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ID PMID Title PublicationDate abstract
17921790 The impact of rheumatoid arthritis on rehabilitation outcomes after lower extremity arthro 2007 Oct BACKGROUND: Medical rehabilitation after lower extremity arthroplasty is an integral part of recovery and a critical step in returning to independent mobility. We hypothesized that rehabilitation may take longer for patients with rheumatoid arthritis (RA) versus osteoarthritis (OA) because joint pain, swelling, and deformities are generally worse among persons with RA. OBJECTIVES: To determine the impact of RA on length of rehabilitation stay and rehabilitation functional status gain after arthroplasty. METHODS: We conducted a retrospective cohort analysis using a national registry of US medical rehabilitation inpatients admitted after a lower extremity arthroplasty between 1994 and 2001. Sample included 1361 patients with RA and 26,096 patients with OA. The main outcome measure was functional status gain as assessed by the functional independence measure (FIM). Our primary analytic method was linear regression. Covariates were age, gender, race/ethnicity, other comorbidity, admission FIM, and site of arthroplasty. RESULTS: Mean length of stay for patients with RA was 11.3 +/- 7.1 days (mean +/- standard deviation) versus 10.3 +/- 6.5 days for those with OA. Mean weekly gain was 18.6 +/- 12.1 for patients with RA versus 20.6 +/- 12.0 for those with OA. After adjusting for covariates, RA was associated with longer stay (0.7 day) and lower FIM gain (2.6). CONCLUSIONS: RA was associated with longer length of rehabilitation stay and lower FIM gain in patients with lower extremity arthroplasty. Such patients may require additional monitoring to ensure sufficient rehabilitation.
18432325 [Alexithymia and immunoendocrine parameters in patients affected by systemic lupus erythem 2008 Jan OBJECTIVE: Aim of this study was to evaluate the prevalence of alexithymia in patients affected by SLE or RA and to investigate the correlation between alexithymia and immunoendocrine parameters (PRL, hGH, IL-6 and TNF-alfa). METHODS: Twenty-five patients (12 and 13 affected by SLE and RA, respectively) were enrolled into the study. The Toronto Alexithymia Scale-20 (TAS-20) was administered. PRL, hGH, IL-6 and TNF-alfa levels were measured by commercially available ELISA kits. RESULTS: Alexithymia prevalence (TAS-20 > or = 51) was 54% in RA and 42% in SLE patients. hGH serum levels were 3.1+/-4.2 and 1.1+/-0.9 IU/ml in SLE and RA, respectively. PRL concentration was 18.4+/-6.5 ng/ml and 14.2+/-4.0 ng/ml in SLE and RA patients, respectively (p=0.03). In RA group, TNF-alpha was 20+/-36.2 whereas in SLE it was 4.9+/-12.8 pg/ml (p=0.03); IL-6 serum concentrations were 24.4+/-25.1 and 2.9+/-5.4 pg/ml, in RA and SLE respectively (p=0.004). The serum level of hGH showed slight increase in alexithymic group (A) compared to non alexithymic group (NA) in both SLE and RA patients. PRL serum levels in SLE-A patients was 26.7+/-17.3 ng/ml while in SLE-NA patients was 12.4+/-3.3 ng/ml (p=0.04). In RA patients increased values of IL-6 and TNF-alpha were present in the A group compared to NA group (IL-6: 35.3+/-28 pg/mL vs 3.5+/-3.9 pg/mL, p=0.01; TNF-alpha: 34.7+/-39 pg/mL vs 3.1+/-3.4 pg/mL, p=0.01). CONCLUSIONS: In this preliminary results we found an high prevalence of alexithymia and a correlation between immunoendocrine parameters and alexhytimic features in SLE and RA, suggesting that an immunomodulatory pathway could influence this cognitive style in patients with autoimmune disorders. Other studies should contribute to find a common biological pathway linking alexithymia and autoimmunity.
16891223 Frequency and significance of antibodies to cyclic citrullinated peptide in type 1 autoimm 2006 Jun OBJECTIVES: Determine the frequency, clinical phenotype, and prognostic implications of antibodies against cyclic citrullinated peptides in patients with type 1 autoimmune hepatitis. METHODS: Three hundred and ninety-five serum samples from 179 patients were tested by enzyme-linked immunosorbent assay, and findings correlated with clinical and histological features, frequency of HLA DR3 and DR4, and treatment outcome. RESULTS: Twenty patients (11%) had antibodies against cyclic citrullinated peptides. Seropositivity was associated with a higher frequency of rheumatoid arthritis (RA) (25 vs. 0%, P < 0.001). Patients with antibodies against cyclic citrullinated peptides also had a significantly greater occurrence of histological cirrhosis at presentation (47 vs. 20%, P = 0.01) and death from hepatic failure than seronegative patients (25 vs. 9%, P = 0.04). Cirrhosis at presentation occurred more commonly in the patients with antibodies against cyclic citrullinated peptides and RA than in the other patients (100 vs. 21%, P = 0.005). CONCLUSIONS: Antibodies against cyclic citrullinated peptides occur in a subgroup of patients with type 1 autoimmune hepatitis who have a greater occurrence of cirrhosis at presentation and death from hepatic failure. Their presence with RA at accession characterizes a subgroup with cirrhosis.
18511475 The incidence of rheumatoid arthritis in Spain: results from a nationwide primary care reg 2008 Jul OBJECTIVE: To estimate the incidence of early arthritis (EA) and of RA in adults (>16 yrs) in Spain. METHODS: Primary care physicians were instructed in the detection of new cases using a checklist. All cases were evaluated at EA units (EAUs) within 15 days of detection. ACR criteria for the classification of RA were assessed every 6 months thereafter. RESULTS: In an area covering 4,342,378 inhabitants over the age of 16 yrs, 2467 patients were referred to the EAU, of whom 1063 fulfilled EA criteria (43.1%). After 6 months, 362 patients fulfilled RA criteria. The estimated annual incidence of EA was 25/100,000 population (95% CI: 23, 26). The annual incidence of RA was 8.3 cases/100,000 (95% CI: 7.5, 9.2): 11.3/100,000 in women (95% CI: 10.0, 12.8), and 5.2/100,000 in men (95% CI: 4.3, 6.3). The incidence of RA increased with age in both sexes. At the 6 months' assessment, 187 (51.7%) of the patients with RA were RF positive. The presentation of RA was mainly polyarticular (n = 268; 74.0%). There were 701/1063 patients with EA who did not fulfil RA criteria by 6 months after the first rheumatologist visit. If all cases of undifferentiated arthritis (n = 118; 17%) became RA, the incidence would be in the range of 10 cases/100,000 population. CONCLUSIONS: RA incidence in Spain is in the lower range of published data. The incidence of EA is about three times that of RA.
18050383 Subclinical coronary artery calcification and relationship to disease duration in women wi 2008 Jan OBJECTIVE: To examine the association between disease duration of rheumatoid arthritis (RA) and the presence and extent of coronary artery calcification (CAC) in women with RA. METHODS: In this cross-sectional study, 185 women with RA duration of at least 2 years and no clinical cardiovascular disease completed electron-beam tomography (EBT) scans and risk factor assessment. Multivariable logistic regression was used to associate RA duration quartiles with subclinical CAC and extent of CAC. RESULTS: Age was similar across the quartiles of RA duration. Patients with RA > 23 years had significant increased odds (unadjusted OR 2.60, 95% CI 1.21 5.53) of having more extensive CAC compared to the referent group, those with RA for 2 7 years. This association remained significant after adjustment for traditional coronary heart disease (CHD) risk factors and RA-related covariates. Patients with intermediate RA duration (8 13 yrs) were more likely to have presence of any CAC (OR 3.03, 95% CI 1.06 8.66) compared to the referent group only after adjusting for age, race, and traditional CHD risk factors. Patients with longer RA duration were more likely to have cumulative joint damage, manifested as prior joint surgery, joint deformity, and greater functional disability. Lower body mass index also was associated with longer RA duration. CONCLUSION: Patients with longstanding RA have more extensive subclinical atherosclerosis or CAC compared to patients of the same age, independent of other CHD risk factors. RA duration may be a surrogate for factors related to the disease process or its treatment that may promote coronary atherogenesis.
16511935 Neurological complications of infliximab. 2006 May The use of anti-tumor necrosis factor-a (TNF-a) therapies has led to improved outcomes in the treatment of rheumatoid arthritis (RA). However, the use of these new therapeutic agents requires careful monitoring for adverse effects. We describe 3 patients who developed neurological disease closely associated with the use of infliximab, a monoclonal antibody that binds to and inactivates TNF-a. All had evidence of polyneuropathy, demyelinating in one and axonal in 2. One patient had a central nervous system syndrome. Physicians should be aware of these potential adverse effects when treating patients with infliximab.
18576354 Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled 2008 Jul OBJECTIVE: CCR2 is a chemokine receptor expressed by monocytes, macrophages, and a subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), is abundantly present in the synovium of patients with rheumatoid arthritis (RA). Blocking CCR2 prevents CCL2-mediated chemotaxis in vitro and modulates arthritis in animal models of RA. In this study we examined the effects of CCR2 blockade on synovial inflammation in RA. METHODS: The study was designed as a phase IIa clinical trial with a human CCR2 blocking antibody (MLN1202) in patients with active RA. Thirty-two patients received 3 infusions, over a period of 6 weeks, with either placebo (n = 9) or anti-CCR2 monoclonal antibody at 0.5 mg/kg (n = 7), 1.5 mg/kg (n = 7), or 4.0 mg/kg (n = 9). Safety was monitored with laboratory tests, immunotoxicity assessments, and documenting of adverse events, and European League Against Rheumatism and American College of Rheumatology response criteria were used to assess clinical improvement. Synovial tissue was obtained at baseline and after 43 days of treatment, for pharmacodynamic analysis using immunohistochemistry and digital image analysis. The Kruskal-Wallis test was used to compare groups, and the Wilcoxon signed rank test was used to assess changes within the groups. RESULTS: All patients completed the study. Treatment with CCR2 blocking antibody reduced the levels of free CCR2 on CD14+ monocytes by at least 57% and up to 94% (P < 0.001), demonstrating the biologic activity of the compound. However, there was no reduction in the levels or expression of any of the synovial biomarkers. Accordingly, no clinical improvement was observed. CONCLUSION: Treatment with anti-CCR2 blocking antibody did not result in amelioration of synovial inflammation in active RA. The results do not support the notion that blockade of CCR2 may be sufficient to induce clinical improvement in RA.
18452992 VIP reverses the expression profiling of TLR4-stimulated signaling pathway in rheumatoid a 2008 Jun Since recent evidences point out the potential involvement of Toll-like receptors (TLRs) in the therapeutic effect of vasoactive intestinal peptide (VIP), the purpose of this study is to elucidate the role of VIP as a negative regulator of TLR-signaling. To this aim, we analyzed in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), the expression profile of TLR-pathway related molecules, as well as the alterations induced by LPS stimulation in RA-FLS and the effect of VIP treatment. Cultured FLS were obtained from patients with RA or OA. RA-FLS were next stimulated with lipopolysaccharide (LPS) in presence or absence of VIP. The gene expression profiling of molecules involved in LPS-mediated TLR4-signaling was studied by cRNA microarray analysis. Twenty three molecules involved in TLR signaling resulted over-expressed at mRNA level in basal RA-FLS compared to OA-FLS. Moreover, in RA-FLS, 23 of the analyzed genes were found to be up-regulated by LPS stimulation whereas 30 were not affected. VIP down-regulated the LPS-induced RNA expression of molecules involved in TLR signaling pathway. Up-regulation of RNA expression of CD14, MD2, TRAM, TRIF, IRAK4, TAB2, TRAF6 and TBK1 was corroborated by RT-PCR as well as the VIP regulatory effect. Increased protein levels of TRAF6, TBK1 and pIRAK1 after exposure to LPS, and the inhibitory effect of VIP, were described by Western blotting. As functional consequences, it was observed the VIP-induced impaired production of IL-6 and RANTES/CCL5 after LPS stimulation. In conclusion, VIP acts as a negative modulator of the TLR4-signaling by overturning the production of several checkpoints molecules of the cascade and thus, widening its potential therapeutic effects.
17786275 Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin 2007 Oct We conducted our study to assess the antiproliferative and proapoptotic potential of hecogenin and tigogenin, two saponins which are structurally similar to diosgenin. We particularly focused our attention on mitogen-activated protein kinase (MAPK) activation in relation to apoptosis but also with the COX-2 expression and activity. Rheumatoid arthritis (RA) synoviocytes were isolated from fresh synovial biopsies obtained from five RA patients undergoing hip arthroplasty. Measurement of cell proliferation was determined using the MTT assay. Apoptosis was evaluated by studying caspase-8, caspase-9 and caspase-3 activities but also by quantification of DNA fragmentation. Quantification of human phospho-MAPKs was realized by ELISA. COX-2 expression was demonstrated by Western blot analysis and COX-2 activity by assay of endogenous prostaglandin E2 (PGE2) production. Tigogenin was more effective than hecogenin in inducing apoptosis in human RA fibroblast-like synoviocytes (FLS) which was caspase dependent but poly(ADP-ribose) polymerase independent and characterized by DNA fragmentation. Our results demonstrated hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2. These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways. This study also confirms the discussed appearance of the downregulation or upregulation of COX-2 in cell apoptosis as a function of cell type.
17493863 How TNF was recognized as a key mechanism of disease. 2007 Jun This review summarizes the origins of the insight that excess production of pro-inflammatory cytokines caused a constellation of changes that contribute to pathophysiology of disease. This connection was made following the original 1975 TNF (tumor necrosis factor) publication from New York describing how activated macrophages kill tumors. The study caught the eye of a group in London who were trying to understand how the same in vivo macrophage activation would protect mice against the erythrocytic protozoan parasites that cause malaria and babesiosis. Based on collaborative research between these two groups, it was argued in 1981 that TNF and related cytokines initiated events that caused pathology, as well as parasite death within red cells in these infectious diseases. This proved to be a key conceptual advance. It was also argued that the pathology of bacterial sepsis logically had TNF origins. Once TNF was cloned in 1985, allowing its specific analysis in serum and neutralization in vivo, the involvement of this cytokine in infectious disease pathology was pursued by a number of groups. Some researchers found that once "their" cytokine was cloned and sequenced, they had been unwittingly expanding knowledge on TNF for several years. By the late 1980s excess TNF production was proposed to be central to acute systemic viral diseases. This family of cytokines is now at the centre of investigations to understand the mechanisms of acute systemic viral diseases, including influenza and the hemorrhagic viral diseases. With its implication as the master regulator of other inflammatory cytokines in the synovial membrane, TNF has also become the major cytokine in the pathogenesis of chronic inflammatory disease. Its neutralization has proven to be a potent treatment for rheumatoid arthritis and Crohn's disease.
16814399 Mannan binding lectin and its interaction with immunoglobulins in health and in disease. 2006 Aug 15 In humans there are five classes of immunoglobulins (Igs), IgG, IgM, IgA, IgE and IgD, all of which are glycoproteins. The Igs are the major secretory product of the adaptive immune system, and they bind to antigens via variable sequences on their Fab regions. The binding to antigen results in neutralization or agglutination of bound material and also initiates effector functions via the Fc regions, such as opsonisation and activation of the classical complement pathway through binding of C1q. Mannan binding lectin (MBL), the 'recognition' molecule of the lectin pathway of complement activation, is homologous in structure to C1q, and binds in a calcium-dependent manner to terminal mannose and GlcNAc residues which have been identified on the oligosaccharides N-linked to the Igs. MBL binds agalactosylated glycoforms of IgG (IgG-G0), polymeric forms of IgA and certain glycoforms of IgM which have a high incidence of GlcNAc-terminating glycans. This interaction provides a route of clearance of immune complexes from the serum, and a mechanism of complement activation to Ig-coated pathogens. In disease, MBL contributes to inflammation in Rheumatoid Arthritis, a condition in which serum IgG-G0 concentrations can increase significantly compared to healthy individuals. MBL has recently been demonstrated to bind Ig in the B cell receptor complex which expresses abnormal variable region glycosylation, in follicular lymphoma.
18683125 Sinomenine versus NSAIDs for the treatment of rheumatoid arthritis: a systematic review an 2008 Oct Sinomenine (SIN), an alkaloid isolated from CAULIS SINOMENII, has been used in the treatment of rheumatoid arthritis (RA) clinically. This study aimed to systematically evaluate the efficacy and safety of SIN by a comparison between SIN and non-steroidal anti-inflammatory drugs (NSAIDs). Forty-three electronic databases were systematically searched. The quality of eligible trials was assessed by Jadad's scale. Revman 5.0 software was used for data syntheses and meta-analyses. The results showed that (i) of the 121 potential studies identified, 10 clinical trials involving 1185 patients met the inclusion criteria; (ii) improved patients and rheumatoid factor disappearance patients after SIN treatments were significantly more than those treated by NSAIDs ( P < 0.00001 and P = 0.008); (iii) compared with NSAIDs, SIN was more effective in amelioration of morning stiffness ( P < 0.00001), painful joints ( P = 0.03), and erythrocyte sedimentation rate ( P < 0.00001), but there was no significant difference between the two remedies in the treatment of swollen joints, grip strength, and C-reactive protein ( P > 0.05); and (iv) adverse events occurred less frequently in the digestive system during SIN treatment than during NSAID treatment ( P = 0.0003) but occurred more frequently in the dermatomucosal system with SIN treatment ( P = 0.03), while adverse events of the nervous system were similar for both treatments ( P = 0.31). In conclusion, SIN may be a valuable remedy to treat RA clinically, although current evidence needs to be further verified by more high-quality trials.
19004044 The minimally important difference for the fatigue visual analog scale in patients with rh 2008 Dec OBJECTIVE: To estimate the minimally important difference (MID) for a fatigue visual analog scale (VAS) using patient-reported anchors (fatigue, pain, and overall health). METHODS: Patients with rheumatoid arthritis (RA; n = 307) had 2 clinic visits at a median of 5.9 months apart. They completed a fatigue VAS (0-10 scale) and the retrospective anchor items, "How would you describe your overall fatigue/pain/overall health since the last visit?" with response options: Much worsened, Somewhat worsened, Same, Somewhat better, or Much better. The fatigue anchor was used for primary analysis and the pain/overall health anchors for sensitivity analyses. The minimally changed group was defined by those reporting they were somewhat better or somewhat worsened. RESULTS: The mean [standard deviation (SD)] age was 59.4 (13.2) years, disease duration was 14.1 (11.5) years, and 83% of patients were women. The baseline mean (SD) Health Assessment Questionnaire-Disability Index score was 0.84 (0.75). The baseline fatigue VAS score was 4.2 (2.9) and at followup was 4.3 (2.8) [mean change of -0.07 (2.5); p = not significant]. The fatigue change score (0-10 scale) for Somewhat better and Somewhat worsened for the fatigue anchor averaged -1.12 and 1.26, respectively. Using the pain anchor, the fatigue change score for Somewhat better and Somewhat worsened averaged -0.87 and 1.13; and using the global anchor, the fatigue change score for Somewhat better and Somewhat worsened averaged -0.82 and 1.17, respectively. Effect size estimates using 3 anchors were small for the Somewhat better (range 0.27-0.39) and Somewhat worsened (0.40-0.44) groups, but larger than for the no-change group (0.03-0.08). CONCLUSION: The MID for fatigue VAS is between -0.82 for -1.12 for improvement and is 1.13 to 1.26 for worsening on a 0-10 scale in a large RA clinical practice, and is similar to that seen in RA clinical trials. This information can aid in interpreting fatigue VAS in day-to-day care in clinical practice.
17823284 Molecular interactions between T cells and fibroblast-like synoviocytes: role of membrane 2007 Nov The mechanism of fibroblast-like synoviocyte (FLS) transformation into an inflammatory phenotype in rheumatoid arthritis (RA) is not fully understood. FLS interactions with invading leukocytes, particularly T cells, are thought to be a critical component of this pathological process. Resting T cells and T cells activated through the T-cell receptor have previously been shown to induce inflammatory cytokine production by FLS. More recently, a distinct population of T cells has been identified in RA synovium that phenotypically resembles cytokine-activated T (Tck) cells. Using time lapse microscopy, the interactions of resting, superantigen-activated, and cytokine-activated T cells with FLS were visualized. Rapid and robust adhesion of Tck and superantigen-activated T cells to FLS was observed that resulted in flattening of the T cells and a crawling movement on the FLS surface. Tck also readily activated FLS to produce interleukin IL-6 and IL-8 in a cell contact-dependent manner that was enhanced by exogenous IL-17. Although LFA-1 and ICAM-1 co-localized at the Tck-FLS synapse, blocking the LFA-1/ICAM-1 interaction did not substantially inhibit Tck effector function. However, antibody blocking of membrane tumor necrosis factor (TNF)-alpha on the Tck surface did inhibit FLS cytokine production, thus illustrating a novel mechanism for involvement of TNF-alpha in cell-cell interactions in RA synovium and for the effectiveness of TNF-alpha blockade in the treatment of RA.
17613557 A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid 2007 Sep BACKGROUND: A Mediterranean-type diet rich in fish, fruit and vegetables and low in saturated fats has been associated with health benefits, including improved cardiovascular profile and benefit in RA. OBJECTIVE: To overcome obstacles to healthy eating by a community-based intervention promoting a Mediterranean-type diet in patients with RA living in socially deprived areas of Glasgow. METHODS: 130 female patients with RA aged 30-70 years (median 55), disease duration 8 years were recruited from three hospital sites. The intervention group (n = 75) attended weekly 2-hour sessions for 6 weeks in the local community, including hands-on cooking classes backed up with written information. The control group (n = 55) were given dietary written information only. Both groups completed food frequency questionnaires (FFQs), and clinical and laboratory measures were assessed at baseline, 3 and 6 months. RESULTS: Significant benefit was shown in the intervention group compared with controls for patient global assessment at 6 months (p = 0.002), pain score at 3 and 6 months (p = 0.011 and 0.049), early morning stiffness at 6 months (p = 0.041) and Health Assessment Questionnaire score at 3 months (p = 0.03). Analysis of the FFQs showed significant increases in weekly total fruit, vegetable and legume consumption and improvement in the ratio of monounsaturated:saturated fat intake and systolic BP in the intervention group only. The cooking classes were positively received by patients and tutors; cost/patient for the 6 week course was 84 pounds (124 euro). CONCLUSIONS: Results demonstrate that a 6 week intervention can improve consumption of healthier foods. If implemented more widely it may prove a popular, inexpensive and useful adjunct to other RA treatment.
17560936 Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial fibroblasts fro 2007 Aug 10 The transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel, which is mainly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. However, there is increasing evidence that TRPV1 expression is not limited to primary afferent neurons but that the receptor is expressed in various cell types throughout the body. Here, we demonstrate the expression of TRPV1 in synovial fibroblasts (SF) from patients with symptomatic osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, the mRNA expression of TRPV1 was shown in PBMCs from healthy controls and from OA patients. The presence of TRPV1 was confirmed at the protein level. Stimulation of cultured OA- and RA-SF with the TRPV1 agonist capsaicin led to increased expression of IL-6 mRNA as well as of IL-6 protein in the cell culture supernatants. IL-6 protein expression could be antagonized with capsazepine. Thus, we hypothesize that TRPV1 may play a role in non-neuronal mechanisms that might modulate nociception in symptomatic OA and RA patients.
18951300 Ocrelizumab, a humanized monoclonal antibody against CD20 for inflammatory disorders and B 2008 Nov Biogen Idec Inc, Genentech Inc, Roche Holding AG and Chugai Pharmaceutical Co Ltd are developing ocrelizumab, a humanized mAb against CD20, for the potential treatment of inflammatory disorders and B-cell malignancies. Ocrelizumab is undergoing phase III clinical trials for rheumatoid arthritis and lupus nephritis, and phase II trials for multiple sclerosis and hematological cancer. Previously, ocrelizumab was also being developed for the treatment of systemic lupus erythematosus (SLE) and neuromyelitis optica; however, development for SLE has been discontinued. No development has been reported for neuromyelitis optica and as of January 2007, this indication had been removed from the company pipeline.
18077486 Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte supp 2008 Jan OBJECTIVE: Rheumatoid arthritis (RA) is a T-cell-mediated systematic disease and is usually accompanied by articular cartilage damage. In the present study, we explored the effects of bone marrow-derived mesenchymal stem cells (MSCs) and MSC-differentiated chondrocytes (MSC-chondrocytes) on the responses of antigen-specific T cells in RA to type II collagen (CII) to evaluate the potential therapeutic value of MSCs in RA treatment. METHODS: The effects of both MSCs and MSC-chondrocytes on the proliferation, activation-antigen expression (CD69 and CD25) and cytokine production [interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-10 and IL-4] of CII-reactive T cells in RA patients were investigated with the stimulation of CII or otherwise. CD3/annexin V staining was used to evaluate T-cell apoptosis in the inhibition. The role of transforming growth factor-beta1 (TGF-beta1) underlying the inhibition was also investigated. RESULTS: MSCs failed to elicit positive responses of CII-reactive T cells, whereas they significantly suppressed CII-stimulated T-cell proliferation and activation-antigen expression in a dose-dependent fashion without inducing T-cell apoptosis. The inhibition was observed even after MSCs were added as late as 3 days after the initiation of stimulation. Moreover, MSCs inhibited both CD4+ and CD8+ T cells from producing IFN-gamma and TNF-alpha, while they up-regulated the levels of IL-10 and restored the secretion of IL-4. TGF-beta1 was confirmed to play a critical role in the inhibition. Throughout our study, MSC-chondrocytes shared similar properties with MSCs. CONCLUSION: Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell responses to CII in RA, which suggested that MSCs could be a potential candidate for RA treatment in future if further confirmed in vivo.
19110522 [Megaloblastic anemia associated with salazosulfapyridine treatment for rheumatoid arthrit 2008 Dec A 70-year-old man was diagnosed as having rheumatoid arthritis (RA) in 2005. He was treated with 1 g salazosulfapyridine (SASP) daily for two years. Hematological investigations conducted since 2005 demonstrated hemoglobin concentrations of 8 approximately 9 g/dl, which then dropped to 4.9 g/dl on November 21, 2007, following which he was admitted to our hospital. Megaloblastic anemia associated with SASP treatment and anemia of chronic disorders were diagnosed on the basis of folate deficiency and bone marrow examination. This report describes a case of megaloblastic anemia, which developed two years after starting SASP and promptly recovered after its withdrawal and treatment with folic acid and prednisolone. The doses of SASP prescribed for RA in Japan are less than those prescribed abroad. Megaloblastic anemia associated with SASP treatment for RA is not usually detected in Japan. Currently, SASP is widely used and one of the key drugs in the treatment of RA. This case suggests that SASP therapy in RA might result in megaloblastic anemia.
16925056 [Impact of sodium chloride concentration on pH-metricdetermination of the rate of erythroc 2006 Jul The impact of the concentration of a base electrolyte (0.57; 0.85, 2.28% NaCl) on the pH-metric study of ionic equilibrium was studied in theerythrocytic suspensions obtained from the peripheral blood of healthy individuals, patients with various diseases and in the latter after their treatment. The use of the isotonic concentration of the base electrolyte at an ionic force of micro = 0.15 (0.85% NaCl) is optimal in terms of the accuracy of establishment of the most important parameters of denaturation erythrograms at an elevated temperature (58 degrees C), by continuously recording the pH value of a native red blood cell suspension.