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ID PMID Title PublicationDate abstract
22547986 Natural killer cells and their role in rheumatoid arthritis: friend or foe? 2012 Rheumatoid arthritis (RA) is a long-term disease that leads to inflammation of the joints and surrounding tissues. Natural killer (NK) cells are an important part of the innate immune system and are responsible for the first line of defense against pathogens during the initial immune challenge before the adaptive immune system eventually eliminates the infectious burden. NK cells have the capacity to damage normal cells or through interaction with other cells such as dendritic cells, macrophages, and T cells cause autoimmune diseases, such as RA. NK cells isolated from the joints of patients with RA suggest that they may play a role in this disease. However, the involvement of NK cells in RA pathology is not fully elucidated. Both protective and detrimental roles of NK cells in RA have recently been reported. A better understanding of NK cells' role in RA might help to develop new therapeutic strategies for treatment of the RA or other autoimmune diseases. We have decided in this paper to focus on the NK cell biology, and attempt to bring the interested readership of this Journal up to date on the NK cell, specifically its possible relation to RA.
21193999 The effect of body mass index on the spread of spinal block in patients with rheumatoid ar 2011 Apr PURPOSE: Body mass index (BMI) has a significant effect on the spread of sensory spinal block in rheumatoid patients. We tried to achieve the same spread of spinal block for patients in three different BMI groups and, on the basis of the results from a preliminary study, used a simple method feasible for clinical practice. We hypothesized that BMI-related inverse dosing of plain bupivacaine according to low, normal, and high BMI would result in no difference in block extent. METHODS: Together 75 patients with seropositive rheumatoid arthritis were included in three equal-sized groups according to BMI: low (<23 kg/m(2)), normal (23-28 kg/m(2)), and high (>28 kg/m(2)). Spinal anesthesia was induced with plain bupivacaine using doses 3.3, 3.0, and 2.7 ml, respectively. The spread of sensory block was recorded 30 min after injection of bupivacaine by use of a pin-prick test and a cold ice-filled container. RESULTS: Spreads of sensory block were different in low, normal, and high BMI groups (mean (SD); 14.0 (2.6), 14.5 (2.5), and 16.3 (2.5) dermatomes, respectively, P = 0.006) because of greater block extent in the high-BMI group. CONCLUSIONS: Despite three-step dosing of plain bupivacaine inversely related to BMI (low, normal, or high), comparable block extent was not achieved because of greater spread in the high-BMI group. Adjustment of plain bupivacaine dose according to BMI could be used to achieve a more predictable spread of spinal block, but further reduction of dose is needed in patients with high BMI.
22941906 Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid art 2012 Dec OBJECTIVE: JAK inhibitors have been developed as antiinflammatory and immunosuppressive agents and are currently undergoing testing in clinical trials. The JAK inhibitors CP-690,550 (tofacitinib) and INCB018424 (ruxolitinib) have demonstrated clinical efficacy in rheumatoid arthritis (RA). However, the mechanisms that mediate the beneficial actions of these compounds are not known. The purpose of this study was to examine the effects of both JAK inhibitors on inflammatory and tumor necrosis factor (TNF) responses in human macrophages. METHODS: In vitro studies were performed using peripheral blood macrophages derived from healthy donors and treated with TNF and using synovial fluid macrophages derived from patients with RA. Levels of activated STAT proteins and other transcription factors were detected by Western blotting, and gene expression was measured by real-time polymerase chain reaction analysis. The in vivo effects of JAK inhibitors were evaluated in the K/BxN serum-transfer model of arthritis. RESULTS: JAK inhibitors suppressed the activation and expression of STAT-1 and downstream inflammatory target genes in TNF-stimulated and RA synovial macrophages. In addition, JAK inhibitors decreased nuclear localization of NF-κB subunits in TNF-stimulated and RA synovial macrophages. CP-690,550 significantly decreased the expression of interleukin-6 in synovial macrophages. JAK inhibitors augmented nuclear levels of NF-ATc1 and cJun, followed by increased formation of osteoclast-like cells. CP-690,550 strongly suppressed K/BxN serum-transfer arthritis, which is dependent on macrophages, but not lymphocytes. CONCLUSION: Our findings demonstrate that JAK inhibitors suppress macrophage activation and attenuate TNF responses and further suggest that suppression of cytokine/chemokine production and innate immunity contribute to the therapeutic efficacy of JAK inhibitors.
23099471 Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizu 2013 Sep OBJECTIVES: The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks. METHODS: One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels. RESULTS: Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks. CONCLUSIONS: Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.
22753658 Differential gene expression profiles may differentiate responder and nonresponder patient 2012 Aug OBJECTIVE: We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-α (anti-TNF) combined therapy. METHODS: We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received infliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. RESULTS: Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF non-responders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. CONCLUSION: Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1, CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study.
21906423 Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the I 2011 May Given the availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), various national scientific societies have developed specific recommendations in order to assist rheumatologists in prescribing these drugs. The Italian Society for Rheumatology (Società Italiana di Reumatologia, SIR) decided to update its recommendations and, to this end, a systematic literature review was carried out and the evidence derived from it was discussed and summarised as expert opinions. Levels of evidence, strength of recommendations and levels of agreement were reported. The recommendations reported are intended to help prescribing rheumatologists to optimise the use of biologic agents in patients with RA seen in everyday practice; they are not to be considered as a regulatory rule.
22572888 A retrospective study of serum KL-6 levels during treatment with biological disease-modify 2013 Mar OBJECTIVE: We investigated associations between treatment with methotrexate (MTX) or biological disease-modifying antirheumatic drugs (DMARDs) and elevation of serum Krebs von den Lungen-6 (KL-6) levels in Japanese patients with rheumatoid arthritis (RA). METHODS: Using a standardized form, data were collected retrospectively from medical records and analyzed descriptively. RESULTS: Of a total of 198 RA patients with KL-6 serum levels measured at initiation of treatment (month 0) and two or more times by month 12, 27 (17.9 %) of 151 RA patients treated with biological DMARDs, including infliximab, etanercept, adalimumab, and tocilizumab (the biological DMARDs group), and 5 (10.6 %) of 47 patients treated without biological DMARDs but with MTX (MTX group), met criterion B (max. KL-6 ≥500 U/ml and >1.5-fold from baseline) by 12 months. The majority of patients (n = 28) meeting criterion B had no apparent interstitial lung disease or malignancy. Of these 28 patients, 21 had serum KL-6 levels available after reaching their maximum level, and 13 (61.9 %) of the 21 then met criterion R [decrease to less than 500 U/ml or to less than (baseline + 0.5 × (maximum - baseline))] by month 12. CONCLUSION: Serum KL-6 levels may increase during treatment with MTX or these biological DMARDs without significant clinical events.
22235146 Inactivating PSMB5 mutations and P-glycoprotein (multidrug resistance-associated protein/A 2012 Apr Bortezomib (BTZ), a registered proteasome inhibitor (PI) for multiple myeloma, has also been proposed as a potential antirheumatic agent. Its reported side effects, however, make it unappealing for long-term administration, and resistance may also develop. To overcome this, second-generation PIs became available. Here, we investigated whether a novel class of peptide epoxyketone-based PIs, including carfilzomib, N-((S)-3-methoxy-1-(((S)-3-methoxy-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)-2-methylthiazole-5-carboxamide (ONX0912), and (S)-3-(4-methoxyphenyl)-N-((S)-1-((S)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide (ONX0914), might escape two established BTZ-resistance mechanisms: 1) mutations in the proteasome β5 subunit (PSMB5) targeted by these PIs, and 2) drug efflux mediated by ATP-binding cassette transporters. THP1 myeloid sublines with acquired resistance to BTZ (54- to 235-fold) caused by mutations in the PSMB5 gene displayed marked cross-resistance but less pronounced cross-resistance to carfilzomib (9- to 32-fold), ONX0912 (39- to 62-fold), and ONX0914 (27- to 97-fold). As for ATP-binding cassette transporter-mediated efflux, lymphoid CEM/VLB cells with P-glycoprotein (Pgp)/multidrug resistance 1 overexpression exhibited substantial resistance to carfilzomib (114-fold), ONX0912 (23-fold), and ONX0914 (162-fold), whereas less resistance to BTZ (4.5-fold) was observed. Consistently, β5 subunit-associated chymotrypsin-like proteasome activity was significantly less inhibited in these CEM/VLB cells. Ex vivo analysis of peripheral blood mononuclear cells from therapy-naive patients with rheumatoid arthritis revealed that, although basal Pgp levels were low, P-glycoprotein expression compromised the inhibitory effect of carfilzomib and ONX0914. However, the use of P121 (reversin 121), a Pgp transport inhibitor, restored parental cell inhibitory levels in both CEM/VLB cells and peripheral blood mononuclear cells. These results indicate that the pharmacologic activity of these PIs may be hindered by drug resistance mechanisms involving PSMB5 mutations and PI extrusion via Pgp.
23253931 Autoimmunity in rheumatoid arthritis: different antigens--common principles. 2013 Apr Since the identification of antibodies directed against citrullinated protein antibodies (ACPA) as specific serological markers for rheumatoid arthritis (RA) the insight into the pathogenesis of RA has made significant progress. It is now realised that RA does not represent one disease entity, as ACPA-positive and ACPA-negative RA differ in several important aspects. For example, the most prominent genetic risk factors, the human leucocyte antigen shared epitope alleles only predispose to ACPA-positive RA, but not to ACPA-negative disease. Likewise, ACPA-positive RA is characterised by a more severe disease course as well as by a lower chance to enter drug-free remission. More recently, it became apparent that next to ACPA, another autoantibody system is also present in RA patients that is directed against a structurally similar determinant. These antibodies recognise carbamylated proteins and thus are called anticarbamylated protein (anti-CarP) antibodies. During carbamylation lysine residues are post-translationally modified to a homocitrulline, the antigenic identity crucial for recognition by anti-CarP antibodies. In this review we will discuss novel insight into the immune responses directed against citrullinated and carbamylated proteins.
22212836 [Prevalence of risk factors for fragility fracture in men aged 40 to 90 years of a Spanish 2011 Oct BACKGROUND: Osteoporosis and as a consequence fragility fractures have emerged in recent years as a major public health issue in developed countries. Although its epidemiology and risk factors in postmenopausal women are well known, few studies exist focused on analyzing this pathology in men. Our objective is to determine the prevalence of fragility fracture risk factors in men belonging to our population and to calculate the absolute risk of major osteoporotic fracture and hip fracture. METHODS: Cross-sectional study conducted in a Rural Health Basic Area. The target population was composed by males between 40 and 90 years old. Causes of exception were not considered. Personal interviews were carried out collecting the following data: age, weight, height, body mass index (BMI), previous fractures, background on parent hip fracture, smoking habits, use of corticosteroids, background on rheumatoid arthritis, secondary osteoporosis, alcohol and bone mineral density (BMD). With this data, later in our Health Center, the Absolute Fracture Risk and the Hip Fracture Risk were calculated using the FRAX ® tool. RESULTS: 431 cases were studied. Mean age 65,8 ± 13,9 years old and BMI 28,4 ± 4,3 kg/m². BMD had not been determined for any of the patients. Prevalence of risk factors: previous fracture 3,7%; parents with hip fractures 10,4%; smokers 21,1%; glucocorticoids 2,8%; rheumatoid arthritis 0,9%; secondary osteoporosis 2,3%; alcohol 30,9%. Absolute fracture risk, 3,7 ± 3,1 95% CI (3,43-4,02); hip fracture risk 1,7 ± 2,5 95% CI (1,51-1,98). CONCLUSION: Particularly important for males, the elimination of alcohol and tobacco.
21110028 A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α 2012 Feb Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.
21773833 Primary total knee arthroplasty using rotating-hinge prosthesis in severely affected knees 2012 Mar PURPOSE: A rotating-hinge total knee prosthesis may be utilized for the treatment of global instability or severe bone loss around the knee. The outcome of primary total knee arthroplasty (TKA) using Endo-Modell (Link(®)) rotating-hinge prosthesis was evaluated. METHODS: Retrospectively, review of 50 cases (40 patients) at a mean follow-up of 15 years (range, 10-18) who underwent primary TKA using Endo-Modell (Link(®)) was performed. Indications included severe primary osteoarthritis with substantial ligament laxity, severe rheumatic arthritis with extreme ligament instability and bone loss, supracondylar nonunion, charcot arthropathy, and posttraumatic arthritis. Knee Society Score (KSS) and radiographic analysis were done for preoperative and at latest follow-up. Statistical analysis was done using the Student's t test with the level of significance of p < 0.05. RESULTS: Overall, the rotating-hinge arthroplasty resulted in improved knee functioning. The KSS improved (p < 0.001) from a preoperative mean of 38 ± 14.3 (SD) points to a postoperative mean of 73 ± 12.8 points; the functional score improved (n.s.) from 36 ± 19.5 points to 47 ± 23.5 points. Mean range of motion at the most recent clinical follow-up evaluation was 102 ± 9°. However, all (100%) patients needed some form of assisted devices for walking and a relatively large number of deep infections (14%) were encountered. CONCLUSIONS: Reconstruction with a rotating-hinge total knee prosthesis provided substantial improvement in function and reduction in pain. However, the possibility of assisted walking and high rate of deep infection should be encountered. LEVEL OF EVIDENCE: Retrospective therapeutic study, Level IV.
20559831 Birmingham hip resurfacing: five to eight year results. 2011 Aug Hip resurfacings have been performed in our hospital since May 2001, and in this retrospective study, we analysed the clinical and radiological outcome of the first 144 prostheses (126 patients). One hundred and seven patients have visited our hospital for regular follow-up examination; 16 are not in regular follow-up and were sent a Harris Hip Score (HHS) questionnaire. Three patients live abroad. Mean follow-up was six years. One patient was lost during follow-up. Four prostheses have been revised. The six year cumulative survival rate was 96.7%. Two female patients required revision for aseptic lymphocyte-dominated vascular associated lesions (ALVAL) and two male patients due for femoral head necrosis. Both reoperated female patients had cup inclination > 60°. Mean HHS in the follow-up was 95.3, and mean patient satisfaction 2.53 on a scale 0-3. Neck thinning > 10% was seen in seven hips and impingement in 12 hips.
23166616 Study of association of CD40-CD154 gene polymorphisms with disease susceptibility and card 2012 OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients. METHODS: One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography. RESULTS: Nominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p=0.038). Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p=0.0047) between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis. CONCLUSION: Data from our pilot study indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also, the CD40 rs1535045 gene variant may influence development of subclinical atherosclerosis in RA patients.
21169999 Fine tuning NF-κB: new openings for PKC-ζ. 2011 Jan NF-κB is a critical transcription factor that is regulated by several post-transcriptional modifications. The characterization of their roles would help in the design of new therapeutic targets in cancer and inflammation.
22269731 Transcatheter aortic valve-in-valve-in-valve implantation for a failed xenograft. 2012 Feb A 78-year-old gentleman with a diagnosis of symptomatic severe xenograft aortic stenosis with multiple comorbidities was referred for transcatheter aortic valve implantation, that is, a "valve-in-valve" procedure. Transcatheter aortic valve implantation was performed by transapical approach using a balloon-expandable bioprosthesis. During valve deployment, the prosthesis moved toward the left ventricle and a second balloon-expandable valve was implanted within the first one-a "valve-in-valve-in-valve" to avoid further ventricular embolization of the first bioprosthesis. Echocardiography at hospital discharge showed a residual mean transvalvular gradient of 17 mm Hg and trivial paravalvular aortic regurgitation. At 1 year follow-up, the patient was in New York Heart Association functional class II.
20570414 Epitrochlear and axillary lymph node visualization on FDG-PET/CT imaging in a patient with 2011 May An 38 year-old female with oral tongue cancer was referred for FDG-PET/CT scan for evaluating axillary lymph nodes and restaging malignancy. Bilateral uptake of axillary and epitrochlear lymph nodes were observed on PET/CT imaging. The uptake pattern was unexpected for the patient with this malignancy and she had a history of rheumatoid arthritis. Additionally, the wrists were included in the field of view and showed elevated FDG uptake. In this case report, we report benign axillary and epitrochlear tracer uptake on FDG-PET/CT scan in a patient with a history of rheumatoid arthritis.
23054009 Marked diversity of IL23R gene haplotype variants in rheumatoid arthritis comparing with C 2013 Jan Haplotype tagging SNPs of interleukin-23 receptor gene rs1004819, rs7517847, rs7530511, rs2201841, rs1343151 and rs10889677 were determined in 396 patients with rheumatoid arthritis, 190 patients with Crohn's disease, 206 patients with ankylosing spondylitis and 182 controls. Using regression analysis models the rs1004819, rs2201841, and rs10889677 SNPs were found to confer risk for Crohn's disease and ankylosing spondylitis, while rs1343151 had a protective effect in both of these diseases, and the rs2201841 and rs10889677 SNPs showed susceptibility nature for rheumatoid arthritis. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to the rheumatoid arthritis, first in the literature. Seven different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks: thus, for rheumatoid arthritis the rs1343151 SNP was risk factor only in a specific haplotype surrounding; this can explain the controversial results published so far about this variant. More importantly, we observed, that while a specific haplotype can confer risk for rheumatoid arthritis, the same haplotype tended to protect against the development of the other two diseases. The data presented here serve evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility to or protection against a certain disease are interpreted.
21266447 A double-blind, randomized, placebo-controlled study to explore the efficacy of a dietary 2011 Jun OBJECTIVES: There is increased interest in the potential benefits of complementary therapies, of which dietary plant-derived polysaccharides (dPPs) are an important component. We examined the impact of oral ingestion of a pre-biotic dPP supplement active compound (AC) on serum glycosylation and clinical variables associated with inflammation and general health in patients with RA. METHODS: A double-blind, placebo-controlled, parallel-group clinical trial was used. Participants were randomly assigned to receive AC (n = 33) or placebo (n = 36) for 6 months. Serum protein N-glycosylation was determined by mass spectrometry. Patient outcomes were assessed by validated clinical trial health questionnaires. The primary clinical efficacy variable was DAS-28. RESULTS: The groups had comparable baseline clinical characteristics. AC was well tolerated with low drop-out rates. Supplementation resulted in a 12% significant drop in the levels of the agalactosylated (G0F) glycans [8.10 (0.89) to 7.16 (0.60); P = 0.03], but had no significant overall effect on patient outcomes. The placebo-treated group showed no change in G0F but exhibited a reduction in the levels of fully digalactosylated (G2) glycans (11%; P = 0.03). Although not clinically significant, DAS scores were, however, marginally lower in the placebo group [difference = 0.63 (0.23) s.e.; 95% CI 0.17, 1.10; P = 0.009], as were two of the secondary variables. CONCLUSIONS: Short-term dietary supplementation with AC resulted in a moderate, but significant, reduction in G0F levels, but did not result in any clinically significant improvement in disease activity when assessing the study group as a whole.
22329647 Hypoxia induces nitric oxide synthase in rheumatoid synoviocytes: consequences on NADPH ox 2012 May We investigated the effects of hypoxia on inducible NO synthase (iNOS) activity and expression in rheumatoid arthritis (RA) synoviocytes. We further studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions. Human cultured synoviocytes were treated for 24 hours with IL-1β, TNF-α or neither, and submitted to hypoxia or normoxia for the last 6 hours. Nitrite production and iNOS expression were increased under hypoxia conditions in RA cells in comparison to normoxia. Hypoxia did not potentate the basal and cytokine-induced superoxide productions, while NOXs' subunit expression and p47-phox phosphorylation were increased. Nitrosylation of NOXs and p47-phox was not raised under hypoxia conditions. Finally, peroxynitrite production was significantly increased under hypoxia conditions, in comparison to normoxia. Our results provide evidence for upregulation of iNOS and NOX activities in RA synoviocytes under hypoxia conditions, associated to an increased peroxynitrite production. Synovial cell metabolism under hypoxia conditions might be different from that in normoxia.