Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

Pathological and behavioral risk factors for higher serum c-reactive protein concentrations in free-living adults - A Brazilian community-based study

Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1;<3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO2max, serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet. © 2012 Springer Science+Business Media, LLC.

Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women.

Silibinin is a polyphenolic plant flavonoid with anti-inflammatory properties. The present study investigated the effect of silibinin on oxidative metabolism and cytokine production - tumor necrosis factor-alpha (TNF-α), interleukin (IL)12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-10, and transforming growth factor beta (TGF-β1) - by peripheral blood monocytes (PBM) from preeclamptic pregnant women. It is a case-controlled study involving women with preeclampsia (PE, n = 30) compared with normotensive pregnant (NT, n = 30) and with non-pregnant (NP, n = 30) women. Monocytes were obtained and cultured with or without silibinin (5 μM or 50 μM) for 18 h. Superoxide anion (O2-) and hydrogen peroxide (H2O2) release were determined by specific assays, and cytokine levels were determined by immunoenzymatic assays (ELISA). Monocytes from preeclamptic women cultured without stimulus released higher levels of O22, H2O2 and TNF-α, and lower levels of IL-10 and TGF-β1 than did monocytes from NT and NP women. Treatment in vitro with silibinin significantly inhibited spontaneous O2- and H2O2 release and TNF-α production by monocytes from preeclamptic women. The main effect of silibinin was obtained at 50 μM concentration. Thus, silibinin exerts anti-oxidative and anti-inflammatory effects on monocytes from preeclamptic pregnant women by inhibiting the in vitro endogenous release of reactive oxygen species and TNF-α production.

Manifestações clínicas, bioquímicas, ultrassonográficas e metabólicas da síndrome dos ovários policísticos em adolescentes

PURPOSE: To evaluate the clinical, ultrasonographic, biochemical and metabolic alterations of adolescents with polycystic ovary syndrome (PCOS). METHODS: Retrospective observational study conducted on 44 adolescents aged 12 to 19 years, diagnosed with PCOS according to the Rotterdam Consensus. Metabolic changes were assessed according to the recommendations of the International Diabetes Federation, considering: waist circumference (WC) ≥90th percentile (10-15 years of age) or >80 cm (age >16 years), fasting glucose >100 mg/dL, triglycerides >150 mg/dL, HDL <40 mg/dL, and blood pressure ≥Hg 130/85 mm. RESULTS: Mean age was 16.7±2.2 years and age at menarche was 11.8±1.4 years. The menstrual irregularity most frequently observed was amenorrhea (72.7%) followed by oligomenorrhea (27.3%); hirsutism was observed in 86.4% and acne in 56.8%. Polycystic ovaries were observed by ultrasound only in 27.3%. Mean BMI was 30.3±6.6 kg/m2. According to BMI, 52.3% of adolescents were obese, 13.6% were overweight and 6.8% had a healthy weight. Increased waist circumference (63.6%, 28/44) and the reduction of HDL-C (34.1%, 15/44) were the metabolic changes most frequently observed. Increased triglycerides were observed in 27.3% (12/44) and increased blood pressure and impaired fasting glucose were found in 9.1% (4/44) and 4.5% (2/44) of cases, respectively. Acanthosis nigricans was observed in 52.3% and insulin resistance in 62.8% of the adolescents with PCOS. Metabolic syndrome was identified in six children (13.6%), all of them obese or overweight. CONCLUSION: In the adolescents with PCOS studied here, menstrual irregularity and hirsutism were the most common clinical manifestations, while the sonographic findings consistent with polycystic ovaries were less prevalent. Obesity associated with insulin resistance predisposes these adolescents to a higher frequency of metabolic disorders.

Energy and fat intake are not associated with abdominal adiposity

Background and objective: Central or abdominal obesity (AA) is a highly prevalent determinant of the metabolic syndrome and its control requires intervention strategies. This study investigated the risk factors associated with the presence of AA in hospitalized individuals. Patients and methods: A total of 1626patients were studied. The investigated risk factors possibly associated with AA were gender, age, body mass index (BMI), habitual energy intake (HEI) and fat intake (FI). AA was determined by waist circumference (WC) and waist-to-hip ratio (WHR). The chi2, Mann-Whitney and Kruskal-Wallis tests were used to compare the data and univariate and multiple logistic regressions were used to identify the predictive factors of AA. Results: Women were at higher risk of developing AA than men (P. <. 0.0001). The HEI and FI of individuals with and without AA and of women and men were not significantly different. According to multivariate analysis, HEI was not a predictive factor of AA, contrary to gender and age. The risk factors for AA, determined by WC, were gender (OR. = 6.8; CI. = 5.3-8.7) and age (OR. = 1.0; CI. = 1.0-1.0). Women were six times more likely to develop AA than men. Conclusions: Evidence of an association between AA and HEI or FI was not found, but gender and age were associated with AA. © 2013 Elsevier Masson SAS.

Different tools for estimating cardiovascular risk in Brazilian postmenopausal women

Objective: To compare estimation of cardiovascular risk using the Framinghan Risk Score (FRS) and the presence of the metabolic syndrome (MetS) in postmenopausal women to prevent primary cardiovascular disease (CVD). Methods: This cross-sectional study included 497 Brazilian women (aged 45 years and amenorrhea >12months). Cardiovascular risk was calculated using the FRS that includes age, total cholesterol, HDL, systolic blood pressure and smoking status. Women showing three or more of the following criteria were diagnosed with MetS: waist circumference (WC) >88cm, blood pressure 130/85mmHg, triglycerides 150mg/dl, HDL<50mg/dl and glucose 100mg/dl. For statistical analysis, the Chi-square, Fisher's exact, and logistic regression (odds ratio-OR) were used. Results: The mean age was 55.3±7.0 years and time since menopause 7.2±5.9 years. Based on FRS, 72.4% of women were classified as low-risk, 16.5% moderate risk and 11.1% a high-risk. MetS was identified in 40% of the women, and 46.2% were considered of moderate risk for CVD, while 84.9% of those without MetS were classified as low-risk (p<0.001). The risk for CVD increased significantly with age at menopause (OR1.10; 95% CI, 1.04-1.17), time since menopause (OR1.13; 95% CI, 1.08-1.18), elevated triglycerides (OR1.03; 95% CI, 1.0-1.10) and presence of MetS (OR1.72; 95% CI 1.48-1.84). Conclusions: By using only FRS to estimate cardiovascular risk, a substantial number of postmenopausal women showing evidence of MetS were not identified, even though women with MetS are at higher risk of CVD. © 2013 Informa UK Ltd.

Efeitos do treinamento concorrente sobre parâmetros da síndrome metabólica em adolescentes obesos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalência e tratamento dos fatores de risco da obesidade e Síndrome Metabólica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Proposta de modelo experimental para o estudo da síndrome metabólica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exercício físico, dieta rica em frutose e marcadores da síndrome metabólica em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Marcadores da síndrome metabólica e da capacidade aeróbia de ratos (Rattus Norvegicus Albinus, Wistar) em diferentes idades: efeito do exercício

Pós-graduação em Ciências da Motricidade - IBRC

Caracterização do modelo B6D2F1 para obesidade, diabetes e síndrome metabólica e sua potencialidade para terapia celular em lesão aguda

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Níveis séricos de vitamina D associados com indicadores da síndrome metabólica na população brasileira

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Avaliação do estado inflamatório em ilhotas de Langerhans de camundongos portadores do tumor sólido de Ehrlich

Pós-graduação em Biologia Geral e Aplicada - IBB

Prevalência de síndrome metabólica em nipo-brasileiros de acordo com diferentes critérios de definição

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)