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.

Factor V is the liver-synthesized multidomain glycoprotein encoded by a gene localised on chromosome 1q23. The point mutation 1691G>A in this gene results in formation of an altered protein of V Factor resistant to activated protein C (APC) cleavage. This mutation alone is the most frequent cause of inborn thrombophilia and the most widely acknowledged genetic risk factor for venous thrombosis in a Caucasian population. This study was designed to provide the first estimate of the frequency of the allele 1691A FV in the Bosnian female population. The 1691G>A FV mutation was examined by polymerase chain reaction-restriction fragment length polymorphism, in a group of 67 women, mean age of 58.6 years with no history of cardiovascular incident. Our findings revealed an absence of the mutated allele 1691A FV in the studied group. This is the first report on the 1691G>A FV mutation in a population from Bosnia and Herzegovina. Further research is needed to establish prevalence of the mutated allele in the population from Bosnia and Herzegovina.

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.

The Bosnian Journal of Basic Medical Sciences (BJBMS) is an international English-language, peer reviewed journal, publishing original articles from different disciplines and predominantly basic medical sciences. The first issue was published in 1998, followed by a four year period without publication. The second issue was published in February 2002 and since then the BJBMS has been published regularly and in a timely fashion. As BJBMS is now approaching its 10 th  year anniversary of continuous publishing, we believe that it is time to evaluate the achievements in this period.

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.

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

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.

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.

Antiresorptive agents are widely used to treat osteoporosis. Both reduction in bone turnover and increase in BMD may be necessary to decrease the fracture risk. The aim of the study was to evaluate the effects of aledronate on bone turnover markers and bone mineral density in postmenopausal women with osteoporosis. The study involved a group of 56 postmenopausal women with osteoporosis treated with alendronate (70 mg) weekly at the Institute of Nuclear Medicine Clinical Center University of Sarajevo during a 12-months period. Bone mineral density (BMD) at lumbar spine and proximal femur and bone turnover markers (serum β-CrossLaps, urinary N-telopeptides of type I collagen (NTx), total serum alkaline phosphatase (AP) and serum osteocalcin) were measured at baseline and after 12 months of the treatment with aledronate. BMD values significantly increased both at lumbar spine by 13.46% and proximal femur by 21.96% during the study period (-3.12±0.24 vs. -2.7±0.19 and -2.55±0.2 vs. -1.99±0.19 respectively; p<0.001). Bone turnover markers significantly decreased during the study period; C-terminal telopeptides of type I collagen fragment (β-CrossLaps) 49.0% (0.51±0.05 vs.0.26±0.028 ng/mL), NTX 33.4% (48.3±4.9 vs.32.15±3.25 nMBCE/mM Cr), AP 24.3% (81.1±5.2 to 61.43±5.2 IU/L) and serum osteocalcin by 29.7% (34.3±2.65 to 24.1±1.36 ng/mL)(p<0.001). Alendronate treatment increased BMD and reduced the level of bone turnover markers. Therefore, the treatment with aledronate during 12 months period can be recommended in postmenopausal women with osteoporosis.

AIM To assess the association between total homocysteine (tHcy) and traditional and nontraditional risk factors in patients with atherosclerotic vascular disease (ASVD). METHODS This cross-sectional study included 99 ASVD patients and 40 control subjects in whom we determined lipid profile, high sensitivity C-reactive protein (hsCRP), uric acid (UA) and tHcy. RESULTS The median tHcy concentration was significantly higher in ASVD group compared to the controls ((18.7(13.65-24.45) vs. 11.48 (10.03-14.2) micromol/L (p < 0.001)). Mean serum cholesterol, low-density lipoprotein cholesterol levels (LDLc) and atherogenic index were significantly lower, while mean serum UA concentration was significantly higher in hyperhomocysteinemic compared to normohomocysteinemic ASVD patients and control subjects. In hyperhomocysteinemic ASVD patients a significant negative correlation between serum logtHcy and cholesterol (r = -0.32), LDLc (r = -0.24), very-low-density lipoprotein cholesterol (VLDLc) (r = -0.295) and atherogenic index (r = -0.25) was observed. In normo-homocysteinemic ASVD patients serum logtHcy was significantly positively correlated with UA (r = 0.46) and hsCRP (r = 0.383). Multivariate linear regression analysis revealed that serum logtHcy was independently positively associated only with UA in normohomocysteinemic ASVD patients. CONCLUSION The results of our study have shown that the association between tHcy and traditional and non-traditional risk factors depends on tHcy serum level. It was observed a negative association between serum tHcy and lipids in hyperhomocysteinemic ASVD patients. On the other hand, in ASVD patients with serum tHcy levels within the reference range a positive independent association between serum tHcy and UA might reflect an underlying elevated tension of redox stress.

AIM To develop a rat model of myocardial infarction induced by isoproterenol (ISO). We investigated a type of histological myocardial changes and cardiac troponin I (TnI) kinetic. METHODS The study has used adult, male, Wistar strain rats. Rats were distributed in ISO and control groups. Rats treated with ISO were divided into groups according to the time of cTnI and myocardial lesion analyses: ISO I (30'), ISO II (60'), ISO III (120') and ISO IV (240'). We determined cTnI (Life Diagnostics Inc. West Chester PA, USA) in the serum by ELISA method. We performed histological analysis on the specimens of left ventricular wall stained by hematoxillin-eosin (HE) method. RESULTS The first statistically significant rise of cTnI was noted 30 minutes after the ISO administration. There was no statistically significant difference between cTnI mean values among the ISO groups. Observed myocardial histological changes were time dependent. CONCLUSIONS This model can be suitable for cardioprotective and cardiotoxicity supstance investigations followed by cTnI measurement in blood. The similarity between induced myocardial lesion on animal model in our study and human myocardial lesion in ischemia give us sufficient impulse for further preclinical researches of new cardiac markers.

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.

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