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PubMed2001

Alternatively spliced EDA-containing fibronectin in synovial fluid as a predictor of rheumatoid joint destruction.

OBJECTIVES: Fibronectin containing the EDA region (EDA(+)Fn), a molecule important for rheumatoid joint destruction, was measured in relation to the progression of joint destruction in rheumatoid arthritis (RA). METHODS: Total Fn and EDA(+)Fn were measured by ELISA, and the concentrations of Fn in plasma and synovial fluid were compared prospectively for 2 yr with the progression of joint destruction in 41 knee joints of 37 patients with RA. The extent of joint destruction was assessed by the Larsen score and joint space narrowing in X-ray films taken before and 2 yr after measurement of EDA(+)Fn. RESULTS: The concentration of synovial fluid EDA(+)Fn showed a positive correlation with the progression of joint destruction in RA (r=0.78). While total Fn in synovial fluid also showed a correlation with joint destruction (r=0.54), total Fn and EDA(+)Fn in plasma showed no correlation with joint destruction. The concentration of synovial fluid EDA(+)Fn was significantly higher in patients who underwent joint replacement after the measurement of EDA(+)Fn than in those who did not receive surgery (P<0.029). CONCLUSION: Synovial fluid EDA(+)Fn can be a predictor of subsequent joint destruction in RA.

Alternative Splicing↗

PubMed1995

Plasma and synovial fluid interleukin-1, interleukin-6 and substance P concentrations in rheumatoid arthritis patients: effect of the nonsteroidal anti inflammatory drugs indomethacin, diclofenac and naproxen.

We performed an open, between patients, placebo controlled study in order to evaluate the effect of the treatment with the non steroidal anti inflammatory drugs indomethacin, diclofenac and naproxen on the concentrations of the cytokines IL-1 beta and IL-6 and of the neuropeptide substance P in plasma and synovial fluid of 24 rheumatoid arthritis patients. All patients had high synovial fluid cytokine and substance P levels, and high plasma cytokine levels at the beginning of the study. The treatment with the non steroidal anti inflammatory drugs significantly decreased both plasma and synovial fluid IL-6 and synovial fluid substance P in comparison to placebo, but did not affect IL-1 beta concentrations. This effect can participate in the therapeutic effect of non steroidal anti inflammatory drugs in rheumatoid arthritis.

Adult↗

PubMedDate not supplied

Correlation of synovial fluid interleukin 6 (IL-6) activities with IgG concentrations in patients with inflammatory joint disease and osteoarthritis.

Synovial fluids of patients with rheumatoid arthritis, osteoarthritis, psoriatic arthritis, reactive arthritis and Reiter's syndrome were examined for their concentrations of interleukin 6 (IL-6) in a proliferation assay with the IL-6 dependent hybridoma cell line B13.29 (subclone B9). IL-6 activity was significantly higher in the synovial fluids of patients with rheumatoid arthritis and psoriatic arthritis than in patients with osteoarthritis. Significant correlations were shown between the concentrations of synovial fluid IL-6 and IgG. These findings may contribute to the understanding of the enhanced immunoglobulin production by synovial mononuclear cells in patients with inflammatory joint disease.

Adult↗

PubMed2003

Synovial fluid depletion: successful arthrodesis without operative cartilage removal.

Operative arthrodesis has been thought to require surgical removal of remaining joint cartilage, but we have found in rabbits that even a joint with intact cartilage can fuse if rigidly fixed. This may enable new percutaneous techniques for arthrodesis. Rigid adaptation of the joint surfaces deprives the cartilage of mechanical stimulation and depletes the cells of synovial fluid transport of oxygen and nutrition. To better understand the requirements for successful arthrodesis, we studied the histological consequences of the complete absence of mechanical stimulation alone or in combination with synovial depletion by placing a metal cap over part of the joint cartilage in rabbits. The cap was either closed or had an opening to permit synovial fluid to reach the cartilage. We also studied if penetration of the bone-cartilage junction by a drill hole would facilitate cartilage resorption. Synovial fluid depletion in combination with a drill hole through the bone-cartilage junction led to disappearance of all cartilage matrix after 7 weeks. Synovial fluid depletion with an intact bone-cartilage junction led to complete disappearance of the cartilage matrix in four of seven rabbits after 7 weeks. With a hole in the cap for synovial fluid, the cartilage matrix was still present to varying degrees after 7 weeks in all the rabbits. In conclusion, percutaneous arthrodesis by rigid adaptation may lead to cartilage disappearance due to synovial depletion rather than due to the absence of mechanical stimulation. A combination with perforation of the bone-cartilage junction appears to lead to reasonably quick removal of the cartilage matrix.

Animals↗

PubMed1992

Markers of inflammatory activation: upregulation of complement receptors CR1 and CR3 on synovial fluid neutrophils from patients with inflammatory joint disease.

Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from paired peripheral blood and synovial fluid samples from 34 patients with inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD)). Using monoclonal antibodies (anti-CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages of positively labeled cells and the relative fluorescence intensities (as a measure of receptor number) were determined. CR1 and CR3 were found to be present on the majority (> 85%) of circulating neutrophils from normal subjects, RA and OAD patients, and on synovial fluid neutrophils from both patient groups. A strong correlation between neutrophil CR1 and CR3 expression was observed in peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r = 0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels of CR3 expression were approximately twice those recorded for CR1. Both CR1 and CR3 expression was upregulated on synovial fluid neutrophils compared with that observed on the corresponding peripheral blood cells. Mean percentage increases observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001); and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3 expression failed to demonstrate any significant relationship between the concentrations of these soluble factors and receptor expression. Upregulation of CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed joint, is a consistent finding in patients with inflammatory arthropathies.

Adult↗

PubMed1988

Identification of cartilage matrix glycoprotein in synovial fluid in human osteoarthritis.

Cartilage matrix glycoprotein (CMGP) is a high molecular weight protein found in hyaline cartilage and fibrocartilage. It consists of disulfide-bonded subunits, each with an apparent molecular weight of 116,000. Fragmentation of CMGP is noted in extracts of osteoarthritic canine cartilage. CMGP has been identified in the serum and synovial fluid of dogs with experimentally induced osteoarthritis. It has now been identified in synovial fluid from osteoarthritic human joints but not in synovial fluid from joints of patients with other arthritides or joint abnormalities. The possible significance of CMGP in synovial fluid in human osteoarthritis is discussed.

Adult↗

PubMed1993

Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells.

The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases.

Adult↗

PubMed1982

Gas-liquid chromatographic analysis of synovial fluid. Succinic acid and lactic acid as markers for septic arthritis.

Nonvolatile short-chain fatty acids from 80 synovial fluids were quantified by gas-liquid chromatography. Succinic acid was detectable in all 23 septic synovial fluids infected with either gram-positive or gram-negative organisms and in only 5 of 57 nonseptic synovial fluids. Lactic acid was present in all of the effusions but was correlated with septic arthritis only when present in concentrations greater than 250 mg%. Neither short-chain fatty acid was more sensitive than high white blood cell counts (greater than 50,000 mm3) or depressed glucose concentration (less than 40 mg/dl) in diagnosing septic arthritis before antibiotic therapy; however, the detection of succinic acid was helpful in identifying patients with septic arthritis who had been given antibiotic treatment before arthrocentesis. Thus, gas-liquid chromatography, a rapid and sensitive method for the detection of short-chain fatty acids, may complement the currently available methods used to diagnose septic arthritis.

Arthritis, Infectious↗

PubMed1985

A method for the quantification of cartilage proteoglycan structures liberated to the synovial fluid during developing degenerative joint disease.

An enzyme linked immunosorbent assay for the quantification of proteoglycans or proteoglycan fragments in biological fluids is presented. The assay has been used to determine concentrations of articular cartilage proteoglycans and/or fragments thereof in synovial fluid in early stages of osteoarthrosis. Osteoarthrosis was induced in one knee joint of nine German wire haired pointers by transection of the anterior cruciate ligament. All dogs developed osteoarthrosis in terms of macroscopic as well as microscopic criteria. Attempts were made to aspirate synovial fluid, prior to surgery and at various times in the postoperative period, from the joint operated on as well as from the contralateral joint. Concentrations of proteoglycans (fragments) of one type of aggregating proteoglycan were significantly higher in the synovial fluid samples from the joint operated on compared to the contralateral joint (p less than 0.001), while the difference observed when the other type of aggregating proteoglycan was used as the test antigen was less significant (p less than 0.05). The concentration of proteoglycans (fragments) in synovial fluid samples from joints operated on was significantly higher after the operation when compared with the preoperative concentration (p less than 0.001). No correction has been made for the increased dilution due to hydrops of the joints operated on.

Animals↗

PubMed1986

Synovial fluid nutrient delivery in the diathrial joint: an analysis of rabbit knee ligaments.

The role of synovial fluid in providing nutrition to rabbit knee ligaments and menisci was evaluated by intraarticular injection of a labeled collagen precursor, tritiated proline. Incorporation of this substrate as tritiated hydroxyproline was measured in collateral and cruciate ligaments and menisci. The injectate volume (0.35 ml) did not appreciably change the overall joint pressure as measured by a wick catheter; therefore, no alteration of synovial membrane diffusion characteristics resulted. The concentration of the injected proline (0.52 mg%) was well below that normally present in serum (2.65 mg%). Therefore, incorporation of this substrate was not driven by a concentration gradient and represented normal uptake of synovial fluid and physiological incorporation of label as measured by the presence of tritiated hydroxyproline. Autoradiography was performed on all ligaments and menisci, and demonstrated concentration of the isotope and its metabolite (tritiated proline and tritiated hydroxyproline, respectively) in and around fibroblasts. This study indicates that rabbit knee ligaments and menisci can derive nutrition from a synovial fluid source.

Animals↗

PubMed2003

Development of a dog microdialysis model for determining synovial fluid pharmacokinetics of anti-arthritis compounds exemplified by methotrexate.

PURPOSE: The purpose of this study was to develop and validate an animal model of drug disposition in synovial fluid (SF) by comparing microdialysis with arthrocentesis using the anti-arthritic drug methotrexate (MTX). METHODS: Microdialysis probes were calibrated in vitro with the no net flux method using dog synovial fluid. The probes were implanted surgically into the stifle joint space of four dogs and were dialyzed overnight using a portable microinfusion pump. The membrane integrity of the probes was monitored by retrodialysis using an internal standard. After an intravenous bolus of 2.5 mg/kg of MTX, unbound concentrations in synovial fluid, as well as total plasma concentrations, were measured by liquid chromatography tandam mass spectrometer (LC/MS/MS) in samples collected from 0 to 48 h postdose. RESULTS: The probe membrane remained intact at least 48 h after implantation. The mean probe recovery and unbound fraction of MTX in SF were 46.8% and 44.8%, respectively. The unbound fraction of MTX was 44% in synovial fluid. MTX penetrated into the joint space rapidly, with maximal concentrations of 6.6 microM reached at approximately 1 h postdose. The unbound MTX area under the curve in SF was approximately 40% of the total area under the curve in plasma. These data agree well with the previous data obtained for MTX using arthrocentesis. CONCLUSION: In contrast with arthrocentesis, microdialysis enables the collection of multiple serial SF samples from individual animals with minimal trauma and potential blood contamination. This animal model should prove valuable for studying the disposition of new antiarthritis compounds or biomarkers in SF.

Animals↗

PubMed1980

A latent collagenase from rheumatoid synovial fluid. Purification and partial characterization.

1. A latent collagenase (EC 3.4.24.3) has been isolated from rheumatoid synovial fluids and purified by (NH4)2SO4 precipitation and column chromatography, utilising Sephadex G-150, DEAE Sephadex A-50 and Sephadex G-100 superfine grade. 2. The final preparation activated by trypsin (EC 3.4.21.4) had a specific activity against thermally reconstituted collagen fibrils of 259 micrograms collagen degraded/min per mg enzyme protein, representing a nearly 800-fold increase over that of the original rheumatoid synovial fluid. 3. The latent collagenase preparation can be activated by trypsin and to some extent by HgCl2 but not by 3 M NaSCN, 3.5 M NaCl, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) or p-chloromercuribenzoate. 4. Inhibition studies and the acrylamide gel electrophoretic pattern of collagen degradation products showed that the trypsin-activated enzyme has the essential features of a neutral collagenase. 5. The molecular weights, determined by calibrated gel filtration, were 52 000 and 43 000 for the latent and the activated enzyme, respectively. 6. The nature of the latency of synovial fluid collagenase is discussed.

Arthritis, Rheumatoid↗

PubMed1990

Clinical assessment of rheumatic diseases using viscoelastic parameters for synovial fluid.

For the first time it is clearly exhibited that synovial fluid (SF) is thixotropic. Although no hysteresis loops were observed for SF, not even at high shear rates, thixotropy may be exhibited by measuring the rate of recovery after extensive shearing. The rebuilding of the structure in a small-amplitude oscillatory state following the high-shear-rate state reveals the thixotropic behaviour. Five different viscoelastic parameters for various synovial fluids (SF) were obtained using oscillatory rheometry. It was also shown that for SF in the low frequency range, corresponding to a knee joint almost at rest, the shear loss modulus G" is greater than the shear storage modulus G', since the system is allowed to dissipate energy at rest. However, with movement, G' increases and eventually becomes greater than G" at a characteristic frequency above which the system has insufficient time to dissipate energy and hence responds as an elastic body. This functional behaviour, characteristic for normal SF, broke down in the SF of rheumatoid arthritis. It was also absent in the SF of knee joints with meniscus lesions and ligament defects.

Elasticity↗

PubMed1991

C reactive protein and immunoglobulin G in synovial fluid and serum in joint disease.

C reactive protein (CRP) and immunoglobulin G (IgG) were measured in synovial fluid and serum of 72 patients (29 with rheumatoid arthritis (RA), 17 with osteoarthritis, 11 with crystal synovitis, seven with undifferentiated arthritis, and eight with seronegative arthritis). The synovial fluid:serum (SF:S) ratios were compared with those calculated from the SF:S ratios of transferrin, caeruloplasmin, and alpha 2 macroglobulin, using the binomial test within groups and the Mann-Whitney test between groups. In RA synovial fluid CRP concentrations were lower than expected and IgG concentrations higher than expected. In osteoarthritis CRP concentrations were higher than expected. In seronegative arthritis IgG concentrations were raised. The ratio of CRP:IgG was depressed in RA. These findings are consistent with a role for CRP in the inflammatory process of RA, while the CRP:IgG ratio may be of value in the differential diagnosis of joint disease.

Arthritis↗

PubMed1988

Increased concentrations of proteoglycan components in the synovial fluids of patients with acute but not chronic joint disease.

Synovial fluid samples (139) from 121 patients with rheumatoid arthritis, osteoarthritis, pseudogout, chronic pyrophosphate arthritis, gout, and reactive arthritis were analysed for cartilage proteoglycan components. Keratan sulphate (KS) epitope was determined by a competitive radioimmunoassay, and total sulphated glycosaminoglycans (S-GAG) were determined after papain digestion by a specific dye binding assay. Increased concentration of both KS epitope and S-GAG were found in synovial fluid from joints with acute inflammatory arthropathy (gout, pseudogout, and reactive arthritis). Analysis of consecutive samples from the same joint at different stages showed that the concentration of KS epitope or total S-GAG varied with acute inflammatory activity. In samples from patients with chronic conditions during active and inactive inflammatory phases concentrations were much lower and not distinguishable among these disease groups. The detection of raised concentration of proteoglycan components may reflect the rapid depletion or greatly increased turnover of proteoglycan in the articular cartilage during acute inflammation in the joint. This did not appear to be sustained in most patients with chronic joint diseases.

Acute Disease↗

PubMed2001

Culture with BACTEC Peds Plus/F bottle compared with conventional methods for detection of bacteria in synovial fluid.

An evaluation was undertaken to determine the utility of the BACTEC Peds Plus/F bottle and the BACTEC 9240 instrument (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) for the detection of clinically significant microorganisms in synovial fluid specimens. The Peds Plus/F bottle was used because in our laboratory the quantity of synovial fluid available for culture is frequently in the range of 0.5 to 3.0 ml. The culture results obtained with the Peds Plus/F bottle were compared to those obtained by a conventional agar plate method for a total of 805 synovial fluid specimens. Microbial growth was produced by 74 cultures (9.2%) from 60 patients, yielding a total of 77 microorganisms. Organisms were classified as pathogens (n = 62), contaminants (n = 12), or indeterminate (n = 3) on the basis of a review of the patients' medical histories. Culture using BACTEC Peds Plus/F bottle detected statistically significantly more pathogens overall (62 versus 51 pathogens [P = 0.001]) and statistically fewer contaminants overall (1 versus 11 contaminants [P = 0.006]) than culture by the agar plate method. These results indicate the superior performance of the BACTEC Peds Plus/F bottle over the conventional agar plate method for the detection of clinically significant microorganisms from synovial fluid specimens.

Arthritis, Infectious↗

PubMed2004

Trisomy 7 in synovial fluid cells of patients with rheumatoid arthritis.

OBJECTIVE: Recent studies revealed trisomy 7 as a chromosomal abnormality in non-neoplastic disorders such as rheumatoid arthritis (RA). In the present study, we investigated the presence of trisomy 7 in the synovial fluid cells of patients with RA using fluorescence in situ hybridisation (FISH) analysis. METHODS: Synovial fluid from 15 patients with RA was collected from knee joints. The control group consisted of seven patients with traumatic synovial effusion in their knee joints. The arthrocenteses were performed under aseptic conditions. Dual-colour FISH analysis was performed using chromosome-7-specific LSI D7S522 (7q31) and chromosome-5-specific LSI EGR1 (5q31)/D5S721 (5p15.2) probes on the slides prepared from synovial fluid of RA patients and controls. RESULTS: The slides of our cases were analysed using two different DNA probes. When the slides hybridised with chromosome-5-specific probes were analysed, no trisomic or monosomic cells were revealed in both patients and controls. However, in eight of 15 patients, trisomy 7 occurred in variable percentages of cells (23% to 48%) of synovial fluid. No monosomic 7 cells were detected in these specimens. All control cases were disomic for chromosome 7. CONCLUSION: The results of the present investigation suggest that trisomy 7 may play a role in the pathogenesis of synovial hyperproliferation in RA.

Adult↗

PubMed1990

Quantitative microanalysis of equine synovial fluid glycosaminoglycan concentration.

An alcian blue precipitation method for quantifying the hyaluronic acid (HA) and sulphated glycosaminoglycan concentration (SGAG) in solutions containing both compounds was assessed. The assay was found to be rapid and reliable in solutions containing 0 to 200 mg of HA/dl and 50 to 1,000 micrograms of SGAG/dl, and was not affected by the presence of protein, hemoglobin, or methemoglobin in concentrations normally found in synovial fluid. The HA and SGAG concentrations in intercarpal synovial fluid from 13 clinically normal and 11 arthritic horses were evaluated. A relationship was not found between the concentration of HA and SGAG and any other synovial fluid variable. The SGAG concentration was found to be markedly high in several of the synovial fluid samples from arthritic horses, but did not correlate with the degree of articular cartilage erosion.

Alcian Blue↗