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    Deregulation of c-Src tyrosine kinase and its downstream targets in pre-eclamptic placenta
    (Wiley, 2017) Irtegun, Sevgi; Akcora-Yildiz, Dilara; Pektanc, Gulsum; Karabulut, Cagla
    AimPre-eclampsia is a serious pregnancy disorder characterized by the new onset of hypertension and proteinuria in the second trimester of pregnancy. The determination of a key signaling regulatory mechanism involved in placental functions is critical to understanding the pathogenesis of pre-eclampsia. The aim of this study was to examine the activity of c-Src and its downstream targets, extracellular signal-regulated kinase 1/2, p38 and Jun N-terminal kinase, as well as nuclear factor (NF)-?B in placental tissues collected from women with pre-eclampsia. MethodsTen pre-eclamptic (PE) placentas and 10 control placentas were used in this study. The Western blot method was performed to evaluate the c-Src/ mitogen activated protein kinase/NF-?B signaling pathway in each group. Resultsc-Src phosphorylation at Tyr-416, used as a measure of c-Src activity, was significantly decreased in PE placentas relative to the control. Reduced c-Src activity resulted in the suppression of extracellular signal-regulated kinase 1/2 phosphorylation and a significant reduction in the phosphorylation of p38 and Jun N-terminal kinase in PE placentas. Moreover, I?B phosphorylation was significantly elevated, while NF-?B phosphorylation was suppressed in PE placentas. ConclusionsThe c-Src/MAPK/NF-?B signaling pathway may contribute to the pathogenesis of pre-eclampsia.
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    Effects of Potentilla fulgens as a Prophylactic Agent in Tibial Defects in Rats
    (Sci Printers & Publ Inc, 2016) Koparal, Mahmut; Irtegun, Sevgi; Alan, Hilal; Deveci, Engin; Gulsun, Belgin; Seker, Ugur
    OBJECTIVE: To investigate the effects of Potentilla fulgens as a prophylactic agent on tibial defects in the rat. STUDY DESIGN: Twenty-eight male Wistar albino rats weighing 200-215 g each were divided into 3 experimental groups. The tibial bone defect group served as the control group. The experimental groups were Potentilla fulgens with tibial defect (14 days) and Potentilla fulgens with tibial defect (28 days). Extract of Potentilla fulgens was mixed with water (400 mg/kg/day) and given to groups 14 and 28 as drinking water. The histopathological and immunohistochemical characteristics of each tibial bone cavity within each group were observed. The trabecular new bone formation was evaluated by expression rate of osteonectin and osteopontin. RESULTS: In the Potentilla fulgens + tibial defect group (14 days), trabecular bone had started combining extensive new bone formation, osteocyte cells were evident, and lamellar bone was formed. Osteoblasts showed a positive reaction with osteonectin. Osteopontin expression was positively observed between fibrous structures and in the osteoblast and osteocyte cells. This can be considered indicative of new bone formation. In the Potentilla fulgens + tibial defect group (28 days), an increase in expansion in trabecular bone and myeloid tissue was observed. Osteoblastic activity and osteocyte cells began to be observed in new bone fragments. CONCLUSION: In our study we show that Potentilla fulgens extract provided a protective effect on new bone formation and aided in the development of osteocytes and secretion of matrix in osteoblasts. Additionally, we show the inductive effect of the extract on new bone formation. In particular, the expression of osteopontin and osteonectin was also supported with the Western blot technique on the development of osteoblasts and osteocytes, showing a similar trend with our results.
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    Expression of pSTAT3 and TNF-? in Normotensive and Severe Preeclamptic Placentas
    (Sci Printers & Publ Inc, 2017) Togrul, Cihan; Gorkem, Umit; Irtegun, Sevgi; Tahaoglu, Ali Emre; Gungor, Tayfun; Deveci, Engin
    OBJECTIVE: To examine histopathologic changes and correlation between TNF-alpha and pSTAT3 expression levels by western blot and immunohistochemical methods in preeclamptic placentas. STUDY DESIGN: Obstetrical properties and bio-chemical and hematological features of patients with preeclampsia and healthy subjects were compared. Paraffin sections obtained from placenta were stained with hematoxylin-eosin for histopathologic examination. RESULTS: In histopathologic examination of preeclamptic placentas, cytotrophoblastic cellular proliferation, fibrinoid necrosis, endothelial proliferation, and calcified and hyalinized villous spots were observed. CONCLUSION: In preeclamptic placentas, we observed that trophoblastic invasion may downregulate STAT3 phosphorylation and can correlate with TNF-alpha elevation. Even though trophoblast invasion may interfere with both vascular and immune systems, TNF-alpha is not directly involved in the STAT3 signaling pathway in the preeclamptic placenta. (Anal Quant Cytopathol Histpathol 2017; 39: 149-156)
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    Immunohistochemical and Histopathological Changes in the Teeth of Rats After Lead Acetate Application
    (Sci Printers & Publ Inc, 2015) Er, Faruk; Koparal, Mahmut; Deveci, Engin; Irtegun, Sevgi
    OBJECTIVE: To study the toxic processes of lead in teeth by investigating the histopathologic and immunohistochemical effects of lead on incisor teeth of rats. STUDY DESIGN: Thirty Wistar Albino rats weighing 180-200 g were divided into 2 groups: a control group and a lead acetate group (i.e., the experimental group). The experimental group received lead acetate at 500 ppm in their drinking water for 60 days, and the control group received distilled water. The sections of the control group and the experiment group were histopathologically compared. RESULTS: The longitudinal cross-sections of the mandibular incisor teeth were analyzed. Degeneration in the periodontal membrane and vascular dilation in pulp and inflammatory cell infiltration were observed, and vimentin expression was seen in the dental pulp and the periodontal membrane. CONCLUSION: The presence of vimentin in the dentinal tubules indicated that the odontoblast processes in these tubules were positive. In the experimental group the profile of dentinal tubules was found to be impaired and disorganized. These results indicate a loss of collagen fibers in the periodontal membrane of incisor teeth in the experimental group. In the same group the gripping function of the incisor teeth was affected due to the spacing of the intermediate filaments that are located between the alveolar bone and the periodontal ligament. The expression of vimentin on the tooth was reduced by the lead acetate treatment. Lead acetate may affect the adhesion of the tooth to the alveolar bone.
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    Immunohistochemical and Ultrastructural Examination of Changes in the Retina in Diabetic Rats
    (Sci Printers & Publ Inc, 2016) Turgut, Fethiye Gulden; Ozevren, Huseyin; Irtegun, Sevgi; Deveci, Engin
    OBJECTIVE: To study diabetic retinopathy by the immunohistochemical and ultrastructural examination of changes in the retina in diabetic rats. STUDY DESIGN: We examined the blood-retinal barrier and cell-to-cell connections in diabetic rats by immunohistochemistry and ultrastructural level. Twenty adult male Wistar rats were used in this study. The animals were divided into 2 groups. The control group was fed standard rat chow and drinking water for 8 weeks. Single-dose streptozotocin (55 mg/kg) was dissolved in sodium citrate buffer and administered via intraperitoneal injection to induce diabetes in the diabetes group. The diabetes and control groups were compared for glucose values. RESULTS: The blood glucose concentration in diabetic rats was significantly increased (p< 0.05). Dilation of blood vessels, hemorrhage, and edema were observed in the nerve fibers and ganglion layer. An increase in vascular endothelial growth factor expression was confirmed by Western blot method. E-cadherin-positive cells in the immune junctions between cells in the diabetic retina were observed, weakly staining. CONCLUSION: Ultrastructural analysis of diabetic retinopathy showed that dysfunctionality of photoreceptor cells and vision loss are thought to occur due to mitochondrial degeneration. (Anal Quant Cytopathol Histpathol 2016; 38: 357-363)
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    Neuroprotective Effects of Potentilla Fulgens on Traumatic Brain Injury in Rats
    (Sci Printers & Publ Inc, 2017) Ozevren, Huseyin; Irtegun, Sevgi; Deveci, Engin; Ozgur, Mustafa Esref; Asir, Firat; Tekin, Mehmet Ali; Deveci, Senay
    OBJECTIVE: To investigate if Potentilla fulgens (P. fulgens) has any neuroprotective effects on traumatic brain injury in rats. STUDY DESIGN: Sprague-Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g(-1) m weight-height impact. Sixty-four rats were divided into 4 groups: group 1 (vehicle-treated control), group 2 (P. fulgens 400 mg/kg/day, intraperitoneally [i.p.]), group 3 (vehicle-treated trauma), and group 4 (trauma+P. fulgens 400 mg/kg/day, i.p.). Distilled water was used as vehicle. All rats were decapitated 5 days after the induction of trauma, and the protective effects of P. fulgens were evaluated by histological, immunohistochemical, and biochemical analyses. RESULTS: Administration of P. fulgens at a dose of 400 mg/kg/day provided significant improvement in all of the histological, biochemical, and immunohistochemical analyses after the induction of traumatic brain injury. CONCLUSION: Although further studies are necessary to evaluate the time-and dose-dependent neuroprotective effects of P. fulgens, it may be a beneficial therapeutic agent for prevention of secondary neuronal damage following diffuse traumatic brain injury.
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    Pharmacological Inactivation of Src Family Kinases Inhibits LPS-Induced TNF-? Production in PBMC of Patients with Behcet's Disease
    (Hindawi Ltd, 2016) Irtegun, Sevgi; Pektanc, Gulsum; Akkurt, Zeynep M.; Bozkurt, Mehtap; Turkcu, Fatih M.; Kalkanli-Tas, Sevgi
    Behcet's disease (BD) is a multisystemic chronic inflammatory disease characterized by relapsing oral and genital ulcers, uveitis, and skin lesions. The pathogenesis of BD is still unknown. Aberrant production of some cytokines/chemokines plays an important role in the pathogenesis of various inflammatory diseases. Revealing a key signaling regulatory mechanism involved in proinflammatory cytokines/chemokines production is critical for understanding of the pathogenesis of BD. The aim of this study was to determine the role of Src family kinases (SFKs) in production of some LPS-induced proinflammatory cytokines/chemokines in peripheral blood mononuclear cells (PBMC) of active BD patients. Chemical inhibition of SFKs activity impaired LPS-induced TNF-alpha production in PBMC of active BD patients, suggesting that modulating SFKs activity may be a potential target for BD treatment.
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    Protective Effect of Potentilla fulgens on Changes in Cerebellum Following Traumatic Head Injury
    (Sci Printers & Publ Inc, 2018) Ozevren, Huseyin; Irtegun, Sevgi; Deveci, Engin
    OBJECTIVE: To examine protective effects of Potentilla fulgens (P. fulgens) extract on cerebellar tissue damage of head-traumatized rats with respect to biochemical, histopathological, immunohistochemical, and ultrastructural analysis. STUDY DESIGN: Sprague-Dawley rats were subjected to traumatic head injury with a weight-drop device using 300 g-1 m weight-height impact. In our study the occipital lobe region was subjected to moderate trauma. Sixty-four rats were divided into 4 groups: group 1 (control group), group 2 (P. fulgens group [400 mg/kg/day i.p.]), group 3 (trauma group), and group 4 (trauma +P. fulgens [400 mg/kg/day i.p.]). Distilled water was used as vehicle. All rats were decapitated 5 days after the induction of trauma, and the protective effects of P. fulgens were evaluated by histological, immunohistochemical, and biochemical analyses. RESULTS: After trauma, degenerative changes and congestion were observed in Purkinje and glial cells. Elevated expression of E-cadherin in synaptic junctions, increased tumor necrosis factor alpha expression in Purkinje and glial cells, and elevated endothelin-1 expression in vessel endothelium were observed. Ultra-structural analysis showed loss of mitochondrial crista, and dilation of endoplasmic reticulum of Purkinje cells was observed. CONCLUSION: Although further studies are necessary to evaluate the time- and dose-dependent neuroprotective effects of P. fulgens, it may be a beneficial therapeutic agent for prevention of cerebellar damage following diffuse traumatic head injury.