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ID PMID Title PublicationDate abstract
21586441 Arthritogenicity of annexin VII revealed by phosphoproteomics of rheumatoid synoviocytes. 2011 Aug OBJECTIVE: To identify novel proteins involved in the pathogenesis of rheumatoid arthritis (RA) and to characterise the identified proteins based on pathogenic and therapeutic aspects. METHODS: The authors applied differential phosphoproteomic analysis to articular synoviocytes between RA and osteoarthritis (OA) to identify proteins differently phosphorylated between RA and OA. Focusing on annexin VII (Anx7), one of the highly phosphorylated proteins in RA, the authors prepared Anx7-transgenic C57BL/6 (Anx7-Tg-B6) mice to evaluate their susceptibility to collagen-induced arthritis (CIA). In addition, the authors examined the effect of anti-Anx7 antibodies (Abs) on CIA and serum levels of cytokines in wild-type DBA/1J mice, which are known to be susceptible to CIA, and in Anx7-Tg-B6 mice. In vitro, the authors examined the effect of the Anx7 knockdown by small interfering RNA on the secretion of cytokines in rheumatoid synoviocytes and the human synovial sarcoma cell line SW982. RESULTS: The Anx7 transgene altered the CIA-resistant B6 mice to CIA-susceptible ones. The Abs treatment suppressed CIA even in the wild-type DBA/1J mice. The serum levels of cytokines including interleukin 6 (IL-6) and TNFα were not altered by the Abs treatment in vivo. On the other hand, the knockdown of Anx7 by small interfering RNA caused downregulation of IL-8 secretion in vitro. CONCLUSIONS: These results indicate that Anx7 participates in the pathogenesis of RA partly through the secretion of IL-8. The study data have demonstrated the pathogenic roles and therapeutic significance of Anx7 in RA for the first time.
22340997 The impact of coping strategies on mental and physical well-being in patients with rheumat 2012 Feb OBJECTIVE: To investigate the relation of coping strategies to coping effectiveness, helplessness, and mental as well as physical well-being as indicators of quality of life. METHODS: Cross-sectional international study. Coping strategies were assessed by a validated 18-item questionnaire, while coping effectiveness and helplessness were measured by numerical rating scales. The predictability of both and quality of life (SF-36) was evaluated by multiple linear regression including demographic and disease-related factors. RESULTS: Four hundred thirty-four rheumatoid arthritis (RA) patients (77% female; mean age 55.96 ± 13.34 years) were included. Distancing was the coping strategy used most frequently in RA patients (mean ± SD 1.89 ± 0.78 on a scale ranging from 0 to 3). Female RA patients used coping strategies significantly more often than males, whereas age and duration of disease did not seem to influence the use of coping strategies. Cognitive reframing and active problem-solving contributed to coping effectiveness while emotional expression was related to helplessness. Coping effectiveness was positively related to general health perception, suggesting certain coping strategies to be effective in influencing the quality of life of RA patients. CONCLUSIONS: Coping strategies used in RA are dependent on gender, but not on age. The use of problem-focused coping strategies may allow for an improved coping effectiveness in patients with RA, while also influencing mental and physical well-being as indicators of quality of life. Coping should therefore be considered as an important factor in determining the overall health state of patients with RA.
20697895 Resveratrol induces apoptosis MH7A human rheumatoid arthritis synovial cells in a sirtuin 2012 Jan Resveratrol, a phytoalexin, reduced the viability of MH7A cells, a human rheumatoid arthritis synovial cell line. In the apoptosis assay, resveratrol increased TUNEL-positive cells and stimulated H2A.X phosphorylation. Resveratrol disrupted mitochondrial membrane potentials in MH7A cells and stimulated cytochrome c release from the mitochondria to the cytosol. Resveratrol activated caspase-3 and caspase-9 but not caspase-8 in MH7A cells. Resveratrol upregulated the expression of the NAD-dependent deacetylase sirtuin 1 mRNA and downregulated the expression of the Bcl-X(L) mRNA, and resveratrol-induced MH7A cell death, mitochondrial damage, and caspase-3/-9 activation were prevented by sirtinol, an inhibitor of sirtuin 1. The results of the present study show that resveratrol induces MH7A cell apoptosis by activating caspase-9 and the effector caspase-3 along mitochondrial disruption as a result of reduced Bcl-X(L) expression, allowing cytochrome c release from the mitochondria into the cytosol, in a sirtuin 1-dependent manner. This suggests that resveratrol could suppress hyperplasia of synovial cells, a critical factor of rheumatoid arthritis.
22246057 IL-33 regulates TNF-α dependent effects in synovial fibroblasts. 2012 Apr The recently described IL-33 acts as a pro-inflammatory cytokine, inducing the expression of multiple responses in the target cells. Although a nuclear localization of IL-33 has been described, its exact functional relevance is presently unknown. The present study was conducted to analyze the effects of IL-33 on the TNF-α induced synthesis of the pro-inflammatory mediators IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the pro-destructive molecules matrix metalloproteinase-1 (MMP-1), MMP-3, and TIMP-1 of rheumatoid arthritis synovial fibroblast (RA-SFs) using RNA overexpression and silencing. TNF-α significantly induced IL-33 mRNA expression and protein synthesis in RA-SFs. TNF-α-induced IL-33 protein expression was mediated via p38 signaling. Immunohistochemistry for IL-33 clearly showed that nuclear translocation of IL-33 was induced in TNF-α stimulated RA-SFs. IL-33 overexpression enhanced TNF-α-induced pro-inflammatory and pro-destructive functions in RA-SFs. IL-33 silencing significantly downregulated TNF-α-induced pro-inflammatory functions, whereas TNF-α-induced pro-destructive functions were less influenced by IL-33 silencing. This study identifies IL-33 as a critical regulator/enhancer of TNF-α-induced functions in RA-SFs, pointing to a central role of this cytokine in the perpetuation of pro-inflammatory and pro-destructive processes in rheumatoid arthritis (RA) and other inflammatory and degenerative diseases.
22477733 Tight control early rheumatoid arthritis clinic in Hong Kong: a pilot study. 2012 Apr OBJECTIVE: To evaluate disease activity in early rheumatoid arthritis patients in daily practice 1 year after applying a tight control treatment strategy aimed at lowering disease activity (Disease Activity Score 28, ≤ 3.2). DESIGN: Single-arm open trial with historical controls. SETTING: Regional hospital, Hong Kong. PATIENTS: All new rheumatoid arthritis patients (onset < 2 years) attending the tight control clinic from October 2008 to October 2009 were recruited. All the patients were followed up every 3 to 6 weeks and clinically assessed using the Disease Activity Score 28. Disease-modifying agent treatment was stepped up according to a preset protocol ladder and patient tolerance. The treatment target was to achieve a Disease Activity Score 28 of 3.2 or below (low disease activity). These patients were compared to matched historical controls in the rheumatology clinic. RESULTS: Twenty patients in the tight control early rheumatoid arthritis clinic were recruited. Their disease activities were brought into better control than historical control patients who were followed up every 12 weeks. At week 52, clinical variables showed greater improvements in the intensive care group; respective mean scores (based on the Disease Activity Score 28 system) were 2.7 versus 4.2 (P<0.001); respective mean Health Assessment Questionnaire scores were 0.2 versus 1.3 (P<0.001). CONCLUSION: Outcomes of patients attending our locally adapted tight control clinic were consistent with previous reports in the literature. The clinic reduced rheumatoid arthritis activity faster and better. It entailed more frequent follow-up and monitoring, however. To address this strategy more objectively, a randomised trial with parallel controls is necessary.
22231660 Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis. 2012 Jun OBJECTIVE: Whether and how B lymphocytes contribute to the pathogenesis of spondylarthritis (SpA), a seronegative arthritis associated with gut inflammation, remains unknown. Because innate-like CD5+ B lymphocytes with regulatory functions have been identified in colitis models, we undertook the present study to analyze the presence and function of CD5+ B cells in human SpA. METHODS: Peripheral blood B cells from patients with SpA, patients with rheumatoid arthritis (RA), and healthy controls were analyzed by flow cytometry. Synovial biopsy samples were evaluated by immunohistochemistry analysis. Sorted CD5+ and CD5- B cells were analyzed for somatic hypermutation, expression of costimulatory molecules, and cytokine production. RESULTS: The naive, marginal zone-like, and to a lesser extent memory B cell compartments in patients with SpA exhibited a clear and specific increase of CD5+ B cells, which was not found in patients with RA. This increase was not due to either B cell activation or preferential migration of CD5- B cells to the inflamed synovium. Consistent with their phenotype and the low-affinity polyreactive immunoglobulins produced by their murine counterpart cells, CD5+ B cells from patients with SpA showed low levels of somatic hypermutation. With regard to antigen presentation, CD5+ B cells expressed slightly increased HLA-DR levels but low CD80 and CD86 levels. In vitro activation failed to up-regulate these costimulatory molecules but induced significant production of interleukin-10 and interleukin-6 by CD5+ B cells. CONCLUSION: CD5+ B cells are specifically increased in SpA. Analysis of somatic hypermutation, expression of antigen-presenting and costimulatory molecules, and cytokine production indicates that this B cell subset has regulatory capacities. Further investigation of the potential role of CD5+ cells in SpA is warranted.
21892767 Coping with arthritis is experienced as a dynamic balancing process. A qualitative study. 2011 Nov The aim of this study was to investigate the process of coping in people living with chronic inflammatory arthritis. Semi-structured individual face-to-face interviews with 26 persons having rheumatoid arthritis, psoriatic arthritis or unspecified polyarthritis were performed. The informants were asked how they experienced to live with arthritis and how they coped with challenges due to the arthritis. The main finding was that the informants experienced the process of coping with arthritis as a dynamic, iterative, balancing process. They balanced between different states, entitled "go on as usual", "listen to the body", "adjustments" and "attitude towards life". The informants preferred to be in a "go on as usual" state as this was seen as normal life. However, disease fluctuations with pain, fatigue and stiffness disturbed the balance and made the informants "listen to the body", a state where they became aware of how the disease affected them, followed by the "adjustment" state. Adjustments were composed of different efforts to ease the arthritis influence and for regaining balance. The "attitude towards life" influenced the overall process of coping. A redefined view of what the informants considered to be normal life thus happened through longer periods of imbalance. The process of coping with arthritis was found to be a dynamic, iterative, balancing process where patients redefined what they considered as normal life through the course of the disease.
22960198 Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hy 2013 Mar Both hypoxia and interleukin-17A (IL-17A) promote the migration and invasion of fibroblast-like synoviocytes (FLSs), which are critical for the pathogenesis of rheumatoid arthritis (RA). However, the biochemical pathways regulating IL-17A combined with hypoxia are not well defined. In this study, we found that co-stimulating RA-FLSs with IL-17A and hypoxia did not appear to promote the epithelial-mesenchymal transition (EMT), but did increase cell motility. We further showed that a proinvasive effect of IL-17A on FLSs under hypoxia might be through upregulation of matrix metalloproteinase 2 (MMP2) and MMP9. Moreover, IL-17A-induced expression of MMP2 and MMP9 under hypoxia was accompanied by increased activation of nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α). Knockdown or inhibition of HIF-1α and NF-κB by small interfering RNA or specific small molecule inhibitors blocked IL-17A-mediated and hypoxia-mediated MMP2 and MMP9 expression, cell migration, and invasion. In addition, the inhibition of NF-κB led to a marked decrease in the expression of HIF-1α, which indicated that IL-17A activated HIF-1α via the NF-κB pathway in hypoxia. Taken together, our observations suggest a synergetic effect of IL-17A and hypoxia that might contribute to the migration and invasion of RA-FLSs by upregulating the expression of MMP2 and MMP9 by activation of the NF-κB/HIF-1α pathway.
20659309 'I start my day by thinking about what we're going to have for dinner'--a qualitative stud 2011 Jun The aim of this study was to address the question of how older men with somatic diseases living in their own home approach the question of food-related activities (FRA). Further, any adaptations of these activities necessitated by effects of diseases and of altered life circumstances were explored. Interviews were conducted with a purposeful sample of 18 co-living and single-living men, 64-84 years old. They were diagnosed with Parkinson's disease, rheumatoid arthritis or stroke. In the analysis, a thematic framework was used. The findings revealed three food-related approaches, namely 'Cooking as a pleasure', describing joy in cooking; 'Cooking as a need', indicating no habits or skills in cooking; and 'Food is served', that is, being served meals by a partner. It was found that gender-related roles in particular, but also changed life circumstances, activity limitations, personal interests, and a wish to maintain continuity and independence, affected the men's approaches to these activities. This knowledge may be useful in attempts to facilitate and support FRA among elderly men with diseases. Health care efforts to promote FRA should preferably be individualised in respect to older men's approaches to these activities.
22414257 Proinflammatory and anti-inflammatory cytokines in gingival crevicular fluid and serum of 2013 Jan BACKGROUND: The aim of this study is to evaluate proinflammatory and anti-inflammatory cytokine levels in gingival crevicular fluid (GCF) and serum of rheumatoid arthritis (RA) and chronic periodontitis (CP) patients to assess whether cytokine profiles distinguish patients with RA and patients with CP while using healthy patients as background controls. METHODS: A total of 49 patients, 17 patients with RA (three males and 14 females; mean age: 47.82 ± 10.74 years), 16 patients with CP (10 males and six females; mean age: 44.00 ± 7.00 years), and 16 controls (eight males and eight females; mean age: 28.06 ± 6.18 years) were enrolled. Patients with RA were under the supervision of rheumatologists; 15 of the patients with RA were being treated with methotrexate-sulfasalazine combined therapy, and two of the patients were being treated with leflunomid therapy. Periodontal parameters (plaque index, gingival index, probing depth, and clinical attachment level) were recorded. Interleukin (IL)-1β, IL-4, IL-10, and tumor necrosis factor-α (TNF-α) were determined in GCF and IL-1β and IL-10 in serum by enzyme-linked immunosorbent assay. RESULTS: There were significant differences found among RA, CP, and control groups for all periodontal parameters (P <0.05). The total amount and concentration of GCF IL-1 β, IL-4, IL-10, and TNF-α were similar in RA and CP patients (P >0.05). Although the total amount and concentration of serum IL-10 was not significantly different among the groups (P >0.05), serum IL-1β was significantly lower in the RA group compared to CP patients and controls and was higher in GCF of the RA group compared to the CP group. CONCLUSIONS: Although clinical periodontal disease parameters indicated more severe periodontal disease in CP compared to RA patients, immunologic evaluation did not reveal consistent results regarding proinflammatory and anti-inflammatory cytokine levels. This might be a result of the use of non-steroidal anti-inflammatory drugs and rheumatoid agents by patients with RA.
21592822 IL-27-producing CD14(+) cells infiltrate inflamed joints of rheumatoid arthritis and regul 2011 Aug Interleukin (IL)-27, a heterodimeric cytokine, has been reported to be involved in the pathogenesis of autoimmune diseases through mediating differentiation of Th1 or Th17 cells and immune cell activity or survival. However, the origin and effects of IL-27 in joints of rheumatoid arthritis (RA) remain unclear. In this study, we investigated the distribution and anti-inflammatory roles of IL-27 in RA synovium. The IL-27 levels in plasma of RA patients, osteoarthritis (OA) patients, or healthy volunteers (n=15 per group) were equivalent and were at most 1 ng/ml, but the IL-27 level in synovial fluid of RA patients (n=15, mean 0.13 ng/ml; range 0.017-0.37 ng/ml) was significantly higher than that in synovial fluid of OA patients (n=15, mean 0.003 ng/ml; range 0-0.033 ng/ml) and potentially lower than in plasma. We analyzed the protein level of IL-27 produced by RA fibroblast-like synoviocytes (FLSs) or mononuclear cells (MNCs) from RA or OA synovial fluid or peripheral blood and showed that IL-27 in RA joints was derived from MNCs but not from FLSs. We also found by flow cytometry that IL-27-producing MNCs were CD14(+), and that these CD14(+)IL-27(+) cells were clearly detected in RA synovium but rarely in OA synovium by immunohistochemistry. Furthermore, we demonstrated that a relatively physiological concentration of IL-27 below 10 ng/ml suppressed the production of IL-6 and CCL20 from RA FLSs induced by proinflammatory cytokines through the IL-27/IL-27R axis. In the synovial fluid of RA, the IL-27 level interestingly had positive correlation with the IFN-γ level (r=0.56, p=0.03), but weak negative correlation with the IL-17A level (r=-0.30, p=0.27), implying that IL-27 in inflammatory joints of RA induces Th1 differentiation and suppresses the development or the migration of Th17 cells. These findings indicate that circulating IL-27-producing CD14(+) cells significantly infiltrate into inflamed regions such as RA synovium and have anti-inflammatory effects in several ways: both directly through the reduction of IL-6 production, and possibly through the induction of Th1 development and the suppression of Th17 development; and indirectly by regulation of recruitment of CCR6(+) cells, such as Th17 cells, through the suppression of CCL20 production. Our results suggest that such a serial negative feedback system could be applied to RA therapy.
23261243 Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fr 2013 Feb 22 Clinical prediction of bone fracture risk primarily relies on measures of bone mineral density (BMD). BMD is strongly correlated with bone strength, but strength is independent of fracture toughness, which refers to the bone's resistance to crack initiation and propagation. In that sense, fracture toughness is more relevant to assessing fragility-related fracture risk, independent of trauma. We hypothesized that bone biochemistry, determined by Raman spectroscopy, predicts bone fracture toughness better than BMD. This hypothesis was tested in tumor necrosis factor-transgenic mice (TNF-tg), which develop inflammatory-erosive arthritis and osteoporosis. The left femurs of TNF-tg and wild type (WT) littermates were measured with Raman spectroscopy and micro-computed tomography. Fracture toughness was assessed by cutting a sharp notch into the anterior surface of the femoral mid-diaphysis and propagating the crack under 3 point bending. Femoral fracture toughness of TNF-tg mice was significantly reduced compared to WT controls (p=0.04). A Raman spectrum-based prediction model of fracture toughness was generated by partial least squares regression (PLSR). Raman spectrum PLSR analysis produced strong predictions of fracture toughness, while BMD was not significantly correlated and produced very weak predictions. Raman spectral components associated with mineralization quality and bone collagen were strongly leveraged in predicting fracture toughness, reiterating the limitations of mineralization density alone.
22169051 Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in 2012 Jan BACKGROUND: The pharmacokinetics of golimumab, a human monoclonal antibody that inhibits the activity of tumor necrosis factor α, after a single subcutaneous (SC) or intravenous (IV) administration have been previously studied. OBJECTIVES: The purpose of this study was to assess the pharmacokinetics of golimumab after multiple SC or IV administrations in patients with active rheumatoid arthritis (RA). The effect of concomitant methotrexate (MTX) use on golimumab pharmacokinetics was evaluated. METHODS: In this open-label, randomized, Phase I study, 49 adult patients with RA received SC golimumab 100 mg (n = 33) every 4 weeks through week 20 or IV golimumab 2 mg/kg (n = 16) at weeks 0 and 12. Serial blood samples were collected, and serum golimumab concentration was measured with an electrochemiluminescent immunoassay. Golimumab pharmacokinetic parameters were derived with the use of a noncompartmental analysis. Adverse events were monitored at every visit. RESULTS: The population was predominantly Caucasian (84%) and female (76%), and the median age was 57 years. After SC golimumab administration, the serum golimumab concentration achieved steady state by ∼12 weeks with mean trough serum concentrations ranging from 1.15 to 1.24 μg/mL. After the final 30-minute IV infusion of golimumab 2 mg/kg, the mean (SD) clearance (CL) was 7.5 (2.6) mL/d/kg. The mean terminal half-life after SC and IV administrations was ∼13 days. The mean absolute bioavailability for SC golimumab was estimated to be 53%. The geometric mean of golimumab CL/F in patients with and without concomitant MTX use was 13.9 and 21.2 mL/d/kg, respectively, and the geometric mean ratio of CL/F was 65.5% (90% CI: 45.2%-94.9%, P = 0.06). Golimumab was generally well tolerated. No malignancies or deaths occurred during the study. CONCLUSIONS: Pharmacokinetics of golimumab were consistent after SC or IV administration in this population of patients with RA. Golimumab was well tolerated and no unexpected adverse events were observed in this trial.
22749479 Anomalous tendon to the middle finger for sagittal band reconstruction: report of 2 cases. 2012 Aug Multiple techniques with good outcomes have been described for sagittal band reconstruction. We describe 2 cases of sagittal band reconstruction using an anomalous slip of the extensor tendon to the middle finger. This anomalous slip can be a resource for surgical reconstruction that can add stability to primary sagittal band repair.
21993918 Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmark 2012 Aug This interim analysis of postmarketing surveillance data for adalimumab-treated rheumatoid arthritis (RA) patients summarizes safety and effectiveness during the first 24 weeks of therapy for the first 3,000 patients treated in Japan (June 2008-December 2009). Patient eligibility for antitumor necrosis factor therapy was based on the Japanese College of Rheumatology treatment guidelines and Japanese labeling. All patients were screened for tuberculosis. Approximately 50% of the population was biologic naïve, 66% received concomitant methotrexate (MTX), and 72% received concomitant glucocorticoids. The overall incidence rate of adverse events was 31% (5.5% serious) and that of adverse drug reactions (ADRs) was 27% (4.1% serious). Incidence rates of ADRs and serious ADRs were similar regardless of prior biologic therapy or concomitant MTX use but were significantly higher in patients receiving glucocorticoids compared with those not receiving glucocorticoids. Bacterial/bronchial pneumonia occurred in 1.2% of patients; interstitial pneumonia, 0.6%; Pneumocystis jirovecii pneumonia, 0.3%; tuberculosis, 0.13%; and administration-site reactions, 6.1%. Mean 28-joint Disease Activity Scores decreased significantly after 24 weeks from 5.29 to 3.91. All subgroups showed significant improvement, particularly the biologic-naïve patients receiving concomitant MTX. No new safety concerns were identified. ADR Incidence rates were similar to those of other biologic agents approved for RA.
21953001 Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in rheumatoid arth 2011 Sep Rheumatoid arthritis (RA) is an autoimmune disease associated with polyarticular inflammatory synovitis affecting mainly peripheral joints. It affects approximately 1% of the world population, being two to three times more prevalent in women. Rheumatoid arthritis has a complex and multifactorial pathogenesis. The synovium of the affected joints is infiltrated by T and B lymphocytes, macrophages, and granulocytes. The rheumatoid synovium has proliferative characteristics, forming the pannus, which invades cartilage and bone, leading to normal architecture destruction and function loss. The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. This article aimed at reviewing the main aspects related to CS regulation in RA in order to provide a better understanding of the potential role of this system in the pathophysiology and activity of the disease.
21763385 Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B 2011 Sep 2 BACKGROUND: Associations between vaccinations, particularly hepatitis B, and onset of rheumatoid arthritis (RA) have been reported, but examined in few large-scale studies. METHOD: Onset of RA cases and dates of vaccination against hepatitis B, tetanus, and influenza were identified in a retrospective chart review of approximately 1 million Kaiser Permanente Northern California members ages 15-59 years from 1997 through 1999. In a cohort analysis, rates of new-onset RA were compared between vaccinated and unvaccinated within 90, 180, and 365 days. In a case-control analysis, rates of vaccination during exposure intervals (90, 180, 365, and 730 days) were compared between cases and controls using conditional logistic regression. RESULTS: 378 RA cases were included in the cohort analysis; 37 additional cases were included in the case-control analysis. In the cohort analysis the relative risks of RA onset within 90, 180, or 365 days of hepatitis B vaccination were not significant (R.R.=1.44, p=0.53; R.R.=1.67, p=0.22; R.R.=1.23, p=0.59 respectively). We found a possible association between RA and influenza vaccine in the previous 180 and 365 days in the cohort analysis (R.R=1.36, p=0.03; R.R.=1.34, p=0.01 respectively), but in the case-control analysis, cases were no more likely than controls to have received any of the three vaccines. CONCLUSIONS: In this large retrospective study we found no statistically significant association between exposure to hepatitis B vaccine and onset of RA. A possible association between RA and influenza vaccination in the cohort study was not borne out in the larger case-control analysis.
21804202 Unsaturated fatty acids and pain. 2011 Fatty acids, which are the essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. Recently, an increasing number of physiologic and pharmacologic reports on fatty acids have improved our understanding of the association of fatty acids with certain diseases. It has also become apparent that functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs. Recently, the functional relationship between polyunsaturated fatty acids and pain has been the focus of many studies. Both basic and clinical studies have shown that a dietary intake of n-3 series polyunsaturated fatty acids results in a reduction in the pain associated with rheumatoid arthritis, dysmenorrhea, inflammatory bowl disease, and neuropathy. In addition, levels of n-6 series polyunsaturated fatty acids are high in patients with chronic pain. These results indicate that polyunsaturated fatty acids play a vital role in pain regulation. In this review, we summarize a number of basic and clinical studies on polyunsaturated fatty acids and their association with pain.
23321886 Health benefits of deer and elk velvet antler supplements: a systematic review of randomis 2012 Dec 14 AIMS: The aim of this systematic review was to evaluate the evidence from RCTs of velvet antler supplements for any condition, using the QUOROM statement as a guiding framework. METHODS: Four electronic databases (PubMed, Medline, Web of Science and Academic search premier, via the bibliographical platform, Endnote) and two review articles were searched for all randomised clinical trials of velvet antler supplements. Retrieved trials were evaluated according to standardised criteria. RESULTS: Seven RCTs were identified as satisfying all inclusion criteria and examined the effectiveness of velvet antler for rheumatoid arthritis (2), osteoarthritis (1), sexual function (1), and sporting performance enhancement (3). Their methodological quality ranged from 3-5, as measured on the Jadad scale. Two RCTs reported some positive effects of velvet antler supplements, but neither were convincing while the remaining five RCTs found no effect of velvet antler supplements. CONCLUSIONS: Claims made for velvet antler supplements do not appear to be based upon rigorous research from human trials, although for osteoarthritis the findings may have some promise.
22709495 Fractalkine stimulates cell growth and increases its expression via NF-κB pathway in RA-F 2012 Jun BACKGROUND: After the onset of rheumatoid arthritis (RA), fibroblast-like synoviocytes (RA-FLS) which are specialized types of fibroblasts, become tumor-like, keeping their ability to increase proliferation and invasion. The mechanism of their tumor-like growth is unclear. Fractalkine (FKN), also called CX3CL1, plays an important role in the proliferation of cells. FKN may stimulate the proliferation of RA-FLS and the by nuclear factor κB (NF-κB) pathway may be one of the steps in this process. OBJECTIVE: To investigate whether FKN can stimulate cell growth and increase its expression in RA-FLS, and the relationship between the NF-κB pathway and the function of FKN. METHODS: FLS were isolated from primary synovial tissue obtained from three patients with RA who had undergone total joint replacement surgery or synovectomy in the Third Hospital Affiliated to Sun Yat-sen University from February 2009 to January 2010. FKN was used in different concentrations to stimulate RA-FLS with or without NF-κB pathway blocker (PDTC), and to test the proliferation of FLS after 24 h by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RA-FLS was treated with 100 ng/mL FKN or 100 μM PDTC for different periods, and messenger RNA (mRNA) expression of FKN and CX3CR1 in RA-FLS was detected by reverse transcription - polymerase chain reaction. We then tested the protein expression of NF-κBp65 in the cytoplasm and nucleus, respectively by Western blotting after treating the RA-FLS with 100 ng/mL FKN for different time periods. RESULTS: FKN stimulated cell growth in RA-FLS at the concentration of 50 or 100 ng/mL (P = 0.005 and P = 0.022, respectively). NF-κB pathway blocker inhibited FKN, promoting proliferation of RA-FLS. RA-FLS could express FKN and CX3CR1 mRNA in vitro. FKN up-regulated FKN expression after 18-h treatment (P = 0.012). PDTC disturbed the expression of FKN mRNA after 16-18 h treatment (P = 0.001 and P < 0.001, respectively). After stimulation with FKN for 1 h, the expression of NF-κBp65 in cytoplasm began to decrease (P = 0.010), and the expression of NF-κBp65 in the nucleus began to increase after 2 h (P = 0.011). CONCLUSION: These results suggest that FKN stimulates cells growth in RA-FLS and NF-κB pathway blocker inhibits FKN, promoting proliferation of RA-FLS. FKN induced activation of NF-κB activity. FKN up-regulates FKN mRNA expression in RA-FLS via the NF-κB pathway.