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A proteomic study of plasma protein changes under extreme physical stress.
Balfoussia, E, Skenderi, K, Tsironi, M, Anagnostopoulos, AK, Parthimos, N, Vougas, K, Papassotiriou, I, Tsangaris, GT, Chrousos, GP
Journal of proteomics. 2014;:1-14
Abstract
UNLABELLED The Spartathlon race (brisk walking a distance of 246km in less than 36h) was employed as a model of severe physical stress to investigate proteomic alterations in the plasma of athletes at the start (Athens) and finish (Sparta) of the race, as well as 48h after the race (Post). The athletes' plasma was analyzed by 2D gel electrophoresis (2-DE) and the differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The ProteoSeekā¢ Albumin/IgG removal kit and the ProteoMinerā¢ enrichment kit were utilized to detect medium- and low-abundance proteins, whose expression may be masked due to high-abundance proteins. Our results were confirmed by Western blot and biochemical analyses. Overall fifty-two proteins were differentially expressed between the starting point, the finishing line and two days after the end of the race. Of these, thirty proteins were involved in inflammation, while the rest concerned anti-oxidation, anti-coagulation and iron and vitamin D transport. These results indicate that prolonged physical stress affects circulating stress-related proteins, which might be employed as biomarkers of stress-related diseases. BIOLOGICAL SIGNIFICANCE The current study employed the Spartathlon, as a model of prolonged endurance exercise, to identify and isolate putative biomarkers of inflammation under extreme physical stress conditions. These protein quantitative variations may pave the way to exploration and understanding of stress-related physiological processes, the stress response itself and diseases whose onset appears to be linked to stress.
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Effects of mometasone furoate dry powder inhaler and beclomethasone dipropionate hydrofluoroalkane and chlorofluorocarbon on the hypothalamic-pituitary-adrenal axis in asthmatic subjects.
Chrousos, GP, Ghaly, L, Shedden, A, Iezzoni, DG, Harris, AG
Chest. 2005;(1):70-7
Abstract
STUDY OBJECTIVES Mometasone furoate dry powder inhaler (MF-DPI) [400 mug] is an inhaled corticosteroid (ICS) that is effective in the treatment of asthma. MF-DPI has a low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis at its clinical dose. The effect of MF-DPI, 400 microg qd, on the HPA axis was compared to that of beclomethasone dipropionate (BDP) using hydrofluoroalkane (HFA) and chlorofluorocarbon (CFC) propellants via metered-dose inhalers (MDIs) twice daily. DESIGN AND INTERVENTIONS This randomized, third-party blind, parallel-group study compared the effects of MF-DPI 400 mug one puff qd in the morning (n = 18), HFA-BDP 200 microg two puffs MDI bid (n = 18), and CFC-BDP 400 microg two puffs MDI bid (n = 17) for 14 days on the area under the 24-h serum cortisol concentrations curve (AUC(0-24)) and on total 24-h urinary free cortisol excretion in mild asthmatic subjects. Effects on morning/evening peak expiratory flow (PEF) and on inhaled albuterol use were also assessed. Adverse events that occurred during or > or = 30 days after the study were recorded. RESULTS The mean decrease from baseline in the serum cortisol concentrations AUC(0-24) in the MF-DPI group was significantly less than in either the HFA-BDP (p = 0.024) or the CFC-BDP (p = 0.011) groups. Decreases in serum cortisol concentrations AUC(0-24) in the two BDP groups did not differ from one another. The MF-DPI group trended toward higher morning and evening PEF than either BDP group. Treatment-associated adverse events were reported by seven subjects in the MF-DPI group, vs one subject in the HFA-BDP and three subjects in the CFC-BDP groups; these were mild, and no subject discontinued treatment due to an adverse event. CONCLUSIONS Fourteen days of treatment with MF-DPI 400 microg qd was associated with a significantly lesser decrease in the serum cortisol concentrations AUC(0-24) compared with HFA-BDP 200 microg MDI or CFC-BDP 400 microg MDI bid.
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Plasma leptin in men and women with seasonal affective disorder and in healthy matched controls.
Cizza, G, Romagni, P, Lotsikas, A, Lam, G, Rosenthal, NE, Chrousos, GP
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2005;(1):45-8
Abstract
Seasonal affective disorder (SAD) is a specific clinical entity characterized by recurrent episodes of depression, which typically occur during the winter with periods of remission during the spring and summer. These depression episodes are accompanied by hyperphagia with cravings for carbohydrates and moderate weight gain, and usually respond to light therapy. We examined potential relationships between leptin, a hormone known to affect appetite and weight regulation, and seasonal changes in mood and appetite by measuring plasma leptin, clinical severity of depression, appetite scores, and body mass index (BMI) in 19 women and 8 men with SAD and matched controls (20 women and 8 men) in the summer and winter. Plasma leptin was positively correlated with BMI in patients and controls during both seasons. Women and men with SAD both experienced depression in the winter, which was associated with increased appetite, caloric intake, and carbohydrate craving. Increased body weight during the winter in subjects with SAD was paralleled by a lack of concomitant changes in plasma leptin, which suggests that leptin sensitivity to changes in body weight may be influenced by seasons in subjects with SAD, similar to seasonal mammals.
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Stress dose of hydrocortisone is not beneficial in patients with classic congenital adrenal hyperplasia undergoing short-term, high-intensity exercise.
Weise, M, Drinkard, B, Mehlinger, SL, Holzer, SM, Eisenhofer, G, Charmandari, E, Chrousos, GP, Merke, DP
The Journal of clinical endocrinology and metabolism. 2004;(8):3679-84
Abstract
Classic congenital adrenal hyperplasia (CAH) is associated with impaired function of the adrenal cortex and medulla leading to decreased production of cortisol and epinephrine. As a result, the normal exercise-induced rise in blood glucose is markedly blunted in such individuals. We examined whether an extra dose of hydrocortisone, similar to that given during other forms of physical stress such as intercurrent illness, would normalize blood glucose levels during exercise in patients with CAH. We studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with classic CAH. Patients were assigned to receive either an additional morning dose of hydrocortisone or placebo, in addition to their usual glucocorticoid and mineralocorticoid replacement in a randomized, double-blind, crossover design 1 h before exercising. Although plasma cortisol levels approximately doubled after administration of the additional hydrocortisone dose compared with the usual single dose, fasting and exercise-induced blood glucose levels did not differ. In addition, no differences were observed in the serum concentrations of the glucose-modulating hormones epinephrine, insulin, glucagon, and GH and of the metabolic parameters lactate and free fatty acids. Although maximal heart rate was slightly higher after stress dosing (193 +/- 3 vs. 191 +/- 3 beats/min, mean +/- sem, P < 0.05), this did not affect exercise performance or perceived exertion. We conclude that patients with classic CAH do not benefit from additional hydrocortisone during short-term, high-intensity exercise. Although this has not been tested with long-term exercise, a high degree of caution should be used when considering the frequent use of additional hydrocortisone administration with exercise, given the adverse side effects of glucocorticoid excess.