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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 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 Assessment of the Impact of Curcumin on Cell Cultures Derived from the Primary Intervertebral Disc Tissue in Humans(Maltepe Üniversitesi, 2023) Albayrak, Mehmet; Yılmaz, İbrahim; Yüzbaşı, Muharrem Furkan; Akalan, Hande; Şirin, Duygu Yaşar; Karaarslan, Numan; Özbek, HanefiAim: Degenerative disc disease in the lumbar spine is widely observed. Degenerative disc diseases are among the causes of low back pain in older age. Modern drug discovery studies have aimed to identify potential molecules that target multiple pathways with a safer profile against degeneration. This study aimed to evaluate the effects of curcumin, a natural phenolic compound, on primary cell cultures prepared using intervertebral disc (IVD) tissues resected during the surgeries of patients with lumbar disc herniation. Materials and Methods: Primary cell cultures were prepared using human IVD tissues of eight patients. Untreated groups served as the control and curcumin-treated groups as the study sample. In-vitro cytotoxicity analyses were performed in all groups. Acridine orange (AO)/propidium iodide (PI) and Janus Green B staining were performed to evaluate cell surface morphologies. One-way analysis of variance and Tukey HSD, a multiple comparison test, were used to assess the obtained data. Results: Proliferation slightly increased as of 24 h in the curcumin-treated samples, but decreased in the 48 and 72 hour curcumin-treated samples compared to the control samples. The obtained results were statistically significant (pÖğe 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 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 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.Öğe Effects of etanercept, a tumor necrosis factor receptor fusion protein, on primary cell cultures prepared from intact human intervertebral disc tissue(Spandidos Publ Ltd, 2019) Çalışkan, Tezcan; Şirin, Duygu Yaşar; Karaarslan, Numan; Yılmaz, İbrahim; Özbek, Hanefi; Akyuva, Yener; Ateş, Özkan; Şimşek, Abdullah TalhaThe aim of the present study was to investigate the effects of etanercept (ETA), a tumor necrosis factor (TNF) inhibitor, on human cell cultures prepared from intact intervertebral disc tissue. ETA is used as a treatment for cases of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and ankylosing spondylitis accompanied by moderate or severe joint pain. ETA was applied to primary cell cultures [annulus fibrosus and nucleus pulposus (NP) from intact intervertebral disc tissue]. Cell cultures without ETA treatment served as the control group. Morphological and quantitative molecular analyses of the two groups were performed. The number of viable cells and cell proliferation decreased in the ETA-treated cultures as compared with those in the control group. Furthermore, in the treatment group, the chondroadherin gene, an NP-specific marker, was not expressed after 24 h. By contrast, the cartilage oligo matrix protein was expressed 24, 48 and 72 h post-ETA treatment, while its expression was significantly lower than that in the control group. In addition, the expression of interleukin-1 beta, as well as matrix metallopeptidase-7 and -19, was markedly decreased. Overall, the cell proliferation and gene expression in the ETA-treated cells were significantly different from those in the control group (P<0.05). These results suggest that the treatment duration and dosage of TNF inhibitors, which are used to suppress active inflammation, should be considered in the clinical setting. These biological agents may delay the healing of intervertebral disc tissue damage by slowing cell proliferation and altering gene expression via anabolic and catabolic pathways.Öğe Evaluation of Calciferol, Cobalamin, and Stromelysin-1 in Patients with Diabetic Peripheral Neuropathy due to Type-2 Diabetes Mellitus(College of Physicians and Surgeons Pakistan, 2022) Bilir, Bülent; Yılmaz, İbrahim; Karaarslan, Numan; Bilir, B.E.; Kaplan, Nuray; Özbek, HanefiObjective: To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circulating levels in patients with diabetic peripheral neuropathy (DPN), patients with DM type 2 (T2DM) without neuropathy, and healthy control groups. Study Design: Cross-sectional descriptive study. Place and Duration of Study: Department of Internal Medicine, Namik Kemal University of Medicine, Tekirdag, Turkey, between November 2020 and February 2022. Methodology: Healthy, age, and gender matched volunteers who were admitted to the hospital for a check-up with no health problem constituted the control group (n=30). Cases diagnosed with T2DM (n=30) and those with DPN (n=30) comprised the experimental group. Stromelysin-1, calciferol, and cobalamin levels were analysed from blood samples from all groups using enzyme-linked immunosorbent assay (ELISA) with a commercial kit. Tukey's Honest Significant Difference (HSD) test was performed after one-way analysis of variance (ANOVA) for intergroup comparisons. Alpha significance level was accepted as <0.05. Results: There were significant differences in terms of the stromelysin-1, calciferol, and cobalamin levels of both the T2DM and DPN groups compared to healthy volunteers. These differences were statistically significant (p=0.00). There was a very weak negative correlation between stromelysin-1 and calciferol (p=0.972, r=-0.007) and a weak negative correlation between cobalamin and stromelysin-1 (p=0.062, r=-0.345) in DPN patients, without statistical significance. Conclusion: Serum stromelysin-1 expression may be related to DPN progression in diabetic patients and may be a potential marker in DPN. Calciferol and cobalamin levels may also be important in the development of DPN. © 2022 College of Physicians and Surgeons Pakistan. All rights reserved.Öğe Evaluation of inflammatory and biochemical markers in COVID-19 patients treated with tocilizumab alone or with the combination of tocilizumab and convalescent plasma transfusion(2022) Karaarslan, Numan; Doğan, Mustafa; Bilir, Bülent; Yılmaz, İbrahim; Özbek, HanefiAbstract Aim: Macrophage activation syndrome (MAS) develops due to increased expression of systemic pro-inflammatory cytokines in patients with the 2019 novel coronavirus disease (COVID-19). Immune modulators have been used in anti-cytokine therapy, with the hypothesis that they can ensure cytokine inhibition and treat cytokine storm. The present study aimed to evaluate inflammatory and prognostic biomarkers in severe COVID-19 cases treated with tocilizumab (TCZ) alone or with the combination of tocilizumab and convalescent plasma transfusion (CPT). Materials and Methods: In this retrospective study, data archives of patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and who were treated with TCZ alone or the combination of CPT and TCZ were evaluated in line with the literature. The obtained data were statistically evaluated and the alpha significance value was taken as <0.05. Results: Post-treatment C-reactive protein (CRP) (76.19% in TCZ-administered group; 89.32% in TCZ+CPT-administered group) (P<0.05), troponin I (TNI) (25.64% in TCZadministered group; 90.39% in TCZ+CPT-administered group) (P<0.05), and ferritin (FER) (63.63% in the TCZ-administered group; 9.09% in the TCZ+CPT-administered) (P<0.05) levels were decreased compared to pre-treatment stage. The mean length of hospital stay was longer in the patients treated with TCZ alone (21.55±8.89 days) than in the patients treated with the combination of TCZ and CPT (27.09±13.66 days) (P<0.05). Conclusion: There was no significant difference between the groups in terms of demographic characteristics. The combination of TCZ and CPT treatment did not decrease the mortality. A significant decrease in CRP and TNI levels was observed in the patients treated with TCZ alone and with the combination of TCZ and CPT. A decrease in FER levels showed the effectiveness of the treatments.Öğe Evaluation of the effect of apixaban on the primary intact intervertebral disc cell cultures(2019) Akgün, Feride Sinem; Karaarslan, Numan; Yılmaz, İbrahim; Özbek, Hanefi; Şirin, Duygu Yaşar; Şimşek, Abdullah Talha; Ateş, ÖzkanAim: Apixaban is a frequently preferred pharmacological agent in clinics to prevent deep vein thrombosis and pulmonary embolism.Such new oral anticoagulants may cause hemorrhage’s in tissues and/or organs or may cause gastrointestinal symptoms withoutbleeding. It is also reported in the literature that it may lead to mental disorders, unwanted disorders in the urinary tract and skeletalmuscle system. However, when the literature is examined, there are no studies, which are of high-evidential value, evaluating theefficacy of apixaban on healthy, intact intervertebral disc tissue, and matrix-like structures. In this pharmaco-molecular study, itwas aimed to investigate the effects of a new oral anticoagulant agent containing the active ingredient apixaban on the intactintervertebral disc tissue cells, extracellular matrix (ECM) structure and to evaluate its positive and / or negative effects on geneexpressions of cartilage oligo matrix protein (COMP), chondroadherin (CHAD), and Matrix Metalloproteinase (MMP)s.Material and Methods: The primary cell cultures were prepared from the intact tissues of the patients with the traumatic intervertebraldisc herniation. Apixaban was administered to the cultures and molecular analyses were performed for 21 days. The data obtainedfrom the apixaban-administered and non-apixaban-administered samples were evaluated statistically and the significance valuewas accepted as P <0.05.Results: The changes were observed in the cell proliferation and the expressions of the mentioned genes in the apixabanadministered group. The suppression of COMP value and the increase in MMP-13 value may be indicative of the development ofmatrix degeneration in the apixaban-administered group, compared to the non-drug-administered control group.Conclusion: The selectivity is one of the most important features of the drugs. However, it should not be forgotten that no drug willonly produce the desired effect.Öğe Evaluation of the Effect of Daptomycin, a Glycopeptide Agent, on Intact Intervertebral Disc Tissue(Turkish Neurosurgical Soc, 2019) Kaplan, Necati; Yılmaz, İbrahim; Karaarslan, Numan; Yasar Şirin, Duygu; Şimşek, Abdullah Talha; Çalışkan, Tezcan; Özbek, HanefiAIM: To evaluate the effects of pre- and intra-operatively administered daptomycin (DAP) on the intact human primary intervertebral disc tissue cells. MATERIAL and METHODS: Primary cell cultures were established using tissues obtained through decompressive laminectomy, traumatic intervertebral disc herniation excision, and posterior transpedicular stabilization. Non-drug-administered samples were used as a control group. The samples treated with DAP formed the study group. Molecular assays for proliferation and gene expression were performed. The obtained data were evaluated statistically, and results with a value of p<0.05 were accepted as significant. RESULTS: While no reduction was observed in the proliferation, the gene expression of intact intervertebral disc tissue cells was time-dependently decreased compared to the control group, and these results were reported to be statistically significant. CONCLUSION: This study observed the effect that a pharmaceutical preparation, which was used on intervertebral disc tissue before and after the operation, had on normal, healthy, and intact tissue. It concludes that alterations in the expression of genes involved in the anabolic and/or catabolic process, even in adjacent healthy tissue, may slow down the healing process of the damaged tissue or cause undesired cell differentiation.Öğe Evaluation of the expression and proliferation of degenerative markers in primary cell cultures obtained from human intervertebral disc tissue(2020) Kaya, Yasin Emre; Akalan, Hande; Yılmaz, İbrahi?m; Karaarslan, Numan; Şirin, Duygu Yaşar; Özbek, HanefiAim: A major cause of low back pain is disc degeneration. Nevertheless, no specific and reliable markers of the degeneration of thenucleus pulposus (NP) are available. This presented study aimed to examine changes in the expressions of genes in primary cellcultures isolated from intact and degenerated tissues to give insights into the biopathogenesis of intervertebral disc (IVD) tissue.Material and Methods: Tissues of eight patients (n = 8; average age: 41.74 ± 9.86 years) were resected through microdiscectomy,and primary cell cultures were prepared using degenerated disc tissue. The cultured degenerated tissues served as the study group.The samples in the control group comprised the intact tissues of patients (n = 8; average age: 38.68 ± 7.91 years) resected followinga trauma. Morphology of the cell surface were evaluated using an inverted light/fluorescent microscopy at 0 and 24 h on days 10and 21. The expressions of the chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1 beta (IL-1 beta),and matrix metalloproteinase (MMP)-7 and MMP-19 genes were evaluated using the reverse transcription-quantitative polymerasechain reaction (RT-qPCR). The data obtained were statistically analyzed.Results: The four genes investigated, except COMP (P > 0.05), changed significantly in primary cell cultures isolated from degenerativeIVD tissues. This result was statistically significant (P < 0.05). The gene expressions in the samples derived from intact IVD tissueschanged markedly and these changes were associated with proliferation (P < 0.05).Conclusion: Analyzing the changes in gene expression levels associated with IVD should contribute to future studies on theprevention and treatment of such pathologies. The data obtained from the present study will shed light on cellular-based personaltargeted therapies through which genetic information can be transmitted to cells.Öğe In-vitro evaluation of the effects of tigecycline on annulus firosus and nucleus pulposus(2020) Kaya, Yasin Emre; Yılmaz, İbrahi?m; Karaarslan, Numan; Bilir, Bülent; Şirin, Duygu Yaşar; Özbek, HanefiAim: This study aimed to examine the effects of tigecycline on primary cell cultures established using intervertebral disc tissues.Material and Methods: Primary Annulus Fibrosus and Nucleus Pulposus cultures were obtained from human intervertebral disctissue. Untreated samples served as the control group, and treated samples served as the study group. Treated and untreatedsamples were statistically evaluated using an alpha signifiance value of < 0.05.Results: Proliferation and gene expression decreased in the tigecycline administered cultures when compared to the control groupsamples (P < 0.05).Conclusion: Drugs used in clinics may have side effects other than those indicated in their package insert.
