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    Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?
    (J Infection Developing Countries, 2022) Ates, Ozkan; Yilmaz, Ibrahim; Karaarslan, Numan; Ersoz, Emel; Kasim, Fatma Bahar Hacioglu; Dogan, Mustafa; Özbek, Hanefi
    The 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.
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    Curcumin-Impregnated Drug Delivery Systems May Show Promise in the Treatment of Diseases Secondary to Traumatic Brain Injury: Systematic Review
    (Sage Publications Inc, 2022) Yilmaz, Ibrahim; Karaarslan, Numan; Somay, Hakan; Ozbek, Hanefi; Ates, Ozkan
    ObjectiveTo find out whether curcumin can be effective in the treatment of traumatic brain injury (TBI). MethodsA comprehensive and systematic literature search in the PubMed electronic database was performed. Descriptive statistics were used to evaluate the data obtained. The results were presented as frequency and percentage (%) or amount. ResultsTwo clinical trials investigated curcumin for the treatment of TBI. One study tested curcumin in living mammalian subjects using an amyloLipid nanovesicle. In three studies, curcumin was investigated together with the drug delivery system for the treatment of TBI. ConclusionDrug delivery systems prepared with nanomaterials may have a potential therapeutic effect in treating TBI by increasing neuroprotection because they can penetrate the central nervous system more rapidly.
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    The effects of rivaroxaban, an oral anticoagulant, on human IVD primary cultures
    (Termedia Publishing House Ltd, 2022) Caliskan, Tezcan; Akalan, Hande; Yilmaz, Ibrahim; Karaarslan, Numan; Sirin, Duygu Yasar; Özbek, Hanefi
    Introduction: The present study aimed to investigate the potential effects of rivaroxaban, an oral anticoagulant that inhibits the effects of factor Xa, on intact intervertebral disc tissue cells and the extracellular matrix (ECM). Material and methods: Rivaroxaban was applied to primary human cell cultures prepared from tissues of the intervertebral disc. Comparative molecular analyses were performed on non-drug-treated control group samples. Descriptive statistics were presented as the mean +/- standard deviation. An analysis of variance test was performed to determine whether there were significant differences in the mean across the groups. When differences across groups were observed, Tukey's honestly significant difference post-hoc test was used for multiple pairwise comparisons. The significance of the obtained data was determined statistically. The alpha significance value was < 0.05. Results: The cells in the control group and in the rivaroxaban-treated group were viable, healthy, and proliferated (p < 0.05). However, the expression levels of the chondroadherin gene (CHAD), cartilage oligo matrix protein (COMP), matrix metalloproteinase (MMP)-13, and MMP-19 genes were changed (p < 0.05). Conclusions: Although rivaroxaban does not suppress cell proliferation due to morphological, biological, and biochemical changes in the intervertebral disc tissue, it may change the expression of genes that are related to ECM maintenance.
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    Effects of Tocilizumab on Intervertebral Disc Degeneration, Cell Senescence and Inflammation via BMP-2, Hif-1α, IL-1β and SOX9
    (Asian Network Scientific Information-Ansinet, 2023) Yilmaz, Ibrahim; Akalan, Hande; Sirin, Duygu Yasar; Karaarslan, Numan; Kasim, Emin; Ozbek, Hanefi; Ates, Ozkan
    Background and Objective: Immunosuppressive tocilizumab (TCZ), which is frequently used in the treatment of rheumatoid arthritis, can have many side effects as well as an uncontrolled inflammatory response. This study aimed to evaluate the effect of tocilizumab (TCZ) administered to intervertebral disc (IVD) tissues in vitro on the proinflammatory cytokines and proteins of degeneration, senescence and inflammation-related signaling pathways at the pharmaco-molecular level. Materials and Methods: Primary cell cultures were prepared using human IVD tissues obtained during lumbar microdiscectomy. Untreated groups served as the control and TCZ-treated groups as the study sample. Analyses were performed using a commercial kit, supravital and fluorescent dyes. Changes in bone morphogenetic protein (BMP)-2, hypoxia-inducible factor (Hif)1-alpha (Hif1-alpha), interleukin (IL)-1 beta (IL-1 beta) and sex-determining region Y (SRY)-box 9 (SOX9) protein expressions were evaluated using western blotting. An alpha value of less than 0.05 was considered significant. Results: Proliferation decreased in the samples treated with TCZ (10 mu g mLG1 ) on day 15 (p<0.05). Protein expressions of BMP-2, Hif-1 alpha, IL-1 beta and SOX9, which play a vital role in anabolic and catabolic pathways, changed in samples treated with TCZ (10 mu g mLG1 ). Conclusion: This change was statistically significant (p<0.05). Therefore, results concluded that the inflammation, extracellular matrix degradation and nucleus pulposus degeneration after disc herniation are controlled by BMP-2, Hif-1 alpha, IL-1 beta and SOX9.
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    Evaluation of the Effects of HDAC Activity in Hydroxychloroquine Applied Human Primary Chondrocyte and Nucleus Pulposus Cultures
    (Turkish Neurosurgical Soc, 2025) Kaya, Yasin Emre; Karaarslan, Numan; Yilmaz, Ibrahim; Tamdogan, Tamer; Ondul, Sevim; Yasar Sirin, Duygu; Ozbek, Hanefi
    AIM: To evaluate the in vitro effects of hydroxychloroquine (HCQ) on histone deacetylase (HDAC) enzyme activity and interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-alpha) expressions. MATERIAL and METHODS: Primary cell cultures were prepared. Samples that did not receive any medication constituted the control group, while culture samples treated with HCQ served as the study group. The surface morphology of cells and the extracellular matrix (ECM) were evaluated by Giemsa staining and inverted light microscopy. Cell viability, proliferation, and cytotoxicity were determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium-bromide (MTT) analysis. The cultures were simultaneously stained with acridine orange (AO)/propidium iodide (PI) and viewed under fluorescence microscopy. HDAC enzyme activity and IL-6, IL-10, and TNF-alpha expression were evaluated using commercial enzyme-linked immunosorbent assay kits. The obtained data were analyzed using statistical methods. The alpha significance level was accepted as p<0.05. RESULTS: HCQ applied to cell cultures at the tested doses and durations showed cytotoxic effects on cell viability, proliferation, and cell or ECM morphology. It increased HDAC activity in chondrocytes and caused a proinflammatory response, indicated by an increase in TNF-alpha in the cells (p<0.05). CONCLUSION: The results of this study emphasized that the cytotoxic effect of HCQ increased HDAC activity; therefore, this proinflammatory response should be taken into consideration in the clinical use of HCQ.