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ID PMID Title PublicationDate abstract
15195482 [Infliximab (anti-TNF-alpha) treatment in patients with adult Still's disease. Experience 2004 Jan Adult Still's disease is a systemic inflammatory disorder of unknown etiology. First-line treatment for Still's disease includes nonsteroidal anti-inflammatory drugs and corticosteroids. In refractory cases o when the dose of corticosteroid is unacceptably high, other disease modifying antirheumatic drugs have been used. But recent study showed the efficacy anti-TNF therapy in adult Sill's disease refractory to conventional therapy. We report a favourable response to infliximab in two patients who has proved resistant to conventional therapy.
14977774 Anti-Ro/SSA and anti-La/SSB autoantibodies in the tear fluid of patients with Sjögren's s 2004 Mar PURPOSE: To investigate the presence of anti-Ro/SSA and anti-La/SSB antibodies in the tear fluid and serum of patients with Sjögren's syndrome and to evaluate the association of these autoantibodies with the severity of keratoconjunctivitis sicca. METHODS: Tear fluid and serum were obtained from 28 patients with Sjögren's syndrome and 17 age matched normal control subjects. Evaluation of tear fluid and sera anti-Ro/SSA and anti-La/SSB levels was done by using a quantitative enzyme linked immunosorbent assay kit designed for the quantitative measurement of IgG class autoantibodies directed against highly purified SSA and SSB antigens. Tear function and ocular surface were evaluated by Schirmer I test, tear break up time, and rose bengal staining. Dry eye symptom scores were recorded. RESULTS: Increased levels of anti-Ro/SSA and anti-La/SSB antibodies were detected in sera of 57.1% and 50% of SS patients, respectively. Six patients had increased levels of anti-Ro/SSA in the tear fluid, in one case anti-Ro/SSA being detected in tear fluid when it was negative in serum. Ten patients had positive anti-La/SSB titres in tear fluid and in four of these patients, anti-La/SSB titres were not elevated in serum. A positive correlation was observed between serum and tear fluid titres of anti-Ro/SSA (r = 0.43, p = 0.02), but not of anti-La/SSB. Serum anti-Ro/SSA and anti-La/SSB concentrations correlated positively with dry eye symptom scores (r = 0.42, p = 0.02 and r = 0.48, p = 0.01, respectively) and negatively correlated with Schirmer I test scores (r = -0.39, p = 0.04 and r = -0.40, p = 0.03, respectively). Significant correlations were found between tear anti-La/SSB concentrations and dry eye symptom score (r = 0.56, p = 0.02) and also rose bengal staining scores of the ocular surface (r = 0.44, p = 0.02). CONCLUSION: This study shows that autoantibodies against Ro/SSA and La/SSB antigens are present in the tear fluid of some patients with SS and their presence in serum or tear fluid is associated with the severity of keratoconjunctivitis sicca. Additional measurement of tear fluid levels of anti-Ro/SSA and anti-La/SSB may serve as a valuable diagnostic indicator of SS.
11792886 A new defensive mechanism to prevent apoptosis in salivary ductal cells from patients with 2002 Jan OBJECTIVE: In Sjögren's syndrome (SS), salivary acinar cells are destroyed even though ductal cells are frequently spared from destruction and can sometimes proliferate. We made the hypothesis that abnormalities of the tumour suppressor protein p53, either by mutations leading to proliferation or by activation of the functional wild-type p53, explain this phenomenon. METHODS: Immunohistochemistry to detect p53 and its transcription target p21, which is expressed only if p53 is functional and not mutated, was performed on labial salivary glands (LSG) from 10 patients with primary SS, all of whom had a Chisholm grade 4 LSG biopsy, and from 10 control patients with sicca symptoms or systemic diseases and a normal LSG biopsy (grade 0 or 1). RESULTS: The p53 antigen could be detected in ductal cells of nine of 10 LSG from SS patients and only one of 10 LSG from controls. The p21 antigen was detected in ductal cells of eight of 10 LSG from SS patients and two of 10 LSG from controls. The p53 and p21 antigens were localized in the same ductal cells in SS patients, and the positive ducts were those located around lymphoid foci. CONCLUSION: The colocalization of p53 and its transcription factor p21 in salivary ductal cells surrounding lymphoid foci demonstrated that p53 was functional and not mutated. Its expression may be a defensive mechanism that provides ductal cells with time to repair DNA damage and prevents apoptosis. The lack of over-expression of p53 and p21 in acinar cells could be one of the key mechanisms of acinus destruction by apoptosis in SS and could be a target for new therapeutic strategies.
15083898 Sequential changes to clinical parameters and adhesion molecules following intravenous pul 2004 Mar It is believed that the systemic subtype and the positive rheumatoid factor, polyarticular subtype of juvenile idiopathic arthritis (JIA) show the least favorable outcomes for therapy; patients with systemic JIA are often resistant to recommended therapeutic modalities. We report the sequential changes to clinical and laboratory findings from pulse therapy with monthly intravenous cyclophosphamide (0.5 g/m2 body surface area) administration combined with methylprednisolone (30 mg/kg; 1 gm maximum) for 6 months, following which the medication interval was elongated to 3 months for a total of from 7 to 12 courses. Among 4 children suffering from refractory systemic JIA, 3 demonstrated clinical improvement, 2 of whom achieved clinical remission. Furthermore, we also adminstered this therapy to a girl suffering from refractory polyarticular JIA, following which she revealed clinical remission subsequent to 9 courses of such therapy. From our experience, we suggest that patients afflicted with JIA that is unresponsive to traditional medication may experience benefit from this type of pulse therapy.
15164930 [The effectiveness of cevimeline hydrochloride on dry cough in Sjögren's syndrome]. 2004 Apr Dry cough in Sjögren syndrome (SS) is not an uncommon symptom observed in clinical fields. However, effective treatments for the cough have not been established. The recently introduced cevimeline hydrochloride, a muscarinic receptor stimulant, has been confirmed to be definitely effective for xerostomia of SS. In the present study, the effectiveness of cevimeline hydrochloride on dry cough was studied in 9 Sjögren patients and evaluated using the visual analog scale (VAS) and face scale. Improvement of dry cough was observed in 8 out of the 9 patients, suggesting the effectiveness of cevimeline hydrochloride. Although the detailed etiology of dry cough in SS is unknown, the result of the study suggested the mechanism that cevimeline hydrochloride increased the secretion in the airway mucus, improving dry bronchial conditions. Further studies are needed with more subjects.
12470447 A third study on the use of orally administered anhydrous crystalline maltose for relief o 2002 Oct OBJECTIVES: To examine the safety and efficacy of anhydrous crystalline maltose for treatment of dry mouth and other symptoms of dryness in patients with primary Sjögren's syndrome. DESIGN: Anhydrous crystalline maltose was delivered orally as a 200-mg lozenge given three times daily over a 24-week period to a total of 100 subjects. All participants had prominent complaints of persistent dry mouth associated with primary Sjögren's syndrome. Patients were examined at baseline and every 6 weeks of treatment. SETTINGS: Patients were seen in outpatient clinics at a total of 27 sites within the United States. OUTCOME MEASURES: Unstimulated whole saliva output, a measure of basal salivary gland function, was determined at each visit. Symptoms associated with oral and ocular dryness were assessed at the same time with the use of 100-mm visual analogue scales. Safety was assessed by physical examination and laboratory studies. RESULTS: During this clinical trial, a majority of evaluable subjects (39/76) demonstrated an increase in unstimulated whole saliva output, and the treatment exhibited an excellent safety profile. The anhydrous crystalline maltose treatment led to significant improvement in several subjective measures of oral and ocular comfort. CONCLUSIONS: In this study, anhydrous crystalline maltose lozenges administered three times daily for 24 weeks improved salivary output and decreased complaints of dry mouth and eyes in patients with primary Sjögren's syndrome. Side-effects were minimal, and treatment was without significant adverse events. These results are similar to the benefits observed in two prior studies reported by the authors. This safe and simple intervention appears to provide clinical benefit to primary Sjögren's syndrome patients with distressing dry mouth symptoms.
16578972 [Case of subcutaneous and mesenteric acute panniculitis with Sjögren's syndrome]. 2002 Jun We report a case of a 27-year-old Japanese female with Sjogren's syndrome (SS), who suffered from several episodes of subcutaneous and mesenteric panniculitis with a recurrence within one year. After a history of fever and skin rash, the patient underwent surgery at a local hospital with a diagnosis of acute appendicitis complicated with an ileocecal abscess. She was also diagnosed as having SS. After the operation, the fever and skin rash persisted. She was treated with prednisolone (PSL), and her symptoms resolved. A recurrent bout of abdominal pain with fever, annular erythema on the trunk and a nodular erythematous rash on the lower extremities occurred six months after the operation. A skin biopsy from the lower extremities showed findings that were compatible with panniculitis. Abdominal computer tomography (CT) showed a diffuse swelling with soft tissue density in the intestinal mesenterium and para aortic area. A retrospective examination of the operative specimen obtained from the local hospital revealed centrilobular infiltration of neutrophils in the mesenteric adipose tissue with fat necrosis, which is compatible with mesenteric panniculitis. Twenty mg/day of PSL was successful in treating the systemic panniculitis, and the abnormal diffuse soft tissue density on the abdominal CT disappeared after three weeks of PSL administration. Systemic panniculitis is a rare complication in SS, and the pathogenesis is unclear.
15206125 [Significance of the cardiovascular function tests in patients with collagen diseases, esp 2004 May The purpose of this study is to evaluate the cardiovascular function in patients with incomplete type of SSc (SSSD; Scleroderma Sjögren syndrome associated Spectrum Disorders), SSc (Systemic Scleroderma) and SLE (Systemic Lupus Erythematosus) by using ECG and digital plethysmograph. We also preformed ambulatory ECG monitoring for cases of SSSD and SSc with QT interval prolongation. 1) In ECG findings, ischemic myocardial damage, left ventricular hypertrophy or QT interval prolongation was observed in 33% cases of SSSD and 32% cases of SSc, respectively. In addition, parasympathetic disorders were observed in approximately 20% cases of SSSD, SSc and SLE. 2) Digital plethysmogram findings suggested that the peripheral vascular damage was present in both cases of SSSD and SSc, and its severity was lower in SSSD than SSc. The incidence of abnormal cardiovascular function tests in SSSD was relatively less than that in SSc. The cardiovascular function tests are useful to find cardiovascular abnormalities in these collagen diseases.
11980425 [Mixed and palatal salivary secretion in denture-wearing healthy people and in patients wi 2002 Apr Denture retention is related to forces necessary to completely remove the denture from its basal seat. The liquid-joint model for explaining denture retention is accepted by most of the authors. According to this model retentive force is a function of saliva surface tension, liquid film thickness, surface of contact and the liquid-denture contact angle. Based upon the literature, mucosa covered with the least amount of saliva exists at the area of the palate and the upper lip, consequently at the area of the upper denture retention. Dryness is dependent on the volume of saliva present on the oral mucous membranes and the rate of its evaporation of them. However, the hard palate contains few minor glands and it is an area of high evaporation. Based on the above mentioned facts, patients with xerostomia might have problems with the stability of the complete dentures. To verify it, authors investigated 24 healthy people and 11 patients with Sjögren's syndrome (SS). Further aim of the authors was to determine how the new dentures influence the whole resting and the palatal saliva flow rate. According to the results whole resting saliva flow rate is decreased in SS because of the focal inflammation of the salivary glands, but surprisingly the palatal secretion rate does not change in SS related to the initial values of the healthy people. Although every patient had xerostomia (WRS < or = 0.1 ml/min), none of them complained about denture instability. Based upon this study, authors agree with the statement of the literature, that palatal mucous saliva can help to stabilize the maxillary denture. Results suggest that whole resting and palatal saliva flow rates are not influenced by the placement of new dentures in healthy complete denture wearers.
15054216 Profiles of gene expression in human autoimmune disease. 2004 Human autoimmune diseases arise from complex interactions between genetic and environmental factors, result from immune attack upon target tissues, and affect 3-5% of the population. We compared gene expression profiles (>4000 genes) in the peripheral blood mononuclear cells of normal individuals after immunization to individuals with four different autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, and multiple sclerosis). All autoimmune individuals, including unaffected first-degree relatives, share a common gene expression profile that is completely distinct from the immune profile. Therefore, this expression pattern is not simply a recapitulation of the immune response to nonself, is not a result of the disease process, and results, as least in part, from genetic factors. Surprisingly, these genes are clustered in chromosomal domains suggesting there is some genome-wide logic to this unique expression pattern. These data argue that that there is a constant pattern of gene expression in autoimmunity that is independent of the specific autoimmune disease and clinical parameters associated with any individual autoimmune disease.
17143680 Clinical and radiological manifestations of the rheumatoid wrist after the Sauvé-Kapandji 2004 A retrospective study was performed to investigate the clinical and radiological results of the Sauvé-Kapandji (S-K) procedure for the rheumatoid wrist. One hundred and eight rheumatoid wrists in 98 patients were operated on in our institute from 1992 to 2000, and in 82 wrists we used the S-K procedure. In other cases, synovectomy alone was performed on 16 wrists, and partial and total arthrodeses were performed concurrently on 5 wrists each. Carpal bones and/or radiocarpal joints in which the union could not be assessed radiologically were found in 49 wrists (59.8%) after the S-K procedure, and among them there was definite non-fusion of the carpal bone and radiocarpal joints in 29 wrists (35.4%). However, definite fusion of carpal bones and/or radiocarpal joints was found in 33 wrists (40.2%). The formation of carpal bones and partial radiocarpal fusion with some mobility was detected in some cases. Therefore, the S-K procedure may stabilize the carpus in the rheumatoid wrist to some extent while maintaining a functionally important range of motion and relieving pain. However, it does not stop the disease process and cannot reestablish or maintain carpal height. We concluded that the S-K procedure is the treatment of choice for the rheumatoid wrist, and if the wrist is unstable, as seen with arthritis mutilans, we then perform either radio-lunate partial arthrodesis or total wrist arthrodesis.
12222551 A review of methotrexate-induced accelerated nodulosis. 2002 Sep OBJECTIVE: To review the English-language literature on methotrexate-induced accelerated nodulosis, compile case reports of its occurrences, and make recommendations on the clinical management of patients. METHODS: A comprehensive search of MEDLINE, TOXLINE, and EMBASE databases was performed, along with a bibliographic search of key articles. Case reports were compiled separately. The Naranjo adverse drug reaction probability scale was used to assess causality. RESULTS: Twenty-seven case reports of patients with methotrexate-induced accelerated nodulosis were identified along with one series of 10 patients and one series of 21 patients. Probability assessment for most of the case reports was weak and left room for doubt regarding causality. Most patients were older than 50 years, were positive for rheumatoid factor, and had nodules on their fingers but did not have concurrent vasculitis. Some unusual sites of nodulosis were the larynx, lungs, Achilles tendon, and heart. Of 19 patients given hydroxychloroquine, colchicine, sulfasalazine, azathioprine, or D-penicillamine, all except two showed regression of the nodules; the response was unknown for one patient. CONCLUSION: Controversy surrounds the management of patients who develop accelerated nodulosis while receiving methotrexate therapy for rheumatoid arthritis. Our review of these data does not allow definitive conclusions because the available case reports and clinical trials are fragmented and incomplete.
15334485 Lack of requirement of osteopontin for inflammation, bone erosion, and cartilage damage in 2004 Aug OBJECTIVE: Osteopontin (OPN) is a secreted glycoprotein involved in a range of physiologic processes, including inflammation, immunity mediated by Th1 cells, and bone remodeling. It is expressed in the joints of rheumatoid arthritis patients and has been the subject of conflicting reports concerning its role in arthritis induced by antibodies against type II collagen. This study assessed the role of OPN in the K/BxN serum-transfer model of autoantibody-induced arthritis. METHODS: Expression of OPN gene transcripts was assessed by microarray analysis of ankle RNA taken at 6 time points after transfer of K/BxN serum. OPN-sufficient or OPN-deficient littermates backcrossed for 10 generations onto the C57BL/6 genetic background were given K/BxN serum. Arthritis severity was measured by ankle thickening and a clinical index. Hind limb sections were stained with hematoxylin and eosin or toluidine blue and scored for inflammation, cartilage damage, and bone erosion. RESULTS: OPN messenger RNA transcripts progressively increased in ankle joints during the course of K/BxN serum-transferred arthritis. OPN-deficient mice receiving K/BxN serum developed arthritis with kinetics and clinical severity comparable with those of OPN-sufficient littermates. Histologic assessment of arthritic joints from OPN-deficient mice revealed synovial hyperplasia, pannus formation, mononuclear cell infiltration, bone erosion, cartilage damage at sites adjacent to and distal from pannus invasion, and tartrate-resistant acid phosphatase-positive multinucleated cells at sites of bone erosion. Histopathologic scoring demonstrated comparable levels of inflammation, cartilage damage, and bone erosion in OPN-sufficient and OPN-deficient mice. CONCLUSION: OPN does not have a required role in inflammation, bone erosion, and cartilage damage in the K/BxN serum-transfer model.
12610428 [Cutaneous and osteoarticular Scedosporium apiospermum infection]. 2002 Dec Scedosporium apiospermum is a widely distributed fungus that can be found in the soil, manure and decaying vegetation. Human infection with this fungus is facilited by immunodepression. A 65-year-old man, who was taking oral methylprednisolone for rheumatoid polyarthritis had for a few months ulcerated or suppurative nodules whose incision discharged a thick honey-colored exudate. An ulceration over the first right metatarsophalangian articulation had left the bone exposed. The treatment for Pseudomonas aeruginosa, initially isolated in the exudate was unsuccessful. Other microbiology samples exhibited Scedosporium apiospermum, without bacteria. The pathogenic nature of the infection was proven on a skin and bone (head of the first metatarsian) biopsy showing numerous branching and septate hyphae. The patient was successfully treated by itraconazole. Scedosporium apiospermum is the cause of a growing number of human infections due to widespread use of immunosuppressors. Skin and lung localizations predominate. Osteoarticular infection is relatively rare, which contributes to the originality of this observation. Treatment is not well defined and essentially combines surgical drainage with antifungals like itraconazole. This emergent fungal infection, which has non specific clinical manifestations, must be considered in immunocompromised patients.
15161981 Musculoskeletal ultrasound--a state of the art review in rheumatology. Part 2: Clinical in 2004 Jul Rheumatologists remain divided on whether they should introduce musculoskeletal ultrasound (MSUS) into their clinical practice. A central issue in the application of MSUS in clinical rheumatology is the need for proof of clinical relevance and improved patient care. There is now accumulating evidence that MSUS improves clinical diagnosis and intervention skills. High-resolution ultrasound is superior to clinical examination in the diagnosis and localization of joint and bursal effusion and synovitis. MSUS is the imaging modality of choice for the diagnosis of tendon pathology. MSUS is seven times more sensitive than plain radiography in the detection of rheumatoid erosions, allowing earlier diagnosis of progressive rheumatoid arthritis. Ligament, muscle, peripheral nerve and cartilage pathology can also be readily demonstrated by MSUS. There is exciting evidence that MSUS may potentially be used by rheumatologists to non-invasively diagnose and monitor not just joint and muscle disease but also nerve compression syndromes, scleroderma, vasculitis and Sjögren's syndrome. Joint aspiration and injection accuracy can be improved by MSUS, with initial evidence confirming improved efficacy. As the number of rheumatologists performing MSUS increases and the technical capabilities of MSUS improve, there is likely to be a growing number of proven clinical indications for the application of MSUS in rheumatology practice. This paper reviews the evidence for the application of MSUS in rheumatology.
15047492 [How to test at once six cytokines in samples as small as 25 microl?]. 2004 Jan Inflammatory and regulatory or anti-inflammatory cytokines (TNFalpha, IL-1beta, -6, -8, -10 and -12) regulate both the humoral and cellular immune responses. Cytokines have diverse peripheral and central functions. They are critical mediators of protective host responses, including defense against microbial invasion and tumorigenesis. However, the production of specific proinflammatory cytokines must be tightly regulated and compartmentalized to prevent the overexpression of these molecules that can end in chronic inflammation and tissue injury. Many diseases like autoimmune disease (rheumatoid arthritis, multiple sclerosis, arteriosclerosis, Crohn's disease), neurodegenerative disease (Alzheimer's and Parkinson's disease), tumor invasion and metastasis correlate with a deregulation in cytokine action. Thus, cytokines network provides an attractive and intensely competitive area of potential targets for therapeutic intervention. To monitor such secretion patterns in presence of putative drugs obtained by high throughput screening (HTS) some new techniques recently appeared on the market. We here compared results obtained by CBA (BD Cytometric Bead Array) to IC50 values obtained by classical sandwich Elisa. The complexity and cost of this new method is largely compensated by simultaneous testing of 6 cytokines in only 25 micro L of cell supernatant.
14550523 [Treatment of a septic patient with acquired haemophilia]. 2003 Oct INTRODUCTION: Acquired haemophilia is a rare bleeding diathesis caused by auto-immune depletion of factor VIII. It is characterised by spontaneous haemorrhagic syndrome, which can be fatal sometimes. EXEGESIS: A 71 year-old man presents in a dysimmunitary context (rheumatoid arthritis complicates by an acquired haemophilia) a septicemia with a methicillin resistant staphylococcus aureus. At the time of the hospitalization, the patient is febrile (39 degrees C). The activated partial thromboplastin time is very much increased, the level of factor VIII is lowered by 7% and the title of the inhibitor to factor VIII amounts to 140 Bethesda unities. An haematoma of the right root thigh is also noted. In that case, the concomitant presence of septicemia makes difficult the use of immunosuppressive therapy usually recommended to decrease auto-antibody's level. For the management of the septicemia, an adapted antibiotherapy (vancomycin then teicoplanin) is organized to J1. To control haemorrhagic risk, immunoglobulins are prescribed from d12 to d16, without immediate results. Then prednisone is introduced. We observe a very fast decrease of the anticoagulant circulating title with a neat improvement of the clinical state, allowing so to realize a draining puncture of the psoas. This invasive investigation required the use of prothrombinic complex concentrates ((Feiba) in the dose of 80 UI/kg two to three times a day). Biopsy does not show infection source. CONCLUSION: The infection delayed the prescription of immunosuppressive therapy and the surgery. Use of corticoids, following 5 days of intravenous polyvalent immunoglobulin, was the good choice. After 7 weeks of hospitalization the patient has recovered a normal haemostasis results, and a good general state.
15476228 Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression 2004 Oct OBJECTIVE: Methotrexate is one of the most commonly used disease-modifying antirheumatic drugs in the management of psoriatic arthritis (PsA). Despite the differences between the inflammation in PsA and rheumatoid arthritis (RA), the effects of methotrexate on the synovium have been described solely in RA. In this study, we sought to determine the effects of methotrexate on the inflammatory infiltrate and on cytokine and metalloproteinase gene expression in the synovium of PsA patients. METHODS: Ten patients with PsA (median duration 18 months) underwent arthroscopy and synovial biopsy of an inflamed knee before and after clinical improvement induced by methotrexate. Immunohistologic analysis was performed using antibodies to CD3, CD4, CD8, CD68, factor VIII, vascular cell adhesion molecule, E-selectin, and intercellular adhesion molecule (ICAM). Matrix metalloproteinase 3 (MMP-3) and tissue inhibitor of metalloproteinases 1 (TIMP-1) messenger RNA (mRNA) were quantified by competitive reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, interferon-gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) mRNA expression was quantified by real-time PCR. RESULTS: Patients received a median methotrexate dosage of 13.75 mg/week (range 7.5-15) for a median of 11.5 months (range 7-14 months). The Ritchie Articular Index, swollen joint count, and Disease Activity Score were significantly reduced. There was a decrease in all immunohistologic staining, although this was statistically significant only for CD3, CD4, CD8, CD68, E-selectin, and ICAM. Despite clinical improvement in all patients, there was a residual T cell infiltrate in all synovial biopsy tissues. The synovial lining layer thickness, but not hypervascularity, was significantly reduced. There was also a significant reduction in MMP-3, but not TIMP-1, expression. Before treatment, PsA synovium was characterized by a predominant expression of the proinflammatory cytokines IL-15, IFNgamma, IL-1beta, and TNFalpha and the antiinflammatory cytokine IL-10. Methotrexate reduced synovial IL-1alpha, IL-1beta, IL-8, IL-10, IL-15, IFNgamma, and TNFalpha mRNA expression, but the effect was significant only for IL-8. CONCLUSION: Methotrexate produced a clinical response in PsA by reducing, but not abolishing, the inflammatory infiltrate, adhesion molecule expression, and MMP-3 and proinflammatory cytokine gene expression, particularly IL-8, in the synovium. Methotrexate did not reduce hypervascularity, which is a prominent differentiating feature of PsA synovium.
14634130 Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: cr 2003 Dec 1 The IL-1R/Toll-like receptor (TLR) superfamily of receptors has a key role in innate immunity and inflammation. In this study, we report that streptococcal cell wall (SCW)-induced joint inflammation is predominantly dependent on TLR-2 signaling, since TLR-2-deficient mice were unable to develop either joint swelling or inhibition of cartilage matrix synthesis. Myeloid differentiation factor 88 (MyD88) is a Toll/IL-1R domain containing adaptor molecule known to have a central role in both IL-1R/IL-18R and TLR signaling. Mice deficient for MyD88 did not develop SCW-induced arthritis; both joint swelling and disturbance of cartilage chondrocyte anabolic function was completely abolished. Local levels of proinflammatory cytokines and chemokines in synovial tissue washouts were strongly reduced in MyD88-deficient mice. Histology confirmed the pivotal role of MyD88 in acute joint inflammation. TLR-2-deficient mice still allow influx of inflammatory cells into the joint cavity, although the number of cells was markedly reduced. No influx of inflammatory cells was seen in joints of MyD88-deficient mice. In addition, cartilage matrix proteoglycan loss was completely absent in MyD88 knockout mice. These findings clearly demonstrated that MyD88 is a key component in SCW-induced joint inflammation. Since agonists of the Toll-like pathway are abundantly involved in both septic and rheumatoid arthritis, targeting of MyD88 may be a novel therapy in inflammatory joint diseases.
12688421 Aromatic trap analysis of free radicals production in experimental collagen-induced arthri 2003 Mar Many findings demonstrated that Glycosaminoglycans (GAGs) and Proteoglycans (PGs) possess antioxidant activity. Collagen-induced arthritis (CIA) is an experimental animal model similar to human rheumatoid arthritis (RA) in which free radicals are involved. Sodium salicylate can be used as a chemical trap for hydroxyl radicals (OH*), the most damaging reactive oxygen species (ROS), yielding 2,5-dihydroxybenzoic acid), (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA). The measurement of these two acids in the plasma allows to indirectly assess the production of OH* radicals. The aim of the study was to investigate the effect of hyaluronic acid (HYA) (30 mg/kg i.p.) or chondroitin-4-sulphate (C4S) (30 mg/kg i.p.), on free radical production in Lewis rats subjected to CIA. After the immunization with bovine collagen type II in complete Freund's adjuvant, rats developed an erosive hind paw arthritis, that produced high plasma OH* levels assayed as 2,3-DHBA and 2,5-DHBA, primed lipid peroxidation, evaluated by analyzing conjugated dienes (CD) in the articular cartilage; decreased the concentration of endogenous vitamin E (VE) and catalase (CA) in the joint cartilage; enhanced macrophage inflammatory protein-2 (MIP-2) serum levels and increased elastase (ELA) evaluated as an index of activated leukocyte polymophonuclear (PMNs) accumulation in the articular joints. The administration of HYA and C4S starting at the onset of arthritis (day 11) for 20 days, limited inflammation and the clinical signs in the knee and paw, reduced OH* production, decreased CD levels, partially restored the endogenous antioxidants VE and CA, reduced MIP-2 serum levels and limited PMNs infiltration. The results indicate that the GAGs HYA and C4S significantly reduce free radical production in CIA and could be used as a tool to investigate the role of antioxidants in RA.