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ID PMID Title PublicationDate abstract
17133577 Association of citrullinated proteins with synovial exosomes. 2006 Dec OBJECTIVE: In addition to releasing proteins and mediators, cells also release membrane vesicles (exosomes and apoptotic blebs) into the extracellular environment. Apoptotic blebs contain multiple autoantigens, but few data are available concerning the protein content of exosomes. Exosomes are formed during an immune response and can directly stimulate T cells or bind to dendritic cells. The aim of this study was to identify the nature of synovial exosomes from patients with different rheumatic diseases and to examine their potential autoantigenic content, which may be involved in the induction of an autoimmune response. METHODS: Synovial exosomes from patients with rheumatoid arthritis (RA), patients with reactive arthritis, and patients with osteoarthritis were purified, analyzed by electron microscopy, and labeled with immunogold to detect IgG and IgM molecules. Autoantigen content was identified by 2-dimensional electrophoresis-immunoblotting and subsequent mass spectrometry. In order to investigate the presence of citrullinated proteins, immunoblotting with anticitrulline antibodies was performed. RESULTS: Citrullinated proteins were observed in all exosome preparations, in contrast to other autoantigenic proteins (e.g., BiP and heterogeneous nuclear RNP A2) that were previously observed in RA and other autoimmune diseases. These citrullinated proteins included the fibrin alpha-chain fragment, fibrin beta-chain, fibrinogen beta-chain precursor, fibrinogen D fragment, and the Sp alpha (CD5 antigen-like protein) receptor. Purification of synovial exosomes led to the detection of citrullinated fibrinogen and citrullinated Sp alpha associated with IgM and IgG. CONCLUSION: Synovial exosomes contain citrullinated proteins, which are known to be autoantigens in RA. Although immune mechanisms in which exosomes carry citrullinated peptides could play an important role in the induction and distribution of citrullinated proteins, there must be a specific recognition of these proteins that is unique to the RA immune system.
16613612 The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via 2006 S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells from patients with RA spontaneously released larger amounts of S100A8/A9 protein than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages. S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-kappaB) inhibitors. NF-kappaB activation was induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by p38 MAPK inhibitors. These results indicate that the S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses through activation of NF-kappaB and p38 MAPK pathways in RA.
16339575 Mcl-1 is essential for the survival of synovial fibroblasts in rheumatoid arthritis. 2005 Dec 15 Mcl-1 is a Bcl-2-family, antiapoptotic molecule that is critical for the survival of T and B lymphocytes and macrophages; however, its role in nonhemopoietic cells remains to be fully elucidated. The current study focuses on the role of Mcl-1 in rheumatoid arthritis (RA). Mcl-1 was strongly expressed in the synovial lining and was increased in the sublining fibroblasts of patients with RA, compared with control synovial tissue. The expression of Mcl-1 in sublining fibroblasts correlated with the degree of inflammation and TNF-alpha, and IL-1beta treatment of cultured synovial fibroblasts resulted in the increased expression of Mcl-1 at the mRNA and protein levels. Mcl-1 was critical for the survival of RA synovial fibroblasts, because the forced reduction of Mcl-1 using a Mcl-1 antisense-expressing adenoviral vector induced apoptotic cell death, which was mediated through Bax, Bak, and Bim. These observations document a critical role for Mcl-1 in protecting against apoptosis in RA and suggest that Mc1-1 is a potential therapeutic target in this disease.
15744658 [Occupational therapy after rheumatoid hand surgery]. 2005 Feb Occupational therapists face a number of challenges in the after-treatment of rheumatoid hand surgery. They have to take into account the specialties of the surgery and the remaining deformities of the rheumatoid hand. Edema prophylaxis and scar treatment are similar for all patients, while splinting and functional training depend greatly on the different kinds of surgery. Both splinting and mobilization have to be adjusted to patient and process of the therapy. The protracted treatment requires a high compliance of the patient. Instruction and information about operation and postoperative therapy support comprehension and cooperation of the patient.
16552464 Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or pr 2006 Nov The aim of this study was to evaluate the effectiveness of IL-1 inhibition in rheumatic disease using real-life, observational methods. We analyzed data from 47 patients collected from the national ROB-FIN for rheumatic disease. Commonly used, validated measures of efficacy and adverse effects were documented and analyzed. The series contains 47/1,135 patients (mean age 47+/-11 years, range 25-73, females 83%) on anakinra of whom 39 patients suffered from rheumatoid arthritis (RA), two presented with psoriatic arthritis, and four with juvenile RA. At 3 months (26/40), 46% reached American College of Rheumatology (ACR) 20 and 27% ACR 50. In patients naive to biological drugs, the response rate at 3 months was 60% for ACR 20 and 20% for ACR 50. At follow-up of the total series, ACR responses at 6 and 12 months were 69/56% for ACR 20 and 23/22% for ACR 50. These data give room for IL-1 suppression when treating patient with rheumatic disease. Careful selection of patients, together with combining anakinra with disease-modifying antirheumatic drugs, perhaps adds effectiveness. For treating clinicians in Finland, these results are encouraging, as reimbursed treatment alternatives for patients refractory to all other therapies are still few.
15868746 Subcutaneous injections of a TNF-alpha antagonistic peptide inhibit both inflammation and 2005 Mar The cyclic peptide WP9QY (YCWSQYLCY), which was designed to mimic the most critical tumor necrosis factor (TNF) alpha recognition loop on type1 TNF receptor, antagonizes the effects of TNFalpha. In this study, we investigated the effects of WP9QY peptide on collagen-induced arthritis (CIA) mice to evaluate its effects on inflammatory bone destruction. DBA/1J mice were injected intradermally at the base of the tail with bovine type II collagen, emulsified in complete Freund's adjuvant on day 0 and 21. The three sets of WP9QY peptide injections (24 mg/kg x 8 times per day) were performed before the onset of paw swelling. Mice were sacrificed at day 38 and thereafter, the arthritis scores as well as radiographical and histological outcomes were assessed. WP9QY peptide inhibited CIA-induced increase in the arthritis score. Furthermore, histomorphometric analysis of the tibial epiphysis region revealed that WP9QY peptide inhibited the increase of synovial pannus infiltration and the decrease of bone volume, which were induced by the CIA. The WP9QY treatment prevented the inflammation as well as bone destruction of the joints in the CIA mice, suggesting that the administration of WP9QY peptide might be useful for developing a drug to prevent inflammatory bone destruction.
16918692 Genome-scale assessment of molecular pathology in systemic autoimmune diseases using micro 2006 Sep Systemic autoimmune rheumatic diseases are of complex aetiology, characterized by an intricate interplay of various factors. A myriad of genes lies behind the heterogeneous manifestations of these diseases, and the overexpression and repression of particular genes form a specific gene-expression profile (genetic fingerprints) that is characteristic to the given disease phenotype. Besides the description of various cell types by using gene-expression profiling, the data should be directly applicable to the design of individual therapeutic protocols for patients suffering from various autoimmune diseases. In this review, we summarize the gene-expression profile, various genetic signatures of different autoimmune diseases and give an overview on the possible interpretations of the data. The application of recent breakthroughs in high-throughput molecular profiling technologies, such as microarray technology has been the basis for a revolution in biomedical research, as well as diagnostics and pharmaceutical development. It is easy to envision a day when personalized medicine, which is the diagnosis and treatment of a given patient with agents and procedures tailored to that patient's genetics, physiology and pathology, will become the standard of care.
16391893 Leflunomide/chloroquin combination therapy in rheumatoid arthritis: a pilot study. 2006 Jul The objective of this study was to assess the efficacy and tolerability of a combination of leflunomide (LEF) and chloroquin (ChL) in patients with rheumatoid arthritis (RA). Fifteen female RA patients (46-80 years, mean disease duration 100.7 months, ten patients RF+) were enrolled into this open trial. Patients were either treatment failures or partial responders to LEF (n=6) or ChL (n=9). At week 8 and 16, DAS28 and morning stiffness (MST) were evaluated. Moreover, safety was assessed by reporting of side effects, laboratory examinations, and blood pressure measurement. Baseline mean disease activity Index including a 28-joint count (DAS28) amounted to 5.61 and decreased to 4.54 at week 8 (p=0.023) and to 3.79 (p=0.00031) at week 16. MST remained unchanged. DAS28 values significantly decreased statistically in originally ChL-treated patients with additional LEF but did not in LEF patients with additional ChL (DAS28: 1.48; 2.29 vs 0.60; 0.87). Adverse reactions were observed in four patients. Three patients had to be withdrawn from the study. Combination therapy with LEF and ChL was effective and reasonably tolerated. The far higher treatment response could be observed in originally ChL-treated patients after initiation of LEF.
15970510 The toll-like receptor-nuclear factor kappaB pathway in rheumatoid arthritis. 2005 Sep 1 The study of the role cytokines play in the pathogenesis of rheumatoid arthritis (RA) has provided a whole new range of targets for drug development. Many of them (e.g. TNF, IL-1, IL-6, IL-15 and IL-18) are already being targeted in the clinic with success using neutralizing monoclonal antibodies or soluble cytokine receptors. Targeting TNF, in particular, has shown great efficacy in controlling both the inflammation and structural damage of the joints, setting a new gold standard for the treatment of RA. However, what triggers the production of inflammatory cytokines such as TNF in RA remains to be determined. In this article, we review evidence suggesting that the transcription factor Nuclear Factor kappaB (NF-kappaB) is essential for the expression of both inflammatory cytokines and tissue destructive enzymes in RA. Also, we discuss whether Toll-like receptors (TLRs), major receptors involved in pathogen recognition and potent activators of the NF-kappaB pathway, are involved in triggering the inflammatory and joint destructive process in RA and whether they constitute sensible targets for monoclonal antibodies/soluble receptors and small molecule inhibitors. We conclude that although the TLR- NF-kappaB pathway offers ample opportunities for therapeutic intervention, future drugs to be approved will need to match or exceed the efficacy and safety of anti-TNF agents, with safety the most difficult aspect to predict.
15847101 A randomized, open-label, comparative, 6-month trial of oral ultra-low doses of antibodies 2005 Artrofoon (oral ultra-low doses of antibodies to TNF-alpha is a novel drug approved by the Russian Ministry of Health for the treatment of rheumatoid arthritis (RA). The aim of this study was to assess clinical efficacy and safety of artrofoon in RA compared with diclofenac. In a 6-month, randomized, open-label, comparative trial, 60 patients with active RA (eight men and 52 women aged 23 to 62, mean disease duration 10 years) received artrofoon (8 tablets daily, n = 30) or diclofenac (100 mg daily, n = 30). RA signs and symptoms as well as serum levels of inflammatory markers were evaluated before treatment and at months 1, 3 and 6. Most patients in the artrofoon group showed a 20% improvement in major RA symptoms by the end of the study. The clinical effect rose gradually reaching maximum at month 6. In the artrofoon group, 57% of the patients achieved an American College of Rheumatology (ACR) 20% criteria (ACR20) by month 6 versus 20% of those receiving diclofenac. In some patients in the artrofoon arm, serum proinflammatory cytokine levels significantly decreased (> or = 25% reduction). Diclofenac produced a less pronounced clinical effect, and no changes in cytokine profile. Unlike conventional nonsteroidal anti-inflammatory drugs, artrofoon produced no adverse effects and the overall tolerability and safety were excellent. A half-dose treatment with artrofoon (4 tablets daily) was able to sustain clinical improvements over a 6-month follow-up period. To conclude, artrofoon is a safe and effective treatment for rheumatoid arthritis that acts by influencing the inflammatory process.
15934868 Targeting cellular adhesion molecules, chemokines and chemokine receptors in rheumatoid ar 2005 May The development of specific targeted therapies, such as anti-TNF-alpha treatment, for chronic inflammatory disorders such as rheumatoid arthritis, has significantly improved treatment, although not all patients respond. Targeting cellular adhesion molecules and chemokines/chemokine receptors as regulators of the extravasation and migration of leukocytes may provide a novel approach for the treatment of these diseases. Moreover, the possibility of developing small-molecule antagonists offers an excellent method for the oral delivery of compounds with a short half-life.
16806231 Inflammatory suppression rapidly attenuates microvascular dysfunction in rheumatoid arthri 2007 Jun Rheumatoid arthritis (RA) is associated with greater risk of cardiovascular morbidity and mortality, the inflammatory component of RA being strongly linked to this excess risk. Endothelial dysfunction is linked to atherosclerosis and has been demonstrated in larger vessels in RA. In this pilot study, we determined for the first time whether skin microvascular function was impaired in patients with active RA and also determined its response to anti-inflammatory treatment. This was assessed non-invasively using laser Doppler imaging combined with iontophoresis of the vasodilators acetylcholine (ACh, endothelium dependent) and sodium nitroprusside (SNP, endothelium independent) to the forearm. Eight RA patients admitted for acute flare-ups were assessed before and following anti-inflammatory treatment. Standard laboratory indices were obtained along with pain perception (VAS). A control group of eight subjects was included for baseline comparison. Compared to this group, vascular function was substantially and significantly (P<0.00001) lower in RA patients. Following treatment, as CRP and VAS decreased, vascular function improved for both ACh (P<0.00001) and SNP (P=0.001), this improvement being significantly greater for ACh (P<0.001). Vascular dysfunction is evident in RA patients, even at the level of the cutaneous microcirculation, but improves as inflammation regresses. Assessment of cutaneous vascular function may be a useful, non-invasive surrogate indicator of vascular risk in RA, inclusive of myocardial microvascular abnormalities.
14628151 The effect of low-dose prednisone on bone mineral density in Peruvian rheumatoid arthritis 2005 Mar OBJECTIVE: The aim of this study was to determine the difference between bone mineral density (BMD) of rheumatoid arthritis (RA) patients on low-dose prednisone and matched RA patients without prior systemic corticosteroid therapy. METHODS: Ninety patients attending our clinics and receiving 10 mg/day of prednisone or less for at least the previous 3 consecutive months were studied. The control group comprised 90 selected RA patients without corticosteroid therapy matched for age, race, gender, disease duration, use of methotrexate, postmenopause, and Health Assessment Questionnaire score. The BMD was measured using dual X-ray absorptiometry. RESULTS: Patients on prednisone had lower BMD than controls (0.94 +/- 0.17 vs 0.96 +/- 0.17 for L2-4 and 0.73 +/- 0.14 vs 0.76 +/- 0.16 for femoral neck), but these differences were not statistically significant (P > 0.05). In post hoc analysis, postmenopausal women on prednisone had more bone loss in femoral neck than controls (0.68 +/- 0.13 vs 0.74 +/- 0.15). CONCLUSION: Bone mineral density was not significantly reduced by low-dose prednisone in this diverse group of RA patients. A reduction in hip BMD was seen in postmenopausal women on prednisone.
15769913 Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheu 2005 Apr BACKGROUND: Tumour necrosis alpha (TNF alpha) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNF alpha independent pathways play a role in the disease. OBJECTIVES: To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNF alpha independent mechanisms. METHODS: 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38(+) cells was studied by an immunofluorescent double labelling technique. RESULTS: Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNF alpha, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38(+) activated T cells were more resistant to treatment than CD38(+) plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. CONCLUSIONS: Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNF alpha independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.
16342097 Activity limitation in rheumatoid arthritis correlates with reduced grip force regardless 2005 Dec 15 OBJECTIVE: To evaluate activity limitations 3 years after diagnosis of early rheumatoid arthritis (RA) in relation to grip force and sex. METHODS: A total of 217 patients, 153 women and 64 men, with recent-onset RA were included. Activity limitations were reported using the Health Assessment Questionnaire (HAQ) and the Evaluation of Daily Activities Questionnaire (EDAQ). The relationships between activity limitations versus grip force (measured by the Grippit), walking speed, functional impairment, grip ability, pain, plasma C-reactive protein, the 28-joint disease activity score and its components, the physician's global assessment of disease activity, and sex were analyzed by partial least squares (PLS). RESULTS: Women had significantly lower grip force and more activity limitations (HAQ and EDAQ) than men. The PLS analyses demonstrated that grip force was the strongest regressor of activity limitation, closely followed by walking speed. However, within subgroups based on grip force (group 1 = grip force <114 N, group 2 = 116-206 N, group 3 = 214-321 N, group 4 = grip force >328 N) and including sexes, women and men had corresponding degrees of activity limitation as reported by the HAQ and EDAQ. CONCLUSION: Our results indicate that the more pronounced activity limitations seen in women with RA, as compared with men, may be explained by lower grip force rather than sex.
16899502 Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are u 2007 Mar OBJECTIVES: To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab. METHODS: A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software. RESULTS: Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab. CONCLUSION: The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.
17021714 Adenosine and cytokine levels following treatment of rheumatoid arthritis with dipyridamol 2006 Nov Adenosine can suppress the release of tumour necrosis factor-alpha (TNF-alpha) from activated monocytes and macrophages, and may contribute to the anti-inflammatory activities of methotrexate and sulphasalazine. Dipyridamole inhibits the cellular uptake and metabolism of adenosine and we have, therefore, examined the effects of dipyridamole in patients with rheumatoid arthritis in an attempt to alleviate their symptoms. Forty patients aged 18-75 years were randomised to receive dipyridamole 400 mg/day or placebo. Blood samples were taken at baseline and at monthly intervals for 6 months. Purines were determined by HPLC and cytokines by ELISA. After 3 months of treatment there were significant reductions in neopterin levels and in the modified Health Assessment Questionnaire score, but these were not maintained. Dipyridamole had no effect on disease severity or the levels of purine metabolites, interleukin-1beta (IL-1beta), IL-6, TNF-alpha, lipid peroxidation products, erythrocyte sedimentation rate or C-reactive protein. In conclusion, rheumatoid arthritis patients showed no clinical improvement following treatment with dipyridamole for 6 months.
16572444 High-resolution multipinhole single-photon-emission computed tomography in experimental an 2006 Apr OBJECTIVE: To image inflammatory arthritic lesions in experimental arthritis and in patients with arthritis, using a newly developed high-resolution multipinhole single-photon-emission computed tomography (MPH-SPECT) technique. METHODS: Six interleukin-1 receptor antagonist-deficient mice with arthritis of the front and back paws and 2 control BALB/c mice were imaged with MPH-SPECT and scored macroscopically for arthritis. SPECT imaging was performed with a conventional gamma camera upgraded with a pyramidal lead collimator affixed with MPH apertures. All images were reconstructed, and uptake in the paws was quantified in counts/weight and injected activity. To transfer the imaging technique to humans we examined the clinically dominant hand of 6 individuals (3 with established rheumatoid arthritis [RA], 1 with early RA, 1 with osteoarthritis, and 1 healthy control). RESULTS: MPH-SPECT images were high-resolution 3-dimensional tomographic images, which allowed exact localization and quantifiable observation of increased bone metabolism. MPH-SPECT counts of inflamed joints in mice correlated with macroscopic scoring and histologic joint analysis postmortem. In humans, MPH-SPECT images depicted a detailed visualization of tracer accumulation in bony structures of hand and finger joints, and were also capable of imaging increased bone metabolism that had appeared normal with other imaging modalities, e.g., magnetic resonance imaging. CONCLUSION: The MPH-SPECT technique represents a new diagnostic tool in the detection of bone pathology in small-animal arthritis research. Compared with macroscopic scoring, this new method provides a more objective and higher-precision quantifiable measurement of bone reaction, allowing visualization of inflammatory processes of the whole skeleton in vivo. These results suggest that MPH-SPECT may be useful as a diagnostic instrument for monitoring experimental arthritis, with further potential for use in human studies of RA.
16261517 A pilot trial evaluating Meta050, a proprietary combination of reduced iso-alpha acids, ro 2005 Oct The aim of this open-label, 8-week observational trial was to investigate the efficacy of Meta050 (a proprietary, standardized combination of reduced iso-alpha-acids from hops, rosemary extract and oleanolic acid) on pain in patients with rheumatic disease. Osteoarthritis, rheumatoid arthritis and fibromyalgia patients were given 440 mg Meta050 three times a day for 4 weeks, which was changed to 880 mg twice a day for the subsequent 4 weeks in the majority of patients. Pain and condition-specific symptoms were assessed using a standard visual analog scale (VAS), an abridged arthritis impact measurement scale (AIMS2) and the fibromyalgia impact questionnaire. Fifty-four subjects with rheumatic disease completed the trial. Following treatment, a statistically significant decrease in pain of 50% and 40% was observed in arthritis subjects using the VAS (p < 0.0001; Wilcoxon-ranked sums) and AIMS2 (p < 0.0001), respectively. Fibromyalgia subject scores did not significantly improve. A decreasing trend of C-reactive protein, a marker for inflammation, was also observed in those subjects who presented with elevated C-reactive protein. No serious side effects were observed. These observations suggest that Meta050 at a dosage of 440 mg three times a day has a beneficial effect on pain in arthritis subjects.
15608299 Low density of sympathetic nerve fibres and increased density of brain derived neurotrophi 2005 Jan OBJECTIVE: To investigate the correlation between density of nerve fibres and the presence of BDNF(+) cells. METHODS: Densities of nerve fibres and BDNF(+) cells were detected by quantitative immunohistochemistry in fresh synovial tissue from 52 patients with RA, 59 with OA, and 26 controls (Co). BDNF was also detected by in situ hybridisation. RESULTS: Sympathetic nerve fibre density was similar in Co and OA but markedly reduced in RA (p = 0.002), whereas density of substance P positive (SP(+)) sensory nerve fibres was lower in OA than in Co and RA (p = 0.002). The ratio of sympathetic/SP(+) sensory nerve fibre density was highest in OA and Co, followed by RA. The correlation between density of sympathetic nerve fibres and SP(+) sensory nerve fibres in OA (R = 0.425, p = 0.001) was strongly positive, had a positive trend in Co (R = 0.243, NS), but was negative in RA (R = -0.292, p = 0.040). In RA and OA tissue the density of BDNF(+) cells was high in sublining areas but markedly lower in Co (p = 0.001). BDNF(+) cell density correlated positively with the ratio of sympathetic/SP(+) sensory nerve fibre density in Co (R = 0.433, p = 0.045) and in OA (R = 0.613, p = 0.015), but not in RA (R = 0.101, NS). Immunohistochemical double staining demonstrated that some macrophages and fibroblasts were positive for BDNF. CONCLUSIONS: The correlation of density of SP(+) sensory with sympathetic nerve fibres was positive in Co and OA but negative in RA. BDNF may have a stimulatory role on growth of sympathetic in relation to SP(+) sensory nerve fibres in Co and OA, but not in RA.