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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.

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.

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.

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.

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