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Öğe Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats(Academic Press Ltd Elsevier Science Ltd, 2005) Yidirim, Z; Kotuk, M; Iraz, M; Kuku, I; Ulu, R; Armutcu, F; Ozen, SAntioxidant therapy may be useful in diseases with impaired oxidant antioxidant balance such as lung fibrosis. The effects of sulfhydryl-containing antioxidant agents N-acetylcysteine (NAC) and erdosteine on the bleomycin-induced lung fibrosis were compared in rats. The animals were divided into four groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + erdosteine (10 mg/kg), and bleomycin + NAC (3 mmol/kg). Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxylproline content and lung histology which is almost completely prevented by erdosteine and NAC. Hydroxyproline content was 18.7 +/- 3.5 and 11.2 +/- 0.6 mg/g dried tissue in bleomycin and saline treated rats, respectively (P < 0.001), and this level was 11.3 +/- 1.2 and 13.8 +/- 1.2 mg/g dried tissue in erdosteine and NAC pretreated, respectively. Erdosteine and NAC significantly reduced depletion of glutathione peroxidase, and prevented increases in myeloperoxidase activities, nitric oxide, and malondialdehyde levels in lung tissue produced by bleomycin. Data presented here indicate that erdosteine and NAC similarly prevented bleomycin-induced lung fibrosis and their antioxidant effects were also similar in this experiment. (c) 2005 Elsevier Ltd. All rights reserved.Öğe Caffeic acid phenethyl ester to inhibit posterior capsule opacification in rabbits(Elsevier Science Inc, 1997) Hepsen, IF; Bayramlar, H; Gultek, A; Ozen, S; Tilgen, F; Evereklioglu, CPurpose: To assess whether caffeic acid phenethyl ester (CAPE) prevents posterior capsule opacification (PCO) by suppressing the transformation of the lens epithelial cells. Setting: Departments of Ophthalmology, Chemistry, and Pathology, Turgut Ozal Medical Center, University of Inonu, Malatya, Turkey. Methods: Twenty pigmented island rabbits having phacoemulsification in their right eyes were randomized into two groups. In Group 1, 10 mu g/ml of CAPE was added to the anterior chamber irrigating solution and a 1% solution of CAPE was injected subconjunctivally for 3 weeks postoperatively. The irrigating solution in Group 2 (control) did not include CAPE. The development of PCO was assessed weekly and its density was graded by slitlamp biomicroscopy. Histologic analysis was performed 3 months after surgery. Results: Group I had clear capsules or minor PCO. Group 2 developed more severe PCO or complete opacification. The difference between the two groups was statistically significant (P = .04). Conclusion: These preliminary results indicate that CAPE is effective in suppressing PCO in pigmented rabbits and may be beneficial in clinical use in humans because it has no documented harmful effects on normal cells.Öğe Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats(Academic Press Inc Elsevier Science, 2004) Yildirim, Z; Turkoz, Y; Kotuk, M; Armutcu, F; Gurel, A; Iraz, M; Ozen, SReactive oxygen and nitrogen species have been implicated in the pathogenesis of bleomycin -induced lung fibrosis. The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats. The animals were placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5U/kg), bleomycin + aminoguanidine (200mg/kg), bleomycin + erdosteine (10mg/kg), and bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine. A strong staining for nitro tyrosine antibody in lung tissue and increased levels of lung NO were found in bleomycin group, that were significantly reduced by aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly prevented depletion of superoxide dismutase and glutathione peroxidase and elevated myeloperoxidase activities, malondialdehyde level in lung tissue produced by bleomycin. Data presented here indicate that aminoguanidine and erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide mediated tyrosine nitration of proteins plays a significant role in the pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that antifibrotic affect of antioxidants may be due to their inhibitory effect on nitric oxide generation in this model. (C) 2004 Elsevier Inc. All rights reserved.Öğe The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits(Oxford Univ Press Inc, 1999) Ilhan, A; Koltuksuz, U; Ozen, S; Uz, E; Ciralik, H; Akyol, OObjective: Oxygen-derived free radicals have been implicated in the pathogenesis of spinal cord neuronal injury after both trauma and ischemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. This experimental study was designed to determine the effect of CAFE on ischemia-reperfusion of spinal cord in rabbits. Methods: Forty-one New Zealand white rabbits were used in the study. The animals undergone aortic occlusion were divided into three groups each consisting of 11 rabbits: methylprednisolone (MP), CAFE, and control. CAFE 10 mu mol/kg, methyl prednisolone (MP) 30 mg/kg or similar dose saline were injected intraperitoneally before surgical intervention. Animals were subjected to 21 min of cross-clamp time. At the end of occlusion time, the clamps were removed and restoration of the blood flow was verified visually. Animals in sham group (n = 8) underwent a surgical procedure similar to the other groups but the aorta was not occluded. Neurological status was scored by assessment of hindlimb motor function deficit. Results: The scores in CAFE group was different from control groups at 48 h (3.91 +/- 0.5 vs. 2.91 +/- 0.7; P = 0.0013). Spinal cord specimens were obtained to determine the tissue levels of malondialdehyde, superoxide dismutase, catalase, and histological changes. Malondialdehyde levels in control group were increased significantly when compared to sham group (124.22 +/- 24.36 and 41.92 +/- 10.08 nmol/g wet tissue, P = 0.0003). MDA levels in the CAFE group were lower than MP group and differences between the two groups were statistically significant (56.77 +/- 15.265 and 107.74 +/- 19.31 nmol/g wet tissue, P = 0.0001), We did not observe additional tissue injury in CAFE group when compared to control group. SOD and CAT activities were not concordant in all the groups. Conclusions: These results suggest that CAFE may be an available agent to protect the spinal cord from ischemia-reperfusion injury. (C) 1999 Elsevier Science B.V, All rights reserved.Öğe Endothelial nitric oxide synthase expression in leiomyoma and parental myometrium(Karger, 2000) Gokdeniz, R; Mizrak, B; Ozen, S; Bazoglu, NThe aim of this study was to determine the expression of endothelial nitric oxide synthase (eNOS) in leiomyomatous tissue as a possible mediator of the growth process. Nine patients had myoma enucleation during the follicular phase. The myomata and adjacent myometrial tissues were fixed in formol until study. Immunohistochemical localization of leiomyomatous and myometrial tissue eNOS expression was performed using specific monoclonal antibodies to eNOS. Statistical comparisons were made using the Mann-Whitney Wilcoxon rank-sum test for the expression of eNOS. The test was considered significant when p values were <0.05. Immunostaining for eNOS was seen in the cytoplasm of myometrial endothelial and smooth muscle cells in both tissue sections. eNOS expression was significantly higher in the smooth muscle cells of leiomyomata, compared to parental myometrium (p < 0.0005). The expression of eNOS in vascular endothelial cells was not different in the leiomyoma and myometrium (p > 0.05). To our knowledge, this is the first study to document marked expression of eNOS in leiomyomatous tissue, compared to parental myometrium. We also conclude that the mechanism(s) of the growth-promoting effect of estrogen on leiomyomata is mediated by more synthesis of NO. Copyright (C) 2000 S. Karger AG, Basel.Öğe Erdosteine ameliorates neurological outcome and oxidative stress due to ischemia/reperfusion injury in rabbit spinal cord(W B Saunders Co Ltd, 2004) Ege, E; Ilhan, A; Gurel, A; Akyol, O; Ozen, SObjective. Oxygen-derived free radicals have been suggested as important in degeneration after spinal cord ischemia. The aim of this study was to investigate whether erdosteine has a protective effect against spinal cord ischemia during aortic cross clamping. Materials and methods. New Zealand White rabbits (n = 21) were divided into three groups. In the ischemia/reperfusion group (I/R) (n = 8), the infrarenal aorta of rabbits was cross clamped for 21 min and then reperfused. In erdosteine group, the administration of erdosteine solution (50 mg/kg) was started two days before aortic cross-clamping and rabbits (n = 8) were subjected to ischemia and reperfusion. Animals in control group (n = 5) underwent a surgical procedure similar to the other groups but the aorta was not clamped. The animals were sacrificed at 72 h and histopathological, and biochemical analyses were carried out on the lumbar spinal cords. Results. Erdosteine treatment zoos associated with improved neurological function in the postoperative period. Histopathological examination of spinal cord tissues in erdosteine group revealed changes consistent with mild ischemic injury, but rabbits in I/R group with paraplegia had total destruction of the motor neurons. Biochemical analyses of spinal cord tissues, in the I/R group, revealed a significant increase in the superoxide dismutase, xanthine oxidase, adenosine deaminase and myeloperoxidase activities, and a significant depletion in glutathione peroxidase activity when compared to that of control rabbits. Erdosteine treatment prevented the increase of all these enzymes except adenosine deaminase. Ischemia/reperfusion produced a significant increase in the tissue malondialdehyde levels. Ischemia/reperfusion-induced increments in malondialdehyde content of the spinal cord were significantly prevented by erdosteine treatment. Conclusions. The present study demonstrated that erdosteine treatment before aortic cross clamping ameliorates neurological outcome, neuronal injury and oxidative stress in the rabbit spinal cord.Öğe Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats(Elsevier, 2004) Sogut, S; Ozyurt, H; Armutcu, F; Kart, L; Iraz, M; Akyol, O; Ozen, SOxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. Therefore, erdosteine, an antioxidant, is expected to have an inhibitor potential against the disease. Rats were given one dose of bleomycin in pulmonary fibrosis groups and saline in controls. The first dose of oral erdosteine (10 mg/kg/day) was given 2 days before the bleomycin injection to achieve the plateau level in blood and continued until killing. At day 14, fibrotic changes were evaluated, using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine. Myeloperoxidase activities and MDA levels, which were significantly higher in the bleomycin group, were then significantly attenuated by erdosteine. These results revealed that oral erdosteine may prevent the development of acute pulmonary inflammation caused by bleomycin injection via the repression of neutrophil accumulation and lipid peroxidation, resulting in the inhibition of subsequent lung fibrosis. (C) 2004 Elsevier B.V. All rights reserved.Öğe Fracture healing and bone mass in rats fed on liquid diet containing ethanol(Lippincott Williams & Wilkins, 2002) Elmali, N; Ertem, K; Ozen, S; Inan, M; Baysal, T; Güner, G; Bora, ABackground: Studies in animal models for alcohol abuse have suggested that ethanol inhibits bone growth, decreases bone formation, and increases fracture risk. Methods: Experimental tibia fracture healing in rats fed a liquid diet containing 7.2% ethanol for 8 weeks was investigated with histological and osteodensitometric studies with respect to the control group. After 4 weeks of vitamin A- and sucrose-enriched milk containing 7.2% ethanol feeding, we created closed tibia fractures, which were then fixed with intramedullary nails, in 10 rats. After a follow-up time of 4 weeks, the rats were killed for examination. The same procedure was performed in another 10 rats, which were fed on the same diet (isocaloric modified liquid diet) but without ethanol and used as the control group. A histological scoring system was developed for fracture healing. Results: Histological evaluation of fracture region revealed an average fracture healing score of 1.9 in the ethanol-fed group versus 2.6 in the control group (p = 0.014). In the test group, dual-energy x-ray absorptiometry measurements in the fracture region showed a mean bone mineral density of 0.11 +/- 0.03 g/cm(2), whereas it was 0.130 +/- 0.051 g/cm(2) in the control group (p = 0.000). The mean bone mineral content in the fracture region was 0.103 +/- 0.08 g/cm(3) in the test group versus 0.128 +/- 0.06 g/cm(3) in the control group (p = 0.000). A significant correlation was found among histological scores, bone mineral density (r = 0.64, p = 0.04), and bone mineral content (r = 0,63, p = 0.04). Conclusions: This study showed that rats fed on a diet mixed with ethanol have a histologically delayed fracture healing associated with decreased bone density and mineral content. Besides the negative effects of ethanol on bone metabolism, it also interferes with the fracture-healing process.Öğe Giant vascular eccrine spiradenoma(Blackwell Science Ltd, 1998) Senol, M; Ozcan, A; Sasmaz, S; Ozen, S; Ciralik, HA 60-year-old man suffering from cardiac insufficiency consulted the Dermatology Department, Inonu University Turgut Ozal Medical Center, because of a bleeding tumor on his right hypochondrium. The tumor had begun as a small nodule approximately 5 years before, and had grown slowly with time. A small, superficial ulcer had appeared on the lesion approximately 6 months previously, and slight bleeding had occasionally occurred. The patient had no pain and no other complaint except bleeding. Dermatologic examination revealed a violaceous, ulcerated, and bleeding tumoral lesion below the mid-portion of the right costochondral line (Fig. 1). The tumor was a non-tender, hemispheric mass, approximately 3-4 cm in size, adherent to the epidermis, but movable on the underlying tissue. An incisional biopsy was performed with diagnoses of dermatofibrosarcoma protuberans and desmoid tumor. Histopathologic examination revealed prominent blood-filled vascular spaces (Fig. 2) and clearly delimited cords, showing two types of cell (Fig. 3). The vascular spaces contained a periodic acid-Schiff (PAS)-positive, granular, eosinophilic material. There was no malignant transformation. The lesion was totally excised and primarily sutured.Öğe Ginkgo biloba prevents mobile phone-induced oxidative stress in rat brain(Elsevier, 2004) Ilhan, A; Gurel, A; Armutcu, F; Kamisli, S; Iraz, M; Akyol, O; Ozen, SBackground: The widespread use of mobile phones (MP) in recent years has raised the research activities in many countries to determine the consequences of exposure to the low-intensity electromagnetic radiation (EMR) of mobile phones. Since several experimental studies suggest a role of reactive oxygen species (ROS) in EMR-induced oxidative damage in tissues, in this study, we investigated the effect of Ginkgo biloba (Gb) on MP-induced oxidative damage in brain tissue of rats. Methods: Rats (EMR+) were exposed to 900 MHz EMR from NIP for 7 days (1 h/day). In the EMR + Gb groups, rats were exposed to EMR and pretreated with Gb. Control and Gb-administrated groups were produced by turning off the mobile phone while the animals were in the same exposure conditions. Subsequently, oxidative stress markers and pathological changes in brain tissue were examined for each groups. Results: Oxidative damage was evident by the: (i) increase in malondialdehyde (MDA) and nitric oxide (NO) levels in brain tissue, (ii) decrease in brain superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and (iii) increase in brain xanthine oxidase (XO) and adenosine deaminase (ADA) activities. These alterations were prevented by Gb treatment. Furthermore, Gb prevented the MP-induced cellular injury in brain tissue histopathologically. Conclusion: Reactive oxygen species may play a role in the mechanism that has been proposed to explain the biological side effects of MP, and Gb prevents the MP-induced oxidative stress to preserve antioxidant enzymes activity in brain tissue. (C) 2003 Elsevier B.V. All rights reserved.Öğe GnRH agonist decreases endothelial nitric oxide synthase (eNOS) expression in leiomyoma(Elsevier Sci Ireland Ltd, 2000) Gokdeniz, R; Ozen, S; Mizrak, B; Bazoglu, NObjective: To define the effect of GnRH agonist (GnRHa) treatment on endothelial nitric oxide synthase (eNOS) expression in leiomyoma. As eNOS expression is more pronounced in leiomyoma compared to parental myometrium, we hypothesized that the mechanism(s) of tumor shrinkage by GnRHa may be due to decreased nitric oxide (NO) production in leiomyoma. Methods: Eleven patients with leiomyoma ware operated for myoma enucleation by laparatomy. Six of them were treated with GnRHa every 28 days, three times before the operation. The remaining five patients who had no treatment prior to operation formed the control group. flood was drawn from the patients before treatment and on the day of operation for the assay of serum estradiol (E-2). Immunohistochemical localization of eNOS expression in leiomyoma and myometrium in treated patients, and in leiomyoma in the control group, was performed using monoclonal antibodies specific to eNOS. Results: All treated subjects showed a significant reduction of fibroid volume at the end of therapy. eNOS-positive cells were localized primarily within the vascular endothelium and smooth muscle cells, but had weak expression in fibroid and myometrial muscle cells in the treated group. The immunoreactivity was similar for both the leiomyoma and myometrium (P > 0.05). In contrast to this, the control group had shown strong expression in leiomyoma muscle cells (P < 0.005) in addition to the vascular endothelium and smooth muscle cells. Conclusion: GnRHa-induced tumor shrinkage should be due to diminished eNOS expression, most probably by lowering estrogen secretion. (C) 2000 International Federation of Gynecology and Obstetrics.Öğe Late relapse in a patient with acute lymphoblastic leukemia thirteen years after diagnosis(Hemisphere Publ Corp, 1997) Aydogdu, I; Tayfun, E; Ozcan, C; Harputluoglu, M; Ozen, S; Hicsonmez, G[Abstract Not Available]Öğe Metastatic bone marrow tumours: a report of six cases and review of the literature(Vsp Bv, 2001) Sari, R; Aydogdu, I; Ozen, S; Sevinc, A; Buyukberber, SBone marrow aspirations and biopsies are now employed in the investigation of many disorders in haematology, oncology, and internal medicine. In this paper, clinical, laboratory, and pathological findings are presented of patients with bone marrow metastases of solid tumours (n = 6). Anemia was detected in four cases (66.6%), thrombocytopenia in five cases (83.3%), leukopenia in three cases (50%), diffuse bone pain in four cases (66.6%), elevated serum alkaline phosphatase levels in four cases (66.6%), and hypercalcaemia in two cases (33.3%). In conclusion, bone marrow aspiration and biopsy examinations are effective, practical, and cheap in detecting solid tumour metastasis to bone marrow in a selected group of patients.Öğe Occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis(Editrice Kurtis S R L, 2001) Savli, H; Sevinc, A; Sari, R; Ozen, S; Buyukberber, S; Ertas, EA 47-year-old female patient with a previous history of right thyroid lobectomy was admitted to the hospital because of a 3 cm nodule in the thyroid gland. Hormonal evaluation showed subclinical hypothyroidism with serum levels of thyroid stimulating hormone slightly elevated to 4.4 mug/dl (normal: 0.4-4 mug/dl). Thyroid ultrasound showed diffuse irregularity of the gland and the presence of a solitary nodule (30x18 mm in diameter) localized in the left lobe. A fine needle aspiration biopsy was performed. Cytological analysis revealed papillary thyroid carcinoma and Hashimoto's thyroiditis. Total thyroidectomy was performed. During the operation, two of the parathyroid glands were detected to be hyperplastic. Histopathological examination of the thyroid and parathyroid glands revealed Hashimoto's thyroiditis with papillary thyroid carcinoma and synchronous carcinoma of the parathyroid gland. To our knowledge, this association of occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis has not been reported in the literature. Given the high prevalence of autoimmune diseases in elderly women, a random occurrence of this triad represents the most likely explanation. (C) 2001, Editrice Kurtis.Öğe The pathological examinations of gastric mucosa in patients with Helicobacter pylori-positive and -negative pernicious anemia(Blackwell Science Inc, 2000) Sari, R; Ozen, S; Aydogdu, I; Yildirim, B; Sevinc, ABackground. The basic histopathological finding in gastric mucosa is chronic atrophic gastritis in patients with pernicious anemia. Materials and Methods. We evaluated the frequency of Helicobacter pylori and pathological examinations of gastric mucosa in pernicious anemia (n = 30) by endoscopical findings and biopsy. The results were compared with gastric mucosa specimens of patients with H. pylori-positive nonulcer dyspepsia (n = 36) and H. pylori-negative nonulcer dyspepsia (n = 21). Results. H. pylori was diagnosed in 12 patients (40%) with pernicious anemia. Fundal biopsy examinations showed atrophic gastritis in 30 patients (100%), intestinal metaplasia in 13 patients (43.3%), lymphoid follicle in 15 patients (50%), and dysplasia in 6 patients (20%). Antral biopsy examinations showed atrophic gastritis in 8 patients (26.6%), intestinal metaplasia in 8 patients (26.6%), lymphoid follicle in 8 patients (26.6%), and dysplasia in 3 patients (10%). The frequency of fundal inflammation, atrophy, intestinal metaplasia, lymphoid follicle, and dysplasia and antral intestinal metaplasia and mild antral dysplasia were found to be higher in those in the pernicious anemia group than in the nonulcer dyspeptic patients. Antral inflammation, atrophy, and moderate and severe antral dysplasia were found to be higher in chose in the nonulcer dyspeptic group. Conclusions. Particularly, fundal precancerous lesions were found to be more frequent in patients with pernicious anemia independent of H. pylori.
