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    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; Yilmaz, Ibrahim; Yasar Sirin, Duygu; Akgun, Feride Sinem; Caliskan, Tezcan; Simsek, Abdullah Talha; Ozbek, Hanefi
    AIM: 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.
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    Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue
    (Spandidos Publ Ltd, 2019) Akgün, Feride Sinem; Sirin, Duygu Yasar; Yılmaz, Ibrahim; Karaarslan, Numan; Özbek, Hanefi; Simsek, Abdullah Talha; Kaya, Yasin Emre
    The present study aimed to evaluate the effects of dipyrone, an indispensable analgesic, anti-pyretic and anti-spasmodic used in emergency departments, on nucleus pulposus and annulus fibrosus cells in vitro. After surgical biopsy, primary cell cultures were prepared from intact intervertebral disc tissues. Dipyrone was administered to the cultures in the experimental groups except for the control group. The data obtained were statistically evaluated. The proliferation was identified to be suppressed via MTT analysis. The gene expression profile of the intervertebral disc cells in the dipyrone-treated groups was significantly changed. The expression of chondroadherin, cartilage oligo matrix protein, interleukin-1 beta and metalloproteinase (MMP)-19 genes were decreased, but MMP-13 and MMP-7 genes expressions were increased, as determined via reverse transcription-quantitative PCR. AO/PI staining revealed that no apoptotic or other type of cell death was detectable after administration of dipyrone does not mean that the drug is innocuous. The occurrence of cellular senescence and/or the halt of cell proliferation may also be important mechanisms underlying the adverse inhibitory effects of dipyrone. Therefore, prior to administering dipyrone in clinical practice, all possible adverse effects of this drug should be considered.