The effect of age on the relationship between negative life events and current and new depressive episodes: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: There is scarce data concerning the relationship between negative life events (NLEs)* and current and new depressive episodes by age. METHODS: Cross-sectional (baseline) and prospective analyses (4-year/8-year follow-ups) were performed in 15,105 civil servants in 6 cities in Brazil classified according to age strata at baseline: 1st(35-44), 2nd(45-54), 3rd(55-64), and 4th(65-74) years. The independent variable was NLEs in the last year (robbery, hospitalization, death of a relative, financial hardship, and rupture of a love relationship) collected at baseline. The dependent variable was depressive episodes assessed at baseline (current), and 4-year/8-year follow-ups (new). We built logistic (Odds Ratio[OR];95 % Confidence Interval[CI]) in the cross-sectional analysis and Poisson regression models (Relative Risk[RR], [CI]) in the prospective analysis. RESULTS: Robbery, hospitalization, financial hardship, rupture of a relationship were associated with current depressive episodes concentrated in the 35-44 age range, while for new depressive episodes, the association of hospitalization, death of a relative, and financial hardship were concentrated in the 45-54 age stratum. Financial hardship was associated with current depressive episodes in all age-strata: 1st: OR, 2.77(CI, 1.83-4.19); 2nd: OR, 1.71(CI, 1.26-2.34); 3rd: OR, 1.68(CI,1.15-2.46); 4th, OR, 4.07(CI, 1.24-13.34), and new depressive episodes: 1st: RR, 1.45(CI, 1.09-1.93); 2nd RR, 1.46(CI: 1.15-1.84); 3rd: RR, 1.97(CI, 1.38-2.82). Rupture of a relationship was associated only with current depressive episode, while death of a relative only with new depressive episode. LIMITATION: We cannot rule out the possibility of recall bias, since NLEs` information was self-reported. CONCLUSION: The association between NLEs with depressive episodes was concentrated in youngers.

Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10(-8) M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10(-6) M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10(-4) M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm2), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial-independent microvascular reactivity was similar between groups, suggesting that only endothelial damage had occurred. Our results indicate that an aerobic routine and/or dietary modification may cause significant improvements to high fat fed animals, diminishing visceral depots, increasing eNOS expression and reducing microcirculatory dysfunction.

High fat diet induces central obesity, insulin resistance and microvascular dysfunction in hamsters.

Microvascular dysfunction is an early finding in obesity possibly related to co-morbidities like diabetes and hypertension. Therefore we have investigated changes on microvascular function, body composition, glucose and insulin tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD, n=20) or standard (Control, n=21) diet during 16 weeks. Total body fat and protein content were determined by carcass analysis, aorta eNOS and iNOS expression by immunoblotting assay and mean blood pressure (MAP) and heart rate (HR) by an arterial catheter. Microvascular reactivity in response to acetylcholine and sodium nitroprusside, functional capillary density (FCD), capillary recruitment induced by a hyperinsulinemic status and macromolecular permeability after 30 min ischemia was assessed on either cheek pouch or cremaster muscle preparations. Compared to Control, HFD animals have shown increased visceral fat (6.0 ± 0.8 vs. 13.8 ± 0.6g/100g BW), impaired endothelial dependent vasodilatation, decreased FCD (11.3 ± 1.3 vs. 6.8 ± 1.2/field) and capillary recruitment during hyperinsulinemia and increased macromolecular permeability after ischemia/reperfusion (86.4 ± 5.2 vs.105.2 ± 5.1 leaks/cm(2)), iNOS expression and insulin resistance. MAP, HR, endothelial independent vasodilatation and eNOS expression were not different between groups. Our results have shown that HFD elicits an increase on visceral fat deposition, microvascular dysfunction and insulin resistance in hamsters.

Maternal protein restriction during early lactation induces changes on neutrophil activation and TNF-alpha production of adult offspring.

Maternal nutritional environmental in early life has been often associated with long term effects on the immune response in adulthood. The effects of maternal protein deprivation during early lactation on neutrophil-mediated innate immunity were investigated in adult rats, offspring of dams fed with a protein-free diet during the first days of lactation (PD), and compared to controls (22% protein diet). Inflamed PD animals showed an inhibited neutrophil migration and an impaired recruitment of leukocytes from bone marrow pool to circulation. In resting conditions, blood neutrophils from PD present reduced phagocytic activity, increased production of O(2) (-) and NO, basal iNOS expression and constitutive NF-kappaB activation. Moreover, PD rats also show high circulating levels of TNF-alpha and increased expression of TNF-alpha mRNA in the spleen and liver. The data indicate that maternal nutritional stress can interfere on the innate immune response in adulthood, imprinting permanent alterations on cytokine production and neutrophil activation.

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition.

Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin-stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters (SL). The normal litter (NL) served as control group. We also investigated glycemia, insulinemia, plasma lipid levels, and glucose tolerance. Our data demonstrated that early postnatal overfeeding induced a persistent hyperphagia accompanied by a significant increase in body weight until 90 days of age. The SL group also presented a significant increase ( approximately 42%) in epidydimal fat weight. Blood glucose, plasma insulin, and lipid levels were similar among the animals from the SL and NL groups. While insulin-stimulated glucose uptake was approximately twofold higher in adipocytes from the NL group, no stimulatory effect was observed in the SL group. The impaired insulin-stimulated glucose transport in adipose cells from the SL rats was associated with a significant decrease in GLUT-4, IRS-1 and PI3K expression, and Akt activity. In contrast, IR and Akt expression in adipocytes was not different between the SL and NL groups. Despite these alterations, our results showed no differences in glucose tolerance test in rats raised under different feeding conditions. Our findings reinforce a potent and long-term effect of neonatal overfeeding, which can program major changes in the metabolic regulatory mechanisms.

Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation.

The deregulation of inflammatory response during sepsis seems to reflect the overproduction of mediators, which suppress leukocyte functions. We investigated the intracellular mechanisms underlying the inability of neutrophils from severe septic patients to migrate toward chemoattractants. Patients with sepsis (52) and 15 volunteers were prospectively enrolled. Patients presented increased circulating levels of tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-8, and IL-10. Patients showed reduced neutrophil chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) or IL-8. No difference in the transcription or expression of the IL-8 receptor, CXCR1, was detected in neutrophils from controls and patients. However, septic neutrophils failed to increase tyrosine phosphorylation and actin polymerization in response to IL-8 or LTB4. In contrast, septic neutrophils, similar to controls, showed phagocytic activity that induced actin polymerization and augmented phosphotyrosine content. Treatment of control neutrophils with cytokines and lipopolysaccharide (LPS) to mimic endogenous septic environment inhibited actin polymerization and tyrosine phosphorylation in response to IL-8 or LTB4. High expression of G protein-coupled receptor kinase 2 (GRK2) and GRK5 was detected in septic neutrophils and control cells treated with cytokines plus LPS. Data suggest that endogenous mediators produced during sepsis might continually activate circulating neutrophils, leading to GRK activation, which may induce neutrophil desensitization to chemoattractants.