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Öğe Anti-inflammatory effect of cortistatin in rat endotoxin-induced uveitis model(Wolters Kluwer Medknow Publications, 2020) Balbaba, Mehmet; Dal, Ali; Çolakoğlu, Neriman; Bulmuş, Özgür; Ulaş, Fatih; Yıldırım, Hakan; Aydemir, OrhanPurpose: To evaluate the anti-inflammatory effect of cortistatin (CST) in endotoxin-induced uveitis (EIU) model and to compare the results with corticosteroid treatment. Methods: A total of 35 healthy Wistar albino rats were randomly divided into five groups. EIU was induced by a single subcutaneous injection of lipopolysaccharide (LPS). Group I received intraperitoneal (ip) normal saline (NS), Group II received ip 150 mu g LPS plus NS, Group III received ip 150 mu g LPS plus 250 mu g/kg CST, Group IV received ip 150 mu g LPS plus 1mg/kg dexamethasone, and Group V received ip 250 mu g/kg CST only. The aqueous humor was collected 24 h after injection and the infiltrating cells were determined. Moreover, histopathological and immunohistochemical examinations were also performed. Results: The clinical score and infiltrated cell count were reduced in Groups III and IV compared with Group II (P < 0.001). The pathological findings of Groups III and IV were significantly reduced compared with Group II (P < 0.001). These findings were similar between Groups III and IV (P = 1.000). Tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) immunoreactivity in the ciliary body of Group III and Group IV were significantly reduced compared with Group II (P < 0.001). TNF- and IL-1 beta immunoreactivity in the ciliary body of Group III and Group IV were similar compared with Group I and Group V (range of P values was 0.539-0.958). Conclusion: CST administration as a therapeutic agent might ameliorate the severity of intraocular inflammation in uveitis patients. In conclusion, effect of CST and dexamethasone in EIU model was comparable.Öğe Effect of decorin and bevacizumab on oxygen-induced retinopathy in rat models: a comparative study(Wolters Kluwer Medknow Publications, 2021) Güler, Seda Duran; Balbaba, Mehmet; Çolakoğlu, Neriman; Bulmuş, Özgür; Ulaş, Fatih; Eröksüz, YesariPurpose: The aims of this study were to evaluate the effects of decorin (DCN) in rat oxygen-induced retinopathy (OIR) model and to compare the results with those of bevacizumab. Methods: Twenty-eight newborn Sprague-Dawley rats were randomly divided into four groups. Group I (control): normoxia plus intraperitoneal (ip) normal saline (NS), Group II (sham): OIR plus ip NS, Group III (DCN): OIR plus ip 0.1 mg/kg DCN, and Group IV (bevacizumab): OIR plus ip 2.5 mg/kg bevacizumab. The OIR model was induced by cycling the oxygen concentration between 50% and 10% every 24 h for 14 days following their birth. In all groups, injections were administered on postnatal day (PD) 15. All animals were sacrificed and their right eyes were enucleated on PD 18. The nuclei of neovascular endothelial cells on the vitreal side of the inner limiting membrane were counted, and vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF)-? immunoreactivity were detected in histopathological and immunohistochemical examinations. One-way analysis of variance and post hoc Tukey tests were used for statistical analyses of the data. Results: In Groups II, III, and IV, the mean neovascular cell nuclei counts were 13.14 ± 1.34, 6.57 ± 1.51, and 6.71 ± 1.49, respectively. The mean neovascular cell nuclei count was significantly reduced in treatment groups compared with sham group (P < 0.001). In immunohistochemical staining, the immunoreactivity of VEGF was 0.07 ± 0.02, 0.97 ± 0.21, 0.37 ± 0.12, and 0.23 ± 0.17, respectively. Likewise, immunoreactivity of TNF-? was 0.02 ± 0.02, 1.11 ± 0.36, 0.37 ± 0.13, and 0.62 ± 0.21, respectively. VEGF and TNF-? immunoreactivity increased markedly in the sham group compared with those in the control group (P < 0.001). VEGF and TNF-? immunoreactivity of treatment groups decreased significantly compared to sham group (P < 0.001). Conclusion: The beneficial effects obtained by DCN administration in OIR model were comparable to the effects of bevacizumab.Öğe The effects of combined vitamin C and vitamin E in streptozotocin-induced diabetic rat kidney(2009) Kükner, Aysel; Çolakoğlu, Neriman; Özoğlu, Candan; Naziroğlu, Mustafa; Fırat, TülinDiabetic nephropathy is a serious complication of diabetes mellitus. Oxidative stress has been suggested to play a key role in the pathogenesis of diabetic nephropathy. Vitamins C and E play important roles in the antioxidant defense system. It is likely that both vitamins act in a synergistic manner, with vitamin E primarily being oxidized to the tocopheroxyl radical and then reduced back to tocopherol by vitamin C. The purpose of the study was to determine the effects of supplementation of Vitamins C and E (VCE) on diabetic rat kidney. Adult female Wistar rats were used in the study. The animals were divided into three groups. Group I: the control group; Group II: diabetic group, streptozotocin (40 mg kg-1) was administered group; Group III: diabetes + VCE group, received a diet containing a combination of ascorbic acid and dl-?-tocopheryl acetate per kg of feed. Rats were killed on 21st day and renal tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic examination. When compared with the control group, congestion of the glomerular capillaries, increased mesangial cells and distinct mesangium, shortened podocyte processes and disappearance of filtration slit pore of diabetic rat kidney were observed. In the group treated with VCE, glomerular changes were less distinct than the diabetic group. Lengths of the pedicles were similar to the control group. VCE reduced the changes in the glomerular structures due to diabetes. © Medwell Journals, 2009.Öğe Effects of high dose retinoic acid on TGF-beta 2 expression during pancreatic organogenesis(Springer, 2005) Çolakoğlu, Neriman; Kükner, Aysel; Öner, Jale; Sönmez, M. Fatih; Öner, Hakan; Ozan, EnverThe aim of this study was to investigate the effects of excess all-trans retinoic acid, a vitamin A metabolite, on pancreatic organogenesis and TGF-beta 2 expression during prenatal development in rats. First group of animals used as control while a single dose of 60 mg/kg all-trans retinoic acid was ingested by the mothers, at day 8 of gestation (before the neurulation period) in group II and at day 12 of gestation (after the neurulation period) in group III, and all embryos were sacrificed at day 18 of gestation. TGF-beta 2 expression was detected in the capsule, acini and Langerhans islets in the control group. In the pancreas of group II, dilatation and congestion of interlobular vessels were observed. Langerhans islet structures were completely absent. Moreover acinar TGF-beta 2 immune reactivity was not determined. In group III, acinar expression of TGF-beta 2 in acid was similar to that in the controls but their Langerhans islets TGF-beta 2 immune reactivity was significantly less than the controls. In view of the present findings we suggest that TGF-beta 2 plays important role in pancreatic morphogenesis and administration of excess all-trans retinoic acid before neurulation inhibit TGF-beta 2 expression disrupted pancreatic morphogenesis particularly Langerhans islets. However, its administration after neurulation had less adverse affect on pancreatic organogenesis and TGF-beta 2 immune reactivity.Öğe The effects of triiodothyronine on rat testis: a morphometric and immunohistochemical study(Springer, 2006) Öner, Jale; Öner, Hakan; Çolakoğlu, Neriman; Kükner, Aysel; Ozan, EnverThe aim of present study was to investigate the effects of 3,3',5-triiodothyronine (T(3)) on rat testis both morphometrically and immunohistochemically with determining of insulin-like growth factor I (IGF-I) expression. Adult male Wistar-albino rats used in the study were divided into two groups; control and T(3)-treated groups. After T(3) treatment there was observed to be a decrease in testicular weights, diameters of seminiferous tubules and the number of sertoli cells, and an increase in the number of leydig cells (P < 0.05). Some of the seminiferous tubule lumens of T(3) administrated rats had cellular debris. IGF-I was localized in sertoli cells, late spermatids and leydig cells of all groups. IGF-I immunoreactivity in T(3) treated rats was higher than in controls in all stages of the cycle of rat seminiferous epithelium, but the staining intensity of leydig cells were similar in both groups. In conclusion, the present results suggest that T(3) may modulate the testicular function by affecting IGF-I activity at the gonadal level.Öğe Immunolocalization of TGF-beta 2 in the rat thymus during late stages of prenatal development(Elsevier Gmbh, 2009) Sönmez, Mehmet Fatih; Çolakoğlu, Neriman; Kükner, Aysel; Ozan, Enver; Dabak, Dürrin ÖzlemThe aim of this study was to investigate the immunolocalization of transforming growth factor beta (TGF-beta 2) in rat thymic stromal cells and thymocytes and investigate the roles of TGF-beta 2 in thymopoiesis during the late stages of fetal development. Twelve adult pregnant female Wistar rats weighing 250-270g were used in this study. The rats were killed by cervical dislocation on gestation days 16 (GD 16), 18 (GD18) and 20 (GD20). Fetal thymus glands were prepared and examined by an immunohistochemical technique to reveal binding of an anti-TGF-beta 2 rabbit polyclonal antibody. The thymic primordium was surrounded with a connective tissue capsule at GD16 and at this stage TGF-beta 2 immunoreactivity was not observed. At GD18, the connective tissue capsule had formed septa which subdivided the tissue into lobules and at this stage TGF-beta 2 immunolocalization was detected in the capsule and in thymocytes. Lobulation was more evident at GD20 and TGF-beta 2 immunoreactivity of thymocytes was more extensive than on GD18. Results indicate that TGF-beta 2 may play an important role in the organization or development of thymocytes in the late stages of thymopoiesis. (C) 2008 Elsevier GmbH. All rights reserved.Öğe Kadmiyum klorürün sıçan böbrek dokusunda oluşturduğu yapısal değişiklikler ve bu değişiklikler üzerine metallothioneinin etkileri: Işık mikroskobik çalışma(2004) Kara, Haki; Çolakoğlu, Neriman; Kükner, Aysel; Ozan, EnverAmaç: Bu çalışmada kadmiyum klorür uygulaması ile böbrek dokusunda meydana gelen yapısal değişiklikler ve kadmiyum klorür ile birlikte ekzojen uygulanan metallothioneinin koruyucu etkilerinin ışık miroskobik incelenmesi amaçlandı. Gereç ve Yöntemler: Çalışmada 36 adet Wistar cinsi ergin erkek sıçan kullanıldı. Denekler 3 gruba ayrıldı. Birinci grup sıçanlara (n: 16) deri altı yolla 3.5 mg/kg/gün kadmiyum klorür (Sigma; St Louis MO, USA), ikinci grup sıçanlara (n: 16) deri altı yolla 3.5 mg/kg/gün kadmiyum klorür ve periton içi 30 µmol/kg/gün metallothionein (Sigma; St Louis MO, USA) enjekte edildi. Üçüncü grup sıçanlar (n: 4) ise kontrol grubu olarak kullanıldı. Çalışmanın 1., 3., 5. ve 7. günlerinde deneklerden eter anestezisi altında böbrek dokuları alındı, %10'luk formaldehit solüsyonunda tespit edildi, parafin bloklar hazırlandı. Alınan kesitlere (5 µm) Hematoksilen & Eosin, Periodic acid Schiff ve Masson'un üçlü boyaları uygulandı. Bulgular: Bu çalışmada her iki deney grubunda da kadmiyum klorür ve metallothionein uygulama süresinin artışına paralel olarak renal korpuskül ve tübüllerin bazal membranlarında kalınlaşma, proksimal tübüllerde dejenerasyon, korteksteki damarlarda konjesyon saptandı. İkinci grupta ayrıca intramezengial hücrelerde artış, tübüllerde PAS (+) granüller ve kortiko medullar bölgedeki tübüllerde PAS (+) hiyalin madde birikimi gözlendi. Sonuç: Sonuç olarak kadmiyum klorür'ün böbrekler için oldukça toksik olduğu ve önemli yapısal hasara yol açtığı belirlendi. Metal bağlayan protein olarak bilinen metallothioneinin oluşan bu yapısal hasarları önlemede yetersiz kaldığı ve benzer yapısal bozuklukların metallothionein uygulanan gruplarda da oluştuğu saptandı.Öğe Leptin in corneas from keratoconus and infectious keratitis patients(Mary Ann Liebert, Inc, 2005) Aydemir, Orhan; Nazıroğlu, Mustafa; Çolakoğlu, Neriman; Yılmaz, Turgut; Kükner, Aysel; Kükner, A. ŞahapPurpose: Leptin is produced primarily by adipose tissue. More recent studies have shown extra sites of leptin production in physiologic and ill human tissues. However, whether leptin originates from human corneas in infectious keratitis and keratoconus is not known. The aim of this study was to demonstrate and quantitate leptin expression in corneas with infectious keratitis and keratoconus and make comparisons to control corneas. Methods: We examined the immunohistochemical staining of leptin in nine corneas surgically excised from patients with infectious keratitis (3 patients), keratoconus (3 patients), and donor corneas (3 patients). Results: The results were analyzed using a semi quantitative scoring system of mild, moderate, and strong. Cells of the infectious keratitis group had the strongest leptin staining intensity, the control group had moderate, and the keratoconus group had mild staining intensity. The more vascular corneas in the infectious keratitis group were also associated with the greatest leptin staining. Conclusions: Our findings indicate that leptin expression was present in all three sources of corneas (infectious keratitis, keratoconus, and normal control). Quantitative scoring would imply it may play a role in infectious keratitis, although further experiments are necessary to establish any causal relationship.Öğe Protective effects of intraperitoneal vitamin c, aprotinin and melatonin administration on retinal edema during experimental uveitis in the guinea pig(Wiley, 2004) Kükner, A. Şahap; Kükner, Aysel; Nazıroğlu, Mustafa; Çolakoğlu, Neriman; Çelebi, Serdal; Yılmaz, Turgut; Aydemir, OrhanA considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen substances (ROS) in the actiology of uveitis. The activated phagocytic system of polymorphonuclear leucocytes in uveitis is involved in the generation of ROS. In addition to their direct free radical scavenging action, aprotinin, melatonin and vitamin C are known to protect against oedema formation and can preserve plasma membrane fluidity and free radical production. Histological changes in the retina that occur during uveitis are not well explained. The purpose of this study was to determine whether vitamin C, aprotinin and melatonin can protect the retina from damage accompanying experimental uveitis (EU). Thirty adult male guinea pigs were divided into five groups of six animals each. The first group was used as control. The right eyes of groups 2, 3, 4 and 5 received an intravitreal injection of bovine serum albumin for induction of experimental uveitis. At the same time and also on the consecutive third day, groups 3, 4 and 5 received intraperitoneal injections of vitamin C (ascorbic acid, 100 mg kg(-1) body wt), aprotinin (20 000 mg kg(-1) body wt) and melatonin (10 mg kg(-1) body wt), respectively. The animals were killed on the sixth day. The average thickness of the retina and inner plexiform layer for each eye was measured in sagittal section near the optic nerve and expressed in microns. The thickness of the retina and inner plexiform layer in the control group was significantly (p < 0.01) lower than in the group EU as compared with the group EU plus vitamin C, group EU plus aprotinin, group EU plus melatonin (p < 0.05). The thicknesses of the retina and inner plexiform layer in group EU plus vitamin C, group EU plus aprotinin and group EU plus melatonin were significantly (p < 0 01) lower than that in the group EU. The difference in thickness of the retina and inner plexiform layer among the groups 3, 4 and 5 was not significant (p > 0.05). In conclusion, this study demonstrated that oedematous effects of EU on the retina were reduced by the administration of intraperitoneal vitamin C, aprotinin and melatonin, i.e. these antioxidants had significant protective effects on the retina of guinea pigs against oedematous damage in EU. However, the reductive effect of vitamin C on EU was greater than that of aprotinin and melatonin. The intraperitoneal vitamin C, aprotinin and melatonin supplementations may strengthen the antioxidant defence system because of decreased ROS, and these agents may play a role in treating uveitis.Öğe Sıçan testis dokusunda kadmiyum klorür’ün oluşturduğu yapısal değişiklikler ve bu değişiklikler üzerine metallothionein’nin etkileri: Elektron mikroskobik çalışma(2011) Çolakoğlu, Neriman; Kükner, Aysel; Ozan, Enver; Kara, Haki; Koyutürk, LeylaAmaç: Bu çalışmada, testiküler dokuda kadmiyum klorürün sebep olduğu yapısal değişiklikler ve bu değişiklikler üzerine koruyucu amaçla uygulanan metallothioneinin etkilerinin belirlenmesi amaçlandı. Gereç Yöntem: 36 adet erişkin Wistar rat 3 gruba ayrıldı. Birinci gruba (n:16) 3.5 mg/kg/gün kadmiyum klorür subkutan yolla enjekte edildi. İkinci grup ratlara (n:16) ise 3.5 mg/kg/gün kadmiyum klorür subkutan yolla ve metallothionein (30 ?mol/kg/gün) intraperitoneal yolla birlikte enjekte edildi. Üçüncü grup ratlar (n: 4) kontrol olarak kullanıldı. Deneysel çalışmanın 1., 3., 5. ve 7. günlerinde eter anestezisi altında testiküler doku örnekleri 2.5% ‘luk glutaraldehit solusyonuna alınarak tespit edildi. Elektron mikroskobik incelemeler için bloklar hazırlandı. Bulgular: Elektron mikroskobik incelemelerde, kadmiyum klorür enjeksiyonunun özellikle 3. gününden sonra şiddetli doku hasarı gözlendi. Bu hasar deneyin ilerleyen günlerinde giderek artmaktaydı. Kadmiyum klorür toksikasyonu sonucunda testis dokusunda interstisyel alanda kollagen artışı, leydig hücrelerinde mitokondri artışı, spermatogenik hücrelerde lipid birikimi ve apoptozis tespit edildi. Benzer yapısal değişiklikler kadmiyumla birlikte koruyucu amaçla metallothionenin enjekte edilen grupta da gözlendi. Sonuç: Çalışmanın sonucunda kadmiyumun, testis dokusunda oldukça ciddi yapısal bozukluklar meydana getirdiği saptandı. Uzun süre kadmiyum maruziyetinin infertiliteye sebep olan ciddi hasarlar oluşturabileceği söylenebilir.Öğe Ultrastructural changes in the kidney of rats with acute exposure to cadmium and effects of exogenous metallothionein(Humana Press Inc, 2007) Kükner, Aysel; Çolakoğlu, Neriman; Kara, Haki; Öner, Hakan; Özoğul, Candan; Ozan, EnverUltrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT) were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride (CdCl2) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 mu mol/kg MT was administered in addition to CdCl2. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7 after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic observations. Tissue damage in kidney increased as time passed since the administration of CdCl2 in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules, deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted, and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused structural damage. Exogenous MT partly prevents CdCl2-induced damage.
