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 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.

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.

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.

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.

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.

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.

This study was performed in order to investigate possible role of brain beta-endorphins as markers of antidepressive drugs therapy monitoring. Experiment was done using amitriptyline and trazodone as antidepressants. For quantification of brain beta-endorphins we used RIA technique. Our results showed significant decrease of brain beta-endorphins concentration in drug-pretreated animals, vs. those in of control group treated with 0,95% NaCl. The lower values were obtained in trazodone pre-treated animals. This study shows that use of psychoactive drugs have influence on brain beta-endorphins concentration. beta-endorphins could be of great importance, used as markers for evaluation of patient treatment.

The aim of our study was to establish the influence of antidepressive drugs on serum and brain beta-endorphins in experimental animals. Experiment was performed on albino Wistar rats. Antidepressant amitryptiline was used, and for quantification of sera and brain beta-endorphins RIA technique. Our results showed difference between sera and brain beta-endorphins concentration in amitryptiline pretreated animals, vs. those in serum and brain of control group treated with 0.95% NaCl. This study shows that use of psychoactive drugs have influence on sera and brain beta-endorphins concentration. Beta-endorphins could be of great importance, used as markers for evaluation of antidepressant drug effects.

We have studied the consequences of two homoplasmic, pathogenic point mutations (T7512C and G7497A) in the tRNASer(UCN) gene of mitochondrial (mt) DNA using osteosarcoma cybrids. We identified a severe reduction of tRNASer(UCN) to levels below 10% of controls for both mutations, resulting in a 40% reduction in mitochondrial protein synthesis rate and in a respiratory chain deficiency resembling that in the patients muscle. Aminoacylation was apparently unaffected. On non-denaturating northern blots we detected an altered electrophoretic mobility for G7497A containing tRNA molecules suggesting a structural impact of this mutation, which was confirmed by structural probing. By comparing in vitro transcribed molecules with native RNA in such gels, we also identified tRNASer(UCN) being present in two isoforms in vivo, probably corresponding to the nascent, unmodified transcripts co-migrating with the in vitro transcripts and a second, faster moving isoform corresponding to the mature tRNA. In cybrids containing either mutations the unmodified isoforms were severely reduced. We hypothesize that both mutations lead to an impairment of post-transcriptional modification processes, ultimately leading to a preponderance of degradation by nucleases over maturation by modifying enzymes, resulting in severely reduced tRNASer(UCN) steady state levels. We infer that an increased degradation rate, caused by disturbance of tRNA maturation and, in the case of the G7497A mutant, alteration of tRNA structure, is a new pathogenic mechanism of mt tRNA point mutations.

Long term stress exposure results in somatisation symptoms appearance. Cardiovascular, respiratory, gastrointestinal and muscle-bone symptoms arise because of intensified activity of autonomic nervous system caused by chronic stress. The aim of the study was to examine the relationship between long term war stress exposure and appearance of somatisation. 40 students of health-care faculties in Sarajevo, of both sexes, were included in investigation and divided in two groups-somatisation and control. Somatisation group subjects (N=20) lived in B&H under war conditions, from 1992-1995. Control subjects (N=20) spent the same period outside B&H. For evaluation of somatisation symptoms we used SCL-90-R test. The obtained data were statistically evaluated using Student's t-test and chi2 test. Confidence level was set at p < 0.05. Our results showed statistically significant difference in somatisation level between somatisation and control subjects group. Different intensity of appearance of certain symptoms in male and female was established. The score of somatisation dimension between somatisation and control group showed statistically significant level (p < 0.0001). Study results confirmed correlation of chronic stress exposure (living in war environment) and somatisation symptom appearance. Individual organic systems had various level of symptom expression. The influence of sex on intensity of individual symptoms of somatisation is possible.