Svetozar Damjanovic

University of Belgrade, Beograd, Central Serbia, Serbia

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Publications (49)132.55 Total impact

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    ABSTRACT: Background The hypothalamo-pituitary-adrenocortical (HPA) axis self-regulation is achieved via cortisol binding to mineralocorticoid (MR) and glucocorticoid receptors (GR). It is often disturbed in mental disorders, particularly in those where traumatic stress has been implicated, such as posttraumatic stress disorder and depression. Although dexamethasone suppression test (DST) is often used as diagnostic aid, the findings still vary. In search of the factors influencing the DST outcome, we examined the glucocorticoid receptor (GR) gene BclI polymorphism. Methods A total of 229 male subjects were classified into three BclI groups: two groups with homozygous carriers (of the G allele, N=108, and of the C allele, N=26), and one with heterozygous carriers (N=95). Multiple hierarchical linear regression analysis was done, where the dependent variable was the dexamethasone-induced cortisol suppression, and predictors included receptor variables. The interactions of the count of ‘G׳s with the predictors were introduced to single out the effects of the G allele. Results The means of all studied variables, including suppression, are statistically the same in the three groups. However, the mechanism of suppression involves MRs only in the G allele carriers. Limitations The subjects were selected by criteria suited for the aim of the large project whose part is this study, hence the relatively small number of CC carriers. Also, we did not assess MR functional properties that would probably sharpen the results. Conclusion Our finding that MRs participate in cortisol suppression in the G allele carriers suggests that research aimed at refining HPA axis-based therapy might require its adjustment for such patients.
    Journal of Affective Disorders 10/2014; 168:1–4. · 3.71 Impact Factor
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    ABSTRACT: The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5 g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10 min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00 ± 0.00 to 1.25 ± 0.54‰ (P < 0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2 = 3008 ± 638 vs. 2900 ± 543 ml/min, ns; peak workload = 269 ± 53 vs. 249 ± 40 W, ns; test duration 13.7 ± 2.2 vs. 13.3 ± 1.7 min, ns; VE/VCO2 22.1 ± 1.4 vs. 23.3 ± 2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28 ± 2.5 vs. 30.4 ± 3.2, P = 0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17 ± 0.02 vs. 1.14 ± 0.04, P = 0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism.
    Journal of Cardiovascular Medicine 07/2014; · 1.41 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the predictive value of adrenocorticotropic hormone (ACTH), cortisol and ACTH receptor polymorphism (ACTHRP) for left ventricular (LV) remodeling. Thirty-six elite male athletes, as chronic stress adaptation models, and twenty sedentary age and sex-mached subjects emabarked on standard and tissue Doppler echocardiography to assess cardiac parameters at rest. They performed maximal cardiopulmonary test, which was used as an acute stress model. ACTH and cortisol were measured at rest (10 min before test), at beginning, at maximal effort, at 3rd min of recovery, using radioimmunometric and radioimmunoassey techniques, respectively. Promoter region of ACTHR gene (18p11.2) was analysed from blood samples using reverse polymerisation reaction with the analysis of restriction fragment lenght polimorphisam by SacI restriction enzyme. Normal genotype was CTC/CTC, heterozygot for ACTHRP CTC/CCC and homozygot CCC/CCC. In all participants, ACTH and cortisol increased during acute stress, whereas in recovery ACTH increased and cortisol remained unchanged. 49/56 examiners manifested CTC/CTC, 7/56 CTC/CCC and 0/56 CCC/CCC. There was no difference in ACTHRP frequency between groups (χ2(1) = 0,178, p = 0.67). LV mass (LVM) and LV end-diastolic volume (LVVd) were higher in athletes than in controls (p < 0.01) and lower in CTC/CTC than in CTC/CCC genotype (219.43 ± 46.59(SD)g vs. 276.34 ± 48.86(SD)g, p = 0.004; 141.24 ± 24.46(SD)ml vs. 175.29 ± 37.07(SD)ml, p = 0.002; respectively). In all participants, predictors of LVM and LVVd were ACTH at rest (B = -1.00,-0.44; β=-0.30;-0.31; p = 0.026,0.012, respectively) and ACTHRP (B = 56.63,34; β=0.37,0.40; p = 0.003,0.001, respectively). These results demonstrate that ACTH and ACTHRP strongly predict cardiac morphology suggesting possible regulatory role of stress system activity and sensitivity in cardiac remodeling.
    Peptides 07/2014; · 2.61 Impact Factor
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  • Endocrine Abstracts. 04/2014;
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    ABSTRACT: Abstract Introduction: Although numerous studies indicated a link between antithyroid antibodies and recurrent spontaneous abortions (RSA), consensus on the treatment of this condition is still lacking. Case report: We present a case of a 35-year-old pregnant woman (gestation week 4) with primary hypothyroidism, total alopecia, high level of positive antithyroid antibodies, and history of two recurrent spontaneous abortions in early pregnancy. Along with L-thyroxin substitution, intravenous human immunoglobulin (IVIg) combined with anticoagulation and antiaggregation therapy was introduced. During pregnancy her scalp hair completely re-grew, and following gestation week 39 she delivered healthy female child. Conclusion: Thyroid antibodies could contribute to previous recurrent abortions in our patient. It is suggested that in older primiparas with Hashimoto thyroiditis and history of RSA, a combined treatment with IVIg, anticoagulation and antiaggregation therapy should be considered.
    Gynecological Endocrinology 12/2013; · 1.14 Impact Factor
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    ABSTRACT: Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.
    Psychiatry research. 12/2013;
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    ABSTRACT: Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C).Plasma levels of NT-pro-BNP, cortisol and adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich technique, radioimmunoassay and radioimmunometric techniques, respectively, 10min before test (1), at beginning (2), at maximal effort (3), at 3rd min of recovery (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3; remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol increased from 1 to 3 and stayed elevated at 4. In all groups together, ΔNT-pro-BNP2/1 predicted peak oxygen consumption (B=37.40, r=0.38, p=0.007); cortisol at 3 predicted heart rate increase between 2 and 3 (r=-0.38,B=-0.06, p=0.005); cortisol at 2 predicted peak carbon-dioxide output (B=2.27, r=0.35, p<0.001); ΔACTH3/2 predicted peak ventilatory equivalent for carbon-dioxide (B=0.03, r=0.33, p=0.003).The relation of cortisol at 1 with NT-pro-BNP at 1 and 3 was demonstrated using logistic function in all the participants together (for 1/cortisol at 1 B=63.40, 58.52; r=0.41, 0.34; p=0.003,0.013, respectively).ΔNT-pro-BNP2/1 linearly correlated with ΔACTH4/3 in WP and W (r=-0.45, -0.48; p=0.04, 0.04,respectively).These results demonstrate for the first time that HPA axis and NT-pro-BNP interface in physical stress probably contributing to integrative regulation of cardiopulmonary performance.
    Peptides 07/2013; · 2.61 Impact Factor
  • Endocrine Abstracts. 03/2013;
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    ABSTRACT: Brain natriuretic peptide (NT-pro-BNP) is used as marker of cardiac and pulmonary diseases. However, the predictive value of circulating NT-pro-BNP for cardiac and pulmonary performance is unclear in physiological conditions. Standard echocardiography, tissue Doppler and forced spirometry at rest were used to assess cardiac parameters and forced vital capacity (FVC) in two groups of athletes (16 elite male wrestlers (W), 21 water polo player (WP)), as different stress adaptation models, and 20 sedentary subjects (C) matched for age. Cardiopulmonary test on treadmill (CPET), as acute stress model, was used to measure peak oxygen consumption (peak VO2), maximal heart rate (HRmax) and peak oxygen pulse (peak VO2/HR). NT-pro-BNP was measured by immunoassey sandwich technique 10min before the test - at rest, at the beginning of the test, at maximal effort, at third minute of recovery. FVC was higher in athletes and the highest in W (WP 5.60±0.29 l; W 6.57±1.00 l; C 5.41±0.29 l; p<0.01). Peak VO2 and peak VO2/HR were higher in athletes and the highest in WP. HRmax was not different among groups. In all groups, NT-pro-BNP decreased from rest to the beginning phase, increased in maximal effort and stayed unchanged in recovery. NT-pro-BNP was higher in C than W in all phases; WP had similar values as W and C. On multiple regression analysis, in all three groups together, ΔNT-pro-BNP from rest to the beginning phase independently predicted both peak VO2 and peak VO2/HR (r=0.38, 0.35; B=37.40, 0.19; p=0.007, 0.000, respectively). NT-pro-BNP at rest predicted HRmax (r=-0.32, B=-0.22, p=0.02). Maximal NT-pro-BNP predicted FVC (r=-0.22, B=-0.07, p=0.02). These results show noticeable predictive value of NT-pro-BNP for both cardiac and pulmonary performance in physiological conditions suggesting that NT-pro-BNP could be a common regulatory factor coordinating adaptation of heart and lungs to stress condition.
    Peptides 02/2013; · 2.61 Impact Factor
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    ABSTRACT: Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK, N363S, Bcl I, and 9β) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p < 0.001). GR gene variants, larger allele of Bcl I (odds ratio [OR] 2.9; 95% confidence interval [CI] 1.7-5.1; p < 0.001] and minor allele of 9β (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of AI. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p ≤ 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of Bcl I and minor allele of 9β, are associated with AIs. Their concurrent presence in patients reduces GC sensitivity. Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects.
    Molecular Medicine 01/2013; 18:1456-65. · 4.82 Impact Factor
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    ABSTRACT: OBJECTIVE: Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD. METHODS: Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting. RESULTS: Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (B(max)) in PBMCs. Hormone-binding potential (B(max)/K(D) ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between B(max) and K(D) that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting B(max) data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD. CONCLUSIONS: Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between B(max) and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecules population in PBMCs.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2013; · 4.03 Impact Factor
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    ABSTRACT: Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat-shock proteins (Hsps). We investigated whether common GR gene (ER22/23EK, N363S, BclI, 9β) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsps expression in tumorous (n=19), peritumorous (n=13) and normal adrenocortical (n=11) tissues. Patients (n=112), population-matched controls (n=100), and tumor tissues (n=32) were genotyped for these polymorphisms. Post-dexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI [odds ratio (OR)=2.9; 95% confidence interval (CI): 1.7-5.1; p<0.001] and minor allele of 9β (OR=3.0; 95% CI: 1.6-5.7; p<0.001) were independent predictors of AI. In patients, the first allele is linked with larger tumors (p=0.002) and the latter with higher post-dexamethasone cortisol levels (p=0.025). Both allele carriers had lesser waist circumference (p=0.02), similar adrenocorticotropin, higher basal (p=0.024) and post-dexamethasone cortisol concentrations (p<0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western-blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p<0.001), underexpression of chaperones (p≤0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9β, are associated with AIs. Their concurrent presence in patients reduces GC sensitivity. Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of Hsps perhaps permanently impair GC signalling, which could promote dysregulated cortisol production and the tumor growth. The innate GC sensitivity probably modifies these effects.
    Molecular Medicine 11/2012; · 4.82 Impact Factor
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    ABSTRACT: To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing.
    Croatian Medical Journal 08/2012; 53(4):328-35. · 1.25 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Autoimmune polyglandular syndromes are defined as a spectrum of association between 2 or more organ specific endocrinopaties and non-endocrine autoimmune diseases. Autoimmune polyglandular syndromes type 2 is characterized by the coexistence of adrenal failure with autoimmune thyroid disease and diabetes mellitus type 1. Inflammatory bowel diseases are rarely associated with these autoimmune disorders. Here, we report about a case of 33years old male with known history of Crohn's colitis diagnosed in childhood. In 2003 the patient experienced sudden loss of hair, eyebrows, eyelashes, beard and body hair - alopecia universalis was diagnosed. At the age of 28, the patient was hospitalized with severe dehydration and clinical signs of ketoacidosis. Increased blood glucose (40mmol/L), ketonuria and metabolic acidosis indicated diabetes mellitus type 1. In 2005, he had severe relapse of Crohn's disease and was treated with systemic corticosteroid. Although patient responded well to the induction therapy, fatigue, hypotension, bradycardia called for further investigations: free thyroxine - 6.99pmol/L, thyroid-stimulating hormone >75U/ml, anti-thyroid peroxidase antibodies >1000U/mL, so diagnosis of Haschimoto thyroiditis was confirmed. Persistent hypotension and fatigue, recurrent hypoglycemic crises indicated a possible presence of hypo-function of adrenal glands. After complete withdrawal of corticosteroid therapy, low cortisol levels (69.4nmol/L) and positive tetracosactide stimulation test proved adrenal cortex failure. Regardless of the intensive treatment for diabetes, hypothyroidism, adrenal insufficiency and Crohn's disease, it was extremely difficult to achieve and maintain control of all four diseases.
    Journal of Crohn s and Colitis 06/2012; 7(4). · 3.56 Impact Factor
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    ABSTRACT: The use of the low-dose dexamethasone suppression test (DST) as a potentially discriminative marker between post-traumatic stress disorder (PTSD) and depression is still under discussion. In order to compare the influence of these psychopathologies on the DST results, we examined suppression in war-traumatized subjects with one or both of these disorders, as well as in healthy controls. Based on our previous findings, we hypothesized that subjects with any disorder would exhibit higher dexamethasone suppression than healthy controls due to traumatic experiences. This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions on 399 male participants: 57 with PTSD, 28 with depression, 76 with PTSD+depression, and 238 healthy controls. Cortisol was measured in blood samples taken at 0900 h before and after administering 0.5mg of dexamethasone (at 2300 h). Group means ± standard deviation of cortisol suppression were: 79.4±18.5 in the PTSD group, 80.8±11.6 in the depression group, 77.5±24.6 in the group with PTSD+depression, and 66.8±34.6 in healthy controls. The first three groups suppressed significantly more than the fourth. When the number of traumas was introduced as a covariate, the differences disappeared. The hypothesis was confirmed: in respect to DST, the examined trauma-related psychopathologies showed the same pattern: hypersuppression, due to multiple traumatic experiences.
    Psychoneuroendocrinology 03/2012; 37(9):1516-20. · 5.59 Impact Factor
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    ABSTRACT: Studies of cortisol in post-traumatic stress disorder (PTSD) have yielded mixed results. We hypothesize that personality traits and traumatic experiences could be the confounders of cortisol measures and disease symptoms. This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions on 400 male participants categorized by four groups: (A) 133 with current PTSD, (B) 66 with lifetime PTSD, (C) 102 trauma controls, and (D) 99 healthy controls (matched by age and education). Cortisol and ACTH were measured in blood samples taken hourly from 22:00 h to 09:00 h, with an additional sample at 07:30 h (resting state and morning rise). The next night, dexamethasone (0.5mg) suppression test was performed. No significant differences in basal cortisol and ACTH were found between study groups. The trait Conscientiousness, negatively modulated by Extraversion (assessed by NEO Personality Inventory-Revised) was found to correlate with cortisol (but not with ACTH). Group differences are found on suppression. Structural equation modeling shows excellent fit only when the paths (influences) from Conscientiousness to basal cortisol and from traumatic events to suppression are present. The paths connecting suppression and PTSD symptoms do not contribute. Two sources of differences of hypothalamo-pituitary-adrenocortical axis functioning are implied, both only indirectly connected to PTSD. It seems that basal cortisol secretion is associated more tightly with personality (introvertively modulated Conscientiousness), while the regulation by glucocorticoid receptor system is sensitized by repeated traumatic situations.
    Psychoneuroendocrinology 11/2011; 37(7):937-47. · 5.59 Impact Factor
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    ABSTRACT: To review the expression of the glucocorticoid receptor (GR) in anterior pituitary and adrenocortical cells and tumors derived from these tissues as well as factors that may influence its expression. We present an overview of the relevant literature, with a focus on data generated from our studies. The expression of the GR is an essential element of the negative feedback that closes the loop formed by corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol in the context of the hypothalamic-pituitary-adrenal (HPA) axis. Although the GR expression in anterior pituitary cells-and in particular the corticotrophs-was first demonstrated several years ago, it was not known until relatively recently where, by what cells, and in what form the GR is expressed in the adrenal cortex. The variability in the expression of the GR in pituitary and adrenocortical cells may underlie the substantial differences in HPA axis function across individuals, especially when testing for tumors associated with hypercortisolemia. This expression is influenced by a multitude of tissue-specific factors, which may explain why it is so difficult to interpret (or reproduce) studies that are based on GR functional polymorphisms on different cohorts of patients or even different sets of laboratory animals. This review highlights the variability in expression and function of the GR in pituitary and adrenocortical cells as one of the reasons for the appreciable differences in HPA axis function across individuals. Particular attention was paid to interactions that may affect the interpretation of diagnostic testing of the HPA axis in patients with pituitary adenomas (Cushing disease) or adrenocortical tumors (Cushing syndrome).
    Endocrine Practice 07/2011; 17(6):941-8. · 2.49 Impact Factor
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    ABSTRACT: Data pertaining to whether stress-induced aldosterone release is associated with cardiac disorders are lacking. This study was designed to compare whether the modulation of intra-operative aldosterone release by epidural analgesia had an effect on the brain natriuretic peptide (BNP) levels. Design, Patients, A study was pilot prospective, open label randomized one. Patients were randomized to one of two anaesthesia protocols: group 1 included 13 patients who received general anaesthesia, and group 2 included 12 patients who received combined general anaesthesia and epidural analgesia. Study protocol was by completed 25 male patients, median age 56 years, without significant comorbidities, who underwent radical cystectomy because of urinary bladder tumour. Serum aldosterone, BNP, cortisol (measured by radioimmunoassay), adrenocorticotropine hormone (ACTH) (by solid-phase ELSA), blood chemistry, complete blood count and vital signs were compared preoperatively, intra-operatively and at postoperative days (POD) 1 and 7. Hemodynamics was stable in both groups. Group 1 showed threefold serum aldosterone, (P = 0·001) 20-fold ACTH (P = 0·003) and twofold cortisol (P = 0·001) increases intra-operatively, unlike group 2. Both groups had a twofold BNP increase in POD 1 that remained above normal on POD 7 only in group 1 (P = 0·02; P = 0·019 vs group 2). Alleviation of aldosterone release by epidural analgesia modulated the postoperative serum BNP pattern in patients with a low risk for cardiac diseases who underwent noncardiac surgery.
    Clinical Endocrinology 05/2011; 74(5):649-56. · 3.35 Impact Factor

Publication Stats

376 Citations
132.55 Total Impact Points


  • 1996–2014
    • University of Belgrade
      • • School of Medicine
      • • Institute of Endocrinology
      Beograd, Central Serbia, Serbia
  • 1993–2013
    • Klinički centar Srbije
      • • Institute of Endocrinology, Diabetes and Diseases of Metabolism
      • • Institute of Otorhinolaryngology and Maxillofacial Surgery
      Beograd, Central Serbia, Serbia
  • 2008–2009
    • University Children's Hospital, Belgrade, Serbia
      Beograd, Central Serbia, Serbia
  • 2006
    • Aristotle University of Thessaloniki
      • Endocrinology of Reproduction Unit
      Saloníki, Central Macedonia, Greece
  • 2005
    • Clinic for Endocrinology, Diabetes and Diseases of Metabolism
      Skopie, Karpoš, Macedonia
  • 2002
    • University of Santiago de Compostela
      Santiago, Galicia, Spain