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    The Effect of CYP1A1 and GSTP1 Isozymes on the Occurrence of Aortic Aneurysms
    (Georg Thieme Verlag Kg, 2015) Simsek, Erdal; Kilic, Murat; Simsek, Gulcin; Oguztuzun, Serpil; Moran, Busra; Saritas, Ahmet; Ulus, A. Tulga
    Background Aortic aneurysms are vascular diseases that are associated with high mortality and morbidity. Cytochrome P450 CYP1A1 and glutathione S-transferase (GSTP1) isozymes were searched and compared with the patients who had experienced aortic surgery due to aortic aneurysm and atherosclerotic patients without aneurysm to find the relation of the oxidative stress with the aneurysms. Materials and Methods Study group consisted of the patients with the diagnosis of aortic aneurysm (group I, n: 12) and control group who were operated for coronary bypass surgery: preoperatively drug users (group II, n: 21) and nonusers (group Ill, n: 15). Paraffin sections (4 pm thick) of aortic biopsy materials were stained with hematoxylin and eosine, CYP1A1 and GSTP1 immunohistochemical markers. The specimens were evaluated using light microscopy at 40- to 400-fold magnification. Results The expressions of CYP1A1 and GSTP1 isozymes were found statistically significantly higher in the patients who have an aortic aneurysm than both the control groups (p < 0.05). There was no significant association between protein expressions, drugs and duration of usage, patient's demographic variables, and smoking (p > 0.05). Conclusions In this pioneering study, CYP1A1 and GSTP1 isozymes are related with the aneurysms. The strategy that prevents the oxidative stress for the patients who had aortic aneurysms could be a valuable choice of searching to effect the aneurysmal progression.
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    The expression of GST isoenzymes in acinar adenocarcinoma, intraepithelial neoplasia, and benign prostate tissue: correlation of clinical parameters with GST isoenzymes
    (Tubitak Scientific & Technical Research Council Turkey, 2012) Simsek, Gulcin; Oguztuzun, Serpil; Guresci, Servet; Kilic, Murat; Bozkurt, Omer Faruk; Unsal, Ali
    This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase (GST) alpha, pi, mu, and theta in prostatic acinar adenocarcinoma (PCA), prostatic intraepithelial neoplasia (PIN), and benign prostatic tissues from 19 patients. Relationships between GST isoenzyme expression in benign, PIN, and PCA tissue were examined by the Wilcoxon signed-rank test and clinicopathological data were examined by the Spearman correlation rank test. When the benign, PIN, and PCA tissues from these cases were compared according to their staining intensity, GST alpha, pi, mu, and theta expressions in tumor cells were significantly lower than in benign epithelial cells (P<0.05). The GST alpha class displayed the lowest level of expression in PIN and PCA. Expression of GST pi was lower in PCA tissue than in PIN and benign epithelial tissue (P<0.05). We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST isoenzymes and other detoxifying and antimutagenesis agents. This study confirms the down-regulation of GST isoenzymes in PCA of the prostate and shows that the loss of GST isoenzyme expression is a phenotype associated with malignant transformation. There was no statistical relationship between GST isoenzyme expression and the clinicopathological data (age, Gleason score, and total serum prostate-specific antigen levels) (P>0.05).
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    Immunohistochemical Expressions of the Antimicrobial Peptides (hBD-3 and hCAP-18/LL-37) in Colon, Stomach and Lung Adenocarcinomas
    (Akad Doktorlar Yayinevi, 2015) Kilic, Murat; Oguztuzun, Serpil; Simsek, Gulcin; Cakir, Ebru
    This study investigated the immunohistochemical staining characteristics of human beta defensin-3 (hBD-3) and human cationic antimicrobial peptide-18/cathelicidin (hCAP-18/LL-37) in colon, stomach and lung adenocarcinomas and normal tissues (periphery to tumor tissues) from 22, 24 and 24 patients, respectively. Expressions of hBD-3 and hCAP-18/LL-37 were assessed by immunohistochemistry for colon, stomach and lung adenocarcinomas of 70 patients from Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital and Kecioren Training and Research Hospital. both located in Ankara, Turkey. The differences between the expressions of hBD-3 and hCAP-18/LL-37 in normal and carcinoma tissues were analyzed by Mann-Whitney U Test. When the normal and tumor tissues of these cases were compared according to their staining intensity of positive staining, the hBD-3 and hCAP-18/LL-37 expressions in colon, stomach and lung adenocarcinomas cells were significantly higher than those in normal cells (p<0.05). Immunostaining of HBD-3 and hCAP-18/LL-37 was found to be a marker of malignancy in colon, stomach and lung adenocarcinomas. The expressions of hBD-3 and hCAP-18/LL-37 were, for the first time, shown to be significantly altered in colon, stomach and lung adenocarcinomas as compared to controls. In conclusion, the present findings suggest that beside the antimicrobial activity of Antimicrobial Peptides (AMPs), hBD-3 and hCAP-18/LL-37 can also play a role in the pathogenesis of colon, stomach and lung adenocarcinomas.
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    An investigation of human beta-defensins and cathelicidin expression in patients with pterygium
    (Consel Brasil Oftalmologia, 2017) Karadag, Remzi; Bayram, Nurettin; Oguztuzun, Serpil; Bayramlar, Huseyin; Bozer, Busra; Simsek, Gulcin; Rapuano, Christopher J.
    Purpose: To investigate human beta-defensins (HBDs) and cathelicidin LL-37 (LL-37) expressions in patients with pterygium. Methods: In this retrospective consecutive case series, 26 pterygium specimens and 15 normal conjunctival specimens of 15 control subjects were in-vestigated. Expressions of HBD-1, HBD-2, HBD-3, and LL-37 were assessed using immunohistochemical staining. A brown color in the cytoplasm and/or nuclei of epithelial cells indicated positive staining for HBDs and LL-37. For each antibody, the intensity of the reaction (negative [-], weak [1+], moderate [2+], or strong [3+]) was determined to describe the immunoreactions. Results: The median age was 52 years in both groups. There were no significant differences in age and sex between the groups (p=0.583, p=0.355, respectively). Of the 26 pterygium specimens, 15 (57.7%) (14 weak, 1 moderate staining) showed HBD-2 expression, which was not observed in any of the control specimens. One (3.8%) pterygium and one (6.7%) control specimen demonstrated weak staining for HBD-3. HBD-2 expression was significantly higher in the pterygium specimens than in the controls (p=0.002). None of the tissue specimens had positive staining for HBD-1 or LL-37 in either group (both; p=1.00). Conclusions: HBD-2 expression was higher in pterygium specimens than in the controls. HBD-2 expression that might be stimulated by inflammatory cytokines may be related to inflammation and fibrovascular proliferation and may play a role in pterygium pathogenesis.
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    Is montelukast effective in regression of endometrial implants in an experimentally induced endometriosis model in rats?
    (Elsevier, 2015) Altinbas, Sadiman Kiykac; Tapisiz, Omer Lutfi; Cavkaytar, Sabri; Simsek, Gulcin; Oguztuzun, Serpil; Goktolga, Umit
    Objective: Montelukast, a selective antagonist of Type 1 cysteinyl leukotriene receptors (CysLT(1)Rs), antagonizes the proinflammatory and proasthmatic activities of CysLT(1)Rs. We investigated the effect of montelukast on a surgically induced endometriosis rat model. Study design: Thirty-two sexually mature, cycling, female Wistar-Albino rats, in which endometriotic implants were surgically induced, were randomly divided into three groups. Group I [Montelukast (M), 10 rats)] was given 1.6 mg/kg/day of oral montelukast sodium. Group II [Leuprolide acetate (L), 11 rats] was given 1 mg/kg single dose of s.c.leuprolide acetate. Group III [Control (C), 11 rats] received saline solution through an orogastric tube and served as controls. After a 3-weeks medication, the rats were sacrificed to investigate the endometriotic implants for size and morphological and histological characteristics, including immunoreactivity of MMP-2 and VEGF. Results: The mean area of implants decreased from 48.2 +/- 24.7 to 293 +/- 15.8 mm(2) in Group I (M) (P = 0.008) and from 62 +/- 32.1 to 39.9 +/- 18.1 mm(2) in Group II(L) (P = 0.003). In Group III (C), the mean area increased from 41.1 +/- 31.1 to 60.4 +/- 37.1 mm(2) (P = 0.025). Histopathological analysis showed statistically significant lower scores in rats treated with montelukast compared to leuprolide and controls. MMP H scores were not different between the groups in both epithelial and stromal MMP-2 immunostaining. VEGF H scores were statistically lower in Group I (M) in epithelial VEGF immunostaining when compared to Group II(L) and Group III (C) (P = 0.006). Conclusion(s): Montelukast may effectively cause a significant decrease in the area of endometriotic implants. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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    The Administration of Steroids and its Impact on Caspase-3 Expression in Pediatric Adenoid Hypertrophy
    (Springer India, 2024) Apaydin, Emre; Yasar, Buse; Simsek, Gulcin; Kaygin, Pinar; Sarialtin, Sezen Yilmaz; Dirican, Onur; Cetin, Hazal Eylem
    ObjectiveAdenoid hypertrophy is a prevalent pediatric condition, often necessitating surgical intervention. Intranasal steroid administration shows promise as a conservative treatment, particularly by inducing apoptosis in adenoidal cells, leading to a reduction in adenoid size and inflammation. This study aims to characterize the expression profile of caspase-3 as an apoptotic inducer protein in inflammatory and epithelial adenoid tissues and explore its association with steroid administration. MethodsWe performed immunohistochemical staining for caspase-3 proteins in adenoid tissues obtained from 51 pediatric patients aged between 2.5 and 12 years (mean age: 6.09 +/- 2.1 years) who underwent adenoid surgery. A retrospective analysis of clinical data was conducted, categorizing participants into steroid treatment receivers (n = 25) and non-receivers (n = 26). Subsequently, the lymphoid inflammatory tissue and epithelial tissue from the adenoid were compared in terms of caspase-3 protein expression, and associated clinical variables were assessed. ResultsImmunohistochemical analysis revealed significant caspase-3 expression in inflammatory tissues. The expression levels were scored, and no significant correlation was observed between inflammation and epithelium based on caspase-3 expression (correlation coefficient = 0.143; p > 0.05). Furthermore, demographic and clinical characteristics did not show a statistically significant difference in caspase-3 expression levels. ConclusionCaspase-3 expression was significant in inflammatory adenoid tissue, but it showed no association with nasal steroid administration.