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ID PMID Title PublicationDate abstract
20203095 Continuing professional development is associated with increasing physical therapists' rol 2010 Apr BACKGROUND AND OBJECTIVE: This study explored the relationships among the roles assumed by physical therapists in arthritis care and their previous participation in arthritis courses for continuing professional development (CPD). DESIGN: A cross-sectional mail survey was conducted. METHOD: A total of 600 Canadian physical therapists and 461 Dutch physical therapists practicing in orthopedics were randomly selected to participate in a mail survey. The questionnaire covered areas related to their clinical practice, previous participation in arthritis-related CPD courses, and roles in the management of osteoarthritis (OA) and rheumatoid arthritis (RA). Poisson regression was used to explore the associations between physical therapists' participation in arthritis-related CPD courses and the number of roles they assumed in OA and RA care, after adjusting for personal characteristics, arthritis caseload, and country of practice. RESULTS: The survey response rates were 47.7% in Canada and 50.5% in the Netherlands. A total of 424 participants (Canada=224, the Netherlands=200) had treated patients with OA in the previous month, and 259 participants (Canada=68, Netherlands=191) had treated patients with RA in the previous month. The most common roles reported by participants were providing traditional physical therapy interventions and providing postsurgical care. Arthritis-related CPD courses significantly increased (ie, multiplied) the expected number of roles assumed by physical therapists by a factor of 1.32 (95% confidence interval=1.11, 1.56) in OA management and 1.69 (95% confidence interval=1.34, 2.13) in RA management. LIMITATIONS: Physical therapists' roles in arthritis management were obtained through self-reporting, which might differ from their actual clinical practice. CONCLUSIONS: This exploratory analysis highlights the association between participation in arthritis-related CPD courses and the roles assumed by physical therapists in OA and RA management. Further research is needed to understand the effects of CPD activities on other areas of physical therapist practice and on patients' outcomes.
20132965 Serum procalcitonin in systemic autoimmune diseases--where are we now? 2010 Oct OBJECTIVES: To review the current evidence regarding the value of measuring procalcitonin (PCT) levels in patients with systemic autoimmune diseases, with a focus on the evidence for diagnostic and analytical performance of this biomarker. A brief description of the pathophysiological basis of this biomarker is also included. METHODS: Using PubMed from the National Library of Medicine, relevant English literature on PCT in patients with different systemic autoimmune diseases, from 1990 to 2009, was reviewed. The search used keywords referring to procalcitonin and systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated systemic vasculitis, Goodpasture syndrome, rheumatoid arthritis, and giant cell arteritis. RESULTS: When used in the appropriate clinical setting, the measurement of serum PCT levels is valuable as a marker of severe systemic bacterial and fungal infections and sepsis. Information regarding plasma PCT levels in patients with active underlying systemic autoimmune diseases is limited, primarily from observational studies and case series, with considerable variability of patient characteristics and clinical settings. In the detection of systemic infection concomitant with autoimmune diseases, PCT had a diagnostic sensitivity of 53 to 100% and a specificity of 84 to 97% (depending on the selection criteria) and was superior to other inflammatory markers tested. Most of the studies used a semiquantitative test for PCT measurement (functional assay sensitivity <0.5 ng/mL), which can explain the low sensitivity of the test. PCT levels were not significantly affected by renal function abnormalities or immunosuppressive agents. Although high PCT levels commonly occurred with infection, elevated levels of PCT could be found in patients with vasculitis without evidence of infection, often correlated with high disease activity scores. CONCLUSIONS: Significantly elevated PCT levels offer good specificity and sensitivity for systemic infection in patients with systemic autoimmune diseases, regardless of the use of corticosteroids or immunosuppressive agents. PCT measurement may add to diagnostic accuracy in patients with systemic autoimmune diseases who present with a febrile illness, especially when highly sensitive PCT assays and specific PCT cutoff ranges are used in a predefined clinical setting (reflecting the likelihood of infection versus an autoimmune disease flare). However, there are limitations when using this biomarker in patients with systemic autoimmune diseases. PCT levels should not replace the necessary extensive diagnostic workup, which should include a thorough history and physical examination, combined with appropriate immunological, microbiological, radiological, and histological data.
20957659 Safety and efficacy of etanercept beyond 10 years of therapy in North American patients wi 2011 Mar OBJECTIVE: To evaluate the long-term safety and efficacy of etanercept therapy in rheumatoid arthritis (RA) patients. METHODS: Adult patients with early RA or longstanding RA received etanercept in open-label extension studies following initial double-blind trials of etanercept. RESULTS: Of 558 early RA patients and 714 longstanding RA patients who received at least 1 dose of etanercept, a total of 194 early RA patients and 217 longstanding RA patients were treated with 25 mg of etanercept twice weekly through 10 years. Five opportunistic infections were reported: in early RA, 1 Candida septicemia; in longstanding RA, 1 herpes zoster, 1 atypical mycobacterium infection, 1 meningoencephalitis (unspecified), and 1 fungal sepsis (unspecified). Twenty-nine cases of sepsis occurred (10 early RA, 19 longstanding RA). Occurrence of all malignancies was similar to that expected in the general population, but the occurrence of lymphomas was higher than expected in the general population. Fourteen lymphomas (7 early RA, 7 longstanding RA) and 2 cases of demyelinating disease (1 early RA, 1 longstanding RA) were reported. Deaths occurred in 18 early RA patients and 43 longstanding RA patients. Both patient groups showed sustained improvement in American College of Rheumatology responses, swollen joint counts, Health Assessment Questionnaire disability index scores, and C-reactive protein levels. CONCLUSION: Etanercept maintained therapeutic benefits beyond 10 years of therapy in both early RA and longstanding RA patients, suggesting that etanercept is well tolerated and effective as a long-term, continuous therapy for the treatment of RA, with a favorable risk/benefit ratio.
19317362 Aspergillus colonisation of pulmonary rheumatoid nodules: a rare cause of 'bull's eye' app 2009 Jan Pulmonary rheumatoid nodules [PRNs] are a well described manifestation of rheumatoid arthritis [RA]. Fungal colonisation of these nodules is a rare phenomenon. We report a case of Aspergillus colonisation of multiple cavitary rheumatoid nodules in a young female patient with long-standing seropositive RA with 'bull's eye' appearance on computed tomography [CT]. The 'bull's eye' appearance inside PRNs should raise the suspicion of possible fungal colonisation. In patients with RA, a high index of suspicion for the fungal colonisation should be considered by the clinicians treating pulmonary cavitary nodules.
20635919 Prevention of hepatitis B virus reactivation under rituximab therapy. 2009 Nov Rituximab is a useful drug for the treatment of B-cell non-Hodgkin's lymphoma, and its use has been extended to other diseases such as idiopathic thrombocytopenic purpura and chronic rheumatoid arthritis. One serious complication associated with rituximab use is reactivation of hepatitis B virus, and the search for methods to prevent this occurrence has resulted in a rapid accumulation of knowledge in recent years. In this review, we will discuss case studies from our group, as well as other groups, and outline current knowledge on the topic together with issues that remain to be resolved.
21087445 Identification of a novel cell type-specific intronic enhancer of macrophage migration inh 2011 Feb The aim of this study was to determine the genetic regulation of macrophage migration inhibitory factor (MIF). DNase I hypersensitivity was used to identify potential hypersensitive sites (HS) across the MIF gene locus. Reporter gene assays were performed in different human cell lines with constructs containing the native or mutated HS element. Following phylogenetic and transcription factor binding profiling, electrophoretic mobility shift assay (EMSA) and RNA interference were performed and the effects of incubation with mithramycin, an antibiotic that binds GC boxes, were also studied. An HS centred on the first intron of MIF was identified. The HS acted as an enhancer in human T lymphoblasts (CEMC7A), human embryonic kidney cells (HEK293T) and human monocytic cells (THP-1), but not in a fibroblast-like synoviocyte (FLS) cell line (SW982) or cultured FLS derived from rheumatoid arthritis (RA) patients. Two cis-elements within the first intron were found to be responsible for the enhancer activity. Mutation of the consensus Sp1 GC box on each cis-element abrogated enhancer activity and EMSA indicated Sp1 binding to one of the cis-elements contained in the intron. SiRNA knock-down of Sp1 alone or Sp1 and Sp3 together was incomplete and did not alter the enhancer activity. Mithramycin inhibited expression of MIF in CEMC7A cells. This effect was specific to the intronic enhancer and was not seen on the MIF promoter. These results identify a novel, cell type-specific enhancer of MIF. The enhancer appears to be driven by Sp1 or related Sp family members and is highly sensitive to inhibition via mithramycin.
19565475 The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: R 2009 Jul OBJECTIVE: To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response. METHODS: Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks. RESULTS: By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms. CONCLUSION: Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.
19473568 Classification models for disease: the effect of associations between markers on calculati 2009 Mar OBJECTIVES: The risk for disease or a bad prognosis can be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables in prediction or classification models. PATIENTS AND METHODS: Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included in the differential diagnosis and final diagnoses (RA or non-RA) were established after 1 year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. RESULTS: When two features are similarly associated in cases and controls, risks for disease will be overestimated by neglecting dependency between variables. In the presented datasets, this resulted in a up to 12% overestimation of the risk. CONCLUSIONS: We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations in controls.
19936743 Semi-quantitative analysis of rheumatoid finger joint synovitis using power Doppler ultras 2010 May PURPOSE: To determine the timing for follow-up study of power Doppler ultrasonography (PDUS) by evaluating the response of finger joint synovitis in patients with rheumatoid arthritis (RA) to treatment including infliximab, an antitumor necrosis factor alpha agent. METHODS AND MATERIALS: Bilateral second/third metacarpo-phalangeal (MCP) joints and second proximal inter-phalangeal (PIP) joints (total of six joints) in 21 patients (18 women and three men; median age 53 years) with chronic active RA were assessed by PDUS before and after 2 weeks, 6 weeks, 14 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks of infliximab infusion. Pulse Doppler settings were standardized for each patient and optimized for the detection of synovial blood flow by adjustment of color gain, pulse repetition, and flow optimization. Power Doppler signal was graded for each joint [joint grade for power Doppler (JGPD) signals], and the sum of the grades of six joints was defined as the PDUS index [joint index for power Doppler signals (JIPD)] at each visit. PDUS and clinical parameters [28-joint disease activity score (DAS28), health assessment questionnaire, and C-reactive protein (CRP) level] were independently assessed and compared with baseline values. The American College of Rheumatology (ACR) core set responders and non-responders at week 54 were compared for clinical parameters and PDUS index at each visit. RESULTS: Fourteen patients completed the planned treatment for 1 year, while six patients dropped out for various reasons and one died suddenly. PDUS was performed a total of 146 times on 467 joints. DAS28 was assessed 127 times. Both DAS28 and JIPD had decreased at the follow-up. Comparative analysis between DAS28 and PDUS was available 125 times. The transverse correlation between the PDUS index and DAS28 was not significant throughout the follow-up period. When responders and non-responders were discriminated at week 54, a logistic regression model for the binary endpoint of responder vs non-responder, with PDUS index as explanatory variable at time point 0, and follow-up revealed statistical significance from week 38 and on. CONCLUSION: PDUS reflected infliximab's effect on pannus vascular signals; this effect was observed as early as 2 weeks after treatment had begun. Also, the responders to treatment at 54 weeks tended to have fewer JIPD than non-responders in the follow-up period. PDUS may be performed at week 38 or later to foresee the response to the treatment at week 54.
19790073 Estrone/17beta-estradiol conversion to, and tumor necrosis factor inhibition by, estrogen 2009 Oct OBJECTIVE: The role of estrogens in rheumatoid arthritis (RA) is debated since both proinflammatory and antiinflammatory effects have been reported. Important evidence of the dual role of estrogens is conversion to various proinflammatory or antiinflammatory metabolites. This study was undertaken to examine the downstream conversion of estrogens in synovial cells from patients with RA or osteoarthritis (OA). METHODS: We studied serum levels of estrone, estrone sulfate, and estrone sulfate membrane transporters, intracellular interconversion of estrone and 17beta-estradiol, and conversion of estrone/17beta-estradiol to various estrogen metabolites in RA and OA synovial cells. The effect of estrogen metabolites on tumor necrosis factor (TNF) secretion was also studied in RA and OA synovial cells. RESULTS: Serum levels of estrone sulfate were similar in healthy controls and RA patients. Estrone sulfate transporters were present in synovial tissue. Interconversion of estrone and 17beta-estradiol and the expression of converting enzymes of the cytochrome P450 family were similar in RA and OA cells. Using estrone and 17beta-estradiol as substrates, RA and OA synovial cells produced 16alpha-, 4-, and 2-hydroxylated estrogens and their 4- and 2-methylation products. The levels of 16alpha-hydroxylated estrone/17beta-estradiol (16alphaOH-estrone/16alphaOH-17beta-estradiol) were higher than the levels of all other estrogen metabolites. RA synovial cells produced more 16alphaOH-estrone than did OA synovial cells. Importantly, the 16alphaOH estrogens did not inhibit TNF secretion, whereas all other estrogen metabolites had marked inhibitory effects. CONCLUSION: Our findings indicate that precursor estrogens are converted to proinflammatory metabolites, particularly in RA synovial cells. RA synovial cells mainly produce the proproliferative 16alphaOH-estrone, which, in addition to 16alphaOH-17beta-estradiol, is one of the only 2 estrogens studied that does not inhibit TNF secretion. A preponderance of 16alpha-hydroxylated estrogens is an unfavorable sign in synovial inflammation.
20804602 Effect of taurine chloramine on the production of matrix metalloproteinases (MMPs) in adip 2010 Aug 24 BACKGROUND: Adiponectin greatly stimulated the expression of matrix metalloproteinases (MMPs) in fibroblast-like synoviocytes (FLSs) as did IL-1beta. We wondered whether taurine chloramine (TauCl) inhibits the production of MMPs stimulated by adiponectin in the same pattern as by IL-1beta stimulation in vitro METHODS: Synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin or interleukin (IL)-1beta for 24 hr in the presence or absence of TauCl. The culture supernatant was collected and the levels of MMPs were measured by enzyme-linked immunosorbent assay (ELISA). The IkappaB signaling pathways stimulated by adiponectin were studied and the levels of NF-kappaB in the nuclei of the cells were analyzed by ELISA. RESULTS: TauCl (600 microM) inhibited MMP-13, but not MMP-1, expression in IL-1beta-stimulated RA FLSs. However, TauCl at the same concentration significantly inhibited the production of both adiponectin-stimulated MMP-1 and MMP-13 expression. TauCl inhibited the degradation of IkappaB-alpha stimulated by adiponectin, but not by IL-1beta. Similarly, the level of NF-kappaB in the nucleus was increased by adiponectin stimulation and was inhibited by 600 microM TauCl. However, the levels of NF-kappaB increased by IL-1beta stimulation were not inhibited by 600 microM TauCl. CONCLUSIONS: TauCl more effectively inhibited MMPs expression induced by adiponectin than that by IL-1beta in RA FLS, suggesting that TauCl plays an important role in down-regulating the expression of MMPs in arthritic joints.
20141485 Self-reported food intolerance and mucosal reactivity after rectal food protein challenge 2010 Aug OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.
20437073 Mathematical basis of affected sib-pair analysis: an extension to X-linked loci. 2010 Aug Most clinical genetic studies are done without knowing their mathematical basis. However, because the results of such studies rely on the correctness of the mathematical calculations involved, we cannot ignore the mathematics of genetic studies. In this study, the mathematical basis of the sib-pair method, which has been widely used in recent genome-wide studies, was extended to studies focusing on the X chromosome, and then applied to study a clinical microsatellite marker on the X chromosome. Our calculation involves classifying marker types on the X chromosome for an affected sib-pair and an unaffected sib, together with their sexual information and the possible parental marker types applicable to a genome-wide genetic study. The method proposed in this study was then applied to 41 Japanese rheumatoid families, and the locus DXS984 was found to be most likely to be linked with rheumatoid arthritis (RA). This locus, which we found nicely, was also highlighted in a previous study that used the Mapmaker/sibs program, so we can conclude that our calculation provides a solid foundation for understanding and confirming the results obtained using the sib-pair method.
19775920 Dual-energy X-ray absorptiometry and evaluation of the osteoporosis self-assessment tool i 2009 Oct Males with rheumatoid arthritis (RA) are at risk for osteoporosis but infrequently undergo dual-energy X-ray absorptiometry (DXA). We examined the frequency of DXA in males enrolled in the Veterans Affairs Rheumatoid Arthritis Registry. The Osteoporosis Self-Assessment Tool (OST) index, a formula using age and weight, was calculated for all subjects. DXA was performed on 282 (35.5%) of the males who were younger (p < 0.01), had lower mean OST index score (p < 0.05), and were more likely to have been prescribed prednisone (p < 0.01) than subjects without DXA. Low bone mass (T-score < -1) was present in 73% of subjects with DXA; 37% of subjects with low-risk OST index scores had normal bone mineral density (BMD) compared with 5.6% of those with high-risk OST index scores (p < 0.01). There was a significant but modest correlation between BMD and the OST index (r = 0.17, p < 0.01). No OST score had a sensitivity and specificity of more than 80%. Association between OST index and BMD was strongest in non-Hispanic whites, subjects older than 60 yr, and smokers. DXA was underutilized in males with RA. The OST index correlated with low bone mass but could not reliably predict osteoporosis in this population.
20150560 Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysi 2010 May OBJECTIVE: To perform a systematic review and meta-analysis to examine whether rheumatic disease is associated with an increased carotid intima-media thickness (CIMT; increasingly used as a surrogate marker for atherosclerosis) when compared with healthy control subjects. METHODS AND RESULTS: A prespecified search strategy was used to identify relevant studies in the MEDLINE and EMBASE databases (January 1, 1986 to December 31, 2008). Methodological quality was assessed using the Newcastle-Ottawa score for observational studies. A total of 68 controlled comparisons from 60 different studies were reviewed: 25 (37%) on rheumatoid arthritis, 24 (35%) on systemic lupus erythematosus, 6 (9%) on systemic sclerosis, and 13 (19%) on other rheumatic diseases. Random-effects meta-regression analysis was performed. The estimated summary effect size between control and study subject CIMT measurement comparisons, with preexisting cardiovascular disease excluded, was 0.64 (95% CI, 0.46 to 0.82). This represented an overall absolute mean difference of 0.06 mm (95% CI, 0.05 to 0.06 mm). Preexisting cardiovascular disease, rheumatic disease type, and disease duration contributed to heterogeneity. CONCLUSION: Accelerated atherosclerosis is a common complication of autoimmune rheumatic diseases, with early changes seen even in pediatric patients. CIMT was significantly increased in rheumatic disease populations. Future studies need to use a standardized protocol to ensure clinically meaningful results when measuring CIMT as a surrogate for premature atherosclerosis.
19772356 Branch-specific sialylation of IgG-Fc glycans by ST6Gal-I. 2009 Oct 20 Sialylated forms of the Fc fragment of immunoglobulin G, produced by the human alpha2-6 sialyltransferase ST6Gal-I, were identified as potent anti-inflammatory mediators in a mouse model of rheumatoid arthritis and are potentially the active components in intravenous IgG anti-inflammatory therapies. The activities and specificities of hST6Gal-I are, however, poorly characterized. Here MS and NMR methodology demonstrates glycan modification occurs in a branch-specific manner with the alpha1-3Man branch of the complex, biantennary Fc glycan preferentially sialylated. Interestingly, this substrate preference is preserved when using a released glycan, suggesting that the apparent occlusion of glycan termini in Fc crystal structures does not dominate specificity.
20222014 Phagocytosis of apoptotic cells modulates mesenchymal stem cells osteogenic differentiatio 2010 May Osteogenic differentiation of mesenchymal stem cells (MSC) is important to homeostatic bone remodeling. Infiltration of mesenchymal progenitor cells to inflamed joints has been reported in collagen-induced arthritis murine model and in patients with rheumatoid arthritis (RA). Therapeutic application of MSC in RA has been suggested and under investigation. However, the underlying mechanisms on what triggers the migration of MSC from bone marrow (BM) to inflamed joints and how MSC acts in the joints remains elusive. As hemopoietic stem cells and MSC act reciprocally and excessive apoptotic cells (AC) are observed in the BM of patients with RA, we hypothesize that AC may alter MSC osteogenic differentiation resulting in bone erosion in RA. In this study, we demonstrated for the first time that MSC were able to phagocytose AC and this phagocytosis enhanced MSC osteogenic differentiation. AC-treated MSC under osteogenic differentiation expressed CXC-chemokine receptor (CXCR)-4 and CXCR5, which might enable them to migrate toward the inflamed joints. In addition, AC-treated MSC secreted interleukin (IL)-8, monocyte chemoattractant protein-1, and RANTES, which might induce chemotaxis of CD4+ T cells to the inflamed joints. Interestingly, by coculturing AC-treated MSC under osteogenic differentiation with CD4+ T cells, T helper (Th) 17 cells development was significantly enhanced and these Th17 cells promoted osteoclasts formation and bone resorption. Furthermore, the induction of Th17 cells was dependent on increased IL-6 production from major histocompatibility complex class II-expressing AC-treated MSC under osteogenic differentiation. This data provide a novel insight on the role of AC in modulating MSC osteogenic differentiation and function in inflammatory bone diseases.
20494123 Thioredoxin and thioredoxin reductase: current research with special reference to human di 2010 May 21 Thioredoxin (Trx) and thioredoxin reductase (TrxR) plus NADPH, comprising the thioredoxin system, has a large number of functions in DNA synthesis, defense against oxidative stress and apoptosis or redox signaling with reference to many diseases. All three isoenzymes of mammalian TrxR contain an essential selenocysteine residue, which is the target of several drugs in cancer treatment or mercury intoxication. The cytosolic Trx1 acting as the cells' protein disulfide reductase is itself reversibly redox regulated via three structural Cys residues. The evolution of mammalian Trx system compared to its prokaryotic counterparts may be an adaptation to the use of hydrogen peroxide and nitric oxide in redox regulation and signal transduction.
19542430 A microbial polysaccharide reduces the severity of rheumatoid arthritis by influencing Th1 2009 Jul 1 Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease characterized by chronic joint inflammation with subsequent cartilage and bone destruction. RA is emerging as a model of IL-17-driven autoimmune inflammatory disease. IL-17 is a marker for Th17 cells, with its master regulator being the retinoic acid receptor-related orphan receptor (RORgammat) regulated by STAT3 signaling. Glucuronoxylomannan (GXM), a polysaccharide representing the main component of the capsular material of the opportunistic yeast Cryptococcus neoformans, exhibits potent immunosuppressive properties both in vitro and in vivo. The present study investigates the effects of GXM treatment on the progression of collagen-induced arthritis. GXM suppressed clinical signs of collagen-induced arthritis and blocked joint erosion progression. This effect was mediated by down-regulation of key cytokines involved in the pathogenesis of RA such as TNF-alpha and IL-1beta, and up-regulation of the inhibitory cytokine IL-10. Moreover, a reduction of IL-6 and TGF-beta, which inhibit Th17 differentiation with consequent decreased IL-17 production at the local and systemic level, was observed. The effect of GXM on Th17 differentiation mirrored the reduction in STAT3 activation and inhibition of RORgammat synthesis. Consequently, this work highlights the beneficial properties of an efficacious compound that could eventually be destined to the clinic.
20025215 Anti-arthritic effects and toxicity of the essential oils of turmeric (Curcuma longa L.). 2010 Jan 27 Turmeric (Curcuma longa L., Zingiberaceae) rhizomes contain two classes of secondary metabolites, curcuminoids and the less well-studied essential oils. Having previously identified potent anti-arthritic effects of the curcuminoids in turmeric extracts in an animal model of rheumatoid arthritis (RA), studies were undertaken to determine whether the turmeric essential oils (TEO) were also joint protective using the same experimental model. Crude or refined TEO extracts dramatically inhibited joint swelling (90-100% inhibition) in female rats with streptococcal cell wall (SCW)-induced arthritis when extracts were administered via intraperitoneal injection to maximize uniform delivery. However, this anti-arthritic effect was accompanied by significant morbidity and mortality. Oral administration of a 20-fold higher dose TEO was nontoxic, but only mildly joint-protective (20% inhibition). These results do not support the isolated use of TEO for arthritis treatment but, instead, identify potential safety concerns in vertebrates exposed to TEO.