MCBÜ Açıkerişim Sistemi :: Browsing by Author "Ozbilgin K."

Browsing by Author "Ozbilgin K."

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Clomiphene citrate does not affect the secretion of α3, αv and β1 integrin molecules during the implantation window in patients with unexplained infertility
(Oxford University Press, 2001) Lacin S.; Vatansever S.; Kuscu N.K.; Koyuncu F.; Ozbilgin K.; Ceylan E.
Background: The expression of integrin molecules on the endometrium suggest that certain integrins may participate in the cascade of molecular events leading to successful implantation. A prospective, controlled study was carried out to investigate the effect of clomiphene citrate (CC) on secretions of β1, α3 and αv integrin molecules in the endometrium of patients with unexplained infertility during the implantation window. Methods: A total of 40 endometrial samples was evaluated in both spontaneous (n = 13) and ensuing clomiphene-treated cycles (100 mg on days 5-9) and also from fertile women serving as controls (n = 14) during postovulatory 7th or 8th day of menstrual cycle. A semiquantitative grading system (H-score) was used to compare the immunohistochemical staining intensities. Endometrial thickness and serum oestradiol and progesterone concentrations were also measured on the day of sampling. Results: Staining of αv but not β1 and α3 integrins was significantly less intense in infertile cases than fertile control cases (1.42 ± 0.12 versus 2.21 ± 0.13 respectively, P = 0.012) and this was not restored to normal concentrations with treatment. Conclusions: Our study indicated that cc treatment significantly decreased the endometrial thickness and increased oestradiol and progesterone concentrations. However, secretion of αv, β1 and α3 integrin molecules, which might play a role in implantation, was not affected.
The effect of tibolone on endometrial IGF-1 and IGFBP-1 levels in ovariectomized rats
(2002) Kuşcu N.K.; Koyuncu F.M.; Inan S.; Tuglu I.; Uyar Y.; Ozbilgin K.
Objective: The goal of this study was to search the effects of two different doses of tibolone on endometrial IGF-1 and IGFBP-1 levels in ovariectomized rats. Methods: Eighteen adult, female, 80-90-days-old, Wistar rats with an average weight of 250 g underwent bilateral ovariectomy under general anesthesia. After waiting for 4 weeks, they were randomized into three groups to receive either oral tibolone in two different doses or placebo. The treatment was continued for 5 weeks, and then the rats were sacrificed and the endometria were analyzed. Results: Low columnar epithelium of the endometrial surface, longer epithelium and stratified squamous epithelium were seen in the control, low-dose and high-dose groups, respectively. The staining intensity of IGF-1 was mild in control, and moderate in both treatment groups, the difference between control the treatment groups was significant (P=0.015 for group L, and P=0.03 for group H). The staining intensity of IGFBP-1 was moderate in control, and strong in groups L and H. Again the difference was significant between control and both treatment groups (P=0.039 for grup L, and P=0.03 for group H). No significant difference was noted between each treatment group for both IGF-1 and IGFBP-1. Conclusion: Tibolone caused histological changes in endometrium and stimulated IGF-1 and IGFBP-1 staining. Both low and high dose treatments led to moderate and strong staining intensities for IGF-1 and IGFBP-1, respectively. The strong staining intensity of IGFBP-1 is likely due to the progestagenic effect of tibolone. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
A histological analysis of the protective effect of ischemic preconditioning in the rat retina
(2002) Toprak A.B.; Ozbilgin K.; Toprak V.; Tuglu I.; Guler C.
Purpose. Ischemic preconditioning (IP) protects the retina from the damaging effect of subsequent ischemia in vivo. We aimed to investigate the histological alterations induced by the protective effect of IP to the retina. Methods. The eyes of the rats were rendered ischemic by intra-ocular pressure (IOP) elevation. IP procedure consisted of producing ischemia for 5 minutes. Sham operation was similar to IP procedure except the pressure elevation. The operational eyes of sham and IP group underwent 60 minutes of ischemia 24 hours after the first procedure. The eyes contralateral to the experimental eyes made up the control group. The eyes were histologically analysed one week after the ischemia. Results. The total retinal thickness of the sham group was significantly less than total retinal thickness of the control group (p < 0.001). There was not a significant difference between control and IP group regarding the total retinal thickness (p > 0.05). The thickness of the inner retinal layers of the sham group were significantly less than corresponding retinal layers of the control group (p < 0.001). The inner plexiform layer (IPL) and inner nuclear layer (INL) thickness values of the sham group were significantly less than same layers of the IP group (p < 0.001). Ganglion cell layer (GCL) thickness of the IP group was significantly less than GCL thickness of the control group (p < 0.001). IPL thickness of the IP group was significantly less than that of control group's (p < 0.05). The GCL and total retinal thickness of the IP group were significantly more than thickness of the corresponding layers of the sham group (p < 0.05). Conclusion. IP considerably protects inner retinal layers from subsequent ischemic damage in a high IOP ischemic model. This endogenous process could further be utilized to tailor specific neuroprotective strategies for retinal cells.
Immunohistochemical staining of IGF-I, IGF-binding proteins-1 and -3, and transforming growth factor beta-3 in the umbilical cords of preeclamptic patients
(2002) Inan S.; Vatansever S.; Kuscu N.K.; Laçin S.; Ozbilgin K.; Koyuncu F.
Background. To detect the immunoreactivity of insulin-like growth factor-I, insulin-like growth factor-binding proteins-1 and -3 and transforming growth factor beta-3 in the umbilical cords of normal and preeclamptic patients. Methods. Umbilical cords were obtained from 15 normal and 15 preeclamptic patients. Immunoreactivities were determined using either indirect immunofluorescence or immunoperoxidase techniques on formalin-fixed, paraffin-embedded sections. Staining intensity was graded by a semiquantitative scoring method. The results were compared by Mann-Whitney U-test. Results. The umbilical cords were thinner and the vessels were hypoplastic in the preeclamptic group. Moderate staining intensity for insulin-like growth factor-I, insulin-like growth factor binding protein-1 and -3 and transforming growth factor-beta 3 was observed in normal patients. The preeclamptic group had mild and strong intensities for insulin-like growth factor-I and insulin-like growth factor binding protein-1, respectively, and intensity for insulin-like growth factor binding protein-3 did not change, but diffuse and increased intensity was observed for transforming growth factor-beta 3. Conclusion. Changes in the intensity of insulin-like growth factor-I and its major binding protein and the transformation of growth factor-beta 3 may play a role in the pathogenesis of preeclampsia by altering the structure and responsiveness of the umbilical cord.
Increased vascular surface density in ovarian endometriosis
(Parthenon Publishing Group Ltd, 2003) Inan S.; Kuscu N.K.; Vatansever S.; Ozbilgin K.; Koyuncu F.; Sayhan S.
Our goal in this study was to investigate the presence of angiogenesis-related factors in endometriomas by evaluating their vascular surface densities. Thirty ovarian samples were included in the study. Of these, ten were histologically confirmed endometriomas, ten were ovarian specimens in the follicular phase and ten were ovarian specimens in the luteal phase, serving as controls. Histological specimens were immunostained for von Willebrand factor (vWF: factor VIII-related antigen) and CD34. The area with the highest microvessel density in endometriosis and in the normal ovary was evaluated by using an intercept grid. All microvessels in a specific field (x 100 magnification) were counted and vascular surface density was measured, as 164.01 ± 21.26 vs. 125.15 ± 11.28 and 117.44 ± 9.27 by using vWF, and as 172.97 ± 25.64 vs. 138.65 ± 32.21 and 120.34 ± 18.40 by using CD34 in endometriotic, follicular and luteal ovarian samples, respectively (p < 0.001). The mean vascular surface density was significantly higher in endometriosis than in the ovarian samples of the follicular phase or the luteal phase. No significant difference was seen between normal ovarian samples. Endometriosis was associated with angiogenic properties. Having demonstrated elevated angiogenic factors in endometriotic samples, we concluded that activation of angiogenesis might be a key factor in the pathogenesis of endometriosis.
Protective Effect of Leukotriene Receptor Antagonist Montelukast on Smoking-Induced Lung Injury in Wistar Rats
(2003) Yüksel H.; Ozbilgin K.; Coskun S.; Tuglu I.
Increased activation of alveolar macrophage, neutrophil and mast cell has been proven in cigarette smoking (CS)-related lung disorders (CSLD). An increased production of cysteinyl-leukotrienes (LTs), which are mediators secreted from the mentioned cells, in response to CS has been shown in humans. The protective effect of LT1 receptor-1 antagonist (LTR-1AT) on CSLD is, however, not known. In this study we aimed to determine whether there is any protective effect of a LTR-1AT, montelukast (MK), on CSLD in Wistar rats. Nine controls and twenty-three smoke-exposed rats were enrolled into this study. Controls were exposed to non-filtered air, and the smoke-exposed rats were exposed to CS for 6 h/day, 6 days/week for three weeks. The CS-exposed rats were also treated with 0.1 mg/kg/day of MK or saline. Morphometric criteria for lung injury were determined as the mean linear intercept of alveolar septa (Lm), the volume density of alveolar septa (Vvspt) and the density of the alveolar surface area per unit volume of lung parenchyma (Sva.pa). Lung mast cells (LMC), which are a major source of LTs, were also counted. Results showed that Lm of the control group was significantly lower and Vvspt, Sva.pa of the controls were significantly higher compared to those of the CS-exposed groups. Animals treated with MK had significant protection against CSLD. Lm was significantly higher and Vvspt, Sva.pa were lower in the saline group than in the MK-treated group. The number of LMC in the CS-exposed groups was also significantly higher than that in the control group. Based on these results, one can suggest that some part of the pathogenesis of CSLD may be related to an enhanced LTs synthesis and LTR-1AT. Therefore, montelukast may protect against active or passive smoking-induced lung injury and related disorders.
Effect of insulin on rat ovarian leptin expression by immunohistochemical staining
(2003) Kuscu N.K.; Ozbilgin K.; Inan S.; Giray G.; Ceylan E.; Koyuncu F.
Aim: Leptin and insulin may interact in regulating ovarian steroid synthesis. The objective of this study was to investigate immunohistochemical staining of leptin in normal rat ovarian tissues and in rats treated with insulin and insulin plus human chorinoic gonadotropin (hCG). Methods: Paraffin blocks of rat ovarian tissues from a previous study, in which 18 adult, female Wistar rats with an average weight of 250 g were divided into three groups to receive either saline solution, human insulin (2 U/day) or human insulin (2 U/day) plus hCG (4 U/day) for 4 weeks, were used in this study to compare the effects on leptin staining. The results were analysed using a semiquantitative scoring system, such as mild, moderate and strong. Results: No staining was observed in granulosa cells and theca interna cells of normal ovarian tissues. Theca externa cells had mild staining intensity (+), corpus luteum had moderate (+ +) and stroma had mild (+) staining intensity. Histological structure was impaired in the insulin group, luteinized cells had-mild staining, there was no difference in other cell groups. Only theca externa cells of the developing follicles were stained in insulin plus hCG group, luteinized cells again had mild staining. Conclusions: Besides damaging the rat ovarian structure, insulin reduced staining intensity of leptin in luteinized cells. Insulin may stimulate ovarian steroid synthesis not only through its own receptors, but also by acting on the leptin expression of these cells.
Immunolocalization of integrins and fibronectin in tubal pregnancy
(Elsevier GmbH, 2004) Inan S.; Giray G.; Vatansever H.S.; Ozbilgin K.; Kuscu N.K.; Sayhan S.
Integrins are a large family of cell adhesion molecules that serve as receptors involved in cell-to-cell and cell-to-matrix interactions during implantation. We studied immunohistochemical staining of integrins (α3, αV, β1, and α2β1) and fibronectin in ectopic tubal pregnancy. Thirty fallopian tube samples with ectopic pregnancies and five normal tubal segments were obtained during ligation operations; the latter specimens served as controls in the study. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against α3, β1, αV, and α2β1 integrins and fibronectin, using the avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare staining intensities. In the control samples, immunostaining of all integrins was found in a single layer of tall columnar epithelial cells, the lamina propria (Lp) and the muscular layer. Fibronectin staining was detected in the Lp and the muscular layer. Staining intensities of α3 and β1 integrins and fibronectin were increased in the normal part of fallopian tubes with ectopic pregnancies. Staining of β1 integrin was more intense than staining of α3 and fibronectin, whereas there was no difference in αV and α2β1 integrin expression between normal tubal tissue in the ectopic pregnancy group and control tubal tissue. In the tubal pregnancy group at the site of implantation, staining intensity of α3 and β1 integrins and fibronectin was strong in decidual cells, supporting tissue and placental villi, whereas αV and α2β1 staining was mild. We concluded that integrins, especially β1 and α3, and fibronectin may play a role in progression of tubal implantation. Although the role of integrins has not yet been clearly defined, these molecules may function as markers of normal and abnormal states of receptivity. We like to suggest that integrins and fibronectin, which are needed in utero implantation, are expressed in tubal tissues during ectopic pregnancy and are involved in ectopic implantation. © 2004 Elsevier GmbH. All rights reserved.
Increased expression of angiogenic markers in patients with seasonal allergic rhinitis
(2004) Kirmaz C.; Ozbilgin K.; Yuksel H.; Bayrak P.; Unlu H.; Giray G.; Kiliccioglu B.
Background. Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis.Objective: We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. Methods. Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immunohistochemical analysis methods (HSCORE, MVD and VSD). Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. Conclusion. There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR.
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.
In vivo study to evaluate the protective effects of amifostine on radiation-induced damage of testis tissue
(2005) Andrieu M.N.; Kurtman C.; Hicsonmez A.; Ozbilgin K.; Eser E.; Erdemli E.
Objective: To investigate the early protective effects of amifostine against radiation-induced damage on rat testis tissue. Methods: Eighty adult male Wistar rats were randomized to 4 groups: Saline solution was given to group A for control, 200 mg/kg amifostine (WR-2721) to group B, a single fraction of 6 Gy local irradiation to testes in group C and 200 mg/kg amifostine 15-30 min before 6 Gy testicular irradiation to group D. Animals were sacrificed 3 weeks after treatment and their testes were removed for macroscopic, microscopic and ultrastructural histopathological examination. Results: The weights, widths and lengths of testes in the lasts groups had decreased significantly when compared with the control group, but the decrease in widths after irradiation was found to be significantly less only in the amifostine plus radiation group. There was a significant reduction of testis weights in relation to the individual body weights in the irradiated testes compared with the other groups (p < 0.005), while there was no significant change of testis weight/total body weight ratio in amifostine plus irradiation group. Spermatogonium A and primary spermatocyte counts were also less in the treatment groups, and primary spermatocyte numbers were significantly higher in amifostine plus radiation group when compared with radiation alone group (p < 0.005). Pretreatment with amifostine reduced the decrease of primary spermatocyte counts by a factor of 1.28. Electron microscopic analysis did not show any cytotoxic effect of amifostine alone, and furthermore, ultrastructural findings were normal with the addition of amifostine prior to irradiation, though there was damage in the radiation exposure group. Conclusion: Amifostine when given alone by itself appears to cause adverse alterations in testis tissue; however, it has a radioprotective effect on spermiogenetic cells when used prior to radiation. Copyright © 2005 S. Karger AG.
Two oestrous cycles. Ten days insulin treatment reduced ovarian leptin expression of rat
(2005) Ozbilgin K.; Kuscu N.K.
Objective: Previous studies have reported a role for insulin in leptin secretion from rat ovarian cells although the time dependent effect of insulin has yet to be obtained. The study aim is to determine the time dependent effect of insulin on leptin staining intensity in the rat ovary. Methods: Normally cycling rats were investigated in a spontaneous cycle (control, n=6), one cycle with insulin treatment 2U/day for 5 days (D5) (n=6), and 2 cycles with insulin treatment 2 U/day for 10 days (D10) (n=6) in the Department of Histology and Embryology, Celal Bayar University, Manisa, Turkey, from May 2004 to August 2004. Histological structures and leptin staining of the ovarian cells were investigated with immunohistochemical technique and evaluated by a semi-quantitative scoring system. Results: Number of follicles and stromal cells decreased with longer insulin treatment. No leptin staining was observed in granulosa cells of all groups. Staining intensity and H-score of the controls, D5 and D1O groups were (+++)/204, (++)/80 and (+)/9.5 for theca externa cells; (+++)/289.5, (++)/126 and (+)/65 for stroma; (++)/140, (++)/70 and (+)/21 for corpus luteum. The difference between H-scores of control and D1O groups was statistically significant in all tissue types (P<0.0 1). Conclusion: Insulin treatment for 10 days (2 estrous cycles) reduced leptin-staining intensity in various tissues of the rat ovary and decreased follicle development in a time dependent manner.
Histopathological and ultrastructural effects of Losartan on embryonic rat kidney
(Elsevier GmbH, 2005) Akil I.; Inan S.; Gurcu B.; Nazikoglu A.; Ozbilgin K.; Muftuoglu S.
The aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10 mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-β (TGF-β 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-β's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p<0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system. © 2005 Elsevier GmbH. All rights reserved.
The effect of oestradiol and neta on immunohistochemical staining of iNOS and eNOS in coronary arteries of ovariectomized rats
(2006) Koyuncu F.M.; Ozbilgin K.; Kuscu N.K.; Inan S.; Vatansever S.; Ceylan E.
Aim: The postmenopausal period is associated with increased risk for coronary atherosclerosis, and the effect of hormone replacement therapy in reducing this risk is controversial. Previous studies reported that nitric oxide synthetase (NOS) level might be important for the development of atherosclerosis, but no study has shown the interaction between hormone replacement therapy and endothelial NOS and inducible NOS intensity on coronary arteries yet. Our goal was to find out the immunostaining intensity of endothelial NOS and inducible NOS in ovariectomized rats which received oestradiol and norethisterone treatment. Methods: We performed bilateral ovariectomy in 15, female, 90-day-old Wistar rats with an average weight of 250 grams. After waiting for 4 weeks for the menopausal state, they were divided into 3 groups to receive either placebo, 0.1 mg/day 17-β-oestradiol (group E2), or 0.1 mg/day 17-β-oestradiol + 0.1 mg/day norethisterone acetate (group E2-NETA) for 5 weeks. Another group included 5, normal, adult, female intact rats and served as controls. At the end of the treatment, all rats were sacrificed and coronary arteries were stained with inducible NOS and endothelial NOS polyclonal antibodies using streptavidin-biotin technique. Results: The immunostaining of inducible NOS was prominent in perivascular connective tissue of the ovariectomized group but not in the control group. The inducible NOS immunostaining immunoreactivity was not detected in either treated groups. Immunostaining intensity of endothelial NOS did not differ in any 4 groups with similar staining. Conclusion: The present findings indicate that hormone replacement therapy down-regulates iNOS expression in coronary arteries of ovariectomized rats, and reduced iNOS may likely be involved in estrogen's beneficial effects.
Increased expression of tissue vascular endothelial growth factor and foetal liver kinase-1 receptor in seasonal allergic rhinitis and relevance to asthma component
(2007) Yuksel H.; Kose C.; Yilmaz O.; Ozbilgin K.; Degirmenci P.B.; Pinar E.; Kirmaz C.
Background: There is a difference in the extent of remodelling in allergic rhinitis (AR) and asthma. This may be attributed to the difference in local tissue response to these mediators. Objectives: The aim of this study was to compare vascular endothelial growth factor (VEGF) and its receptor foetal liver kinase (Flk)-1 expression between seasonal AR patients with or without asthma and non-allergic controls as well as that between AR patients with and without asthma. Methods: Thirteen subjects with seasonal AR and six non-allergic controls were included in the study. Allergic sensitization was demonstrated by a skin prick test. Inferior turbinate thiny biopsies were obtained from both groups. Monoclonal mouse antibodies were used to demonstrate VEGF and Flk-1. Nasal mucosal endothelial cells' staining intensity was graded semi-quantitatively and the histochemical score (HSCORE) was calculated. In all samples, VEGF- and Flk-1-labelled vessels were counted for the assessment of vascular surface density (VSD). Results: The mean HSCORE for VEGF and anti-VEGF-based VSD were significantly higher in the patient group (P=0.001 and 0.002, respectively). The mean HSCORE for Flk-1 and anti-Flk-1-based VSD in the patient group were significantly higher than those in the control group (P=0.016 and 0.028, respectively). Differences between the mean HSCORE for VEGF and anti-VEGF-based VSD in patients with pure AR and AR and asthma were insignificant (P=0.16 and 0.39, respectively). The mean HSCORE for Flk-1 and anti-Flk-1-based VSD in patients with pure AR were significantly lower than those in patients with AR and asthma (P=0.004 and 0.018, respectively). Conclusion: Angiogenic factor VEGF and its receptor Flk-1 is increased in AR. A similar increase in VEGF in AR with and without asthma despite a higher Flk-1 in AR patients with asthma may be a possible explanation for the presence of angiogenesis in the airway wall in patients with asthma but not in those with pure AR. © 2007 Blackwell Publishing Ltd.
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.
Effect of recombinant human activated protein C on apoptosis-related proteins
(2007) Sakar A.; Vatansever S.; Sepit L.; Ozbilgin K.; Yorgancioglu A.
The recombinant human activated protein C (rhAPC) has been reported to reduce mortality in patients with severe sepsis. An anti-apoptotic effect of rhAPC in sepsis is known, but the mechanism through which it acts on the apoptotic pathway is still unclear. Therefore, immunopositivity of the apoptosis-related proteins Bcl-2, an anti-apoptotic protein, c-myc, a proliferative protein, p-21 and p-53, two apoptotic proteins, was determined after rhAPC treatment in a mouse sepsis model. Sepsis was induced by Escherichia coli endotoxin injection. Increased neutrophil infiltration and immunoreactivity to p53 and p21 were observed in the group with sepsis and these immunoreactivities were decreased by rhAPC treatment. In the sepstic group; immunopositivity of Bcl-2 and c-myc was mild and moderate, respectively. In conclusion; p21- and p53-mediated apoptosis was increased in the sepsis model, and for the first time it has been shown that rhAPC decreases sepsis-induced apoptosis resulting from increased p21 and p53 proteins. ©2007 European Journal of Histochemistry.
Antenatal administration of granulocyte-macrophage colony-stimulating factor increases fetal lung maturation and endothelial nitric oxide synthase expression in the fetal rat lung
(Elsevier Ireland Ltd, 2008) Baytur Y.B.; Ozbilgin K.; Yuksel H.; Kose C.
Objectives: We investigated how maternal administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) induced fetal lung maturation compared with dexamethasone and whether maternal administration of GM-CSF and dexamethasone influenced the fetal lung eNOS expression. Study design: Thirty pregnant rats were divided into three groups of 10 rats each to receive GM-CSF, dexamethasone or saline solution at 16 days of gestation. Lung maturation using bronchial area and immunohistochemical lung airway epithelium and the vascular endothelial eNOS expression, using H Scores, were evaluated at 18 and 20 days of gestation. The statistical analysis was done with the Kruskal-Wallis test for comparisons of more than two groups and the Mann-Whitney U-test as a post hoc test using SPSS for windows release 10.0. Values of p > 0, 0.05 were considered significant. Results: On the 20th day of gestation both GM-CSF and dexamethasone injections caused a significant increase in fetal lung bronchial area, as compared with the controls (24.9%, 36.8%, 13.4%, respectively, p = 0.001). eNOS immunoreactivity was observed in the endothelium of large pulmonary vessels and large and small airway epithelium on the 18th and 20th day of gestation. Maternal GM-CSF and dexamethasone increased lung eNOS expression in the airway epithelium when compared to controls. Conclusion: Maternal administration of GM-CSF induced fetal lung maturation and this effect may be mediated, at least partly, by an increase in the eNOS expression. © 2007 Elsevier Ireland Ltd. All rights reserved.
Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma
(American College of Allergy, Asthma and Immunology, 2008) Yuksel H.; Kirmaz C.; Yilmaz O.; Pinar E.; Vatansever S.; Degirmenci P.B.; Ozbilgin K.
Background: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. Objective: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. Methods: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. Results: The mean ± SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 ± 0.78 vs 1.63 ± 0.54; P = .12). On the other hand, the mean ± SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 ± 0.75 vs 0.71 ± 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean ± SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 ± 0.78 vs 1.65 ± 0.55; P = .01). Conclusion: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.
Prenatal administration of granulocyte-macrophage colony-stimulating factor increases mesenchymal vascular endothelial growth factor expression and maturation in fetal rat lung
(2008) Yuksel H.; Yilmaz O.; Baytur Y.B.; Ozbilgin K.
The aim of this study was to determine influence of prenatal granulocyte-macrophage colony-stimulating factor (GM-CSF) administration on lung growth, maturation, and vascular endothelial growth factor (VEGF) expression. Twenty Wistar rats received sterile saline (1 mL) or recombinant human GM-CSF (50 μg/kg) on day 16 of pregnancy. Rats were sacrificed on days 18 and 20 of gestation. H-score for VEGF was calculated immunohistochemically. Alveolar VEGF expression on days 18 and 20 of gestation was significantly higher in the GM-CSF group (P <.01). Increase in VEGF with prenatal GM-CSF administration indicates that GM-CSF may stimulate lung growth and maturation and may be protective against lung disease due to prematurity. Copyright © Informa Healthcare USA, Inc.

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