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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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    Evaluation of the effect of apixaban on the primary intact intervertebral disc cell cultures
    (2019) Şimşek, Abdullah Talha; Özbek, Hanefi; Şirin, Duygu Yaşar; Yılmaz, İbrahim; Ateş, Özkan; Akgün, Feride Sinem; Kaplan, Necati
    Aim: 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.