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

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

The aim of this study was to assess echocardiographic changes in female patients with untreated dysfunctional thyroid states and whether the therapy aimed to normalize the thyroid dysfunction could lead to improvement in cardiac systolic and diastolic function. The study included 90 female subjects who performed control of thyroid hormonal status at the Institute of Nuclear Medicine at the University of Sarajevo Clinics Centre and who previously were untreated for the thyroid functional disorders. The study sample was divided in three groups based on the thyroid hormones levels: a) hyperthyroid group (n= 30) b) hypothyroid group (n=30) and c) euthyroid (control). Echocardiography measurements were performed on commercially available Toshiba, SSH 140. Before the therapy no statistically significant differences in the peak early and late mitral inflow velocities (E/A) values between the study groups was observed, but the mean left ventricular ejection fraction (LVEF) in hypothyroid group was significantly lower (58.30+/-1.05) compared to control (64.96+/-0.71) and hyperthyroid group (64.69+/-1.31) (p<0.001). In hypothyroid group we found significant increase in mean LVEF (58.30+/-1.05 vs. 64.95+/-0.86, p<0.01) and E/A (1.06+/-0.07 vs. 1.17+/-0.08; p=0.01) values after the normalization of thyroid hormone status.Thyroid dysfunctional states were not associated with impaired diastolic function, probably due to the short duration of thyroid dysfunction and timely and successful conversion therapy. Systolic function however was significantly reduced in hypothyroid patients but subsequently improved after the adequate therapy. Early diagnostic approach in patients with thyroid dysfunctional states is important for avoidance of cardiac complications that accompany these disorders.

Aim: Nitric oxide is involved in pathological processes that lead to tissue damage partly because of its free radical nature. Oxidative stress and vascular dysfunction are recognized contributors in the pathogenesis of Alzheimer disease and vascular dementia. We investigated the serum concentration of nitric acid in 20 patients with probable Alzheimer disease, 20 patients with probable vascular dementia and in 19 control subjects. We also aimed to determine the association between this concentration and cognitive impairment tested by Mini-Mental State Examination in the disease groups.

SUMMARY The extent of hantavirus seroprevalence in the healthy population from Bosnia and Herzegovina has not yet been investigated; therefore, the aim of this study was to assess the hantavirus seroprevalence in the population from different regions of Bosnia and Herzegovina and in different risk groups. The serosurvey included 1331 subjects from endemic and non-endemic regions in Bosnia and Herzegovina. All sera samples were examined using IgG ELISA, and Western blot (Bunyavirus IgG) tests. Hantavirus seroprevalence was 7·4% in the endemic region and 2·4% in the non-endemic region (P<0·05). Former soldiers from the endemic region had significantly the highest seroprevalence (16·1%) compared to the general population from the endemic region (6·2%), the occupational risk group from the non-endemic region (5·6%) and the general population from the non-endemic region (0·8%) (P<0·01). No difference in hantavirus seroprevalence between gender or age groups was observed. Hantavirus seroprevalence in different populations in Bosnia and Herzegovina was found to be highest compared to other central European countries.

Alzheimer;s disease (AD) is a multifactorial disease but its aetiology and pathophisiology are still not fully understood. Epidemiologic studies examining the association between lipids and dementia have reported conflicting results. High total cholesterol has been associated with both an increased, and decreased, risk of AD and/or vascular dementia (VAD), whereas other studies found no association. The aim of this study was to investigate the serum lipids concentration in patients with probable AD, as well as possible correlation between serum lipids concentrations and cognitive impairment. Our cross-sectional study included 30 patients with probable AD and 30 age and sex matched control subjects. The probable AD was clinically diagnosed by NINCDS-ADRDA criteria. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels were determined at the initial assessment using standard enzymatic colorimetric techniques. Low-density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) levels were calculated. Subjects with probable AD had significantly lower serum TG (p<0,01), TC (p<0,05), LDL-C (p<0,05) and VLDL-C (p<0,01) compared to the control group. We did not observe significant difference in HDL-C level between patients with probable AD and control subjects. Negative, although not significant correlation between TG, TC and VLDL-C and MMSE in patients with AD was observed. In the control group of subjects there was a negative correlation between TC and MMSE but it was not statistically significant (r = -0,28). Further studies are required to explore the possibility for serum lipids to serve as diagnostic and therapeutic markers of AD.

The evolution of homocysteine (Hcy) changes after acute myocardial infarction is still not elucidated. Serum Hcy concentration has been shown to increase between acute and convalescent period after myocardial infarction and stroke. Also a decrease in serum Hcy during acute phase was observed. It is still not clear whether the Hcy is a culprit or an innocent bystander in cardiovascular diseases. Addressing the discrepancies in Hcy changes in patients with acute myocardial infarction might give insight in Hcy role in cardiovascular diseases and offer implications both for the clinical interpretation and patients risk stratification. The aim of the study was to evaluate serum Hcy concentration changes during early post myocardial infarction. The study included 55 patients with AMI from the Clinics for Heart Diseases and Rheumatism at University of Sarajevo Clinics Centre. For Hcy analysis blood was collected on day 2 and 5 after the AMI onset. Serum Hcy concentration was determined quantitatively with fluorescent polarisation immunoassay on AxSYM system. Cluster analysis revealed two groups of AMI patients with different trends of serum Hcy changes. Increase in serum Hcy concentration was observed in 33 (60,0%) patients (AMI 1 group), while in 22 (40,0%) patients a decrease was observed (AMI 2 group). On day 2, patients in AMI 2 group had significantly higher mean Hcy concentration compared to AMI 1 group of patients (15,27+/-0,96 and 11,59+/-0,61 micromol/L p<0,05). On day 5, no significant difference in mean Hcy level between AMI 1 and AMI 2 group of patients was observed (14,86+/-1,1 vs. 12,75+/-0,74 micromol/L respectively). Significant differences between AMI 1 and AMI 2 patients were observed in VLDLC levels and CK-MB activity on day 2. Patients in AMI 1 group had significant increase in platelets count from day 2 to day 5 (230,1+/-11,6 vs. 244,2+/-11,0; p<0,05). Our study of serial Hcy changes in patients with AMI revealed two different patterns of Hcy changes in early post infarction period which might reflect two distinct populations of AMI patients. Although further research is necessary, possible explanation for the observed findings could be a different genetic background, vitamin and oxidative status of patients with AMI.

The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in gentamicin-induced acute tubular necrosis in rats using the iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). Wistar rats, both sexes (n=18), were equally divided into three groups. Gentamicin group received intraperitoneally (i.p.) gentamicin in 0.9 % NaCl at a dose of 80 mg/kg/day for five consecutive days. L-NIL+gentamicin group received L-NIL at a dose of 3 mg/kg i.p. 36, 24 and 12 h before first dose of gentamicin. Control group received 0.9 % NaCl i.p. for five consecutive days at the equal volume as gentamicin group. Griess reaction was used for determination plasma level of NO. Semiquantitative histological analysis was used for the evaluation of kidney damage level. The plasma NO level and the level of kidney damage were statistically higher in gentamicin group in comparison to the control group (p=0.046). Application of L-NIL prior to gentamicin led to certain decrease in the plasma level of NO as well as in the level of kidney damage. Application of L-NIL, prior to gentamicin administration, did not provide complete protective effects of L-NIL on the kidney, which was demonstrated on kidney sections. The lack of anticipated protective effect of L-NIL on kidney tissue might be explained with the fact that we have used L-NIL prior but not during/after gentamicin administration. It would be necessary to examine the effects of L-NIL administration not only before, but as well during and possibly after the administration of gentamicin.

We investigated serum concentration of C-reactive protein (CRP) and measures of adiposity in 30 patients with type 2 diabetes mellitus (15 male, 15 female) and 30 age and sex-matched apparently healthy subjects. CRP concentration was determined by laser nephelometry (BN II Analyzer) and CardioPhase high-sensitivity CRP (DADE BEHRING) was used as reagent which consists of polystyrene particles coated with mouse monoclonal antibodies to CRP. Results have shown that serum CRP concentration in patients with type 2 diabetes mellitus was statistically significantly higher compared to control group of healthy subjects (p<0,05). Body mass index (BMI) correlated significantly with serum concentration of CRP in patients with type 2 diabetes mellitus (r=0.614; p<0.001). Statistically significant positive correlation was also found between waist to hip ratio and serum CRP concentration in patients with type 2 diabetes mellitus (r=0.426; p<0.05). Elevated serum CRP concentration in patients with type 2 diabetes mellitus is probably caused by the presence of chronic low-grade inflammation in these patients. It is possible that determined increase of CRP concentration reflects activation of innate immune system components in patients with type 2 diabetes mellitus. Implications of established association between measures of adiposity and serum CRP level in type 2 diabetes mellitus remain unclear.

Metabolic syndrome is a group of factors which increase the risk for development of diabetes, cardiovascular diseases and includes insulin resistance, abdominal adiposity, hyperlipidemia, hypertension and other disorders. Changes in prothrombotic and proinflammatory markers have been observed. Aim of this study was to asses the concentration of fibrinogen and other humoral markers of metabolic syndrome in type 2 diabetic patients. 77 patients both sexes, age 46-83 years have been included. Based on ATP III criteria patients were divided in two groups. Group I - diabetic patients with metabolic syndrome and Group II - diabetic patients without metabolic syndrome. Each group was divided in two subgroups, males and females. The plasma concentration of fibrinogen and humoral markers of metabolic syndrome (triglycerides, cholesterol and glucose) have been evaluated. There were 49.4% patients out of total who met the criteria for metabolic syndrome. Patients in Group I weight in average more then the patients in Group II. Average systolic and diastolic blood pressure values were in all groups and subgroups higher than recommended. Humoral markers of metabolic syndrome were significantly higher (p<0.05) in Group I (triglycerides 2.7+/-0,2 mmol/L, total cholesterol 6.0+/-0.2 mmol/L) compared to Group II (triglycerides up to 1,7 mmol/L, total cholesterol in serum up to 5,2 mmol/L ). Concentration of glucose in both groups was significantly higher compared to referral values. Average plasma fibrinogen concentration was 4.0+/-0.1 g/Lwithout significant differences between Group I and II. Females from Group I had significantly higher fibrinogen concentration (p=0.003) then the males from the same group (females 4.4+/-0.2 g/L vs. males 3.7+/-0.1 g/L). There was no difference in fibrinogen concentration between female and male patients in Group II. Fibrinogen plasma concentration is elevated in all type 2 diabetic patients without significant differences between subjects with or without metabolic syndrome.

Studies indicate that inflammatory mechanisms may play an important role in the pathogenesis of Alzheimer's disease (AD). C-reactive protein (CRP), marker and mediator of inflammation, has been detected in lesions typical for the affected areas of AD brain. There have been conflicting reports on serum CRP concentration in AD. Scarce data exist on association of CRP and measures of adiposity in AD patients. Thus, we investigated serum CRP concentration in fifteen overweight institutionalized patients with probable AD and fifteen age-matched control subjects. Body mass index (BMI) and waist/hip ratio (WHR) were calculated for each subject included in the study. Age, systolic and diastolic blood pressure, BMI and WHR did not differ significantly between the two groups. Serum CRP concentration was significantly higher in patients with AD compared to controls (p<0.0001). Although not significant, positive correlations between serum levels of CRP and BMI and WHR were found. Obtained results support the notion that low-grade inflammation is present in patients with AD. Absence of significant association between CRP and measures of total and central adiposity in overweight AD patients needs further investigation and explanation.

Metabolic syndrome is a group of factors which increase the risk for development of diabetes, cardiovascular diseases and includes insulin resistance, abdominal adiposity, hyperlipidemia, hypertension and other disorders. Changes in prothrombotic and proinflammatory markers have been observed. Aim of this study was to asses the concentration of fibrinogen and other humoral markers of metabolic syndrome in type 2 diabetic patients. 77 patients both sexes, age 46-83 years have been included. Based on ATP III criteria patients were divided in two groups. Group I - diabetic patients with metabolic syndrome and Group II - diabetic patients without metabolic syndrome. Each group was divided in two subgroups, males and females. The plasma concentration of fibrinogen and humoral markers of metabolic syndrome (triglycerides, cholesterol and glucose) have been evaluated. There were 49.4% patients out of total who met the criteria for metabolic syndrome. Patients in Group I weight in average more then the patients in Group II. Average systolic and diastolic blood pressure values were in all groups and subgroups higher than recommended. Humoral markers of metabolic syndrome were significantly higher (p<0.05) in Group I (triglycerides 2.7+/-0,2 mmol/L, total cholesterol 6.0+/-0.2 mmol/L) compared to Group II (triglycerides up to 1,7 mmol/L, total cholesterol in serum up to 5,2 mmol/L ). Concentration of glucose in both groups was significantly higher compared to referral values. Average plasma fibrinogen concentration was 4.0+/-0.1 g/Lwithout significant differences between Group I and II. Females from Group I had significantly higher fibrinogen concentration (p=0.003) then the males from the same group (females 4.4+/-0.2 g/L vs. males 3.7+/-0.1 g/L). There was no difference in fibrinogen concentration between female and male patients in Group II. Fibrinogen plasma concentration is elevated in all type 2 diabetic patients without significant differences between subjects with or without metabolic syndrome.

Objec ti ves: The purpose of the present study was to assess neck ­ to ­ height ra ti o (NtHR) and its possible associa ti on with other anthropometric measures of obesity and blood pressure (BP) values in Bosnian university students stra ti fi ed by new 2017 American College of Cardiology/American Heart Associa ti on Task Force hypertension (HT) guidelines. Methods: The present study included 417 subjects with median age 20 (19 ­ 21) years that were divided into normal BP, el ­ evated BP, stage 1 HT, and stage 2 HT groups based on BP measurements using auscultatory methods. Standard anthropo ­ metric indices including neck circumference (NC) were measured. NtHR (cm/m) was calculated in each par ti cipant based on the NC and height. Di ff erences between groups were assessed by Kruskal ­ Wallis followed by Man ­ Whitney test and correla ti ons were determined by Spearman test. Results : The prevalence of elevated BP was 19.2%, stage 1 HT 21.6%, and stage 2 HT 11.0 %. NtHR was highest in the stage 2 HT group. NtHR correlated signi fi cantly with all anthropometric measures in all groups. No correla ti on between NtHR, systolic BP, and diastolic BP was found, except in the stage 1 HT group, where a signi fi cant correla ti on between NtHR and systolic BP was uncovered. Conclusions: Based on the observed correla ti ons between NtHR and standard measures of obesity, NtHR could be included in clinical prac ti ce, since it is simple and does not induce discomfort. The high prevalence of elevated BP found in the present study suggests HT preven ti on requires the implementa ti on of programs aimed at promo ti ng healthy dietary habits, physical ac ti vity, as well as e ff ec ti ve stress management and coping mechanisms.