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.

Are We Using Slow-Acting Symptomatic Chondroprotective Drugs Conscious Enough?

BACKGROUND: Osteochondral injuries constitute an entity that is widespread and can be seen in patients of all ages. Actual treatment modalities aim to relieve pain, obtain full range of movement of the joint, and improve the quality of life. There are many slow-acting chondroprotective agents prevalently used in the United States that are classified as nutritional support but not as medicines . This study presents the importance of clinical adverse effect profiles as well as the pharmacological mechanism of action and application of combinations of drugs that are widely prescribed and not subjected to control. METHODS: Electronic databases were searched with keywords about the chondroprotective drugs without any language restriction. Evaluations of the descriptive statistics were represented via Microsoft Office Excel 2010 lists in the form of a mean±standard deviation or frequency (%). The first evaluation showed that 1502 studies were potentially relevant. Following exclusion of the 1277 studies which were not clinical, full versions of the remaining 225 studies were subjected to further evaluation. No controlled, blinded, randomized and/or comparative studies met the inclusion criteria of the study, and no studies evaluated the comparative clinical results of the hyaluronan of different molecular weights. RESULTS: The findings of this study concluded that especially when prescribing drugs with ingredients like GS and CS, many patients' pre-existing conditions must be considered, such as whether the patient has a glucose intolerance or not. Additionally, mineral toxication should be considered since the drugs contain minerals, and after the application of injected hyaluronan, complications should be considered. CONCLUSION: Clinical, controlled and comparative studies about the use of chondroprotective drugs must be performed to define the benefits of these drugs, if any, in order to determine the most suitable time for operative intervention.

Are chondrocytes damaged when rheumatologic inflammation is suppressed?

AIM: The use of biological agents (BAs) for treating diseases such as rheumatoid arthritis (RA), spondyloarthropathy, and systemic lupus erythematosus to reduce inflammation has been fruitful. Especially as part of the increasing number of studies on the intra-articular application of BAs, the effects of BAs on cartilage have been widely investigated. In the present study, the effects of rituximab, abatacept, and adalimumab, all approved antirheumatic agents, on human primary chondrocytes were investigated comparatively and on the molecular level through viability, proliferation, and toxicity analyses. MATERIALS AND METHODS: Osteochondral tissues from the distal femur and proximal tibia were resected during total knee arthroplasty from patients (n = 3) with confirmed gonarthrosis in whom all medical or conservative treatments had failed. Standard human primary chondrocyte cell culturing was carried out. Immunophenotyping was performed on the cells that adhered to the flask, and their chondrotoxicity was observed using a flow cytometry device. Images of the cells showing chondrotoxicity were analyzed using invert and environmental scanning microscopes, and microimages were obtained. The MTT-enzyme linked immunosorbent assay was performed to observe the toxic effects of BAs on the proliferation of chondrocytes at 24 and 48 h. The results were analyzed using the number of cells and proliferation; statistical comparisons among the groups were carried out using one-way ANOVA. The alpha significance level was set at <0.01. RESULTS: These pharmaceutical agents were chondrotoxic, especially on viability and proliferation (p = 0.0000). CONCLUSION: BAs are generally used during active inflammation, and following the management of inflammation, their dosage should be determined taking into consideration their cellular-level toxic effects on chondrocytes.

Calprotectin levels in patients with rheumatoid arthritis to assess and association with exercise treatment.

Rheumatoid arthritis (RA) is a chronic, inflammatory, and autoimmune disease that can cause permanent joint damage. In our study, we aim to analyze the change in calprotectin levels following the low-density exercise levels applied to the patients with RA. Twenty-eight patients with RA and 30 healthy controls were included in this study. To evaluate the activity of disease in RA, scores of disease activity that has increased (DAS-28) are figured. Calprotectin, nitric oxide (NO), white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) levels are tested as the laboratory evaluation. Calprotectin, NO, CRP, ESR, WBC, and RF levels were significantly higher in the patient group compared to the control group (p < 0.01, p < 0.001, p < 0.01, p < 0.01, p < 0.01, and p < 0.05, respectively). In correlation analysis applied to the patient group with RA, there has been determined a positive relation with calprotectin, and DAS-28, CRP, NO, RF, and WBC (p < 0.001, p < 0.05, p < 0.001, p < 0.05, and p < 0.05, respectively). In result of the low-density exercise treatment applied to patients with RA for 8 weeks, there has been determined a significant decrease in calprotectin, DAS-28, NO, CRP, ESR, and RF levels (p < 0.05, p < 0.001, p < 0.01, p < 0.05, p < 0.05, and p < 0.05, respectively). As a result, a significant relation is found between RA disease activity and calprotectin levels and other inflammatory parameters. At the same time, it shows that calprotectin which is a significant indicator of local inflammation can be used as a good identifier in following up exercise treatment.

Are biological agents toxic to human chondrocytes and osteocytes?

PURPOSE: The aim of the present study is to investigate the effects of biological agents (BAs) on human chondrocytes and osteocytes in vitro. METHODS: Primary cell cultures obtained from gonarthrosis patients were divided into four groups, two of which were designated as control cultures of chondrocyte and osteocyte, and the other two groups were exposed to BAs administered via the culture medium. Cultured cells were characterized by immunophenotyping. Before and after administration of the agents, the cultures were observed by inverted and environmental scanning electron microscopy (ESEM). The number of live cells and the proliferation rate were monitored by MTT assay. RESULTS: Rituximab and adalimumab were the least toxic agents to chondrocytes, whereas adalimumab and etanercept were to osteocytes. CONCLUSION: During periods of intense active inflammation, the concentration of the preferred BAs after inhibition of inflammation needs to be emphasized when their effects on cartilage and bone tissue are considered at the cellular level if the clinical practice is to continue.

Is 25(OH)D Associated with Cognitive Impairment and Functional Improvement in Stroke? A Retrospective Clinical Study.

BACKGROUND: In recent years, vitamin D deficiency has been suggested as a risk factor for ischemic stroke and stroke severity in both animal models and clinical studies. In this retrospective study, we investigated the relationship between 25-hydroxyvitamin D [25(OH)D] levels and functional outcomes in stroke patients during neurological rehabilitation program. We also investigated whether there is an association between 25(OH)D levels and cognitive impairment. METHODS: The study included the medical records of 120 stroke patients who participated in a neurological rehabilitation program. The motor and cognitive components of the Functional Independence Measurements of all patients at admission and discharge were recorded. The Functional Ambulatory Scale was used to assess motor functional status, and the Turkish-validated version of the minimental state examination test was used to assess cognitive status. RESULTS: A significant correlation was found between 25(OH)D level and cognitive impairment among patients who had ischemic strokes. High levels of 25(OH)D were associated with greater functional gain during the rehabilitation program in both ischemic stroke patients and hemorrhagic stroke patients. CONCLUSIONS: High 25(OH)D levels might be associated with greater functional improvement and with less cognitive impairment in stroke patients.

Effects of 12-week combined exercise therapy on oxidative stress in female fibromyalgia patients.

The aims of this study were to investigate the effect of exercise therapy on the oxidative stress in fibromyalgia patients and relationship between oxidative stress and fibromyalgia symptoms. Thirty women diagnosed with fibromyalgia according to the American College of Rheumatology preliminary criteria, and 23 healthy women whose age- and weight-matched women were enrolled the study. Pain intensity with visual analog scale (VAS), the number of tender points, the fibromyalgia impact questionnaire (FIQ), the Beck depression inventory (BDI) were evaluated. The oxidative stress parameters thiobarbituric acid reactive substances, protein carbonyls, and nitric oxide, and antioxidant parameters thiols and catalase were investigated in patients and control group. After, combined aerobic and strengthen exercise regimen was given to fibromyalgia group. Exercise therapy consisted of a warming period of 10 min, aerobic exercises period of 20 min, muscle strengthening exercises for 20 min, and 10 min cooling down period. Therapy was lasting 1 h three times per week over a 12-week period. All parameters were reevaluated after the treatment in the patient group. The oxidative stress parameters levels were significantly higher, and antioxidant parameters were significantly lower in patients with fibromyalgia than in the controls. VAS, FIQ, and BDI scores decreased significantly with exercise therapy. The exercise improved all parameters of oxidative stress and antioxidant parameters. Also, all clinical parameters were improved with exercise. We should focus on oxidative stress in the treatment for fibromyalgia with the main objective of reducing oxidative load.

Is there a new finding added to the fibromyalgia syndrome?

OBJECTIVE: The aim of this study is to examine depression and anxiety related arrhytmia risk in fibromyalgia syndrome (FMS). METHODS: Fifty-nine patients with the diagnosis of FMS and 20 control participants were included in the study. Fibromyalgia Impact Questionnaire (FIQ), Visual Pain Scale (VPS) surveys were applied to determine the severity of the disease. Beck Anxiety (BAS) and Beck Depression scales (BDS) were applied to all participants. Electrocardiograms were obtained from all participants. P-wave dispersions (Pd) were estimated to determine the risk of the atrial arrhythmia, and QT wave dispersion (QTd) and corrected QT(QTdd) values were used to predict the risk of ventricular arrhythmia. RESULTS: BAS and BDS results were significantly higher in the patient group compared to the control group (p˂0001). In the patient group, Pd was significantly longer (p=0.034). Other clinical, and demographic data did not differ significantly between groups. CONCLUSION: In this study, the risk of arrhythmia in FMS was evaluated and increased Pd in patients with FMS compared to the control group was detected. This finding shows increased risk of atrial fibrilation (AF) in patients with FMS. If we consider that patients with fibromyalgia consist relatively of young patients together with the increased risk of AF with age, it is important to follow-up these patients in later ages for AF risk.

Relationship between the size of bone marrow edema of the talus and ankle pain.

BACKGROUND: We sought to determine the changes in the size of the edema observed on MRI scans and its relation to the patient's pain during activity and pain during rest in bone marrow edema. METHODS: A total of 26 patients were followed up at 3-month intervals for a period of 1 year. During the follow-ups, magnetic resonance imaging scans of the patients' ankles were obtained; the scores obtained on the American Orthopaedic Foot and Ankle Society functional rating scale and visual analog scale were determined. The changes in these parameters and the correlation between them were examined. RESULTS: The size of the edema as observed on magnetic resonance imaging scans decreased, and the pain during activity and rest decreased. Although there is a correlation between the decrease in the edema size observed on magnetic resonance imaging scans and decrease in the pain during activity, there is no correlation between the decrease in the edema size observed on magnetic resonance imaging scans and the decrease in pain during rest. CONCLUSIONS: Patients can be informed more precisely, that the pain during rest and activity may not decrease after the third and sixth month, respectively. Magnetic resonance imaging may not alter after the ninth month, so it may not be necessary to be performed again.