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Objectives: Postmenopausal period is associated with the decline in antioxidant levels due to gradual loss of estrogen, increased body weight and central adiposity. The present study aimed to evaluate association of adiposity and regional fat distribution with total antioxidant capacity in postmenopausal women. Methods: This cross-sectional study included 90 apparently healthy postmenopausal women. We measured anthropometric indices including body mass index (BMI), waist circumference (WC) and waist-hip ratio (W/H ratio). Total fat mass (TFM), total lean mass (TLM), percentage fat mass (%FM), visceral fat diameter (VFD) and subcutaneous fat diameter (SFD) were measured using ultrasound. Serum total antioxidant capacity (TAC) was measured by quantitative colorimetric determination using Total antioxidant Capacity -QuantiCromAntioxidant Assay Kit (BioAssay systems, USA; DTAC-100). Results: Out of 90 postmenopausal women, 35.9% were overweight and 25.0% obese, while 60.9% had central obesity. Postmenopausal obese women had significantly lower median TAC level [308.3 (283.0-375.1)] mM Trolox equivalents compared to overweight [383.38 (356.5-389.4) mM Trolox equivalents; p<0.001] and normal weight women [376.3 (318.0-388.7) mM Trolox equivalents; p<0.005]. Serum logTAC level was inversely associated with BMI, TFM, TLM and WC in postmenopausal women. However, when stratified by central obesity, inverse associations between serum logTAC level and BMI (r=-0.503; p<0.001), TFM (r=-0.383, p=0.004) and WC (r=-0.408; p=0.002) were observed only in postmenopausal women with central obesity. Conclusion: Our results provide evidence that obesity and central obesity during postmenopausal period are associated with decreased total antioxidant capacity and depleted antioxidant defenses possibly due to elevated oxidative stress. Larger prospective studies are needed to evaluate whether obese postmenopausal women might benefit from antioxidants supplementation for the prevention of obesity related diseases. Keywords: total antioxidant capacity, oxidative stress, obesity, overweight

The endothelial cell layer is responsible for molecular traffic between the blood and surrounding tissue, and endothelial integrity plays a pivotal role in many aspects of vascular function. Cardiovascular disease (CVD) is the main cause of death in patients with chronic kidney disease (CKD) and its incidence and severity increase in direct proportion with kidney function decline. Non-traditional risk factors for CVDs, including endothelial dysfunction (ED), are highly prevalent in this population and play an important role in cardiovascular (CV) events. ED is the first step in the development of atherosclerosis and its severity has prognostic value for CV events. Several risk markers have been associated with ED. Reduced bioavailability of nitric oxide plays a central role, linking kidney disease to ED, atherosclerosis, and CV events. Inflammation, loss of residual renal function, and insulin resistance are closely related to ED in CKD. ED may be followed by structural damage and remodelling that can precipitate both bleeding and thrombotic events. The endothelium plays a main role in vascular tone and metabolic pathways. ED is the first, yet potentially reversible step in the development of atherosclerosis and its severity has prognostic value for CV events. Therefore, evaluation of ED may have major clinical diagnostic and therapeutic implications. In patients with CKD, many risk factors are strongly interrelated and play a major role in the initiation and progression of vascular complications that lead to the high mortality rate due to CVD.

Objectives: Aim of the present study was to investigate serum concentration of leptin and its association with values of body mass index (BMI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in hemodialysis (HD) patients. Methods: This cross-sectional study included 60 HD patients (34 male, 26 female) and 30 age- and sex-matched (4 males, 26 females) apparently healthy subjects. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA). Serum CRP concentration was measured by means of particle-enhanced immunonephelometry. ESR value was determined by Western Green method. BMI was calculated as weight (kg) divided by height squared (m2). Results: Results have shown that median serum leptin concentration (30.65 ng/mL; 12.48-86.40 ng/mL) was statistically significantly higher in HD patients compared to median serum leptin concentration (15.75 ng/mL; 9.15-30.65 ng/mL) in the control group of healthy subjects (p<0.05). Likewise, median serum CRP concentration (5.5 mg/L; 1.93-8.9 mg/L) and median ESR value (57.5 mm/h; 40.5-77.0 mm/h) were significantly higher in HD patients compared to median serum CRP concentration (0.8 mg/L; 0.38-1.43 mg/L) (p<0.001) and median ESR value (10.0 mm/h; 6.5-14.0 mm/h) (p<0.001) determined in the control group. Statistically significant positive correlation was found between BMI values and serum leptin concentration in HD patients (rho=0.434; p<0.001). Positive, although not significant, correlation was observed between serum CRP and leptin levels in HD patients (rho=0.171; p>0.05). Negative correlation between ESR values and serum leptin concentrations in HD patients was determined but it was not statistically significant (rho= -0.029; p>0.05). Conclusions: Increased serum concentration of leptin as pro-inflammatory cytokine as well as elevated serum values of CRP and ESR indicate presence of systemic micro inflammation in HD patients. Results of the present study point to possible use of serum leptin concentration as an indicator of nutritional status in HD patients based on observed significant positive correlation between serum leptin concentrations and BMI values. However, absence of significant association between serum leptin and CRP levels as well as between serum leptin concentrations and ESR values in HD patients requires further investigation and clarification.

Objectives : Alternations in adipokines secretion associated with obesity could play an important role in diet-induced diabetes. The aim of our study was to estimate the impact of high-fat diet on serum adiponectin and leptin levels in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM). Methods : The study included 40 adult male Wistar rats were divided into four groups: Standard food control group (C-Non-HF)(n=10), standard food STZ group (STZ-NonHF)(n=10), high-fat diet control group (C-HF)(n =10) and high-fat diet STZ group (STZ-HF)(n =10). C-NonHF and STZ-NonHF group was fed with regular chow, and other two groups were given high-fat diet for 5 weeks. Type 2 DM was induced by single intra-peritoneal STZ injection (60 mg/kg). All the rats were fasted for 12 hours; when blood samples were taken for the measurement of serum leptin and adiponectin level by ELISA. Results : Mean serum adiponectin level was significantly lower in STZ-HF (1.34±0.57 ng/mL) compared to STZ-NonHF (2.61±0.79 ng/mL), C-NonHF (3.13±0.74 ng/mL) and C-HF group (3.04±0.63 ng/mL) (p<0.01). Mean serum leptin level was significantly higher in STZ-HF (1792.0}1378.8 pg/mL) compared to STZ-NonHF (634.0}149.1 pg/mL), C-NonHF (671.5}164.0 pg/mL) and C-HF group (593.8}200.8 pg/mL) (p<0.05). In STZ-HF group, a significant positive correlation between leptin and glucose level was observed (r=0.71; p=0.048). Conclusion : Our study results show that high fat diet induces an increase in serum leptin and the decrease in adiponectin levels in STZ diabetic rats and suggests that high fat diet impairs glucose control by increasing leptin secretion. Key words: Diabetes mellitus, leptin, adiponectin, obesity

Exercise training may increase production of free radicals and reactive oxygen species in different ways. The training type and intensity may influence free radicals production, which leads to differences in oxidative stress status between athletes, but the results of the previous studies are incosistent. The aim of our study was to estimate oxidative stress status in elite athletes engaged in different sport disciplines. The study included 39 male highly skilled professional competitors with international experience (2 Olympic players): 12 wrestlers, 14 soccer players and 13 basketball players in whom we determined the levels of advanced oxidation protein products (AOPP) and malondialdehyde (MDA), as markers of oxidative stress and the total antioxidative capacity (ImAnOX) using commercially available assay kits. The mean AOPP concentration was not significantly different between soccer players, wrestler and basketball players (60.0 ± 23.0 vs. 68.5 ± 30.8 and 80.72 ± 29.1 μmol/L respectively). Mean ImAnOX concentration was not different between soccer players (344.8 ± 35.6 μmol/L), wrestlers (342.5 ± 36.2 μmol/L) and basketball players (347.95 ± 31.3 μmol/L). Mean MDA concentration was significantly higher in basketball players (1912.1 ± 667.7 ng/mL) compared to soccer players (1060.1 ± 391.0 ng/mL, p=0.003). In spite of this fact, oxidative stress markers levels were increased compared to referral values provided by the manufacturer. Type of sports (soccer, wrestler or basketball) have no impact on the levels of oxidative stress markers. Elite sports engagement is a potent stimulus of oxidative stress that leads to the large recruitment of antioxidative defense. Oxidative stress status monitoring followed by appropriate use of antioxidants is recommended as a part of training regime.

E. Kučukalić-Selimović, A. Valjevac, Almira Hadžović-Džuvo

The utility of procollagen type 1 N-terminal propeptide (P1NP) in the management of metabolic bone diseases remains a subject of debate since the reference ranges are not rigorously established and fail to account for many of the preanalytical variables. We aimed to establish reference intervals for P1NP level in healthy and osteoporotic postmenopausal females stratified by age, body mass index and menopausal duration. We also aimed to assess the relationship between P1NP and BMD. This cross-sectional study enrolled 183 postmenopausal females who were divided in osteoporosis group (N=93) and control group (N=90) with preserved bone mass based on BMD assessed by DXA. In the osteoporosis group median P1NP was significantly higher (51.7 ng / mL; 95%CI 43.2-53.7) compared to control group (38.9 ng/mL; 95%CI 34.2-43.9)(p<0.01). After controlling for age, BMI and years since menopause, there was significant inverse association between BMD and P1NP at the femoral neck (r=-0.18), total hip (r=-0.207) and lumbar spine (r=-0.236). There was no significant difference in P1NP concentration across quartiles of age in postmenopausal females. P1NP was significantly lower in obese postmenopausal females with preserved bone mass compared to normal weight and overweight females in control and in osteoporosis group. In conclusion, we showed that P1NP is inversely associated with BMD even after controlling for age, BMI and years since menopause. Although, P1NP is significantly higher in postmenopausal females with osteoporosis compared to postmenopausal females with preserved bone mass its low specificity does not warrant its utility is diagnosing osteoporosis.

B-type natriuretic peptide (BNP) and adiponectin play important role in the cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum levels followed by isoproterenol (ISO) administration to rats and explored the relationship between them. Cardiac troponin I (cTnI) blood level was used as biochemical evidence of myocardial damage development. Adult male Wistar rats (average body weight 273.33 ± 21.63 g) were distributed into groups: control group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous single dose 100 mg/kg of rat body weight). ISO group was divided into two groups according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2 hours after ISO administration); ISO II (n=6; 4 hours after ISO administration). Blood for determination of parameters was taken from rat abdominal aorta. BNP, adiponectin and cTnI were determined by ELISA method. Data were statistically analysed by using SPSS version 13 computer program. P value less 0.05 was considered statistically significant. Blood BNP and adiponectin were lower at 2 hours after ISO administration in comparison with control group (p=0.004 for BNP and p=0.174 for adiponectin). Four hours after ISO administration, we have noted significant elevation of both parameters compared to ISO I group (p=0.004 for BNP; p=0.02 for adiponectin). Test of correlation have showed significant relation between their blood levels during experimental period (rho=0.577; p=0.01). BNP and adiponectin are not simple indicators of myocardial damage development. They have possible associated and additive effects in cardiovascular homeostasis regulation.

E. Kučukalić-Selimović, J. Alagić, A. Valjevac, Almira Hadžović-Džuvo, A. Begić, N. Bešlić

Serum thyreoglobulin (Tg) and whole body scintigraphy (I-131 WBS) have been used to detect recurrent and metastatic thyroid cancers postoperatively. However, discordant results of Tg measurement and 131I WBS have been reported. Negative 131I WBS and a positive Tg test are usually found, but less common occurrence of positive 131I WBS and a negative Tg test has also been demonstrated in a small but significant number of cases. Therefore, the aim of the study was to retrospectively analyse patients with positive 131I WBS after total thyreoidectomy and again 1 year after the radioactive iodine. There were 52 patients included in the study. Four weeks after surgery, during which thyroid hormone treatment was not introduced, each patient received an ablative dose of 131I. The evaluation of the WBS was qualitative and considered positive if thyroid remnant, lymphatic node or metastasis were detected. WBS and serum Tg was measured 12 months after 131I ablation with thyroid hormone suppression. We considered positive any Tg level above the sensitivity values and negative if lower than this level. Tg levels were related to the existence of a positive scan or a negative one. In our 52 WBS positive patients concordant positive Tg levels were observed in 42 patients while in 10 patients we found a negative Tg levels after the surgery. After 1-year follow-up, out of initially 42 concordant patients 8 patients showed remaining concordant positive Tg and WBS values. Discordant results were observed in 13 patients (4 patients were Tg- and WBS+ while 9 patients were Tg+ and WBS-). In the majority of patients (50%) remained with concordant results but changed from Tg+ and WBS+ to Tg- and WBS-. Diagnostic WBS is an additional valuable tool, besides Tg levels, in the follow up of patients after total thyreoidectomy.

The aim of this study was to investigate possible differences in blood glucose levels between male and female rats immediately after acute bout of forced swimming exercise. Adult male Wistar rats (weight 300350 g) were divided into two groups by gender: males (n =8) and females (n =8). All the rats were given standard rat chow and tap water ad libitum and were housed at 25±3o C on a 12-hour dark/light cycle. Both groups of rats were exposed to forced swimming stress daily, for 6 days. Duration of each swimming session progressively increased from 5 minutes on the first day to 30 minutes on sixth day, allowing adaptation to swimming conditions. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep) containing tap water (temperature ca. 25 degrees C). The depth of water was 40 cm. Seventh day we performed acute bout of 40 minutes swimming exercise. Animals were fasted 12 hours before start of last swimming sessions to obtain fasting blood glucose levels. Preexercise blood samples were taken immediately before th last swimming session (7 day) and postexercise samples immediately after the last swimming session from rat's tail vein. Glucose levels in blood were determined using Optium XceedTM Diabetes Monitoring System (Abbot). Before last swimming session male rats had slightly lower glucose levels in comparation with female rats, but this difference was not statistically significant (3.77vs4.64 mmol/l). Acute bout of forced swimming exercise raised blood glucose level and established values in postexercise period were significantly higher in both study group in comparation to values before exercise. Male rats had greater postexercise glucose blood levels (11.85 mmol/l) in comparation with female rats (6.26 mmol/l). Our findings document the existence of gender impact on the glucose postexercise concentrations confirming the differences in the energy substrates utilization and glucose metabolism regulation during and after exercise.

AIM γ-glutamyl transferase (GGT) is an independent prognostic marker for cardiac death and reinfarction in patients with coronary artery disease, but its clinical significance during early postmyocardial infarction period is unclear. PATIENTS & METHODS This short-term prospective study included 40 patients with acute myocardial infarction (AMI) in whom we determined GGT activity, lipids, uric acid, homocysteine (Hcy), high sensitivity C-reactive protein (hsCRP) and left ventricular (LV) function on admission and on day 5 following AMI. RESULTS In AMI patients on admission, logGGT was associated with logHcy (r = 0.36), uric acid (r = 0.48) and CK-MB activity (r = -0.41). Uric acid remained an independent determinant of serum GGT activity on admission. Significant increase in GGT activity (77.7%) was observed following AMI. On day 5 serum logGGT was significantly associated with LV relative wall thickness (r = -0.37), LV end-diastolic diameter (r = 0.41) and LV fractional shortening (r = -0.36). In addition, a significant positive correlation was found between serum logGGT and loghsCRP (r = 0.41) and logHcy values (r = 0.395), but only LV end-diastolic diameter remained independently associated with serum GGT activity on day 5 following AMI. CONCLUSION GGT is associated with oxidative/inflammatory markers and LV diastolic diameter suggesting its potential role in predicting LV dilatation and dysfunction during the early postmyocardial infarction period.

This study investigated whether serum C-reactive protein (CRP) concentration is increased in patients with type 1 diabetes mellitus with a normal body mass index (BMI) and whether BMI, glycated haemoglobin (HbA1c) and CRP are correlated in patients with type 1 diabetes. High-sensitivity CRP was determined by immunonephelometry and HbA1c by an immunoturbidimetric method in 30 patients with type 1 diabetes and 30 healthy individuals matched for age, sex and BMI. Median serum CRP concentration in patients with type 1 diabetes (1.34 mg/L) was significantly higher than healthy individuals (0.2 mg/L; p<0.0001). Positive correlation between CRP and BMI was observed (rho=0.598; p<0.0001), but no significant correlation was observed between CRP and HbA1c (rho=0.285; p=NS) in patients with type 1 diabetes. Increased CRP levels in type 1 diabetes patients do not appear to be associated with glycaemic control, and may reflect low-grade inflammation associated with atherosclerosis, as well as activation of innate immune activity. Br J Diabetes Vasc Dis 2011;11:249-252

Endothelial dysfunction is associated with diabetic micro- and macroangiopathy as well as with the decline in creatinine clearance. It has been suggested that endothelial dysfunction presents in patients (pts) on continuous ambulatory peritoneal dialysis (CAPD). The objective of this study was to examine the plasma biomarkers of endothelial dysfunction and their association with IMT of carotid arteries in diabetic and non-diabetic patients on CAPD. This study included 37 CAPD pts (25 with type II diabetes and 12 non-diabetic pts) mean age 59.2 years ± 2.48. Plasma von Willebrand factor (vWF) activity, serum albumin, glucose, total cholesterol, triglycerides and lipoprotein (a) levels, as well as serum level of homocysteine, parathyroid hormone (PTH) in plasma and microalbuminuria was determined. Ultrasound examination of carotid arteries was performed in all patients by measured bilateral intima-media thickness of carotid artery (CIMT). Mean IMT value was significantly higher in type 2 DM patients (0.86 ± 0.04 mm) compared to non-diabetic patients (0.52 ± 0.06 mm) on peritoneal dialysis (p<0.0001). There was also a significant difference in lipids /triglycerides and Lp (a)/, procoagulation (fibrinogen, von Wilebrand factor, factor VIII) and inflammatory markers (CRP) level between type 2 DM and non-diabetic CAPD patients. A stepwise multiple regression analysis revealed that log triglycerides and factor VIII were independent factors for the IMT. The results of this research impose that diabetic type 2 CAPD patients have developed systemic alteration of endothelial function and higher risk of cardiovascular complications compared to non-diabetic CAPD patients.

E. Kučukalić-Selimović, A. Valjevac, Almira Hadžović-Džuvo, A. Skopljak-Beganović, R. Alimanović-Alagić, A. Brković

Antiresorptive agents are widely used to treat osteoporosis. Both reduction in bone turnover and increase in BMD may be necessary to decrease the fracture risk. The aim of the study was to evaluate the effects of aledronate on bone turnover markers and bone mineral density in postmenopausal women with osteoporosis. The study involved a group of 56 postmenopausal women with osteoporosis treated with alendronate (70 mg) weekly at the Institute of Nuclear Medicine Clinical Center University of Sarajevo during a 12-months period. Bone mineral density (BMD) at lumbar spine and proximal femur and bone turnover markers (serum β-CrossLaps, urinary N-telopeptides of type I collagen (NTx), total serum alkaline phosphatase (AP) and serum osteocalcin) were measured at baseline and after 12 months of the treatment with aledronate. BMD values significantly increased both at lumbar spine by 13.46% and proximal femur by 21.96% during the study period (-3.12±0.24 vs. -2.7±0.19 and -2.55±0.2 vs. -1.99±0.19 respectively; p<0.001). Bone turnover markers significantly decreased during the study period; C-terminal telopeptides of type I collagen fragment (β-CrossLaps) 49.0% (0.51±0.05 vs.0.26±0.028 ng/mL), NTX 33.4% (48.3±4.9 vs.32.15±3.25 nMBCE/mM Cr), AP 24.3% (81.1±5.2 to 61.43±5.2 IU/L) and serum osteocalcin by 29.7% (34.3±2.65 to 24.1±1.36 ng/mL)(p<0.001). Alendronate treatment increased BMD and reduced the level of bone turnover markers. Therefore, the treatment with aledronate during 12 months period can be recommended in postmenopausal women with osteoporosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is characterized by loss of myelin, the fatty tissue that surrounds and protects nerve fibres allowing them to conduct electrical impulses. Recent data indicate that oxidative stress (OS) plays a major role in the pathogenesis of multiple sclerosis (MS). The aim of this study was to estimate level of serum total antioxidative capacity in patients with multiple sclerosis. Our cross-sectional study included 33 patients with MS and 24 age and sex matched control subjects. All our patients had a Poser criteria for definite diagnostic categories of multiple sclerosis. Serum total antioxidant capacity (TAC) was measured by quantitative colorimetric determination, using Total antioxidant Capacity-QuantiCromAntioxidant Assay Kit (BioAssay systems, USA; DTAC-100). Mean serum TAC in multiple sclerosis group of patients was 119.2 mM Trolox equivalents and was significantly lower (p<0.001) compared to the control group of subjects (167.1 mM Trolox equivalents). Our results showed that oxidative stress plays an important role in pathogenesis of multiple sclerosis. This finding, also, suggests the importance of antioxidants in diet and therapy of MS patients.

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