OBJECTIVE The aim was to study the association of the use of an oral antihyperglycemic agent metformin with the presence of ocular complications in patients with type 2 diabetes (T2D). METHODS Medical records were reviewed for 234 patients with diagnosed T2D. 81.2% (n=190) patients were using metformin and 18.8% (n=44) using other oral antihyperglycemic agents. Plasma glucose concentration, glycated haemoglobin, and the presence of ocular complications in patients treated with metformin were compared to those in patients treated with other oral antihyperglycemic agents. RESULTS Ocular complications occurred in 65 patients (27.8%). Patients treated with metformin had fewer ocular complications compared to patients treated with other oral antihyperglycemic agents (χ2=19.985; p<0.0001). After adjustment for gender, age, duration of T2D, serum concentration of cholesterol, smoking, body mass index and presence of other diseases, treatment with metformin decreased the odds of both glaucoma (OR=0.14, 95% CI: 0.03-0.57, p=0.006) and diabetic retinopathy (OR=0.33, 95% CI: 0.14-0.82, p=0.017) compared with other oral antihyperglycemic agents. CONCLUSION Our results suggest that metformin may have a protective effect on ocular complications, especially glaucoma, in patients with T2D. The effects of metformin either regarding prevention of ocular complications or ocular complications already developed in patients with T2D, should be further investigated.

Aim In order to increase the database related to the antineoplastic potential of metformin, association between the use of metformin and risk of cancer occurence in patients with diabetes mellitus type 2 (DM2) was investigated. Methods In this cross-sectional study, medical records of patients with DM2 were reviewed for cancer occurence. Data on age, body mass index (BMI), alcohol and nicotine consumption, glucose and HbA1c levels, duration of DM2, medication used in the treatment of DM2 and cancer occurence were collected and analyzed. Unpaired Student's t-test or Mann-Whitney U test were used for comparisons between treatment groups, and logistic regression to asses how well our set of predictor variables predicts occurence of carcinoma. P-value less than 0.05 was considered statistically significant. Results The mean age of 234 included patients was 66.8±11.5 years, and DM2 duration was 7± 6.49 years. Mean glucose value was 8.51±4.17mmol/L, and HbA1c 7.74±1.53. Metformin therapy was prescribed in 190 (81%) patients. Cancer was diagnosed in 16 (6.8%) patients: prostate cancer in eight (3.4%), breast cancer in four (1.7%), rectal cancer in two (0.9%) and cancer of the uterus and cervix in one patient. Age, duration of DM2 and BMI did not contribute significantly to the model, while metformin use was shown to be a significant independent predictor (OR=0.049; 95% CI=0.013-0.181; p=0.001). Conclusion Our findings support the hypothesis that the use of metformin compared to the use of other oral antidiabetic drugs is associated with a lower risk of cancer in patients with DM2.

Introduction: We studied the chemical composition and antimicrobial, antioxidant, and antiproliferative activities of essential oils from flowers of Lavandula angustifolia grown in Southern Bosnia and Herzegovina. Methods: The chemical profile of essential oil was evaluated by means of gas chromatography-mass spectrometry. Antimicrobial activity was tested against six bacterial strains. The antioxidant activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test and the antiproliferative activity against three human cancer cell lines, MCF-7, NCI-H460, and MOLT-4, were investigated using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide tests. Results: In L. angustifolia essential oil, monoterpene alcohols were the most represented class of volatiles (51.8%), including linalool, lavandulol, and terpinen-4-ol, α-terpineol as the major components, followed by monoterpene esters (22.6%). The most important antibacterial activity of essential oil was expressed on Gram-negative strains. Investigated essential oil was able to reduce DPPH radicals into the neutral DPPH-H form (inhibitory concentration 50% [IC50] = 0.421 mg/ml), and this activity was dose dependent. The essential oil showed significant antiproliferative activity against three cancer cell lines, MOLT-4, MCF-7, and NCI-H460 cells, with IC50 values of 17, 94, and 97 µg/ml, respectively. The result of the antiproliferative assay indicates that MOLT-4 cell line was the most sensitive to investigated essential oil. Conclusion: The results revealed that L. angustifolia essential oil may be important growth inhibitor against the microbes studied. It also possesses significant antioxidant activity and demonstrated excellent antiproliferative activity against MOLT-4 cells.

Introduction: The met-enkephalin (1-5 Adrenorphin) and tridecactide (alpha-corticotropin 1-13) combination is used in the multiple sclerosis (MS) immuno-modulatory treatment. A testing of cytogenetic effects of met-enkephalin resulted in reductions of lymphocytic aberrations in the in the lymphocytes of the peripheral blood (PBL) of patients with immune-mediated diseases. The aim of this research is to evaluate the in vitro effects of the combination of the met-enkephalin and tridecactide on the number and the type of chromosome aberrations in PBL of the MS patients. Methods: We used blood samples from seven female patients with the diagnosis multiple sclerosis based on a McDonald Diagnostic Criteria. The tested combination, met-enkephalin and alpha-ACTH 1-13 was added at three different concentrations and constant volume. Results: Results showed that the combination of tested substances did not reduce the number of structural aberrations, although the treatment did not result in severe aberrations such as ring, fragmented, and dicentric chromosomes. Furthermore, it elicited an increase in the number of numerical aberrations and aneuploidy after the treatment with the test combo. Conclusion: As the changes in ploidy significantly change the DNA as well as the biochemical cell phenotype, we concluded that more research in this field should be conducted, including both toxicological as well as the pharmacodynamic considerations.

Introduction: According to the guidelines of The European Association of Urology, the following are considered as first choice drugs in the treatment of acute uncomplicated urinary tract infections (UTIs): fosfomycin trometamol, pivmecillinam and nitrofurantoin. Cotrimoxazole and/or trimethoprim can be considered as drugs of first choice in areas with known E. coli resistance rates of <20%. The aim of the present study was to determine the drug of first choice for the empirical treatment of UTIs in primary health care in our community and to determine the treatment cost differences. Results: Out of 500 medical records of women older than 18 years reviewed in two units of family medicine, 115 (23%) had at least one uncomplicated urinary tract infection in the period January 2010 to May 2013. Empirical treatment for them was chosen based on the official guide (3/7), physician’s own experience (2/7) or a recommendation of a colleague (2/7). UTIs were most commonly treated during 7.3 days with ciprofloxacin (46/115), which is not officially recommended as a first-line drug. This is also longer than the recommended three day course. The annual cost for ciprofloxacin was 2.5 times higher compared to the nitrofurantoin officially recommended as the first choice drug and 3.5 times higher compared to cotrimoxazole which is the second most commonly prescribed drug. Conclusion: It is necessary to increase awareness of the importance of following therapeutic guides, as well as the availability of therapeutic guides in primary medical practice. Key words: Acute uncomplicated urinary tract infections, women, empirical treatment, therapeutic guide

The aim of the paper was to investigate the types and frequency of supplementation during pregnancy in the city of Sarajevo. This study was conducted in two pediatric outpatient clinics in Sarajevo using a questionnaire. Five hundred women who had been pregnant in the past five years were questioned. The results showed that most pregnancies were unplanned. The prevalence of pre-term delivery was 5.2%, and the prevalence of low birth weight infants was 4%. There were seven cases of birth defects. Multivitamin supplements were taken by one woman before pregnancy and by 55.6%, 31.2% and 18.8% women during the first, second and third trimester, respectively. Simultaneously with multivitamin supplements, folic acid was taken by 10% women. Further efforts in terms of planning pregnancy are needed to improve prenatal care. These efforts should include the continuous education of both health professionals and women of childbearing potential, which should also enable the adequate implementation of the recommended supplementation. Key words: women of childbearing potential, pregnancy, vitamin-mineral supplements, folic acid

Introduction: Non-critical and irrational use of antibiotics is the most important reason for the ever faster development of infectious diseases causative agents’ resistance to those drugs. The aim of this study was to determine the most frequent bacterial causative agents of urinary infections and their resistance to antibiotics. Methods: The study was carried out in the Microbiological Laboratory of the Institutefor Public Health of Canton Sarajevo, during the period of January-March 2007, 2008, and 2009. The identification of the causative agents was conducted with classical biochemical series and the sensitivity test to antimicrobial drugs with the disc-diffusion method. The CLSI protocols that precisely define the kind of antibiogram discs used for particular bacteria were used. Results: The most common causative agents of urinary infections were E scherichia coli , Gr. Klebsiella-Enterobacter , Proteus mirabilis and Pseudomonas spp. The highest prevalence of the studied infections was at the age of 71-90 years for all four bacterial species. Women are more exposed to E. coli and Proteus mirabilis infections, and men to Pseudomonas spp . infections. The highest resistance of E. coli was to ampicillin and to trimethoprim+sulfomethoxazole, and the least towards cefixime. For Proteus mirabillis , there was significantly more nonresistant strains than resistant ones toall tested antibiotics except to nitrofurantoin. The least was shown in case of cefixime and gentamicin. Gr. Klebsiella-Enterobacter showed generaly high resistance towards all antibiotics, the least to gentamicin. Documented resistance of Pseudomonas spp . to all antibiotics was also very high. Key words: urine culture, antibiotics, antibiogram, sensitivity,resistance

AIM To evaluate differences in the treatment quality between often used oral anticoagulants, warfarin and acenocoumarol in patients with nonvalvular atrial fibrillation (NVAF). METHODS This was an observational, comparative, one-year clinical study, conducted in the Blood Transfusion Institute of Sarajevo, Bosnia & Herzegovina. All patients who were using warfarin/ acenocoumarol and monitored were eligible. Patients who met inclusion criteria (the age of 40-80, diagnosed NVAF, CHADS index score > or = 2, the planned long-term treatment) were includes in two parallel groups of 60 patients, composed according to the warfarin/acenocoumarol treatment as well as the gender and age. Routinely measured International normalised ratio (INR) values were the basic parameter for individual quality and stability assessment. RESULTS All average, monthly INR values were in therapeutic range (2.0-3.0) in both therapeutic groups. There were no significant differences either in the number of therapeutic INR values per patient (50.53 +/- 23.72% vs. 51.74 +/- 26.68%, P = 0.795) or in individual quality of treatment: > 50% therapeutic INR values (60.0% vs. 64.9%, P = 0.721) and > 75% therapeutic INR values (18.3% vs. 22.8%, P = 0.714) in the warfarin and acenocoumarol group, respectively. Significantly better stability was determined for acenocoumarol as compared with warfarin treatment in terms of a longer period of the total observed time during which therapeutic INR values were stable (37.6% vs. 35.7%, P = 0.0002). CONCLUSION Both drugs have shown similar quality of individual anticoagulation control, but acenocoumarol have shown significantly better anticoagulation stability with therapeutic INR values covering significantly longer time of treatment.

Exposure to the lead is public health problem and threat to environment with proven harmful impact on human, including industrial workers and general population. Harmful impacts of exposition to nervous, endocrine, hematological, cardiovascular, immune and reproductive system to the lead are well known. This article addresses the results of retrospective research carried out with attendants at gas station and those who are professionally exposed to inorganic lead (n=73; n=81), during the course of two periodic reviews performed in 2003 and 2008. All subjects underwent physical examination, ECG, were measured blood pressure and laboratory tests encompassing basic hematological parameters, including measuring of blood lead level (BLL), as bioindicators of exposure and biomarkers of toxic impact of the lead, by the means of determining concentration of 6-aminolevulinic acid in urine (ALA).Valued obtained included (arithmetic mean +/- standard deviation): for BLL 42.5 +/- 26.2 microg/L(-1), for ALA 35.2 +/- 10.6 micromol/L(-1). Quoted values are within normal values for general population. Correlation test established positive correlation between BLL and hematological parameters, number of erythrocytes, concentration of hemoglobin and MCV, and the same correlation ratio was established between BLL and years of age, years of service and exposition years of service as well as BLL and GGT. There was not established correlation between ALA and observed hematological parameters, BLL and systole pressure. Data from our research indicate unification between professional exposure to lead and duration of exposure and increase of concentration of BLL, which are far bellow marginalvalue, but do exceed average values of BLL for people of industrial countries with possible generation of harmful impact of lead. Likewise, the results suggest the increase of overall lead load in the body does not have to be necessarily only the result of professional exposure, but of the intake through other channels as well.

Due to heightened risk for thromboembolic complications, nonvalvular atrial fibrillation (NVAF) presents an absolute indication for long-term oral anticoagulation therapy. This was an observational, analytical, randomised, one-year clinical study, conducted in the Blood Transfusion Institute Sarajevo, Bosnia & Herzegovina. The aim of this study was to present the oral anticoagulation treatment in terms of International normalised ratio (INR) monitoring and warfarin/acenocoumarol dose titration in 117 patients with NVAF. INR values, the doses of warfarin and acenocoumarol, as well as the tendency and adequacy of their changes were monitored. Percentages of the therapeutic INR values were 51,77% and 53,62%, subtherapeutic 42,84% and 35,86%, and supratherapeutic 5,39% and 10,53% for the warfarin and acenocoumarol treatment, respectively. The average total weekly doses (TWD) which most frequently achieved the therapeutic INR values were 27,89+/-12,34 mg and 20,44+/-9,94 mg, for warfarin and acenocoumarol, respectively. The dose changes with the INR values 1,7 or lower/3,3 or higher were omitted in 13,46% and 15,63%, and with the INR values 1,8-3,2 were noted in 8,62% and 13,48% of all the check-up visits in the warfarin and acenocoumarol group, respectively. The annual dose changes were noted in 24,65% and 31,41%, and the daily dose changes in 74,43% and 73,36% of all the check-up visits of warfarin and acenocoumarol group, respectively. We can conclude that the management of the oral anticoagulation treatment in our country is in accordance with the relevant recommendations, but with the present tendency toward underdosing and unnecessary frequent dose changing.

PURPOSE Combination FAR4 consists from two peptide components: met-enkephalin and alpha adrenocorticotropine 1-13 (ACTH 1-13) named before as alpha-melanocyte-stimulating hormone-like (alpha-MSH-like). Met-enkephalin and alpha-MSH exhibited cytoprotective effects individually and statistically significant additive effect was registered when both peptides were applied in combination on the model of ethanol induced gastric lesions in rats. We performed subacute toxicity study with subcutaneous application. WORK METHOD Wistar rats were randomized in 3 test groups (treatments) consisted of 10 male and to female rats and one control group consisted of 20 male and 20 female rats. One daily dose was applied 3 days a week. Three dose ranges as multiplication of expected maximal human therapeutic dose (10 mg of met-enkephalin and 2 mg of alpha-ACTH 1-13) were estimated: equivalent dose, dose that was 5 times higher and 10 times higher dose. Animals were treated during 4 weeks with 10-days long observation period without the treatment after. After the planned scarification at the end of study, necropsy with histopathology examination was performed. RESULTS No lethality, toxic signs or histopathological changes were observed during the subacute toxicity testing. Variation of laboratory animals body mass was observed through six terms of body mass deternimation. Increase in body mass was noted in all test and control groups. Statistical analysis with Kruskal Wallis single variance test showed statisticaly significant difference in the number of respirations between the groups of ma-. les for the first measurement (p = 0.040332) and second measurement (p = 0.016852), but multiple comparation with control group showed statisticaly significant difference. Afterthe planned scarification at the end of the study, necropsy did not reveal changes in macroscopic structure of organs and tissues. Histopathology examination was performed on the samples of liver, kidneys, lungs, heart, brain, spleen and thymus and no pathological changes were noted, while microscopic structure of tissues was perserved. The changes regarding postmortem organ mass as percentual ratio towards total group mass were not noted nor for males, nor for females. DISCUSSION Study was conducted following the rules of the Guide for the Care and Use of Laboratory Animals made by the U.S. National Institutes of Health. Methodologicaly our study complys with rutine design of thistipe of studies. Subacute toxicity studies usually last for fourweeks and the way of test substance application to laboratory animals should comply to future way of application in human use. In our study no lethality was registered and low toxicity