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Objectives: We hypothesized that cardiac biomarker levels could be elevated in patients with dementia due to high frequency of cardiovascular risk factors in older patients with vascular and neurodegenerative type of this disease. The aim was to determine possible association between cardiac Troponin I (cTnI) blood levels and dementia. Methods: The cross-sectional study included 88 patients, female gender, and mean age 81 years, who were recruited from specialized unit of the Health Care Hospice for persons with disabilities in Sarajevo, Bosnia and Herzegovina. According to the Hachinski ischemic score, 59 patients with dementia were classified in two groups- vascular (VD) and neurodegenerative dementia (ND), while 29, age-matched asymptomatic persons, were used as a control group(CG). The cTnI was measured using ELISA kit Humani Tn-I/TNNI3 (Elabscience Biotechnology Co., Ltd), using immunoanalayzer STAT FAX 2100, USA. Results: The Mini-Mental State Examination (MMSE)score was significantly lower in dementia patients than in control group (p<0.01). No significant difference in cardiac TnI levels was found in Alzheimer’s (AD), vascular dementia (VD)  and control group (AD: Me = 3.41, VD: Me = 3.49, control group: Me=3.57; (p=0.737). Conclusion: The participants’age and comorbidities are probable factors causing no association between dementia and cTnI. It is known that troponins are associated with risk of dementia but cTnI levels are as well under influences of a possible epigenetic modification of cTnI that should be the objects of the future investigation.

Introduction: Serum uric acid (SUA) is the final product of purine metabolism in humans. Aim: The present study aimed to identify a potential association between serum UA and cardiac troponin I (cTnI) levels and to find out whether uric acid could differentiate patients presenting with the acute myocardial infarction (AMI) and unstable angina pectoris (UAP) in hyperuricemic and normouricemic acute coronary syndrome (ACS) patients. Methods: Eighty ACS patients, aged 50-83 years, were enrolled in the study, 40 of them presenting with AMI and 40 with UAP. Frequency of patients with serum uric level over threshold for hyperuricemia was investigated and two groups of patients were formed such as hyperuricemic and normouricemic groups (A and B groups, respectively) independently of type of ACS. Those groups of patients were also subjected to cTnI measurement. Results: Levels of SUA are associated with the type of ACS in the hyperuricemic ACS patients (AMI versus UAP, 499(458-590), 425(400-447) mmol/L, p=0.007, respectively). Uric acid correlated significantly with cTnI, moderate positively in the group A (rho=0.358, p=0.038) and moderate negatively in the group B (r=-0.309, p=0.037) of ACS patients. Multiple logistic regression analysis revealed that cTnI and age were independently associated with the SUA levels in the group A of ACS patients. Conclusions: Serum uric acid differentiates AIM and UAP patients in hyperuricemic group of acute coronary syndrome. Therefore it can be used as nonspecific parameter for evaluation of the myocardial lesion extent only in hyperuricemic ACS patients. This is supported by finding that cTnI along with age predicts SUA level in hyperuricemic ACS patients.

Objectives: We hypothesized that serum heart fatty acid binding protein (HFABP) levels could be affected by hypertension in addition to renal impairment in patients on hemodialysis. The aim was to find out possible association between serum HFABP and hypertension in patients treated by hemodialysis. Methods: The cross-sectional study included 72 patients, both gender, age 18-78 years who were recruited from Clinic for Hemodialysis, University Clinical Center Sarajevo. According to Kidney Disease Outcomes Quality Initiative criteria for hypertension, patients were distributed into 2 groups: normotensive (HD-N) and hypertensive (HD-H) group. The cardiac biomarker HFABP was measured using ELISA kit Human FABP3 (Elabscience Biotechnology Co.,Ltd), on immunoanalyzer STAT FAX 2100, USA. The kidney functional biomarkers were measured spectrophotometrically using automated analyzer. Results: Serum HFABP level was lower in HD-H group (3.02(1.96-4.13) ng/mL) compared to serum HFABP in HD-N group (3.38(1.98-5.37) ng/mL)(p=0.359). Patients in HD-N group were older and treated by hemodialysis for a longer time than those in HD-H group (p<0.001 and p=0.029, respectively). Conclusion: Serum HFABP level in normotensive patients on hemodialysis is not significantly different compared to hypertensive patients suggesting that heart type fatty acid binding protein might not be significantly affected by hypertension in hemodialysis patients. Keywords: HFABP, hemodialysis, blood pressure, cardiovascular risk

Lejla Ibričević-Balić, E. Ićindić-Nakas, S. Hasić, E. Kiseljaković, A. Sofo-Hafizović, Šefkija Balić

Introduction: Anemia occurs in 60% to 80 % of patients with newly diagnosed myeloma multiplex (MM). The cause of anemia in MM is probably multi factorial and involved among the others hepcidin and some cytokines, especially interleukine-6. Anemia in MM is one of the risk factor used in Durie-Salmon classification for staging and prognostic score. Treatment options are set according to this score with most significant impact on survival. Aim: To estimate baseline level of serum hepcidin, IL-6 and iron metabolism markers in anemic MM patients, possible role of hepcidin and its interaction with IL-6. Methods: 27 patients with newly diagnosed MM were enrolled in this observational, prospective study and age, gender matched 60 healthy controls. Erythrocyte count, hemoglobin, serum hepcidin, interleukin-6, iron, ferritin and transferrin were measured. Results: Anemia was diagnosed in 70% of MM patients. Serum hepcidin was significantly higher in MM group (55.5 ng/mL) than in control 5.9 ng/mL (p=0000). In myeloma patients serum IL-6 was 3.59 pg/mL, anemic 3.80 pg/mL, non-anemic 0.33 pg/mL, without significant difference. It was not found significant correlation between hepcidin and IL-6 in anemic myeloma patients. Conclusion: High level of hepcidin probably causes anemia in MM but its high expression is not due only to IL-6.

Background: Advanced paternal and/or maternal age is a classic risk factor for Down syndrome. The aim of the study was to investigate the frequency of Down syndrome types in children and its association with maternal and paternal age in Bosnia and Herzegovina. Subjects and Methods: The cross sectional, observational study included 127 children, 49 girls and 78 boys, aged 1-180 months suspected to have Down syndrome, admitted to the Centre for Genetics, Faculty of Medicine University of Sarajevo, for cytogenetic analysis and differential diagnosis of Down syndrome during the period from January 2010 to May 2015. Standard method of 72 hours cultivation of peripheral blood lymphocytes has been applied. The accepted level of statistical significance was p<0.05. Study Results: The most common type of Down syndrome was standard trisomy (86.6%), comparing to translocation and mosaicism (7.1%; 6.3%, respectively). The highest frequency of Down syndrome cases was in mother and father’s group from 30-39 years old (57; 57 children, respectively) compared to mother and father’s groups with younger than 30 (44; 29, respectively) and 40 and older (26; 41, respectively). The significant difference was found in maternal age between translocation and mosaicism groups (p=0.036). Difference between parental years and type of Down syndrome was significant when Standard trisomy 21 and translocation (p=0.045), as well as mosaicism and translocation (p=0.036), were compared. Conclusion: The most common type of Down syndrome was standard trisomy 21, with highest occurrence in parents from 30 to 39 years old. Parents were the youngest in translocation group. Obtained results suggest that multidisciplinary approach to identifying the trigger for trisomy appearance and the influence of maternal age is required.

Damira Kadić, S. Hasić, Emina Spahić

AIM To investigate association of mean platelet volume (MPV) and glycemic control markers, and whether MPV could be used as a predictor of deterioration of glucoregulation in Diabetes mellitus type 2 (DMT2) patients. METHODS The cross-sectional study included 106 DMT2 patients, treated at the Primary Health Care Centre in Zenica, distributed into groups according to glycated haemoglobin (HbA1c) values: A(n=44, HbA1c ≤7.0%) and B (n=62, HbA1c>7.0%). Spearman's correlation coefficients were calculated to evaluate the relationships between MPV and glycemic control markers. Binomial logistic regression analysis was performed to estimate the relationship between glycemic control, as dichotomous outcome, and MPV as the main predictor. Diagnostic value of MPV as a marker for poor glucoregulation was estimated by using ROC analysis. RESULTS Mean platelet volume was significantly higher in the group B compared to the group A (p<0.0005). Significant positive correlations of MPV with fasting blood glucose and HbA1c were found in the total sample (rho=0.382, p<0.0005; rho=0.430, p<0.0005, respectively). Mean platelet volume was positively associated with the risk of inadequate glycemic control, with 2 times increased odds of inadequate glycemic control per femtoliter greater MPV (Exp (β) =2.195; 95% CI=1.468 - 3.282, p<0.0005). The area under ROC curve for MPV was 0.726 (95% CI: =0.628- 0.823, p <0.0005). At the best cut-off value 9.55 fL, MPV showed sensitivity of 82% and specificity of 54.5%. CONCLUSION Mean platelet volume correlates with glycemic control markers in DMT2 patients. It could be used as a simple and cost-effective predictor of deterioration of glucoregulation.

Introduction: Renalase is a protein secreted in kidneys and considered as a blood pressure modulator. High rates of hypertension and its regulation in patients on hemodialysis demands search for potential cause and treatment. The aim of this study was to determine the genotype and allele frequencies of renalase gene rs2576178 polymorphism in population from Bosnia and Herzegovina. Also, the objective of present study was to find the possible association between renalase gene rs2576178 polymorphism and hypertension in patients on hemodialysis. Material and Methods: The genotype of renalase gene rs2576178 polymorphism was determined in 137 participants (100 patients on hemodialysis and 37 controls), using polymerase chain reaction (PCR) and subsequent cleavage with MspI restriction endonuclease. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium using a Chi-squared test. The value of P<0.05 was considered as statistically significant. Results: Comparison of genotype distribution and allele frequency in participants on hemodialysis with and without hypertension, and healthy control showed no statistical difference. Conclusion: The results of the study suggest that renalase gene rs2576178 polymorphism is not a factor that influences blood pressure in patients on hemodialysis.

Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (P < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P < 0.05) and plaque score on CA in these patients (P < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS.

AIM To assess serum levels and correlation between uric acid (UA) and C-reactive protein (CRP) in acute coronary syndrome (ACS) and apparently healthy individuals. METHODS The cross-sectional study included 116 examinees of age 44 to 83 years, distributed in two groups: 80 ACS patients including 40 with acute myocardial infarction (AMI), and 40 with unstable angina pectoris (UAP), and 36 apparently healthy (control group) individuals. Patients with ACS were hospitalized at the Cardiology Clinic, Clinical Centre Sarajevo in the period October- December 2012. Laboratory analyses were conducted by standard methods. The accepted statistical significance level was p<0.05. RESULTS Serum levels of CRP and UA were higher in patients with ACS as compared to control group (p<0.01). The median serum UA was insignificantly lower, and CRP was significantly higher in patients with AMI compared to UAP (p=0.118 and p=0.001, respectively). CRP and UA correlated positively in both ACS and control groups (rho=0.246; p=0.028 and rho=0.374; p=0.027). A positive correlation between serum CRP and UA was noted in patients with AMI, but negative in patients with UAP (p>0.05). CONCLUSION The correlation between CRP and UA in the patients with ACS indicates the association of oxidative stress and inflammation intensity in damaged cardiomyocytes. Correlation between UA and CRP in apparently healthy individuals indicates a possible role of UA as a marker of low-grade inflammation and its potential in risk assessment in cardiovascular diseases.

AIM To investigate effects of post-sampling analysis time, a type of blood samples and collection tubes on blood gas testing. METHODS This study included 100 patients at the Clinic for Pulmonary Diseases, Clinical Centre Sarajevo. The partial pressure of oxygen (pO2) and carbon dioxide (pCO2), and the oxygen saturation level of hemoglobin (sO2) were analyzed in the arterial blood samples (ABS) and capillary blood samples (CBS) by a potentiometric method using a blood gas analyzer ABL 555 (Radiometer, Copenhagen, Denmark). Paired measurements of ABS were performed within 15 minutes and after 60 minutes from sampling and compared. The results of CBS obtained within 15 minutes were compared with matching ABS results, as well as the results obtained from CBS within 15 minutes taken into glass and plastic tubes. RESULTS pO2 and sO2 values were significantly lower after 60 minutes compared to those within 15 minutes in ABS (9.20±1.89 vs. 9.51±1.95 and 91.25±5.03 vs. 92.40±4.5; p<0.01, respectively). Values of pO2 and sO2 in CBS were significantly lower than values obtained in ABS (8.92±2.07 vs. 9.51±1.95 and 91.25±4.86 vs. 92.40±4.50; p<0.01, respectively). Obtained pO2 and sO2 values in CBS in the plastic tubes were higher than those in the glass tubes (8.50±1.98 vs. 7.89±2.0 and 89.66±11.04 vs. 88.23±11.22, p<0.01 respectively). pCO2 blood values were not influenced significantly (p>0.05). CONCLUSION The length of post-sampling analysis time, a type of blood samples and collection tubes have significant impact on blood oxygen parameters. Analysis within 15 minutes after blood sampling is considered as appropriate.

Objective: Renalase is an enzyme that circulates in the blood and modulates the cardiac function, sympathetic tone and systemic blood pressure. It can be synthesized in the kidneys, liver and cardiomyocytes. The active enzyme degrades circulating catecholamines, causing a significant fall in blood pressure. Changes in renalase concentration in hemodialysis patients may explain the frequent occurrence of hypertension among patients with end-stage kidney disease. The aim of this study was to asses’ serum renalase levels in hemodyalisis patients and apparently healthy subjects, and association of renalase and blood pressure in patients group. Design and method: 160 subjects were recruited in the study: 120 with end-stage renal disease, divided into two groups, according to their blood pressures (normotensive and hypertensive), and 40 apparently healthy individuals matched in age and sex. Blood pressure was measured before and after a hemodialysis session. The target values, according to ESH/ESC guidelines, were lower than 140/90 mmHg before, and 130/90 mmHg after hemodialysis. The blood for the estimating serum renalase concentration was taken before dialysis. Enzyme-linked immunosorbent assay (ELISA) kit with monoclonal antibody specific to renalase, was used. Results: Mean serum renalase levels in normotensive as well as hypertensive hemodialysis patients were significantly higher compared to control group {89.32 (45.77–170.22) and 42.7 (32.79–63.35) &mgr;g/ml, respectively; p < 0.0005}. No significant difference of renalase levels among normotensive and hypertensive patients was noted {64.04 (40.76–173.84) and 91.86 (56.77–149.75.35)&mgr;g/ml; (p > 0.05)}. There was a highly significant difference between systolic and diastolic pressure measured before and after the dialysis in normotensive and hypertensive groups of patients (p < 0.0005). It was noted that there is a significant, negatively directed association between patients’ age at the beginning of dialysis and the duration of hemodialysis. Also, the correlation between blood pressure and renalase activity among normotensive and hypertensive hemodialysis patients was not shown (p > 0.05). Conclusions: Further studies are needed to define the role of renalase and its complex pathophysiological link with blood pressure regulation, kidney function and sympathetic tone. Renalase may become a new therapeutic target that leads to a better prognosis for patients with end-stage kidney disease.

ABSTRACT The study aim was to explore the pattern of the changes in haematological and iron status parameters of acute coronary syndrome patients through period 1-7 day of hospital admission in order to define the type of anaemia. Forty-one patients (15 female and 26 male patients, aged 36-81years) of the Clinic for Heart Disease and Rheumatism, University Clinical Center Sarajevo have been included in the cross-sectional study. Haematological and serum iron status parameters have measured on days 1 and 7 of hospital admission. A decrease in haemoglobin levels to <13g/dl in men and <12g/dl in women was notified as anaemia. A significant reduction in red blood cells count, haemoglobin, haematocrit (p<0.01), iron, total iron binding capacity (p<0.05) and significant ferritin elevation (p<0.05) within period the 1-7 day were noted. Percent of anemic patients on day 1 was 17.07 % with increase of number on day 7 (36.36%). Serum ferritin has been elevated with reduction of red blood cells count, mean cell volume, mean corpuscular haemoglobin (p<0.05); haemoglobin, haematocrit (p<0.01) at first 24 hours of admission in anemic versus non-anemic patients. Anemic patients had significantly lower values of percent transferrin saturation (p<0.05), red blood cells count, haemoglobin, haematocrit (p<0.01) compared to non anemic on day 7. A statistically significant negative correlations were obtained between serum iron and C-reactive protein; cardiac troponin I and total iron binding capacity (rho=-0.389, p<0.05; rho=-0.331; p<0.05, respectively). Observed changes in laboratory parameters through period 1-7 day indicate inflammatory type of anaemia in acute coronary syndrome. Key words: anaemia, acute coronary syndrome, haematological, iron status, parameters

E. Kiseljaković, S. Hasić, A. Valjevac, M. Mačkić-Đurović, R. Jadric, B. Mehić, E. Kučukalić-Selimović, S. Ibrulj

The aim of the study was to detect prevalence of MBL2 exon 1 (codons 52, 54 and 57) genetic polymorphism in postmenopausal women in Bosnia and Herzegovina and its possible role as genetic risk factor for susceptibility to occurrence of osteoporosis in this study group. Also, we investigated association between MBL serum concentrations and osteoporosis in postmenopausal women. Genetic codons' variations were determined by PCR-RFLP and MBL in serum was measured by ELISA method in 75 postmenopausal women (37 with osteoporosis and 38 apparently healthy, non-osteoporotic women serving as a control). Serum MBL levels were not significantly different between osteoporosis and control group (492 (37-565.1) and 522.6 (477-559.4) ng/mL respectively, p=0.206). Genotype frequencies were not significantly different (p=0.997) between the studied groups of postmenopausal women. Genotype frequencies A/A, A/0 and 0/0 in osteoporosis group were 0.576; 0.405; 0.018 and in control group 0.562; 0.412; 0.026, respectively. Frequencies of A and 0 allele were 0.78 and 0.22 in osteoporosis and 0.77 and 0.23 in control group. The results do not suggest association of functional polymorphism of MBL2 gene and MBL serum concentration with osteoporosis in postmenopausal females.

Studies that investigated an association between asymmetric dimethylarginine (ADMA) and glycated haemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) have given discordant results. The aim of this study was to determine and compare serum ADMA concentration in patients with T2DM and healthy controls, and to assess correlation between ADMA and HbA1c in patients with T2DM. Serum ADMA concentration was determined by ELISA method with the use of ADMA ® - ELISA kit (DLD Diagnostics, Hamburg, Germany) and HbA1c levels were determined by an immunoturbidimetric method in 60 patients with T2DM and 60 healthy individuals matched for age and sex. Results have shown that mean serum ADMA concentration was significantly higher in T2DM patients (1.54±0.06 μmol/L) compared to mean serum ADMA concentration (0.62±0.02 μmol/L; p<0.0001) in healthy subjects. A significant, positive, correlation between serum ADMA concentration and HbA1c levels was observed (r=0.494; p<0.01) in T2DM patients. Our results suggest that there is an association between endothelial dysfunction and glycaemic control in type 2 diabetes mellitus. Possible explanation for obtained results may be oxidative stress that is increased in conditions of hyperglycaemia and it also promotes endothelial dysfunction. Larger, longitudinal studies are required that will evaluate relation between metabolic abnormalities and increased ADMA levels in patients with type 2 diabetes mellitus.

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.

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