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1.
Clin Exp Med ; 18(4): 495-504, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30008151

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease characterized by endothelial activation. The main objective of this study was to verify the profile of cell adhesion molecules (CAM) in RA patients, and the influence of metabolic syndrome (MetS) and drugs used in the treatment of RA in this profile. A second objective was to propose models of prediction of activity in RA using these biomarkers. A total of 115 healthy individuals and 144 RA patients were enrolled. Disease activity was determined by DAS28 (disease activity score 28) based on erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). Serum CAM and plasminogen activator inhibitor type-1 (PAI-1), anthropometric and immunological parameters were measured. Vascular cell adhesion molecule-1 (VCAM-1) was significantly decreased, and PAI-1 was significantly higher in RA patients as compared to controls. Binary logistic regression analysis showed that VCAM-1, CRP, and tumor necrosis factor-α (TNF-α) predicted RA with a sensitivity of 95.9% and a specificity of 89.5%. 42.9% of the variance in DAS28-ESR and 49.2% of the variance in DAS28-CRP are explained by increased PAI-1, TNF-α, body mass index (BMI) and decreased platelet endothelial cell adhesion molecule 1 (PECAM-1). Our data show that lower levels of VCAM-1 are associated with RA independently of MetS, while increased PAI-1 levels were associated with both RA and MetS and increased selectins (E-selectin and P-selectin) were exclusively associated with MetS and not with RA. A model to predict disease activity based on PECAM-1, PAI-1, TNF-α, age and BMI is proposed.


Assuntos
Artrite Reumatoide/diagnóstico , Moléculas de Adesão Celular/sangue , Síndrome Metabólica/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Adulto , Idoso , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Sedimentação Sanguínea , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Sensibilidade e Especificidade , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue
2.
Clin Exp Med ; 18(3): 363-372, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29644482

RESUMO

Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP). NOx and the NOx/TRAP ratio were significantly increased in RA, while no significant differences in lipid hydroperoxides, AOPP, UA, and TRAP levels were found between both groups. Treatment with leflunomide was associated with increased levels of carbonyl protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further increased. NOx and the NOx/TRAP ratio were significantly higher in women than in men, while TRAP and UA were significantly lower in women. MetS was accompanied by increased AOPP and UA levels. RA was best predicted by increased NOx/TRAP ratio, CRP, and BMI. In conclusion, our data demonstrated that NOx and NOx/TRAP are strongly associated with RA physiopathology. Our findings suggest that inhibition of iNOS may become an interesting therapeutic approach for the treatment of RA. In addition, the presence of MetS and a decrease in levels of UA by leflunomide favor redox imbalance in RA patients. More studies are needed to evaluate the impact of antioxidant capacity reduction on RA progression.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Ácido Úrico/sangue , Adolescente , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Produtos da Oxidação Avançada de Proteínas/genética , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Leflunomida , Peróxidos Lipídicos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Fatores Sexuais , Ácido Úrico/antagonistas & inibidores
3.
Immunol Res ; 66(1): 158-171, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29185130

RESUMO

This study investigated nitro-oxidative stress in patients with systemic lupus erythematosus (SLE) in association with disease activity, immune-inflammatory biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256 healthy volunteers were enrolled in this case-control study, which measured nitro-oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation protein products (AOPPs), nitric oxide metabolites (NOx), sulfhydryl (-SH) groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP and LOOH were significantly and positively associated with SLE disease activity index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double-stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant positive associations between AOPP and LOOH and immune-inflammatory markers, indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were associated with adhesion molecule expression. A model predicting SLE was computed showing that, using LOOH, AOPP, NOx, adhesion molecules, and body mass index, 94.2% of the patients were correctly classified with a specificity of 91.5%. Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology of SLE and modulates severity of illness and adhesion molecule expression.


Assuntos
Biomarcadores/metabolismo , Inflamação/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Células Th1/imunologia , Células Th17/imunologia , Adulto , Produtos da Oxidação Avançada de Proteínas/metabolismo , Anticorpos Antinucleares/sangue , Moléculas de Adesão Celular/metabolismo , Feminino , Humanos , Peróxidos Lipídicos/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Estresse Nitrosativo , Estresse Oxidativo
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