatory immunophenotypical changes.
Biogerontology 02/2003; 4(5):289-96. · 3.34 Impact Factor
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ABSTRACT: We have investigated the normal variations in basal DNA damage detected by Comet assay in leukocytes and micronucleated erythrocytes (MNE) using the Micronucleus test (MN) in peripheral blood cells from 45 female and male mice from different age groups (newborns, 3.5, 12, and 104 weeks) to clarify age and sex-related changes. Comparison of basal DNA damage detected by Comet assay showed significantly increased values in 104 weeks old mice in relation to the other ages (P ≤ 0.01), and newborn mice showed higher values in MNE frequency when compared to all the other groups (P ≤ 0.01). A positive correlation was observed between Damage Frequency (r = 0.382, P = 0.010) and Damage Index (r = 0.640, P < 0.001) and age. Age was also correlated with the ratio of polychromatic erythrocytes/normachromatic erythrocytes (PCE/NCE) (r = − 0.473, P = 0.001), and the MNE frequency was positively correlated with the ratio of PCE/NCE (r = 0.454, P = 0.002). These results suggest an age-related slow down of DNA repair efficiency of DNA damage and/or DNA damage accumulation. Furthermore, data on the spontaneous MNE frequency indicate that the reticuloendothelial system matures with age, and there is a close relationship between erythropoiesis and micronucleus induction in erythrocytes. The influence of sex in the parameters analyzed was less clear. In conclusion, age seems to influence in basal DNA damage and should be considered in genotoxicity studies using mice. Finally, comparisons between assays must be made with care when different cells are compared (e.g. leukocytes and erythrocytes), as found with the Comet assay and MN test.
Cell Biology International.
