Mixture of probiotics reduces inflammatory biomarkers and improves the oxidative/nitrosative profile in people with rheumatoid arthritis.

OBJECTIVES: Studies have demonstrated that the gut microbiota of people with rheumatoid arthritis (RA) is different from that of healthy individuals and could influence inflammation and oxidative stress. In this study, we sought to evaluate the effects of supplementation with a mixture of probiotics on cytokine plasma levels, inflammatory biomarkers, oxidative/nitrosative stress profile, and Disease Activity Score-28 in people with RA. METHODS: A randomized and double-blind placebo-controlled study was carried out with 42 participants with RA divided into two groups-the probiotic group (n = 21), who over 60 d took a daily ingestion of probiotics in a sachet containing 109 CFU/g each of five freeze-dried strains: Lactobacillus acidophilus La-14, Lactobacillus casei Lc-11, Lactococcus lactis Ll-23, Bifidobacterium lactis Bl-04 and B. bifidum Bb-06; and the placebo group (n = 21) who over 60 d took a daily ingestion of maltodextrin. RESULTS: The probiotic group showed a significant reduction in white blood cell count (P = 0.012) and tumor necrosis factor-α (P = 0.004) and interleukin 6 plasma levels (P = 0.039). However, no differences were observed in interleukin-10, adiponectin, C-reactive protein, erythrocyte sedimentation rate, ferritin, or Disease Activity Score-28 between the two groups. Regarding oxidative/nitrosative stress biomarkers, the probiotic group showed lower nitric oxide metabolites (P = 0.004) and higher sulfhydryl group (P = 0.028) and total radical-trapping antioxidant parameters (P = 0.019) than the placebo group. However, lipid hydroperoxide and protein carbonyl did not differ between groups (P > 0.05). CONCLUSIONS: The mixture of probiotics reduced inflammatory biomarkers and improved the oxidative/nitrosative profile in people with RA.

Haplotypes of FOXP3 genetic variants are associated with susceptibility, autoantibodies, and TGF-ß1 in patients with systemic lupus erythematosus.

The aim of this study was to evaluate the association of rs2232365 (-924 G > A) and rs3761548 (-3279 C > A) FOXP3 variants with systemic lupus erythematosus (SLE) susceptibility, TGF-ß1 plasma levels, autoantibodies, and LN nephritis, and SLE disease activity index (SLEDAI). The study included 196 SLE female patients and 157 female controls. FOXP3 variants were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of TGF-ß1 were determined using immunofluorimetric assay. The AA genotype [OR: 2.650, CI 95%(1.070-6.564), p = 0.035] and A allele [OR: 2.644, CI 95%(1.104-6.333), p = 0.029] were associated with SLE diagnosis in the -3279 C > A. The A/A haplotype was associated with SLE [OR: 3.729, CI 95%(1.006-13.820), p = 0.049]. GCGC haplotype patients had higher TGF-ß1 levels (p = 0.012) than other haplotypes. Patients with -924 AA genotype showed higher frequency of anti-dsDNA (p = 0.012) and anti-U1RNP (p = 0.036). The A/C haplotype had higher SLEDAI score [OR: 1.119, CI 95%(1.015-1.234), p = 0.024] and ACAC haplotype higher frequency of anti-dsDNA [OR: 3.026, CI 95%(1.062-8.624), p = 0.038], anti-U1RNP [OR: 5.649, CI 95%(1.199-26.610), p = 0.029] and nephritis [OR: 2.501, CI 95%(1.004-6.229), p = 0.049]. Our data demonstrate that the G/C haplotype provides protection for SLE. While the presence of allele A of both variants could favor autoimmunity, disease activity, and LN.

Beneficial effects of fish oil and cranberry juice on disease activity and inflammatory biomarkers in people with rheumatoid arthritis.

OBJECTIVES: We sought to determine whether cranberry juice consumption would ameliorate laboratory and clinical measurements of disease activity in people with rheumatoid arthritis receiving fish oil supplementation. METHODS: A prospective study was performed with 62 people with rheumatoid arthritis. We analyzed C-reactive protein modification of the Disease Activity Score-28 (DAS28-CRP) and inflammatory markers. The first group was assigned to eat their typical diet, a second group was asked to consume 3 g of fish oil ω-3 fatty acids daily, and a third group received both 3 g of fish oil n-3 fatty acids and 500 mL of reduced-calorie cranberry juice daily. RESULTS: Compared with baseline values, the group receiving both fish oil and cranberry juice showed reductions in erythrocyte sedimentation rate (P = 0.033), C-reactive protein (P = 0.002), DAS28-CRP (P = 0.001), adiponectin (P = 0.021), and interleukin-6 levels (P = 0.045), whereas the fish oil group showed decreased DAS28-CRP (P = 0.0261) and adiponectin (P = 0.0239). Differences across treatments showed that the group receiving both fish oil and cranberry experienced reductions (P < 0.05) in erythrocyte sedimentation rate and C-reactive protein compared to the control group and the group treated with fish oil alone, and a reduction in DAS28-CRP was verified when the fish oil and cranberry group was compared to the control group. CONCLUSIONS: The ingestion of cranberry juice adds beneficial effects to fish oil supplementation, decreasing disease activity and inflammatory biomarkers in people with rheumatoid arthritis.

Low Plasmatic 25-hydroxyvitamin D at Diagnosis is Associated with Axillary Invasion, Chemoresistance and Metastasis in Women with Breast Cancer.

PURPOSE: In this study, we investigated the circulating levels of 25-hydroxyvitamin D (25[OH]D) in Brazilian women with breast cancer in samples collected at diagnosis, and correlated these with clinicopathological parameters relevant to disease prognosis. METHODS: This study involved 147 women diagnosed with infiltrative ductal carcinoma whose peripheral blood samples were collected, to have 25(OH)D levels measured in plasma. RESULTS: Our findings indicated that circulating 25(OH)D levels at diagnosis were insufficient in patients with breast cancer. Further, 25(OH)D reduced plasmatic levels at diagnosis correlated significantly with poor prognosis parameters, including axillar positivity, chemoresistance and metastasis. Patients bearing triple-negative tumors also presented reduced 25(OH)D in plasma when compared to those who carried Luminal tumors. Our data suggest relevant correlations when 25(OH)D is reduced in plasma at diagnosis, such as advanced disease with axillar positivity, chemoresistance with advanced disease, early age at diagnosis with high histological grade and dead with axilla positivity. CONCLUSIONS: Altogether, our findings reinforce that 25(OH)D reduction can be a plausible marker of disease prognosis in breast cancer.

Thiol Groups as a Biomarker for the Diagnosis and Prognosis of Prostate Cancer.

Oxidative stress (OS) is associated with the onset of prostate cancer (PCa). The aims of this study are to examine whether OS biomarkers may be employed as external validating criteria for the diagnosis PCa. This case-control study recruited 204 subjects, 73 patients with PCa, 67 patients with benign prostate hyperplasia (BPH), and 64 healthy controls (HC) and assayed plasma prostate-specific antigen (PSA), protein thiol (-SH) groups, lipid hydroperoxides, carbonyl proteins (PCB), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant parameter (TRAP). -SH groups were significantly and inversely associated with PSA levels. PCa was characterized by lowered -SH groups and red blood cell TRAP levels, and higher PSA, AOPP and PCB levels as compared with BPH and HC. Support vector machine with 10-fold cross-validation showed that PSA values together with -SH groups, PCB and AOPP yielded a cross-validation accuracy of 96.34% for the differentiation of PCa from BPH and HC. The area under the ROC curve using PSA and -SH differentiating PCa from BPH and controls was 0.945. Moreover, lowered -SH, but not PSA, are associated with PCa metastasis and progression. Inflammatory biomarkers were not associated with PCa or BPH. PCa, its progression and metastatic PCa are characterized by lowered antioxidant defenses, especially lowered thiol groups, and increased oxidative stress toxicity, suggesting that these processes play a key role in the pathophysiology of PCa. An algorithm based on -SH and PSA values may be used to differentiate patients with PCa from those with BPH and controls.

Correction to: Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis.

The original version of this article unfortunately contained a mistake. Camila Cataldi de Alcantara was not listed among the authors. The corrected author group should be.

Influence of treatments on cell adhesion molecules in patients with systemic lupus erythematosus and rheumatoid arthritis: a review.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are autoimmune diseases characterized by changes in cell adhesion molecules (CAMs). OBJECTIVE: To review the influence of the main drugs used in the treatment of SLE and RA on CAM levels. METHODS: A bibliographic search was performed using electronic databases. The research included human studies, in vivo or in vitro, with an experimental or observational design, and with no limit of publication date or number of subjects. Animal studies and non-standard treatments were not considered. RESULTS: We included 21 studies, 3 on SLE and 18 on RA with monotherapy or combined trials. The most used drugs were cyclophosphamide (CY, in 2 studies) and methylprednisolone pulse (pMP, n = 2) in SLE; and methotrexate (MTX, n = 9) and infliximab (IFX, n = 4) in RA. In addition, the most frequently examined CAMs to predict response to treatment were vascular cell adhesion molecule-1 (VCAM-1, n = 2) in SLE, and intercellular adhesion molecule-1 (ICAM-1, n = 12), VCAM-1 (n = 12), and E-selectin (n = 14) in RA. After treatment, CAM levels were decreased in SLE and RA patients with active disease. CONCLUSIONS: It is concluded that the CAM biomarkers may reflect disease activity and the response to treatment in SLE and RA patients.

Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis.

The objective of this study is to delineate the cellular adhesion molecule (CAM) profile and plasminogen activator inhibitor type 1 (PAI-1), and their association with metabolic syndrome (MetS) and carbohydrate metabolism biomarkers in psoriasis patients with mild and moderate severity. Sixty-seven patients with psoriasis as well as 102 healthy subjects were recruited. Insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), but not glucose, were significantly higher in psoriasis than in controls. Psoriasis was characterized by increased plasma levels of platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PAI-1 as compared with controls. Psoriasis diagnosis could explain 59.0% of CAM and PAI-1 variance, with a particularly strong impact on E-selectin (45.6%), VCAM-1 (32.7%), and PAI-1 (24.8%). Subjects with MetS showed significantly higher E-selectin and PAI-1 than those without MetS. Using VCAM-1, E-selectin, PAI-1 (all positively), and P-selectin (inversely) in a binary regression equation, it was found that 87.6% of all patients were correctly classified with a sensitivity of 92.5% and a specificity of 84.3%. CAM and PAI-1 were correlated with carbohydrate metabolism biomarkers (glucose, insulin, and HOMA-IR). In conclusion, CAM levels are associated with psoriasis diagnosis and MetS may influence E-selectin and PAI-1 concentrations. More studies are needed to verify the causality among these factors, as well as their relation to the different degrees of disease severity.

TNF-ß +252 A>G (rs909253) polymorphism is independently associated with presence of autoantibodies in rheumatoid arthritis patients.

The TNF-ß +252 A>G (rs909253) polymorphism has been associated with a risk of development of rheumatoid arthritis (RA) and could influence plasma tumor necrosis factor alpha (TNF-α) levels. The aim of the present study was to evaluate the association between the TNF-ß +252 A>G polymorphism with plasma TNF-α levels, the presence of autoantibodies, and the susceptibility for RA. This cross-sectional study included 261 patients with RA and 292 controls. The polymorphism was studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Soluble TNF-α and receptors swere measured by multiplex assay. Rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) were measured using immunoassay. No differences were observed in allele frequency and genotype distribution among patients and controls. The presence of RF (p = 0.020) and anti-CCP (p = 0.001) increased 4.23-fold and 8.13-fold, respectively, in patients with B1 allele (B1/B2 + B1/B1 genotypes) independently of demographic, clinical, and inflammatory markers. Among patients with B1/B2 + B1/B1 genotypes, higher TNF-α levels were associated with positive RF (p = 0.040), anti-CCP (p = 0.011), or both (p = 0.038). In patients carrying B1 allele, the increased sTNFR1 together with RF or anti-CCP or both explained about 39.0% the variations in TNF-α level. However, in B2/B2 genotype, the presence of those autoantibodies was not associated with TNF-α level. Our findings indicate that the TNF-ß +252 A>G polymorphism was not associated with RA susceptibility and TNF-α plasma levels. However, B1 allele was associated with the presence of autoantibodies. In addition, interaction between the presence of B1 allele and autoantibodies was associated with the increase of plasma TNF-α level in RA patients.

Proinflammatory and anti-inflammatory cytokine profiles in psoriasis: use as laboratory biomarkers and disease predictors.

OBJECTIVE: The objectives of this study were to delineate the pro and anti-inflammatory cytokine profiles of psoriasis and cytokine profile models that externally validate the diagnosis. SUBJECTS AND METHODS: This study recruited 70 patients with psoriasis and 76 healthy controls. Cytokine profiles were evaluated, including pro-inflammatory M1 (IL-1 + IL-6 + TNF-α), Th1 (IL-2 + IL-12 + IFN-γ), Th17 (IL-6 + IL-17), and immune-inflammatory response system (IRS = M1 + Th1 + Th17) profiles. Moreover, the anti-inflammatory potential included Th2 (IL-4), Th2 + T regulatory (Th2 + Treg, namely IL-4 + IL-10 + TGF-ß), anti-inflammatory (Th2 + Treg + adiponectin), and the pro-inflammatory/anti-inflammatory index. RESULTS: There was a highly significant association between psoriasis and cytokine levels with an effect size of 0.829 and a particularly strong impact on IL-2 (0.463), IL-12 (0.451), IL-10 (0.532) and adiponectin (0.401). TGF-ß and adiponectin were significantly lower while all other cytokines (except IFN-γ) were significantly higher in psoriasis than in controls. In addition, M1, Th1, Th17, Th2 + Treg, and IRS/Anti-inflammatory index were significantly higher in psoriasis patients than in controls. The IRS index, Th2 + Treg, and adiponectin predicted psoriasis with 97.1% sensitivity and 94% specificity. CONCLUSION: In conclusion, psoriasis is characterized by increased M1, Th1, Th2 and Th17 profiles together with lowered TGF-ß and adiponectin. In addition, we propose a model based on a higher IRS and Th2 + Treg index coupled with lower adiponectin values, which may be used to externally validate the diagnosis of psoriasis. The most important single biomarker of psoriasis is adiponectin. Because the latter may play a role in the modulation of the chronic inflammatory response in psoriasis, adiponectin could be a new drug target to treat psoriasis.

Trace Elements Associated with Systemic Lupus Erythematosus and Insulin Resistance.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of multifactorial origin. Studies have shown that trace elements such as zinc and copper may help maintain optimum function of the immune system and metabolism, while toxic metals such as lead may increase systemic autoimmunity. The current study aimed to assess the relationship between serum concentration of lithium (Li), vanadium (V), copper (Cu), zinc (Zn), molybdenum (Mo), cadmium (Cd), and lead (Pb) and SLE diagnosis, disease activity measured by SLE disease activity index (SLEDAI) and insulin resistance (IR). This case-control, cross-sectional study included 225 patients, 120 healthy controls, and 105 SLE patients. Serum concentration of Li, V, Cu, Zn, Mo, Cd, and Pb was measured. Serum concentrations of V (p < 0.001), Zn (p < 0.001), and Pb (p < 0.001) were lower and Mo (p < 0.001) and Li (p < 0.001) were higher in patients with SLE compared to healthy controls. SLE diagnosis was associated with higher serum Li (p < 0.001) concentration and lower V (p < 0.001), Zn (p = 0.003), and Pb (p = 0.020). Toxic metals and trace elements were not associated with disease activity. Levels of Cd were higher in patients with IR (p = 0.042). There was no significant association between IR and the other metals. The results indicate that SLE patients have different profiles of trace elements and toxic metals compared to healthy controls. While some toxic metals and trace elements were found to be associated with SLE diagnosis, they had no effect on disease activity and IR.

Cranberry juice decreases disease activity in women with rheumatoid arthritis.

OBJECTIVES: Studies have shown that cranberry (Vaccinium macrocarpon) has antiinflammatory and antioxidant effects; however, to our knowledge, the effects of cranberry juice consumption have not been studied in patients with rheumatoid arthritis (RA). The aim of this study was to verify the effect of cranberry juice consumption on several inflammatory biomarkers and on the disease activity of patients with RA. METHODS: A prospective study was conducted with 41 women diagnosed with RA. The disease activity measured by Disease Activity Score 28 (DAS28) and anticyclic citrullinated peptide (anti-CCP) antibodies, and several inflammatory and biochemical biomarkers were analyzed. The control group (n = 18) maintained their usual diet. The cranberry group (n = 23) consumed 500 mL/d of low-calorie cranberry juice. RESULTS: Regarding the baseline values, the cranberry group presented a decrease in the values of DAS28 (P = 0.048) and anti-CCP (P = 0.034) after 90 d of treatment, whereas changes in inflammatory biomarkers were not found. CONCLUSION: The present study indicated that cranberry juice decreases disease activity and therefore has beneficial effects for RA patients, although larger and long-term studies are needed to definitively probe this effect and to clarify the mechanisms involved.

Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in patients with rheumatoid arthritis.

BACKGROUND: Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood. OBJECTIVE: To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RA patients. METHODS: A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date. RESULTS: Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage. CONCLUSIONS: The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA.

Effect of Bifidobacterium lactis HN019 on inflammatory markers and oxidative stress in subjects with and without the metabolic syndrome.

Beneficial effects of probiotics have been reported on body weight, lipid and carbohydrate metabolism, inflammatory state and oxidative stress in healthy subjects and in many metabolic and inflammatory diseases. The aim of this study was to evaluate the effects of Bifidobacterium lactis HN019 on inflammatory state and nitro-oxidative stress in patients with and without the metabolic syndrome (MetS). The usual diets of the thirty-three subjects were supplemented with probiotic milk for 90 d. Inflammatory markers and oxidative measurements were performed. In relation to the baseline values, subjects in both groups showed a decrease in homocysteine (P=0·02 and P=0·03, respectively), hydroperoxides (P=0·02 and P=0·01, respectively) and IL-6 levels (P=0·02). Increases in adiponectin (P=0·04) and nitric oxide metabolites (NOx, P=0·001) levels were only seen in the group with the MetS in relation to the baseline values, whereas only the individuals without the MetS had increases in total radical-trapping antioxidant parameter levels (P=0·002). In conclusion, B. lactis HN019 have several beneficial effects on inflammatory and oxidative biomarkers in healthy subjects and the MetS patients. Patients with the MetS showed a specific improvement in adiponectin and NOx levels, whereas a specific favourable effect was shown in the antioxidant defenses in healthy subjects. If the results obtained in the present study are confirmed, supplementation of fermented milk with probiotics in healthy subjects and patients with the MetS must be further discussed.

Cell adhesion molecules and plasminogen activator inhibitor type-1 (PAI-1) in patients with rheumatoid arthritis: influence of metabolic syndrome.

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.

Metabolic syndrome components are associated with oxidative stress in overweight and obese patients.

OBJECTIVE: The aim of this study is to evaluate the influence of the body mass index (BMI) and the metabolic syndrome (MetS) parameters on oxidative and nitrosative stress in overweight and obese subjects. SUBJECTS AND METHODS: Individuals were divided into three groups: the control group (G1, n = 131) with a BMI between 20 and 24.9 kg/m2, the overweight group (G2, n = 120) with a BMI between 25 and 29.9 kg/m2 and the obese group (G3, n = 79) with a BMI ≥ 30 kg/m2. RESULTS: G3 presented higher advanced oxidation protein products (AOPPs) in relation to G1 and G2 (p = 0.001 and p = 0.011, respectively) whereas G2 and G3 had lower levels of nitric oxide (NO) (p = 0.009 and p = 0.048, respectively) compared to G1. Adjusted for the presence of MetS to evaluate its influence, the levels of AOPPs did not differ between the groups, whereas NO remained significantly lower. Data adjusted by the BMI showed that subjects with higher triacylglycerol levels had higher AOPPs (p = 0.001) and decreased total radical-trapping antioxidant parameter/uric Acid (p = 0.036). Subjects with lower high-density lipoprotein (HDL) levels and patients with higher blood pressure showed increased AOPPs (p = 0.001 and p = 0.034, respectively) and lower NO levels (p = 0.017 and p = 0.043, respectively). Subjects who presented insulin resistance had higher AOPPs (p = 0.024). CONCLUSIONS: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects.

Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis.

The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 µmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p < 0.001), tumor necrosis factor alpha (TNF-α, p < 0.001), TNF receptor 1 (TNFR1, p = 0.038), TNF receptor 2 (TNFR2, p < 0.001), and lower levels of PECAM (p = 0.001), ICAM (p < 0.001) and VCAM (p = 0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p < 0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.

Metabolic syndrome components are associated with oxidative stress in overweight and obese patients

ABSTRACT Objective: The aim of this study is to evaluate the influence of the body mass index (BMI) and the metabolic syndrome (MetS) parameters on oxidative and nitrosative stress in overweight and obese subjects. Subjects and methods: Individuals were divided into three groups: the control group (G1, n = 131) with a BMI between 20 and 24.9 kg/m2, the overweight group (G2, n = 120) with a BMI between 25 and 29.9 kg/m2 and the obese group (G3, n = 79) with a BMI ≥ 30 kg/m2. Results: G3 presented higher advanced oxidation protein products (AOPPs) in relation to G1 and G2 (p = 0.001 and p = 0.011, respectively) whereas G2 and G3 had lower levels of nitric oxide (NO) (p = 0.009 and p = 0.048, respectively) compared to G1. Adjusted for the presence of MetS to evaluate its influence, the levels of AOPPs did not differ between the groups, whereas NO remained significantly lower. Data adjusted by the BMI showed that subjects with higher triacylglycerol levels had higher AOPPs (p = 0.001) and decreased total radical-trapping antioxidant parameter/uric Acid (p = 0.036). Subjects with lower high-density lipoprotein (HDL) levels and patients with higher blood pressure showed increased AOPPs (p = 0.001 and p = 0.034, respectively) and lower NO levels (p = 0.017 and p = 0.043, respectively). Subjects who presented insulin resistance had higher AOPPs (p = 0.024). Conclusions: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects.

Metabolic syndrome and the decreased levels of uric acid by leflunomide favor redox imbalance in patients with rheumatoid arthritis.

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.

Increased lipid and protein oxidation and lowered anti-oxidant defenses in systemic lupus erythematosus are associated with severity of illness, autoimmunity, increased adhesion molecules, and Th1 and Th17 immune shift.

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.