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Background: It is known that a possible decrease in disc height (DH) and foraminal size after open lumbar microdiscectomy (OLM) may cause pain in the long term. However, there is still insufficient information about the short- or long-term pathoanatomical and morphological effects of microdiscectomy. For example, the exact temporal course of the change in DH is not well known., Objective: The purpose of this study was to examine morphological changes in DH and foramen dimensions after OLM., Methods: In patients who underwent OLM for single-level lumbar disc herniation, MRI scans were obtained before surgery, and at an average of two years after surgery. In addition to DH measurements, foraminal area (FA), foraminal height (FH), superior foraminal width (SFW), and inferior foraminal width (IFW), were measured bilaterally., Results: A postoperative increase in DH was observed at all vertebral levels, with an average of 5.5%. The mean right FHs were 15.3 mm and 15.7 mm before and after surgery, respectively (p= 0.062), while the left FHs were 14.8 mm and 15.8 mm before and after surgery (p= 0.271). The mean right SFW was 5.4 mm before surgery and 5.7 mm after surgery, while the mean right IFW ranged from 3.6 mm to 3.9 mm. The mean left SFW was 4.8 mm before surgery and 5.2 mm after surgery, while the mean left IFW ranged from 3.5 mm to 3.9 mm. Before surgery, the FAs were, on average, 77.1 mm2 and 75.6 mm2 on the right and left sides, respectively. At the 2-year follow-up, the mean FAs were 84.0 mm2 and 80.2 mm2 on the right and left sides, respectively., Conclusions: Contrary to prevalent belief, in patients who underwent single-level unilateral OLM, we observed that there may be an increase rather than a decrease in DH or foramen size at the 2-year follow-up. Our findings need to be confirmed by studies with larger sample sizes and longer follow-ups.

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., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Ozkan Ates, Ibrahim Yilmaz, Numan Karaarslan, Emel Ersoz, Fatma Bahar Hacioglu Kasim, Mustafa Dogan, Hanefi Ozbek.)

Aim: To evaluate the effects of favipiravir (FVP) on cell viability and cytotoxicity in human degenerated primary intervertebral disc (IVD) tissue cell cultures. Furthermore, the protein expressions of hypoxia-inducible factor 1 alpha (HIF-1α), nuclear factor-kappa-b (NF-kB), and interleukin-1 beta (IL-1β) were also examined., Material and Methods: Untreated cell cultures served as the control group, named group 1. Cell cultures treated with FVP served as the study group, named group 2. Pharmacomolecular analyses were performed in all groups at 0, 24, 48, and 72 hours (h). Obtained data were evaluated statistically., Results: Cell proliferation was suppressed in the FVP-treated samples compared to the control group samples at 24 and 72 h, and this was statistically significant (p < 0.05). Decreased or increased protein expression levels of HIF-1α, NF-κB, and IL-1β in FVPtreated samples may be an indication of suppression in anabolic events as well as proliferation in IVD cultures. FVP administration showed that AF/NP cells in a culture medium may induce a strong inflammatory response to FVP. This strong inflammatory response is likely to cause slowed proliferation. It may also be a trigger for many catabolic events. NF-κB expression increased within the first 24 h and then decreased rapidly. Based on the data obtained, it may be suggested that the rapidly increasing NF-kB may have stimulated the expression of many antiproliferative genes., Conclusion: The suppression of IL-1β and NF-kB protein expressions in IVD cells treated with FVP is important in the treatment of IVD degeneration (IDD). If the protein expression of HIF-1α could be increased along with the suppression of IL-1β and NF-kB, FVP would perhaps be a promising pharmacological agent in the treatment of IDD.

Aim: To investigate the supplementation of alpha-lipoic acid (ALA) at the molecular level to determine its effect on primary cell cultures prepared from human intervertebral disc (IVD) tissue in an in vitro environment., Material and Methods: Human primary cell cultures were prepared from IVD tissue resected during surgery. While cell cultures without ALA supplementation formed the control group, those with ALA supplementation formed the study group. All cell groups were stained using acridine orange/propidium iodide (AO/PI), and the incidence of apoptotic cell death was determined under a fluorescent microscope. Cell surface morphology and extracellular matrix (ECM) structures were evaluated under an invert light microscope. Simultaneously, cell proliferation was evaluated by MTT?ELISA analysis, and the expressions of chondroadherin (CHAD), cartilage oligomeric protein (COMP), interleukin-1 beta (IL-1?), and matrix metalloproteinase (MMP)-7 and-19, which are genes associated with ECM regulation, were tested using qRT?PCR. The data obtained were evaluated statistically using Tukey?s honestly significant difference (HSD) test after analysis of variance (ANOVA) was performed. The alpha significance value was accepted as < .05., Results: Compared to the cells in the control group, it was observed that both proliferation was suppressed and ECM structures deteriorated in the cells in the study group., Conclusion: Also, it was reported that the all-gene expression levels changed. ALA supplementation can negatively affect human IVD primary cell cultures in an in vitro environment.

Aim: To evaluate the preoperative and postoperative clinical and radiological findings of patients treated surgically for cervical spondylosis., Material and Methods: The patients included in the study (n=32) were divided into three groups according to their preferred surgical approach. These surgical approaches are posterior cervical laminectomy, posterior cervical laminectomy plus fusion, and anterior approach. Then, pre-and postoperative modified Japanese Orthopaedic Association Myelopathy (mJOA) scores, Torg- Pavlov ratios measured on direct cervical radiography, and pre-and postoperative lordosis angles were recorded. The data obtained were evaluated statistically., Results: The radiological examinations revealed that the average preoperative Torg-Pavlov ratio was < 1 in 29 patients. The average sagittal spinal canal diameter was 9 mm, and myelomalacia was detected in 25 patients. Postoperative mJOA scores in patients who underwent anterior corpectomy and fusion and posterior laminectomy were statistically significant (p < 0.05). The highest symptomatic recovery rate was found in patients with preoperative neck pain. This finding was not statistically significant (p > 0.05). Changes in the postoperative lordosis angles and recovery rates were also observed, depending on the preferred surgical approach., Conclusion: If there is no kyphotic deformity or straightening of the cervical lordosis, a posterior laminectomy can be performed to avoid the long-term complications caused by an anterior corpectomy. It should be kept in mind that multi-segment and wide laminectomies may cause instability problems.

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 α 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., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

The present study aimed to investigate the effects of paracetamol, an analgesic and antipyretic that is used in emergency departments and neurosurgery departments for postoperative pain management on intervertebral disc tissue. Paracetamol-treated human primary cell cultures and untreated cell cultures were compared using molecular analyses. Cell proliferation and gene expression were statistically analyzed. Cell proliferation was suppressed on days 10 (P=0.05) and 20 (P<0.05) in the paracetamol-treated groups. Gene expression of chondroadherin, matrix metalloproteinase (MMP)-7, MMP-13 and MMP-19 was higher in the paracetamol-treated samples while gene expression of Cartilage Oligomeric Matrix Protein and interleukin-1β was lower (P<0.05). Paracetamol, which appears innocuous compared with many analgesics, may increase the expression of MMPs, which serve a significant role in catabolic reactions and suppress the proliferation of intact intervertebral disc tissue cells., (Copyright: © Karaarslan et al.)

Aim: To explain how to resect hippocampal tissue in rats used as live mammalian subjects for the resection of fresh cerebral tissue in laboratories., Material and Methods: Adult male Wistar-Albino rats (n=50) were used for this purpose., Results: The average bodyweight of the rats was 316.4 ± 11.71 g, and the average weight of the resected hippocampal tissues was 1.01 ± 0.03 g; however, there were no statistically significant differences between the body weights and the hippocampal tissue weights (p > 0.05). The hippocampal tissues to be used in the study were excised practically by preserving the original anatomical configuration without injury to the tissue., Conclusion: This paper elucidates a simple, step-by-step methodology for performance in the laboratory in order to improve the standardization of hippocampal tissue dissection.

Background: In the present study, the first aim was to address the detrimental effects of the fluoroscopy procedure performed by physicians and other health-care professionals in neurosurgery clinics, then to examine precautions that should be taken to avoid harmful effects of radiation and radioactive substances during this process. The second aim was to handle the rights provided for health-care professionals exposed to the radiation in workplaces., Methods: A standardized questionnaire was used for a multicenter survey. Volunteer, intellectual, and cooperative participants ( n = 41) were randomly chosen. The survey was prepared considering reports drawn up by the International Atomic Energy Agency. The questions concerning safe and effective fluoroscopy procedure were asked to the participants. The answers received were statistically evaluated. The alpha significance value was accepted as 0.05., Results: Two neurosurgeons only knew the legal rights that they might possess due to the exposure to the radiation or radioactive substances., Conclusion: The survey conducted among the health-care professionals revealed the insufficiency of knowledge about the protection from the radiation exposure or radioactive substances in workplaces. Furthermore, both health-care professionals working in radiology clinics, and those in neurosurgery and other clinics who are likely to be exposed to the radiation or radioactive substances have the rights afforded by the law., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Aim: To investigate the effects of metformin, a drug used widely for the treatment of type 2 diabetes mellitus, on human primary cell cultures prepared from uninjured segment of disc material intervertebral disk tissues., Material and Methods: Primary cell cultures were prepared using the tissues of six patients (three males and three females) who had undergone lumbar microdiscectomy and sequestrectomy. Untreated samples served as the control group, and metformintreated samples served as the experimental group. All the samples were evaluated using an inverted light microscope, acridine orange/propidium iodide staining (AO/PI), and a fluorescence microscope. The cytostatic and cytotoxic effects of metformin, which was administered to the samples using a commercial MTT assay kit, were also evaluated. The data obtained were statistically assessed, and the alpha significance value was accepted as less than 0.05. In addition, for the groups’ changes in the expressions of chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1β (IL-1β) matrix metalloproteinase 7 (MMP-7), and matrix metalloproteinase 19 (MMP-19), genes related to the extracellular matrix synthesis and degradation were determined using gene-specific TaqMan Gene Expression Assays., Results: The administration of the drug adversely affected nucleus pulposus (NP)/annulus fibrosus (AF) cells and extracellular matrixâ€"like structures. This was statistically significant (p < 0.05)., Conclusion: Clinicians should not disregard the adverse effects of metformin, which is used widely in clinical practice, on the components of intervertebral disk tissues.

Aim: 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?, 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.

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-1β 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.

The 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-1β, 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.

In 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., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Aim: 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-1α) 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-1α gene expressions and HIF-1α 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.

Aim: To investigate the effects of methylphenidate (MPH), on intervertebral disc tissue (IVD) cell cultures and extracellular matrix structures. Changes in the expression of some important marker genes involved in anabolic and catabolic mechanisms of IVD extracellular matrix formation were also evaluated., Material and Methods: Primary cultures of nucleus pulposus cells (NPCs) and annulus fibrosus cells (AFCs) were isolated from tissues obtained from the operated patients. Cell viability and proliferation were tested, and the cell surface morphologies were evaluated by microscopy. The expressions of the chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1 beta (IL-1β) and matrix metalloproteinase (MMP) -7 and MMP-19 genes were evaluated using the quantitative real-time polymerase chain reaction (qRT-PCR). A value of p < 0.05 was considered statistically significant., Results: The viability and proliferation of intervertebral disc tissue cells decreased in response to MPH treatment and the expression of the investigated genes also changed., Conclusion: The data obtained from in-vitro studies may not directly adaptable to clinical applications. However, the fact that the central nervous system stimulant MPH can suppress proliferation of cells derived from IVD tissue should be considered carefully by clinicians.

Background: The study aimed to investigate the effects of the active ingredient, nimodipine, on chondrocyte proliferation and extracellular matrix (ECM) structures in cartilage tissue cells., Methods: Chondrocyte cultures were prepared from tissues resected via surgical operations. Nimodipine was then applied to these cultures and molecular analysis was performed. The data obtained were statistically calculated., Results: Both, the results of the (3-(4,5 dimethylthiazol2-yl)-2,5-diphenyltetrazolium (MTT) assay and the fluorescence microscope analysis [a membrane permeability test carried out with acridine orange/ propidium iodide staining (AO/PI)] confirmed that the active ingredient, nimodipine, negatively affects the cell cultures., Conclusion: Nimodipine was reported to suppress cellular proliferation; chondroadherin (CHAD) and hypoxia-inducible factor-1 alpha (HIF-1α) expression thus decreased by 2.4 and 1.7 times, respectively, at 24 hrs when compared to the control group (p < 0.05). Furthermore, type II collagen (COL2A1) expression was not detected (p < 0.05). The risk that a drug prescribed by a clinician in an innocuous manner to treat a patient by relieving the symptoms of a disease may affect the proliferation, differentiation, and viability of other cells and/or tissues at the molecular level, beyond its known side effects or adverse events, should not be forgotten., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: To evaluate the effects of pre- and intra-operatively administered daptomycin (DAP) on the intact human primary intervertebral disc tissue cells., Material and Methods: Primary cell cultures were established using tissues obtained through decompressive laminectomy, traumatic intervertebral disc herniation excision, and posterior transpedicular stabilization. Non-drug-administered samples were used as a control group. The samples treated with DAP formed the study group. Molecular assays for proliferation and gene expression were performed. The obtained data were evaluated statistically, and results with a value of p < 0.05 were accepted as significant., Results: While no reduction was observed in the proliferation, the gene expression of intact intervertebral disc tissue cells was time-dependently decreased compared to the control group, and these results were reported to be statistically significant., Conclusion: This study observed the effect that a pharmaceutical preparation, which was used on intervertebral disc tissue before and after the operation, had on normal, healthy, and intact tissue. It concludes that alterations in the expression of genes involved in the anabolic and/or catabolic process, even in adjacent healthy tissue, may slow down the healing process of the damaged tissue or cause undesired cell differentiation.

Aim: To investigate the efficacy of empirical antibiotic treatment in culture-negative pyogenic vertebral osteomyelitis (PVO) cases., Material and Methods: The records of patients with culture-negative PVO who were treated at infectious diseases and neurosurgery outpatient clinics in the past four years were examined retrospectively. The control group comprised healthy subjects with similar age, gender, and body mass index but without pathology. The comparison of the groups was performed by analysis of variance. Statistical significance was accepted as p < 0.05., Results: No statistically significant difference in the white blood cell count and erythrocyte sedimentation rate was found between the spondylodiscitis and the healthy subject groups when the blood parameters obtained before and after the treatment (p > 0.05). However, a statistical significance was assessed in the results of the comparison for C-reactive protein (p < 0.05)., Conclusion: In the context of evidence-based medicine and the rational use of antibiotics, it is clear that antibiotics should be preferred according to the culture antibiogram results in the treatment of infectious diseases.

Aim: 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.

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.

Introduction: The aim of the present study is to investigate the effects of pregabalin (PGB) on chondrocyte proliferation and collagen type II ( COL2A1 ), hypoxia-inducible factor 1-α ( HIF-1 α), and chondroadherin ( CHAD ) gene expression in osteoarthritic chondrocytes., Material and Methods: Standard primary chondrocyte cultures were prepared using osteochondral tissues that were surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted microscope, and cell death and proliferation were determined through MTT analysis, which was confirmed by AO/PI staining and statistically evaluated. The expression levels of CHAD , COL2A1 , and HIF-1 α genes were assessed using gene-specific TaqMan Gene Expression Assays., Results: MTT analyses showed that PGB administration did not have a negative or toxic effect on cell viability and proliferation in cultured chondrocytes ( p < 0.001), but in our morphological evaluation extracellular matrix development was observed to be weaker in cultures treated with PGB. After 24 h of treatment, COL2A1, HIF-1α, and CHAD gene expression decreased in the groups to which PGB was applied compared to gene expression before the experiment (at 0 h); at 48 h, CHAD and HIF-1α expression increased to the same level as the control group, but the expression of COL2A1 continued to decrease., Conclusions: Further studies need to be conducted with more participants to prove that there is a negative correlation between extracellular matrix formation and PGB administration. Our preliminary data show that even at low doses and over short-term administration, PGB may affect chondrocyte cells at the gene-expression level., Competing Interests: The authors declare no conflict of interest.

Non-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 µM). 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.

The 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-1α (HIF-1α) 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-1α. 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.

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 ® , medium MW Viscoplus ® and high MW Durolane ® , on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1α (HIF-1α) 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-1α 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-1α 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.

Aim: 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.

Aim: Our aim was to determine whether a combination of sagittal index (SI), canal compromise (CC), and loss of vertebral body height (LVBH) is associated with the severity of neurological injury in patients with thoracolumbar burst fractures., Materials and Methods: Seventy-four patients with thoracolumbar burst fracture undergoing instrumentation between 2010 and 2015 were analyzed retrospectively. The degree of neurological injury was determined using the American Spinal Injury Association (ASIA) scoring system. The association between the morphology of the fracture and the severity of neurological injury was analyzed., Results: There was a strong association between fracture morphology and the severity of neurological injury. Of the patients, 77.5% with SI ≥20°, 81.6% with CC ≥40%, and 100% with LVBH ≥50% had lesion according to ASIA. All of 7 patients with ASIA A had SI ≥20°, CC ≥40%, and LVBH ≥50%. On the other hand, 79% of the patients with ASIA E had SI <20°, 83.7% of the patients with ASIA E had CC <40%, and all of the patients with ASIA E had LVBH <50%. SI, CC, and LVBH were lower in neurologically intact patients (ASIA E), whereas they were higher in patients with neurological deficits (ASIA A, B, C, D) ( P = 0.001; P < 0.01). These measurements had 100% negative predictive values and relatively high positive predictive values., Conclusion: SI, CC, and LVBH are significantly associated with the severity of neurological injury in patients with thoracolumbar burst fractures. The patients with SI >25°, the patients with CC >40%, and the patients with LVBH >50% are likely to have a more severe neurological injury., Competing Interests: There are no conflicts of interest.

Aim: To analyse the effect of MMP-3 (Matrix Metalloproteinase Enzyme-3)-one of the extracellular matrix proteins- on the prognosis and biological behaviour of meningiomas., Material and Methods: 79 cases of meningioma that were operated in our clinic between 2005 and 2010 were retrospectively analysed. Age, sex, preoperative peritumoral edema, histological subtype, grade, Ki-67 expression, MMP-3 staining pattern and recurrence rate were analysed. Pathological preparations were graded according to the WHO (World Health Organisation) 2007 grading system., Results: Of the MMP-III positive cases; 24 cases (60%) were grade I, 16 cases were grade II. The MMP-3 staining pattern was significantly positive (80%) in grade II meningioma. 14 of the MMP-3 positive cases were atypical meningiomas. Of the 20 cases with high Ki-67 proliferation index (PI), 12 cases (60%) were MMP-3 positive and 8 cases (40%) were MMP-3 negative. Rates of recurrence and preoperative peritumoral edema were high in cases with MMP-3 positivity., Conclusion: In this study it was determined that MMP-3 positivity has a strong relationship with meningiomas having an aggressive character. MMP-3 may be used as a proliferation marker for biological behaviour, recurrence rate and prognosis of meningiomas.