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Almira Hadžović-Džuvo, O. Lepara, A. Valjevac, N. Avdagić, Asija Začiragić

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

A. Ćatović, A. Dervišević, O. Lepara, Semir Gorčević, Jasna Gorčević

Introduction: There are wide variations in diet patterns among population subgroups. Macronutrients content analyses have become necessary in dietary assessment. The purpose of this study is to analyze dietary saturated fatty acids intake in students, detect differences between men and women, and compare with nourish status and nutrition recommendations.Methods: A cross-sectional survey of 60 graduate students was performed during the spring 2013, at the Sarajevo University. Food-frequency questionnaire was conducted during seven days. Body mass index was used to assess students' nourish status. Statistical analyses were performed using the Statistical Package for Social Sciences software (version 13.0).Results: Mean age of males was 26.00±2.72, and of females was 27.01±3.93 years. The prevalence of overweight was more common among males compared to females (55.56% vs. 6.06%). Median of total fat average intake for men and women was 76.32(70.15;114.41) and 69.41(63.23;86.94) g/d, respectively. Median of saturated fatty acids average intake for men and women was 28.86(22.41;36.42) and 24.29(20.53;31.60) g/d, respectively. There was significant difference in average intake of total fat between genders (Mann-Whitney U test: p=0.04). Macronutrient data were related to requirement of reference person. Total fat intake was beyond recommended limits in 37.04% of males and 54.55% of females. Saturated fatty acids intake was beyond the upper limit in 55.56% of males and 51.52% of females.Conclusion: Diet pattern of the average student is not in accordance with the recommendations of saturated fatty acids contribution as a percentage of energy.

Z. Lepara, D. Junuzović, B. Kulovac, S. Sadović, J. Kovačević, Almir Fajkić, O. Lepara, E. Bašić

Objectives: The aim of this study was to evaluate serum C-reactive protein (CRP) concentration in patients with bladder cancer, as well as to determine its potential role as biomarker in the differentiation of different stages of the disease. Methods: The study included 90 patients with bladder carcinoma who were divided into 3 groups: 30 patients with non-invasive, superficial (Ta), 30 patients with superficial (T1), and 30 patients with invasive (T2-T4) bladder cancer. Serum CRP level was determined by laser nephelometry. Results: Serum CRP levels in T2-T4 group of patients was 8.65 (3.20-18.20) mg/dL and significantly higher compared to the serum CRP level in Ta group of patients (1.55 (0.67 - 3,35) mg/dL; p<0.005), T1 group (1.90 (1.27-7.20) mg/dL, p=0.006) and compared to the control group of patients (1.20 (0.90-2.10) mg/dL; p<0.005). Multiple linear regression revealed that serum CRP level was independently associated with the tumor size (β = 0.376; p<0.001). There was an independent positive association between CRP and high progressing potential of the bladder cancer. Conclusion: CRP might have a significant role as a biomarkerin the diagnosis of this disease, with special attention on its potential role in differentiating different stages of the disease. Keywords: C-reactive protein, bladder cancer, biomarker, inflammation

Almira Hadžović-Džuvo, A. Valjevac, O. Lepara, Samra Pjanić, A. Hadžimuratović, Amel Mekić

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.

N. Avdagić, N. Babic, Asija Začiragić, Almira Hadžović Džuvo, O. Lepara, Emina Nakaš Ićindić

Aim: To investigate the capacity of mean platelet volume (MPV) in detecting CD disease activity and in differentiating CD patients from healthy controls. Methods : MPV values were measured in 30 CD patients and 30 healthy individuals matched for age and gender. Based on the result of Crohn’s Disease Activity Index, CD patients were subdivided into two subgroups: active and inactive phase of disease. MPV was measured by standard methods for all study participants. Results: A significant decrease in MPV was noted in CD patients compared to healthy controls (p=0.002). When active CD patients were compared with inactive CD patients, a  significant decrease in MPV was also found (p=0.031). The overall accuracy of MPV in discriminating CD patients from healthy controls as well as active from inactive CD patients was 66% (cut-off level of 8.83 fL). Significant negative correlation between MPV and platelet count (PLT) (rho= -0.570; p=0.01) and significant positive correlation between MPV and platelet distribution width (PDW) (rho= 0.615; p=0.01) was observed in CD patients. Conclusion: Based on our results that have shown significant difference in MPV that was related to Crohn’s disease activity, we consider that MPV could be added to other serological markers of CD, especially in differentiating the active from the inactive phase of disease. Key words: mean platelet volume, Crohn’s disease, inflammatory bowel disease

N. Avdagić, Asija Začiragić, N. Babic, M. Hukić, M. Šeremet, O. Lepara, E. Nakas-ićindić

The aim of this study was to investigate changes in serum nitric oxide (NO) concentration in inflammatory bowel diseases (IBD) patients and its use as potential biomarker in differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) and in disease activity assessment. In 60 patients of both genders - 30 with ulcerative colitis and 30 with Crohn's disease - and 30 controls serum nitric oxide concentration was determined by measuring nitrite concentration, a stable metabolic product of NO with oxygen. Conversion of nitrates (NO3-) to nitrites (NO2-) was done with elementary zinc. The nitrite concentration was determined by classic colorimetrical Griess reaction. Median serum NO concentration was statistically different (p=0,0005) between UC patients (15.25 µmol/L; 13.47 - 19.88 µmol/L), CD patients (14.54 µmol/L; 13.03 -16.32 µmol/L) and healthy controls (13.29 µmol/L; 12.40 - 13.92 µmol/L). When active UC and CD patients were compared with inactive UC and CD patients respectively a significant difference in serum NO level was found (p=0.0005). With a cut-off level of 17.39 µmol/L NO had a sensitivity of 100% and a specificity of 100% in discriminating between active and inactive UC patients. With cut-off value of 14.01 µmol/L serum NO level had a sensitivity of 88% and a specificity of 69% in distinguishing between patients with active CD and inactive CD. Serum NO concentration is a minimally invasive and rapid tool for discriminating between active and inactive IBD patients and could be used as useful biomarker in monitoring of disease activity in IBD patients.

I. Potolicchio, V. Cigliola, S. Velazquez-Garcia, P. Klee, A. Valjevac, Dina Kapić, E. Ćosović, O. Lepara et al.

Almira Hadžović-Džuvo, Eldan Kapur, A. Valjevac, O. Lepara, N. Avdagić, Jasmin Alajbegović

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.

A. Valjevac, A. Džubur, E. Nakas-ićindić, Almira Hadžović-Džuvo, O. Lepara, E. Kiseljaković, R. Jadric

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.

Asija Začiragić, N. Mulabegović, J. Huskic, A. Valjevac, N. Avdagić, Almira Hadžović-Džuvo, O. Lepara, S. Dobraca et al.

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

Almira Hadžović-Džuvo, O. Lepara, A. Valjevac, N. Avdagić, S. Hasić, E. Kiseljaković, Saida Ibragić, A. Alajbegović

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.

Almira Hadžović-Džuvo, A. Valjevac, N. Avdagić, O. Lepara, Asija Začiragić, R. Jadric, Jasmin Alajbegović, B. Prnjavorac

AIM To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. METHODS Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n = 8) and stress group (n = 8). Rats in the stress group were exposed to forced swimming stress daily, for 7 days. 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. Duration of each swimming session progressively increased from 10 minutes on the first day to 40 minutes on days 6 and 7. Rats were sacrificed and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.). RESULTS There was no statistically significant difference between mean BNP serum level in the stress group after the swimming period (0.81 +/- 0.14 ng/ml) as compared to the unstressed group of rats (0.8 +/- 0.08 ng/ml). After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs. 272.8 g), but this difference was not statistically significant. The stress period had no influence on food intake in the stress rat group. CONCLUSION The workload consisting of 40-minutes long swimming session is not sufficient to provoke BNP release from myocardium in rats.

Salih Valjevac, Almira Hadžović-Džuvo, A. Valjevac, E. Kučukalić-Selimović, O. Lepara

Thyroid hormones might lead to significant decrease in pulmonary ventilation in patients with dysfunctional thyroid disorders. The aim of the study was to assess the pulmonary ventilation in patients with thyroid dysfunctional states. This observational, cross-sectional study included 20 patients with hyperthyroidism, 20 patients with hypothyroidism and 20 euthyroid subjects. Serum FT3, FT4 and TSH levels were determined with the ElectroChemiLuminiscent immunoassay. Spirometry analysis was performed on portable spirometer SpiroUSB using the software Spida 5 for the analysis. We determined VC%, FVC%, FEV1% and FVC/ FEV1% Mean VC% was significantly lower in hyperthyroid (94,18±1,24%) and hypothyroid (96,13±1,09%) compared to euthyroid group of subjects (98,54±0,93%)(p

Almira Hadžović-Džuvo, E. Kucukalic, E. Nakas-ićindić, O. Lepara, A. Valjevac, S. Rašić, A. Begić, E. Sofić

Aim: Cardiovascular changes that accompany thyroid disorders could be stimulus for the release of BNP from heart ventricles. Different factors, including stress environment conditions, have important role in pathogenesis of thyroid disorders and could possibly affect this response. The aim of this study was to assess the relationship between NT-proBNP and thyroid hormones levels in females with different thyroid functional states. Materials and methods: The study included 104 female patients, age 18-55 years, divided into three groups: hyperthyroid, hypothyroid and euthyroid (control). Serum NT-proBNP, FT3, FT4 and TSH levels were determined in all groups, but in hyper- and hypothyroid group before and after the adequate therapy aimed to the regulation of thyroid status. NT-proBNP concentration was determined by Electrochemiluminescent Immunoassay “ECLIA” method on Roche Elecsys 2010 system. Results: Mean serum NT-proBNP level in hyperthyroid group, before the therapy was 99.35 pg/mL and was significantly higher compared to serum NT-proBNP levels in control (65.90 pg/mL) and hypothyroid group (56.82 pg/mL, p<0.05). After therapy, serum NT-proBNP levels significantly decreased in hyperthyroid (53.64 pg/ml, p<0.01) and significantly increased in hypothyroid group (69.95pg/mL, p<0.04). A significant correlation between serum thyroid hormones, TSH and NT-proBNP levels were observed in hyperthyroid patients, but in hypothyroid patients only between NT-proBNP and FT3 levels. Multiple regression analyses demonstrated that FT3 level was independently associated with serum NT-proBNP levels in hyperthyroid group, after normalization of thyroid status. Conclusion: Thyroid hormones possibly effect BNP secretion and therefore affect the serum

Almira Hadžović-Džuvo, E. Kučukalić-Selimović, E. Nakas-ićindić, O. Lepara, A. Valjevac, S. Rašić, Dinan Al Tawil, A. Begić et al.

1Institute of Physiology and Biochemistry, Faculty of Medicine, University of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina 2Institute of Nuclear Medicine, University of Sarajevo Clinical Center, Bolnicka 25, 71000 Sarajevo, Bosnia and Herzegovina 3Clinic of Nephrology, University of Sarajevo Clinical Center, Bolnicka 25, 71000 Sarajevo, Bosnia and Herzegovina 4Policlinic of Internal Medicine “Al Tawil,” Koste Hermana 1, 71000 Sarajevo, Bosnia and Herzegovina 5Faculty of Science, University of Sarajevo, Bosnia and Herzegovina

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