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    Are we using slow-acting symptomatic chondroprotective drugs conscious enough?
    (Bentham Open, 2017) Gümüştaş, Seyit Ali; Öznam, Kadir; Mutlu, Çağrı Ata; Kaya, Yasin Emre; Yılmaz, İbrahim; İşyar, Mehmet; Yıldırım Güzelant, Aliye; Güler, Olcay; Akkaya, Semih; Mahiroğulları, Mahir
    Background: Osteochondral injuries constitute an entity that is widespread and can be seen in patients of all ages. Actual treatment modalities aim to relieve pain, obtain full range of movement of the joint, and improve the quality of life. There are many slow-acting chondroprotective agents prevalently used in the United States that are classified as nutritional support but not as medicines . This study presents the importance of clinical adverse effect profiles as well as the pharmacological mechanism of action and application of combinations of drugs that are widely prescribed and not subjected to control.Methods: Electronic databases were searched with keywords about the chondroprotective drugs without any language restriction. Evaluations of the descriptive statistics were represented via Microsoft Office Excel 2010 lists in the form of a mean±standard deviation or frequency (%). The first evaluation showed that 1502 studies were potentially relevant. Following exclusion of the 1277 studies which were not clinical, full versions of the remaining 225 studies were subjected to further evaluation. No controlled, blinded, randomized and/or comparative studies met the inclusion criteria of the study, and no studies evaluated the comparative clinical results of the hyaluronan of different molecular weights.Results: The findings of this study concluded that especially when prescribing drugs with ingredients like GS and CS, many patients' pre-existing conditions must be considered, such as whether the patient has a glucose intolerance or not. Additionally, mineral toxication should be considered since the drugs contain minerals, and after the application of injected hyaluronan, complications should be considered.Conclusion: Clinical, controlled and comparative studies about the use of chondroprotective drugs must be performed to define the benefits of these drugs, if any, in order to determine the most suitable time for operative intervention.
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    Can a biodegradable implanted bilayered drug delivery system loaded with BMP-2/BMP-12 take an effective role in the biological repair process of bone-tendon injuries? A preliminary report
    (Hindawi Ltd, 2017) Kömür, Baran; Akyuva, Yener; Karaslan, Numan; İşyar, Mehmet; Gümüştaş, Seyit Ali; Yılmaz, İbrahim; Akkaya, Semih; Şirin, Duygu Yaşar; Mutlu, Çağri Ata; Batmaz, Ahmet Güray; Güler, Olcay; Mahiroğulları, Mahir
    Background. Use of biodegradable and biocompatible materials in the orthopedic surgery is gaining popularity. In this research, the rate of controlled release of a bilayered prototype biomaterial designed to promote osteoblastic and tenoblastic activity was calculated using pharmacochemical methods. Methods. The first part of the design, composed of a sodium tetraborate, polyvinyl alcohol, and starch based hydrogel, was loaded with bone morphogenic protein-2. The second part which was composed of a sodium tetraborate, polyvinyl alcohol, and chitosan based hydrogel was loaded with bone morphogenic protein-12. Osteochondral and tendon tissue specimens were obtained from patients with a diagnosis of gonarthrosis and primary bone cells and tendon cells cultures were prepared following treatment with collagenase enzyme. Cell samples were collected from the groups by means of an invert light microscope and environmental scanning electron microscope underwent at the 1st and 21st days. Thelevel of osteogenic differentiation was measured by the activity of alkaline phosphatase. For the statistical evaluation of the obtained data, groups were compared with post hoc Tukey test following analysis of variance. Level of significance was accepted to be <0,01. Results. Both osteogenic and tenogenic stimulation were observed in the cultured specimens. In comparison to the control groups, the rate of proliferation of healthy cells was found to be higher in the groups to which the design was added (P < 0.01). Conclusions. Our research is a preliminary report that describes a study conducted in an in vitro experimental setting. We believe that such prototype systems may be pioneers in targeted drug therapies after reconstructional surgeries.
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    Iopromide- and gadopentetic acid-derived preparates used in MR arthrography may be harmful to chondrocytes
    (BMC, 2017) Öznam, Kadir; Şirin, Duygu Yaşar; Yılmaz, İbrahim; Kaya, Yasin Emre; İşyar, Mehmet; Gümüştaş, Seyit Ali; Özbek, Hanefi; Akkaya, Semih; Kayhan, Arda; Mahiroğulları, Mahir
    Background: Magnetic resonance arthrography, a procedure through which contrast agents containing gadolinium and/or iopromide are administered intra-articularly, has become a useful tool in musculoskeletal diagnosis. Nevertheless, despite being considered safe for systemic use, certain tissue toxicities have been identified for both drugs. In this study, the effects of short-term exposure of human primary chondrocyte cell cultures to gadolinium and/or iopromide contrast agents were examined by assaying for stage-specific embryonic antigen-1 (SSEA-1) protein expression (a chondrogenic differentiation marker), cell viability, toxicity, and proliferation. Methods: Human articular chondrocytes were grown in monolayer culture and were exposed to iopromide and/or gadolinium diethylenetriamine-pentaacetate (Gd-DPT) for 2 and 6 h. Cell cultures with no drug exposure were used as the control group. Cell differentiation status was assessed according to SSEA-1 protein expression. Contrast agent effects on cell viability and proliferation were analyzed using MTT analysis. Further, changes in cell morphology in relation to the control group were evaluated using inverted light microscopy, environmental scanning electron microscopy (ESEM), and 3-tesla magnetic resonance imaging. The obtained data were statistically compared. Results: When compared with the control group, both SSEA-1 protein expression and cell proliferation were lowest in the Gd-DPT group (P = 0.000). There was a statistically significant correlation between SSEA-1 expression and MTT results (rho = 0.351; P = 0.003). Conclusions: Nevertheless, the data obtained from in vitro experiments may not directly correspond to clinical applications. However, the mere fact that a drug used solely for diagnostic purposes may repress chondrocyte cell proliferation should be carefully considered by clinicians.
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    Is it possible to treat osteosarcoma using oligonucleotides confined into controlled release drug delivery systems?
    (Bentham Science Publishers Ltd, 2017) Topuk, Savaş; Akyuva, Yener; Karaaslan, Numan; Mutlu, Çağri Ata; Yılmaz, İbrahim; İşyar, Mehmet; Şirin, Duygu Yaşar; Akkaya, Semih; Özbek, Hanefi; Mahiroğulları, Mahir
    Purpose: The present study aimed to analyze the researches that are at the experimental phase concerning osteosarcoma treatment. The researches included drug delivery systems which allow controlled release and imbue small interfering-/micro-ribonucleic acid. Methods: Without any language preference, we searched US National Library of Medicine National Institutes of Health, Embase, OVID, Cochrane Library database of clinical trials from 1843 to May 25, 2016 and traced all the references of incorporated documents. The data were evaluated using descriptive statistics and the results are shown as frequency (%). Results: We haven't encountered any drug delivery system in which Small interfering ribonucleic acid/ micro ribonucleic acid oligonucleotides were embedded successfully against osteosarcoma. There has been only one research in which hairpin-ribonucleic acid was embedded. Conclusion: It was considered that drug delivery system enabling controlled oligonucleotide release in the treatment period of osteosarcoma was not projected for the clinical use. However, it cannot be neglected that the mentioned experimental studies with regard to osteosarcoma treatment establish the basis of target therapies. The method in question looks promising regarding effective treatment of osteosarcoma in the future.
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    Is there a treatment protocol in which platelet-rich plasma is effective?
    (Elsevier Science Bv, 2016) Yılmaz, İbrahim; Akkaya, Semih; İşyar, Mehmet; Batmaz, Ahmet Güray; Güler, Olcay; Öznam, Kadir; Uğras, Akın; Mahiroğulları, Mahir
    Aim: We aimed to reveal whether there are prospective suggestions for effective and standard platelet-rich plasma applications. Methods: We searched for clinical trials and traced all the references of incorporated documents. Results: In literature, there was no study indicating which disease is treated by which mechanism of action, how much dose and content are prepared and applied, when the treatment is applied and how many cures are applied. Conclusion: Guides introducing which concentrations of PRP are used for which diseases are to be prepared immediately by a committee which is comprised of primarily orthopedists, clinical pharmacologists and toxicologists.
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    The association between different molecular weights of hyaluronic acid and CHAD, HIF-1 alpha, COL2A1 expression in chondrocyte cultures
    (Spandidos Publications Ltd, 2018) Yaşar Şirin, Duygu; Kaplan, Necati; Yılmaz, İbrahim; Karaarslan, Numan; Özbek, Hanefi; Akyuva, Yener; Kaya, Yasin Emre; Öznam, Kadir; Akkaya, Nuray; Güler, Olcay; Akkaya, Semih; Mahiroğulları, Mahir
    The aim of the present study was to investigate the effects of three different formulations of hyaluronic acid (HA): Low molecular weight (MW) Sinovial One((R)), medium MW Viscoplus((R)) and high MW Durolane((R)), on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1 alpha (HIF-1 alpha) and chondroadherin (CHAD) expression in primary chondrocyte cultures. Standard primary chondrocyte cultures were established from osteochondral tissues surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted light microscope; cell proliferation was determined with a MTT assay and confirmed with acridine orange/propidium iodide staining. Levels of CHAD, COL2A1 and HIF-1 alpha expression were assessed using specific TaqMan gene expression assays. The results demonstrated the positive effect of HA treatment on cell proliferation, which was independent from the MW. COL2A1 expression increased in the medium and high MW HA treated groups. It was observed that HIF-1 alpha expression increased in the high MW treated group alone. CHAD expression increased only in the medium MW HA treated group. Evaluation of gene expression revealed that levels of expression increased as the duration of HA application increased, in the medium and high MW HA treated groups. In terms of increased viability and proliferation, a longer duration of HA application was more effective. Taken together, it may be concluded that the administration of medium and high MW HA may be a successful way of treating diseases affecting chondrocytes in a clinical setting.