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ID PMID Title PublicationDate abstract
12236618 Tides of inflammation: impact of biologics. 2002 Sep Increased knowledge about the mechanisms of joint inflammation and damage has profoundly shaped the development of new therapies for rheumatoid arthritis (RA). The first stop on this remarkable bench-to-bedside journey has been the biologics targeting tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1). These engineered adaptations of naturally occurring molecules function to neutralize the biological activity of proinflammatory cytokines overproduced in the joints of patients with RA. The successful translation of this approach into the clinic has had a substantial effect on the care of patients with RA.
12654130 Prolonged cholestasis and ductopenia following gold salt therapy. 2003 Apr Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.
12756895 [Approximation to the cost of pharmacological treatment of rheumatoid arthritis in Spain]. 2003 Mar OBJECTIVE: To study the direct cost derived of utilization of pharmaceutical compounds in the treatment of rheumatoid arthritis(RA). MATERIAL AND METHODS: A prospective study with 150 patients (125 women/25 men) suffered of RA was carry out in Galicia-Spain public hospital. The mean age was 60.2 years, with a mean lengthy of disease of 11.2 years (1-53); the 64.4% come from rural areas. A personal interview was made with a complete registry of all data: demographic, activity score (ESR, Swollen joints), radiological status, functional class (ACR), extrarticular manifestations and co-morbid diseases. Such data was accomplished with all the medications employees with a calculation of monthly or annual cost for the different therapeutic groups and a final total cost. The statistical study was made with Excel's (Microsoft) and the Analysis Tool Pack. RESULTS: The 53% of patients was in functional class I and 52% in radiological stage I or II (Steinbrocker) whereas 16 patients was considered in remission. Non-steroideal ant-inflammatory drugs (NSAID) were used in the 82.7% of patients with a monthly cost of 12.71 [symbol: see text] (1.10-80). Corticosteroids at low doses were used in 90.7% with a monthly cost of 5.17 [symbol: see text] (1.24-33.7). The Disease Modifying Anti-rheumatic Drugs (DMARD) was used in 94% of cases, the most common methotrexate and association of two or more in 21%. The mean monthly cost for a single DMARD was 3.63 [symbol: see text] and for two, 13.75 [symbol: see text]. Gastroprotection and therapy for co-morbid diseases was employee in 80% and 95% of cases, with a monthly cost of 36.9 [symbol: see text] and year cost of 568.6 [symbol: see text], respectively. The study included 23 patients under treatment with anti-TNF therapy with a monthly mean cost of 933.8 [symbol: see text]. For pharmaceuticals exclusively for RA, annual cost was 342.8 [symbol: see text] excluding anti-TNF therapy, but with wide variation (6.4-2.910 [symbol: see text]). If we include all patients with anti-TNF therapy, gastro-protection and co-morbid situations in a calculation, the mean cost was 2.587 [symbol: see text] year. The most important cost was found in patients with 50-70 years-old and existing a good correlation between the final burden and use of medications for co-morbid conditions, gastro-protection, use of anti-TNF, age, lengthy of disease between 5-10 years and number of swollen joints, but not radiological stage. CONCLUSIONS: The economic burden for pharmaceuticals used in RA is very variable depending of some variables, including the proper disease and other related conditions. The most important cost occur in case of use of anti-TNF therapy. In the most frequent conditions, gastro-protection and therapy for co-morbid diseases lead the 62% of total annual burden, followed by the use of DMARD and in a minor load, the NSAIDs and corticosteroids.
12115178 Increased thickness of the arterial intima-media detected by ultrasonography in patients w 2002 Jun OBJECTIVE: To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA. METHODS: We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). IMT was measured on digitized still images of the common carotid and femoral arteries obtained by high-resolution ultrasonography (10-MHz in-line Sectascanner). Laboratory variables relevant to RA activity were measured by routine methods. The degree of RA progression was assessed by scoring (Larsen method) metacarpophalangeal (MCP) joints on hand radiographs. Activities of daily living were determined by a modified Health Assessment Questionnaire (M-HAQ) score, and physical activity levels were assessed by ultrasound measurement of the calcaneus (expressed as the osteo-sono assessment index [OSI] Z score). RESULTS: Common carotid and femoral artery IMTs were significantly higher (P < 0.05) in RA patients (mean +/- SD 0.641 +/- 0.127 and 0.632 +/- 0.125 mm, respectively) compared with controls (0.576 +/- 0.115 and 0.593 +/- 0.141 mm, respectively). Multiple regression analysis revealed a significant association between RA and the common carotid artery IMT. Moreover, the common carotid artery IMT in RA patients was positively associated with disease duration, the MCP joint Larsen score, and the M-HAQ score, and was negatively associated with the calcaneus OSI Z score. No significant association was found between corticosteroid treatment and common carotid artery IMT. CONCLUSION: RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.
12707569 Is there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rh 2003 May Rheumatoid arthritis is a chronic and debilitating disease, affecting an estimated 1% of the population worldwide. The past decade has witnessed an explosion in our understanding of the pathophysiology of rheumatoid arthritis and therefore in our ability to more effectively target the disease process. Although a cure remains elusive, remission is an approachable goal. There has been a complete remodeling of the traditional "pyramid" by rheumatologists, who now treat rheumatoid arthritis earlier and more aggressively than ever before. Standard single therapy with disease-modifying antirheumatic drugs, which was previously the final step in treating rheumatoid arthritis, is now practically bypassed in the deluge of information suggesting that combinations of disease-modifying antirheumatic drugs or newer biologic therapy is more effective. It is difficult to assimilate all the data and develop a rational approach; however, the bottom line is often the deciding factor: the newer agents are tremendously expensive. The intent of this article is to review recent and relevant trials in the treatment of rheumatoid arthritis, suggest a treatment algorithm, and argue that traditional disease-modifying antirheumatic drugs continue to play a pivotal role.
12759297 In vitro growth rate of fibroblast-like synovial cells is reduced by methotrexate treatmen 2003 Jun BACKGROUND: Fibroblast-like synovial cells (FLS) can be cultured and expanded in vitro in monolayer. Little is known about the growth characteristics of FLS derived from different patients. OBJECTIVE: To study FLS cultures, with particular attention to differences in growth rate of FLS from patients with rheumatoid arthritis (RA) and from other arthritic patients. Additionally, to analyse the influence of methotrexate (MTX) treatment, patient age, and disease duration on FLS growth characteristics. MATERIALS AND METHODS: FLS were isolated from needle arthroscopy biopsy specimens. Twenty four patients (11 RA, 8 spondyloarthropathy, 1 osteoarthritis, and 4 undifferentiated arthritis) were studied. FLS population doubling time was determined between passage 2 and passage 5. Differences in population doubling time between RA and non-RA FLS and between FLS from patients receiving MTX and those not receiving this drug were analysed. In addition, possible correlations between FLS population doubling time and patient age or disease duration were examined. RESULTS: In vitro monolayer FLS cultures from needle arthroscopy biopsy specimens showed linear growth characteristics. Cell growth rate was not correlated with type of disease. Cells from patients undergoing treatment with MTX showed a longer population doubling time than FLS from patients not receiving this drug (Mann-Whitney test, p<0.05). No correlation was found with patient age or disease duration. CONCLUSION: The results suggest that FLS growth in monolayer is not dependent on the disease affecting the joint. MTX treatment, however, was more relevant in determining FLS growth rate.
14673985 Rheumatoid arthritis of the shoulder joint: comparison of conventional radiography, ultras 2003 Dec OBJECTIVE: To determine the role of ultrasound and magnetic resonance imaging (MRI) compared with conventional radiography in the detection of chronic and acute inflammatory manifestations of rheumatoid arthritis (RA) of the shoulder joint. METHODS: Forty-three consecutive patients with known RA prospectively underwent clinical examination, radiography, ultrasound, and MRI of the shoulder joints. Each patient was assigned a clinical/laboratory score consisting of 7 parameters, including measurements of shoulder mobility, the erythrocyte sedimentation rate, and C-reactive protein level. Conventional radiography was standardized and performed in 2 planes. Ultrasound was performed in 10 predefined planes using a 7.5-MHz linear transducer. MRI at 1.5T comprised transverse and oblique coronal T1- and T2*-weighted fast spin-echo, gradient-echo (GRE), and inversion-recovery sequences with a matrix size of up to 512 pixels. A dynamic T1-weighted GRE sequence was acquired with intravenous administration of contrast medium. Erosions were assessed using all 3 imaging techniques on a 4-point scale. Soft-tissue involvement was evaluated according to the presence of synovitis, tenosynovitis, and bursitis on ultrasound and MRI. The results in the study group were compared with those obtained in a control group of 10 patients with shoulder pain. RESULTS: In the study group, erosions of the humeroscapular joint were detected by conventional radiography in 26 patients, by ultrasound in 30 patients, and by MRI in 39 patients; the differences were statistically significant for the comparisons of conventional radiography with MRI and for ultrasound versus MRI (P < 0.0001). Conventional radiography detected 12 erosions of the scapula and MRI detected 15. Synovitis was demonstrated in 12 patients by ultrasound and in 27 patients by MRI (P = 0.0003). Tenosynovitis was observed in 15 patients by ultrasound and in 28 patients by MRI (P = 0.0064). Bursitis was detected in 13 patients by ultrasound and in 18 patients by MRI. The findings on dynamic contrast-enhanced MRI correlated significantly with the detection of synovitis by ultrasound and erosions by static MRI (P < 0.05). CONCLUSION: Ultrasound and MRI supplement conventional radiography in assessing the shoulder joint. Although conventional radiography can be used as the sole method of following up known joint destruction in RA, ultrasound and, preferably, MRI are recommended as additional techniques in the initial diagnostic evaluation when radiography yields negative results.
12730749 Comparison of ultrasound and X-ray absorptiometry bone measurements in a case control stud 2003 Jun To compare quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA) bone measurements in female rheumatoid arthritis (RA) patients and controls were randomly selected from the population; secondly, to examine disease and demographic factors associated with these bone measurements. In a total of 115 RA patients (mean age 63.0 years) and 115 age- and gender-matched controls demographic and clinical variables were collected and heel QUS parameters [speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI)] as well as DXA bone mineral density (BMD) at spine and hip were measured. The differences in QUS and DXA measurements between RA patients and controls were tested both on a group and on an individual level. Univariate and multivariate statistical tests were applied to explore for associations to the bone measurements. In the RA patients mean disease duration was 16.6 years, erythrocyte sedimentation rate 23.6 mm/h, M-HAQ 1.68, 28-swollen joint count 7.7, 18-deformed joint count 4.5, 50.0% were rheumatoid factor (RF) positive and 44.2% were current users of prednisolone. All bone measurements were reduced in RA patients compared with controls (SOS 1.9%, BUA 9.4%, SI 19.5%, femoral neck BMD 7.4%, total hip BMD 7.5%, spine L2-L4 BMD -3.0%). Only at spine was the BMD reduction not statistically significant ( P=0.21). In the subgroup of never users of prednisolone SOS was decreased by 1.4%, BUA by 3.7%, SI by 11.0, femoral neck BMD by 2.7%, and total hip BMD by 0.6%, whereas for spine L2-L4 BMD was increased by 4.3% and only for SOS and SI was the decrease statistically significant. The QUS discriminated better than DXA between patients and controls on a group level, but this difference in favor of QUS disappeared on an individual level when the measurement errors were taken into account. Age, BMI, RF and deformed joint count, but not corticosteroids, were independently associated with at least one of the QUS and one of the DXA measures; however, the association between disease-related variables was stronger with the QUS bone measures than with the DXA bone measures. The results for the quantitative QUS bone measures seem to mainly reflect bone mass. Disease-related variables in multivariate analysis remained independently associated with all QUS measures even when adjusting for DXA bone measures. Further studies are needed to examine if QUS may reflect other aspects than bone mass and be a potential better predictor for fracture risk in RA and corticosteroid-induced osteoporosis.
15202722 CCR1 antagonists for the treatment of autoimmune diseases. 2004 May Chemokines are 8- to 10-kDa proteins that regulate leukocyte infiltration into inflammatory sites. The therapeutic potential of inhibiting these proteins is supported by their increased expression in human diseases, numerous studies in animal models of disease and, in some cases, by human genetic association studies. These findings, combined with the ability of chemokines to interact with 7-transmembrane G protein-coupled receptors, render them attractive drug discovery targets. This article reviews the evidence that supports a role for the chemokine receptor CCR1 in the pathogenesis of autoimmune diseases, progress made in identifying low molecular-weight antagonists and the current status of agents undergoing clinical evaluation.
12810422 Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associat 2003 Jul OBJECTIVES: To investigate determinants of joint destruction and reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) not treated with bisphosphonates or hormone replacement therapy and to evaluate if there are common markers of erosive disease and bone loss. METHODS: BMD was measured using dual x ray absorptiometry and joint damage was examined by x ray examination according to the Larsen method in 88 patients with RA. Associations between BMD and Larsen score, and between demographic and disease related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and markers of bone and cartilage turnover, were examined bivariately by simple and multiple linear regression analyses. RESULTS: 49/88 (56%) patients had osteoporosis in at least one site. Reduced BMD and increased joint destruction were associated with: at the forearm and femoral neck, high Larsen score, low weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at the total hip, low weight, high Larsen score, and dose of injected glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight, reduced cartilage oligomeric matrix protein, and increased carboxyterminal propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was associated with long disease duration and increased C reactive protein (CRP) (R(2)=0.545, p<0.001). CONCLUSIONS: Osteoporosis is common in postmenopausal patients with RA. Low weight and high Larsen score were strongly associated with BMD reduction. Increased CRP and long disease duration were determinants of erosive disease in postmenopausal women with RA. These findings indicate common mechanisms of local and generalised bone loss in RA.
12611144 Long-term follow-up of intra-articular injections into the temporomandibular joint in pati 2002 A long-term (12 years) follow-up of treatment with intra-articular injections into the temporomandibular joint (TMJ) of steroid or non-steroid agents was performed in 21 patients with rheumatoid arthritis (RA) and symptomatic TMJs. The aim of the study was to compare symptoms, signs and radiological appearance of the TMJ initially and at the follow-up in this group of patients. Eleven patients were assigned to a steroid group and 10 patients to a non-steroid group. Initial and follow-up clinical and radiological examination procedures were the same. The radiological evaluation was based on a grading system using standard reference films. At follow-up, 14 patients reported no pain from the TMJ and positive changes in most clinical variables were found in both groups. Radiographic follow-up examination was performed on 12 patients. Initially, all but 4 of the 24 joints had structural bone changes. At follow-up, 2 joints had lower, 11 joints had unchanged and 11 joints had higher radiological grades. Two out of 5 and 3 out of 10 joints in the steroid and non-steroid group, respectively, showed progression of structural bone changes. Among 9 untreated joints, 6 had higher radiological grades and 3 were unchanged. In the 11 TMJs with higher radiological grades at follow-up, there was in most cases moderate progression of erosive changes. The results suggest that the long-term development of symptoms and signs from the TMJ in patients previously treated was good and the long-term progression of joint destruction was low for both steroid and non-steroid agents in this patient group with RA.
12563673 Neutrophil migration and production of reactive oxygen species during treatment with a ful 2003 Feb OBJECTIVE: To evaluate the effects of therapy with a fully human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody on the production of superoxide and other reactive oxygen species (ROS) and on the migration capacity of neutrophils in patients with rheumatoid arthritis (RA). METHODS: A total of 29 patients with active RA and 25 healthy controls participated. Assessments were performed at baseline and 2 weeks after the first administration of anti-TNF-alpha. The production of ROS was studied in unstimulated conditions and after stimulation of receptor dependent (serum treated zymosan, STZ) and receptor independent (phorbol mystrate acetate, PMA) pathways by luminol enhanced chemiluminescence. As well, the PMA induced burst production of superoxide was measured using the cytochrome-c reduction assay. Potential changes in neutrophil migration to joints were assessed by scintigraphy with autologous leukocytes. RESULTS: Baseline production of ROS (both spontaneously and after STZ stimulation) and superoxide and the ex vivo chemotaxis were similar in RA patients (n = 25) and controls (n = 25) and remained unchanged after administration of anti-TNF-alpha. The production of ROS after PMA stimulation was slightly higher in patients than in controls (p = 0.04) and this difference disappeared 2 weeks after the first dose of anti-TNF-alpha (p < 0.05). The scintigraphic study showed that a single dose of anti-TNF-alpha, but not placebo, markedly decreased the influx of leukocytes to inflamed joints. CONCLUSION: In patients with RA, anti-TNF-alpha therapy rapidly decreases the influx of leukocytes into inflamed joints but does not impair neutrophil chemotaxis and production of ROS.
12091338 Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis o 2002 Jul 15 Circumstantial evidence has implicated tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-alpha in erythropoiesis of patients with active RA (n = 40) and the effect of anti-TNF-alpha antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36-/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-alpha levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36-/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti-TNF-alpha antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-alpha on patients' erythropoiesis. We conclude that TNF-alpha-mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis.
12126345 Treatment of AA amyloidosis in rheumatoid arthritis. 2002 Jul Four patients of rheumatoid arthritis (RA) with biopsy confirmed AA amyloidosis were treated with chlorambucil. All had established but uncontrolled RA with a persistently raised ESR. Moderate (> 1 gm, < 3.5 gm/d) to nephrotic range (> 3.5 gm/d) proteinuria and a relatively well preserved renal function was noted in three patients. One patient had deranged renal function and required dialysis. On chlorambucil, there was complete recovery, partial improvement and no improvement in one patient each. The fourth patient required haemodialysis, did not tolerate chlorambucil and succumbed to the illness. Therapy with chlorambucil can benefit some patients of RA with AA amyloidosis. Leucopenia is the most important dose limiting side effect.
15161335 New drug targets in rheumatoid arthritis: focus on chemokines. 2004 Rheumatoid arthritis is a chronic inflammatory disease where the synovial tissue is characterized by heavy infiltration of leukocytes. Chemokines and chemokine receptors play an important role in cell migration and positioning of leukocytes within the inflamed rheumatoid synovium. There is now much focus on the specific contribution and role of each chemokine and chemokine receptor in the chronic inflammatory process in the synovial tissue. Recent evidence indicates that interference with the chemokines released from the inflamed synovial cells or the chemokine receptors expressed on the cells infiltrating the synovial tissue may lead to discovery of new therapeutics for this disease.
12847674 Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentati 2003 Jul OBJECTIVE: Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. METHODS: We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. RESULTS: At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44). CONCLUSION: MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease.
12707582 RANKL and RANK as novel therapeutic targets for arthritis. 2003 May The TNF-family molecule receptor activator of nuclear factor kappa B (NFkappaB) ligand (RANKL) (OPGL, TRANCE, ODF) and its receptor activator of NFkappaB (RANK) are key regulators of bone remodeling and regulate T cell/dendritic cell communications, and lymph node formation. Moreover, RANKL and RANK are expressed in mammary gland epithelial cells and control the development of a lactating mammary gland during pregnancy. Genetically, RANKL and RANK are essential for the development and activation of osteoclasts and bone loss in response to virtually all triggers tested. Inhibition of RANKL function via the natural decoy receptor osteoprotegerin (OPG, TNFRSF11B) prevents bone loss in postmenopausal osteoporosis and cancer metastases. Importantly, RANKL appears to be the pathogenetic principle that causes bone and cartilage destruction in arthritis, and OPG treatment prevents bone loss at inflamed joints and has partially beneficial effects on cartilage destruction in all arthritis models studied so far. Modulation of these systems provides a unique opportunity to design novel therapeutics to inhibit bone loss and crippling in arthritis.
12087911 [Clinical efficacy of xefocam and its effect on arterial pressure and heart rhythm variabi 2002 AIM: To try clinical response to xefocam, its safety, effects on arterial pressure and heart rhythm variability in rheumatoid arthritis (RA) patients with arterial hypertension (HT). MATERIAL AND METHODS: Xefocam (lornoxicam), a new non-steroid antiinflammatory drug, was given for 12 weeks in a daily dose 12 mg/day to 44 RA patients (mean age 54.5 +/- 7.3 years). 24-h arterial pressure monitoring was made with Cardiotens-01 device. RESULTS: Xefocam in a dose 12 mg/day has shown good tolerance, a high analgetic and antiinflammatory effect as indicated by a positive response of articular syndrome, a significant fall of systolic arterial pressure, decreased heart rate, better heart rhythm variability. CONCLUSION: In hypertensive RA patients xefocam in a dose 12 mg/day proved effective and safe.
15481928 [Antibodies to Yersinia enterocolitica and Proteus mirabilis in blood sera of rheumatoid a 2004 Jul Data on specific antibodies to the bacterial antigens of Yersinia enterocolitica (serovars 03, 09) and Proteus mirabilis in rheumatoid arthritis (RA) patients are presented. According to the data of some researchers, these organisms play some role in the pathogenesis of RA. The highest level of IgG antibodies to Y. enterocolitica antigens of both serovars was noted. The activity of specific IgG antibodies to serovar 03 was higher than that to serovar 09. In the sera of RA patients with P. mirabilis antgens the activity of IgM antibodies was higher.
12391302 Glycosaminoglycans are a potential cause of rheumatoid arthritis. 2002 Oct 29 Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome- or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4(+) T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.