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    The genotoxicity of Tenofovir disoproxil fumarate in HBV-infected patients
    (2018) Yüksel, Şengül; Ersoy, Yasemin; Korkmaz, Selcen
    Tenofovir disoproxil fumarate (TDF) is an acyclic nucleotide reverse transcriptase inhibitor used as antiviral therapeutic drug in hepatitis B virus (HBV) infection treatment. We investigated whether HBV itself or TDF could enhance genotoxicity in HBV infected patients. A total of 30 HBV-infected patients were included in this study: 10 were untreated, 10 took therapy for 6 months, 10 took therapy for 12 months and a further 15 were control group. We used the micronucleus test (MN) and mitotic index (MI) to assess the genotoxic effects of TDF. MN and MI frequency were significantly increased in all the HBV-infected patient groups when compared to control. However, significant differences were not found between different time points within the therapy groups. The current data indicate that chronic HBV infection without treatment has an effect on MN and MI. TDF administration at therapeutic doses for 12 months also did not reduce the MI and MN, suggesting its protective action against HBV induced genotoxic damage. Larger-scale and longtime studies are required for a better understanding of the genotoxicity of TDF.
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    Prevalence of Pericentric Inversion of Chromosome 9 in Eastern Anatolia Region and Relationship to Reproductive Efficiency
    (Kare Publ, 2018) Yuksel, Sengul; Savaci, Serap; Ekici, Cemal; Kurtoglu, Elcin Latife; Korkmaz, Selcen; Yesilada, Elif
    Objectives: One of the most common, structurally balanced chromosome rearrangements is the pericentric inversion of chromosome (inv[9]). It is considered to be a variant of the normal karyotype, and has been found in both normal populations and patients with various abnormal phenotypes. The aim of this study was to determine the frequency of chromosome 9 rearrangement in the Malatya Province and check whether it is correlated with certain diseases. Methods: In this study, we investigated the karyotype analysis of 4168 patients admitted in the Turgut Ozal Medical Center and Research Hospital, Genetic Disease Diagnosis Center Laboratory, between 2014 and 2016 and retrospectively reviewed their clinical data. Chromosomes from cultured peripheral blood lymphocytes were analyzed using Giemsa Trypsin-Giemsa (GTG) banding. Results: Pericentric inversion was detected in 71 (1.7 %) of 4168 cases, including 32 (45.1%) cases with inv(9) causing infertilty, 21 (29.6%) causing growth retardation, four (5.6%) causing multiple spontaneous abortion, and 14 (19.7%) causing other abnormalities, all of which were referred to our laboratory. Conclusion: In this study, the distribution of inv (9) in the Malatya Province was shown, and it is believed that these results would contribute to the knowledge regarding the incidence of inv (9) in the Eastern Anatolia Region and Turkey.
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    A Rare Mosaic Karyotype of 45,X/46,X,psu idic(Y)(p11.32)/46, XY with SHOX Haploinsufficiency, External Male Genitalia, and Short Stature
    (Karger, 2019) Ekici, Cemal; Esener, Zeynep; Korkmaz, Selcen; Salturk, Nihal; Yuksel, Sengul; Koc, Ahmet
    In this case study, we describe a 3-year-old boy who was referred to the Inonu University Hospital with short stature complaint. His height was 86 cm (-2.96 SDS), weight was 12 kg (-2.43 SDS), and head circumference was 46.5 cm (-2.34 SDS). Chromosomal analyses were performed on cultured peripheral blood lymphocytes of the patient and his parents and showed the patient's karyotype mos 45, X[20]/46, X, idic(Y)(p11.32)[29]/46, XY[1]. The karyotypes of the parents were normal. Subsequently, specific FISH probes were hybridized to the related regions of the sex-determining region Y (SRY), centromere X/Y (CEP X/Y), and short stature homeobox (SHOX) genes. Simultaneous SNP array-CGH was conducted. As to our knowledge, we present the first patient with mosaic isodicentric Y chromosome with 3 different cell lines and normal male external genitalia. Our results suggest that it would be beneficial to study cytogenetic and molecular cytogenetic methods together for better diagnostic accuracy and treatment. (C) 2018 S. Karger AG, Basel
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    Tenofovir'in mikronükleus sıklığına etkileri ve APE1, XRCC1 VE XPD DNA tamir genlerindeki polimorfizm ile ilişkisinin araştırılması
    (İnönü Üniversitesi, 2014) Korkmaz, Selcen
    Tenofovir, HBC ve HIV gibi viral enfeksiyonlarda nükleotid ters transkriptaz inhibitörü olarak çalışan adenozin monofosfat analoğu bir ilaçtır. Çalışmaya; sağlıklı kişiler (15), ilaç kullanmamış HBV hastaları (10), 0-6 ay tenofovir kullanmış HBV hastaları (10) ve 12+ ay tenofovir kullanmış HBV hastaları (10) dâhil edildi. Çalışmaya katılan kişilerden sitogenetik analizler için mikronükleus (MN) ve mitotik indeks (MI) frekansları saptandı. Ayrıca DNA tamir genlerinden APE1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg399Gln ve XPD Lys751Gln gen polimorfizmleri ile MN ilişkisini belirlemek üzere moleküler analizler yapıldı. Günlük 245 mg dozda tenofovir kullanımının MI ve MN frekanslarını etkilemediği ancak tüm HBV hasta gruplarında kontrole göre MN ve MI frekansları daha yüksek değerde saptandı. MN'deki bu artış ile APE1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg399Gln ve XPD Lys751Gln tamir gen polimorfizmi arasında anlamlı ilişki bulunamadı. HBV ve tenofovirin genotoksisitesine ilişkin benzer bir çalışmaya rastlanamamıştır. Sonuç olarak, çalışma gruplarının küçük olmasına rağmen 245 mg dozda kronik kullanılan tenofovirin genotoksik etkisi olmadığı ancak HBV'nin genotoksisite potansiyelinin yüksek olduğunu söyleyebiliriz.