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Publikacije (25)

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B. Pehlivanovic, M. Ðurovic, A. Sapcanin, S. Ibrulj, F. Becic

: Antigenotoxic and Antioxidative activites of Curcumin Modern biomedical science has proven beneficial effects of curcumin as potential therapeutic candidate for various conditions due to its pleiotropic and pharmacological properties. The aim of the present study was to investigate antigenotoxic effects of curcumin against cisplatin induced genotoxicity as well as its antioxidative effects. In vitro cytokinesis block micronuclei assay in human lymphocytes was used for evaluation of antigenotoxic properties of curcumin. Evaluation of antioxidative properties of curcumin was determined with 2,2-Diphenyl-1-picrylhydrazyl free radical scavenging assay. Results demonstrated significant antigenotoxic and antioxidative properties of curcumin, dependent upon the tested concentrations. Consideration should be given to performing a study with broad dose interval of tested substances. Findings from the present study emphasized application of curcumin as potential antigenotoxic and antioxidative supplementary agent.

The aim of this study was to determine the values of micronuclei (MN) and structural chromosomal aberrations (CA) in peripheral blood lymphocytes from 200 healthy participants of both genders from general population of FBH and of the age in both genders. Frequency distribution of CTAs and CSAs between male and female groups showed predominance of CTAs over CSAs, independently of gender. The results of this study will be incorporated into reference data base for comparative research in future.

A. Haverić, S. Haverić, M. Hadzic, N. Lojo-Kadrić, S. Ibrulj

Genotoxic and cytotoxic effects of curcumin and sunset yellow were tested by the chromosome aberration analysis and cytokinesis-block micronucleus cytome assay in human lymphocyte culture. Water solutions of food dyes, in concentrations of 1, 2, 4 and 8 mM, were added to the cultures at the beginning of the cultivation period. Concentrations of 4 and 8 mM of sunset yellow induced significant increase in frequencies of cells with chromosome aberrations. Tested concentrations of sunset yellow significantly associated with frequencies of structural aberrations, chromatid-type aberrations, total aberrant cells and micronuclei showing considerable dose dependent clastogenic activity. In higher analyzed concentrations, curcumin significantly increased only nuclear buds frequency, suggesting its potential genotoxicity, while sunset yellow showed dose-dependent genotoxic potential. Obtained results point toward favorization of natural coloring agents in food consumption and emphasize the need of controlled use of food colorants.

Mirela Mackic-Djurovic, S. Hasić, E. Kiseljaković, D. Rukavina, S. Ibrulj

Introduction One of the important causes of male infertility is aberration at the chromosomes. Aim The main purpose of this study was to determine the frequency and types of chromosomal aberration in infertile/sterile men whose samples were analyzed in the Center for Cytogenetics of Faculty of Medicine University of Sarajevo in the last four years. Methods A total of 353 infertile/sterile men, between the ages of 22-55 years, referred for cytogenetic analysis to the Center for Genetics of Faculty of Medicine during the period 2013-2016. Karyotyping was performed on peripheral blood lymphocytes by using the Giemsa trypsin banding (GTG) technique. Results The structural and numerical chromosomal aberration in infertility/ sterility of men found with the incidence of 6% (20/353). Out of the 20 patients with abnormal cytogenetic diagnosis, structural chromosome abnormalities were observed in 17 (85%) patients and 3 (15%) with numerical aberrations. The type of aberrations mostly found were Robertsonian and reciprocal translocations (35%, 35%, respectively). Conclusions The incidence of chromosomal abnormalities in infertile/sterile males suggests that the cytogenetics analysis is an important in male infertility, especially if it will be used for the purpose of assisted reproduction techniques.

M. Mačkić-Đurović, Meliha Stomornjak-Vukadin, S. Ibrulj

We report an extremely rare case of Turner syndrome mosaicism in a 30-year-old woman. At least 100 metaphases were observed and analyzed through GTG banding with over 550 band resolutions observed. G-banded chromosome analysis revealed a mosaic female karyotype involving 3 different cell lines. One cell line (90% of the analyzed metaphases) presented monosomy X, while 6% of the cells showed trisomy of chromosome 21 and 4% of the cells exhibited a normal female karyotype. Fluorescence in situ hybridization with a locus-specific probe for trisomy 21 and CEP X for monosomy X substantiated the results obtained from karyotyping. Our patient had 2 natural pregnancies, both of which produced children with Down syndrome. In our patient, as is the case with other women with infertility, the necessary routine is cytogenetic analysis (together with genetic counseling). The same analysis can be helpful in implementing assisted reproductive techniques.

Sanita Maleškić, Nina Jurić, Mirela Mačkić - Đurović, S. Ibrulj

: Aim: Evaluation of the significance of micronuclei (MN) as biomarkers for evaluation the risk of malignant transformation in uterine cervix. MN are intracytoplasmic inclusion bodies from chromatin fragments or whole chromosomes. Their presence in cells is a reflection of chromosomal aberration during cellular mitosis. Patients and methods: MN screening was done in all selected cytopathological smears (conventional Papanicolaou test) by counting 1000 cervical squamous cells with a light microscope at a magnification of 1000x. Results: Comparisons between women with progressive increases in cervical intraepithelial neoplasia (CIN) and control group. The MN frequencies observed were significantly higher in the groups with cellular changes compared to the control group. Conclusion: The results described that the MN test in cervix smears could be incorporated into routine screening procedures as an additional criterion for early detection of cytopathologocal damage. However, additional detailed, systematic studies are needed to confirm this suggestion.

Introduction: Cigarette smoking is associated with severe health problems, especially cancers. In addition, cigarette smoking causes different genotoxic effects. Chromosome aberrations are one of well-known intermediate end points in carcinogenesis. The aim of this study was to compare frequencies of chromosome aberrations in peripheral blood lymphocytes between young smokers and non-smokes groups.Methods: The study was conducted with 30 smokers (average age 26.93 years) and 30 non-smokers (average age 26.96 years), and included the analysis of 100 metaphases per each blood sample. Differences in the arithmetic means of determined frequencies of chromosome aberrations were tested by two-tailed t-test for independent samples with the significance level of p < 0.05.Results: The results showed a significant increase in the frequencies of chromatid-type aberrations and total structural chromosome aberrations in smoker group. Frequencies of numerical aberrations did not differ significantly between two groups.Conclusions: This study confirmed genotoxicity of cigarette smoking and provided new evidence about its clastogenic activity.

M. Sotonica, Mirela Mackic-Djurovic, S. Hasić, E. Kiseljaković, R. Jadric, S. Ibrulj

Background: Advanced paternal and/or maternal age is a classic risk factor for Down syndrome. The aim of the study was to investigate the frequency of Down syndrome types in children and its association with maternal and paternal age in Bosnia and Herzegovina. Subjects and Methods: The cross sectional, observational study included 127 children, 49 girls and 78 boys, aged 1-180 months suspected to have Down syndrome, admitted to the Centre for Genetics, Faculty of Medicine University of Sarajevo, for cytogenetic analysis and differential diagnosis of Down syndrome during the period from January 2010 to May 2015. Standard method of 72 hours cultivation of peripheral blood lymphocytes has been applied. The accepted level of statistical significance was p<0.05. Study Results: The most common type of Down syndrome was standard trisomy (86.6%), comparing to translocation and mosaicism (7.1%; 6.3%, respectively). The highest frequency of Down syndrome cases was in mother and father’s group from 30-39 years old (57; 57 children, respectively) compared to mother and father’s groups with younger than 30 (44; 29, respectively) and 40 and older (26; 41, respectively). The significant difference was found in maternal age between translocation and mosaicism groups (p=0.036). Difference between parental years and type of Down syndrome was significant when Standard trisomy 21 and translocation (p=0.045), as well as mosaicism and translocation (p=0.036), were compared. Conclusion: The most common type of Down syndrome was standard trisomy 21, with highest occurrence in parents from 30 to 39 years old. Parents were the youngest in translocation group. Obtained results suggest that multidisciplinary approach to identifying the trigger for trisomy appearance and the influence of maternal age is required.

The aim of this study was to determine the value of micronuclei test (MN) on peripheral blood lymphocytes from 200 healthy participants of both gender from general population of FB&H, as well as to determine if the gender, age or smoking habit have influence on MN frequency. Standard protocol for MN test cultivating and micronuclei analyzing from peripheral blood binuclear lymphocytes have been applied. Results have presented that range of singe values are from 0 to 8 MN in 1000 binuclear cells. It has been determined that gender, age and smoking habit do have influence on MN frequency, especially on 2 MN frequencies. Females on average do have higher values of all variables of MN test than men. It has been proven that smoking habit do have influence on increased number of cells with 2MN, as well. The results of this study will help to form data base as start for comparative research in

M. Rakanovic-Todic, S. Ibrulj, L. Burnazović-Ristić, A. Ćatović, I. Aganović-Mušinović, J. Kusturica

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.

E. Kiseljaković, S. Hasić, A. Valjevac, M. Mačkić-Đurović, R. Jadric, B. Mehić, E. Kučukalić-Selimović, S. Ibrulj

The aim of the study was to detect prevalence of MBL2 exon 1 (codons 52, 54 and 57) genetic polymorphism in postmenopausal women in Bosnia and Herzegovina and its possible role as genetic risk factor for susceptibility to occurrence of osteoporosis in this study group. Also, we investigated association between MBL serum concentrations and osteoporosis in postmenopausal women. Genetic codons' variations were determined by PCR-RFLP and MBL in serum was measured by ELISA method in 75 postmenopausal women (37 with osteoporosis and 38 apparently healthy, non-osteoporotic women serving as a control). Serum MBL levels were not significantly different between osteoporosis and control group (492 (37-565.1) and 522.6 (477-559.4) ng/mL respectively, p=0.206). Genotype frequencies were not significantly different (p=0.997) between the studied groups of postmenopausal women. Genotype frequencies A/A, A/0 and 0/0 in osteoporosis group were 0.576; 0.405; 0.018 and in control group 0.562; 0.412; 0.026, respectively. Frequencies of A and 0 allele were 0.78 and 0.22 in osteoporosis and 0.77 and 0.23 in control group. The results do not suggest association of functional polymorphism of MBL2 gene and MBL serum concentration with osteoporosis in postmenopausal females.

M. Mačkić-Đurović, Petar Projić, S. Ibrulj, J. Cakar, D. Marjanovic

The goal of this study was to examine the effectiveness of 6 STR markers application (D21S1435, D21S11, D21S1270, D21S1411, D21S226 and IFNAR) in molecular genetic diagnostics of Down syndrome (DS) and to compare it with cytogenetic method. Testing was performed on 73 children, with the previously cytogenetically confirmed Down syndrome. DNA isolated from the buccal swab was used. Previously mentioned loci located on chromosome 21 were simultaneously amplified using quantitative fluorescence PCR (QF PCR). Using this method, 60 previously cytogenetically diagnosed DS with standard type of trisomy 21 were confirmed. Furthermore, six of eight children with mosaic type of DS were detected. Two false negative results for mosaic type of DS were obtained. Finally, five children with the translocation type of Down syndrome were also confirmed with this molecular test. In conclusion, molecular genetic analysis of STR loci is fast, cheap and simple method that could be used in detection of DS. Regarding possible false results detected for certain number of mosaic types, cytogenetic analysis should be used as a confirmatory test.

M. Rakanovic-Todic, L. Burnazović-Ristić, S. Ibrulj, Nedžad Mulbegović

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect 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). The goal of the present research was to evaluate met-enkephalin in vitro effects 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 (1.2 μg/mL). However, this research did not detect any significant effects 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 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

M. Rakanovic-Todic, L. Burnazović-Ristić, S. Ibrulj, N. Mulabegović

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

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