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Öğe Clastogenicity of selective serotonin-reuptake inhibitors(Elsevier Science Bv, 2004) Bozkurt, G; Abay, E; Ates, I; Karabogaz, G; Ture, M; Savran, FO; Palanduz, SObjective: Selective serotonin-reuptake inhibitors (SSRIs) are used in the treatment of various forms of psychiatric disorders. Preclinical studies in laboratory animals have indicated that SSRIs were not genotoxic, but clear results from in vitro testing of SSRIs in a human cell system are currently scarce. The purpose of this study was to investigate whether SSRIs might be genotoxic. Sertraline was chosen as model SSRI, since it appears to be at least as well-tolerated as other SSRIs and may even have a more favourable side-effect profile. Unlike fluoxetine, fluvoxamine and paroxetine, sertraline has low potential for pharmacokinetic drug interactions. So, sertraline would be considered first in the treatment of psychiatric disorders requiring SSRI therapy in the future. We therefore examined peripheral lymphocytes from sertraline-treated patients for both sister chromatid exchanges (SCEs), cells with a high frequency of SCEs (HFC) and chromosome aberrations (CA) to evaluate the elastogenicity of SSRIs. Method: Ten sertraline-treated patients meeting 'Structured Clinical Interview for DSM-IV' criteria for both generalized anxiety disorder and major depression were compared with 18 healthy volunteers and 18 non-treated patients with similar psychopathology. Sertraline hydrochloride was administered orally at 50 mg daily for 10 months to I year. The participants were selected on the basis of similar responses to a questionnaire assessing risk of genotoxicity related to other aspects of life. All participants had very similar lifestyles, medical histories, biological and dietary factors. All subjects were non-smokers. Result: A statistically significant difference between patients with both generalized anxiety disorder and major depression (sertraline-treated or non-treated) and healthy volunteer groups was found by both SCE frequencies and HFC percentages. Both patient groups showed higher frequencies of SCEs than the healthy controls. No statistically significant difference was found between SCE frequencies or HFC percentages observed in sertraline-treated and non-treated patient groups. No statistical difference was found between groups with respect to the frequency of CA. Conclusion: There are no adequate studies analysing the clastogenicity of SSRIs, in particular of sertraline. The SCE frequency, the percentage HFC and the frequency of CA in patients with both generalized anxiety disorder and major depression exposed to daily doses of sertraline do not indicate a possible clastogenic hazard. The increased SCE frequencies in patients with both generalized anxiety disorder and major depression in our study-irrespective of sertraline treatment-indicate a possible genotoxic effect. However, our observations were based on a limited number of patients; the results may be explained by psychogenic stress. (C) 2003 Elsevier B.V. All rights reserved.Öğe A different approach to telomere analysis with ddPRINS in chronic lymphocytic leukemia(Elsevier Science Bv, 2006) Palanduz, S; Serakinci, N; Cefle, K; Aktan, M; Tutkan, G; Ozturk, S; Bozkurt, GTelomeric sequences, located at the very end of the chromosomes, compensate for the chromosomal shortening as it happens after each round of cell division. Telomeric sequences influence the progress of cellular senescence and cancer progression. It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia (CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique. Twenty patients with CLL and four healthy donors as a control group were included. We found short telomeres and no detectable telomeric repeats at the sites of chromosome fusion. We hypothesise that the telomeric erosion in CLL may reflect the dominance of malignant cells with an abnormally long life span. These cells may have encountered many antigenic stimulants in the past and hence underwent multiple clonal expansions. Our findings imply that shortened telomeres in CLL may be reflecting the history of the disease and serve as an independent prognostic factor. (c) 2004 Published by Elsevier SAS.Öğe Genotoxicity of waste anaesthetic gases(Australian Soc Anaesthetists, 2002) Bozkurt, G; Memis, D; Karabogaz, G; Pamukcu, Z; Ture, M; Karamanlioglu, B; Gunday, IBackground and aim: The possibility of a potential mutagenic or carcinogenic action of chronic exposure to low concentrations of inhalational anaesthetics has been previously studied, with conflicting results. The purpose of this study was to assess whether occupational exposure to waste anaesthetic gases increases genotoxic risk. We examined peripheral lymphocytes from anaesthetists for both sister chromatid exchange (SCE) and for cells with high-frequency SCEs (HFCs). Method: A group of 16 non-smoking anaesthetists with occupational exposure to anaesthetic gases and a sex- and age-matched group matched 16 non-smoking matched physicians without occupational exposure to anaesthetic gases were studied. The participants were also selected on the basis of similar responses to a questionnaire assessing risk of genotoxicity relating to other aspects of life. Result: SCEs, and HFC percentages obtained from the exposed anaesthetists (6.6 +/- 2.4 and 12.2 +/- 15.9) were greater but not statistically significantly so than in the reference group (5.2 +/- 1.6 and 5.9 +/- 10.0). Conclusion: This study does not support the existence of an association between occupational exposure to waste anaesthetic gases and an increase in SCEs in lymphocytes. The nature of our anaesthesia practice suggests exposure was likely to be low. It should be noted that some anaesthetic gases produce lesions that can be efficiently repaired in mitogen-stimulated lymphocytes in vitro but not in circulating lymphocytes.Öğe HLA B-27 subtypes in turkish patients with spondyloarthropathy and healthy controls(Hindawi Ltd, 2004) Oguz, FS; Ocal, L; Diler, AS; Ozkul, H; Asicioglu, F; Kasapoglu, E; Bozkurt, GThe frequency and the distribution of HLA-B27 subtypes in spondylarthropathy (SpA) patients and controls were investigated in a sample Turkish population. B27 subtyping was performed by PCR-SSP method in two groups: 49 unrelated HLA-B27 positive Turkish patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group Criteria, and 55 HLA-B27 positive healthy controls. The frequency of HLA-B*27 was 2.6% in the Turkish population, and B*2705 was the predominant allele among patients with SpA. The difference was mainly between male patients and male controls The proportion of B*2705 among B27-positive patients and controls was significantly different (P = 0.02). Our study supports other reports from different populations which showed that B*2705 and B*2702 were more frequent in Caucasian patients with SpA.Öğe Sister chromatid exchanges in lymphocytes of nuclear medicine physicians(Elsevier Science Bv, 2003) Bozkurt, G; Yuksel, M; Karabogaz, G; Sut, N; Savran, FO; Palanduz, S; Yigitbasi, ONObjective: The aim of this study was to assess whether occupational exposure to chronic, low doses of Iodine 131 (I-131) and Technetium 99m (Tc-99m) may lead to genotoxicity. Medical personnel occupied in nuclear medicine departments are occupationally exposed to low doses of I-131 and Tc-99m. The determination of the frequency of sister chromatid exchanges (SCEs) and of cells with a high frequency of SCEs (HFC) is considered to be a sensitive indicator for detecting genotoxic potential of mutagenic and carcinogenic agents. Therefore, we examined peripheral lymphocytes from nuclear medicine physicians for the presence of both SCE and HFC. Methods: Sixteen exposed nuclear medicine physicians (non-smokers) were compared to 16 physicians (non-smokers) who had not been exposed to chemical or physical mutagens in their usual working environment at the same hospital. Results: A statistically significant difference was found between SCE frequencies and HFC percentages measured in lymphocytes from the exposed and control groups. Conclusions: The present observation on the effect of chronic low doses of I-131 and Tc-99m indicates the possibility of genotoxic implications of this type of occupational exposure. Hence, the personnel who work in nuclear medicine departments should carefully apply the radiation protection procedures and should minimize, as low as possible, radiation exposure to avoid possible genotoxic effects. (C) 2002 Elsevier Science B.V. All rights reserved.Öğe Thrombosis in systemic lupus erythematosus(Springer-Verlag, 2003) Pamuk, GE; Turgut, B; Vural, Ö; Demir, M; Soy, M; Bozkurt, G; Çelik, HThrombosis in the venous or arterial system is quite common in systemic lupus erythematosus (SLE). We describe a young female patient whose first presentation was in the form of deep venous thrombosis of the right lower extremity. Her family history for thrombosis was positive and further studies revealed her to have SLE. Genetic studies showed that she had thrombophilic mutations of factor V, prothrombin and methylene tetrahydrofolate reductase genes. Her therapeutic response to anticoagulant therapy was satisfactory. The presence of inherited thrombophilic mutations must be searched for in SLE patients with thrombosis, especially in cases with a positive family history.
