MCBÜ Açıkerişim Sistemi :: Browsing by Author "Vatansever H.S."

Browsing by Author "Vatansever H.S."

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Immunolocalization of αV, α3 and β1 integrins in the human placenta with pre-eclampsia
(Elsevier GmbH, 2003) Vatansever H.S.; Inan V.S.; Lacin S.; Koyuncu F.
Signs of pre-eclampsia are considered to be caused by maternal endothelial dysfunction due to circulating factors of placental origin. Integrins are a large family of cell surface proteins that serve as receptors involved in cell-cell and cell-matrix interactions during placentation. Therefore, low expression of integrins or the lack of it may be encountered during pre-eclampsia. In the present study, we investigated the immunolocalisation of integrins αV, α3 and β1 in placentas of normal and preeclamptic women. Thirty-two placentas from pre-eclamptic (n = 14) and normotensive (n = 18) women were used. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue specimens, using anti-αV, anti-α3 and anti-β1 antibodies and the indirect immunoperoxidase technique. A semi-quantitative grading system (HSCORE) was used to compare immunohistochemical staining intensities. Distribution patterns of αV, α3 and β1 integrins were detected in cytotrophoblasts and Hofbauer cells in normal and pre-eclamptic placentas. Immunostaining of αV and β1 integrins was slightly decreased in pre-eclamptic samples but α3 integrin immunostaining was similar in pre-eclamptic and normal placentas. Decreased immunostaining of integrins in the cytotrophoblasts may considered to be a structural basis for decreased placental perfusion in pre-eclampsia.
Histopathologic effect of chronic use of sildenafil citrate on the choroid & retina in male rats
(2003) Vatansever H.S.; Kayikcioglu O.; Gumus B.
Background & objectives: Sildenafil citrate is an oral medication used to treat male impotence by the inhibition of phosphodiesterase-5 in the corpus cavernosum and subsequent facilitation of penile erection. Though the ocular side effects of sildenafil have been reported, no information is available on the histopathologic effects of chronic use of sildenafil citrate on the ocular vasculature. The present study was undertaken to study the histopathologic effects of chronic use of sildenafil on the retina and choroid of male rats. Methods: Twelve adult male Wistar rats were used in the study. Six of them were given 8 mg/kg/day sildenafil citrate orally on alternate days, the other six rats were used as control. The animals were sacrificed after 4 wk of treatment, and the eyes were fixed in 10 per cent formalin solution and sectioned after embedding in paraffin. Sections were cut, stained with haematoxylin-eosin (HE) or periodic acid Schiff (PAS) and examined under light microscope. The choroidal capillary diameter was also measured. Results: The choroidal capillaries were more dilated in the sildenafil citrate treated group (mean capillary diameter 3.44 ± 1.68 μm versus the control of 1.78±1.36 μm, P<0.001). The retinal layers and their configuration were unchanged in both the groups. Interpretation & conclusion: Chronic use of sildenafil citrate can cause dilatation and congestion in the choroidal vasculature of male rats.
The Effects of Methotrexate on the Development of Neural Tube Defects in the Chick Embryo
(2003) Vatansever H.S.; Umur A.Ş.; Inan V.S.; Selçuki M.
During chick development, one of the earliest differentiated tissues is the neural tube. After 24 h of incubation, a chick egg starts to differentiate and 30-48 h after incubation the neural plate is closed from head to tail to form the neural tube. If factors controlling the neural tube's closing are disrupted, this consequently causes neural tube closure defects during this time. In this study, the effect of methotrexate on the developing neural tube was investigated during early chick development. For this research, 40 specific pathogen free (SPF) white Leghorn type chick embryos were used. They were incubated for 30 h at 37.8 ± 2°C. Methotrexate, which inhibits the dihydrofolate reductase enzyme by a competitive mechanism, was injected within therapeutic dosage limits (10 mg/m2, 20 mg/m2, 40 mg/m2) in ovo. Ten eggs were injected with 0.9% NaCl and used as a control group. All groups, after the injection, were incubated for 48 and 72 h. They were then dissected and the embryos were fixed in 10% (v/v) formalin for 2 h. The embryos were embedded in paraffin wax and 5 μ serial sections were taken. Sections were stained with haematoxylin and then observed under light microscopy. While 20 mg/m2 or 40 mg/m2 methotrexate embryos were not alive when they were opened at 48 h incubation, 10 mg/m 2 methotrexate embryos maintained normal development after 48 and 72 h incubation. However, there was developmental retardation in the methotrexate injected group when compared with the control group with development of the brain being retarded; the volume of brain vesicles was lower than in the control group. Our results suggested that methotrexate, an antimetabolite of folic acid, caused neural tube closure defects when injected at therapeutic dosage levels. Folic acid is essential for normal development of the nervous system; therefore, folate antagonists might be more harmful to the central nervous system than to other parts of the developing body.
Histopathological effects of sildenafil citrate on rat corpus cavernosum
(Elsevier GmbH, 2004) Gümüs B.; Vatansever H.S.; Müezzinoǧlu T.; Müftüoǧluc S.; Kaymaz F.; Büyüksu C.
Sildenafil citrate (Viagra) is widely used for the treatment of erectile dysfunction with various etiologies. The aim of the present study was the investigation of histopathological effects of sildenafil citrate on rat corpus cavernosum using light and electron microscopical techniques. Twenty male rats were divided into two groups. The first group (n = 10) was used as a control and the second group (n = 10) was treated with sildenafil citrate. Penile tissue was collected, fixed with formalin and embedded in paraffin for light microscopy, or fixed with gluteraldehyde and osmium tetroxide and embedded in Epon for electron microscopy. Light microscopical analysis showed that the corpus cavernosum was elongated and the number of blood vessels was increased. The amount of connective tissue in the penis was increased and dense collagen and smooth muscle fibers were observed in treated rats. Electron microscopical analysis showed that stromal structures of the corpus cavernosum (collagen fibers and number of cellular elements) were increased in treated rats. Fibroblasts showed signs of activation and the number of other stromaL cells was increased. Immature newly synthesized collagen fibers were observed and penetrated endothelial basement membranes. In addition, endothelial cells also showed signs of activation such as cytoplasmic granules in treated rats, whereas the surface area of blood vessels was increased and basement membranes were thickened. These histopathological changes due to treatment with sildenafil citrate indicate that prolonged use of sildenafil citrate may increase the risk of fibrosis in the penis. © 2003 Elsevier GmbH. All rights reserved.
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.
The maturity of intestinal neomucosa: Integrin expression and ultrastructural aspects
(2004) Günşar C.; Vatansever H.S.; Arslan O.A.; Şencan A.; Müftüoǧlu S.; Özbilgin K.; Kaymaz F.; Mir E.
Background/purpose The maturity of neomucosa growing on a serosal surface for the treatment of short bowel syndrome still is questionable. The aim of this study was to evaluate the intestinal neomucosa to assess its histologic maturity. Methods A 6-cm-long isolated ileal segment (IS) was prepared in 8 Wistar albino-type rats. The IS was divided from the antimesenteric side, and 2 intestinal tubes were established, which shared a common wall and a common pedicle. After ileal biopsy sampling for the control group (CG), the IS was fashioned into a mucous fistula. Eight weeks later, all the rats were killed, and the ISs were investigated for neomucosal growth. Sections were prepared with periodic acid shift (PAS) and H & E staining for light microscopy. They also were evaluated by transmission electron microscopy. The microscopic morphology of the 2 groups was evaluated. Immunohistochemical staining was performed to show the expression of the tissue β1, α3 and α2β1 integrin subunits of both the neomucosa (NS) and control group (CG) segments. Results Sections of the NS showed a well-arranged columnar epithelial cell layer with goblet cells that were generally located superficially and with a complete basement membrane. Under the electron microscope, the sections from the NS group showed an epithelial cell layer with proper microvilli of the same height, although they were shorter than those of the CG, and tight intercellular junctions between the epithelial cells. Significant differences between the NS and CG groups were found in the measurements of villus width at base, microvillus surface, and microvillus height. The lamina propria consisted of rich collagen fibers and active fibroblasts in the NS group. In the immunohistochemical staining, although β1 integrine showed a dense distribution (+++) in the lamina propria, particularly localizing at the depth of the tunica mucosa layer, α3 integrin was observed to have a less dense immunoreactivity (++) in both groups. The expression of α2β1 integrin showed slight and dispersed (+) staining. Conclusions The NS showed histologic maturity and ultimate structural similarity with the native small bowel mucosa, which provides strong indirect evidence for the proper functioning of the neomucosa. © 2004 Elsevier Inc. All rights reserved.
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.
Effect of thermal energy produced by drilling on the facial nerve: Histopathologic evaluation in guinea pigs
(2005) Aslan A.; Vatansever H.S.; Aslan G.G.; Eskiizmir G.; Giray G.
The effect of thermal energy due to drilling around the facial nerve canal on the facial nerve was histopathologically evaluated in four guinea pigs. The bony canal of the facial nerve was drilled using a 3-mm diamond burr for one minute. The temperature changes on the facial nerve canal were noted before and after dissection. The temporal bones of the animals were histopathologically examined under light microscopy using haematoxylin & eosin (H&E) and solochrome cyanine staining for myelin, and immunohistochemical staining for neuronal nitric oxide synthase (nNOS). Compared to the control group, it was observed with H&E staining that there was oedema among the axonal fibres and with solochrome cyanine staining that the thickness of the myelin fibres was decreased, and that the severity and extent of nNOS activity was decreased in the axonal fibres. It was concluded that a temperature increase on the facial canal may potentially lead to inflammation of the nerve, and may also cause deterioration of nerve conduction to some extent.
Changes in distribution patterns of integrins in endometrium in copper T380 intrauterine device users
(Elsevier GmbH, 2005) Oruç S.; Vatansever H.S.; Karaer Ö.; Eskicioǧlu F.; Narlikuyu B.
Intrauterine contraception is the most cost-effective reversible method of contraception today, but its mechanism of action is not well understood. Our objective was to investigate immunohistochemical distribution patterns of αv, α3, β1 integrins in women using a copper T380 intrauterine device (IUD) for different periods of time to obtain insight into the role of integrins in intrauterine contraception. Endometrial biopsies were obtained from patients using T Cu380A IUD in follicular and luteal phases and in menopausal women grouped according to the period of time of IUD use (group 1: <3 year, and group 2: ≥3 years). Each group consisted of 10 patients, with a total number of 60 patients. Labelling intensity of all integrins, except for β1 which increased in the follicular phase, were decreased in women who used IUD for ≥3 years when compared with group 1 in the follicular and luteal phases and in the menopause. We conclude that long-term use of IUD affects integrin expression in endometrium not only in follicular and luteal phases of premenopausal women but also in postmenopausal women. Copper IUD can inhibit binding of integrins to the extracellular matrix and it may cause inhibition of the implantation stage, which is crucial for pregnancy. © 2005 Elsevier GmbH. All rights reserved.
Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility
(Elsevier GmbH, 2005) Vatansever H.S.; Lacin S.; Ozbilgin M.K.
Apoptosis has been shown to be an important regulator of endometrial function during the menstrual cycle and implantation. Recently, some possible implantation defects were identified in patients with unexplained infertility. In this study, we investigated the role of spontaneous apoptosis, which is regulated by death regulatory genes, such as Bcl-2, Bax, p53, and isoenzymes of nitric oxide synthases; eNOS and iNOS during the implantation window in women with unexplained infertility. Endometrial samples were evaluated from fertile (n=15) and unexplained-infertile women (n=15) during post-ovulatory 7th or 8th day of their menstrual cycles. Apoptotic cells were detected using the dUTP nick-end labelling assay and Bcl-2, Bax, p53, iNOS and eNOS were assessed immunohistochemically. Reduced apoptotic cells, weak immunoreactivity of p53 and strong immunoreactivity of Bcl-2 were observed in the unexplained-infertile group compared with the fertile group (p<0.001). Bax intensity was similar in both groups. While weak iNOS immunoreactivity was detected in both groups, moderately increased eNOS immunoreactivity was observed in infertile cases. Spontaneous apoptosis is reduced in the endometrium of unexplained-infertile women, and is associated with the changed Bcl-2:Bax ratio. This finding may be a contributing factor to defective implantation causing infertility in this group of patients. © 2005 Elsevier GmbH. All rights reserved.
Characterization of osteoblasts derived from bone marrow stromal cells in a modified cell culture system
(Elsevier GmbH, 2006) Deliloglu-Gurhan S.I.; Vatansever H.S.; Ozdal-Kurt F.; Tuglu I.
Bone marrow is a complex tissue composed of hematopoietic and stromal stem cells with the potential to differentiate into adipogenic, fibroblastic, reticular, osteogenic and chondrogenic lineages. Identification of differentiation markers during transformation of stromal cells into osteoblasts in a time-dependent manner may be informative for cell-based tissue engineering. Therefore, we investigated the effects of osteogenic medium (OM) on the proliferation and differentiation of rat bone marrow stromal cells (BMSCs). BMSCs from adult male rat tibia and femur were collected and cultured in α-MEM medium with 10% fetal bovine serum, penicillin, streptomycin and gentamycin. After three days of culture, the medium covering the adherent cells in culture was changed to OM containing dexamethasone, Na-β-glycerophosphate and ascorbic acid. As a control, cell culture was also continued in the original medium for the same time period. Differentiated osteoblast cells were collected after 7, 10, 14, 21 and 30 days of culture, fixed with 4% paraformaldehyde and their immunolabelling for osteoblast markers osteonectin (ON) and osteocalcin (OC) was assessed using an indirect immunoperoxidase technique. Immunoabelling of ON and OC was detectable from day 10 of culture, began to increase on day 14, and increased steadily through to day 21. Labelling was highest on day 30 and was more intense in cells cultured with OM compared to the culture without OM. The control cells cultured in the absence of OM produced negligible levels of both markers. In conclusion, our culture system facilitated differentiation of BMSCs into osteoblasts featuring osteoblast markers, and these cells may be useful in autologous bone implant for the treatment of bone wound healing. © 2005 Elsevier GmbH. All rights reserved.
The effect of osteogenic medium on the adhesion of rat bone marrow stromal cell to the hydroxyapatite
(2006) Deliloglu-Gurhan I.; Tuglu I.; Vatansever H.S.; Özdal-Kurt F.; Ekren H.; Taylan M.; Sen B.H.
Objective: To investigate the adhesive properties of bone marrow stromal cell (BMSC) on the hydroxyapatite (HA) particles and analyze their behavior. Methods: The study took place in the Department of the Histology and Embryology, Celal Bayar University, Manisa and in the Department of Bioengineering, Ege University, Izmir, Turkey between 2004 and 2005. We cultured BMSC from the mature rat tibia and differentiated to the osteoblasts by osteogenic medium. The BMSCs were subcultured and were taken to the HA substrate. We measured their proliferation capacity and viability with MTT assay using the spectrophotometric method. Furthermore, we identified the osteoblast-like cells by inummohistochemical staining of osteonectin and osteocalcin and we analyzed the behavior of the cells on different sized HA particles by SEM at the end of 3 days incubation. Results: Osteogenic medium caused the proliferation capacity of BMSC to speed up and the effects appeared earlier. We confirmed the osteoblastic differentiation by staining of most cells with osteoblastic markers. Subcultured cells were similarly adhesive to the HA particles and the osteogenic medium did not alter this behavior. They spread on the substrate similarly. Most of the cells demonstrated the cytoplasmic protrusion. Morphology of the cells did not change much with or without osteogenic medium. Different sizes of HA particles did not affect the adhesive properties of these cells except HA gel. The spreading and attachment ratios of the cells on HA gel were more than the others. Conclusion: We found that there was heterogeneity in BMSC on differentiation capacity to the osteoblast, which was a sign of a subpopulation. Adhesive cells showed similar morphology and behavior under the effect of osteogenic medium. The only difference was the spreading capacity on the HA gel where cell used this substrate more effectively for adhesion.
Inhibitory effects of propolis on human osteogenic sarcoma cell proliferation mediated by caspase patway; [Kaspaz yolaǧı ile yönlendirilen i̇nsan osteojenik sarcoma hücre çoǧalmasına propolisin baskılayıcı etkisi]
(KAFKAS UNIVERSITY, 2010) Ozdal Kurt F.; Vatansever H.S.; Sorkun K.; Deliloǧlu Gurhan S.I.; Turkoz E.; Gencay O.; Salih B.
A natural product Propolis, is a resinous material gathered by honeybees from the buds and bark of certain trees and plants. Propolis contains various chemical components of biological activities, including antimutagenic, antioxidant, antibacterial, antiviral and anticarsinogenic. Therefore, the aim of this study is to investigate the antiapoptotic effect of propolis extracts (PE) using caspase pathway in the human osteogenic sarcoma cell line SAOS-2 in culture. The extracts which produced in ecologic environment were taken from the Hacettepe University, Beytepe Campus area-Ankara were used. Seven different PE at 0.5, 0.25, 0.125 and 0.063 mg/ml were added to SAOS-2 cell line for two days incubation. For cell proliferation and cytotoxicty analyses MTT, for apoptotic cell death determination TUNEL method, for distribution of caspase 6, caspase 8 and caspase 9 indirect immunocytochemistry analyses were used. After MTT analyses, the most effect was observed PE 7 at the 0.125 mg/ml dilution. The number of TUNEL positive cells was more detectable at PE 4 and 5 at the 0.063 mg/ml, and PE 7 at the 0.125 mg/ml dilutions. The immunoreactivity of caspase 6 was stronger than caspase 8 and 9. Moreover, density of caspase 6 staining was much better especially in PE 7 at the 0.125 mg/ml dilution. In conclusion, the mechanisms of apoptosis induction by PE may appear via caspase pathway because of its anticanserogenic effect. PE may be usefull in the cancer treatment protocol.
The effects of meloxicam on neural tube development in the early stage of chick embryos; [Meloksikamın erken dönem civciv embriyosunda nöral tüp geliflimine etkileri]
(Turkish Neurosurgical Society, 2010) Cetinkal A.; Colak A.; Topuz K.; Demircan M.N.; Simsek H.; Berber U.; Umur A.S.; Selcuki M.; Vatansever H.S.
AIM: The aim of this study is to demonstrate the effect of meloxicam in early stage chick embryos on neural tube development. MATERIAL and METHODS: One hundred specific pathogen-free (SPF) chicken eggs were used to investigate the neurulation. SPF eggs were invastigated in four groups (n:25). All of the groups were incubated at 37.2 ± 0.1°C and 60 ± 5 % relative humidity for 30 hours, and an embryological development in the ninth stage as classified by Hamburger and Hamilton was obtained. In the end of the 30th hour, group A(control group) was administered 0.1 ml of saline (0.9% NaCl) in ovo and the other groups were administered meloxicam in increasing doses. At the end of 72 hours, all of the embryos were extracted from eggs and they underwent pathological examination with hematoxylin eosine and immunohistopathological examinations with CD138 and tubulin beta II. RESULTS: While the groups Aand B showed no neural tube defects, totally eight defective embryos were detected in the groups C and D (three in group C and five in group D. CONCLUSION: Our results suggested that meloxicam, a nonselective COX inhibitor, caused neural tube closure defects when injected at supratherapeutic doses. However, further studies with larger numbers of subjects are needed for its use in lower doses.
The effects of Gemcitabine and Vinorelbine on inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) distribution of MCF-7 breast cancer cells
(Elsevier GmbH, 2011) Zeybek N.D.; Inan S.; Ekerbicer N.; Vatansever H.S.; Karakaya J.; Muftuoglu S.F.
Gemcitabine, which induces S-phase arrest, and Vinorelbine, which arrests microtubule organization, are two agents that have demonstrate preferred anti-tumor activity. Nitric oxide acts in diverse functions including anti-tumor and anti-pathogenic activities. In this study, we aimed to examine the distribution of immunoreactivities of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in cells of the MCF-7 breast cancer cell line in response to treatment with Gemcitabine (G), Vinorelbine (V) and combination of Gemcitabine and Vinorelbine (G+V). The distributions of iNOS and eNOS were determined by using indirect immunoperoxidase or immunofluorescence methods and ELISA. Cells incubated with G, V and G+V for 24, 48 and 72. h were immunolabelled with anti-eNOS and anti-iNOS primary antibodies. Apoptosis was determined by TUNEL assay. A significant increase of eNOS immunolabelling on MCF-7 cells treated with G and G+V was observed. Apoptotic cells were also detected in G, V and G+V treated MCF-7 cells. The immunolabelling of iNOS was detected in all groups but this immunoreactivity was not different among the groups. In conclusion, while G treatment, induced S-phase arrest, triggered the NOS pathway after treatment of MCF-7 cells, V treatment, arrested microtubule organization and did not change the NOS pathway. Detection of increased eNOS immunolabelling and apoptosis after G treatment of MCF-7 cells could be important to the treatment of human breast cancer. © 2009 Elsevier GmbH.
Effects of 5-fluorouracil and gemcitabine on a breast cancer cell line (MCF-7) via the JAK/STAT pathway
(2012) Uluer E.T.; Aydemir I.; Inan S.; Ozbilgin K.; Vatansever H.S.
Aberrant activation of the JAK/STAT pathway may predispose to malignancy as a consequence of the deregulation of cell proliferation, differentiation or apoptosis such as in cancer of the blood, head and neck, and breast. In our study we aimed to investigate the effects of 5-fluorouracil (5-FU) and gemcitabine on a breast cancer cell line (MCF-7 cells) via the JAK/STAT pathway. Distribution of JAK1, JAK2, JAK3 and STAT2, STAT3, STAT4, STAT5 were evaluated on MCF-7 cells following gemcitabine and 5-FU treatment and in the absence of drug treatment by an indirect immunohistochemical method. It was observed that JAK1, JAK3, STAT5 and particularly STAT2 activation were more effective than the other JAK/STATs in breast cancer progression. Following treatment with 5-FU, JAK1 and STAT5 immunoreactivities were decreased in MCF-7 cells in comparison with both gemcitabine-treated and non-treated groups. These results suggest that the JAK/STAT pathway plays an important role in breast cancer pathogenesis and may be more affected after 5-FU treatment rather than gemcitabine. Drugs which block STAT5 may provide a novel therapeutic approach for the treatment of breast cancer. © 2011 Elsevier GmbH.
Simultaneous folate intake may prevent advers effect of valproic acid on neurulating nervous system
(2012) Umur A.S.; Selcuki M.; Bursali A.; Umur N.; Kara B.; Vatansever H.S.; Duransoy Y.K.
Purpose: The aim of this study is to elucidate the preventive effect of folic acid (FA) on teratogenic effects of valporic acid (VA) in early stage chick embryos on neural tube development. Materials and methods: One hundred and fifty specific pathogen-free (SPF) chick eggs were used to investigate the neurulation in five groups. Group A was the control group. Group B was injected 0.02 ml of saline (0.9% NaCl) and was used for sham group. VA (0.72 mg) in 0.02 ml saline was injected in Group C, and 0.342 mcg of FA in 0.02 ml NaCl were administered to the embryos in Group D. VA (0.72 mg)+0.342 mcg of FA in 0.02 ml saline were administered simultaneously to the eggs in Group E. At the end of 72 h, all embryos were extracted from eggs and were fixed, and for histological analyses hematoxylin and eosine was used, for detection of apoptotic cells terminal deoxyribonucleotide transferase-mediated dUTP-X nick end labeling (TUNEL) was used and for distribution of P53, bcl-2 and caspase-3, caspase-6, caspase-8 and caspase-9 immunoperoxidase techniques were used. Results: While there were no neural tube defects in the embryos of groups A, B and D, eight embryos died in group C and there were 12 embryos with retarded embryological development. In contrast to that, no death was observed in group E, but only eight embryos were detected with maldevelopmental delay stage. Conclusion: These results suggested that VA may induce apoptotic mechanisms but not through the p53 pathway. In addition, FA effectively prevents the teratogenic influence of VA on chick embryo at neurulation stages by stopping cascade of apoptosis before caspase 3 expression. © 2012 Springer-Verlag.
EVect of lisinopril on renal tissue damage in unilateral ureteral obstruction in rats
(2012) Karabuga Ä.; Akbay K.; Turna B.; Vatansever H.S.; Altay B.; Güzel E.; Uluer E.T.; Ustun G.; Ekren F.; Nazli O.; Muftuoglu S.; Apaydin E.
In this study, it was aimed to investigate apoptosis in renal injury and the eVect of lisinopril in rat model, which constitute unilateral ureteral obstruction. The retroperitoneal ureter was ligated with a 4.0 silk for the experimental model of ureteral obstruction in Wistar albino rats. Untreated group (n = 20) received no treatment. For the lisinopril-treated group (n = 20), 20 mg/kg/day of drug was given orally. Ultrastructural diVerences were analyzed using electron microscopic technique; apoptotic distribution was analyzed using the TUNEL method. After electron microscopic evaluation, on the 4th and 14th day in the untreated group, edema in the glomeruli, loss of microvillus and apoptotic cells in proximal tubule cells and sclerosis in the glomeruli were detected. On the 4th day in the lisinopril-treated group, the kidney was ultrastructurally normal and a less number of apoptotic cells were only observed on the 14th day. On light microscopic examination on the 4th and 14th day in the untreated group, while the glomeruli were normal in structure, the boundary of the proximal tubule was disrupted and some picnotic cells in both the proximal and collecting tubules were observed. In both 4th and 14th day of the lisinopril-treated group, kidney showed normal structure, although in some places picnotic cells in the collecting tubules were observed. In conclusion, lisinopril was eVective and it may prevent early renal damage in the direct obstruction model. © Springer-Verlag 2011.
TGF-βs and SMADs activities at the site of failed neural tube in the human embryos
(Turkish Neurosurgical Society, 2013) Barutcuoglu M.; Umur A.S.; Vatansever H.S.; Umur N.; Ozbilgin K.; Sayhan S.; Selcuki M.
Aim: Transforming growth factor β (TGF-β) and Smads control intracellular signaling pathways in neurulation. Although previously reported similar experimental animal studies, the aim of this human study is to investigate the expression of TGF-β (1,2,3) and Smads (1,2,3,6,7) in aborted human fetuses with myeloschisis. Material and Methods: Twelve human fetuses with neural tube defect were obtained. They were stained with antibodies against TGF-β1, TGF-β2, TGF-β3, Smad (1,2,3), Smad 6 and Smad 7 using the indirect immunohistochemical technique. Results: We noted mild immune reactivity of TGF-β1 and TGF-β2 in the open neural plate, motor neurons and surrounding tissue. Strong immune reactivity of TGF-β3 was shown in only open neural plate and surrounding tissue. Immunoreactivity of all Smads noted negative except Smad7. ConclusIon: These results suggested at the site where the neural tube failed to close, TGF-β 1,2 and Smads 1,2,3,6 do not continue their activity and decrease with internal timing of embryonic development. Additionally ectodermal layers are considered by embryo as "not closed wound" and TGF-β3 activity may be an effort to repair the failed closure.
Analysis of transferred keratinocyte-like cells derived from mouse embryonic stem cells on experimental surgical skin wounds of mouse
(2013) Vatansever H.S.; Uluer E.T.; Aydede H.; Ozbilgin M.K.
Autologous/allogenic skin grafts constituted from differentiated adult or embryonic stem cells can be used in treatment of skin disorders. In our study we aimed to differentiate keratinocytes from mouse embryonic stem cells and the transfer of viable keratinocyte-like cells to a model of surgical skin wound of mouse. Embryoid bodies, derived from mouse embryonic stem cells, were cultured on basement membrane matrix with added BMP-4 for 10 days. The identification of differentiated keratinocyte-like cells was done by detection of cytokeratin-8 and cytokeratin-14 localization using an indirect immunoperoxidase technique and transmission electron microscopy evaluation. Distribution of BrdU, cytokeratin-8 and cytokeratin-14 were evaluated using an indirect immunoperoxidase technique from the experimental (dressing including BrdU labelled cells applied after the surgical wound was created on mouse), control (only the surgical wound was created on mouse) and sham (only the dressing applied after the surgical wound was created on mouse) in groups after 3, 5 and 7 days. Immunohistochemically and ultrastructurally, cells derived from mouse embryonic stem cells were similar to differentiated keratinocyte-like cells. Differentiated keratinocyte-like cells were demonstrated by positive BrdU, cytokeratin-8 and cytokeratin-14 staining after transfer to the wound area. In the experimental group wound healing was better after transferring differentiated keratinocytes when compared to the sham and control groups. In vivo continuity and usability of derived cells are very important issues. In wound repair mechanisms, keratinocyte-like cells could provide positive effects during the wound healing and could be used in clinical treatments of wound repair process. © 2012 Elsevier GmbH.

Browsing by Author "Vatansever H.S."

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