Introduction. Every patient with type 2 diabetes mellitus secretes less insulin than necessary for his/her level of insulin sensitivity, and many of them have some degree of insulin resistance. The mix of insulin defi ciency and insulin resistance is different for each patient and, in any patient, it may vary during the course of the disease. The aim of our study was to examine the degree of -cells function and the presence of insulin resistance in patients with a long-standing type 2 diabetes. Methods. The study included 30 patients of both sexes (12 males, 18 females), with the mean values of age 59 years (SD=7.88) and the disease duration of 10 years (SD=5.36). The mean value of BMI was 31 kg/m2 (SD=4.74). The fasting glucose and insulin concentrations and HbA1c in the blood were determined by the standard laboratory methods. The percentages of functional -cells in the pancreas (HOMA%B), insulin sensitivity (HOMA-%S) and insulin resistance (HOMA-IR) were calculated using a HOMA calculator v2.2. Then, the data were analyzed by statistical software SPSS 19. Results. The mean HbA1c was 10 % (SD=1.52) and FBG 12 mmol/L (SD=4.15). The mean insulin was 13 μmol/L (SD=6.11) and HOMA-%B 31 % (SD=18.99). The median value of HOMA-%S was 49% (32.2-82.4) and HOMA-IR 2 (1.2-3.1). 87% of patients had a HOMA-IR >1. Conclusion. The highly reduced -cells function and the consequent insulin defi ciency, usually combined with the moderate insulin resistance was determined in the patients with a long-standing type 2 diabetes mellitus.

Introduction. Chronic,low-grade infl ammation is important in the development and progression of type 2 diabetes mellitus (T2DM). Indicators of increased infl ammatory activity include elevated values of circulating acute phase proteins like C-reactive protein (CRP) and fi brinogen. The aim of the study was to test sex-related differences in CRP and fi brinogen blood levels in T2DM patients. Patients and Methods. The cross-sectional study included 40 T2DM patients, both sexes (19 males and 21 females), median age 70 (36-90) years. Patients were hospitalized at the Clinic of Endocrinology, Clinical Center University of Sarajevo. The fasting glucose levels, glycated haemoglobin, fi brinogen and CRP in the blood of T2DM patients were determined by standard laboratory methods. The data were analysed by statistical software SPSS 19. Results. The median values of CRP and fi brinogen in blood were not statistically different between female and male T2DM patients, although values had tendency to be higher in female patients [17.30 mg/L (3.40-61.35) vs. 9.60 mg/L (3.50-28.90); p=0.573]; [5.70 g/L (4.20-6.35) vs. 3.80 g/L (3.60-6.00); p=0.078]. A positive correlation between CRP and fi brinogen was found in samples from female T2DM patients (rho=0.606;p<0.01). Conclusion. Elevated CRP and fi brinogen indicate the presence of infl ammation in T2DM patients. Female patients had higher values of both infl ammatory markers in blood in comparison to males, but we did not prove statistically signifi cant sex-related differences.

We have investigated heart type fatty acid binding protein (H-FABP) rat serum values at different time point following subcutaneous (s.c) isoproterenol (ISO) administration and their correlation with severity of myocardial lesion. Thirty adult, male, Wistar rats were used for this study. Six rats per group were treated with a single dose of either ISO (ISO groups, dose 100 mg/kg, s.c.) at different time point (30', 60', 120', 240') or with saline (control group). Serum H-FABP was determined by enzyme-linked immunosorbent assay (ELISA) and histological analysis was performed by hematoxylin-eosin (HE) method of staining. The first serum H-FABP increase was obtained 30' following ISO administration, but maximal value was reached after 240'. Myocardial histological changes were time-dependent and correlated with serum H-FABP values (p<0.001). The results of the study suggest that H-FABP is sensitive marker for acute rat myocardial injury and its possible inclusion in myocardial injury screening studies in rats.

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.

In this paper we would like to briefly introduce readers to the situation in the field of laboratory medicine in Bosnia and Herzegovina, with a focus on training in the field of medical biochemistry. As in some of neighboring countries, term Medical biochemist is the usual name for the Clinical biochemist or Clinical chemist in Bosnia and Herzegovina. Despite the difficult period through which the profession had passed in the last two decades, laboratory work, particularly clinical biochemistry, has managed to retain the necessary quality and keep pace with the developed world. In post war period, Society of Medical Biochemists of Bosnia and Herzegovina held regular meetings each year as a part of "life long learning" process, where both scientific and vocational lecturers presented their work. A single law on the state level would provide us with more defined and precise answers, such as: who can get a specialization, how long should last the training for medical biochemistry specialists (duration in years). This law should be in consent with the program described in EC4 or other documents given by the EFCC (European Federation of Clinical Chemistry and Laboratory Medicine) and IFCC (International Federation of Clinical Chemistry and Laboratory Medicine).

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 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 determine the lipoprotein profile of voluntary blood donors, and on the basis of parameters to evaluate the risk of atherosclerosis. METHODS The study included voluntary blood donors of both sexes. Participants were divided into two groups. The first group of subjects consisted of men and women in menopause (BD 1). The second group consisted of women in reproductive age (BD 2). Analysis of concentration of lipoproteins was performed by direct determination of total cholesterol, LDL-C and HDL-C. From the total serum cholesterol and concentration of lipoproteins ratios of total cholesterol/HDL-C ratio and LDL-C/HDL-C were calculated. RESULTS Significantly higher concentration of LDL-C was obtained in the serum of BD 1, compared to LDL-C in the serum of BD 2, within the reference range. Mean concentration of HDL-C in the serum of BD 2 group was higher than the values measured in the BD group 1, without significant difference. The ratio of total cholesterol/HDL-C showed significantly higher values in the BD 1 group compared with results in the BD 2 group. Significantly higher values in the BD group 1 were observed for the ratio of LDL-C/HDL-C. Obtained results showed that all voluntary blood donors had a concentration of individual lipoprotein fractions in a lower risk range for atherosclerosis development. CONCLUSION Female voluntary blood donors in reproductive age have a more favorable lipid status in relation to the voluntary blood donors, men and women in menopause, indicating that this population of women is exposed to lower risk of developing atherosclerosis.

Methylenetetrahydrofolate Reductase (MTHFR) is key enzyme in metabolism of homocysteine. Homozygotes for mutation (TT genotype) have hyperhomocysteinemia, risk factor for atherosclerosis development. The aim of the study was to find out distribution of genotype frequencies of C677T MTHFR among patients on maintenance hemodialysis. Possible association of alleles and genotypes of C677T polymorphism of the MTHFR gene with age of onset, duration of dialysis and cause of kidney failure was studied also. Cross-sectional study includes 80 patients from Clinic of Hemodialysis KUCS in Sarajevo. In order to perform genotyping, isolated DNA was analyzed by RFLP-PCR and gel-electrophoresis. From total of 80 patients, 42.5% (n=24) were female, 57.5% (n=46) were male, mean age 54.59+/-1.78 years and duration of dialysis 79.92+/-6.32 months. Genotype distribution was: CC 51.2% (n=41), CT 37.5% (n=30) and TT 11.2% (n=9). Patients with wild-type genotype have longer duration of dialysis in month (87.1 +/- 63.93) comparing to TT genotype patients (67.06 +/- 39.3), with no statistical significance. T allele frequency was significantly higher in group of vascular and congenital cause of kidney failure (Pearson X2 =6.049, P<0.05) comparing to inflammation etiology group. Genotype distribution results are within the results other studies in Europe. Obtained results indicate that C677T polymorphism is not associated with onset, duration and cause of kidney failure in our hemodialysis population. There is an association of T allele of the MTHFR gene and vascular and congenital cause kidney failure.

It has been recognized that some people have a genetic variant which leads to elevated levels of homocysteine and impairs ability to process folate. This condition was recognized as independent risk factor of coronary heart disease. Recently, connection between this termolabile mutation of the methylenetetrahydrofolate reductase and numerous conditions and diseases has been established. Aim of this review is to draw attention to this interesting area in medicine. Additionally, well defined study about presence and frequency of gene polymorphism in our region will provide proper diagnosis and achieve possible delay of development of diseases with vitamin supplementation.

The aim of this prospective study was to evaluate and compare the relative increase of serum myoglobin level and total creatine kinase (CK) activity in acute myocardial infarction (AMI) patients (n=36). We measured serial changes in total CK activity and myoglobin serum level in three-time periods (6-9 hours, 24 hours and 6-7 days) from chest pains onset. Myoglobin peaked during the first 6-9 hours but total CK reached its peak activity after 24 hours from AMI symptoms onset. Results of this study showed that as non-specific cardiac marker myoglobin had better sensitivity and earlier rise in serum than total CK activity in AMI patients. Rapid kinetic of myoglobin level is important for its utility as marker for re-infarction diagnosis. Early myoglobin increase in serum is important for early triage of AMI patients and early "ruling out" of AMI diagnosis if there is no evidence of its elevation in circulation.

Over the past 13 years mitochondrial defects have been involved in wide variety of degenerative diseases - Parkinson disease, Alzheimer dementia, arteriosclerosis, ageing and cancer. Mitochondria are believed to control apoptosis or programmed cell death. Disturbance in mitochondrial metabolism has also been implicated in many common diseases such as congestive hart failure, diabetes and migraine. Scientific investigations have showed complexities in mitochondrial genetics, but at the same time, pathophysiology of mitochondrial diseases is still enigma. Mitochondria and their DNAs are opening the era of "mitochondrial medicine". What we today call "a mitochondrial medicine" is only a part of the whole panorama of diseases based on disordered mitochondrial function.

In our investigation,we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP). We investigated cardiac troponin T blood level (cTnT) and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12). Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g) and ISP II (BW 250-400g).Control group (n=9) was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA) sandwich immunoassay in rat serum 4 hours after ISP application. Rats' hearts were dissected and examined by qualitative histological method (HE). Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001) vs. control and ISP I (p<0,05) vs. control. Significant difference was between ISP I and ISP II subgroups (p<0.001). The accent of histological changes of myocardium was on nuclei of cell. Cells showed acidophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different between ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Subendocardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis.

The aim of our study was to establish the extent of influence of different psychotropic drugs to brain Beta-endorphins in experimental animals. The study was performed on albino Wistar rats (weight 250 g), treated with different psychoactive drugs. RIA technique was employed for quantification of brain beta-endorphins. Brain beta-endorphins were higher in experiment group treated with trazodone (929 pg/g +/- 44,43; X+/-SD), and dibenzepine (906,63 pg/g +/- 74,06), yet with lower brain content in rats treated with diazepam (841,55 pg/g +/- 68,47), compared to brain beta-endorphins content of control group treated with saline solution (0,95% NaCl) (873,5 pg/g +/- 44,89). Significant differences were obtained comparing brain beta-endorphins of trazodone vs. diazepam treated animals, with diazepam group having lower values (p<0,02). This study showed differences in changes of rat brain beta-endorphins contents when different psychoactive drugs are used. Therefore, we consider that beta-endorphins could be used for evaluation of effects of psychoactive drugs, as a useful parameter in therapy with these psycho-pharmaceuticals.