AIM To analyze usefulness of measurement amino-terminal pro-B type natriuretic peptide of (NT pro-BNP) as the one of parameters of water overload in patients with chronic kidney diseases. METHODS A total number of 277 patients with chronic kidney diseases (CKD) were followed up in the period often years between January 2000 and July 2010. Patients with creatinine clearance of 60 ml/min or less were included in the study. Changes of creatinine clearance, and in last five years changes of NT pro-BNP were followed. Water overload was analyzed using chest x-ray in relation with concentration of NT pro-BNP in the blood. RESULTS Decrease of clearance of creatinine ranged from average 54.7 ml/min in the first year to 14.6 ml/min in the fifth year of the monitoring. Average NT pro-BNP level in patients without any sign of water overload was 94 pg/ml (SD 21), mean value in those with Kerley lines was 231 pg/ml/L (SD 64), in those with clear signs of water overload but without pleural effusion it was 525 pg/ml (SD 223), and in those with water retention including pleural effusion it was 1606 pg/ml (SD 1134). Using test of multiple correlation a statistically significant correlation between X-ray signs of water overload and NT pro-BNP concentration was shown, p < 0.05. CONCLUSION Measurement of NT pro-BNP was increased in the beginning of water overload in patients with CKD. Increased value of NT pro-BNP may be found earlier than any other signs of water overload. NT pro-BNP was a useful parameter in estimation of water overload in these patients.

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.

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

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

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.

The metabolic syndrome (MS) is a multi-factorial disorder which includes a main risk factors associated with the development of cardiovascular, neurologic, renal and endocrine diseases, especially type 2 diabetes. This study has been conducted to estimate the prevalence of the MS in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and its association with cardiovascular morbidity. The study included 37 patients (25 type 2 diabetic patients and 12 non-diabetic patients), who had been on peritoneal dialysis for > 3 months. At the beginning of CAPD treatment (baseline) and at the end of follow-up, we measured: body mass index (BMI), blood pressure, fasting blood glucose, triglycerides and high-density lipoprotein cholesterol (HDLC) and defined the prevalence of the MS using the modified National Cholesterol Education Program (NCEP; Adult Treatment Panel III) for peritoneal dialysis patients. The overall prevalence of the MS was 89.2%. The metabolic syndrome was estimated in all (100%) type 2 diabetic patients (vs. 60% patients on the beginning of CAPD treatment). In non-diabetic peritoneal patients, the MS was estimated in 50% cases, according to 33.3% at the beginning CAPD treatment. Development of the MS was significantly higher in the type 2 diabetic patients in compared with non-diabetic patients until the end of follow-up examination (p=0.0005). The prevalence of LVH in type 2 diabetic patients with the MS was significantly higher (p=0.002) than in non-diabetic peritoneal patients with the MS. We didn't found statistical significantly difference in the prevalence of ischemic heart disease between this two category of peritoneal dialysis patients (p=0.076). The results indicate that the metabolic syndrome is presented in high percentage in peritoneal dialysis patients, and it's also important risk factor of high cardiovascular morbidity rate in these patients, especially in type 2 diabetic patients.

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.

Anemia is common in patients with chronic kidney disease (CKD) and contributes to cardiovascular alterations. Recent findings suggest that B-type natriuretic peptide (BNP) is a sensitive biomarker for left ventricular dysfunction, but relationship between hemoglobin and BNP in CKD patients is unclear. Hemoglobin, plasma BNP and serum creatinine levels were measured in 49 patients with CKD (without heart failure), divided in two groups according to the hemoglobin status (cut-off point 110 g/L). All patients underwent echocardiography in order to assess left ventricular (LV) morphology and function. The results showed that in the group of patients with hemoglobin levels under 110 g/L BNP levels were significantly elevated (p < 0.001), as well as left ventricular mass index (p < 0.001). Systolic and diastolic LV function were significantly better in patients with hemoglobin levels above 110 g/L (p < 0.001). Hemoglobin levels were inversely related to BNP values (r = -0.451, p < 0.001). Significantly negative correlation between BNP level and creatinine clearance (p = 0.009), and significantly positive correlation between BNP level and left ventricular mass index (LVMI) were established. A similar but positive relationship was observed between hemoglobin levels and creatinine clearance (p < 0.01). We established statistically significant negative correlation between hemoglobin levels and LVMI (r = -0.564, p < 0.001). In conclusion, BNP and hemoglobin levels depend on the renal function. Anemia may contribute to elevated BNP levels in CKD patients, and may represent an important confounder of the relationship between BNP and cardiac alteration in these patients.

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 present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.

AIM To evaluate relationship between echocardiography finding of LV mass and function and B-type natriuretic peptide (BNP) plasma level in patients with chronic kidney disease on different type of treatment. METHODS We performed comparative examine on a parallel groups of kidney patients with no clinical signs of heart failure: 25 patients with chronic kidney disease (CKD, creatinine klirens < 60 ml/min), 25 patients on peritoneal dialysis (PD), 34 patients on hemodialysis (HD) and 22 renal transplant patients. Each patient underwent echocardiography investigations and measured plasma level B-type natriuretic peptide. RESULTS It was determined that hemodialysis patients had higher value of left ventricular mass index (LVMI). The incidence of left ventricular hypertrophy (LVH) progressive increased from CKD patients to HD patients (78.6% vs. 88.9%), as well as a plasma level of B-type natriuretic peptide (174.2 vs. 1020.2 pg/ml). There was a significant positive correlation between LVMI and BNP plasma level in CKD (p = 0.008) and HD patients (p = 0.001), as well as significant negative correlation between BNP plasma level and LV diastolicfunction in CKD patients (p = 0.002). CONCLUSION Plasma BNP concentration was elevated in renal dysfunction. Plasma BNP levels and the incidence of LVH were significantly grater in HD patients than in other renal patients. Significant positive correlation between plasma BNP level and LVMI suggested simultaneous influence of renal dysfunction and plasma BNP level on development of LV dysfunction.

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.

Brain natriuretic peptide (BNP) is a cardiac hormone secreted predominantly from the ventricles. This hormone is produced as pre-prohormone BNP (pro BNP), than cleaved by corine to biologically active 32-aminoacid BNP and non-biologically active N-terminal-pro brain natriuretic peptide (NTproBNP). NTproBNP has been found to be a useful marker for the diagnosis of heart failure and left ventricular systolic dysfunction. Recent studies showed that concentration of BNP and NTproBNP predict cardiovascular disease in apparently healthy individuals but their full screening characteristics are not firmly established. As NTproBNP serum concentration is altered by numerous factors there are also interindividual variations in NTproBNP values. There are no previous results for Bosnian population so the aim of this study was to asses normal range of NTproBNP serum concentrations in apparently healthy women using electrochemiluminescence immunoassay (Elecsys, Roche Diagnostic). A group of 45, healthy females, aged 39.19 (+/-6.62), were enrolled in this study. Mean serum concentration of NTproBNP was 60.32 (+/-36.25) pg/ml, with the range of 112,60 pg/ml (minimum-maximum: 13.6-126.00 pg/ml). We conclude that NTproBNP serum concentration in apparently healthy Bosnian women was not different from the average values of NTproBNP obtained on Europen's population. Thus, we suggest that the NTproBNP serum upper cut off values measured by using electrochemiluminescence immunoassay "ECLIA" (Elecsys 2010, Roche Diagnostic) for Bosnian females, aged < or =50 years, should be 155 pg/ml as reported by Roche Diagnostic.