A Study on the Effects of Dırect Factor Xa Inhibitors and Direct Thrombin Inhibitors on Human Primary Chondrocyte Cultures

Aim:This study investigates the effects of two direct factor Xa inhibitors, apixaban and rivaroxaban, and a direct thrombin inhibitor, dabigatran, on human primary chondrocyte cultures.Materials and Methods:Monolayer cultured chondrocytes were prepared. Cell cultures were treated with dabigatran, apixaban, and rivaroxaban. Cultures without drug treatments served as the control group. Using an inverted light microscope, the cell surface morphology was examined. Cell viability and the toxicity of drugs were evaluated using a commercial assay kit, and the results were confirmed using two nucleic acid binding dyes, acridine orange and propidium iodide. The expressions of cartilage oligomeric protein, matrix metalloproteinase-7, and matrix metalloproteinase-19 were assessed using the real-time polymerase chain reaction analysis. All the analyses were performed within 21 days. The data obtained were statistically evaluated.Results:The administration of the three drugs changed the cell viability, proliferation, and expressions of cartilage oligomeric protein, matrix metalloproteinase-7, and matrix metalloproteinase-19. The results were statistically significant (P<0.05).Conclusion:Results obtained from in vitro studies may not provide accurate and reliable insight for clinical practices. However, clinicians should know that drugs used for the prevention or treatment of diseases may suppress chondrocyte proliferation and damage the extracellular matrix formation

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 (approximate to 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

Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

WOS: 000208224700016PubMed: 16425361AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an experimental model. METHODS: Male Wistar albino rats were assigned into 4 groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis. RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue. CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved

The susceptibility to autoxidation of erythrocytes in diabetic mice: Effects of melatonin and pentoxifylline

Oxidative stress had a great importance in development of complications in diabetes. We investigated effects of melatonin and pentoxifylline in diabetic mice. Swiss albino mice (n=40) were divided into four groups: alloxan-induced diabetes mellitus (DM), alloxan-induced diabetes with melatonin supplementation (DM+MLT), alloxan-induced diabetes with pentoxifylline supplementation (DM+PTX), and control. Glutathione-peroxidase (GSH-Px) activity, malondialdehyde (MDA) and reduced glutathione (GSH) levels, and susceptibility to oxidation of erythrocytes were measured. MDA levels were higher than control in the DM and DM+MLT. The DM had more MDA level than the DM+MLT and DM+PTX (P<0.001). After in vitro oxidation, MDA levels of all groups were found higher than the control. However, they were significantly lower than the DM in DM+PTX and DM+MLT (P<0.001). Although GSH levels of the DM and DM+PTX were less than the control, GSH-Px activity of the DM was lower than the control and DM+PTX (P<0.05). We suggest that there is increased oxidative stress and compromised antioxidant status of erythrocytes in diabetes; however, it can be effectively prevented by melatonin or pentoxifylline supplementation

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

Objective: To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circu-lating 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 experi-mental 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 <0.05. Results: There were significant differences in terms of the stromelysin-1, calciferol, and cobalamin levels of both the T2DM and DPN groups compared to healthy volunteers. These differences were statistically significant (p=0.00). There was a very weak negative correlation between stromelysin-1 and calciferol (p=0.972, r=-0.007) and a weak negative correlation between cobalamin and stromelysin-1 (p=0.062, r=-0.345) in DPN patients, without statistical significance. Conclusion: Serum stromelysin-1 expression may be related to DPN progression in diabetic patients and may be a potential marker in DPN. Calciferol and cobalamin levels may also be important in the development of DPN

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-1 alpha), nuclear factor-kappa-b (NF-kappa B), and interleukin-1 beta (IL-1 beta) 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-1 alpha, NF-kappa B, and IL-1 beta in FVP-treated 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-kappa B 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-1 beta 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-1 alpha could be increased along with the suppression of IL-1 beta and NF-kB, FVP would perhaps be a promising pharmacological agent in the treatment of IDD

Evaluation of the Antidiabetic Property of Capparis Ovata Desf. Var. Palaestina Zoh. Extracts Using In vivo and In vitro Approaches

WOS: 000445417300007PubMed ID: 29595118Background and Objective: This paper is focused on evaluating the various biological activities of C. ovata var. palaestina extracts which could beneficially influence diabetes and its complications. Methods: Alloxan-induced diabetic BALB-c mice were administered intraperitoneally with 100, 300, 500mg/kg doses of ethanol and aqueous extracts of buds and fruits. Furthermore, HPLC, phenolic and flavonoid compounds analysis, ABTS and DPPH free radical scavenging activity, anti-inflammatory activity, agar well diffusion and MIC tests were carried out. Results: Fruit-aqueous; 100mg/kg, 300mg/kg and bud-aqueous; 500mg/kg extracts showed significant hypoglycemic activity. All extracts indicated important antioxidant activity, however, bud-aqueous extract demonstrated the most potent activity. HPLC study exhibited that rutin is found in high amounts in bud-aqueous and bud-ethanol extracts. Furthermore, the bud-aqueous extract depicted stronger and broader antimicrobial activity than other extracts. Fruit-ethanol and bud-ethanol extracts denoted the most potent anti-inflammatory effect even though this effect was significantly shown by all extracts. Finally, high levels of phenolic and flavonoid content were involved in all extracts, but the highest levels were found in fruit-ethanol and bud-ethanol extracts. Conclusion: The results showed that extracts which indicated hypoglycemic, antioxidant, anti-inflammatory, antimicrobial activities may provide a valuable contribution to the management of diabetes and its complications

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