Browsing by Author "Cilaker S."
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Item Effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial dysfunction, lipid peroxidation, and hepatocyte morphology in rats with sepsis-induced liver damage(2004) Kara E.; Var A.; Vatansever S.; Cilaker S.; Kaya Y.; Coşkun T.Sepsis remains a difficult problem for clinicians, with its systemic effects and high morbidity and mortality rates. The roles of oxidative stress, endothelial dysfunction, and lipid peroxidation in sepsis-induced organ damage are being investigated. The aim of this study was to investigate the effects of selective cyclooxygenase (COX)-2 inhibition on tissue lipid peroxidation, endothelial dysfunction, and hepatic cell morphology in a rat model of sepsis. Thirty rats with sepsis induced by cecal ligation and puncture were divided equally into 3 groups: treatment group (rofecoxib 1 mg/kg PO), control group (saline 1 mL PO), and sham group (sham surgery only). All the rats were sacrificed 1 day after sepsis induction. The livers were removed using a median laparotomy for histopathologic and biochemical analysis. Histomorphologic hepatic damage and lipid peroxidation were significantly reduced in the rofecoxib treatment group compared with the control group (P < 0.05 and P = 0.001, respectively). Endothelial nitric oxide synthase and inducible nitric oxide synthase staining of liver samples was statistically significantly reduced in the treatment group compared with the control group (both, P < 0.001). The hepatic nitric oxide level and malonyldialdehyde activity decreased significantly (P < 0.001 and P = 0.001, respectively) in the rofecoxib group compared with the control group. Hepatic myeloperoxidase activity was similar between the treatment and control groups. Further investigation of selective COX-2 inhibition as an alternate therapeutic choice for sepsis-induced hepatic damage should be considered. Copyright © 2004 Excerpta Medica, Inc.Item Clinical and histological changes of intrathecally administered gadopentate dimeglumine (Gd-DTPA) in normal rats(Centauro SRL, 2005) Mavioglu H.; Tuglu I.; Temiz C.; Ozbilgin K.; Cilaker S.; Selcuki D.; Selcuki M.Objectives: This study is carried out to explore clinical and histological changes induced in rats by intrathecal administration of Gd-DTPA via suboccipital spinal injection. 2.5, 5, 10 μmol/g-brain of Gd-DTPA were injected intrathecally to 43 adult male rats and sucrose as control solution with same volume and osmolarity were injected to 18 rats. Animals were sacrificed on day 4 and 14. Sections from the cortex, brain stem, cerebellum and medulla spinalis were obtained to examine for cell loss and apoptosis. In this study, no clinical abnormalities were observed in 69.8% of rats of Gd-DTPA group and in 83.3% of rats of sucrose group. Transient neurological signs such as ataxia and paresis were seen in 11.6% of rats in the Gd-DTPA group and in 5.5% of rats in the sucrose group. They were seen more frequently in the Gd-DTPA group especially in the highest dose and volume. Histological examination did not revealed necrosis or apoptosis in both groups. This study suggests that intrathecally administered Gd-DTPA may be safe in humans when lower doses per gram of brain are used than rats.Item The aromatase inhibitor anastrozole is associated with favorable embryo development and implantation markers in mice ovarian stimulation cycles(2005) Karaer Ö.; Vatansever H.S.; Oruç S.; Özbilgin K.; Cilaker S.; Koyuncu M.F.Objective: To investigate the embryonic and endometrial effects of anastrozole in preimplantation and implantation phases in FSH-induced cycles in mice. Design: Blind randomized study. Setting: University research laboratory. Animal(s): Twenty-seven mature female mice. Intervention(s): Single-dose anastrozole (25 mg/kg [0.75 mg]), recombinant FSH (5 IU/mL), and hCG (5 IU/mL) (n = 9); recombinant FSH (5 IU/mL) and hCG (5 IU/mL) (n = 9); or sterile saline (1 mL) (n = 9). The morning of finding the vaginal plug was designated as day 1 of embryonic development (E1). Three mice from each group were sacrificed on E1 and embryos aspirated from uterine tubes. The rest of the mice were sacrificed on E2.5-3 and uteruses removed. Main Outcome Measure(s): Embryo quality, endometrial histologic evaluation, and immunohistochemical analysis of tumor necrosis factor-α, leukemia inhibitory factor, laminin, and collagen IV staining. Result(s): Anastrozole use in FSH-induced cycles not only caused an increase in preimplantation receptivity and implantation but also supported release of implantation markers. The enhanced embryo development seen in this study would explain the higher implantation because embryo development is synchronized with endometrial development. Conclusion(s): In mice, the use of anastrozole in FSH-induced cycles has a positive effect on embryo quality and implantation. This effect might be species dependent, and human studies are needed. ©2005 by American Society for Reproductive Medicine.Item Histophysiological effects of fluid resuscitation on heart, lung and brain tissues in rats with hypovolemia(Elsevier GmbH, 2006) Ekerbicer N.; Inan S.; Tarakci F.; Cilaker S.; Ozbek M.The efficacy of using colloids and crystalloids in the treatment of hypovolemia still remains controversial. An important aspect in treating hypovolemia is to re-establish normal tissue hemodynamics after fluid resuscitation. Production of nitric oxide (NO) or growth factors such as transforming growth factor beta (TGF-β) has been identified as a key mechanism in physiological and pathological processes in the different systems. This study was designed to investigate the histophysiological effects of resuscitation with different plasma substitutes on the heart, lung and brain tissues following acute blood loss in male Sprague-Dawley rats weighing 250-280 g (n=30). After anesthesia with sodium pentobarbital, the left femoral vein and artery were cannulated for the administration of volume expanders and for direct measurement of arterial pressure and heart rate. Twenty rats were bled (5 ml/10 min) and infused (5 ml/10 min) with one of four randomly selected solutions, (a) human albumin, (b) gelatin (Gelofusine), (c) dextran-70 (Macrodex); or (d) physiological saline (0.9% isotonic saline). Five control rats were bled without infusion. Tissue samples were taken and fixed in 10% formalin solution, then processed for embedding in paraffin wax. Sections were cut and stained with hematoxylin and eosin. Indirect immunohistochemical labelling was performed to reveal binding of primary antibodies against endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and TGF-β. Mild immunoreactivity of eNOS was observed in endothelial cells of vessels in brain, heart and lung tissues. Increased immunoreactivities of eNOS, iNOS and TGF-β were observed in the non-fluid resuscitated group in these organs; mild, moderate, moderate and strong immunoreactivities were seen in the albumin, gelatin, physiological saline and dextran-70 treated groups, respectively. Immunoreactivities of iNOS and TGF-β in the non-fluid resuscitated group were increased significantly, in comparison to the other groups, apart from the dextran-70 treated group. The results of this study show that gelatin solution and physiological saline may be of use after acute blood loss, and dextran-70 is not the preferred resuscitation fluid in the early stages of acute blood loss. It was concluded that albumin solution is the preferred fluid for resuscitation. © 2006 Elsevier GmbH. All rights reserved.Item The role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial ischemia/reperfusion-induced apoptosis(Elsevier GmbH, 2006) Gok S.; Vatansever S.; Vural K.; Sekuri C.; Izanli A.; Tezcan A.; Cilaker S.During ischemia, ATP-sensitive K+ channels (KATP channels) open, and this triggers necrotic processes and apoptosis. In this study, we investigated whether selective sarcoplasmic and mitochondrial KATP channel blockers affected myocardial apoptosis and nitric oxide synthase (NOS) activity in a rat model of myocardial ischemia/reperfusion in vitro. Isolated rat hearts were subjected to 30 min of coronary artery occlusion followed by 30 min of reperfusion. A selective sarcKATP channel blocker, HMR1098 and a selective mitoKATP channel blocker, 5-hydroxydecanoate, were added to the perfusion fluid 10 min before occlusion. Myocardial apoptosis was detected immunohistochemically using the TUNEL method. Myocardial inducible NOS (iNOS) and endothelial NOS (eNOS) were determined immunohistochemically. In control hearts, apoptosis induction was associated with a greater immunoreactivity of iNOS than eNOS. Treatment with HMR1098, at a concentration of 3 μmol/l, significantly reduced the TUNEL-positive cardiomyocytes and this was associated with decreased iNOS and increased eNOS immunoreactivity. When this drug was administered at a higher concentration, at 30 μmol/l, a more marked reduction in apoptosis was observed but, in contrast to the effects observed at the lower drug concentration, eNOS immunoreactivity was almost completely abolished while iNOS was strong. Moreover, ischemia-induced cardiac dysfunction (e.g. contractile force and recovery of coronary flow) was increased by the higher concentration of HMR 1098. In hearts treated with 5-hydroxydecanoate, myocyte apoptosis was slightly reduced, and this was associated with an almost equal increase in both iNOS and eNOS immunoreactivity. These findings suggest that iNOS appears to be more important than eNOS in the reduction of apoptosis. However, the further inhibition of apoptosis by the higher concentration of HMR 1098 was associated with poorer cardiac function. © 2006 Elsevier GmbH. All rights reserved.Item Effect of portal vein occlusion on the pancreas: An experimental model(2006) Aydede H.; Erhan Y.; Ikgül O.; Cilaker S.; Sakarya A.; Vatansever S.Background: The effects of portal vein occlusion on the pancreas are not clearly understood. Therefore, we studied histomorphological changes induced in the rat pancreas by various periods of portal vein occlusion. Materials and methods: Sixty female Wistar albino rats were randomly allocated into four groups of 15 each. In Group I (control), rats underwent sham laparotomy to expose the portal vein proximal to its bifurcation. In Groups II-IV, rats underwent laparotomy followed by portal vein occlusion by clamping for 15, 30, and 60 minutes respectively. The pancreas was removed immediately after sham laparotomy in Group I and immediately after clamp release in Groups II-IV. Pancreatic tissue specimens were subjected to histochemical analysis for cell typing and diagnosis, immunohistochemical analysis for identification of the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), endothelial nitric oxide synthase (eNOS), and inducible NOS (iNOS), and TUNEL analysis was carried out for identification of apoptotic cells. Results: Histochemistry revealed signs of inflammation in pancreatic tissue from rats subjected to portal vein occlusion. Immunohistochemistry revealed that the expression of proinflammatory cytokines TNF-α and IL-1β and the oxidative damage indicator iNOS in rat pancreatic tissue increased progressively with the duration of portal vein occlusion. TUNEL assay revealed no signs of apoptosis in any of the groups. Conclusion: We conclude that portal vein occlusion triggers an inflammatory response in the pancreas that worsens the longer the occlusion lasts. © 2006 by the Société Internationale de Chirurgie.Item The effect of Misoprostol, a prostaglandin E1 analog, on apoptosis in ischemia-reperfusion-induced intestinal injury(Elsevier GmbH, 2007) Topcu I.; Vatansever S.; Var A.; Cavus Z.; Cilaker S.; Sakarya M.The aim of this study was to investigate whether Misoprostol, a synthetic prostaglandin (PG) E1 analog, has any effect on the prevention of apoptosis in ischemia-reperfusion (I/R)-induced intestinal injury. Thirty adult male Wistar albino rats were divided into three groups: group I=sham operated+saline; group II=I/R+saline; and group III=I/R+Misoprostol. Misoprostol (50 μg/kg/d) was administered as an intragastric meal for 3 days. The terminal ileum was collected for histological and biochemical investigations. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelled (TUNEL) reaction. Immunohistochemical analysis was performed to determine the distribution of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS). Samples were also analyzed for malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The number of TUNEL-positive cells was higher in group II when compared to the other two groups (p<0.05). In group III this value was higher when compared to group I, but lower than group II (p<0.05). iNOS immunoreactivity was not detected in ileum sections of group I animals, but moderate immunoreactivity was seen in group II and mild immunoreactivity in group III. The immunoreactivity of eNOS was moderate in ileum sections of all three groups. In ileum tissue, MDA was found to be higher in group II compared to group I (p<0.05), but there was no difference in group III. SOD was not different between groups I and III, but was significantly higher in group II (p<0.05). In our experimental model of I/R-induced intestinal injury, apoptosis is induced in enterocytes, whereas Misoprostol decreases enterocyte apoptosis in this experimental model. Our results indicate that Misoprostol may play a key role in the pathophysiologic events leading to failure of the intrinsic gut barrier defense mechanisms of intestinal epithelium. © 2007 Elsevier GmbH. All rights reserved.Item A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically in premenopausal women(Elsevier Ireland Ltd, 2007) Baytur Y.B.; Ozbilgin K.; Cilaker S.; Lacin S.; Kurtul O.; Oruc S.; Koyuncu F.M.Objective: To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically. Study design: Thirty-two premenopausal women affected by uterine leiomyomas were randomized into two equal groups. Group A was treated with gosereline (3.6 mg subcutaneous injection monthly) and group B was treated with raloxifene (60 mg daily per os) for 3 months before undergoing surgery. At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and p53 were calculated. The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared between groups. Results: The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm 3 to 35 cm 3 , and in raloxifene group from 68 cm 3 to 50 cm 3 , p < 0.05. The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant. H-score of ER expression was significantly lower in gosereline group compared to control group (54.4 versus 113.2, p = 0.001), whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene versus 94.7 for control, p = 0.001). The p53 expression was only lower with gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there was no significant change between the raloxifene group and the control group (201.9 versus 205.6) (p > 0.05). Conclusion: Raloxifene was as effective as gosereline in reducing leiomyoma volumes. Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment. In both treatment modalities, the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies. © 2006 Elsevier Ireland Ltd. All rights reserved.Item Comparison of the effects of collagenase and extract of Centella asiatica in an experimental model of wound healing: An immunohistochemical and histopathological study(2008) Ermertcan A.T.; Inan S.; Ozturkcan S.; Bilac C.; Cilaker S.In this study, we compared the effects of collagenase and Centella asiatica in the rat model. Twenty-seven female rats were divided into three groups, and two full-thickness wounds were made for each animal. Collagenase ointment was applied topically to Group I and C. asiatica ointment to Group II rats. In Group III, no treatment was applied. On the third day of treatment, wounds on the left side of three animals of each group were excised. On the fifth and eighth day of the treatments, the same procedure was performed for the remaining animals. Indirect immunohistochemical examination was performed to detect transforming growth factor beta (TGF)-β, endothelial and inducible nitric oxide synthase (eNOS and iNOS), vascular endothelial growth factor, TGF-α, laminin, fibronectin, collagen I, and interleukin-1β. According to the measurements of the wound areas and wound healing periodo, collagenase was superior to the control group. Immunohistochemical examinations showed strong (+++) iNOS and TGF-β immunoreactivities in C. asiatica group. eNOS immunoreactivity was moderate (++) in this group. For the collagenase group, iNOS, eNOS, and TGF-β immunoreactivities were moderate (++). In the collagenase group, while TGF-β and iNOS immunoreactivities were weaker, laminin and fibronectin reactivities were stronger than in C. asiatica and control groups. Collagenase was superior to C. asiatica according to the immunohistochemical findings. Collagenase ointment significantly improves the quality of wound healing and scar formation and is a more appropriate treatment choice than extract of C. asiatica in the early stages of the wound healing process. © 2008 by the Wound Healing Society.