Impact of vitamin D supplementation on modulating heat-shock proteins in postmenopausal women: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of this study was to examine the effect of vitamin D (VitD) supplementation on serum heat-shock proteins (HSP) in postmenopausal women (PW). METHODS: In this double-blind, placebo-controlled trial, 160 PW aged 45 to 65 years with amenorrhea 12 months or more were randomized into two groups: 80 PW in VitD group (oral supplementation with 1,000 IU VitD 3 /d) or 80 PW in placebo group. The PW were assessed at baseline and after 10 months of intervention. Plasma concentrations of 25-hydroxyVitD (25[OH]D) were measured by high-performance liquid chromatography. HSP27/pS78/pS82, HSP27/total, HSP60, HSP70/72, and HSP90α levels were assessed in serum using a multiplexed bead immunoassay. RESULTS: HSP27 (pS78/pS82 [ P < 0.035] and total [ P < 0.001]) levels increased in the supplemented group when compared with the control group. There was no effect of VitD supplementation on HSP60, HSP70/72, and HSP90α levels. CONCLUSIONS: Vitamin D supplementation increases serum HSP27 level in PW.

Association of altered serum glucose and lipid profiles with headaches in young women: clinical, cross-sectional study / Associação de perfis séricos glicêmicos e lipídicos alterados com cefaleias em mulheres jovens: estudo clínico transversal

Introduction: Headaches, including migraines and tension headaches, affect millions of people globally. Migraines are the most common neurological disorder, with around 14.4% of the world's population affected. It is suggested that dysregulation of biochemical markers and individual metabolic differences may contribute to headaches. Objective: We evaluated the frequency of headaches or migraines with changes in lipid, glucose and vitamin D serum levels in young women. Methods: Clinical, cross-sectional study with 139 young women, aged at least 18 years, based on the third edition of the International Classification of Headache Disorders (ICHD-3). The individuals were divided into two groups: one without headache and another with headache. Anthropometric analyzes (BMI, WC, BP and DBP) and blood samples were collected for analysis of vitamin D, glycemia and lipid profile. Results: Mean age was 22 (±4.6) years. We observed associations between headache and the following factors: high glucose levels (97 mg/dL, p=0.028), total cholesterol (180.4 mg/dL, p=0.002), HDL (44.2 mg/dL, p=0.017), and LDL (121.6 mg/dL, p=0.005). Longer duration of headache attacks was associated with increased levels of glucose (97.9 mg/dL, p=0.028), total cholesterol (186.8 mg/dL, p=0.05), diastolic blood pressure (74 mmHg, p=0.038), and BMI (24.6 kg/m2, p=0.024). High glucose levels were found to be directly related to the presence of migraine, particularly those with aura (105 mg/dL, p=0.034). However, there was no significant difference in vitamin D levels (p=0.640). Conclusion: Elevated levels of blood glucose and total plasma cholesterol and its fractions seems to be associated can increase with bouts of headache attacks, especially migraine, prolonging the duration of pain.

Introdução: Dores de cabeça, incluindo enxaquecas e dores de cabeça tensionais, afetam milhões de pessoas em todo o mundo. As enxaquecas são o distúrbio neurológico mais comum, afetando cerca de 14,4% da população mundial. Sugere-se que a desregulação dos marcadores bioquímicos e as diferenças metabólicas individuais possam contribuir para as dores de cabeça. Objetivo: Avaliamos a frequência de dores de cabeça ou enxaquecas com alterações nos níveis séricos de lipídios, glicose e vitamina D em mulheres jovens. Métodos: Estudo clínico, transversal, com 139 mulheres jovens, com idade mínima de 18 anos, baseado na terceira edição da Classificação Internacional de Cefaleias (ICHD-3). Os indivíduos foram divididos em dois grupos: um sem cefaleia e outro com cefaleia. Foram coletadas análises antropométricas (IMC, CC, PA e PAD) e amostras de sangue para análise de vitamina D, glicemia e perfil lipídico. Resultados: A média de idade foi de 22 (±4,6) anos. Observamos associações entre cefaleia e os seguintes fatores: níveis elevados de glicose (97 mg/dL, p=0,028), colesterol total (180,4 mg/dL, p=0,002), HDL (44,2 mg/dL, p=0,017) e LDL (121,6 mg/dL, p=0,005). A maior duração das crises de cefaleia foi associada ao aumento dos níveis de glicose (97,9 mg/dL, p=0,028), colesterol total (186,8 mg/dL, p=0,05), pressão arterial diastólica (74 mmHg, p=0,038) e IMC (24,6kg/m2, p=0,024). Verificou-se que níveis elevados de glicose estão diretamente relacionados à presença de enxaqueca, principalmente naqueles com aura (105 mg/dL, p=0,034). Entretanto, não houve diferença significativa nos níveis de vitamina D (p=0,640). Conclusão: Níveis elevados de glicose no sangue e colesterol plasmático total e suas frações parecem estar associados e podem aumentar com crises de dor de cabeça, especialmente enxaqueca, prolongando a duração da dor.

Interleukin-15 are associated with insulin resistance in postmenopausal women with metabolic syndrome.

OBJECTIVE: To determine if higher levels of circulating interleukin (IL)-15 are positively associated with improvement in insulin resistance in postmenopausal women (PW) with metabolic syndrome (MS). METHODS: According to the median value of IL-15 at baseline, PW older than or equal to 45 years were divided into two groups: higher (n = 43) and lower (n = 42) IL-15. There was a 9-month follow-up period with clinical assessments at baseline and at 9 months (criteria of metabolic syndrome, body fat, and insulin resistance). Insulin resistance (IR) was calculated according to the Homeostasis Model Assessment-estimated insulin resistance (HOMA-IR). For IL-1ß, IL-6, IL-10, IL-13, IL-33, IL-15, and TNF-α was determined using immunoassay Magnetic Bead Panel. RESULTS: There was an interaction between the time and group only for insulin (p = .008) and HOMA-IR (p = .024). After adjusting for confounding variables (clinical and ILs), the HOMA-IR (p = .006) and insulin (p = .003) were lower in the higher-IL-15 group [HOMA-IR: 2.2 (95% CI: 1.9-2.5) and insulin: 9.1 µIU/mL (95% CI: 7.9-10.3)] when compared to the lower-IL-15 group [HOMA-IR: 3.1 (95% CI: 2.6-3.6) and insulin: 12.9 (95% CI: 11.1-14.9)] after 9 months of follow-up. CONCLUSION: Higher levels of circulating IL-15 are positively associated with improvements in IR in PW with MS.

Higher levels of circulating interleukin (IL)-15 are positively associated with improvement in insulin resistance (IR) in postmenopausal women (PW) with metabolic syndrome (MS).This relationship is independent of levels of other cytokines (IL-1ß, IL-6, IL-10, IL-13, IL-33, and TNF-α).The levels of circulating IL-15 may be used as a prognostic biomarker for IR in PW with MS.The study opens the door for future studies on IL-15's role in treating IR among PW with MS.

Heterogeneity in resistance training-induced muscle strength responses is associated with training frequency and insulin resistance in postmenopausal women.

BACKGROUND: In older adults, muscle strength (MS), a key component of sarcopenia, is essential to maintaining independence and physical capacity. The rate of MS decline typically accelerates during the menopausal transition. Although MS has been shown to increase with resistance training (RT), the response to training is quite heterogeneous. Thus, if contributing factors to RT non-responsiveness to MS gains are identified, it may be possible to develop more effective and personalized ways to improve MS or identify individuals who may benefit from RT interventions. This study assessed potential factors that may contribute to MS response heterogeneity in postmenopausal women: training frequency, serum FSH and estrogen levels, adiposity, inflammation marker, and insulin resistance. METHODS: One hundred and thirteen individuals participated in a 16-week program of supervised RT (3 sets, 8-12 repetitions, and 2-3 times/week). A control group (CTL, n = 63 - no performed the RT) was used as the comparator arm. Body composition (skinfold) and blood samples (metabolic and inflammatory indicators and hormones) were measured at baseline. Knee extensor strength (1RM) was measured at baseline, 8 weeks, and 16 weeks. RESULTS: Only the RT group increased 1RM after 8 weeks (RT = 14 ± 12% vs. CTL = 6 ± 15%). Both groups increased 1RM after 16 weeks, with the RT group showing a greater increase than the CTL group (RT = 31 ± 23% vs CTL = 13 ± 25%). After 8 weeks of RT, 41 (36% of total) individuals were considered non-responders (based on control group responses) and 27 (24% of total) individuals after 16 weeks. At week 8, lower RT frequency (2 times/week vs. 3 times/week) was associated with higher odds of being non-responder (3 times, P = 0.048). At week 16, lower RT frequency (13 times, P = 0.009) and higher HOMA-IR (for every unit increase, odds increase by 40%, P = 0.022) were associated with higher odds of being non-responder. Higher QUICKI was associated with lower odds of being non-responder (for every unit increase, odds decrease by 16%, P = 0.039). Moreover, higher RT frequency (17 times, P = 0.028) and higher QUICKI (for every unit increase, odds increase by 41%, P = 0.017) were associated with higher odds of becoming a responder at week 16, being a non-responder at week 8. CONCLUSION: Heterogeneity in RT-induced MS responses is associated with training frequency and insulin resistance in postmenopausal women.

Different cutoff points to diagnose low muscle mass and prediction of osteoporosis in postmenopausal women.

OBJECTIVE: This study aimed to verify which of the different cutoff points of low muscle mass (LMM) based on appendicular lean mass (ALM) is associated with osteoporosis in postmenopausal women (PMW). METHODS: Cross-sectional study. PMW (n = 355) were classified for the presence of osteoporosis (score <-2.5 standard deviations) at the femoral neck and lumbar spine and LMM (three cutoff points: ALM < 15 kg; ALM/height2 [ALM index] <5.67 kg/m2 and ratio between ALM and body mass index [ALMBMI] <0.512). RESULTS: After adjustments for confounding factors, binary logistic regression showed that ALM and ALM index were associated with osteoporosis at the lumbar spine (odds ratio [OR] = 5.3 [95% CI: 2.3-12.5] and OR = 2.5 [95% CI: 1.0-6.2], respectively) and only ALM was associated with osteoporosis at the femoral neck (OR = 16.1 [95% CI: 4.1-62.5]). When women were classified as having osteoporosis in at least one site, only ALM was associated with osteoporosis (OR = 7.7 [95% CI: 3.3-15.6]). There was no association between ALMBMI and osteoporosis. The predictive value of ALM for osteoporosis decreased after BMI or height were included as a covariate in the model. CONCLUSION: Absolute ALM (<15 kg) seems to be the most suitable for predicting osteoporosis based on LMM in PMW.

Heat Shock Protein 60 Antibodies Are Associated With a Risk Factor for Cardiovascular Disease in Bedridden Elderly Patients.

Frailty, in elderly people, represents multiple deficiencies in different organs and is characterized by decreased physiological reserves and greater vulnerability to stressors. Bedridden elderly, with cardiovascular disease (CVD), have a worse prognosis than non-bedridden patients. Heat-shock proteins (HSPs) are molecular chaperones that under physiological conditions facilitate the transport, folding and assembly of proteins. Serum HSP 60-kDa concentrations and their antibodies are increased, in response to non-physiological conditions, suggesting the involvement of HSPs and their antibodies in the development of CVD. The aim of this work was to evaluate heat shock protein 60 and anti-HSP60 antibody levels, associated with a risk factor for cardiovascular disease, in bedridden elderly patients. Clinical, analytical and cross-sectional analyses were performed with 57 elderly (>65 years). HSP60 and anti-HSP60 plasma levels were measured by ELISA. Bivariate analysis using a linear regression model adjusted for risk factors used Framingham Score. Among the 57 elderly, with an average age of 69.89 years, 39% are bedridden; 26% with pre-existing cardiovascular disease and 44% are dyslipidemic. The relationship of risk factors in the Framingham Score was positive for the anti-HSP60 antibody (p = 0.042) measurement. Our data show a positive correlation among the elevation of the Framingham score and the profile of anti-HSP60 antibodies. These results suggest a greater immune activation that is associated with cardiovascular risk and bedridden fragility.

High risk for cardiovascular disease in postmenopausal breast cancer survivors.

OBJECTIVE: Breast cancer patients have a higher mortality risk of cardiovascular disease (CVD) than women from the general population. CVD risk may increase significantly in postmenopausal women with early-stage breast cancer. The aim of this study was to evaluate risk factors for CVD in postmenopausal breast cancer survivors. METHODS: In this cross-sectional study, 96 postmenopausal breast cancer survivors were compared with 192 postmenopausal women. The main group included women with amenorrhea >12 months, aged ≥45 years, with breast cancer, and without established CVD. The control group fulfilled the same criteria, but did not have breast cancer. Groups were matched by age, time since menopause, and body mass index, in a ratio of 1 case to 2 controls (1:2). Women with three or more of the following criteria were diagnosed with metabolic syndrome: waist circumference >88 cm; triglycerides ≥150 mg/dL; high-density lipoprotein cholesterol <50 mg/dL; blood pressure ≥130/85 mm Hg; and glucose ≥100 mg/dL. Immunoassays were used (enzyme-linked immunosorbent assay test) for measurement of plasma heat shock proteins (HSP) 60 and 70 concentrations. Atherosclerotic disease was determined by intima-media thickness (>1 mm) of the carotid arteries and/or the presence of atheromatous plaque assessed by carotid artery ultrasound (scanner duplex). RESULTS: Breast cancer patients had higher HSP60 levels and lower HSP70 levels than controls (P < 0.05). Analysis showed that the odds of developing metabolic syndrome (odds ratio [OR] = 4.21, 95% CI, 2.28-7.76), atheromatous plaque (OR = 2.61, 95% CI, 1.19-5.72), diabetes (OR = 4.42; 95% CI, 1.86-10.49), hypertriglyceridemia (OR = 2.32, 95% CI, 1.33-4.0), and increased waist circumference (OR = 11.22, 95% CI, 4.0-31.65) was significantly higher in women treated for cancer than in women without breast cancer. CONCLUSIONS: Postmenopausal breast cancer survivors had a stronger association with risk factors for cardiovascular disease than postmenopausal women without breast cancer.

Autophagy-related 16-like 1gene polymorphism, risk factors for cardiovascular disease and associated carotid intima-media thickness in postmenopausal women.

BACKGROUND: Early identification of asymptomatic postmenopausal women (PW), who are more predisposed to developing cardiovascular disease (CVD), is an important preventive strategy. Autophagy-related 16-like 1 (ATG16L1) is an autophagy gene known to control host immune responses and is associated with a variety of diseases, including CVD. OBJECTIVE: The aim of the study was to associate the ATG16L1 polymorphism variant with subclinical carotid atherosclerosis in asymptomatic PW. STUDY DESIGN: This cross-sectional study included 210 Brazilian postmenopausal women (age ≥ 45 years with amenorrhea ≥12 months). Clinical, anthropometric and biochemical assessments were performed to evaluate the cardiovascular risk factors. DNA was extracted from buccal cells and the ATG16L1 (T300A) polymorphism was determined by the polymerase chain reaction (PCR). The carotid intima-media thickness and/or the presence of plaques were evaluated by carotid duplex ultrasound. For statistical analysis, the t-test, logistic regression and analysis of covariance (ANCOVA) were used. RESULTS: The presence of the polymorphic allele forATG16L1 (T300A) was found in 77.47% (A/G = 49.87%, G/G = 27.60%). The ATG16L1 (T300A) polymorphism is significantly associated with increased carotid intima-media thickness (IMT) after adjustments of the confounding variables (P < .037). No significant associations were observed between the polymorphism with other risk factors for CVD in PW. CONCLUSION: In postmenopausal women, the ATG16L1 (T300A) polymorphism is significantly associated with increased carotid IMT (marker of atherosclerotic disease) after adjustments of the confounding variables (P < .037). Thus, identifying the ATG16L1 polymorphism is an important strategy for screening asymptomatic PW who are more predisposed to developing CVD.

Isolated vitamin D supplementation improves the immune-inflammatory biomarkers in younger postmenopausal women: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effect of vitamin D (VitD) supplementation on immune-inflammatory biomarkers in younger postmenopausal women. METHODS: In this double-blind, placebo-controlled trial, 160 postmenopausal women aged 50 to 65 years with amenorrhea ≥12 months were randomized into two groups: VitD group, oral supplementation with 1000 IU VitD3/day (n = 80) or placebo group (n = 80). The intervention time was 9 months, and the women were assessed at baseline and endpoint. Serum levels of interleukins (ILs)-1ß, IL-5, IL-6, IL-10, IL-12ρ70, IL-17α, tumor necrosis factor-alpha, and interferon-gamma were determined by immunoassay. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance liquid chromatography. Per-protocol analysis was adopted as the statistical method using a gamma distribution and repeated measures design, followed by Wald's multiple comparisons test. RESULTS: The two groups were similar at baseline in terms of clinical and laboratory parameters. After 9 months, there was a significant increase of 25(OH)D levels in the VitD group (+45.4%, P < 0.001) and a decrease (-18.5%, P = 0.049) in the placebo group. A significant decrease in IL-5, IL-12p70, IL-17α, tumor necrosis factor-alpha, and interferon-gamma levels was observed in the VitD group (P < 0.05). IL-5 and IL-6 levels were significantly lower in the VitD group compared to the placebo group (P < 0.05). There were no significant intervention effects on serum IL-1ß or IL-10 levels in either group (P > 0.05). CONCLUSIONS: In younger postmenopausal women, isolated supplementation with 1000 IU of VitD3 for 9 months was associated with a reduction in proinflammatory biomarkers.

Vitamin D deficiency is associated with metabolic syndrome in postmenopausal women.

OBJECTIVE: To evaluate the association between vitamin D (VD) deficiency and risk factors for metabolic syndrome (MetS) in postmenopausal women. STUDY DESIGN: Observational, cross-sectional cohort study. MAIN OUTCOME MEASURES: In this study, 463 women, aged 45-75 years, with amenorrhea >12months, without VD supplementation or established cardiovascular disease were included. Clinical and anthropometric data were collected. Biochemical parameters, including total cholesterol (TC), HDL, LDL, triglycerides, glucose, insulin and 25-hydroxyvitamin-D [25(OH)D] were measured. Women meeting three or more of the following criteria were diagnosed with MetS: waist circumference >88cm, triglycerides ≥150mg/dL, HDL <50mg/dL, blood pressure ≥130/85mmHg and glucose ≥100mg/dL. Serum 25(OH)D levels were classified as sufficient (≥30ng/mL), insufficient (20-29ng/mL) or deficient (<20ng/mL). ANOVA, chi-square test and logistic regression (odds ratio, OR) were used for statistical analysis. RESULTS: Serum 25(OH)D levels were sufficient in 148 women (32.0%), insufficient in 151 (32.6%) and deficient in 164 (35.4%). Women with low 25(OH)D levels had higher TC, triglycerides, insulin and HOMA-IR levels (p<0.05). MetS was detected in 57.8% (182/315) of women with hypovitaminosis D (insufficient and deficient) and in 39.8% (59/148) of those with sufficient VD​​ (p=0.003). In a multivariate logistic regression analysis, a low 25(OH)D level (<30ng/mL) was significantly associated with MetS (OR1.90, 95%CI=1.26-2.85), high triglyceride levels (OR1.55, 95%CI=1.13-2.35), and low HDL levels (OR1.60, 95%CI=1.19-2.40) (p<0.05) compared with women with sufficient 25(OH)D levels, after adjusting for age, time since menopause, body mass index, smoking and physical exercise. The mean concentration of 25(OH)D decreased with increasing numbers of MetS components (p=0.016). CONCLUSIONS: VD deficiency in postmenopausal women was associated with a higher prevalence of MetS. Women with VD deficiency had a higher risk of MetS, hypertriglyceridemia and low HDL than those with adequate levels.

Effect of resistance training on muscular strength and indicators of abdominal adiposity, metabolic risk, and inflammation in postmenopausal women: controlled and randomized clinical trial of efficacy of training volume.

This study evaluated the effect of resistance training (RT) volume on muscular strength and on indicators of abdominal adiposity, metabolic risk, and inflammation in post-menopausal women (PW). Thirty-two volunteers were randomly allocated into the following three groups: control (CT, no exercise, n = 11), low-volume RT (LV, three sets/exercise, n = 10), and high-volume RT (HV, six sets/exercise, n = 11). The LV and HV groups performed eight exercises at 70 % of one maximal repetition, three times a week, for 16 weeks. Muscular strength and indicators of abdominal adiposity, metabolic risk, and inflammation were measured at baseline and after 16 weeks. No differences were found in baseline measures between the groups. The PW showed excess weight and fat percentage (F%), large waist circumference (WC), high waist-hip ratio (WHR), and hypercholesterolemia and borderline values of glycated hemoglobin (HbA1c%). Following the RT, a similar increase in muscle strength and reduction in F% from baseline were found in both trained groups. In HV, a decrease in total cholesterol, LDL-c, WC, and WHR was noted. Moreover, the HV showed a lower change (delta%) of interleukin-6 (IL-6) when compared to CT (HV = 11.2 %, P 25-75 = -7.6-28.4 % vs. CT = 99.55 %, P 25-75 = 18.5-377.0 %, p = 0.049). In LV, a decrease was noted for HbA1c%. There were positive correlations (delta%) between WHR and IL-6 and between IL-6 and TC. These results suggest that while a low-volume RT improves HbA1c%, F%, and muscular strength, a high-volume RT is necessary to improve indicators of abdominal adiposity and lipid metabolism and also prevent IL-6 increases in PW.

Effect of isolated vitamin D supplementation on the rate of falls and postural balance in postmenopausal women fallers: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of isolated vitamin D supplementation (VITD) on the rate of falls and postural balance in postmenopausal women fallers. METHODS: In this double-blind, placebo-controlled trial, 160 Brazilian younger postmenopausal women were randomized into two groups: VITD group, vitamin D3 supplementation 1,000 IU/day/orally (n = 80) and placebo group (n = 80). Women with amenorrhea at least 12 months, age 50 to 65 years, and a history of falls (previous 12 months) were included. Those with neurological or musculoskeletal disorders, vestibulopathies, drugs use that could affect balance and osteoporosis were excluded. The intervention time was 9 months. Postural balance was assessed by stabilometry (computerized force platform) and investigation on the occurrence/recurrence of falls was performed by interviews. The plasma concentration of 25-hydroxyvitamin D [25(OH)D] was measured by high-performance liquid chromatography. Statistical analysis was achieved by intention-to-treat, using analysis of variance, Student's t test, Tukey test, chi-square, and logistic regression. RESULTS: After 9 months, mean values of 25(OH)D increased from 15.0 ±â€Š7.5 ng/mL to 27.5 ±â€Š10.4 ng/mL (+45.4%) in the VITD group, and decreased from 16.9 ±â€Š6.7 ng/mL to 13.8 ±â€Š6.0 ng/mL (-18.5%) in the placebo group (P < 0.001). The occurrence of falls was higher in the placebo group (+46.3%) with an adjusted risk of 1.95 (95% confidence interval [CI] 1.23-3.08) times more likely to fall and 2.80 (95% CI 1.43-5.50) times higher for recurrent falls compared to the VITD group (P < 0.001). There was reduction in body sway by stabilometry, with lower amplitude of antero-posterior (-35.5%) and latero-lateral (-37.0%) oscillation, only in the VITD group (P < 0.001). CONCLUSIONS: In Brazilian postmenopausal women fallers, isolated vitamin D supplementation for 9 months resulted in a lower incidence of falls and improvement in postural balance.

Influence of sex on cytokines, heat shock protein and oxidative stress markers in response to an acute total body resistance exercise protocol.

BACKGROUND/OBJECTIVE: This study evaluated the influence of sex on changes in cytokines, heat shock proteins (HSPs), and oxidative stress in response to a single bout of total body resistance exercise. METHODS: Sixteen healthy volunteers (8 men and 8 women), active and recreationally trained in resistance exercise, were subjected to a single bout of total body resistance exercise (3 × 8-10 repetition maximum, 10 exercises, rests periods of 90-120 seconds). Serum creatine kinase (CK), interleukin (IL)-6, IL-10, tumor necrosis factor-α, HSP60, HSP70, thiobarbituric acid reactive substance, and reduced glutathione were assessed at pre-protocol, and 1 hour, 4 hours, and 24 hours post-protocol. RESULTS: Both men and women had a similar increase in CK (p < 0.05) activity at 24 hours post-exercise. Significant sex differences were observed for IL-6. In the men, an increase from baseline was noted at 1 hour for IL-6. In women, an increase from baseline was noted at 4 hours only for IL-6. There was a significant correlation between peak IL-6 blood level and CK level at 24 hours only in the women. No significant changes were observed in IL-10, tumor necrosis factor-α, HSP60, HSP70, thiobarbituric acid reactive substance, and reduced glutathione. CONCLUSION: Acute total body resistance exercise altered circulating levels of IL-6 and sex differences existed in the temporal pattern and magnitude of this response.

Evaluation of Toll-Like receptor 2 and 4 RNA expression and the cytokine profile in postmenopausal women with metabolic syndrome.

OBJECTIVE: To evaluate the gene expression of Toll-Like (TLR-2 and TLR-4) receptors and cytokine profile in postmenopausal women with or without metabolic syndrome (MetS). METHODS: In this cross-sectional study, 311 Brazilian women (age≥45 years and amenorrhea≥12 months) were included. Women showing three or more of the following diagnostic criteria were diagnosed as positive for MetS: waist circumference>88 cm, triglycerides≥150 mg/dL, HDL cholesterol<50 mg/dL, blood pressure≥130/85 mmHg, and fasting glucose≥100 mg/dL. The expression of TLR-2 and TLR-4 in peripheral blood was evaluated by RNA extraction and subsequent real time PCR analysis. The cytokine profile, tumor necrosis factor alpha (TNF-α) and interleukins 1ß, 6, and 10, were measured by ELISA. RESULTS: The expression of TLR-2 RNA was demonstrated in 32.5% and TLR-4 in 20.6% of the subjects. There was no association between the expression of TLR-2 and TLR-4 and the presence or absence of MetS (P>0.05). A greater production of IL-6 was associated with TLR-2 and TLR-4 expressions and greater production of TNF-α was associated only with TLR-2 expression (P>0.05). Only the lower quartile of IL-10 was associated with the presence of the MetS (P>0.05). CONCLUSIONS: TLR-2 and TLR-4 expressions were associated with increased pro-inflammatory cytokines, IL-6 and TNF-α, with no association with biomarkers of MetS. The low concentrations of IL-10 may suggest an anti-inflammatory modulation in postmenopausal women with MetS.

Mannose-binding lectin gene polymorphism and risk factors for cardiovascular disease in postmenopausal women.

BACKGROUND: Inflammatory responses may be altered in postmenopausal women and predispose to cardiovascular disease (CVD). Genetic factors can also influence susceptibility to CVD. Mannose-binding lectin (MBL) is a component of the innate immune system and an activator of the complement cascade. We evaluated the association of genetic polymorphism of MBL (MBL2) on risk factors for CVD in postmenopausal women. METHODS: In this cross-sectional study, 311 Brazilian women (age ≥45 years and amenorrhea ≥12 months) were included. EXCLUSION CRITERIA: presence of previous or current CVD, insulin dependent diabetes, chronic kidney disease, autoimmune diseases and cancer. Clinical, anthropometric and biochemical assessments were performed to evaluate the cardiovascular risk factors. DNA was extracted from buccal cell and polymorphisms at codons 54 and 57 in the MBL2 were determined by polymerase chain reaction (PCR). For statistical analysis, the chi-square and logistic regression (odds ratio, OR) were used. RESULTS: The presence of the polymorphic allele for codon 54 was found in 25.8% of women (A/B=22.6%, B/B=3.2%) and for codon 57 in 12.2% (A/C=10.8%, C/C=1.4%). The polymorphism at codon 54 was significantly associated with the presence of hypertension (OR 0.55, 95% CI 0.31-0.99, p=0.044) and insulin resistance assessed by HOMA-IR (OR 0.46, 95% CI 0.24-0.91, p=0.025). No significant associations were observed between the polymorphism at codon 57 with risk factors for CVD. CONCLUSION: In postmenopausal women, the polymorphism at codon 54 of the MBL2 was associated with lower risk for hypertension and insulin resistance that are important risk factors for CVD.

Evaluation of clinical and inflammatory markers of subclinical carotid atherosclerosis in postmenopausal women.

OBJECTIVE: This study aims to evaluate clinical and inflammatory markers of subclinical carotid atherosclerosis (ATS) in asymptomatic postmenopausal women. METHODS: This cross-sectional study included 268 Brazilian women (aged ≥45 y and amenorrhea ≥12 mo). Subclinical ATS was defined as increased carotid intima-media thickness (>1.0 mm) and/or the presence of plaques evaluated by carotid duplex ultrasound. Inflammatory markers included C-reactive protein (CRP), as well as heat shock protein (HSP) 60 and HSP70 and their antibodies. Pearson's correlation and stepwise logistic regression were used for statistical analysis. RESULTS: Among the women studied, 45.9% (123 of 268) had a diagnosis of ATS, and 54.1% (145 of 268) had normal carotid ultrasound scans (controls). Women with ATS were older (56.6 vs 52.5 y), and their time since menopause was longer (6.0 vs 4.0 y). In addition, higher prevalences of metabolic syndrome (39.0% vs 25.5%), hypertension (52.0% vs 30.3%), and diabetes (11.4% vs 4.8%), and elevated circulating levels of CRP and HSP60, were observed in women with ATS compared with controls (P < 0.05). Intima-media thickness was positively correlated with anti-HSP70 antibodies (r = 0.110, P = 0.049) and CRP (r = 0.167, P = 0.009). ATS risk increased with age at menopause (odds ratio [OR], 1.18; 95% CI, 1.10-1.26), time since menopause (OR, 1.12; 95% CI, 1.02-1.14), and glucose of 100 mg/dL or higher (OR, 2.17; 95% CI, 1.12-4.20). Serum HSP70 levels (OR, 0.71; 95% CI, 0.47-0.98) were associated with a lower ATS risk (P < 0.05). CONCLUSIONS: In postmenopausal women, age, menopause status, and hyperglycemia are associated with a higher prevalence of ATS, whereas elevated serum HSP70 is associated with a lower prevalence of ATS.

Efeito do treinamento contrarresistência e isoflavona na densidade mineral óssea em mulheres na pós-menopausa / Effects of isoflavone and counter-resistance training on bone mineral density in postmenopausal women

O estudo teve como objetivo investigar o efeito isolado e combinado do treinamento contrarresistência (TCR) e da suplementação de isoflavona da soja (ISO) sobre a densidade mineral óssea (DMO) e a remodelação óssea em mulheres na pós-menopausa (MPM). Tratou-se de estudo clínico, prospectivo, placebo-controlado, duplo-cego (ISO) e randomizado, envolvendo 80 MPM sedentárias, com idade entre 45-70 anos, randomizadas em quatro grupos (71 completaram nove meses): TCR+ISO (n=15); sem TCR+ISO (n=20); TCR+ placebo (n=18); sem TCR + placebo (n=18). As participantes randomizadas no grupo ISO receberam 100mg/dia/VO (via oral) de isoflavona e as no grupo TCR realizaram sessões supervisionadas de exercícios contrarresistência (mínimo de 2 dias/ semana). Nos momentos inicial e final do estudo, a DMO do colo do fêmur e da coluna lombar foram estimadas pela absortometria radiológica de feixes duplos de energia (DXA) e a força muscular pelo teste de 1-RM. Os valores plasmáticos de telopeptídeos carboxiterminais do colágeno tipo I (CTX), osteocalcina e fator de crescimento semelhante à insulina (IGF-1) foram dosados como marcadores de remodelação óssea. Após 9 meses de intervenção não foram observados efeitos independentes ou aditivos do TCR e ISO sobre a DMO bem como sobre os valores de osteocalcina, CTX e IGF-1 (p>0,05). Houve aumento da força muscular (+ 35,2%) somente nos grupos submetidos ao TCR (p=0,02). Conclui-se que o TCR e ISO não apresentam efeitos combinados ou independentes sobre a DMO do fêmur e da coluna lombar e marcadores da remodelação óssea em MPM após nove meses de intervenção.

This study aimed to investigate the independent and additive effects of counter-resistance training (RT) and soy isoflavone supplement (ISO) on bone mineral density (BMD) and bone turnover in postmenopausal women. This study used a placebo-controlled, double-blinded (soy), randomized two (ISO vs. placebo) x two (RT vs. no RT) design. Eighty sedentary postmenopausal women, aged 45-70 years, were randomly assigned to one of four groups (71 completed a 9-month intervention): RT+ISO (n=15); no RT+ISO (n=20); RT+placebo (n=18); no RT+placebo (n=18). Participants randomized to ISO received 100mg/ day/oral of soy isoflavone; and those to RT attended supervised counter-resistance training sessions at least twice a week. At baseline and 9-month, BMD was estimated by dual-energy X-ray absorptiometry (DXA). Serum levels of C-terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin, and insulin-like growth factor-1 (IGF-1) were measured as bone turnover. ANOVA with time as the repeated measure and test t were used in the statistical analysis. After 9 months of intervention, neither ISO nor RT alone affected BMD at any site or levels of CTX, osteocalcin, and IGF-1 (p>0.05). ISO and RT had no additive effects on BMD and bone turnover. RT groups showed significantly increased muscle strength (+ 35.2%) (p=0.02). We found no additive effects of resistance training and soy isoflavone on bone mineral density or bone turnover in postmenopausal women after 9-months.

Propolis immunomodulatory activity on TLR-2 and TLR-4 expression by chronically stressed mice.

Our group has been investigating the immunomodulatory activity of propolis in stressed mice. In this work, we wish to report the action of propolis in chronically stressed mice, assessing the Toll-like receptor (TLR-2 and TLR-4) expression by spleen cells and corticosterone levels as a stress indicator. Male C57BL/6 mice were divided into four groups: G1 was considered the control; G2 was treated with propolis (200 mg kg(-1)); G3 was submitted to restraint stress for 14 days; and G4 was treated with propolis and immediately submitted to stress. After sacrifice, spleens were removed and TLR-2 and TLR-4 gene expression was analysed. TLR-2 and TLR-4 expression was increased in propolis-treated mice, and propolis administration to stressed mice prevented the inhibition of TLR-2 and TLR-4 expression. No differences were seen in the corticosterone levels among the groups. Propolis exerted an immunomodulatory action in chronically stressed mice, upregulating TLR-2 and TLR-4 mRNA expression, contributing to the recognition of microorganisms and favouring the initial steps of the immune response during stress.

Effects of resistance training and soy isoflavone on body composition in postmenopausal women.

Objective. To investigate the independent and additive effects of resistance training (RT) and soy isoflavone (ISO) on body composition in postmenopausal women (PW). Method. This study used a placebo-controlled, double-blind (soy), randomized (ISO versus placebo) x (RT versus No RT) design. A total of 80 PW, aged 45-70 years, were randomly (71 completed 9-months intervention): RT + ISO (n = 15), No RT + ISO (n = 20), RT + placebo (n = 18), and No RT + placebo (n = 18). ISO received 100 mg a day of isoflavone; and to RT attended supervised resistance training sessions. At baseline and 9-months, fat and muscle mass were estimated by DXA. ANOVA and test t were used. Results. RT groups showed significantly increased muscle strength (35.2%) and muscle mass (1.4%). Exercising attenuated gains in fat trunk and % body fat (P < .05). Significant decreases in muscle mass (-1.8%) and increases in fat mass of the whole-body (1.6%) and trunk (9.7%) was found in no-RT groups (P < .05). In ISO groups, there were no differences in body composition and muscle strength. ISO and RT had no additive effects. Conclusion. In PW: RT improved muscle mass and strength and attenuated gain of fat mass; ISO did not alter body composition and muscle strength; there were no additive effects of RT and ISO.