The effectiveness of a stress-management intervention program in the management of overweight and obesity in childhood and adolescence

Background: Obesity in childhood and adolescence represents a major health problem of our century, and accounts for a significant increase in morbidity and mortality in adulthood. In addition to the increased consumption of calories and lack of exercise, accumulating evidence suggests that childhood obesity is strongly associated with prolonged and excessive activation of the stress system. Aim: The aim of our study was to assess the effectiveness of a stress-management intervention program, which included progressive muscle relaxation, diaphragmatic breathing, guided imagery and cognitive restructuring, in overweight and obese children and adolescents. Methods: Forty-nine children and adolescents (mean age ± SEM: 11.15 ± 1.48 years) were prospectively recruited to participate in this randomized controlled study. Of those, 23 participants were assigned into the intervention group, while 26 participants represented the control group. Anthropometric measurements were recorded at the beginning and at the end of the study, and participants were asked to complete the Screen for Child Anxiety Related Disorders (S.C.A.R.E.D.), the Child Depression Inventory (C.D.I.), the Child Behavior Checklist (C.B.C.L.) and the Youth Self Report (Y.S.R.). Results: The applied stress-management methods resulted in a significant reduction in the body mass index (BMI) in the intervention group compared with the control group [ΔBMI=1.18 vs 0.10 kg/m2 (p˂0.001)]. In addition to BMI, these methods ameliorated depression and anxiety, and reduced the internalizing and externalizing problems in the intervention group. Conclusions: Our study demonstrated that the application of an 8-week stress management program could facilitate weight loss in Greek overweight and obese children and adolescents. Further larger studies are required to evaluate the effectiveness of stress-management methods in overweight and obese subjects

The Role of S-Palmitoylation of the Human Glucocorticoid Receptor (hGR) in Mediating the Nongenomic Glucocorticoid Actions

Background: Many rapid nongenomic glucocorticoid actions are mediated by membrane-bound glucocorticoid receptors (GRs). S-palmitoylation is a lipid post-translational modification that mediates the membrane localization of some steroid receptors. A highly homologous amino acid sequence (663YLCM KTLLL671) is present in the ligand-binding domain of hGRα, suggesting that hGRα might also undergo S-palmitoylation. Aim: To investigate the role of the motif 663YLCMKTLLL671 in membrane localization of the hGRα and in mediating rapid nongenomic glucocorticoid signaling. Methods and Results: We showed that the mutant receptors hGRαY663A, hGRαC665A and hGRαLL670/671AA, and the addition of the palmitoylation inhibitor 2-bromopalmitate did not prevent membrane localization of hGRα and co-localization with caveolin-1, and did not influence the biphasic activation of mitogen-activated protein kinase (MAPK) signaling pathway in the early time points. Finally, the hGRα was not shown to undergo S-palmitoylation. Conclusions: The motif 663YLCMKTLLL671 does not play a role in membrane localization of hGRα and does not mediate the nongenomic glucocorticoid actions.  

Metallothionein expression in the high-risk carotid atherosclerotic plaque

Objective: Metallothioneins (MTs) are antioxidant proteins expressed in response to injury. We evaluated MT immunoreactivity in carotid plaques obtained from asymptomatic and symptomatic patients. We also assessed the relationship between ultrasonic plaque echodensity, histological grading, computed tomography findings and MT expression. Methods and results: In this ongoing prospective study, patients (n = 123, mean age (+/- SD) 68.4 +/- 7.7 years, 97 men) with high-grade carotid stenosis underwent carotid endarterectomy. Specimens were assessed histologically and immunohistochemically. Echolucent plaques (types 1+2) were more common in symptomatic patients (p < 0.0001) and had more advanced histological lesions (p < 0.0001). Echolucent plaques expressed MTs (in macrophages, fibroblasts and T-lymphocytes) significantly more than echogenic plaques (types 3+4) (all p < 0.0001). MT expression was mainly related to carotid plaque echolucency rather than the presence of symptoms. MT expression was significantly more common in advanced histological lesions. Plaques from asymptomatic or symptomatic patients with abnormal computed tomography findings also showed increased MT expression. There was a time-dependent fall in MT expression after cerebrovascular events (p <= 0.011). Conclusions: MT overexpression may be triggered in unstable plaques as a local protective factor. There is a need to identify both causative and protective predictors of the ‘vulnerable plaque’ in the ‘vulnerable patient’. Further studies are needed to resolve these issues

Low expression of p27 protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large B-cell lymphomas

The expression of the cyclin-dependent kinase inhibitor (CDKI) p27 protein was investigated in relation to (1) the expression of the cell cycle regulators p53, Rb and p16 and (2) the proliferation profile as determined by the expression of Ki67, cyclin A, and cyclin BI in 80 cases of de novo diffuse large B-cell lymphomas (DLBCL). P27 expression was low/null in large tumor cells in 58/80 cases and intermediate/high in 22/80 cases. Increased expression of p53 protein was observed in 39/80 cases. Decreased expression of Rb and p16 proteins was mutually exclusive and was observed in 5/80 and 14/80 cases, respectively. The analysis of the p27 expression status (low/null versus intermediate/high) with respect to the p53 and/or Rb/p16 expression status showed that low/null p27 expression was significantly correlated with increased p53 expression (P = .018) and showed a strong trend for correlation with concurrent increased p53 expression and decreased Rb or p16 expression (P = .050). These findings suggest a tendency for concurrent alterations of the cell cycle regulators p27, p53, and Rb or p16 in DLBCL, which might result in impaired tumor growth control. Indeed, the analysis of the combined p27/p53/Rb/p16 expression status with respect to the proliferation profile showed that (1) three alterations in the combined p27/p53/Rb/p16 status (i.e., low/null P27 expression, increased expression of p53, and decreased expression of Rb or p16) were significantly correlated with increased expression of cyclin B1 (P = .005) and (2) two or three alterations were significantly correlated with increased expression of cyclin A (P = .014). These findings suggest combined impairment of a complex cell-cycle control network involving the CDK inhibitor p27, the P53 pathway, and the Rbl pathway, which exerts a cooperative effect resulting in enhanced tumor cell proliferation