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Introduction/Objective. Intensive oxidative stress is proven in patients with diabetes mellitus and important in the development of a microvascular complication of type 2 diabetes mellitus. The aim of the study was to investigate the relationship between morphometric parameters of retinal blood vessels in patients with diabetic retinopathy (DR) and the levels of parameters of oxidative stress: advanced oxidation protein product (AOPP), thiobarbituric acid reactive substances (TBARS), and total sulfhydryl (SH) groups in blood samples. Methods. The patients (the group with DR and controls) were sex- and age-matched. Glycaemia, hemoglobin A1C HbA1C, total cholesterol and its fractions, and triglycerides were measured in blood samples. AOPP and total SH groups were determined in the plasma by specific methods. Modification of the thiobarbituric acid method was used for the determination of TBARS. The number and diameter of retinal blood vessels, as morphometric parameters on digital retinal photography, was determined by using the ImageJ software. Student’s t-test was used as the statistical method for the evaluation of differences between the morphometric and blood test parameters. The significance of differences in morphometric parameters of retinal blood was establish by one-way ANOVA. Results. Significantly higher levels of parameters of oxidative stress (AOPP and TBARS) were in the group of patients with DR than in the controls. This difference was also present among the patients with mild and severe forms of DR (AOPP F 77.03, p < 0.001) (TBARS F 63.28, p < 0.001). The diameter of retinal blood vessels correlated with levels of AOPP, but only in patients with mild DR. Conclusion. Parameters of oxidative stress, AOPP and TBARS, may be important for the follow-up of DR. In early stages in diabetic retinopathy, AOPP can be a valuable biomarker.

The paper focuses on studying students' motivation when they sign up for a foreign language course at the non-affiliated departments at the Faculty of Philosophy, Niš. These courses are created with the conviction that they will develop motivation for foreign language learning if they are better suited to students' interests and needs. The paper deals with students' behaviour during the English language course at the non-affiliated departments and with their attitudes towards the course they chose. This course is often conceived as English for specific purposes (ESP). Students' behaviour and motivation during the English language course will be determined on the basis of the complex dynamic systems theory. This theory is based on the assumption that students' motivation depends on personal interest and students' engagement during the English language course, but also on the dynamic factors in the classroom. The paper is based on the results of a questionnaire and observations made during the course. The results show that most students sign up for the English language course because of the contents of the course and that most students want to acquire general knowledge of English language and culture during the course.

Introduction: Two most common pharmaceutical formulation of tacrolimus (Tac) used after kidney transplantation (Tx) are immediate-release one, administered twice-daily (TacTD), and prolonged-release one, administered once-daily (Tac-OD). Aim: The aim of this study was to compare daily doses, trough concentrations (C0 ) and dose-adjusted trough concentrations (C0 /D) of Tac between patients who administered different drug formulations, Tac-TD or Tac-OD, during the first year after Tx. Additionally, the aim of the study was to compare the distribution of C0 within and beyond the target therapeutic range (8-12 ng/mL for the first 90 days and 6-10 ng/mL afterwards) after the administration of different drug formulations. Subjects and Methods: A retrospective pharmacokinetic study included 84 patients (56 on Tac-TD and 28 on Tac-OD), with a follow-up period between the first and twelfth month post-transplantation. Following pharmacokinetic data were used: daily dose, daily dose according to patient's body weight, concentration C0 and C0 /D of Tac. Results: The results of the study showed that patients on Tac-OD formulation had higher daily doses and higher C0 during 4-6 months (p

Oxytocin achieves its effects after binding the oxytocin receptor (OXTR). Oxytocin plays an important role in empathy. The aim of this study was to examine the influence of two single nucleotide polymorphisms (SNPs) of the OXTR gene (rs53576 and rs2254298) on empathy measures and plasma oxytocin levels. Seventy-four university students were screened for the OXTR rs53576 and rs2254298 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The level of oxytocin in the plasma was measured by the enzyme linked immunosorbent assay (ELISA). All subjects were assessed with the empathy quotient (EQ) questionnaire and Reading the Mind in the Eyes Test (RMET). Subjects carrying the rs53576 GG genotype had a higher EQ score, compared to GA/AA genotype carriers. By gender analysis, significance was reached only in females. Considering the influence of both examined polymorphisms on empathy, participants with the GGGG diplotype had a higher EQ in comparison with GAGG/AAGG carriers. These hormone effects were not correlated with plasma oxytocin levels. This is the first study implying that higher empathy in rs53576 GG genotype carriers may not depend on plasma oxytocin levels, but possibly on the number and function of OXTRs in the brain. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41018]

This paper deals with an impact of receiving antenna placed in a metal enclosure on an electromagnetic field distribution within the enclosure, and thus on its shielding effectiveness. In an experimental setup, a frequently used tool for measuring the electromagnetic field level at certain points within the enclosure is a dipole antenna connected to a measuring instrument via a coaxial cable. For modeling a coupling between the electromagnetic field and antenna in the protective enclosure we use the Transmission-Line Matrix (TLM) method, enhanced with the compact wire model. The numerical model is verified through comparison with the available experimental results and then used to investigate the influence of physical dimensions of dipole antenna and its cable connection on the detected level of shielding effectiveness. [ABSTRACT FROM AUTHOR]

Introduction/Objective. An unfavorable prognosis of membranous nephropathy (MN) is determined by the presence of persistent proteinuria and extensive tubulointerstitial lesions at initial biopsy. Our study investigated the value of markers of renal cell dysfunction (glomerular filtration rate, urinary excretion of protein, ectoenzyme proximal tubular epithelial cells, and oxidative stress) in patients with MN, and points to the use of these markers in a possible therapeutic modification. Methods. The study included 28 patients with MN and 30 healthy individuals as control. In addition to the basic laboratory studies, enzyme [aminopeptidase N (APN), plasma cell glycoprotein-1 (PC-1), N-acetyl- β-D-glucosaminidase (NAGA), and dipeptidyl peptidase-4] activity was determined in serum and urine, as well as parameters of oxidative damage [thiobarbituric acid concentration of substance-responders (TBARS), malondialdehyde, and the concentration of the total sulfhydryl (SH) group]. Results. In patients with MN, serum activity of PC-1 and APN and urinary excretion of NAGA were significantly higher than in the control group. Also, significant correlation between daily proteinuria and serum PC-1 activity and urinary excretion of NAGA was found in patients with MN. Serum and urine levels of TBARS as well as total SH group levels were significantly lower in patients with MN than in healthy controls. Conclusion. Kidney damage in MN is accompanied by the release of several tubular enzymes, with potential diagnostic and prognostic significance. The study suggests a possible role of oxidative stress in pathogenesis of MN and the use of antioxidants in preventing impairment as part of future therapy. [Project of the Ministry of Science and Environmental Protection of Serbia, Grant No. 175092]

Introduction Cytokine network plays an important role in pathogenesis of chronic periapical lesions. The aim of this study was to determine the concentration of interleukin-6 (IL-6) in tissue homogenates of human periapical lesions and correlate its levels with symptomatology and size of the lesions. Materials and Methods 93 samples of chronic periapical lesions were obtained after extraction of teeth. Samples were divided according to the clinical presentation as symptomatic and asymptomatic, and according to the size as large and small. The concentration of IL-6 was analyzed using ELISA. Results Statistically significant difference in IL-6 concentration was observed in symptomatic lesions compared to asymptomatic (p

The influence of ultraviolet (UV) radiation on the leaching of di(2- -ethylhexyl) phthalate (DEHP) from 8 different parts of plastic medical devices made of poly(vinyl chloride) (PVC) that are used in two important medical procedures (peritoneal dialysis and transfusion) was investigated. The investigation was performed for three different extraction times (6, 15 and 30 days). DEHP determination was realized by gas chromatography–mass spectrometry (GC-EI– –MS). All the investigated samples contained a significant amount of DEHP. The results showed that some of the set for peritoneal dialysis contained DEHP in higher amounts than samples from the transfusion set. All samples of tubing material showed higher concentration levels of DEHP than the coupled bags. Results obtained after UV treatment showed that UV radiation has a certain influence on DEHP leaching from samples of PVC medical devices. The smallest difference was in the case of the quadruple blood bag from the transfusion set (about 73 % remained), while the biggest difference was obtained for the SAG-M transfer bag, also from the transfusion set, where just 25 % of total content of DEHP remained. The results obtained for DEHP leaching from investigated samples by time showed that most of the samples showed significant differences in the amounts of DEHP leached after 6 and 30 days. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 41018]

Immunosuppressive drugs play a crucial role in the inhibition of immune reaction and prevention of graft rejection as well as in the pharmacotherapy of autoimmune disorders. Effective immunosuppression should provide an adequate safety profile and improve treatment outcomes and the patients' quality of life. High-risk transplant recipients may be identified, but a definitive prediction model has still not been recognized. Therapeutic drug monitoring (TDM) for immunosuppressive drugs is an essential, but at the same time insufficient tool due to low predictability of drug exposition and marked pharmacokinetic variability. Parallel therapeutic, biochemical and clinical monitoring may successfully optimize and individualize therapy for transplanted recipients, providing optimal medical outcomes. Modern pharmacotherapy management should include new biomarkers with better sensitivity and specificity that can identify early cell damage. The aim of this study was to point out the importance of finding new biomarkers that would enable early detection of adverse drug events and cell damage in organ transplant recipients. We wanted to confirm the importance of routine biochemical monitoring in improving the safety of immunosuppressive treatment.

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An interaction of Co(II), Ni(II) and Zn(II) with humic acid and O-donor humic-like ligands was studied by ion-exchange and electrospray ionization - mass spectrometry (ESI-MS) method. Interactions were confirmed by differences between values of chromatogram peak areas for monocomponent (ligand) and binary systems (ligand with metal ion) by newly developed ESI-MS 5 μL Loop injection technique. Schubert’s ion exchange method was used for determination of stability constants of formed complexes at pH 4.0 and I = 0.01. Comparing the values of log Kmn for complexes formed by dipositive metal ions with humic, benzoic and salicylic acids, it can be concluded that the interaction strengths of transitional series metals follow the Irving-Williams order: Co(II) < Ni(II) < Cu(II) > Zn(II). The obtained values of log Kmn indicate that Pb(II) ions effect the strongest interactions with all investigated ligands. Complexation of humic acids macromolecules possessing O-donor binding sites as major binding sites can be predicted and modelled following the same order of interaction strength like Irving-Williams order. [Projekat Ministarstva nauke Republike Srbije, br. III41018]

The presence of DEHP in dialysis and infusion sets for peritoneal dialysis and parenteral nutrition, which are made of PVC and other plastic polymeric materials, were investigated. Phthalate determination was carried out by gas chromatography - mass spectrometry method (GC-MS). The results showed that the peritoneal dialysis set (bag and tubing) made of PVC contains DEHP in significant amount, about 31 - 34%. Solution for peritoneal dialysis which was stored in the investigated PVC bag, contains low amount of DEHP, about 3.72 μg dm-3. Infusion bottles which are made of LDPE, also contain DEHP but in lower amount than PVC bags. LDPE bottle for packaging physiological saline solution (0.9% NaCl) showed higher amount of DEHP than LDPE bottle for packaging Ringer’s solution. In contrast, solution stored in bottle with lower DEHP level, i.e. Ringer’s solution contained about three times higher concentration of DEHP than physiological saline solution stored in bottle with higher DEHP level. Concentrations of DEHP in Ringer’s solution and physiological saline solution are 17.30 and 5.83 μg dm-3, respectively. The obtained values are under estimated upper-bound dose of DEHP received by adult patients undergoing procedures of peritoneal dialysis and parenteral nutrition. [Projekat Ministarstva nauke Republike Srbije, III 41018]

The oxidative damage of proteins and lipid peroxidation of membranelipoproteins has already been described as a possible pathogenic mechanismfor liver injury. The aim of the present study was to examine the mechanismthat could be responsible for the oxidative modification of rat liver 5'-nucleotidaseduring exposure to different free radical generating systems: FeCl[sub 2] /ascorbate,xanthine/xanthine oxidase and H[sub 2] O[sub 2] . The level of lipidperoxidation products malondialdehyde (MDA), as well as the level of proteincarbonyl groups formation was measured in cells and extracellular medium. The activity of 5'-nucleotidase was linearly decreased in both hepatocytesand extracellular medium after exposure to the FeCl[sub 2] /ascorbatesystem indicating that the possible mechanism for oxidative modification couldbe a metal-binding site of the enzyme. In xanthine/xanthine oxidase systemthe enzyme activity of hepatocytes had decreased in hepatocytes but increasedin the extracellular medium indicating that proteolysis of membrane proteinscould he responsible for enzyme release in the extracellular medium. Whenhepatocytes were exposed to a H[sub 2] O[sub 2] free-radical generatingsystem, the activity of 5'-nucleotidase tended to be decreased in cells anddecreased in extracellular medium too, indicating that H[sub 2] O[sub 2] could be less reactive in producing an oxidative modification of theenzyme. In order to support the hypothesis that the cation-binding site canbe responsible for oxidative modification of the enzyme, the isolated he!pato cytes were preincubated with a Ca[sup 2+] -channel blocker (Verapamil)and then exposed to different radical-generating systems. Verapamil had onlya slight effect in potentiating the inhibition in the FeCl[sub 2] /ascorbatesystem. This probably means that the cellular cation flux and cation bindingmay be included as a vulnerable site with the greatest importance in the oxidativemodification of 5'-nucleotidase. [ABSTRACT FROM AUTHOR]

Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods: The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-b-Dglucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results: The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with T T genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients' genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes' activities. Conclusions: Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug's tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.

Background: The aim of the study was to evaluate parameters of oxidative and nitrosative stress as well as antioxidative parameters in a group of renal transplant recipients with stable graft function and no clinical signs of cardiovascular disease. We also aimed to determine the correlations among these parameters and to evaluate potential differences in all the biomarkers with regard to the immunosuppression protocol. Methods: We enrolled 57 renal transplant recipients and 31 controls who were age and sex matched with the renal transplant recipients. All of the patients included in this study had post-renal transplant surgery at least 12 months earlier and were on standard immunosuppressive therapy. In this study, we determined thiobarbituric acid-reactive substances in plasma and red blood cells and advanced oxidation protein products, nitrosative stress parameters (asymmetric and symmetric dimethylarginine - ADMA and SDMA), and antioxidative parameters (total SH groups and catalase activity). Results: The results of our study demonstrated that the levels of oxidative and nitrosative stress were significantly increased compared to the healthy population (p < 0.01 except for plasma catalase activity p < 0.05). Correlation analysis showed significant positive correlations between: ADM A and SDMA (p < 0.01); ADM A and nitrates (p< 0.05); SDMA and nitrates (p < 0.05); between OS parameters in the experimental group; AOPP and SH groups (p < 0.05) and TBARS in plasma and SH groups (p < 0.01), SDMA and AOPP (p< 0.05); SDMA and TBARS in plasma (p < 0.05); SDMA and SH groups (p < 0.01); nitrates and SH groups (p < 0.05). Conclusion: There was no significant difference in oxidative and nitrosative stress parameters with respect to the immunosuppressive protocol.

Introduction. In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. Objective. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. Methods. The study enrolled 85 patients aged 45.3±9.7 years on the average, with SLE of average duration 10.37±7.99 years, hospitalized at the Institute „Niška Banja“ during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). Results. Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p

Introduction. The balance between proinflammatory and anti-inflammatory cytokines plays an important role in the pathogenesis of chronic periapical lesions. The aim of this study was to determine the concentration of TNF-α in tissue homogenates of periapical lesions and analyze its levels in relation to the symptomatology and the size of lesions. Materials and Methods. 93 samples of chronic periapical lesions were obtained after extraction of teeth. Samples were classified according to the clinical presentation as symptomatic and asymptomatic, and according to the size as large and small. The concentration of TNF-α was analyzed using ELISA. Results. The results showed increased production of TNF-α in symptomatic lesions compared to asymptomatic. Higher concentration of TNF-α was demonstrated in large lesions compared to small. Large symptomatic lesions showed greater concentration of TNF-α compared to small symptomatic lesions, while bigger asymptomatic lesions demonstrated higher amount of the cytokines compared to small asymptomatic lesions. Conclusion. Higher concentration of TNF-α in large symptomatic lesions indicates that TNF-α is an important factor responsible for the progression of lesions.

Bacground/Aim. Hepcidin may play a pathogenetic role in iron metobolism disorders. The aim of this study was to determine the correlation between hepcidin concentration and parameters of iron metabolism in patients with different stage of chronic kidney disease (CKD). Methods. The study involved 104 patients with CKD: 64 on hemodialysis (HD) and 40 patients in pre-dialysis stadium (pre-HD) with adequate erythropoetin therapy and iron supplementation. The HD group was divided in four subgroups according to the level of serum ferritin (up to 100; 100-199; 200-499 and over 500 ng/mL). Parameters of anemia, iron status, inflamation and hepcidin level were evaluated. Results. The HD patients had a significantly lower eritrocyte count, erythrocytes indexes, hemoglobin and transferrin saturation and significantly higher iron, ferritin, hepcidin and total iron binding capacity (TIBC). The HD subgroups up to 199 ng/mL of serum feritin had lower high-sensitivity Creactive protein (hsCRP), iron and higher unbuffered iron binding capacity (UIBC), transferrin saturation and TIBC compared to the HD subgroups over 200 ng/mL. The lowest and the highest ferritin subgroups had the highest hepcidin level and it showed significant correlation with ferritin. Conclusion. Hepcidin may serve as a marker for better diagnosing and monitoring anemia and iron metabolism disorders in CKD.

The complexation of humic acid with certain heavy metal ions (Co(II), Ni(II), Cu(II), Zn(II) and Pb(II)) was investigated. The stability constants of humate complexes were determined by method which is based on distribution of metal ions between solution and resin in the presence and the absence of ligand, known as Schubert’s ion exchange method. Experiments were performed at 25 ºC, at pH 4.0 and ionic strength of 0.01 mol dm-3. It was found that the 1:1 complexes were formed between metal ions and humic acid. Obtained results of the stability constants, log βmn, of complexes formed between the metal ions and humic acid follow the order Co(II) < Ni(II) < Cu(II) > Zn(II) which is the same like in the Irving-Williams series for the binding strength of divalent metal ion complexes. Stability constant of complex between Pb(II) ions and humic acid is greater than stability constants of other investigated metal-humate complexes. The investigation of interaction between heavy metal ions and humics is important for the prediction of the distribution and control of the migration of heavy metals in natural environment. [Projekat Ministarstva nauke Republike Srbije, br. III 41018]