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ID PMID Title PublicationDate abstract
22012868 Use of disease-modifying medications for rheumatoid arthritis by race and ethnicity in the 2012 Feb OBJECTIVE: Disease-modifying antirheumatic drugs (DMARDs) are recommended for virtually all patients with rheumatoid arthritis (RA). We investigated the use of DMARDs in patients with RA in a nationally representative sample of visits to US physicians in the National Ambulatory Care Medical Survey (NAMCS). METHODS: We analyzed the NAMCS visit data from 1996 through 2007 if the physician noted a diagnosis of RA. DMARD utilization was based on the medications listed by the physician. We used generalized linear models to examine the adjusted associations between DMARD use and potential predictors. RESULTS: Of the 859 visits with a diagnosis code of RA identified over the study period, 404 visits (47%; 95% confidence interval [95% CI] 44-50%) had an associated DMARD. The percentage of RA visits with DMARDs increased slightly over the 12 years (P = 0.048), with biologic DMARDs increasing to 20% of visits after their introduction (P for trend <0.001). In fully adjusted models, African American race was associated with a 30% reduction in DMARD prescribing (risk ratio [RR] 0.70, 95% CI 0.48-1.00). A visit to a rheumatologist was the strongest correlate of DMARD prescribing (RR 2.33, 95% CI 1.89-2.86). Among visits to nonrheumatologists, African Americans were significantly less likely than whites to receive a DMARD (RR 0.39, 95% CI 0.17-0.92), but not among visits with rheumatologists (RR 0.81, 95% CI 0.52-1.27). CONCLUSION: In the NAMCS, most visits coded with RA did not have an associated DMARD prescription. African Americans were less likely to receive DMARDs than whites, particularly when visiting nonrheumatologists.
21267728 [Immune senescence and autoimmunity. Does the immune system really age, or just the organs 2011 Feb Degenerative ageing processes are to a great extent responsible for organ-specific morbidity and mortality among our population. The incidence of many autoimmune diseases also increases significantly with age, as is evident with rheumatoid arthritis (RA) for example. From an immunological and pathogenetic perspective, that the changes in the immune system of RA patients is comparable to the physiological ageing process seen in healthy individuals approximately 20 years later is of great interest. Despite the manifold functional changes seen in the immune system of older people, the incidence of infection in very elderly patients with RA is only marginally increased, such that immune suppression in older RA patients should be carried out just as consequently as in younger patients. Age-related changes and diseases in other organ systems should receive particular attention, since such complications can have a negative effect on the course of the autoimmune disease as well as the rate of side effects.
22752090 Risk estimation and risk prediction using machine-learning methods. 2012 Oct After an association between genetic variants and a phenotype has been established, further study goals comprise the classification of patients according to disease risk or the estimation of disease probability. To accomplish this, different statistical methods are required, and specifically machine-learning approaches may offer advantages over classical techniques. In this paper, we describe methods for the construction and evaluation of classification and probability estimation rules. We review the use of machine-learning approaches in this context and explain some of the machine-learning algorithms in detail. Finally, we illustrate the methodology through application to a genome-wide association analysis on rheumatoid arthritis.
22824166 Anti-TNFα therapy transiently improves high density lipoprotein cholesterol levels and mi 2012 Jul 23 BACKGROUND: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function. METHODS: Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment. RESULTS: Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks. CONCLUSION: Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function.
22594821 T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis pati 2012 May 17 INTRODUCTION: Anti-citrullinated peptide antibodies are found in rheumatoid arthritis (RA) patients with HLA-DRβ chains encoding the shared epitope (SE) sequence. Citrullination increases self-antigen immunogenicity, through increased binding affinity to SE-containing HLA-DR molecules. To characterise T-cell autoreactivity towards citrullinated self-epitopes, we profiled responses of SE+ healthy controls and RA patients to citrullinated and unmodified epitopes of four autoantigens. METHODS: We compared T-cell proliferative and cytokine responses to citrullinated and native type II collagen 1,237 to 1,249, vimentin 66 to 78, aggrecan 84 to 103 and fibrinogen 79 to 91 in six SE+ healthy controls and in 21 RA patients with varying disease duration. Cytokine-producing cells were stained after incubation with peptide in the presence of Brefeldin-A. RESULTS: Although proliferative responses were low, IL-6, IL-17 and TNF were secreted by CD4+ T cells of SE+ RA patients and healthy controls, as well as IFNγ and IL-10 secreted by RA patients, in response to citrullinated peptides. Of the epitopes tested, citrullinated aggrecan was most immunogenic. Patients with early RA were more likely to produce IL-6 in response to no epitope or to citrullinated aggrecan, while patients with longstanding RA were more likely to produce IL-6 to more than one epitope. Cytokine-producing CD4+ T cells included the CD45RO+ and CD45RO- and the CD28+ and CD28- subsets in RA patients. CONCLUSION: Proinflammatory cytokines were produced by CD4+ T cells in SE+ individuals in response to citrullinated self-epitopes, of which citrullinated aggrecan was most immunogenic. Our data suggest that the T-cell response to citrullinated self-epitopes matures and diversifies with development of RA.
23179005 Leflunomide in dialysis patients with rheumatoid arthritis--a pharmacokinetic study. 2013 Feb Pharmacokinetic data of disease modifying antirheumatic drugs during hemodialysis are limited to sulfasalazine, methotrexate, and cyclosporine. Only respective anecdotal data have been reported on leflunomide. We repeatedly measured teriflunomide (A77-1726), the active metabolite of leflunomide, during standard hemodialysis sessions and calculated teriflunomide clearances in five patients with rheumatoid arthritis (RA) and end-stage renal disease. The calculated teriflunomide clearances during a standardized dialysis session of 3-4.5 h at a blood flow rate of 160-300 ml/min were between 0 and 4.3 ml/min, the mean clearances of the total dialysis ranged between 1.1 and 3.4 ml/min. Total amount of teriflunomide removed was 5.8-8.8 μg per dialysis session. Dialytic removal of the active metabolite of leflunomide, teriflunomide (A77-1726), is negligible. Leflunomide can be used for RA patients on chronic dialysis without any dosage modification.
21123065 Inhibitory effects of hybrid liposomes on the growth of synoviocyte causing rheumatoid art 2011 Jan 1 Inhibitory effects of HL-n composed of 95 mol% L-α-dimyristoylphosphatidylcholin (DMPC) and 5 mol% polyoxyethylenedodecylether (C(12)(EO)(n), n = 21, 23, or 25) on the growth of human rheumatoid arthritis (RA) fibroblast-like synoviocytes (HFLS-RA) in vitro were examined. Remarkably high inhibitory effects of HL-n on the growth of HFLS-RA cells were obtained. The induction of apoptosis by HL-n was revealed on the basis of TUNEL method. Furthermore, the therapeutic effects of HL-23 using mouse models of arthritis were investigated. Therapeutic effects without joint swelling were obtained in mouse models of RA treated with HL.
20876701 Abatacept treatment for rheumatoid arthritis. 2011 Mar Significant advances in our understanding of RA and its management have been made in the past decade, resulting in earlier intervention with biologic DMARDs, particularly in patients with evidence of aggressive, erosive disease. Here, one such biologic therapy, the T-cell co-stimulation modulator abatacept, is discussed, exploring clinical evidence published to date on its use in patients with very early arthritis/early RA who are MTX naïve, and in patients with established RA and an inadequate response to MTX or TNF antagonists. Data from relevant clinical trials are overviewed, discussing the clinical efficacy of abatacept in early disease, the clinical outcomes over long-term treatment in different patient populations and the effects of abatacept on structural damage. Findings from integrated safety analyses of abatacept clinical trial data, representing 10,366 patient-years of exposure are described, and clinically important safety events, including serious infections, malignancies and autoimmune events, are highlighted. It is concluded that abatacept represents an effective treatment option with an established safety profile across different patient populations, including patients with both early and erosive RA and those with established disease. Furthermore, efficacy data from studies in patients with early disease suggest that the risk-benefit profile of abatacept may be more favourable when introduced earlier in the treatment paradigm.
21807781 Tocilizumab monotherapy reduces arterial stiffness as effectively as etanercept or adalimu 2011 Oct OBJECTIVE: To compare the respective effects of tocilizumab (TCZ) monotherapy, etanercept (ETN) monotherapy, and adalimumab (ADA) monotherapy on arterial stiffness in patients with rheumatoid arthritis (RA) in an open-label, randomized controlled trial. METHODS: Patients with RA were eligible if they had active disease (28-joint Disease Activity Score > 3.2) and no prior treatment with methotrexate or biologics. All 64 patients had no history of cardiovascular disease or steroid treatment. Patients were randomly assigned to receive TCZ alone (n = 22), ETN alone (n = 21), or ADA alone (n = 21). Arterial stiffness was assessed with cardio-ankle vascular index (CAVI) and aortic augmentation index normalized to a fixed heart rate of 75 bpm (AIx@75) at baseline and 24 weeks' followup. Clinical data were collected at regular visits. RESULTS: The characteristics of each group at baseline were not significantly different. In all groups there was significant attenuation from baseline to 24 weeks in CAVI (Week 0-Week 24, TCZ: 0.85 ± 0.15 m/s, p = 0.02; ETN: 0.81 ± 0.18 m/s, p = 0.03; ADA: 0.90 ± 0.21 m/s, p = 0.02) and in AIx@75. There were no significant differences among the groups in measures of CAVI or AIx@75. The 3 therapies made no difference to carotid intima-media thickness and carotid artery plaque. Only TCZ increased fasting serum total cholesterol from baseline to 24 weeks. CONCLUSION: The 3 types of monotherapy limited arterial stiffness in patients with RA to a similar extent.
21325762 Clinical and radiological features of acute-onset diffuse interstitial lung diseases in pa 2011 OBJECTIVE: Acute-onset diffuse interstitial lung disease (AoDILD) in patients with rheumatoid arthritis (RA) has been a serious concern, especially for those under treatment with biological agents which may affect the presentation and outcome of AoDILD, including Pneumocystis pneumonia (PCP). Therefore, we conducted a retrospective, multi-center study of AoDILD in RA patients receiving biological agents. METHODS: Patients who developed AoDILD while receiving biological agents (infliximab, etanercept, adalimumab and tocilizumab) were enrolled in the study. Definite PCP was defined as patients who showed either P. jirovecii organisms in their respiratory samples by microscopic examination, or positive tests for both P. jirovicii DNA-PCR with respiratory samples and an elevated serum 1,3-β-D-glucan level above the cut-off value. Probable PCP was defined as either a positive test for P. jirovicii PCR or an elevated serum β-D-glucan level. Chest HRCT findings were evaluated and scored by two board-certified radiologists. RESULTS: The final diagnoses for 26 patients examined were definite PCP for 13 patients, probable PCP for 11, and methotrexate-associated pneumonitis in 2 patients. Definite and probable PCP cases were clinically indistinguishable. Generalized, diffuse ground-glass opacity (GGO) is the characteristic HRCT finding in patients with definite or probable PCP, which was different from our previous findings in RA patients, mostly without biologics, showing GGO distributed in a panlobular or multilobular manner. The clinical outcome was favorable by treatment with trimethoprim-sulfamethoxazole and glucocorticoids. CONCLUSION: The possibility of PCP should be intensively investigated in RA patients developing AoDILD while receiving biological agents.
22327743 Prevalence of rheumatoid factor and parameters associated with rheumatoid factor positivit 2012 Nov OBJECTIVES: The purpose of this study is to assess the prevalence and titer of rheumatoid factor (RF) in Korean health screening subjects and consecutive subjects with hepatitis B surface antigen (HBsAg) and to examine the factors influencing RF positivity. METHODS: This study was performed in 37,660 patients (23,269 men, 14,391 women) without arthralgia, who participated in a health checkup program in 2009. RESULTS: Approximately 3.7% of health screening subjects (3.3% of males and 4.4% of females) were positive for RF. Among subjects with HBsAg (n = 1,494) and antibody for hepatitis C virus (HCV) (n = 132), 11.8 and 10.6% were RF positive, respectively. There was a significant difference in the RF-positive rate between males and females. The RF-positive rate had a significant linear-by-linear association with aging, but there was no significant relationship between RF positivity and aging among subjects with HBsAg or anti-HCV antibody. Presence of HBsAg and anti-HCV antibody, positive C-reactive protein (CRP), and female sex were factors strongly associated with RF positivity. CONCLUSIONS: The rate of RF positivity in health screening adults and subjects with HBsAg in Korea can be estimated to be 3.7 and 11.8%, respectively. Clinicians should consider hepatitis B or C virus infection status, CRP positivity, and sex when interpreting RF-positive results.
23161899 Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment 2013 May BACKGROUND: Mitogen-activated protein (MAP) kinases are key regulators of cytokine production, and are therefore potential targets for treatment of rheumatoid arthritis (RA). OBJECTIVE: This two-part phase II study investigated the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP kinase-activated protein kinase 5) dose vs placebo (part A). An interim analysis after part A would determine whether the dose-finding part (part B) would be performed. METHODS: In part A, eligible methotrexate (MTX)-refractory patients with RA were randomised to receive either a once-daily 50 mg dose of GLPG0259 or placebo, in addition to a stable dose of MTX, for 12 weeks. The primary efficacy end point was the percentage of patients achieving an American College of Rheumatology 20% improvement (ACR20) response after 12 weeks. RESULTS: The interim analysis showed no difference between the percentage of subjects achieving the primary efficacy variable of ACR20 or the secondary efficacy variables (ACR50, ACR70 and Disease Activity Score 28) at week 12 in the GLPG0259-treated (n=19) and placebo-treated (n=11) groups. Owing to lack of efficacy, the study was terminated, and part B was not initiated. CONCLUSIONS: This innovative study design quickly provided conclusive results on the lack of efficacy of GLPG0259 in patients with RA.
22704547 The PTPN22 C1858T variant as a risk factor for rheumatoid arthritis and systemic lupus ery 2012 Jul OBJECTIVES: C1858T single nucleotide polymorphism in PTPN22 encoding the R620W allele variant of Lyp-PTPN22 (a protein phosphatase negatively regulating T-cell activation) has been associated with autoimmunity. This work has investigated the possible association between PTPN22 C1858T (rs2476601) polymorphism and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in a Colombian population. METHODS: A case-control study included 1,042 samples from 413 RA, 94 SLE and 101 SSc patients and 434 healthy controls. The TaqMan allele discrimination assay was used for genotyping. RESULTS: The case-control study provided robust evidence of association between allele 1858T and RA (p=5E-05), as well as between 1858T and SLE (p=0.004). These observations were confirmed for both diseases by meta-analysis (p=2E-04, pooled OR 1.9; 1.3-2.7 95% CI for RA; p<0.0001, pooled OR 2.8, 1.8-4.5 95% CI for SLE). No significant association was observed between 1858T and SSc (p=0.98, OR 1.11, 0.46-2.65 95% CI). CONCLUSIONS: The study suggested that the PTPN22 1858T variant influences RA and SLE genetic background but not that of SSc in the Colombian population.
21987802 Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheu 2011 Oct 18 Autoimmune responses against posttranslationally modified antigens are a hallmark of several autoimmune diseases. For example, antibodies against citrullinated protein antigens (ACPA) have shown their relevance for the prognosis and diagnosis of rheumatoid arthritis (RA), and have been implicated in disease pathogenesis. It is conceivable that other autoantibody systems, recognizing other posttranslationally modified proteins, are also present in RA. Here, we describe the presence of an autoantibody system that discriminates between citrulline- and homocitrulline-containing antigens in the sera of RA-patients. IgG antibodies recognizing carbamylated (homocitrulline-containing) antigens were present in sera of over 45% of RA-patients. Likewise, anticarbamylated protein (anti-CarP) IgA antibodies were observed in 43% of RA-sera. ACPA and anti-CarP antibodies are distinct autoantibodies because, in selected double-positive patients, the anti-CarP antibody binding to carbamylated antigens could be inhibited by carbamylated antigens, but not by control or citrullinated antigens. Similarly, ACPA-binding to citrullinated antigens could only be inhibited by citrullinated antigens. In line with this observation, 16% of ACPA-negative RA-patients, as measured by a standard ACPA assay, harbored IgG anti-CarP antibodies, whereas 30% of these patients tested positive for IgA anti-CarP antibodies. The presence of anti-CarP antibodies was predictive for a more severe disease course in ACPA-negative patients as measured by radiological progression. Taken together, these data show the presence of a unique autoantibody system recognizing carbamylated, but not citrullinated, protein antigens. These antibodies are predictive for a more severe clinical course in ACPA-negative RA-patients, indicating that anti-CarP antibodies are a unique and relevant serological marker for ACPA-negative RA.
21859696 Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients 2011 Dec BACKGROUND: Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients with rheumatoid arthritis (RA) was recently reported. OBJECTIVES: To evaluate the contribution of age, disease activity, medication and previous antibody levels to this reduced response. METHODS: 340 adult RA patients and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment and pH1N1 antibody titres were collected. Seroprotection, seroconversion and factor increase in geometric mean titre (GMT) were calculated and adverse events registered. RESULTS: RA and controls showed similar (p>0.05) prevaccination GMT (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant reduction (p<0.001) was observed in all endpoints: GMT and factor increase in GMT, seroprotection and seroconversion rates. Disease activity did not preclude seroconversion or seroprotection and remained unchanged in 97.4% of patients. Methotrexate was the only disease-modifying antirheumatic drug associated with reduced responses (p=0.001). Vaccination was well tolerated. CONCLUSIONS: The data confirmed both short-term anti-pH1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate). Extrapolation of immune responses from one vaccine to another may therefore not be possible and specific immunisation strategies (possibly booster) may be needed. Clinicaltrials.gov no NCT01151644.
22083543 The loss of α2β1 integrin suppresses joint inflammation and cartilage destruction in mou 2012 May OBJECTIVE: Integrin α2β1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for α2β1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the α2 integrin subunit (Itga2(-/-) mice) develop normally and are fertile. We undertook this study to investigate the effect of Itga2 deficiency in 2 different mouse models of destructive arthritis: the antigen-induced arthritis (AIA) mouse model and the human tumor necrosis factor α (TNFα)-transgenic mouse model. METHODS: AIA was induced in the knee joints of Itga2(-/-) mice and wild-type controls. Human TNF-transgenic mice were crossed with Itga2(-/-) mice and were assessed clinically and histopathologically for signs of arthritis, inflammation, bone erosion, and cartilage damage. MMP expression, proliferation, fibroblast attachment, and ERK activation were determined. RESULTS: Under arthritic conditions, Itga2 deficiency led to decreased severity of joint pathology. Specifically, Itga2(-/-) mice showed less severe clinical symptoms and dramatically reduced pannus formation and cartilage erosion. Mice lacking α2β1 integrin exhibited reduced MMP-3 expression, both in their sera and in fibroblast-like synoviocytes (FLS), due to impaired ERK activation. Further, both the proliferation and attachment of FLS to cartilage were partially dependent on α2β1 integrin in vitro and in vivo. CONCLUSION: Our findings suggest that α2β1 integrin contributes significantly to inflammatory cartilage destruction by promoting fibroblast proliferation and attachment and MMP expression.
22011479 Soluble urokinase plasminogen activator receptor as a useful biomarker to predict the resp 2011 Sep OBJECTIVES: To determine whether soluble urokinase plasminogen activator receptor is a useful biomarker to predict the response to adalimumab (ADA) in Japanese patients with rheumatoid arthritis. METHODS: Rheumatoid arthritis (RA) patients administrated ADA (n=51) were classified as good responders (n=18) or nonresponders (n=9) according to the EULAR response criteria after 8 weeks of bi-weekly ADA administration. We examined the expression of cytokines and chemokines in these groups by antibody array methods. Positive results obtained by antibody array methods were further confirmed by ELISA. RESULTS: Antibody array has identified that the macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF) and soluble urokinase plasminogen activator receptor (uPAR) decreased in the good responders to ADA whereas these changes were not observed in the non-responders. The decrement of serum uPAR was confirmed by ELISA in the good responders to ADA. Furthermore, serum uPAR at baseline was significantly high in non-responders compared with good responders. CONCLUSIONS: An antibody array is convenient for screening the expression of proteins of interest. Examination of serum uPAR at baseline and thereafter may be useful as a predictive biomarker for primary failure toward ADA in patients with RA.
20889191 Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a 2011 Apr OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease. Carotid intima media thickness (cIMT) is frequently used to identify populations at elevated cardiovascular risk. A systematic literature search and meta-analysis were performed to evaluate cIMT difference between RA and controls. METHODS: The literature was screened to identify all available studies comparing cIMT in RA patients and controls. Random effects meta-analysis was performed to estimate the overall mean cIMT difference between both groups. Meta-regression was performed to assess the influence of age and the degree of comparability regarding established cardiovascular risk factors on cIMT difference. Potential publication bias was examined by a funnel plot and Egger test. RESULTS: From 22 studies, cIMT data were available from 1384 RA patients and 1147 controls. In 17 of the studies, RA patients had a statistically significantly greater cIMT. The overall mean cIMT difference was 0.09 mm (95%CI: 0.07-0.11 mm). Heterogeneity was observed (I(2) 72.5%, P < 0.001). A likely source of heterogeneity was the difference in cardiovascular risk factors between RA patients and controls at baseline, but not age. The funnel plot did not show a skewed or asymmetrical shape, which was supported by the Egger's test (P = 0.87). CONCLUSIONS: Our observations support the current evidence base for an increased cardiovascular burden in RA and support the use of cIMT in observational studies in RA patients. The next step is to determine its utility as a surrogate cardiovascular risk marker in RA in prospective studies.
21676922 Effects of berberine on human rheumatoid arthritis fibroblast-like synoviocytes. 2011 Jul Activated rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of rheumatoid arthritis (RA). Rapid proliferation and defective apoptosis of RAFLSs are two main mechanisms contributing to synovial hyperplasia. Berberine, the major constituent of Coptidis Rhizoma, has been widely used as an antitumor and anti-inflammation agent. Here we show that berberine significantly inhibited cell proliferation of serum-starved human RAFLSs in a dose-dependent manner. Cell cycle analysis of berberine-treated RAFLSs indicated a cell cycle arrest at the G0/G1 phase. The inhibitory effects of berberine correlated with an induction of cyclin-dependent kinase (CDK) inhibitors Cip1/p21 and Kip1/p27 and a reduction of CDK2, CDK4 and CDK6, and cyclins D1, D2 and E. Furthermore, an apoptosis assay showed that berberine treatment increased apoptotic death of RAFLSs, which was associated with an increased expression of proapoptotic protein Bax and decreased expression of antiapoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase. Taken together, these results demonstrate that berberine exerts antiproliferative effects against RAFLSs, likely through deregulation of numerous cell cycle and apoptosis regulators, thus having potential therapeutic implications in the treatment of RA.
22577060 Do sleepy rheumatoid arthritis patients have a sleep disorder? 2012 Dec OBJECTIVE: Subjective reports of sleep dysfunction are common in people with rheumatoid arthritis (RA). Our objective was to determine whether excess sleepiness in RA is associated with polysomnographic (PSG) abnormalities. METHODS: Twelve RA participants with abnormal sleep scores were identified in clinic and age/gender matched to RA participants with normal Epworth Sleepiness Scale (ESS) scores. A total of 25 participants were recruited. All participants underwent overnight PSG studies with measurement of apnoea-hypopnoea indexes (AHI). Questionnaire instruments, including the ESS, Berlin questionnaire for sleep apnoea risk, visual analogue scale for fatigue, modified Health Assessment Questionnaire (mHAQ) and the Center for Epidemiologic Studies - Depression (CES-D) score, along with RA assessments, were reapplied on the PSG study night. RESULTS: Seven men and 18 women participated. Ten participants had abnormal ESS scores and 15 had normal ESS scores on the PSG night. PSG data revealed that 68% of patients had abnormal AHI (≥ 5). Abnormal ESS (> 10) had an 80% positive predictive value (PPV) for abnormal AHI; the negative predictive value (NPV) of normal ESS was 40%. By contrast, high-risk categorization for obstructive sleep apnoea (OSA) by the Berlin questionnaire had a PPV of 77.8%, and for low-risk status, an NPV of 37.5%. CONCLUSIONS: In the present study population, there was a high prevalence of abnormal AHI consistent with OSA. An abnormal ESS had high positive predictive value for an abnormal AHI.