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Öğe ANTINEOPLASTIC MULTI-DRUG CHEMOTHERAPY TO SENSITIZE TUMORS TRIGGERS MULTI-DRUG RESISTANCE AND INHIBITS EFFICIENCY OF MAINTENANCE TREATMENT IN GLIOBLASTOMA CELLS(Excli Journal Managing Office, 2022) Doganlar, Oguzhan; Doganlar, Zeynep Banu; Erdogan, Suat; Delen, EmreCombinations of the well-known antineoplastic agents 5-fluorouracil (5-Fu), cisplatin, and paclitaxel are employed to increase radiotherapy/immunotherapy efficacy against persistent and resistant tumors. However, data remains needed on the hormetic, chronic, and long-term side effects of these aggressive combination chemotherapies. Here we investigated cellular and molecular responses associated with these combined agents, and their potential to induce multi-drug resistance against the temozolomide (TMZ) and etoposide (EP) used in glioblastoma mainte-nance treatment. We analyzed resistance and survival signals in U87 MG cells using molecular probes, fluorescent staining, qRT-PCR, and immunoblot. Repeated treatment with combined 5-Fu, cisplatin, and paclitaxel induced cross-resistance against TMZ and EP. Resistant cells exhibited elevated gene/protein expression of MRP1/ABCC1, ABCC2, BRCP/ABCG2, and GST. Moreover, they managed oxidative stress, cell cycle, apopto-sis, and autophagy signaling to ensure survival. In these groups TMZ and etoposide efficiency dramatically re-duced. Our result suggests that combined high-dose treatments of classical antineoplastic agents to sensitize tu-mors may trigger multi-drug resistance and inhibit maintenance treatment. When deciding on antineoplastic com-bination therapy for persistent/resistant glioblastoma, we recommend analyzing the long-term hormetic and chronic effects on cross-resistance and multi-drug resistance in primary cell cultures from patients.Öğe Comparison of Lumbar Disc Herniation and Degeneration Relationship with the Sagittal Morphology of the Spine(Derman Medical Publ, 2015) Delen, Emre; Birgili, Bans; Akinci, Ahmet Tolgay; Karabulut, Derya; Turan, Fatma Nesrin; Kunduracilar, Nebile Muge; Memis, Muzafferin this study, the relationship between the lower intervertebral disc herniation and the degeneration of the spine with the sagittal morphological values were investigated. The data on this study is obtained retrospectively from patients who were operated in our center with the diagnosis of lower level lumbar disc herniation. A total of 117 patients, 75 female and 42 male are included. Patients are divided into two groups as with degeneration (Pfirmann stage III-IV-V) and without degeneration (Pfirmann stage I-II). Among 117 patients, 13 were in the with degeneration group, while 104 were in the without degeneration group. The mean age of the first group was 43.0 (+/- 11.2) years, while the second group had a mean age of 45.3 (+/- 11.4) years and there were not a statistically significant differences between them (P > 0.05). Mean lumbar lordosis angle was 23.30 (+/- 8.92) degree in the first group and 28.81 (+/- 9.17) degree in the without dejeneration group, thus a lower degree was observed in the group with degeneration (P = 0.050). Segmental lordosis angle was 24.69 (+/- 8.91) and 28.17 (+/- 5.75) degree respectively, in the group with degeneration the angle value was lower (P = 0.088). The sacral surface angle in the group with degeneration was 99.51 (+/- 5.36) degree and in the second group it was 100.56 (+/- 6.03) degree. Nevertheless the difference was not statistically significant (P = 0.509). The sacral kyphosis angle is determined as 170.13 (+/- 5.41) degree and 155.59 (+/- 45.96) degree in the two groups respectively and there was statistically significant difference between them (P = 0.059). For cases with lower level lumbar disc herniation there exists a significant relationship between the disc herniation and degeneration, therefore the lumbar lordosis and the segmental lordosis angles are lower in patients with degeneration.Öğe Demographic Characteristics of 796 Patients Operated for Lumbar Disc Herniation in Thrace Region, Turkey(Derman Medical Publ, 2016) Delen, Emre; Akinci, Ahmet Tolgay; Tutunculer, Banu; Memis, Muzaffer; Kunduracilar, Nebile Muge; Sahin, SonerAim: This study was designed was to determine the demographic characteristics of patients operated for lumbar disc herniation in Thrace Region, Turkey. Material and Method: We retrospectively searched our data to find out patients who had one sided, one level and only one spinal surgical intervention for herniated lumbar disc. Results: Among 796 cases, 336 (4256) were men and 460 (5831:) were women. The level of the pathology is determined as LI - 2 for 4 cases (0.56b), L2 - 3 for 15 cases (1.9%), L3 - 4 for 5 I cases (6.4%), L4 - 5 for 412 cases (51.8%) and as L5 - 51 on 314 cases (39.4%). While a total of 70 cases (8.9%) were identified on upper -levels ( LI - 2. L2 - 3, L3 - 4); 726 cases (91.1%) were found to be on lower -levels ( L4 - 5, L5 - Si). A mild positive correlation between the pathology level and physical activity intensity (P e 0.05, P = 0.103) has been demonstrated: as well as a strong negative correlation between pathology level and mean age (P < 0.05. P = -0.404). Discussion: The demographic characteristics are consistent with the literature. Physical activity intensity influence on lower -level herniations might have significance due to the large sample size. The strong negative correlation between pathology level and mean age suggests that the degeneration raises the frequency of upper -level herniations.Öğe Diagnostic Value of Gait Analysis in Patients with Lumbar Disc Herniation(Wiley, 2019) Delen, Emre; Ozturk, Gulnur; Karahan, Menekse; Ulucam, Enis; Ozturk, Levent[Abstract Not Available]Öğe The Dose Dependent Effects of Ruxolitinib on the Invasion and Tumorigenesis in Gliomas Cells via Inhibition of Interferon Gamma-Depended JAK/STAT Signaling Pathway(Korean Neurosurgical Soc, 2020) Delen, Emre; Doganlar, OguzhanObjective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-alpha/IFN-beta receptor/STAT and IFN-gamma/IFN-gamma receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-alpha and IFN-gamma while no change on the hypoxia-inducible factor-1 alpha and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-alpha and IFN-gamma.Öğe The Effect of Cerebral Oxygen Saturation Changes on Early Postoperative Neuropsychological Function in Patients Undergoing Cranial Surgery(Turkish Neurosurgical Soc, 2023) Hekimoglu Sahin, Sevtap; Copuroglu, Elif; Delen, Emre; Tutunculer, Banu; Sut, Necdet; Colak, Alkin; Sagiroglu, GonulAIM: To compare the incidence of postoperative neuropsychological dysfunction in patients managed with cerebral saturation monitoring versus traditional approaches.MATERIAL and METHODS: A hundred patients undergoing elective intracranial surgery were divided into two groups to receive intraoperative management via cerebral saturation monitoring (Group O) or the conventional approach (Group C). The postoperative neuropsychological function was evaluated by the antisaccadic eye movement test (ASEM) and the Mini-Mental State Examination (MMSE). These tests were performed preoperatively and postoperatively on the first, second, and fifth days. The time for the modified Aldrete score to reach 9 (MAS 9), adverse effects, and pain using a Visual Analog Scale (VAS) scores were recorded.RESULTS: Patient characteristics and surgery data were not statistically different. The MAS 9 of group O was significantly lower than that of group C (p<0.001). The MMSE at the postoperative 1, 2, and 5 days were significantly higher in Group O compared to Group C (p<0.001). ASEM was similar between groups. Group O was subdivided according to the type of surgery applied with diagnosis, and there were no statistically significant between-group differences in terms of areas under the curve for the cerebral regional oxygen saturation. There was no between-group difference regarding the mean arterial pressure at any time perioperatively. The heart rate at 80, 90, 100, and 110 min intraoperatively was significantly higher in group C than in Group O.CONCLUSION: Intraoperative cerebral oxygenation monitoring can reduce patient mortality and morbidity by allowing early postoperative neurological evaluation to detect potential neurocognitive deficits.Öğe Effects of Expression of Matrix Metalloproteinases and Discoidin Domain Receptors in Ligamentum Flavum Fibrosis in Patients with Degenerative Lumbar Canal Stenosis(Korean Soc Spine Surgery, 2023) Torun, Yusuf Mansur; Delen, Emre; Doganlar, Oguzhan; Doganlar, Zeynep Banu; Delen, Ozlem; Orakdogen, MetinStudy Design: This is a retrospective cohort study. Purpose: This study aimed to clarify the role of crosstalk between discoidin domain receptors (DDRs) and matrix metalloproteinases (MMPs) in the ligamentum flavum (LF) fibrosis obtained from patients with degenerative lumbar canal stenosis (DLCS). Overview of Literature: The DDRs, DDR1 and DDR2, are cell surface receptors and have an essential role in collagen fiber accumulation in several fibrotic diseases. MMPs are one of the critical factors in extracellular matrix remodeling and elastic fiber degradation in LF tissues. However, the crosstalk between DDRs and MMPs and the role of this molecular signal in LF fibrosis remain unclear. Methods: A total of 35 patients were divided into two groups in this study. Spinal surgery was performed in 23 of these patients with the diagnosis of DLCS. Twelve patients with lumbar disk herniation (LDH) were included in the control group. On axial T2-weighted magnetic resonance imaging, LF thickness was measured bilaterally at the level of the facet joint. Histology, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analyses were performed on LF tissue samples. LF tissues were stained with hematoxylin and eosin. In addition, the grade of fibrosis was histologically assessed using Masson trichrome triple staining. DDR1 and DDR2 Western blot analyses were performed. DDR1, DDR2, MMP2, MMP3, MMP9, and MMP13 expression levels were measured using qRT-PCR analysis. Results: The grade of fibrosis and LF thickness were significantly higher in the DLCS patients than in the LDH patients. DDR1 and DDR2 gene expression and protein levels in LF tissues are significantly greater in DLCS samples than in control samples, according to both qRT-PCR and Western blot analyses. In addition, we detected a significant expression of the MMP3, MMP9, and MMP13, which are known to have important roles in extracellular matrix remodeling in DLCS. Furthermore, we discovered a link between DDR protein levels and LF thickness, fibrosis, and MMP3/MMP9. Conclusions: Our results indicate that DDR1, DDR2, and MMP3 and MMP9 signals can be correlated with each other in LF tissues and be promoted LF fibrosis leading to spinal canal narrowing in patients with DLCS.Öğe Efficiacy of resveratrol and quercetin after experimental spinal cord injury(Turkish Assoc Trauma Emergency Surgery, 2016) Ciftci, Ulvi; Delen, Emre; Vural, Murat; Uysal, Onur; Cosan, Didem Turgut; Baydemir, Canan; Doganer, FulyaBACKGROUND: The aim of this study was to investigate the effect of natural antioxidants resveratrol and quercetin on oxidative stress and secondary cell damage in rats with acute spinal cord injury. METHODS: In this experimental study, 42 male Sprague-Dawley rats were used. Spinal cord injury was performed with clip compression method at level of T4-5. The study was conducted using 6 groups: control, trauma, trauma and solvent, trauma and resveratrol, trauma and quercetin, and trauma with combined resveratrol and quercetin. All rats were euthanized 48 hours after the procedure. Effects of resveratrol and quercetin on serum and tissue total antioxidant capacity and paraoxanase activity level were examined. RESULTS: Compared to trauma group, there was a significant increase in total antioxidant capacity and paraoxanase activity level in resveratrol, quercetin, and combined treatment groups. There was no significant difference between resveratrol and quercetin groups with regard to total antioxidant capacity and paraoxanase activity level. Total antioxidant capacity and paraoxanase activity level were significantly higher in solvent group than trauma group. In histopathological evaluation, there was a decrease in polymorphonuclear leukocyte infiltration in solvent, resveratrol, quercetin, and combined treatment groups. CONCLUSION: Biochemical and histological staining results of present study showed that resveratrol and quercetin may be effective in preventing secondary damage in spinal cord injury.Öğe The Expression Profiles of Angio-miRs in Glioblastomas Invasion Inhibited by Ruxolitinib(Galenos Publ House, 2022) Delen, Emre; Doganlar, OguzhanAim: MicroRNAs (miR) have an essential role on the regulated gene expression in the human genome. In recent years, a specific miR group was called to angio-miRs due to their role in the angiogenesis, and recent study showed that they involved in the pathogenesis of gliomas. In this study, we investigated the changes in the expression profiles of angio-miRs in glioblastoma cells and identified relationship between these genes and invasion and tumor growth. Materials and Methods: In this study, glioblastoma tumor spheroids were obtained using the human glioblastoma cell line U-87 MG. 50 nM, 100 nM and 200 nM ruxolitinib were applied to tumor spheroids for 48 hours by using Matrigell method. Tumor volume and invasion formation relative olio tumor growth and relative olio invasion area were measured in glioblastoma tumor spheroids after 48 hours of treatment. At the same time, quantitative real-time polymerase chain reaction (qRT-PZR) analysis was performed and miR expression profiles were determined. The most important (importance features) miRNAs selected along with the heatmap and volcano plot analyzes were used to display the pattern of the differentially expressed miRs using normalized miR expression profiles. Results: When the effect of 50 nM, 100 nM and 200 nM ruxolitinib administration to tumor spheroids on tumor volume and invasion was evaluated, a significant difference was found at each dose applied. However, at the dose of 200 nM ruxolitinib, it was observed that the inhibitory effect of tumor invasion was the highest. When miR expression profiles obtained by qRT-PZR test with 200 nM ruxolitinib adminisration were evaluated, it was determined that the expression profiles of 10 miRs increased and the expression profiles of 4 miRs decreased. Conclusion: In conclusion, angio-miR expression profiles are important because they enable us to better understand the prognostic process of gliomas. Because of their multiple silencing properties, they may contribute to the clinic with further studies in terms of their use as new therapeutic targets and prognostic biomarkers for glioblastoma.Öğe Hemangiopericytoma at the Craniovertebral Junction: A Case Report(Kare Publ, 2019) Delen, Emre; Akinci, Ahmet Tolgay; Turkkan, Gorkem; Yalta, Tulin Deniz; Simsek, OsmanIntradural extra medullary hemangiopericytomas (HPCs) are extremely rare and a hemangiopericytoma located at the craniovertebral junction might present radiologic features similar to those of meningioma or schwannoma.To the best of our knowledge, this report is among a few reported cases of HPC at the craniovertebral junction. Although they are very rare, HPCs should kept in mind in the differential diagnosis of the intradural extramedullary lesion due to differences in treatment such as adjuvant radiotherapy.Öğe Inhibition of the Invasion of Human Glioblastoma U87 Cell Line by Ruxolitinib: A Molecular Player of miR-17 and miR-20a Regulating JAK/STAT Pathway(Turkish Neurosurgical Soc, 2020) Delen, Emre; Doganlar, Oguzhan; Doganlar, Zeynep Banu; Delen, OzlemAIM: To determine the interaction between ruxolitinib, JAK/STAT signalling, and two angio-microRNAs (miRs) to expose potential target molecules in the inhibition of glioblastoma invasion. MATERIAL and METHODS: The invasion properties of glioblastoma were analyzed using a cancer cell spheroid invasion assay. Following treatment of 195 nM ruxolitinib, the relative expression levels of miR-17 and miR-20a and genes of IL-6/JAK/STAT3 receptor signaling belonging to the JAK/STAT pathway were measured by qRT-PCR in treated and untreated three-dimensional tumor spheres of U87 cells. RESULTS: Our results indicated that a therapeutic dose of ruxolitinib (195 nM) significantly increased miR-17 and miR-20a expression. Ruxolitinib treatment resulted in the production of IL-6 and active formation of IL-6 receptor complex for the subsequent activation of the IL-6R/JAK2/STAT3 axis. However, ruxolitinib treatment significantly decreased the expression of JAK2 and PI3K. Pearson correlation analyses revealed a strong negative correlation of miR-17 with JAK2, STAT3, and PI3K expressions, and also miR-20a has a negative correlation with expression levels of JAK2 and PI3K. The only positive correlation was found to be between miR-20a and IL-6, gp130 expressions. CONCLUSION: The specific JAK2 inhibitor ruxolitinib plays an important role in glioblastoma angiogenesis biology via inhibiting IL-6 receptor-dependent JAK/STAT signaling. Additionally, both miR-17a-3p and miR-20a overexpression induced by ruxolitinib treatment may be playing a major role in downregulated JAK2, STAT3, and PI3K proteins. Our results suggest that miR-17-3p and miR-20a-5p may serve as new therapeutic targets for the treatment of glioblastoma.Öğe Lomber spinal stenoz hastalarında propriosepsiyon, postür ve yürüme analizi(Trakya Üniversitesi Sağlık Bilimleri Enstitüsü, 2023) Delen, Emre; Öztürk, LeventTez çalışmamızın amacı, yürüme analizinin lomber spinal stenoz hastalığı için tanı koyma amacıyla kullanılabilirliğini araştırmaktı.Bu çalışmaya 17 LSS ile 14 LDH hastası olmak üzere toplam 33 hasta ve 9 sağlıklı gönüllü dahil edildi. Ağrı skorlaması için vizüel anlog skalası kullanıldı. Ağrının fonksiyonel sakatlık üzerine etkisini belirlemek için de oswetri engellilik indeksi kullanıldı. Hastaların klinik değerlendirmelerinde propriosepsiyon duyusunun muayenesi de eklendi. Radyolojik değerlendirme de yer alan parametreler ligamentum flavum kalınlığı, omurilik kanalının kapladığı alan, intervertebral disk ve faset eklem dejenerasyon skorlaması idi. Yürüme ve denge analizleri tüm katılımcılara yapıldı. Gruplar arasında anlamlı fark olup olmadığını belirlemek için istatistiksel değerlendirme yapıldı, p<0,05 istatistiksel olarak anlamlı kabul edildi.Gruplar arasında VAS ve ODI indeksinde istatistiksel olarak anlamlı fark yoktu. LSS ve LDH grupları arasında radyolojik bulgulardan olan LF kalınlığı ve faset eklem dejenerasyonu bakımından fark tespit edildi. LSS hastalarında tespit edilen propriosepsiyon duyusunda bozulma ise yine istatiksel olarak anlamlı idi (p<0,05). Sağlıklı gönüllülerle karşılaştırıldığında, LDH'li hastalar düşük yürüme hızına sahipti. Ancak yürüyüş ve postüral analizde LSS hastaları ile diğer gruplar arasında istatistiksel olarak anlamlı bir fark yoktur.Sonuç olarak, LSS'nin propriyosepsiyon duyusu üzerinde olumsuz etkileri olduğu ortaya kondu. Yürüyüş analizinden elde edilen bulgular, yürüme analizinin LSS hastalığının teşhisinden ziyade tedavinin etkinliğini veya hastalığın ilerlemesini belirlemek için kullanılabilir olduğu düşündürmüştür.Öğe Osteoporotik Vertebra Kırıklarında Enstrümantasyon - Endikasyonları ve Stabilizasyon Sistemini Güçlendirme Önerileri(2020) Delen, Emre; Kılınçer, CumhurOsteoporoz omurganın kemik kalitesini bozan ve kırıklara yol açabilen metabolik bir hastalıktır. Artan yaşlı nüfus ile berabergiderek daha sık görülmeye başlamıştır. Çoğu osteoporotik vertebra kırığı spontan iyileşme gösterse de bazen ilerleyici çökme,kifotik deformite, spinal kanal ya da intervertebral foramen daralmasına bağlı nöral basılar görülebilir. Cerrahi tedavi seçeneklerivertebroplasti gibi minival invaziv girişimler ve bazı olgularda da enstrümanlı stabilizasyondur. Deformite veya nöral bası gelişmemişçoğu olguda perkütan yolla korpusa sement desteği (vertebroplasti/kifoplasti) yeterli iken bazı olgularda ise dekompresyon veenstrümanlı stabilizasyon gerekli olur. Cerrahi endikasyon ve teknik seçimi sırasında göz önüne alınması gereken çok sayıda etkenvardır. Hasta yaşı, cinsiyeti, komorbiditeleri, kilosu, vücut yapısı, osteoporozun şiddeti, kırık lokalizasyonu, çökme derecesi ve açısı,omurganın sagittal ve koronal planlardaki dengesi, kanal ve foramen darlığı, ağrı şiddeti, nörolojik defisit, hastanın aktivite derecesive cerrahiden beklentisi, cerrahın deneyimi ve olanakları bunların başlıcalarıdır. Osteoporozlu hastaların ileri yaş nedeniyle sahipolabilecekleri morbiditeler, kemiğin mekanik yetersizliği ve füzyon güçlüğü gibi nedenlerle enstrümanlı cerrahinin başarısızlık riskiyüksektir. Bu nedenle ancak mutlak endikasyona sahip hastalarda enstrümantasyon düşünülmelidir. Enstrümantasyon sistemininyetmezliğini önlemek için uygulanabilecek birçok önlem vardır ve bazen bu önlemlerin tümünü uygulamak gerekir. Bu önlemler;osteoporoza yönelik farmakolojik tedavi, uygulanacak fiksasyonun seviyesini uzatarak yükü dağıtmak, sublaminar tel ya da kancakullanımı, vida uygulama tekniğini optimize etmek, vida tasarımındaki değişiklikler, sement destekli vida uygulamak ve ön kolonadestek yerleştirmektir. İyi bir kemik greftleme ile füzyon hızlandırılmaya çalışılmalıdır. Tüm bu önlemlere rağmen osteoporozlu birhastadaki spinal enstrümantasyonun yetmezliğe uğrayabileceği ve revizyon ameliyat(lar)ı gerekebileceği akılda tutulmalıdır.Öğe Our Surgical Treatment Results in Adult Tethered Cord Syndrome: An Experience of 9 Cases(2020) Delen, Emre; Akıncı, Ahmet Tolgay; Şimşek, OsmanObjective: The aim of this study was to present the results of surgical treatment along with demographic and clinical features in cases with tethered spinal cord syndrome seen in adulthood. Method: We retrospectively evaluated 73 cases who underwent tethered cord release operations with the diagnosis of tethered cord syndrome between 2004 and 2015 in our clinic. The mean follow-up period was 21.7 (3-63) months. Adult cases consisted of 5 female and 4 male patients aged between 18-55 years. Clinical and radiological characteristics of the patients and follow-up data related to the surgical treatment were recorded. Pain and neurological findings were graded using the scoring system proposed by Klekamp et al. Results: Nine patients had complaints of back and/or leg pain, two patients had gait ataxia and three patients had bladder dysfunction. Only one patient had a loss of muscle strength. There were cutaneous stigmata in a total of three patients: These were two dermal sinus tracts, one thoracic dermatomal hypertrichosis. Four patients had scoliosis, 4 had syringomyelia and 3 had split cord malformation. The level of conus medullaris was L3 in one patient, L4 in 3 patients, L5 in 2 patients, and S1 in one patient. All patients underwent surgical detethering. Most of the patients reported a decrease in their pain levels. However, sensory dysfunction and sphincter problems remained unresolved. Conclusion: The main difference between adult cases compared to pediatric cases was related to symptomatology. The pain was the cardinal symptom in almost all cases. While the surgery was effective to diminish pain, it was not effective in resolution of neurological deficits.Öğe Postoperative Spinal Epidural Haematoma Causing Cauda Equina Syndrome: Case Report(Derman Medical Publ, 2013) Delen, Emre; Birgili, Baris; Akinci, Ahmet Tolgay; Yavuz, SelcukCauda equina syndrome is a neurological disorder defined by urinary and/or anal sphincter dysfunction, bilateral sciatica and bilateral motor and sensory deficits. Regarding the etiology, lumbar disc disease, spinal stenosis, tumors, haematomas, fractures, infectious diseases and ankylosing spondylitis are pathologies causing this syndrome. Spinal epidural haematomas are common amongst complications after spinal surgery. However the majority of these cases are asymptomatic, thus having little clinical importance. Symptomatic postoperative spinal epidural haematomas is a serious complication, and in order to prevent permanent neurologic deficit it requires urgent surgical intervention. This article aims to present the case of a patient with a spinal epidural haematoma after spinal stenosis surgery, causing cauda equina syndrome.Öğe The Role of JAK-STAT Signaling Activation in Hypertrophied Ligamentum Flavum(Elsevier Science Inc, 2020) Delen, Emre; Daganlar, Oguzhan; Delen, Ozlem; Doganlar, Zeynep Banu; Kilincer, CumhurBACKGROUND: Although previous studies have reported the expression of JAK1, STAT3, and phosphorylated STAT3 in hypertrophied ligamentum flavum (LF), the role of the Janus kinaseesignal transducer and activator of transcription (JAK/STAT) signaling pathway in hypertrophied LF has not been fully elucidated. The aim of this study was to identify the important JAK/STAT gene expression patterns of the 3 main receptors involved in this pathway: interferon (IFN)-gamma receptor (IFN-gamma R), IFN-alpha receptor (IFNAR), and interleukin (IL)-6 receptor (IL-6R). METHODS: The human LF specimens were obtained from 28 patients who underwent lumbar spine surgery for either degenerative lumbar canal stenosis (DLCS) (n [ 28) or lumbar disc herniation (LDH) (n [ 20). In this design, patients with LDH served as the control group. The degree of fibrosis was demonstrated by Masson's trichrome staining. The location and expression profiling of the JAK/ STAT pathway were analyzed by quantitative real-time polymerase chain reaction and Western blotting. The thickness of the LF was measured with axial T1-weighted magnetic resonance imaging. RESULTS: The most severe fibrotic changes were on the dorsal side of the LF. IL-6 and IFN-I expression levels were significantly increased on the dorsal side of the LF. While expression levels of IL-6R and IFNAR on the dural and dorsal side were significantly higher in the DLCS samples, IFN-gamma R and endothelial epidermal growth factor receptor in LF samples showed a significant increase only on the dorsal side. JAK/STAT genes were significantly expressed, especially on the dorsal side. CONCLUSIONS: Our data suggest that IFNAR- and IL-6R-dependent JAK/STAT signaling pathways may be significant targets in drug development strategies for the treatment of LF hypertrophy.Öğe The role of melatonin in angio-miR-associated inhibition of tumorigenesis and invasion in human glioblastoma tumour spheroids(Churchill Livingstone, 2021) Doganlar, Oguzhan; Doganlar, Zeynep Banu; Delen, Emre; Dogan, AytenMicro-RNA (miRNA)-based regulation of hypoxia, angiogenesis and tumour growth provides promising targets for effective therapy in malignant glioblastoma multiforme (GBM). Accumulating evidence suggests a potential role of melatonin in miRNA expression in cancer cells. Despite these findings, the melatonin-miRNA interaction in GBM and the effect of this interaction on GBM tumour development and invasion are not clearly understood. The aim of the present study was to evaluate the effects of melatonin on human GBM tumour spheroid tumorigenesis and invasion in vitro, and to analyse the interaction between 36 angio-miRNAs and the HIF1/VEGF/ MMP9 axis, which is known to be associated with the antitumour effect of melatonin. We found that melatonin is able to selectively induce cell death in single-layer U87-MG cells (a GBM cell line) in a dose- and time-dependent manner, as characterized by MTT assay. The use of tumour spheroids and a Matrigel invasion assay revealed that melatonin impairs tumorigenesis, and it significantly reduced both the tumour spheroid area and invasion rate, especially at the 0.5 mM and 1 mM concentrations. This inhibition was accompanied by strong reductions in hypoxia-inducible factor 1-alpha (HIF1-alpha) and vascular endothelial growth factor (VEGF) gene expression and protein levels in GBM tumour spheroids. In addition, melatonin significantly reduced the relative gene expression and protein levels of matrix metalloproteinase-9 (MMP-9). This study revealed that six differentially expressed angio-miRs (miR-15b, miR-18a-5p, miR-23a-3p, miR-92a-3p, miR-130a-5p, miR-200b-3p) may play important roles in GBM tumorigenesis and invasion, and all respond to melatonin therapy. Our results suggest that melatonin inhibits tumorigenesis and invasion of human GBM tumour spheroids, possibly by suppressing HIF1 alpha/VEGF/MMP9 signalling via regulation of angio-miRNAs.Öğe Spontaneous subarachnoid haemorrhage incidence among hospitalised patients in Edirne, Turkey(Springer Wien, 2019) Simsek, Osman; Akinci, Ahmet Tolgay; Delen, Emre; Sut, NecdetBackground To the best of our knowledge, no data has been published about the spontaneous subarachnoid haemorrhage (sSAH) incidence in Turkey. We aimed to report the estimation of sSAH incidence in Edirne Province, in Turkey for the first time, using the data acquired from a single medical centre which has the biggest and the most comprehensive emergency department in Edirne and to where a great majority of patients are referred. Methods We investigated all the accessible sSAH patients' data obtained from computer-based automation systems and all the written documents in the neurosurgery and the emergency departments. Patients included in the study were diagnosed with sSAH between the dates of January 2007 and December 2011 and were resident in Edirne. We used this data to calculate the crude and age-adjusted incidence rates of sSAH for every decade. Results One hundred fifty-four patients have been diagnosed with sSAH during a 5-year period. Among them, 72 were men (47.8%) and 82 (53.2%) were women. The mean age of the patients was 60.8 years and age range was 23-85 years. The overall annual adjusted incidence rate for sSAH was 10.3 per 100,000 person-years (95% confidence interval = 10.2-10.3). Annual adjusted incidence rate was 10 per 100,000 person-years (95% confidence interval = 10-10.1) for men. For women, it was 10.4 per 100,000 person-years (95% confidence interval = 10.4-10.5). For both sexes, after the 6th decade, the annual incidence rate of sSAH was higher than 10 per 100,000, reaching over 20 per 100,000 person-years after the 7th decade. The overall crude incidence rate for sSAH was 10.3 per 100,000 person-years. For men, the crude incidence rate was 9.4 per 100,000 person-years and for women, it was 11.2 per 100,000 person-years. Conclusions This study showing the first sSAH incidence estimation in Edirne might also be accepted as an estimation of overall epidemiological sSAH aspect in Turkey. Future investigations should be realised in different parts of Turkey to enlighten the epidemiological state of affairs and the course of sSAH in Turkey.Öğe Therapeutic efficacy of tadalafil and eriythropoietin in experimental spinal cord injury(Turkish Assoc Trauma Emergency Surgery, 2016) Kokoglu, Cagri; Delen, Emre; Arslantas, Ali; Arslantas, Didem; Kokoglu, Burcu; Ozbek, Zuhtu; Uslu, SemaBACKGROUND: This experimental study was an investigation of the efficacy of erythropoietin and tadalafil in rats with induced spinal cord injury (SCI). METHODS: Thirty-five Sprague Dawley rats were distributed into 5 groups. First group was used for normal biochemical values. Spinal cord injury was induced in 4 remaining groups with clip compression technique after laminectomy process to T10 vertebra. Second group was designated solvent group and received 1 cc physiological serum after injury. Third group was medicated with intraperitoneal 2000 u/kg single dose erythropoietin after injury. Orogastric 2 mg/kg single dose tadalafil was administered to fourth group after injury. Fifth group did not receive any treatment and was used for biochemical values with injury. All subjects were sacrificed 48 hours after application. Malondialdehyde (MDA) and total antioxidant capacity (TAOC) values were evaluated using blood and tissue samples. RESULTS: Lowest serum and tissue MDA values were found in group with erythropoietin intake. While highest serum TAOC values of all groups were seen in tadalafil group, highest tissue TAOC values were observed in group given erythropoietin. CONCLUSION: It was concluded that by decreasing oxidative stress, tadalafil and erythropoietin can inhibit secondary damage in SCI.