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    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, Necati
    Aim: 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.
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    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, Yener
    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-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.