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Öğe Dexmedetomidine ameliorates TNBS induced colitis by inducing immunomodulator effect(Journal of Surgical Research, 2013) Erdoğan Kayhan, Gülay; Gül, Mehmet; Kayhan, Başak; Gedik, Ender; Özgül, Ülkü; Kurtoğlu, Elçin Latıfe; Durmuş, Mahmut; Ersoy, Mehmet ÖzcanBackground: Since sedatives are often administered to immune-compromised and critically ill patients, our understanding of immunomodulation by sedation will be critical. Dexmedetomidine, a selective a2-adrenergic receptor agonist, is often used for sedation and analgesia especially in intensive care units. There are conflicting and little data concerning both the effect and the mechanism of dexmedetomidine on immune response. In our study, we aimed to investigate the effect of dexmedetomidine on immune system at two different doses (5 mg.kg 1 and 30 mg.kg 1 ) during inflammatory bowel disease by using an experimental model, which resembles both systemic and local inflammation. Methods: The effect of dexmedetomidine on the course of inflammatory bowel disease was investigated by measuring macroscopic and microscopic parameters. We investigated proinflammatory Th1, Th2, and Th17 cytokine levels in serum samples to analyze systemic immune response. Following this, local immune response was investigated by measuring cytokine levels in the presence of dexmedetomidine in spleen cell culture. Results: Dexmedetomidine administration led to amelioration of all disease associated pathological manifestations. According to our in vitro and in vivo results, dexmedetomidine shows anti-inflammatory effect by increasing IL-4 and IL-10 levels responsible from antiinflammatory response via Th2 pathway. Moreover, we showed for the first time in the study that dexmedetomidine administration reduces IL-23, which is responsible from initiation of inflammatory response via Th17 pathway. Conclusions: Dexmedetomidine can have beneficial effect on preoperative or postoperative inflammatory bowel disease patients in intensive care units by down-regulating inflammatory immune response not only in systemic circulation but also in tissue-specific manner.Öğe HLA A B DRB1 allele and haplotype frequencies and comparison with blood group antigens in dialysis patients in the east anatolia region of Turkey(Transplantation proceedings, 2013) Kayhan, Başak; Kurtoğlu, Elçin Latıfe; Taşkapan, Hülya; Pişkin, Turgut; Şahin, İdris; Otlu, Gonca; Ünal, BülentAim. The first aim of that study was to investigate HLA class I and class II allele and haplotype frequencies in renal dialysis patients who live in East Anatolia in Turkey. Our second aim was to investigate whether there was a relationship between ABO and D blood group antigens and HLA alleles and haplotypes for the study group. Materials and methods. HLA class I and II polymorphisms in 408 renal dialysis patients were studied using sequence-specific primers (SSP) and sequence-specific oligonucleotides (SSO). Blood group antigens were detected by agglutination methods on microplates. Results. A total of 16 HLA-A, 34 HLA-B, and 15 HLA-DRB1 alleles were identified. The most frequent HLA-A alleles were HLA-A*02, HLA-A*24, and HLA-A*11. The most frequent HLA-B alleles were HLA-B*35, HLA-B*51, and HLA-B*44. In case of HLADRB1; HLA-DRB1*11, HLA-DRB1*04, and HLA-DRB1*13 were first 3 alleles with higher frequency, in order. In the combination of those 3 alleles, the most frequent HLAA-B-DRB1 haplotypes were HLA-A*02-B*51-DRB1*11, HLA-A*11-B*35-DRB1*11, A*24-B*35-DRB1*11. The frequency of ABO, D blood group antigens were observed as 0.168 for A Rh(þ), 0.019 for A Rh(), 0.057 for B Rh(þ), 0.013 for B Rh(), 0.123 for O Rh(þ), 0.014 for O Rh(), 0.018 for AB Rh(þ), and 0.001 for AB Rh(). While A Rh(þ) samples with HLA-A*02 and HLA-DRB1*11 had the highest frequencies (0.067 and 0.088, respectively), O Rh(þ) samples with HLA-B*51 had the highest frequency (0.06). Conclusion. According to haplotype frequencies HLA-A*02-B*51-DRB1*11 is also found at higher frequencies in Bulgarian and Armenian populations. In case of HLAassociated diseases, the east Anatolian population could be susceptible to myastenia gravis, Behçet’s disease, and systemic sclerosis due to the high frequencies of HLAA*24, HLA-B*51, and HLA-DRB1*11 respectively. We did not observe a correlation between blood group antigens and HLA alleles or haplotypes in renal dialysis patients.Öğe Mystery of immune response in relapsed brucellosis immunophenotyping and multiple cytokine analysis(Mediterrenean Journal of Infection Microbes and Antimicrobials, 2016) Kayhan, Başak; Kayabaş, Üner; Kölgelier, Servet; Otlu, Barış; Gül, Mehmet; Kurtoğlu, Elçin Latıfe; Bayındır, YaşarIntroduction: Brucella spp. are intracellular bacteria that may cause acute, subacute and chronic infections. Although optimum antibiotic treatment is available, relapse of brucellosis occurs in some patients. There isless amount of knowledge about immune response in relapse of brucellosis. Materials and Methods: Twenty patients with acute brucellosis and sixteen patients with relapse brucellosis were enrolled in this study to explore the immune response variation during relapse of brucellosis. The distribution of peripheral blood mononuclear cells investigated by flow cytometry and various cytokines levels involved in inflammatory and anti-inflammatory response, measured by ELISA in serum samples. Results: The most prominent data in phenotyping examination was the significant 1.45 times reduction at the percentage of activated T cell (CD3+HLA-DR+ ) population in the relapse group in comparison to acute brucellosis. However, percentage of activated T cell population in the relapse group was 2.59 times higher than the healthy group (p<0.01). In case of cytokine levels; we observed significant reduction at inflammatory cytokines IL-6, IL-18, IFN-g and IL-17 in relapsed patients in comparison to patients with acute brucellosis. While there was no significant difference in IL-15 and TNF-a levels between relapse and acute brucellosis group; the levels of these two cytokines were significantly higher in the relapse group than healthy subjects. Interestingly, we observed 2.87 times elevation ofIL-4 levels in the relapse group in comparison to acute brucellosis (p<0.01). Similarly; IL-10 levels increased 2.09 times in patients with relapsed brucellosis patients in comparison to acute brucellosis (p<0.01). Conclusion: Elevation of regulatory cytokinesin systemic immune system, and reduction of activated T cell frequency occur during the relapse of brucellosis. These results may have important consequences to understand the immunopathology in the systemic circulation during relapse of brucellosis.Öğe Takrolimus'un genotoksik etkilerinin araştırılması(İnönü Üniversitesi, 2010) Kurtoğlu, Elçin LatıfeTakrolimus (FK-506), immünsüpressif tedavinin temel ilacı olmakla birlikte nefrotoksisite, nörotoksisite ve deri kanseri ile lenfoma gibi malign tümör oluşumunu içeren ciddi yan etkilere sahiptir. Bu çalışmada, Takrolimus'un olası genotoksik etkileri, insan lenfosit kromozomlarında, kromozom aberasyonları (KA), kardeş kromatid değişimleri (KKD), mikronükleus (MN) ve hücre büyüme kinetiği parametreleri kullanılarak araştırıldı. Lenfositler Takrolimus'un dört farklı konsantrasyonuna (5, 25, 50,100 ng/ml) ve iki farklı uygulama süresine (24 ve 48 saat) maruz bırakıldı. Takrolimus 24 ve 48 saatte tüm konsantrasyonlarda KA'larını indükledi. Benzer şekilde uygulama gruplarında toplam MN frekansında kontrole göre istatistiksel olarak anlamlı artış saptandı. Ayrıca, KKD 24 saatlik uygulamada en yüksek konsantrasyonda (100 ng/ml) ve 48 saatlik uygulamada 25 ve 100 ng/ml'lik konsantrasyonda indüklendi. Takrolimus, 24 ve 48 saatte 5 ng/ml hariç tüm konsantrasyonlarda mitotik indeksi (MI) azalttı. Replikasyon indeksi (RI) 48 saatte tüm konsantrasyonlarda, 24 saatte ise 50 ve 100 ng/ml'lık konsantrasyonlarda azaldı. Sonuç olarak, Takrolimus güçlü mutajeniteye sahip olup malignansiye yol açabilecek genetik hasarlara neden olabilmektedir.
