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ID PMID Title PublicationDate abstract
17526929 Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-kappaB 2007 Aug OBJECTIVE: To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: AT1 receptor expression was detected by western blotting and flow cytometry. Apoptosis induction was quantified by nucleosome ELISA and by TUNEL; cell proliferation was determined by a bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-kappaB was obtained by using a specific siRNA. Caspase 3 activation was evaluated by a colorimetric assay and its cleavage by western blotting. RESULTS: AT1 expression resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This protective effect was reverted in the presence of the AT1 receptor antagonist losartan as well as after silencing the expression of NF-kappaB. Moreover, FLS treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on apoptosis. Caspase 3 activation was reduced in presence of Ang II. CONCLUSIONS: Ang II could represent an important mediator involved in FLS expansion, reducing their capacity to undergo apoptosis, through the activation of NF-kappaB and the blockage of caspase cascade.
17102946 Measurement of the serum leptin level could assist disease activity monitoring in rheumato 2007 Apr We investigated whether serum leptin levels are elevated in patients with active rheumatoid arthritis (RA) and whether these levels correlate with disease activity. Fifty RA patients were enrolled in this study, and their disease activity was assessed using the disease activity score 28 (DAS28). The patients were divided into two groups according to this score: a high activity group with DAS28 > 3.2 (n = 26) and a low activity group with DAS28
17763421 Early changes in serum type II collagen biomarkers predict radiographic progression at one 2007 Sep OBJECTIVE: To investigate whether short-term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis. METHODS: Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (DeltaCOL) was calculated. Associations with clinical responses according to the 28-joint count Disease Activity Score and with radiographic progression according to the modified Sharp/van der Heijde score (SHS) were assessed. RESULTS: The 1-year increase in the SHS correlated with the 1-month change in C2C results (r = 0.311, P = 0.028) and the DeltaCOL score (r = 0.342, P = 0.015). Radiographic progression was predicted by increases in serum C2C at 1 month (P = 0.031). The DeltaCOL score was significantly associated with 1-year radiographic progression after 1 (P = 0.022), 3 (P = 0.015), 6 (P = 0.048), and 9 (P = 0.019) months of therapy. Clinical remission was predicted by 1-month decreases in serum levels of C2C (P = 0.008) and C1,2C (P = 0.036). By regression analysis, 1-month changes in C2C, C1,2C, and CPII levels were independently associated with, and correctly predicted radiographic outcome in, 88% of the patients. CONCLUSION: Short-term changes in serum levels of collagen biomarkers following initiation of biologic therapy may better predict long-term clinical and radiographic outcomes. These collagen biomarkers may therefore be valuable new early indicators of short-term biologic treatment efficacy in clinical trials and in individual patients with inflammatory erosive arthritis.
17325656 Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-ind 2007 Apr BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti-cancer agents, have recently been reported to exhibit potent anti-inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS-275, two HDACi currently undergoing clinical investigations for various oncological indications. EXPERIMENTAL APPROACH: The anti-rheumatic effects of SAHA and MS-275 were assessed in both mouse and rat collagen induced arthritis (CIA) models. KEY RESULTS: SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA-induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS-275 displayed dramatic anti-rheumatic activities. In prophylactic intervention, high doses of MS-275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS-275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS-275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction. An anti inflammatory effect of MS-275 was also confirmed through its capacity to decrease serum IL-6 and IL-1beta levels in the CIA induced mouse model. The anti-rheumatic activity of MS-275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice. CONCLUSION AND IMPLICATION: This study strongly supported HDACi as an innovative therapeutic strategy for RA.
18193552 [Systemic autoimmune diseases]. 2008 Jan Since Hench successfully treated a patient with rheumatoid arthritis (RA) with glucocorticoid (GC) in 1948, the clinical usefulness of GC in the management of systemic autoimmune diseases has been established. However, serious adverse reactions of GC are the severe clinical problems. In addition, some of clinical evidences of GC therapy for these diseases are still controversial due to the difficulties for conducting clinical trials. In this review, we summarize the significance of GC therapy in autoimmune diseases such as RA and systemic lupus erythematosus, based upon the clinical reports for these diseases.
19002544 Diagnostic utility of anti-cyclic citrullinated peptide antibodies for rheumatoid arthriti 2009 Mar This study was intended to evaluate the utility of anti-cyclic citrullinated peptide antibodies (second generation, anti-CCP2) as a diagnostic marker for rheumatoid arthritis (RA) in patients with active tuberculosis. Among 89 patients with active tuberculosis, anti-CCP2 was detected in six (6.7%), and three of these (3.4%) were strongly positive for anti-CCP2. The positive rate of anti-CCP2 in patients with newly diagnosed RA was 82.1% (87 of 106 cases), while the rate in healthy control subjects was 0.4% (one of 237 individuals). The mean level of anti-CCP2 among the RA group was 159.3 U/ml, which was significantly higher than both that among the tuberculosis group (15.4 U/ml) and that among the healthy controls (0.7 U/ml). IgM rheumatoid factor (RF) was detected in 16 patients from the tuberculosis group (18.0%) with a mean serum level of 18.6 IU/ml and in 77 patients of the RA group (72.6%) with a mean level of 164.0 IU/ml. Only two cases in the tuberculosis group were positive for both anti-CCP2 and IgM RF. These observations show that measurement of anti-CCP2 seems to be a reliable serological tool for identifying early RA in patients with active tuberculosis.
18787327 Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a ra 2008 Aug BACKGROUND: In contrast to psychological interventions the usefulness of acupuncture as an adjuvant therapy in rheumatoid arthritis (RA) has not yet been demonstrated. OBJECTIVE: The efficacy of auricular electroacupuncture (EA) was directly compared with autogenic training (AT). METHODS: Patients with RA (n = 44) were randomized into EA or AT groups. EA and lessons in AT were performed once weekly for 6 weeks. Primary outcome measures were the mean weekly pain intensity and the disease activity score 28 (DAS 28); secondary outcome measures were the use of pain medication, the pain disability index (PDI), the clinical global impression (CGI) and pro-inflammatory cytokine levels, which were assessed during the study period and 3 months after the end of treatment. RESULTS: At the end of the treatment and at 3-month follow-up a clinically meaningful and statistically significant improvement (p < 0.05) could be observed in all outcome parameters and both groups. In contrast to the AT group, the onset of these effects in the EA group could already be observed after the 2nd treatment week. In the 4th treatment week the EA group reported significantly less pain than the AT group (p = 0.040). After the end of treatment (7th week) the EA group assessed their outcome as significantly more improved than the AT group (p = 0.035). The erythrocyte sedimentation rate in the EA group was significantly reduced (p = 0.010), and the serum concentration of tumor necrosis factor-alpha was significantly increased compared to the AT group (p = 0.020). CONCLUSIONS: The adjuvant use of both EA and AT in the treatment of RA resulted in significant short- and long-term treatment effects. The treatment effects of auricular EA were more pronounced.
16477262 Autoimmune diseases co-occurring within individuals and within families: a systematic revi 2006 Mar BACKGROUND: Autoimmune diseases have been observed to coexist both within individuals and within families. It is unclear whether clinical reports of comorbid autoimmune diseases represent chance findings or true associations. This systematic review evaluates the current level of evidence on the coexistence of selected autoimmune diseases within individuals and families. We reviewed the associations among 4 TH1-associated autoimmune diseases: insulin-dependent diabetes mellitus, autoimmune (Hashimoto) thyroiditis, rheumatoid arthritis, and multiple sclerosis. METHODS: Studies quantifying the coexistence between the selected diseases, published through March 2004, were identified from Medline and Embase searches. Study eligibility was determined on the basis of preestablished criteria, and relevant data were extracted according to a fixed protocol. We determined the prevalence of comorbid autoimmune disease according to index disease and then compiled summary statistics. Heterogeneity among studies was assessed by exact likelihood ratio tests and Monte Carlo inference. RESULTS: We found 54 studies that met the eligibility criteria. Of these, 52 studies examined the coexistence of disease within individuals and 9 studies examined within-family associations. The majority of studies were uncontrolled and did not account for confounding factors. There was substantial evidence for heterogeneity among studies. Although inconclusive, the data appear to support an increased prevalence of autoimmune thyroiditis among patients with rheumatoid arthritis and those with insulin-dependent diabetes mellitus, and an inverse association between rheumatoid arthritis and multiple sclerosis. CONCLUSION: Although the available evidence does not permit firm conclusions regarding comorbidities among the selected autoimmune diseases, results are sufficiently suggestive to warrant further study.
17960169 Serum uric acid is independently associated with hypertension in patients with rheumatoid 2008 Mar Hypertension (HT) is highly prevalent in rheumatoid arthritis (RA). Serum uric acid (SUA) has been associated with HT in the general population. The mutual exclusion of gout and RA, and the systemic inflammatory component of RA may alter this association in this patient population. We explored a potential association between SUA levels and HT in RA and evaluated whether this association is independent of HT risk factors, RA characteristics and relevant drugs. A total of 400 consecutive RA patients were assessed. SUA and complete biochemical profile were measured. Demographic, HT-related factors, RA characteristics and drugs were assessed as potential covariates. Results were analysed using binary logistic models to test the independence of the association between SUA and HT. SUA levels were higher in hypertensive compared to normotensive RA patients (5.44+/-1.6 mg dl(-1) (323.57+/-95.17 micromol l(-1)) vs 4.56+/-1.1 mg dl(-1) (271.23+/-65.43 micromol l(-1)), P<0.001). When adjusted for HT risk factors, renal function, RA characteristics, non-steroidal anti-inflammatory drugs, oral prednisolone, cyclosporine, leflunomide and low-dose aspirin, the odds of being a hypertensive RA patient per 1 mg dl(-1)(59.48 micromol l(-1)) SUA increase were significantly increased: OR=1.59 (95% CI: 1.21-2.1, P=0.001). This was also significant for the subgroup of patients who were not on diuretics (OR=1.5, 95% CI: 1.1-2.05; P=0.011). This cross-sectional study suggests that SUA levels are independently associated with HT in RA patients. Prospective longitudinal studies are needed to confirm and further explore the causes and implications of this association.
17407237 The OMERACT Magnetic Resonance Imaging Inflammatory Arthritis Group - advances and priorit 2007 Apr This article updates the work and research priorities of the OMERACT working group on magnetic resonance imaging (MRI) in inflammatory arthritis, as presented to the OMERACT 8 meeting in Malta in May 2006. This work focused on testing the reliability of dedicated extremity MRI in rheumatoid arthritis and on the initial steps in the development of an MRI score for peripheral psoriatic arthritis.
17346433 Genetic predisposition to rheumatoid arthritis in a Tuscan (Italy) ancient human remain. 2007 Jan Rheumatoid arthritis (RA) is currently believed to have originated in America, and after the discovery of this continent in 1492, to have been exported to the Old World. We evaluated the genetic predisposition to RA in the "Braids Lady" from Arezzo (Italy), a partially mummified woman's body dating back to the end of 1500 AD which presents the anatomical and pathological features of this disease. The study of the polymorphic HLA-DRB1 locus, which includes alleles strongly associated with RA onset, has received much attention over recent years, especially the loci codifying for the DR1 and DR4 antigens, widely represented in the Mediterranean population, and for DR14, widespread among Native Americans. Molecular analysis was performed on extracts of DNA from the mummy, firstly from histological bone sections and then from the whole bone. Two different HLA typing techniques, PCR-sequence-specific oligonucleotides (PCR-SSO) and PCR-sequence-specific primers (PCR-SSP), were employed to identify HLA-DRB alleles. Both genotyping methods showed that the "Braids Lady" carried the DRB1*0101 allele, the serological equivalent of the DR1 antigen. Although the possession of RA risk factor genes cannot be considered a diagnostic marker, the positive result of the Italian mummy for DRB1*0101 and the RA features present, support the idea that this pathology was present in the Old World from at least the mid-16th century. A pathogenetic hypothesis of RA which might well explain its worldwide diffusion is the "molecular mimicry", resulting from a cross-reactive antibody response between certain microbial antigens and shared epitopes of specific HLA-DR1, DR4 and DR14 susceptibility alleles, the frequency of which varies among different ethnic groups.
18258710 The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinic 2008 Dec OBJECTIVES: The aim of this pilot study was to compare clinical examination (CE) and ultrasound (US) with high field MRI (as the reference standard) for the detection of rearfoot and midtarsal joint synovitis and secondly tenosynovitis of the ankle tendons in patients with established rheumatoid arthritis (RA). METHODS: Patients with RA (as determined by the modified American College of Rheumatology (ACR) criteria) with symptoms of midfoot and rearfoot disease were recruited. Demographic data were collected. All underwent CE, US and high field MRI (with intravenous gadolinium contrast) of their right foot. Percentage exact agreement (PEA), sensitivity and specificity were calculated for CE and US when compared to MRI. Inter-reader reliability for CE and US was also assessed. RESULTS: Compared to the gold standard of MRI, for CE (joint synovitis) the ranges for sensitivity, specificity and PEA were 55-83%, 23-46% and 46-60%, and for US were 64-89%, 60-80% and 64-78%, respectively. Compared to the gold standard of MRI, for CE (tenosynovitis) the ranges for sensitivity, specificity and PEA were 0-100%, 20-91% and 55-91%, and for US were 0-67%, 86-100% and 59-86%, respectively. CONCLUSION: CE was sensitive but US more specific in identifying hindfoot pathology in RA when compared to the reference standard of MRI. There was poor interobserver variability between ultrasonographers suggesting a need for standardisation of acquisition and interpretation of US images of the hindfoot.
17567634 Trends in medication and health-related quality of life in a population-based rheumatoid a 2007 Aug OBJECTIVES: To study trends in treatment, health status and health-related quality of life (HRQL) in two cross-sectional surveys over a 5-yr period and in an observational follow-up sub-cohort based on a population-based rheumatoid arthritis (RA) register in Malmö, Sweden. MATERIAL AND METHODS: A continuously updated population-based RA register was established in Malmö city in southern Sweden in 1997. Patient-administered questionnaires in 1997 and 2002 were used to collect information on demographics, medication and health status. Cross-sectional comparisons were made between 1997 and 2002. A longitudinal analysis was also performed in the RA patients participating in both surveys. RESULTS: Increased proportions of patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) (69 vs 52%), corticosteroids (30 vs 23%), methotrexate (52 vs 29%) and biologics (14 vs 0%) in 2002 compared with 1997. In the cross-sectional analysis, the visual analogue scores (VAS) for pain and general health and the short form 36 (SF-36) domains were slightly better in 2002 than in 1997. In the observational sub-cohort, patients treated with biologics improved significantly in several measures of health status, whereas those starting on methotrexate or undergoing other or no changes in DMARD therapy did not. CONCLUSIONS: In this population-based RA cohort, patients were more actively treated in 2002. Small improvements were seen in health status and these improvements were exclusively attributable to treatment with biologics.
18219551 Heme oxygenase-1 participates in the anti-inflammatory activity of taurine chloramine. 2008 Aug Interleukin-6 (IL-6) and interleukin-8 (IL-8) are implicated in the pathogenesis of rheumatic diseases. In affected joints fibroblast-like synoviocytes (FLS) are the major source of these pro-inflammatory cytokines. We have previously found that production of both cytokines is inhibited in vitro by taurine chloramine (Tau-Cl). Heme oxygenase (HO-1) activity was also reported to restrict synthesis of various inflammatory mediators, including IL-6 and IL-8. The aim of present study was to investigate whether this enzyme activity is implicated in the mechanism of Tau-Cl suppressive effect. We have shown that in rheumatoid FLS both hemin (known HO-1 inducer) and Tau-Cl significantly up-regulate HO-1 expression at the mRNA and protein levels and simultaneously inhibit IL-1 beta-triggered production of pro-inflammatory cytokines. However, the inhibitory potency of these compounds differs, because hemin is more potent inhibitor of IL-8 than IL-6 production, while Tau-Cl exerts opposite effect. Importantly, pretreatment of the cells with HO-1 inhibitor completely reverses the inhibitory effect of hemin on both cytokines production. However, in Tau-Cl treated cells this inhibitor fully restores only IL-8 secretion but has weaker effect on IL-6 response. Thus, the present results: (i) support HO-1 activity to be relevant to negatively control production of pro-inflammatory cytokines, and (ii) underline implication of HO-1 in mediating Tau-Cl inhibitory action.
17328059 Suppression of inflammation and structural damage in experimental arthritis through molecu 2007 Mar OBJECTIVE: To determine the disease-modifying activity and mechanism of action of the orally available methionine aminopeptidase type 2 inhibitor, [(1R)-1-carbamoyl-2-methyl-propyl]-carbamic acid-(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro [2.5] oct-6-yl ester (PPI-2458), in a rat model of peptidoglycan-polysaccharide (PG-PS)-induced arthritis. METHODS: Arthritis was induced in rats by administration of PG-PS, causing tarsal joint swelling and histopathologic changes characteristic of rheumatoid arthritis (RA). PPI-2458, a potent irreversible methionine aminopeptidase type 2 inhibitor, was administered orally every other day at 1, 5, or 10 mg/kg. RESULTS: In an in vitro osteoclastogenesis model, PPI-2458 potently inhibited osteoclast differentiation and bone resorption. In the rat PG-PS arthritis model, PPI-2458 afforded significant protection against established disease after therapeutic dosing. This in vivo activity of PPI-2458 was linked to the inhibition of methionine aminopeptidase type 2. Histopathologic assessment of affected joints showed improvement in processes of inflammation, bone resorption, and cartilage erosion, associated with significant improvement in all clinical indices. The protective effects of PPI-2458 against bone destruction in vivo, including the structural preservation of affected hind joints, correlated with improvements in bone histomorphometric markers, as determined by microfocal computed tomography and a significant decrease in systemic C-telopeptide of type I collagen, suggesting decreased osteoclast activity in vivo. Moreover, PPI-2458 prevented cartilage erosion as shown by a significant decrease in systemic cartilage oligomeric matrix protein. CONCLUSION: The findings of this study suggest that PPI-2458 exerts disease-modifying activity in experimental arthritis through its direct inhibition of several pathophysiologic processes of this disease. These results provide a rationale for assessing the potential of PPI-2458 as a novel RA therapy.
18925317 Brazilian version of the foot health status questionnaire (FHSQ-BR): cross-cultural adapta 2008 Oct OBJECTIVE: To conduct a cross-cultural adaptation of the Foot Health Status Questionnaire into Brazilian-Portuguese and to assess its measurement properties. INTRODUCTION: This instrument is an outcome measure with 10 domains with scores ranging from 0-100, worst to best, respectively. The translated instrument will improve the examinations and foot care of rheumatoid arthritis patients. METHODS: The questions were translated, back-translated, evaluated by a multidisciplinary committee and pre-tested (n = 40 rheumatoid arthritis subjects). The new version was submitted to a field test (n = 65) to evaluate measurement properties such as test-retest reliability, internal consistency and construct validity. The Health Assessment Questionnaire, Numeric Rating Scale for foot pain and Sharp/van der Heijde scores for foot X-rays were used to test the construct validity. RESULTS: The cross-cultural adaptation was completed with minor wording adaptations from the original instrument. The evaluation of measurement properties showed high reliability with low variation coefficients between interviews. The alpha-Cronbach coefficients varied from 0.468 to 0.855, while correlation to the Health Assessment Questionnaire and Numeric Rating Scale was statistically significant for five out of eight domains. DISCUSSION: Intra- and inter-observer correlations showed high reliability. Internal consistency coefficients were high for all domains, revealing higher values for less subjective domains. As for construct validity, each domain revealed correlations with a specific group of parameters according to what the domains intended to measure. CONCLUSION: The FHSQ was cross-culturally adapted, generating a reliable, consistent, and valid instrument that is useful for evaluating foot health in patients with rheumatoid arthritis.
16797932 Host resistance to Candida albicans infection of mice with collagen-induced arthritis trea 2006 Jul The dehydro-orotate dehydrogenase inhibitor leflunomide is used for the treatment of rheumatoid arthritis. In the present study, its influence on host resistance to Candida albicans infection in mice with collagen-induced arthritis (CIA) was investigated. Leflunomide administered at a dose of 5 mg/kg for 5 consecutive days in mice with CIA inhibited collagen-specific cellular and humoral responses. The drug did not change the severity of primary C. albicans infection evaluated by kidney and liver colonization. At the early stage of infection leflunomide inhibited IFN-gamma production and enhanced IL-4 secretion. The effect of the drug on IL-4 production was less pronounced at the late phase of infection. Leflunomide enhanced anti-Candida IgM antibody production and diminished anti-Candida IgG antibody synthesis. This correlated with impaired resistance to reinfection. Results demonstrate that leflunomide administration to mice with collagen-induced arthritis might affect mechanisms of the late immune response to C. albicans infection.
17478469 Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. 2007 Jul OBJECTIVES: To assess the risk of severe infections associated with the use of traditional disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoid agents in rheumatoid arthritis (RA). METHODS: Our study was a case-control design nested within a cohort of 23 733 RA patients studied between 1 January 1980 and 31 December 2003. Matching on age and gender, and adjusting for comorbidity and physician use, conditional logistic regression was used to estimate the effect of specific drugs on the rate ratio (RR) for infections requiring hospitalization. RESULTS: The risk for all infections requiring hospitalization appeared to be most elevated with current exposures to cyclophosphamide [RR: 3.26, 95% confidence interval (CI): 2.28-4.67] and systemic glucocorticoid agents (RR: 2.56, 95% CI: 2.29-2.85); azathioprine was associated with a moderate increased risk (RR: 1.52, 95% CI: 1.18-1.97). There was a suggestion of increased risk of pneumonia due to methotrexate (RR: 1.16, 95% CI: 1.02-1.33). The results were similar for the period before and after the introduction of anti-tumour necrosis factor (TNF) agents. The RR point estimate for anti-TNF agents suggested about a 2-fold increased risk for all infections, but the estimate was imprecise. CONCLUSIONS: In this large cohort of RA patients, the most heightened risk of serious infections was seen with the use of glucocorticoid agents and immunosuppressive DMARDs. Assessments of infection risk related to newer and emerging therapies should carefully consider concomitant medication exposures, including traditional DMARDs and glucocorticoid therapy.
17449484 Response to anti-tumour necrosis factor alpha blockade is associated with reduction of car 2007 Jul OBJECTIVES: To determine whether tumour necrosis factor (TNF)-alpha blockers may reduce carotid intima-media thickness (cIMT) in patients with active rheumatoid arthritis (RA) steadily responsive to such therapy. METHODS: From 287 consecutive RA patients attending our out-patient clinic and diagnosed on the basis of the American College of Rheumatology (ACR) criteria, 49 without traditional cardiovascular risk factors and meeting the requirements for TNF-alpha blockers therapy were selected. Among them, 39 actually started TNF-alpha blockers, but only 30, who reached at least a response on the ACR 20% improvement criteria at 14 weeks, maintained during the whole year of treatment, were finally considered (group A). The remaining 10/49, homogeneous for age, sex, traditional cardiovascular risk factors, socioeconomic status, disease activity and duration, who did not consent to TNF-alpha-blocker administration, were used as controls (group B). Disease activity score in 44 joints (DAS44), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were evaluated before starting the study, and 3, 6, 12 months thereafter; cIMT was measured by ultrasound before and 12 months thereafter only. RESULTS: Patients in group A showed a very significant cIMT reduction (P < 0.0001 and P < 0.0001, on the right and left side, respectively), preceded by an early and lasting significant decrease in DAS44, ESR and CRP. Moreover, a significant correlation was found between cIMT and DAS44 (r = 0.435, P < 0.05). CONCLUSIONS: These results demonstrate that TNF-alpha blockade is associated with cIMT reduction in RA patients steadily responsive to therapy, probably by lowering inflammation.
16465611 The pivotal nature of sugars in normal physiology and disease. 2006 Jan Glycopathology has become the focus of considerable research in recent years as the role of glycosylation in the development, regulation, and progression of disease has come under increased scrutiny. Cracking the 'sugar-code' in biological systems that relate to both health and disease holds tremendous promise for deciphering disease mechanisms such as the link between the glycomodification of immunoglobulins and various autoimmune diseases, notably IgG in rheumatoid arthritis (RA), and has exciting implications for the development of novel diagnostic and therapeutic interventions.