Association Between Cardiovascular Risk Factors and Stress Hormones With Cognitive Performance in Mexican Adolescents.

Objective: The objective of this study was to determine whether cardiovascular disease (CVD) risk factors and stress hormones are associated with cognitive performance in Mexican adolescents. Methods: This was a cross-sectional study including 139 Mexican adolescents 10-14 years old. Participants were divided into three categories: 0, 1-2, and ≥3 CVD risk factors. These factors included: high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl; waist circumference (WC) ≥90th percentile for age and sex, systolic or diastolic blood pressure ≥90th percentile for age, sex, and height; and triacylglycerols (TGs) ≥110 mg/dl. Low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), total cholesterol, cortisol, and plasma catecholamines were measured as well. Furthermore, attention, memory, and executive functions were evaluated using a validated test for Spanish-speaking individuals (Neuropsi). Results: Adolescents in the three risk categories did not show significant differences in Neuropsi test performance tasks; however, they presented different lipid and plasma norepinephrine concentrations. TG and VLDL-C were inversely associated with memory (r = -0.19, **p < .01). Multivariate regression analysis showed consistently that TG/HDL-C ratio was inversely related to attention-memory general score (standardized ß = -0.99, t = -2.30, p = .023), memory (standardized ß = -0.83, t = -2.08, p = .039), and attention-executive functions (standardized ß = -1.02, t = -2.42, p = .017). Plasma epinephrine levels presented an inverse and weak relation to the attention-executive functions score (standardized ß = -0.18, t = -2.19, p = .030). Conclusions: Cognitive performance is not completely dependent on the accumulation of risk factors, but instead on the combination of strong predictors of CVD like waist to height ratio, TG/HDL-C, and VLDL-C. Plasma norepinephrine and epinephrine have a stronger association with cognition and CVD risk than dopamine and cortisol.

A Novel Model of Dexamethasone-Induced Hypertension: Use in Investigating the Role of Tyrosine Hydroxylase.

Our objective was to study hypertension induced by chronic administration of synthetic glucocorticoid, dexamethasone (DEX), under nonstressful conditions and examine the role of catecholamine biosynthesis. To achieve this, we did the following: 1) used radiotelemetry to record mean arterial pressure (MAP) and heart rate (HR) in freely moving rats, and 2) administered different doses of DEX in drinking water. To evaluate the involvement of tyrosine hydroxylase (TH), the rate-limiting step in catecholamine biosynthesis, we treated rats with the TH inhibitor, α-methyl-para-tyrosine (α-MPT), for 3 days prior to administration of DEX and assessed TH mRNA and protein expression by quantitative real-time polymerase chain reaction and Western blot in the adrenal medulla. We observed a dose-dependent elevation in blood pressure with a DEX dose of 0.3 mg/kg administered for 10 days, significantly increasing MAP by +15.0 ± 1.1 mm Hg, while concomitantly reducing HR. Although this DEX treatment also significantly decreased body weight, pair-fed animals that showed similar decreases in body weight due to lowered food intake were not hypertensive, suggesting that body weight changes may not account for DEX-induced hypertension. Chronic DEX treatment significantly increased the TH mRNA and protein levels in the adrenal medulla, and α-MPT administration not only reduced DEX pressor effects, but also inhibited TH (serine(40)) phosphorylation. Our study thus validates a novel model to study hypertension induced by chronic intake of DEX in freely moving rats not subject to the confounding factors of previous models and establishes its dependence on concomitant activation of peripheral catecholamine biosynthesis.

Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene.

The human tyrosine hydroxylase (hTH) gene has a 42 bp evolutionarily conserved region designated (CR) II at -7.24 kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7 bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH-CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7 bp 5'-TGACTAA at -7243 bp completely abolished the Dex-stimulated Luc activity of hTH-CRII construct. The AP-1 agonist, tetradeconoyl-12,13-phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP-1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid-responsive element in a 7 bp AP-1-like motif in the promoter region at -7.24 kb of the human TH gene.

Asthma control, quality of life, and the role of patient enablement: a cross-sectional observational study.

BACKGROUND: Self-assessment of asthma and a stronger doctor-patient relationship can improve asthma outcomes. Evidence for the influence of patient enablement on quality of life and the control of asthma is lacking. AIMS: To assess asthma severity, medication use, asthma control, and patient enablement in patients with asthma treated in primary care and to study the relationship between these variables and quality of life. METHODS: A cross-sectional study was conducted in an urban clinic in northern Portugal. Data were collected from both clinical records and questionnaires from a random sample of asthma patients. The modified Patient Enablement Instrument, the Asthma Quality of Life Questionnaire, and the Asthma Control Questionnaire were used. Peak expiratory flow and forced expiratory volume in one second (FEV1) were measured. Receiver operating characteristic curve analysis was performed to establish cut-off values for the quality of life measurements. The associations between enablement, asthma control, and quality of life were tested using logistic regression models. RESULTS: The study sample included 180 patients. There was a strong correlation between asthma control and quality of life (r=0.81, p<0.001). A weak association between patient enablement and asthma control and quality of life was found in the logistic regression models. Poor control of asthma was associated with female gender, concomitant co-morbidities, reduced FEV1, and increased severity of asthma. CONCLUSIONS: The weak correlation between enablement and asthma control requires further study to determine if improved enablement can improve asthma outcomes independent of gender, severity, and concomitant co-morbidities. This study confirms the strong correlation between asthma control and quality of life.

Association of Serum Levels of Plasticizers Compounds, Phthalates and Bisphenols, in Patients and Survivors of Breast Cancer: A Real Connection?

Phthalates and bisphenols are ubiquitous environmental pollutants with the ability to perturb different systems. Specifically, they can alter the endocrine system, and this is why they are also known as endocrine-disrupting compounds (EDCs). Interestingly, they are related to the development and progression of breast cancer (BC), but the threshold concentrations at which they trigger that are not well established. OBJECTIVES: The aim of this study was to compare the concentration measures of parent EDCs in three groups of women (without BC, with BC, and BC survivors) from two urban populations in Mexico, to establish a possible association between EDCs and this disease. We consider the measure of the parent compounds would reflect the individual's exposure. METHODS: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP) and di-ethyl-phthalate (DEP), bisphenol A (BPA) and bisphenol S (BPS) were determined by gas chromatograph-mass spectrometry in 102 subjects, including 37 women without any pathological disease, 46 patients with BC and 19 women survivals of BC of Mexico and Toluca City. RESULTS: All phthalates were detected in 100% of women, two of them were significantly higher in patients with different BC subtypes in Mexico City. Differential increases were observed mainly in the serum concentration of phthalates in women with BC compared to women without disease between Mexico and Toluca City. In addition, when performing an analysis of the concentrations of phthalates by molecular type of BC, DEP and BBP were found mainly in aggressive and poorly differentiated types of BC. It should be noted that female BC survivors treated with anti-hormonal therapy showed lower levels of BBP than patients with BC. BPA and BPS were found in most samples from Mexico City. However, BPS was undetectable in women from Toluca City. DISCUSSION: The results of our study support the hypothesis of a positive association between exposure to phthalates and BC incidence.

Differences in heart rate variability and body composition in breast cancer survivors and women without cancer.

The aim of this study was to explore cardiac autonomic changes assessed by linear and nonlinear indexes of heart rate variability (HRV) and body composition modifications in breast cancer survivors and cancer-free control women. Women who were breast cancer survivors (BCS, n = 27) and without cancer with similar characteristics (Control, n = 31) were recruited for this study. We calculated some relevant linear and nonlinear parameters of 5 min of RR interval time series such as mean RR interval (RRave), the corrected Poincaré index (cSD1/SD2), the sample entropy (SampEn), the long-term fractal scaling exponent (α2) and 2UV from symbolic dynamics. Additionally, we indirectly assessed body composition measures such as body weight, fat mass, visceral fat rating (VFR), normalized VRF (nVFR), muscle mass, metabolic age, and total body water. We found that diverse HRV indexes and only one body composition measure showed statistical differences (p < 0.05) between the BCS and Control groups. RRave: 729 (648-802) vs. 795 (713-852) ms; cSD2/SD1: 3.4 (2.7-5.0) vs. 2.9 (2.3-3.5); SampEn: 1.5 (1.3-1.8) vs. 1.7 (1.5-1.8); α2: 0.6 (0.3-0.6) vs. 0.5 (0.4-0.5); 2UV: 7.1 (4.3-11.5) vs. 10.8 (6.4-15.7) and nVFR 0.12 (0.11-0.13) vs. 0.10 (0.08-0.12) points/kg, respectively. The nVFR was strongly significantly correlated with several indexes of HRV only in the BCS group.Our findings suggest that BCS exhibit lower parasympathetic cardiac activity and changes in HRV patterns compared to Controls. A concomitant increase of visceral fat, among other factors, may contribute to cardiac autonomic disturbances and changes in HRV patterns in BCS.

Visceral Adiposity Index in Breast Cancer Survivors: A Case-Control Study.

BACKGROUND: Breast cancer (BC) is the first cause of cancer morbidity and mortality in women. This disease has been linked to obesity; however, it is not clear how fat accumulation affects women who survive breast cancer. Although the visceral adiposity index (VAI) is a marker of cardiometabolic risk and adipose tissue dysfunction, it is not clear how it changes in breast cancer survivors. The aim of this investigation was to compare VAI in women with and without breast cancer. METHODS: A case-control cross-sectional study was conducted on women who were BC survivors and women without the history of BC (control group). Body composition was assessed using electrical bioimpedance while VAI by means of waist circumference (WC), body mass index (BMI), triacylglycerols (TG), and high-density lipoprotein cholesterol (HDL-C). RESULTS: 49 women in the BC survivor group and 50 in the control group. WC was wider in the survivor group as regards control (93.65 ± 10.48 vs. 88.52 ± 9.61 cm) (p=0.025); at once, TG and VAI were significantly higher for the survivor group (243.55 ± 199.84 vs. 159.84 ± 75.77) (p=0.007) and (11.03 ± 11.15 vs. 6.41 ± 3.66) (p < 0.005), respectively. Body composition parameters were similar in both groups. CONCLUSIONS: VAI is higher in women who are BC survivors in comparison with controls matched by age and bodyweight.

Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves.

Synthetic glucocorticoids (GCs) are widely used to treat inflammatory conditions. However, chronic use of GCs can lead to hypertension. The cause of this undesired side effect remains unclear. Previously, we developed an in vivo rat model to study the mechanisms underlying hypertension induced by the chronic administration of the potent synthetic GC, dexamethasone (DEX) and found that the catecholamine biosynthetic pathway plays an important role. In the current study, we used this model to investigate the role of the adrenal medulla, renal nerves, and other peripheral sympathetic nerves in DEX-induced hypertension. After 5 days of baseline telemetric recording of mean arterial pressure (MAP) and heart rate (HR), rats were subjected to one of the following treatments: renal denervation (RDNX), adrenal medullectomy (ADMX), 6-hydroxydopamine (6-OHDA, 20 mg/kg, i.p.) to induce chemical sympathectomy, or a combination of ADMX and 6-OHDA. On day 11, the animals received vehicle (VEH) or DEX in drinking water for 7 days, with the latter causing an increase in MAP in control animals. ADMX and RDNX by themselves exacerbated the pressor effect of DEX. In the chemical sympathectomy group, DEX still caused a rise in MAP but the response was lower (ΔMAP of 6-OHDA/DEX < VEH/DEX, p = 0.039). However, when ΔMAP was normalized to day 10, 6-OHDA + DEX did not show any difference from VEH + DEX, certainly not an increase as observed in DEX + ADMX or RDNX groups. This indicates that sympathetic nerves do not modulate the pressor effect of DEX. TH mRNA levels increased in the adrenal medulla in both VEH/DEX (p = 0.009) and 6-OHDA/DEX (p = 0.031) groups. In the 6-OHDA group, DEX also increased plasma levels of norepinephrine (NE) (p = 0.016). Our results suggest that the activation of catecholamine synthetic pathway could be involved in the pressor response to DEX in animals even under chemical sympathectomy with 6-OHDA.

Inulin Supplementation Reduces Systolic Blood Pressure in Women with Breast Cancer Undergoing Neoadjuvant Chemotherapy.

INTRODUCTION: Breast cancer is the most frequently diagnosed malignancy in women, and comorbidities like hypertension and obesity diminish their quality of life and negatively affect their response to chemotherapy. Furthermore, inulin supplementation is associated with the reduction of cardiovascular diseases (CVD) risk. OBJECTIVE: To determine whether inulin supplementation prevents the elevation of blood pressure in women with breast cancer undergoing neoadjuvant therapy with cyclophosphamide and doxorubicin. METHODS: This was a randomized, double-blind placebo controlled trial which included women with early-stage breast cancer undergoing neoadjuvant therapy (n=38). Patients were randomly assigned to participate in two different groups to receive either 15 g of inulin or 15 g of placebo (maltodextrin) for 21 days. Body composition and blood pressure were evaluated before and after the supplementation period. RESULTS: Women in the inulin group showed a lower systolic blood pressure (SBP) after the supplementation (-4.21 mmHg, p<0.001). However, SBP increased in the placebo supplemented group. Diastolic blood pressure (DBP) nonsignificantly decreased in the inulin group. Inulin supplementation also increased BMI (p<0.001) but reduced BFP (p=0.288). Furthermore, confounding variables, such as BMI, baseline fasting glucose, age, menopause status, vomiting, constipation, and chronic medication did not have a statistical influence over the inulin effect on SBP. CONCLUSION: Inulin supplementation reduces SBP and prevents increases in DBP in women with breast cancer. This could be an innovative nutraceutical approach to prevent hypertension present in women with this type of cancer at an early stage and may improve the quality of life of the patients and their prognostic development through chemotherapy. TRIAL REGISTRATION NUMBER: This trial is registered with ACTRN12616001532493.

Dietary patterns, central obesity and serum lipids concentration in Mexican adults.

INTRODUCTION: Introduction: dietary patterns (DP) analyse the relationship between consumption of foods or nutrients and disease or health outcomes. High prevalence of obesity in adults in Mexico is associated with factors such as high consumption of certain food groups and nutrients. However, few studies have been conducted to explore associations between dietary patterns and obesity in apparently healthy adults. Objective: to identify major dietary patterns (DP) associated with central-obesity (CO) and lipid concentrations in healthy adults. Methods: longitudinal study including usual dietary intakes derived from multiple 24-hour-recalls. Waist-circumference (WC) and biochemical measurements were obtained by standardized procedures and DP by principal component analysis. Adjusted-logistic regression was used to examine associations between DP, CO and serum-lipid concentrations. Results: three DP were identified: healthy-DP, risky-DP and empty-DP. Participants in the healthy-DP were more likely to have lower risk for central-obesity according to WC criteria (OR = 0.31, CI = 0.12, 0.82), p = 0.017, but also had the highest risk for elevated LDL-cholesterol (OR = 2.98, CI = 1.16, 7.66), p = 0.030. There was no significant association between risky and empty DP with obesity or overweight by body mass index (BMI), central-obesity by WC or serum lipid abnormalities. Conclusions: the healthy-DP is associated with lower risk for CO, with higher risk for elevated LDL-cholesterol. It is necessary to develop longitudinal studies of foods and nutritional analysis of the diet to clarify these associations, to promote the reduction of modifiable risk factors.

INTRODUCCIÓN: Introducción: los patrones de dieta (PD) analizan la relación entre el consumo de alimentos o nutrimentos con la salud y el desarrollo de enfermedades en poblaciones. La elevada prevalencia de obesidad en adultos mexicanos se asocia con factores como el elevado consumo de ciertos grupos de alimentos y nutrimentos. Sin embargo, pocos estudios han explorado la asociación entre los patrones dietéticos y la obesidad en adultos aparentemente sanos. Objetivo: identificar los patrones dietéticos (PD) asociados con la obesidad central (OC) y las concentraciones séricas de lípidos en adultos. Métodos: estudio longitudinal del consumo dietético obtenido de múltiples recordatorios de consumo de 24 horas. La circunferencia de cintura (CC) y las mediciones bioquímicas se obtuvieron mediante procedimientos estandarizados; los PD, por análisis del componente principal. Mediante regresión logística se identificaron las asociaciones entre PD, OC y las concentraciones séricas de lípidos. Resultados: se identificaron tres PD: PD saludable, PD de riesgo y PD vacío. Los participantes del PD saludable presentaron menor riesgo de OC de acuerdo con los criterios de la CC (OR = 0.31, CI = 0.12, 0.82), p = 0.017, pero también fueron los que presentaron mayor riesgo de cifras elevadas de colesterol-LDL (OR = 2.98. CI = 1.16, 7.66), p = 0.030. No hubo asociación estadísticamente significativa entre el PD de riesgo y el PD vacío con obesidad o sobrepeso por IMC, OC por CC o con la presencia de dislipidemias. Conclusiones: el PD saludable se asocia con un menor riesgo para OC pero con mayor riesgo de elevación del colesterol-LDL. Se necesitan estudios longitudinales para esclarecer estas asociaciones para promover la reducción de factores de riesgo modificables.

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats.

RATIONALE: Chronic stress perturbs modulatory brain neurotransmitter systems, including serotonin (5-HT), and is a risk factor for psychiatric disorders such as depression. Deficits in cognitive flexibility, reflecting prefrontal cortical dysfunction, are prominent in such disorders. Orbitofrontal cortex (OFC) has been implicated specifically in reversal learning, a form of cognitive flexibility modulated by 5-HT. OBJECTIVES: The objectives of the study were (1) to assess the effects of chronic intermittent cold (CIC) stress, a potent metabolic stressor, on performance of rats in an attentional set-shifting test (AST), and (2) to assess a possible role for serotonin in CIC-induced deficits and test the effects of acute serotonin reuptake blockade. MATERIALS AND METHODS: Male Sprague-Dawley rats were exposed to CIC stress (14 days x 6 h/day at 4 degrees C) before testing on the AST. In subsequent experiments, brain 5-HT was depleted in naïve rats with para-chlorophenylalanine or 5-HT release was increased acutely in CIC-stressed rats with citalopram (5 mg/kg, s.c.) given 30 min prior to the first reversal task. Microdialysis was used to assess CIC-induced changes in 5-HT release in OFC during testing. RESULTS: CIC-stressed rats exhibited a selective impairment on the first reversal task in the AST. 5-HT depletion induced a similarly selective deficit in reversal learning. The CIC-induced impairment in reversal learning was attenuated by acute 5-HT reuptake blockade. 5-HT release was reduced in OFC of CIC-stressed rats during behavioral testing. CONCLUSIONS: The CIC stress-induced impairment of cognitive flexibility may involve dysregulation of 5-HT modulatory function in OFC. Such deficits may thus model relevant symptoms of neuropsychiatric disorders that respond positively to SSRI treatment.

[Impact of acute exercise intensity on plasma concentrations of insulin, growth hormone and somatostatin]. / Exercício físico e insulina, hormona do crescimento e somatostatina.

Obesity is increasing all over the world, its morbidity justifying a serious effort to improve the situation. Diet and physical exercise constitute major measures to fight obesity. We aimed to investigate the effect of acute exercise intensity over plasma insulin, growth hormone and somatostatin responses. Plasma levels of insulin, growth hormone, somatostatin and glucose were measured at baseline, after 15 minutes of moderate intensity exercise and after 15 minutes of high intensity exercise in a group of young healthy volunteers. Insulin, growth hormone and somatostatin were measured by immunoradioassay and glucose by a glucose oxidase method. After moderate intensity exercise plasma insulin levels tended to decrease, growth hormone tended to increase and somatostatin did not change. A similar period of high intensity exercise led to a similar decrease of plasma insulin, a much higher increase of growth hormone plasma level and no change of somatostatin. Glycemia suffered no significant change throughout the experiment. We conclude that hormonal changes induced by physical exercise depend on the intensity of exercise. When comparing moderate with high intensity exercise, a similar response of plasma insulin and a lower growth hormone/somatostatin ratio may support a healthier cardiovascular effect for moderate intensity exercise.