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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; Ozdemir, CigdemIn 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 Sirin, Duygu; Kaplan, Necati; Akyuva, Yener; Gonultas, AylinAIM: 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 Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?(2018) Karaarslan, Numan; Yılmaz, İbrahim; Şirin, Duygu Yaşar; Baykız, Derya; Demirkiran, Aykut; Ateş, ÖzkanAim: Nimodipine is used to prevent cerebrovascular-originated ischemic neurological deficits, yet its effects on nucleus pulposus (NP) cells or annulus fibrosus (AF) cells weren’t studied. This study aimed to examine nimodipine’s effects on vitality and proliferation of chondroadherin (CHAD), type II collagen (COL2A1), and hypoxia-inducible factor 1 alpha (HIF 1?) gene expression in human primary NP/AF cells.Material and Methods: NP/AF cell cultures obtained from 6 patients who underwent microdiscectomy were treated with 100 µMolar nimodipine and analyzed at 0, 24, and 48 h. Data were evaluated using one-way ANOVA and post-hoc Tukey HSD with 95% confidence interval.Results: We observed suppressed cell proliferation and increased necrosis in nimodipine-treated NP/AF cell cultures, especially degenerated tissue. COL2A1 gene expression wasn’t detected in any experimental groups. CHAD and HIF 1? expression had timedependent decreases in control. CHAD and HIF 1? expression were found to decrease at 24h, but increased at 48h in degenerated tissue. In nimodipine-applied intact tissues, CHAD expression was stable at 24h but 1.62 times higher than control at 48h. HIF 1? levels were lower than control.Conclusion: In nimodipine-treated degenerated AF/NP cultures, CHAD and HIF 1? expressions had time-dependent decreases. However, after complete RT-PCR data evaluation, no correlation between nimodipine application and gene expression occurred.Öğe Does transcription factor, induced by daptomycin and vancomycin, affect HIF-1?, Chondroadherin, and COL2A1?(2018) Karaarslan, Numan; Yılmaz, İbrahim; Yaşar Şirin, Duygu; Özbek, Hanefi; Kaya, Yasin Emre; Akyuva, Yener; Kaplan, NecatiAim: 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 Guray; Yılmaz, İbrahim; Özbek, Hanefi; Çalışkan, Tezcan; Şirin, Duygu Yaşar; Kaplan, NecatiNon-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 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; Kaplan, NecatiThe 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 neutrophil-to-lymphocyte ratio as a marker of inflammatory response in spondylodiscitis(2018) Karaarslan, Numan; Yılmaz, İbrahim; Akgün, Feride Sinem; Calıskan, Tezcan; Doğan, Mustafa; Bilir, Bulent; Ateş, ÖzkanAim: Spondylodiscitis, if not diagnosed on time, can cause morbidity or mortality at high rates. This study was carried out with the aim of testing the hypothesis that “neutrophil-to-lymphocyte ratio can be used” especially in cases where it is difficult to diagnose spondylodiscitis.Material and Methods: This study involved 24 patients admitted to the State Hospital of Ministry of Health and Namik Kemal University for spondylodiscitis between January2014 and June2017. After excluding the cases that did not meet the inclusion criteria (n=6), the remaining cases (n=24) were referred to as the study group. A control group was created from healthy volunteers (n=24) who applied for routine physical checkups at the clinic between the same dates and who were similar in terms of age, sex, and body mass index to the study group. Hemogram parameters of the cases in both groups; white blood cell, C-reactive protein, erythrocyte sedimentation rate, and neutrophil-to-lymphocyte ratio were statistically compared.Results: Patients in the spondylodiscitis group, compared to healthy volunteers had statistically significant neutrophil-to-lymphocyte ratio value.Conclusion: Especially in cases where the diagnosis of spondylodiscitis is not assured, the neutrophil-to-lymphocyte ratio parameter, which is less costly than other diagnostic methods and the analysis results of which can be obtained in a shorter time, may be used to support clinical diagnosis.Öğe Is Implant Washing and Wound Irrigation with Rifampicin Effective for Preventing Surgical Site Infections in Lumbar Instrumentation?(Turkish Neurosurgical Soc, 2018) Karaarslan, Numan; Yılmaz, İbrahim; Özbek, Hanefi; Oznam, Kadir; Ateş, Özkan; Erdem, IlknurAIM: To determine whether the washing of implants and autogenous bone grafts with rifampicin, and the irrigation of the surgical field using diluted rifampicin, have any significant effect on the prevention of spinal implant infections. MATERIAL and METHODS: A total of 166 consecutive lumbar stenosis and spondylolisthesis patients undergoing lumbar instrumentation between 2012 and 2016 were analyzed retrospectively. The patients were divided into two groups. Group I (n=85) included patients whose implants were washed with rifampicin immediately before insertion and whose surgical fields were irrigated with diluted rifampicin immediately after insertion. Group II (n=81) included the cases without rifampicin application. Both groups were matched for age, sex, body mass index, and surgical indication. The infection rates of the groups were compared during the first 2 postoperative years. RESULTS: No significant difference was found between the infection rate in Group I and Group II. Only 1 case had surgical site infection (SSI) in Group I, a rate of 1.17% (1 of 85 patients), whereas 2 patients had SSI in Group II, a rate of 2.46% (2 of 81 patients). CONCLUSION: Peroperative washing of implants with rifampicin and irrigation of the surgical field using diluted rifampicin have not been found to be significantly effective in preventing or reducing spinal implant infections. However, further studies with larger series need to be carried out to verify these results.Öğe Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue(Spandidos Publ Ltd, 2018) Karaarslan, Numan; Yılmaz, İbrahim; Şirin, Duygu Yaşar; Özbek, Hanefi; Kaplan, Necati; Kaya, Yasin Emre; Akyuva, YenerThe aim of the present study was to determine whether pharmaceutical preparations with pregabalin (PGB) as an active ingredient, which are widely prescribed by clinicians, exert toxic effects on human primary nucleus pulposus (NP) and annulus fibrosis (AF). Primary human cell cultures were obtained from intact (n=6) and degenerated (n=6) tissues resected from the two groups of patients. Different doses of PGB were applied to these cultures and cells were subjected to molecular analyses at 0, 24 and 48 h. Cell vitality, toxicity and proliferation were assessed using a spectrophotometer. The expression of chondroadherin (CHAD), a (member of the NP-specific protein family), hypoxia-inducible factor-1 alpha (HIF-1 alpha) and type II collagen (COL2A1) was measured using reverse transcription-quantitative polymerase chain reaction. The results revealed that cell intensity increased in a time-dependent manner and cell vitality continued in the cultures without pharmaceuticals. Cell proliferation was suppressed in the PGB-treated cultures independent from the dose and duration of application. PGB was demonstrated to suppress the expression of CHAD and HIF-1 alpha. In contrast, COL2A1 gene expression was not revealed in any experimental group. The present study utilized an in vitro model and the PGB active ingredient used herein may not be representative of clinical applications; however, the results demonstrated that PGB has a toxic effect on NP/AF cell cultures containing primary human intervertebral disc tissue. In summary, the use of pharmacological agents containing PGB may suppress the proliferation and differentiation of NP/AF cells and/or tissues, which should be considered when deciding on an appropriate treatment regime.Öğe Systematic Evaluation of Desmopressin Administered to Patients with Aneurysmal Subarachnoid Hemorrhage in the Light of the Literature(Turkish Neurosurgical Soc, 2020) Karaarslan, Numan; Yılmaz, İbrahim; Akgun, Feride Sinem; Çalışkan, Tezcan; Özbek, Hanefi; Ateş, ÖzkanAIM: To discuss the management of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) developing after subarachnoid hemorrhage, in a comparative manner in the light of the literature. MATERIAL and METHODS: Without country or language restrictions, articles with high evidential value found in electronic databases were compared to our patients' data. RESULTS: After the literature review, three articles were included for systematic evaluation. Desmopressin was administered to the patients for the treatment of hyponatremia, volume contraction, and negative sodium balance caused by SIADH. However, it was not used for preventing re-bleeding. CONCLUSION: To prevent the development of this complication (SIADH), the use of desmopressin, an analogue of vasopressin, is important in routine clinical practice.Öğe Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma(Turkish Neurosurgical Soc, 2019) Karaarslan, Numan; Yılmaz, İbrahim; Özbek, Hanefi; Çalışkan, Tezcan; Topuk, Savas; Yasar Sirin, Duygu; Ateş, ÖzkanAIM: To systematically investigate the role of artificial small interfering RNA (SiRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. MATERIAL and METHODS: Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms post transcriptional gene silencing, small interfering RNA, siRNA, and glioblastoma, either individually or combined (OR and AND), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). RESULTS: After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. CONCLUSION: To be able to evaluate the clinical use of siRNAs, there is an urgent need for in vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.
