Faculty of Medical Sciences, Kragujevac

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Ligand substitution reactions and cytotoxic properties of [Au(L)Cl2]⁺ and [AuCl2(DMSO)2]⁺ complexes (L=ethylenediamine and S-methyl-l-cysteine)
(2010) Milovanovic, Marija; Kesić, Ana; Volarevic, Vladislav; Petrović, Biljana; Arsenijevic, Nebojsa; Bugarčić Z.
We have studied the kinetics of the complex formation of gold(III) complexes, [AuCl2(en)]+ (dichlorido(ethylenediamine)aurate(III)-ion) and [AuCl2(SMC)] (dichlorido (S-methyl-l-cysteine)aurate(III)) with four biologically N-donor nucleophiles. It was shown that studied ligands have a high affinity for gold(III) complex, which may have important biological implications, since the interactions of Au(III) with DNA is thought to be responsible for the anti-tumour activity. The [AuCl2(SMC)] complex is more reactive than [AuCl2(en)]+. L-His reacts faster than the other N-donor nucleophiles in the reaction with [AuCl2(en)]+, but in the reaction with [AuCl2(SMC)] 5'-GMP is the best nucleophile. Gold(III) complexes are much more reactive than Pt(II) complexes with the same nucleophiles. The activation parameters for all studied reactions suggest an associative substitution mechanism. The cytotoxicity of gold(III) complexes, [AuCl2(en)]+, [AuCl2(SMC)] and [AuCl2(DMSO)2]+ was evaluated in vitro against chronic lymphocytic leukemia cells, obtained from blood of patients with chronic lymphocytic leukemia (CLL). The [AuCl2(en)]+ complex show comparable cytotoxicity profiles compared to cisplatin. © 2010 Elsevier Inc.
Analytical characterization of lichexanthone in lichen: HPLC, UV spectroscopic, and DFT analysis of lichexanthone extracted from Laurera benguelensis (Mull. Arg.) Zahlbr.
(2010) Marković, Zoran; Manojlovic, Nedeljko
Lichexanthone, the major pigment present in the extract of Laurera benguelensis (Mull. Arg.) Zahlbr., was extracted from lichen, purified, and characterized by high-performance liquid chromatography (HPLC) and ultraviolet (UV) spectroscopy. The geometry of the lichexanthone conformers was optimized at the B3LYP/6-31+G** level of theory. It was found that all conformations have similar energies and that the corresponding lichexanthone radical is planar. In spite of its planarity, there is no significant electron delocalization over the radical. The antioxidant properties of lichexanthone were investigated using the colorimetric assay as Trolox-equivalent antioxidant capacity and at B3LYP/6-31+G** level of theory. Both methods revealed that lichexanthone has weak antioxidant properties. The results confirm the potential of HPLC-UV analysis for taxonomic characterization of lichen species. © Springer-Verlag 2010.
Cytosolic pro-apoptotic SPIKE induces mitochondrial apoptosis in cancer
(2010) Nikolic, Ivana; Kastratović, Gordana; Zelen I.; Zivanovic, Aleksandar; Arsenijevic, Slobodan; Mitrovic M.
Proteins of the BCL-2 family are important regulators of apoptosis. The BCL-2 family includes three main subgroups: the anti-apoptotic group, such as BCL-2, BCL-XL, BCL-W, and MCL-1; multi-domain pro-apoptotic BAX, BAK; and pro-apoptotic BH3-only BIK, PUMA, NOXA, BID, BAD, and SPIKE. SPIKE, a rare pro-apoptotic protein, is highly conserved throughout the evolution, including Caenorhabditis elegans, whose expression is downregulated in certain tumors, including kidney, lung, and breast. In the literature, SPIKE was proposed to interact with BAP31 and prevent BCL-XL from binding to BAP31. Here, we utilized the Position Weight Matrix method to identify SPIKE to be a BH3-only pro-apoptotic protein mainly localized in the cytosol of all cancer cell lines tested. Overexpression of SPIKE weakly induced apoptosis in comparison to the known BH3-only pro-apoptotic protein BIK. SPIKE promoted mitochondrial cytochrome c release, the activation of caspase 3, and the caspase cleavage of caspase's downstream substrates BAP31 and p130CAS. Although the informatics analysis of SPIKE implicates this protein as a member of the BH3-only BCL-2 subfamily, its role in apoptosis remains to be elucidated. © 2010 Elsevier Inc. All rights reserved.
Role of Galectin-3 in Tumour Metastasis
(2010) Radosavljevic, Gordana; Jovanovic I.; Knezevic M.; Zdravkovic, Nemanja; Pavlovic S.; Lukic, Miodrag; Arsenijevic, Nebojsa
We used metastatic variant of B16 melanoma (B16F1) to study lung colonization galectin-3-deficient (gal-3-/-) C57BL/6 mice. In vivo study showed that compared with gal-3+/+ mice, gal-3-/-mice exhibited resistance to lung colonization of B16F1 melanoma cells (p < 0.03). In vitro assays showed higher number of attached malignant cells in the tissue section derived from gal-3+/+ mice (p < 0.001) and tumor specific cytotoxicity of lymphoid cells of tumour inoculated gal-3-/- suggesting that galectin-3 is considered as therapeutic target. © 2010 Allerton Press, Inc.
In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population
(2010) Djordjevic, Natasa; CARRILLO, JUAN ANTONIO; Gervasini G.; Jankovic, Slobodan; Aklillu E.
Purpose: The main aim of the study was to investigate the distribution of cytochrome P450 2A6 (CYP2A6) and xanthine oxidase (XO) enzyme activities in the Serbian population. Secondly, we tested the influence of genetics (CYP2A6 polymorphism), sex, and cigarette smoking on both enzymes. Methods: One hundred forty healthy Serbian volunteers were genotyped for common CYP2A6 alleles. In 100 of them, CYP2A6 and XO activities were determined by the urinary 17U/17X and 1U/(1U+1X) ratios, respectively, after oral administration of 100 mg caffeine as a probe. Results: A 21-fold variation in the 17U/17X ratio was observed (range: 0.49-10.28, mean=1.65, 95% CI: 1.49- 1.83). The urinary 1U/(1U+1X) ratios displayed four-fold variation, ranging from 0.17 to 0.71 (mean=0.43, 95% CI: 0.41-0.45). CYP2A6 alleles *1A, *1B1, *9, *4 and *1B1x2 were found with frequencies of 0.579, 0.307, 0.082, 0.029, and 0.004 respectively. CYP2A6*5 was not detected. CYP2A6 genotype influenced interindividual variability in CYP2A6 enzyme activity (P=0.04). Cigarette smoking inhibited CYP2A6 enzyme activity (P=0.02), but had no effect on activity of XO (P=0.16).There was no significant difference between men and women in terms of CYP2A6 or XO activity. Conclusions: Serbs displayed interindividual variations in CYP2A6 activity. CYP2A6 genotype and cigarette smoking, but not sex, influenced CYP2A6 enzyme activity. Unimodal distribution of XO enzyme activity in Serbs implies the absence of subjects with low enzyme activity in this population. XO activity is not influenced by sex or cigarette smoking. © 2010 Springer-Verlag.
Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma
(2010) Radosavljevic, Gordana; Ljujic, Biljana; Jovanovic I.; Srzentic Z.; Pavlovic G.; Zdravkovic, Nemanja; Milovanovic, Marija; Banković D.; Knezevic M.; Aćimović L.; Arsenijevic, Nebojsa
The promotion of tumor growth is due to a combination of several mechanisms, including angiogenesis and the abundance of cell-derived inflammatory cytokines. The aim of this study was to investigate the serum levels of interleukin 17 (IL-17) and the expression of p53 and Vascular Endothelial Growth Factor (VEGF), in order to determine the relationship between these markers and serum IL-17 levels in patients with colorectal carcinoma. Serum levels of the proinflammatory cytokine IL-17 in patients with colorectal carcinoma (CRC) (n=40) and in a healthy group (n=37) were analysed by ELISA. Surgically resected specimens of 59 colorectal carcinomas were studied by immunohistochemical staining for VEGF and p53. Analyses by ELISA showed significantly higher IL-17 serum levels in patients with colorectal carcinoma than in control subjects (IL-17; mean 128.52±47.62 pg/ml vs. mean 101.91±22.46 pg/ml; p=0.022). We also found an inverse correlation between p53 expression and the level of IL-17 in the serum of patients with CRC. In fact, the serum concentration of IL-17 was significantly higher in patients who did not express p53 (p=0.023). There was no significant correlation between the expression of p53 and VEGF. However, concomitant expression of VEGF and p53 showed a significant correlation with the histological and nuclear grade of the carcinoma. The data presented in our study indicate that IL-17 might act as a valuable tumor marker in patients with CRC and that combined analysis of p53 and VEGF expression might provide additional information about tumor features.
A comparative study of complex formation in the reactions of gold(III) with Gly-Gly, Gly-l-Ala and Gly-l-His dipeptides
(2010) Glišić, Biljana; Rajković, Snežana; Zivkovic, Marija; Djuran, Miloš
Proton NMR spectroscopy was applied to study the reactions of the dipeptides glycyl-glycine (Gly-Gly) and glycyl-l-alanine (Gly-l-Ala) with hydrogen tetrachloridoaurate(III) (H[AuCl4]). All reactions were performed at pH 2.0 and 3.0 and at 40 °C. The final products in these reactions were [Au(Gly-Gly-κ3NG1,N G2,OG2)Cl] and [Au(Gly-l-Ala- κ3NG,NA,OA)Cl] complexes. Tridentate coordination of the corresponding dipeptides and square-planar geometry of these Au(III) complexes was confirmed by NMR (1H and 13C) spectroscopy. This study showed that at pH < 3.0 the Au(III) ion was able to deprotonate the amide nitrogen atom. However this displacement reaction was very slow and the total concentration of the corresponding Au(III)-peptide complex formed after 5 days was less than 60% for the Gly-l-Ala or 70% for the Gly-Gly dipeptide. The kinetic data of the reactions between the Gly-Gly and Gly-l-Ala dipeptides and [AuCl4]- were compared with those for the histidine-containing Gly-l-His dipeptide. The differences in the reactivity of these three dipeptides with the Au(III) ion are discussed. © 2010 Elsevier Inc.
Glucagon effects on ischemic vasodilatation in the isolated rat heart
(2010) Rosic, Mirko; Pantović J.; Rosic, Gvozden; Tomic Lucic, Aleksandra; Labudovic T.; Zivkovic V.; Jakovljevic V.
The myocardial reperfusion following ischemia leads to the ischemic vasodilation by affecting the release of various vasoactive substances, such as free radicals, NO, and histamine. In addition, some evidences suggest that glucagon itself may alter the release of those substances. In this study, we investigated the ischemic vasodilation of the isolated rat heart, as well as the concentrations of NO, TBARS, and histamine in the coronary venous effluent either in the presence or in the absence of glucagon. Our results showed that in the presence of glucagon, there was a faster restoration of coronary perfusion pressure during ischemic vasodilation compared to the absence of glucagon (124 ± 5.6 versus 81 ± 5.2 s) with no apparent changes in TBARS concentration. The glucagon's administration leads to the decreased release of histamine by approximately 35%. Biphasic release of NO in the presence of glucagon initially showed augmentation by 60, followed by the significant attenuation of 45%. © 2010 Mirko Rosic et al.
Neonatal outcome following exposure to organophosphorous pesticides
(2010) Đorđević M.; Vujic, Ana; Jovanović, Boris; Djordjevic, Gordana; Sazdanovic, Maja; Sazdanovic, Predrag
The aim of our study was to determine the neonatal outcome in mothers and children exposed to organophosphorous pesticides (OP). We found that 22.4% pregnant women were exposed to organophosphorous pesticides. OP pesticide concentration was higher in breast milk, newborn sera than maternal sera. Newborn parameters such as birth weight, birth length, head circumference, Apgar score and presence of meconium, as well as gestational age of delivery, showed no significant difference between the two groups. However, postpartum weight loss, hospitalization duration, levels of newborn bilirubin and glycaemia differed significantly between the two groups. Morbidity and presence of CNS disorders were six times and more than twelve times higher, respectively, in the OP-exposed than in the OP pesticide non-exposed group.
Specific skin lesions in hairy cell leukemia at presentation: Case report and review of literature
(2010) Čolović N.; Perunicić M.; Jurisic, Vladimir; Colovic, Mirjana
Skin involvement in hairy cell leukemia (HCL) at presentation is a relatively rare manifestation of the disease. A 60-year-old male patient in whom cutaneous lesions were the initial manifestation of hairy cell leukemia together with leukocytosis, monocytopenia, massive splenomegaly, and leukemic maculopapulous infiltration of the almost whole skin is described. The present case is the forth mentioned in the literature with specify of leukocytosis in peripheral blood, consisting mostly of hairy cells. The patient was treated with two courses of 2-chlorodeoxiadenosine (2-CdA, Cladribine) and splenectomy and after this cutaneous lesion disappeared and general condition is improved. © 2009 Humana Press Inc.
Phytochemical and antioxidant studies of Laurera benguelensis growing in Thailand
(2010) Manojlovic, Nedeljko; Vasiljević, Perica; Gritsanapan W.; Supabphol R.; Manojlović I.
The aim of this study was to investigate metabolites of the lichen Laurera benguelensis. A high-performance liquid chromatographic (HPLC) method has been developed for the characterization of xanthones and anthraquinones in extracts of this lichen. Lichexanthone, secalonic acid D, norlichexanthon, parietin, emodin, teloschistin and citreorosein were detected in the lichen samples, which were collected from two places in Thailand. Components of the lichen were identified by relative retention time and spectral data. This is the first time that a detailed phytochemical analysis of the lichen L. benguelensis was reported and this paper has chemotaxonomic significance because very little has been published on the secondary metabolites present in Laurera species. Some of the metabolites were detected for the first time in the family Trypetheliaceae. The results of preliminary testing of benzene extract and its chloroform and methanol fractions showed that all samples showed a weak radical scavenging activity. The chloroform extract showed the highest antioxidant activity.
Population pharmacokinetics of tacrolimus in kidney transplant patients
(2010) Veličković-Radovanović R.; Catić - Djordjević A.; Milovanovic, Jasmina; Djordjevic V.; Paunovic G.; Jankovic, Slobodan
Objective: The purpose of this study was to derive population pharmacokinetics (PPK) model of tacrolimus clearance, identify and describe factors that influence it in Serbian kidney transplant patients. Methods: Population pharmacokinetics analysis was performed using nonlinear mixed-effects model (NONMEM) program from Serbian adult kidney transplant patients receiving triple immunosuppressive therapy, including oral tacrolimus. Details of drug dosage history, sampling time and tacrolimus concentration in 63 patients (44 males and 19 females), 27 - 57 years old (age mean 40.88 ± 7.01 years) were collected retrospectively. Effects of several covariates on tacrolimus clearance were tested: total body weight, gender, age, posttransplantation days, hemoglobin count, CRP, alanine aminotransferase/ aspartate aminotransferase, total daily dose of tacrolimus, co-medication with cotrimoxasole, omeprazole, mycophenolate mofetil and prednisone (> 25 mg). Results: Typical mean value of tacrolimus clearance, estimated by the base model (without covariates), in our population was 1.03 l h-1. The final model showed that tacrolimus clearance increased with total daily dose and concomitant administration of high-dose prednisone (> 25 mg). The magnitude of prednisone effect was + 1.16 l h-1. Final model was validated in a group of 17 patients, showing good predictive performance. Conclusions: The derived model describes well tacrolimus clearance in terms of characteristics of Serbian kidney transplant patients, offering basis for rational individualization of tacrolimus dosing regimens. ©2010 Dustri-Verlag Dr. K. Feistle.
A nonlinear mixed effects modelling analysis of topiramate pharmacokinetics in patients with epilepsy
(2010) Vovk, Tomaz; Jakovljevic, Mihajlo; Kerec Kos M.; Jankovic, Slobodan; Mrhar A.; Grabnar, Iztok
Topiramate pharmacokinetics is influenced by individual factors such as patient age, renal function and co-treatment. The aim of this study was to develop a population pharmacokinetic model of topiramate to assist dosage adjustments in individual patients. Steady-state topiramate plasma concentrations in patients with epilepsy were determined by HPLC using fluorescent labelling. Demographic, biochemical data and dosing history including concomitant drug therapy were collected from patients' charts. Nonlinear mixed effects modelling was used to fit a one-compartment pharmacokinetic model. The influence of patient weight and gender, body surface area, age, creatinine clearance, serum transaminases, topiramate daily dose and co-treatment with carbamazepine, valproic acid, benzodiazepines, and risperidone on topiramate pharmacokinetics was evaluated. Additionally, the relationship between topiramate plasma concentration and clinical response was investigated. Volume of distribution of topiramate was 0.518 l/kg. For a typical patient oral clearance was estimated at 1.47 l/h, with interindividual variability of 39.2%. Clearance was 70% higher in patients co-treated with carbamazepine and was found to increase with patient age. Somnolence was the most frequently observed adverse event. Incidence of headache was associated with topiramate plasma concentration. Somnolence, ataxia, tremor, speech disorders and fatigue were associated with adjunctive therapy with carbamazepine, valproic acid, benzodiazepines, risperidone, and clozapine. No association of topiramate plasma concentration with frequency of seizures or patient quality of life was observed. The developed model can be used for Bayesian estimation of pharmacokinetic parameters based on sparse plasma samples and for selection of optimum dosing in routine patient care. © 2010 Pharmaceutical Society of Japan.
Palladium(II) complexes with R2edda derived ligands. Part IV. O,O′-dialkyl esters of (S,S)-ethylenediamine-N,N′-di-2-(4-methyl)- pentanoic acid dihydrochloride and their palladium(II) complexes: Synthesis, characterization and in vitro antitumoral activity against chronic lymphocytic leukemia (CLL) cells
(2010) Vujic J.; Cvijović M.; Kaluerovic G.; Milovanovic, Marija; Zmejkovski B.; Volarevic, Vladislav; Arsenijevic, Nebojsa; Sabo, Tibor; Trifunović, Srećko
Four novel bidentate N,N′-ligand precursors, including O,O′-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), L1·2HCl-L4·2HCl, of (S,S)-ethylenediamine-N,N′-di-2-(4- methyl)-pentanoic acid dihydrochloride [(S,S)-H4eddl]Cl2 and the corresponding palladium(II) complexes 1-4, were prepared and characterized by IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. In vitro cytotoxicity of all compounds was determined against chronic lymphocytic leukemia cells (CLL). The compounds were found to exhibit higher antitumoral activity than cisplatin. The most active compound 2, [PdCl2{(S,S)-nPr2eddl}], was found to be 13.6 times more active than cisplatin on CLL cells. Compounds R2edda·2HCl-type esters (L1·2HCl-L4·2HCl) and corresponding palladium(II) complexes (1-4) were synthesized, characterized and tested in vitro against chronic lymphocytic leukemia cells. Cytotoxicity depends on ester R substituents in both esters (IC50: nPe < nBu ≈ nPr < Et) and palladium(II) complexes (IC50: nPr < nPe < nBu ≈ Et). The most active compound 2, [PdCl2{(S,S)-nPr2eddl}], was found to be 13.6 times more active than cisplatin on CLL cells. © 2010 Elsevier Masson SAS. All rights reserved.
Out-of-hospital cardiopulmonary resuscitation in four Serbian university cities: Outcome follow-up according to the «Utstein style»
(2010) Andjelic G.; Djordjevic, Natasa
Aims: To investigate the return of spontaneous circulation (ROSC), survival to discharge, six-month and one-year survival of patients with out-of-hospital cardiac arrest in four university cities in Serbia. Methods: A prospective, two-year, multicentre study was designed. Using the Utstein template, we recorded out-of-hospital cardiopulmonary (CPR) and its outcomes, and analyzed the immediate survival (ROSC>20 min.), short-term survival (to discharge), long-term survival (one year after discharge), or death following out-of-hospital CPR. Results: During the study period, 591 patients met the inclusion criteria for enrollment and out-of-hospital CPR. The etiology of arrest was cardiac in 33.8% of patients. Cardiac arrest was witnessed by the advanced life support (ALS) team in 15.6% of cases. Asystole was the most frequent initial rhythm at time of arrest (46.4%). The highest survival rate (P<0,001) was observed in cases with initial VF and pulseless VT, while patients with asystole and pulseless electrical activity (PEA) had theleast chance of survival. Within the whole group of patients, ROSC was detected with a frequency of 69.7%. The frequency of patients who died in the field or during admission to hospital was 58.9%, while 28.6% of admitted patients died before discharge. Thirteen percent of patients survived until discharge, and the overall six-month and one-year survival rates were 11.3% and 10%, respectively. No statistical difference in survival rates among the cities was found. Conclusion: The Utstein template should be implemented in the form of an official protocol for out-of-hospital CPR follow-up in all emergency medical services in Serbia.
Efficient differentiation of human embryonic stem Cells into Functional Cerebellar-Like Cells
(2010) Erceg S.; Ronaghi M.; Zipančić I.; Laínez S.; Roselló M.; Xiong C.; Moreno-Manzano V.; Rodríguez-Jiménez F.; Planells R.; Alvarez-Dolado, Manuel; Bhattacharya S.; Stojkovic, Miodrag
The cerebellum has critical roles in motor and sensory learning and motor coordination. Many cerebellum-related disorders indicate cell therapy as a possible treatment of neural loss. Here we show that application of inductive signals involved in early patterning of the cerebellar region followed by application of different factors directs human embryonic stem cell differentiation into cerebellar-like cells such as granule neurons, Purkinje cells, interneuron, and glial cells. Neurons derived using our protocol showed a T-shaped polarity phenotype and express similar markers to the developed human cerebellum. Electrophysiological measurements confirmed functional electrical properties compatible with these cells. In vivo implantation of differentiated human embryonic stem cells transfected with MATH1-GFP construct into neonatal mice resulted in cell migration across the molecular and the Purkinje cell layers and settlement in the internal molecular layers. Our findings demonstrate that the universal mechanisms involved in the development of cerebellum can be efficiently recapitulated in vitro, which enables the design of new strategies for cell replacement therapy, to study early human development and pathogenesis of neurodegenerative diseases. © Copyright 2010, Mary Ann Liebert, Inc.
Correlation between serum biochemical markers and early amniocentesis in diagnosis of congenital fetal anomalies
(2010) Loncar, Dragan; Varjacic, Mirjana; Novakovic M.; Mllovanović D.; Jankovic, Slobodan
A combined test performed at the 12th week of gestation enables us to classify the pregnancy as high risk (risk higher than 1:300) or low risk (risk lower than 1:300) for congenital foetal anomalies, with great accuracy of 85 - 90%. According to the available data, the frequency of false positive results is estimated at around 5%. The objective of the study was to examine possible correlation between the serum marker values and amniocentesis results in prenatal diagnostics of congenital foetal anomalies. The study included 745 pregnant women monitored by the Genetic Counselling Service of the Clinic of Gynaecology and Obstetrics of the Clinics Centre Kragujevac. The subjects were included in the study under condition that CRL (embryonic crown-rump length) was from 45 to 84 mm and that the gestational age was at 11-13+6 weeks. Free (5 HCG and PAPP-A were determined from venous blood using commercial DPS-USA tests. Tests were based on the analytic principle of the immuno-chemiluminescence technique and were performed by application of the automatic Immulite 2000 analyzer by DPC-USA. The foetal nuchal translucency thickness (NT) and CRL were measured by Colour Doppler. The chromosome identification was performed after a certain number of cell divisions by stopping the cell division in metaphase of mitosis when the chromosomes were the most distinguishable. The foetal karyotype was prepared using G bands. In the total sample of pregnant women (n=745), there were six cases of pathological foetal karyotype. A statistical paradox in the frequency of congenital foetal anomalies in favour of younger population was noticed. A high coefficient of Spearman's rank correlation suggests great importance of the combined test in the detection of congenital foetal anomalies (p
Elevated Serum Level of IL-23 Correlates with Expression of VEGF in Human Colorectal Carcinoma
(2010) Ljujic, Biljana; Radosavljevic, Gordana; Jovanovic I.; Pavlović N.; Zdravkovic, Nemanja; Milovanovic, Marija; Aćimović L.; Knezevic M.; Banković D.; Savić Zdravković, Dimitrija; Arsenijevic, Nebojsa
Background and Aims: Interleukin-23 (IL-23) has a role in inflammatory bowel diseases (IBD) as a condition of higher risk of colorectal carcinogenesis. Vascular endothelial growth factor (VEGF) is overexpressed in IBD and colorectal carcinoma. Therefore, we aimed at uncovering the relationship between serum level of IL-23 and expression of VEGF in colorectal cancer (CRC) patients and to establish the relationship between VEGF and p53 and serum levels of IL-23, as well as its possible role in carcinogenesis of colorectal carcinomas. Methods: Levels of IL-23 from serum samples of patients with colorectal carcinoma (n = 40) and healthy control samples (n = 37) were examined for IL-23-Ab using an ELISA assay. We also determined the expression of VEGF and p53 by immunohistochemistry in 59 cases of CRC. Results: We found significantly higher serum levels of IL-23 in patients with CRC compared to control subjects (IL-23; mean 189.46 pg/mL vs. mean 34.77 pg/mL, p = 0.033). We also detected higher serum levels of IL-23 in patients with overexpressed VEGF (p = 0.028). Our results also showed that concomitant expression of VEGF and increased serum levels of IL-23 are in positive correlation with histological grade 2 (p <0.05). Conclusions: Our data indicate that serum IL-23 levels are significantly elevated in CRC vs. control patients and are strongly associated with overexpression of VEGF, thus they may play an important role in carcinogenesis of CRC. © 2010 IMSS.
Histamine index and clinical expression of rheumatoid arthritis activity
(2010) Tomic Lucic, Aleksandra; Pantovic, Suzana; Rosic, Gvozden; Obradović, Zdravko; Rosic, Mirko
Background/Aim: Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods: Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results: Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significiant difference in the histamine index which was increased proportionally with disease activity. Conclusion: Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.
Recent views on cytohistological characteristics and pathogenic mechanisms of atherosclerotic lesions types I, II and III
(2010) Vukovic, Irena; Lackovic, Vesna; Raičević, Ranko; lazic, zorica; Milosavljevic, Zoran; Kastratović, Tatjana; Mladenović Mihailović, Aleksandra.; Stankovic, Vesna; Lačković, Milena

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