Effect of latanoprost on choroidal thickness in patients with newly diagnosed primary open-angle glaucoma.

OBJECTIVE: The purpose of this study was to assess the influence of latanoprost on choroidal thickness in patients with newly diagnosed primary open-angle glaucoma using Swept-Source Optical Coherence Tomography (SS-OCT). METHODS: The retrospective, non-randomized study comprised 40 newly diagnosed primary open-angle glaucoma patients receiving latanoprost therapy (Group 1). Additionally, 40 age- and sex-matched healthy subjects served as the control group (Group 2). Using SS-OCT, measurements of subfoveal, horizontal temporal, and horizontal nasal quadrants choroidal thickness, as well as intraocular pressure (IOP) and retinal nerve fiber layer (RNFL) thickness values, were collected at baseline and after 1 month for both groups. RESULTS: The mean age was 39.8±4.15 years (range: 18-45 years) in group 1 and 41.67±7.95 years (range: 18-45 years) in group 2 (p>0.05). The mean choroidal thickness in the subfoveal area, horizontal temporal quadrant, and horizontal nasal quadrant prior to latanoprost therapy were 263.57±84.23 µm, 233.05±80.08 µm, and 219.52±83.28 µm in the group 1 whereas 278.9±93.88 µm, 243.8±73.37 µm and 209.85±92.92 µm in the group 2. After latanoprost therapy, the mean choroidal thickness in the subfoveal area, horizontal temporal quadrant, and horizontal nasal quadrant changed significantly to 299.77±41.29 µm, 269.9±43.80 µm, and 261.32±45.60 µm in the group 1 (p=0.02, p=0.016, and p=0.012, respectively) (Table 1). However, the mean choroidal thickness in the subfoveal area, horizontal temporal quadrant and horizontal nasal quadrant in group 2 changed not significant and was 279.25±103.37 µm, 246.42±87.07 µm and 203.62±106.74 µm, respectively (p=0.4, p=0.5 and p=0.9, respectively). The mean IOP decreased significantly in group 1 (p=0.000) but did not change significantly in group 2 (p=0.153). There was no difference in RNFL thickness values at baseline and 1 st month in group 1 and group 2 (p>0.05). CONCLUSION: Topical latanoprost may increase choroidal thickness. Swept Source-OCT may contribute to our understanding of the actions of latanoprost on choroidal thickness.

Evaluation of Calciferol, Cobalamin, and Stromelysin-1 in Patients with Diabetic Peripheral Neuropathy due to Type-2 Diabetes Mellitus.

OBJECTIVE: To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circulating levels in patients with diabetic peripheral neuropathy (DPN), patients with DM type 2 (T2DM) without neuropathy, and healthy control groups. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Department of Internal Medicine, Namik Kemal University of Medicine, Tekirdag, Turkey, between November 2020 and February 2022. METHODOLOGY: Healthy, age, and gender matched volunteers who were admitted to the hospital for a check-up with no health problem constituted the control group (n=30). Cases diagnosed with T2DM (n=30) and those with DPN (n=30) comprised the experimental group. Stromelysin-1, calciferol, and cobalamin levels were analysed from blood samples from all groups using enzyme-linked immunosorbent assay (ELISA) with a commercial kit. Tukey's Honest Significant Difference (HSD) test was performed after one-way analysis of variance (ANOVA) for intergroup comparisons. Alpha significance level was accepted as.

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

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.

The effects of rivaroxaban, an oral anticoagulant, on human IVD primary cultures.

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.

Is Favipiravir a Potential Therapeutic Agent in the Treatment of Intervertebral Disc Degeneration by Suppressing Autophagy and Apoptosis?

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-1ß) 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-1ß 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-1ß 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-1ß and NF-kB, FVP would perhaps be a promising pharmacological agent in the treatment of IDD.

Phosphorylation of PI3K/Akt at Thr308, but not phosphorylation of MAPK kinase, mediates lithium-induced neuroprotection against cerebral ischemia in mice.

Lithium, in addition to its effect on acute and long-term bipolar disorder, is involved in neuroprotection after ischemic stroke. Yet, its mechanism of action is still poorly understood, which was only limited to its modulatory effect on GSK pathway. Therefore, we initially analyzed the dose-dependent effects of lithium on neurological deficits, infarct volume, brain edema and blood-brain barrier integrity, along with neuronal injury and survival in mice subjected to focal cerebral ischemia. Thereafter, we investigated the involvement of the PI3K/Akt and MEK signal transduction pathways and their components. Our observations revealed that 2 mmol/kg lithium significantly improved post-ischemic brain tissue survival. Although, 2 mmol/kg lithium had no negative effect on brain microcirculation, 5 and 20 mmol/kg lithium reduced brain perfusion. Furthermore, supratherapeutic dose of lithium in 20 mmol/kg lead to animal death. In addition, improvement of brain perfusion with L-arginine, did not change the effect of 5 mmol/kg lithium on brain injury. Additionally, post-stroke blood-brain barrier leakage, hemodynamic impairment and apoptosis have been reversed by lithium treatment. Interestingly, lithium-induced neuroprotection was associated with increased phosphorylation of Akt at Thr308 and suppressed GSK-3ß phosphorylation at Ser9 residue. Lithium upregulated Erk-2 and downregulated JNK-2 phosphorylation. To distinguish whether neuroprotective effects of lithium are modulated by PI3K/Akt or MEK, we sequentially blocked these pathways and demonstrated that the neuroprotective activity of lithium persisted during MEK/ERK inhibition, whereas PI3K/Akt inhibition abolished neuroprotection. Collectively, we demonstrated lithium exerts its post-stroke neuroprotective activity via the PI3K/Akt pathway, specifically via Akt phosphorylation at Thr308, but not via MEK/ERK.

Investigation of the Potential Effects of Alpha-Lipoic Acid on Human Degenerated Intervertebral Disc Tissue Primary Cell Cultures.

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.

Effects of Vincamine on Testicular Dysfunction in Alloxan-induced Diabetic Male Rats.

Background: Diabetes mellitus (DM) is frequently linked with problems of several organ systems, including retinopathy, neuropathy, and nephropathy. Additionally, patients have changes in sexual functioning, such as decreased libido and fertility. Vincamine, a monoterpenoid indole alkaloid, has hypoglycemic and antioxidant effects. Objectives: This research assessed the impact of vincamine on testicular dysfunction in alloxan-induced male rats by measuring fasting blood glucose, oxidative stress, seminal analysis, and histological examination of the testis. Methods: Wister-albino male rats were randomized into the following groups at random: Untreated-healthy, untreated-DM, vincamine-treated (20 mg/kg) DM, vincamine-treated (40 mg/kg) DM, and clomiphene-treated DM (5 mg/kg). On day 14, rats were sacrificed, and semen/blood samples were collected. Sperm count, motility, and morphological abnormalities were noted by microscopic examination. The testis was examined histopathologically and assessed using Johnsen's score. Results: Compared with the untreated diabetic group, a dosage of 40 mg/kg vincamine generate a significant reduction in fasting blood sugar (FBG). Compared with the untreated diabetic group, the vincamine-treated rats produced greater plasma testosterone levels and Johnsen scores. In the vincamine 20 mg/kg group, sperm concentration was higher than in the vincamine 40 mg/kg group. Conclusions: It is possible that vincamine has a potential preventive effect against diabetes-related reproductive problems attributable to its antioxidant activity and capacity to restore testicular steroidogenesis.

The levels of nitrite, nitrate and lipid peroxidation in diabetic mouse brain: the effect of melatonin and pentoxifylline.

OBJECTIVE: This study investigated the relationship between diabetes (DM) and nitrite, nitrate and MDA levels and effect of melatonin and pentoxifylline. METHODS: Sixty mice were randomly divided into four groups. Control: no action; Diabetes group (DM): after fasting-blood-glucose (FBG) was measured, 150 mg/kg alloxane was applied intraperitoneally three-times every other day; Diabetes + Melatonin (DM + MLT) and Diabetes + Pentoxifylline groups (DM + PTX): following the same procedures with DM, 10 mg/kg melatonin and 50 mg/kg pentoxifylline were administered subcutaneously six days, respectively. Following FBG analysis, brain tissues were taken under the anaesthesia. Nitrite, nitrate and MDA levels were measured. RESULTS: In the all groups with alloxane, FBG were higher than in before application (p < .05). Also, FBG, nitrite, nitrate and MDA levels in the DM + MLT and DM + PTX groups were lower than in the DM (p < .05). CONCLUSIONS: Nitrite and nitrate may be related to etiopathogenesis of DM, and pentoxifylline and especially melatonin relatively decrease nitrite, nitrate and lipid peroxidation.

The effect of music therapy on the physical and mental parameters of cancer patients during hematopoietic stem cell transplantation.

PURPOSE: Music therapy has been used for relaxation in traditional medicine. This study explored the effect of music therapy on the physical and mental parameters of cancer patients during hematopoietic stem cell transplantation (HSCT). DESIGN AND METHODS: Thirty patients who were hospitalized for bone marrow transplantation were included. Traditional Music Therapy of Islamic Turkish Culture was applied to the patients during the transplantation process. Specific physical and psychological parameters of patients were evaluated before and after music therapy. FINDINGS: A positive relationship between anxiety and distress scores was observed. Music therapy had a significant impact on increasing levels of oxygen saturation, and decreasing anxiety and distress levels of the HSCT patients (P < .05). PRACTICE IMPLICATIONS: Music therapy may provide positive effects for patients during HSCT.

Practical Performance of Hippocampal Tissue Resection in Rats in Pharmacomolecular Research.

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.

Does the Energy Restriction Intermittent Fasting Diet Alleviate Metabolic Syndrome Biomarkers? A Randomized Controlled Trial.

The aim of this study was to determine the efficacy of an energy restriction intermittent fasting diet in metabolic biomarkers and weight management among adults with metabolic syndrome. This randomized controlled study was performed with metabolic syndrome patients, aged 18-65 years, at an academic institution in Istanbul, Turkey (n = 70). All participants were randomized to the Intermittent Energy Restriction (IER) intervention group and Continuous Energy Restriction (CER) control group. Biochemical tests including lipid profile, fasting plasma glucose, insulin, glycosylated hemoglobin Type A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, and body composition were evaluated at baseline and at the 12th week in diet interviews. Dietary intake was measured with the 24-h dietary recall method and dietary quality was evaluated with the Healthy Eating Index-2010. Changes in body weight (≈7% weight loss) and composition were similar in both groups. Blood pressure, total cholesterol, triglyceride, low-density lipoprotein (LDL), fasting glucose, and insulin at the 12th week decreased in both groups (p < 0.05). No significant differences were observed in metabolic syndrome biomarkers between the IER and CER groups. The energy-restricted intermittent fasting diet did not cause any deficiencies in macronutrient and fiber intake in the subjects. Healthy Eating Index (HEI) index scores were achieved similarly in both groups, and subjects' dietary intakes were close to daily reference nutritional intake values. The technique used to achieve energy restriction, whether intermittent or continuous, appears to alleviate the metabolic syndrome biomarkers activated by weight loss.

A Study of the Effects of Metformin, a Biguanide Derivative, on Annulus Fibrosus and Nucleus Pulposus Cells.

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.

Systematic Evaluation of Desmopressin Administered to Patients with Aneurysmal Subarachnoid Hemorrhage in the Light of the Literature.

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.

Effects of etanercept, a tumor necrosis factor receptor fusion protein, on primary cell cultures prepared from intact human intervertebral disc tissue.

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-1ß, 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.

Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue.

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-1ß 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.

Investigation of the Effects of Methylphenidate, an Amphetamine Derivative, on Intervertebral Disc Tissue Cell Cultures and Matrix Structures.

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-1ß) 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.

Are Intervertebral Disc Tissue Cells Damaged When Attempting to Prevent Thrombus Formation Using Dabigatran, A New Oral Anticoagulant?

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.

Does Nimodipine, a Selective Calcium Channel Blocker, Impair Chondrocyte Proliferation or Damage Extracellular Matrix Structures?

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.

Evaluation of the Effect of Daptomycin, a Glycopeptide Agent, on Intact Intervertebral Disc Tissue.

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.