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Studies that investigated an association between asymmetric dimethylarginine (ADMA) and glycated haemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) have given discordant results. The aim of this study was to determine and compare serum ADMA concentration in patients with T2DM and healthy controls, and to assess correlation between ADMA and HbA1c in patients with T2DM. Serum ADMA concentration was determined by ELISA method with the use of ADMA ® - ELISA kit (DLD Diagnostics, Hamburg, Germany) and HbA1c levels were determined by an immunoturbidimetric method in 60 patients with T2DM and 60 healthy individuals matched for age and sex. Results have shown that mean serum ADMA concentration was significantly higher in T2DM patients (1.54±0.06 μmol/L) compared to mean serum ADMA concentration (0.62±0.02 μmol/L; p<0.0001) in healthy subjects. A significant, positive, correlation between serum ADMA concentration and HbA1c levels was observed (r=0.494; p<0.01) in T2DM patients. Our results suggest that there is an association between endothelial dysfunction and glycaemic control in type 2 diabetes mellitus. Possible explanation for obtained results may be oxidative stress that is increased in conditions of hyperglycaemia and it also promotes endothelial dysfunction. Larger, longitudinal studies are required that will evaluate relation between metabolic abnormalities and increased ADMA levels in patients with type 2 diabetes mellitus.

A. Kulo, K. Van Calsteren, M. Van de Velde, N. Mulabegović, R. Verbesselt, J. D. de Hoon, J. Verhaeghe, K. Allegaert

OBJECTIVES Because of the extensive variability in paracetamol clearance in young women, published data were pooled with newly collected observations in search of covariates of paracetamol pharmacokinetics (PK) within this specific population. SUBJECTS AND METHODS PK estimates and clinical characteristics [pregnant, weight, exposure to oral contraceptives (OC)] in young women following IV loading dose (2 g paracetamol) were pooled, using a non-compartmental linear disposition model in individual time-concentration profiles. Data were reported by median and range. Rank correlation was used to link clearance (l/h) to weight, Mann Whitney U test to compare clearance (l/h.m-2) between subgroups (pregnant, OC exposure). Finally, a multiple regression model with clearance (l/h) in all women and all non-pregnant women was performed. RESULTS Based on 73 paracetamol PK estimates, a 8-fold variability in clearance (range 7.1-62.2 l/h) was documented, in part explained by a correlation (r2=0.36) between clearance (l/h) and weight. Clearance (l/h and l/h.m-2) and distribution volume (l) at delivery (n=36) were higher compared to non-pregnant observations. In non-pregnant women, women on OC (n=20) had a higher paracetamol clearance (l/h.m-2) compared to women (n=17) not on OC (p = 0.023). Weight (p = 0.0043) and pregnancy (p = 0.02) were independent variables (r=0.56) of paracetamol clearance (l/h). In non-pregnant women, weight (p = 0.009) and OC exposure (p = 0.03) were independent variables (r=0.51). CONCLUSIONS Weight, pregnancy and OC result in higher clearance of IV paracetamol in young women. Besides compound specific relevance, these findings also unveil covariates of drug metabolism in young women.

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

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-infl ammatory eff ects. Previous research suggests that met-enkephalin has cytogenetic eff ects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive eff ect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). Th e goal of the present research was to evaluate met-enkephalin in vitro eff ects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (. μg/mL). However, this research did not detect any signifi cant eff ects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome , chromosome  and chromosome . Additionally, we confi rmed chromosome  as the most frequently included in translocations. Furthermore, met-enkephalin eff ects on the increase of the numerical aberrations in both concentrations applied were detected. Th ose fi ndings should be interpreted cautiously and more research in this fi eld should be conducted. ©  Association of Basic Medical Sciences of FB&H. All rights reserved

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

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.

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