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Öğe A Study of the Effects of Metformin, a Biguanide Derivative, on Annulus Fibrosus and Nucleus Pulposus Cells(Turkish Neurosurgical Soc, 2020) Kaya, Yasin Emre; Karaarslan, Numan; Yılmaz, İbrahim; Şirin, Duygu Yaşar; Akalan, Hande; Özbek, HanefiAIM: To investigate the effects of metformin, a drug used widely for the treatment of type 2 diabetes mellitus, on human primary cell cultures prepared from uninjured segment of disc material intervertebral disk tissues. MATERIAL and METHODS: Primary cell cultures were prepared using the tissues of six patients (three males and three females) who had undergone lumbar microdiscectomy and sequestrectomy. Untreated samples served as the control group, and metformintreated samples served as the experimental group. All the samples were evaluated using an inverted light microscope, acridine orange/propidium iodide staining (AO/PI), and a fluorescence microscope. The cytostatic and cytotoxic effects of metformin, which was administered to the samples using a commercial MTT assay kit, were also evaluated. The data obtained were statistically assessed, and the alpha significance value was accepted as less than 0.05. In addition, for the groups' changes in the expressions of chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1 beta (IL-1 beta) matrix metalloproteinase 7 (MMP-7), and matrix metalloproteinase 19 (MMP-19), genes related to the extracellular matrix synthesis and degradation were determined using gene-specific TaqMan Gene Expression Assays. RESULTS: The administration of the drug adversely affected nucleus pulposus (NP)/annulus fibrosus (AF) cells and extracellular matrix-like structures. This was statistically significant (p<0.05). CONCLUSION: Clinicians should not disregard the adverse effects of metformin, which is used widely in clinical practice, on the components of intervertebral disk tissues.Öğe A study on legal and medical dimensions of radiation exposure in neurosurgery clinics in Turkish practice(Scientific Scholar, 2020) Karaarslan, Abdulkadir; Kasim, F.B.H.; Karaarslan, Numan; Ateş, ÖzkanBackground: In the present study, the first aim was to address the detrimental effects of the fluoroscopy procedure performed by physicians and other health-care professionals in neurosurgery clinics, then to examine precautions that should be taken to avoid harmful effects of radiation and radioactive substances during this process. The second aim was to handle the rights provided for health-care professionals exposed to the radiation in workplaces. Methods: A standardized questionnaire was used for a multicenter survey. Volunteer, intellectual, and cooperative participants (n = 41) were randomly chosen. The survey was prepared considering reports drawn up by the International Atomic Energy Agency. The questions concerning safe and effective fluoroscopy procedure were asked to the participants. The answers received were statistically evaluated. The alpha significance value was accepted as 0.05. Results: Two neurosurgeons only knew the legal rights that they might possess due to the exposure to the radiation or radioactive substances. Conclusion: The survey conducted among the health-care professionals revealed the insufficiency of knowledge about the protection from the radiation exposure or radioactive substances in workplaces. Furthermore, both health-care professionals working in radiology clinics, and those in neurosurgery and other clinics who are likely to be exposed to the radiation or radioactive substances have the rights afforded by the law. ©2020 Published by Scientific Scholar on behalf of Surgical Neurology InternationalÖğe A study on side effects of antibiotics used in the treatment of patients with head trauma and legal responsibility of clinicians in terms of the right to health(2019) Karaarslan, Abdulkadir; Şimşek, Abdullah Talha; Doğan, Mustafa; Potoglu, Bilgehan; Yılmaz, İbrahim; Karaarslan, NumanAim: Patients with head trauma are routinely, and commonly treated with prophylactic antibiotics, which may also be used for thetreatment of infection that may be developed during hospital stay. The relevant antibiotic may, however, some side effects andadverse event. The present study aimed to investigate whether the side effects and adverse events of the prophylactic antibioticswere considered as a complication or medical negligence.Material and Methods: Descriptive statistics were used for the evaluation of the data.Results: No studies were found in the literature. Ceftriaxone, ampicillin-sulbactam, and cefazolin sodium were preferred forantibiotherapy. Meropenem or vancomycin was solely administered to patients when observed active pathogens in cultureantibiogram.Clinicians should be cautioned the potential side effects and adverse events of some drugs frequently used in clinics.Conclusion: Otherwise, they may legally be held liable for medical negligence.Öğe A Study on the Effects of Direct Factor Xa Inhibitors and Direct Thrombin Inhibitors on Human Primary Chondrocyte Cultures(2019) Kaya, Yasin Emre; Akalan, Hande; Yılmaz, İbrahim; Karaarslan, Numan; Şirin, Duygu Yaşar; Özbek, Hanefi; Ateş, ÖzkanAim:This study investigates the effects of two direct factor Xa inhibitors, apixaban and rivaroxaban, and a direct thrombin inhibitor, dabigatran, on human primary chondrocytecultures.Materials and Methods:Monolayer cultured chondrocytes were prepared. Cell cultures were treated with dabigatran, apixaban, and rivaroxaban. Cultures without drug treatments served as the control group. Using an inverted light microscope, the cell surface morphology was examined. Cell viability and the toxicity of drugs were evaluated using a commercial assay kit, and the results were confirmed using two nucleic acid binding dyes, acridine orange and propidium iodide. The expressions of cartilage oligomeric protein, matrix metalloproteinase-7, and matrix metalloproteinase-19 were assessed using the real-time polymerase chain reaction analysis. All the analyses were performed within 21 days. The data obtained were statistically evaluated.Results:The administration of the three drugs changed the cell viability, proliferation, and expressions of cartilage oligomeric protein, matrix metalloproteinase-7, and matrix metalloproteinase-19. The results were statistically significant (P<0.05).Conclusion:Results obtained from in vitro studies may not provide accurate and reliable insight for clinical practices. However, clinicians should know that drugs used for the prevention or treatment of diseases may suppress chondrocyte proliferation and damage the extracellular matrix formation.Öğe Are Intervertebral Disc Tissue Cells Damaged When Attempting to Prevent Thrombus Formation Using Dabigatran, A New Oral Anticoagulant?(Turkish Neurosurgical Soc, 2019) Kaplan, Necati; Karaarslan, Numan; Yılmaz, İbrahim; Yasar Şirin, Duygu; Akgün, Feride Sinem; Çalışkan, Tezcan; Özbek, HanefiAIM: To investigate the effect of dabigatran, a new oral anticoagulant, on human primary cell cultures isolated from intact intervertebral disc tissue. MATERIAL and METHODS: Cell cultures were prepared from tissues obtained from six cases who had undergone surgery due to spinal trauma. Dabigatran, an active pharmacological agent, was applied to intact annulus fibrosus (AF)/nucleus pulposus (NP) primary cell cultures from the study group. After performing cell viability, toxicity, and proliferation tests on all cultures in the control and study groups, the surface morphologies of the samples were evaluated. Subsequently, chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase (MMP)-13 and -19 expressions were measured via a real-time polymerase chain reaction (RT-PCR). Data were analyzed statistically. RESULTS: In the proliferation assays performed on the 20th day of the study, cells in the dabigatran-supplemented group were reported to have lost 46.37% more viability than those in the control group. Expressions of all genes examined except MMP-13 were evaluated in the control group by time, but in contrast to the control group results, COMP and MMP-19 gene expressions decreased in the dabigatran-treated group. No CHAD or MMP-13 expression was noted in these cultures. CONCLUSION: The potential for a systemically applied drug to accumulate in tissue and negatively affect surrounding tissues and microstructures must be emphasized.Öğe Are radio-contrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells?(Wiley, 2019) Karaarslan, Numan; Yılmaz, İbrahim; Özbek, Hanefi; Şirin, Duygu Yaşar; Kaplan, Necati; Çalışkan, Tezcan; Ateş, ÖzkanIn the literature, there have been no studies showing clear results on how radio-contrast pharmaceuticals would affect intact disc tissue cells. In this context, it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently used in the discography, on intact lumbar disc tissue in pharmaco-molecular and histopathological level. Primary cell cultures were prepared from the healthy disc tissue of the patients operated in the neurosurgery clinic. Except for the control group, the cultures were incubated with the indicated radio-contrast agents. Cell viability, toxicity and proliferation indices were tested at specific time intervals. The cell viability was quantitatively analysed. It was also visually rechecked under a fluorescence microscope with acridine orange/propidium iodide staining. Simultaneously, cell surface morphology was analysed with an inverted light microscope, while haematoxylin and eosin (H&E) staining methodology was used in the histopathological evaluations. The obtained data were evaluated statistically. Unlike the literature, iopromide or gadoxetic acid did not have any adverse effects on the cell viability, proliferation and toxicity (P < 0.05). Although this study reveals that radio-contrast pharmaceuticals used in the discography, often used in neurosurgical practice, can be safely used, it should be remembered that this study was performed in an in vitro environment.Öğe Are Specific Gene Expressions of Extracellular Matrix and Nucleus Pulposus Affected by Primary Cell Cultures Prepared from Intact or Degenerative Intervertebral Disc Tissues?(Turkish Neurosurgical Soc, 2019) Karaarslan, Numan; Yılmaz, İbrahim; Özbek, Hanefi; Yasar Şirin, Duygu; Kaplan, Necati; Akyuva, Yener; Ateş, ÖzkanAIM: To determine the gene expression patterns of nucleus pulposus (NP) in cell cultures obtained from degenerated or intact tissues. MATERIAL and METHODS: Whereas 12 of the cases were diagnosed with lumbar disc herniation and had undergone lumbar microdiscectomy, 12 cases had undergone traumatic intervertebral discectomy and corpectomy, along with discectomy after spinal trauma. NP-specific markers and gene expressions of the reagents of the extracellular matrix in the experimental setup were tested at the 0th, 24th, and 48th hours by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Visual evaluations were simultaneously made in all samples using invert and fluorescence microscopy. Vitality and proliferation analyses were evaluated by UV spectrophotometer. As a method of statistical evaluation, Spearman was used for categorical variants, and the Pearson correlation was used for variants with numerical and plain distribution. RESULTS: No association was found either between the tissue type and times (r=0.000; p=1.000) or between the region that the tissue was obtained from and hypoxia transcription factor-1 alpha (HIF-1 alpha) gene expression (r=0.098; p=0.245). There was no correlation between cell proliferation and chondroadherin (CHAD) expression or between type II collagen (COL2A1) and CHAD gene expressions. It was found that CHAD and HIF-1 alpha gene expressions and HIF-1 alpha and COL2A1 gene expressions affected cell proliferation. CONCLUSION: Cell culture setups are of paramount importance because they may influence the pattern of changes in the gene expressions of the cells used in these setups.Öğe Can transcription factors in the intervertebral disc of lopinavir/ritonavir prevent degeneration in the nucleus pulposus by mediating the regulation of inflammation through signaling pathways?(Verduci Editore s.r.l, 2022) Yılmaz, İbrahim; Akalan, Hande; Karaarslan, Numan; Şirin, Duygu Yaşar; Kaplan, Nuray; Doğan, Mustafa; Ateş, OğuzOBJECTIVE: This study was conducted to examine whether lopinavir/ritonavir (Lop/r), an HIV protease inhibitor, can improve disc physiology and slow down intervertebral disc (IVD) degeneration through in vitro experimental methods, as well as whether it can suppress inflammation with interleukin-1 beta (IL-1?) and sex-determining region Y (SRY) protein-related high-mobility group box genes-9 (SOX9) through hypoxia-inducible factor 1-alpha (HIF-1?) and the nuclear factor kappa B (NF-?B) signaling pathway. The aim was to investigate whether Lop/r application is toxic to IVD cells and the microenvironment simultaneously. PATIENTS AND METHODS: Human primary cell cultures were prepared using herniated IVD tissues obtained from patients with lumbar disc hernia who were unresponsive to conservative and medical treatment, and thereby, were operated on. The untreated culture samples served as control group, and the samples treated with Lop/r served as study group. Microscopic evaluations were performed simultaneously using fluorescent and supravital dyes in all groups. In addition to cell viability, toxicity, and proliferation analysis through a commercial kit, IL-1?, SOX9, HIF-1?, and NF-?B protein expressions were evaluated using Western blotting. In the statistical comparison of the obtained data, an alpha value less than 0.05 was considered significant. RESULTS: Cell proliferation decreased in the Lop/r group, but no cell death was observed (p < 0.05). Moreover, at the end of 72 hours after Lop/r application, IL-1? and NF-kB protein expressions decreased by 40% and 52%, respectively, while HIF-1? and SOX9 protein expressions increased by 4% and 59%, respectively (p < 0.05). CONCLUSIONS: Although these data were obtained from an in vitro experimental study, it is believed that these findings could make significant contributions to the pharmaco-regenerative treatment modalities of IVD degeneration. Lop/r suppresses the IL-1? and NF-?B and induces SOX9 and HIF-1?, since these signaling pathways may be related to human IVD degeneration. © 2022 Verduci Editore s.r.l. All rights reserved.Öğe Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?(J Infection Developing Countries, 2022) Ateş, Özkan; Yılmaz, İbrahim; Karaarslan, Numan; Ersöz, Emel; Kasim, Fatma Bahar Hacioglu; Doğan, Mustafa; Özbek, HanefiThe objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.Öğe Comparison of the Surgical Results for Foramen Magnum Decompression with and without Duraplasty in Chiari Malformation Type 1(Turkish Neurosurgical Soc, 2015) Gürbüz, Mehmet Sabri; Karaarslan, Numan; Çalışkan, Tezcan; Ünal, Emre; Berkman, Mehmet ZaferAIM: The surgical results for foramen magnum decompression (FMD) with and without duraplasty in Chiari Malformation type 1 (CM-1) were compared retrospectively. MATERIAL and METHODS: Thirty-nine cases of CM-1 with and without syringomyelia (SM) were included.There were 18 patients in the non-duraplasty and 21 in the duraplasty group. Syringomyelia, tonsillar herniation (TH), preoperative symptom duration, and postoperative SM size were compared. RESULTS: No significant difference was found between improvement in the duraplasty group (81%) and the non-duraplasty group (61.1%). In cases whose symptom duration was 0-36 months, improvement in the duraplasty group (93%) was significantly better than in the non-duraplasty group (50%) (p<0.01). The rate of syrinx regression was 92.3% in the duraplasty group and 12.5% in the non-duraplasty group (p<0.05). In cases with SM, the improvement was 21.4% in the non-duraplasty group compared to 78.6% in the duraplasty group (p=0.056). In cases with TH greater than 10 mm, the improvement was 66.7% in the non-duraplasty group, whereas all six cases (100%) in the duraplasty group had improved. CONCLUSION: In SM associated cases, cases with TH greater than 10 mm, and whose symptom duration is less than 36 months, duraplasty is a more reliable choice despite a slightly higher rate of complications.Öğe Complications of 200 cervical anterior surgery cases and the management of these complications in light of the literature(2019) Kaplan, Necati; Hacıoğlu Kasım, Fatma Bahar; Özger, Özkan; Karaarslan, NumanAim: The aim of this retrospective study was to evaluate the possible complications and the complication management of cervicalanterior discectomies and fusions in light of the literature.Materials and Methods: The study population consisted of patients who presented to the clinic with neck pain and/or arm pain, lossof strength, and sensory disturbances who were operated on after a lack of response to conservative/medical treatment. This studyincluded 200 cervical discopathy and/or cervical spondylosis cases. The literature review was performed according to the PreferredReporting Items for Systematic Reviews and Meta?analyses guidelines without language or country restrictions.Results: The most common complication was dysphagia. The complications also included dural tears, cerebrospinal fluid leakage,graft extrusions, neurological deterioration, postoperative hematomas, and recurrent laryngeal nerve injuries. These were found tobe consistent with the literature.Conclusion: In order to minimize the incidence of complications, the preoperative clinical examinations and radiological imaging ofeach patient should be examined carefully, and the appropriate surgical planning should be performed. It is also important to complywith the rules of asepsis and antisepsis, make sure the surgical time is as short as possible, and perform a dissection based on thepatient’s anatomy with the appropriate surgical equipment. In addition, it is important to wash the surgical area frequently, drain thesystem at the end of the operation, close the tissues in accordance with anatomical integrity, and perform close clinical follow-ups.Öğe CT-guided stereotactic microsurgical resection of cerebral mass lesions(Logos Medical Publishing, 2018) Erşahin, M.; Gürbüz, Mehmet Sabri; Karaarslan, Numan; Gezen, A.F.Stereotactic microsurgical techniques allow for the precise localization and resection of lesions in critical areas of cortex or deep within the brain and minimize operative exposure to the surrounding tissues. This study presents our experience with CT-guided stereotactic microsurgical resection of cerebral lesions using the Leksell frame. A total of 42 patients undergoing computerized tomography guided stereotactic microsurgical resection of cerebral lesions between June 2000 and September 2017 were included in the study. Clinical, radiological, histological and follow-up data were retrospectively evaluated. Pre-and post-operative general status of the patients was assessed by Karnofsky Performance Scale (KPS). Except for the subjects with high-grade gliomas, complete resection could be accomplished in all cases. Of the 24 cases with convulsions, a complete cessation of epileptic attacks was attained in 20 and a decrease in their number and frequency was noted in 4 cases. Overall, 20 patients had no change in the KPS score, while 28 patients had increased and two had decreased KPS scores. No postoperative mortality occurred. CT-guided stereotactic microsurgical craniotomy is a safe, reliable and effective technique, which is particularly useful for the surgical treatment of small, benign cranial lesions and cerebral metastases. © 2018, Logos Medical Publishing. All rights reserved.Öğe Delivering Growth Factors through a Polymeric Scaffold to Cell Cultures Containing both Nucleus Pulposus and Annulus Fibrosus(Turkish Neurosurgical Soc, 2019) Akyuva, Yener; Kaplan, Necati; Yılmaz, İbrahim; Özbek, Hanefi; Şirin, Duygu Yaşar; Karaarslan, Numan; Ateş, ÖzkanAIM: To design a novel, polyvinyl alcohol (PVA)-based polymeric scaffold that permits the controlled release of insulin-like growth factor 1 (IGF-1)/bone morphogenetic protein (BMP)-2 following intervertebral disc administration. MATERIAL and METHODS: The drug delivery system was composed of two different solutions that formed a scaffold within seconds of coming into contact with each other. Swelling, pH, and temperature tests and analysis of the controlled release of growth factors (GFs) from this system were performed. The release kinetics of the GFs were determined through enzyme-linked immunosorbent assay (ELISA). Cell proliferation and viability were monitored with microscopy and analyzed using an MTT assay and acridine orange/propidium iodide (AO/PI) staining. Chondroadherin (CHAD), hypoxia inducible factor-1 alpha (HIF-1 alpha), and collagen type II (COL2A1) gene expressions were determined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis to show the effects of IGF-1/BMP-2 administration on annulus fibrosus cell (AFC)/nucleus pulposus cell (NPC) cultures. For the statistical evaluation of the obtained data, experimental groups were compared with a post hoc Tukey's test following an analysis of variance. RESULTS: The scaffold allowed for the controlled release of IGF-1 and BMP-2 in different time intervals. It was observed that as the application time increased, the number of cells and the degree of extracellular matrix development increased in AFC/NPC cultures. AO/PI staining and an MTT analysis showed that cells retained their specific morphology and continued to proliferate. It was observed that HIF-1 alpha and CHAD expression increased in a time-dependent manner, and no COL2A1 expression in the AFC/NPC cultures was observed. CONCLUSION: The designed scaffold may be used as an alternative method for intervertebral disc administration of GFs after further in vivo studies. Such prototype scaffolds may be an innovative technology in targeted drug therapies after reconstructive neurosurgical interventions.Öğe Do Endocrinopathies Cause Changes in Transverse Carpal Ligament Thickness and Carpal Tunnel Area in Carpal Tunnel Syndrome?(2020) Karaarslan, Numan; Şimşek, Abdullah Talha; Öznam, Kadir; Bülbül, Ahmet MuratObjective: The purpose of this study was to investigate the effect of transverse carpal ligament (TCL) thickness and the size of carpal tunnelarea on clinical findings and electrophysiological changes through the wrist magnetic resonance imaging (MRI).Methods: In this prospective study, the thickness of the TCL and the carpal tunnel areas of preoperative cases diagnosed with carpal tunnelsyndrome (CTS) were measured via wrist MRI results. The effect of TCL thickness and carpal tunnel area on endocrinopathies such as diabetesmellitus (DM) and hypothyroidism and the effect of these variables on clinical findings and electrophysiologic changes were evaluated in thelight of the literature.Results: TCL thickness and carpal tunnel area were not statistically significant among DM, hypothyroidism and electrophysiological changes(p>0.05).Conclusion: This study include one of the limited researches comparing the carpal tunnel area and TKL thickness in cases with and withoutendocrinopathy CTS. However, there is a need for further researches that have a greater number of cases, including multi-centered, differentwinged people.Öğe Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?(2018) Karaarslan, Numan; Yılmaz, İbrahim; Şirin, Duygu Yaşar; Baykız, Derya; Demirkiran, Aykut; Ateş, ÖzkanAim: Nimodipine is used to prevent cerebrovascular-originated ischemic neurological deficits, yet its effects on nucleus pulposus (NP) cells or annulus fibrosus (AF) cells weren’t studied. This study aimed to examine nimodipine’s effects on vitality and proliferation of chondroadherin (CHAD), type II collagen (COL2A1), and hypoxia-inducible factor 1 alpha (HIF 1?) gene expression in human primary NP/AF cells.Material and Methods: NP/AF cell cultures obtained from 6 patients who underwent microdiscectomy were treated with 100 µMolar nimodipine and analyzed at 0, 24, and 48 h. Data were evaluated using one-way ANOVA and post-hoc Tukey HSD with 95% confidence interval.Results: We observed suppressed cell proliferation and increased necrosis in nimodipine-treated NP/AF cell cultures, especially degenerated tissue. COL2A1 gene expression wasn’t detected in any experimental groups. CHAD and HIF 1? expression had timedependent decreases in control. CHAD and HIF 1? expression were found to decrease at 24h, but increased at 48h in degenerated tissue. In nimodipine-applied intact tissues, CHAD expression was stable at 24h but 1.62 times higher than control at 48h. HIF 1? levels were lower than control.Conclusion: In nimodipine-treated degenerated AF/NP cultures, CHAD and HIF 1? expressions had time-dependent decreases. However, after complete RT-PCR data evaluation, no correlation between nimodipine application and gene expression occurred.Öğe Does Nimodipine, a Selective Calcium Channel Blocker, Impair Chondrocyte Proliferation or Damage Extracellular Matrix Structures?(Bentham Science Publ Ltd, 2019) Kaplan, Necati; Yılmaz, İbrahim; Karaarslan, Numan; Kaya, Yasin Emre; Şirin, Duygu Yaşar; Özbek, HanefiBackground: The study aimed to investigate the effects of the active ingredient, nimodipine, on chondrocyte proliferation and extracellular matrix (ECM) structures in cartilage tissue cells. Methods: Chondrocyte cultures were prepared from tissues resected via surgical operations. Nimodipine was then applied to these cultures and molecular analysis was performed. The data obtained were statistically calculated. Results: Both, the results of the (3-(4,5 dimethylthiazol2-yl)-2,5-diphenyltetrazolium (MTT) assay and the fluorescence microscope analysis [a membrane permeability test carried out with acridine orange/propidium iodide staining (AO/PI)] confirmed that the active ingredient, nimodipine, negatively affects the cell cultures. Conclusion: Nimodipine was reported to suppress cellular proliferation; chondroadherin (CHAD) and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression thus decreased by 2.4 and 1.7 times, respectively, at 24 hrs when compared to the control group (p < 0.05). Furthermore, type II collagen (COL2A1) expression was not detected (p < 0.05). The risk that a drug prescribed by a clinician in an innocuous manner to treat a patient by relieving the symptoms of a disease may affect the proliferation, differentiation, and viability of other cells and/or tissues at the molecular level, beyond its known side effects or adverse events, should not be forgotten.Öğe Does oseltamivir protect human chondrocyte and nucleus pulposus cells from degeneration by inhibiting senescence and proinflammation mediated by the NLRP3 inflammasome and NF-kappa B?(Verduci Publisher, 2022) Yılmaz, İbrahim; Akalan, Hande; Öznam, K.; Karaarslan, Numan; Şirin, Duygu Yaşar; Özbek, HanefiOBJECTIVE: Recent drug design studies suggest that inflammation is among the most important factors in the development of both intervertebral disc (IVD) degeneration (IVDD) and osteoarthritis (OA) due to cartilage damage. This study aimed to investigate whether the anti-inflammatory drug oseltamivir has a toxic effect on IVD and cartilage tissue cells. It assessed what effect oseltamivir has on hypoxia-inducible factor (HIF)-1 alpha (HIF1 alpha), which plays an important role in anabolic pathways in IVD and cartilage tissue. In addition, the study analyzed whether oseltamivir could inhibit the release of inflammatory interleukin-1 beta (IL-1 beta) via the nuclear factor kappa-B (NF-kappa B) signaling pathway by activating the nucleotide-binding oligomerization domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. MATERIALS AND METHODS: Human lumbar IVD (n = 8) tissues were isolated for annulus fibrosus (AF) and nucleus pulposus (NP) primary cell cultures. and human tibial and femoral cartilage tissues (n = 8) were isolated for primary chondrocyte cultures. Untreated groups served as the control and oseltamivir-treated groups as the study sample. Cell viability and cytotoxicity were evaluated at 0, 24, 48. and 72 h in all groups for changes in HIF-1 alpha, IL-18, NF-kappa B. and the NLRP3-inflammasome protein expressions using Western blotting. The a significance value was < 0.05. RESULTS: In the oseltamivir-treated groups, cell proliferation decreased in both AF/NP cell and chondrocyte cultures obtained from IVD cartilage tissues. After Western blotting analysis, changes were observed in the protein expressions of HIF-1 alpha, IL-1 beta, NF-kappa B, and the NLRP3 inflammasome in both AF/NP cells and chondrocytes. The results were statistically significant (p < 0.05). CONCLUSIONS: Oseltamivir treatment may be a promising regenerative strategy to manage IVDD and osteoarthritic cartilage tissues.Öğe Does transcription factor, induced by daptomycin and vancomycin, affect HIF-1?, Chondroadherin, and COL2A1?(2018) Karaarslan, Numan; Yılmaz, İbrahim; Şirin, Duygu Yaşar; Özbek, Hanefi; Kaya, Yasin Emre; Akyuva, Yener; Doğan, Mustafa; Erdem, İlknurAim: In this study, it was firstly aimed to investigate the effect of Daptomycin (DAP) on the proliferation in Vancomycin (VCM)-administered primary chondrocyte cultures and non-drug-administered primary chondrocyte cultures. Our second objective was to investigate the effects of DAP and VCM on the NP-specific marker protein chondroadherin (CHAD), which is associated with spinal cord and dorsal column growth, on the transcription factor-1 alpha (HIF-1?), which is induced by hypoxia, and on a type II collagen (COL2A1), which is also known to play a significant role in the development of extracellular matrix, at the pharmaco-molecular level.Material and Methods: Standard human primary chondrocyte cultures were established. DAP and VCM were added to the samples. In all groups, molecular analysis was performed at 0th, 24th and 48th hours. In addition, the surface morphology of the cells was evaluated.Results: Changes in cell morphology and cell death in cultures were observed 24 hours after administration of antibiotics to cell cultures. It was observed that drug administration was associated with the cell viability and that cell viability rate for two antibiotics was similar at the 0th and 48th hours. The expression of three genes decreased at the 24th hour in the experimental group where DAP was administered.Conclusion: Thanks to this molecular-based research, it should not be forgotten that DAP and VCM active pharmacological agents, especially used in the treatment of Methicillin-resistant Staphylococcus aureus induced surgical infections, have a negative effect on human chondrocyte and ECM components.Öğe Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue(Spandidos Publ Ltd, 2018) Karaarslan, Numan; Batmaz, Ahmet Güray; Yılmaz, İbrahim; Özbek, Hanefi; Çalışkan, Tezcan; Şirin, Duygu Yaşar; Ateş, ÖzkanNon-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1-1,000 mu M). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by analysis of variance with Tukey's honest difference post hoc test. P<0.01 was considered to indicate a statistically significant difference. The research revealed significant changes to proliferation and differentiation of chondrocytes in all treatment groups (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and differentiation, which may be an important factor to consider when prescribing this medication to patients.Öğe Effects of an acetylcholinesterase inhibitor and an N-methyl-D-aspartate receptor antagonist on inflammation and degeneration of the nucleus pulposus(Verduci Publisher, 2022) Yılmaz, İbrahim; Akalan, Hande; Şirin, Duygu Yaşar; Karaarslan, Numan; Kaplan, Nuray; Özbek, HanefiOBJECTIVE: The study aimed to examine the effects of two drugs, an acetylcholinesterase inhibitor (AChEI) and an N-methyl-D-aspartate receptor (NMDAR) antagonist, on degenerated annulus fibrosus (AF) and nucleus pulposus (NP) cells and the extracellular matrix (ECM) structure in vitro. PATIENTS AND METHODS: Tissue samples were obtained from patients with intervertebral disc herniation (four males and four females; classified as Pfirmann stage IV) and used to prepare cell cultures. Untreated cell culture samples served as the control group. Study group samples were treated with donepezil, memantine or a combination of the two drugs. Cell viability, toxicity and proliferation were evaluated in all groups. Western blotting was used to examine changes in protein expression of signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (ser727), hypoxia-inducible factor (HIF)-1 alpha (HIF-1 alpha) and nucleotide-binding oligomerisation domain (NOD) leucine-rich repeat (LRR)-containing proteins (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. The alpha significance value was < 0.05. RESULTS: Analysis of the microscopy and commercial kit results revealed that cell proliferation was suppressed. and no cell death was observed. The protein expression levels of NLRP3, STAT3, ser727 and HIF-1 alpha were lower in the samples treated with donepezil and memantine at 72 h (p < 0.05). The protein expression levels of NLRP3, STAT3, ser727 and HIF-1 alpha were higher in the samples treated with the combination of donepezil and memantine (p < 0.05). CONCLUSIONS: The combined administration of memantine a NMDAR antagonist which can prevent neurodegeneration and donepezil an AChEI used for pain relief increased the protein expression levels in the anabolic pathway. However, it did not reduce the protein expression levels in the catabolic pathway. Therefore, further studies are needed to provide extensive insight into whether it may be among the potential targets for the therapy of intervertebral disc (IVD) diseases.
