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[Synovial tissue levels in comparison with synovial fluid and serum concentrations following a single daily administration of 20 mg piroxicam (Felden)].

Serum, synovial fluid and synovial tissue was taken from a total of 25 patients of both sexes on whom a synovectomy had been performed, after a 1, 3, 5, 6 or 7 day treatment with a daily administration of 20 mg Piroxicam (5 patients in each group) and the concentration of Piroxicam (Felden) determined. Parallel to this a part of the synovial tissue taken was histologically examined and classified. The analytical results presented here show that in the mean appr. 33% of the Piroxicam passed from the serum into the synovia, appr. 26% into the non or partially florid synovial tissue and appr. 32% into the florid or highly florid synovial tissue. Felden 20 (Piroxicam) thus fulfills the requirement of a good acting, non-steroidal, antiinflammatory substance (NSAID), namely of being available at the location of the inflammatory process.

Adolescent↗

The distribution of proquazone and three of its metabolites in serum and synovial fluid.

In 13 patients with hydrarthrosis of the knee, samples of synovial fluid and blood were drawn at regular intervals, following a single oral dose of 600 mg proquazone. The concentrations of the unchanged drug were measured fluorimetrically and those of its three principal, active metabolites by high pressure liquid chromatography. The absorption and distribution of proquazone and its metabolites were rapid. Measurable--in some cases considerable--concentrations were to be found in both the synovial fluid and serum as early as 30 minutes after intake. High concentrations were still present up to 7 hours after intake. Considerable variations were observed, both between patients and over time for each patient, so that only qualitative rather than quantitative kinetic conclusions could be drawn from the results. The concentrations were generally lower in the synovial fluid than in the serum, which may be ascribed to the drug's high protein binding.

Administration, Oral↗

Chemotaxis and chemiluminescence responses of synovial fluid polymorphonuclear leucocytes during acute reactive arthritis.

The chemotaxis and chemiluminescence responses of polymorphonuclear leucocytes (PMN) of synovial fluid and peripheral blood from patients with acute reactive arthritis were studied. Rates of chemotactic and chemokinetic migration of synovial fluid PMN were significantly decreased. In addition, chemiluminescence responses tended to be depressed, suggesting that the cells were deactivated for both chemotaxis and production of oxygen derived free radicals. Such deactivation has been described previously as a characteristic of synovial fluid PMN in rheumatoid arthritis. Compared with those with a mild disease, patients with severe acute reactive arthritis had higher chemiluminescence responses of synovial fluid PMN to phorbol myristate acetate during acute disease and developed increased migration of peripheral blood PMN towards zymosan treated serum after recovery from the disease. This supports the view that hyperreactive PMN contribute to the development of severe inflammatory symptoms in acute reactive arthritis.

Acute Disease↗

Comparison of modern marker proteins in serum and synovial fluid in patients with advanced osteoarthrosis and rheumatoid arthritis.

Numerous studies have focused on the significance of modern marker proteins in the synovial fluid of the knee joint and in the serum both, for osteoarthritis (OA) and rheumatoid arthritis (RA). The relationship between the serum concentrations and the concentrations in the synovial fluid is still unclear. Synovial fluid and serum samples were obtained from 13 patients with advanced OA and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13, TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against the total protein concentrations. Serum concentrations of MMP-13 in the RA-group were statistically higher than the synovial values (P<0.05). MMP-13 was the only marker protein that revealed distinct higher levels in the serum than in the synovial fluid. The study design allows only conclusions about advanced stages of RA and OA. Longitudinal investigations may provide further information about the value of MMP-13 as a potential marker to monitor the course of RA and OA.

Aged↗

Immunological detection of myeloperoxidase in synovial fluid from patients with rheumatoid arthritis.

We have used rocket immunoelectrophoresis and immunoblotting to detect myeloperoxidase in synovial fluid from patients with rheumatoid arthritis. This protein was enzymatically inactive but its identity as myeloperoxidase was confirmed by comparing its subunit structure with that of the purified enzyme. When neutrophils were stimulated to secrete myeloperoxidase in vitro, a polypeptide with an apparent molecular mass of 62 kDa was detected extracellularly by immunoblotting. Neutrophils isolated from synovial fluid showed a reduced level of this 62 kDa polypeptide but it was detected extracellularly in synovial fluid by immunoblotting. Thus, we conclude that neutrophils in synovial fluid from patients with rheumatoid arthritis have been activated in vivo to secrete myeloperoxidase and propose that the products of this enzyme system can contribute to the tissue damage associated with this disease.

Arthritis, Rheumatoid↗

Lubrication of the human ankle joint in walking with the synovial fluid filtrated by the cartilage with the surface zone worn out: steady pure sliding motion.

A mixture model of synovial fluid filtration by cartilage in the human ankle joint during walking is presented for steady sliding motion of the articular surfaces. In the paper the cartilage surface zone is assumed worn out. The same model has been recently applied to the squeeze-film problem for the human hip joint loaded by the body weight during standing (Hlavácek, Journal of Biomechanics 26, 1145-1150, 1151-1160, 1993; Hlavácek and Novák, Journal of Biomechanics 28, 1193-1198, 1199-1205, 1995). The linear biphasic model for cartilage (elastic porous matrix + ideal fluid) due to Prof. V. C. Mow and his co-workers and the biphasic model for synovial fluid (viscous fluid + ideal fluid), as used in the above-mentioned squeeze-film problem, are applied. For the physiologic parameters of the ankle joint during walking, a continuous synovial fluid film about 1 microm thick is maintained under steady entraining motion according to the classical model without the fluid transport across the articular surface. This is not the case in the filtration model with the cartilage surface zones worn out. On the contrary, this filtration model indicates that synovial fluid is intensively filtrated by such cartilage, so that no continuous fluid film is maintained and a synovial gel layer, about 10(-8) m thick, develops over the majority of the contact. Thus, if the cartilage surface zones are worn out, boundary lubrication should prevail in the ankle joint under steady sliding motion for the mean values of loading and the sliding velocity encountered in walking cycle.

Ankle Joint↗

Correlation of metal-binding proteins and proteinase inhibitors with immunological parameters in rheumatoid synovial fluids.

Metal-binding proteins (ceruloplasmin, transferrin, ferritin, and lactoferrin), proteinase inhibitors (alpha 1-antitrypsin, alpha 2-macroglobulin and inter-alpha-trypsin inhibitors), and albumin were assayed in synovial fluid obtained from 20 patients with rheumatoid arthritis (RA) and 15 with osteoarthritis (OA). The levels of proteinase inhibitors and metal-binding proteins, except transferrin, were significantly increased in synovial fluid from RA patients as compared with synovial fluid from OA patients. Metal-binding proteins significantly correlated with rheumatoid factor and immune complexes in synovial fluid from RA patients. Proteinase inhibitor levels also significantly correlated with C-reactive protein, and complement components. These results suggest that the raised level of metal-binding proteins and proteinase inhibitors in synovial fluid from RA patients reflect inflammatory activity, and hence may play an important role in the pathogenesis of inflammatory joint diseases.

Adult↗

Expression of CD44 on rheumatoid synovial fluid lymphocytes.

OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.

Arthritis, Rheumatoid↗

[[Nitroblue tetrazolium tests of blood and synovial fluid cells in rheumatoid arthritis and osteoarthritis (author's transl)].

Nitroblue tetrazolium (NBT) test, widely performed to investigate the physiology and function of blood polymorphonuclear leukocytes, was evaluated using blood and synovial fluid cells of 20 patients with rheumatoid arthritis and 19 patients with osteoarthritis. There were no significant differences among two joint diseases and healthy controls in NBT test values on blood polymorphonuclear leukocytes. Seropositive and CRP positive patients with rheumatoid arthritis, however, revealed low values. NBT test value on polymorphonuclear leukocytes of synovial fluids was lower than that of blood in rheumatoid arthritis and was higher than that of blood in osteoarthritis. Negative correlations were seen between NBT test value and nucleated cell count of synovial fluids in these diseases. On the other hand, NBT test by mononuclear cells did not differ from the by polymorphonuclear leukocytes in rheumatoid synovial fluids and these two values correlated well. There was correlation between nucleated cell count and NBT test value on mononuclear cells in osteoarthritic synovial fluids. From these results it was suggested that the severity of joint inflammation might influence the function of not only polymorphonuclear leukocytes but also mononuclear cells of synovial fluids.

Adult↗

Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis.

The predominant lipoxygenase products of arachidonic acid were extracted and purified from synovial fluid and sonicates of synovial tissue of patients with rheumatoid arthritis (RA), spondyloarthritis (SA), or a noninflammatory arthropathy (NIA). The concentration of 5(S),12(R)-dihydroxy-6,8,10-(trans/trans/cis)-14-cis-eicosatetraenoic acid (leukotriene B4) in synovial fluid was elevated significantly in patients with RA and a positive latex test for rheumatoid factor (P < 0.05, n = 14) and in patients with SA (P < 0.05, n = 10), compared with that of subjects with NIA (n = 9). The content of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), but not of leukotriene B4, was elevated significantly in synovial tissue of seven patients with RA in comparison with that of four subjects with NIA (P < 0.05). A single intra-articular injection of corticosteroid significantly lowered the synovial fluid level of leukotriene B4 in six patients with RA. These data suggest an involvement of the potent chemotactic factors 5-HETE and leukotriene B4 in human inflammatory disease.

Arachidonic Acids↗

Synovial fluid levels of complement SC5b-9 and fragment Bb are elevated in patients with rheumatoid arthritis.

To determine whether complement turnover in synovial fluids of patients with rheumatoid arthritis (RA) reflects activation by the classical or alternative pathway, we used novel immunoassays to measure products of complement activation (the membrane attack complex SC5b-9 and the cleavage fragments Bb and C4d). Mean synovial fluid levels of SC5b-9 were more than 8 times higher in RA than in crystal-induced arthritis (gout and pseudogout) and over 16 times higher than in degenerative joint disease (DJD). Similarly, Bb levels were more than 3 times higher in RA synovial fluids than in crystal-induced arthritis and over 7 times higher than in DJD. Levels of C4d did not differ among the groups. SC5b-9 levels correlated with synovial fluid C3 anaphylatoxin (C3a), Bb, and C4d levels (r = 0.81, 0.62, and 0.51, respectively). In patients with RA, synovial fluid SC5b-9 levels correlated with C3a and Bb (r = 0.6 and 0.56, respectively) but not with C4d. Therefore, novel assays for complement activation indicate that both classical and alternative pathways are involved in complement turnover and that the alternative pathway contributes more to complement activation in RA than in DJD or crystal-induced arthritis.

Arthritis, Rheumatoid↗

I-Naphthyl acetate esterase isoenzymes in synovial fluids and radiography of temporomandibular and knee joints.

Esterase isoenzymes of synovial fluids were presented in cases of pain-dysfunction syndrome, osteoarthrosis, osteochondroma, malignant fibrous histiocytoma of temporomandibular joint, and hemarthrosis, rheumatoid arthritis of the knee joint. Radiographic features of them were also comparatively presented in several cases. The electrophoretogram of I-Naphthyl acetate esterase of pain-dysfunction syndrome showed the esterase-I, while when inflammatory process developed at joints, electrophoretic pattern of synovial fluids revealed a rather similar feature of sera with variable stainabilities of esterase-I, and -III, irrespective of any inflammation. Osteochondroma showed two components of esterase-I and -III, on the other hand malignant fibrous histiocytoma presented esterase-I and -III in the early stage but a more complicated pattern in recurrence. Among these conditions, the most similarity between synovial fluid and serum was demonstrated in the case of hemarthrosis on the electrophoretogram of I-Naphthyl acetate esterases.

Adult↗

Synovial fluid cytokine levels in Behçet's disease.

OBJECTIVE: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behçet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme-linked immunosorbent method. RESULTS: Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL-1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients. CONCLUSION: The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL-1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process.

Adult↗

Detection of crystals in synovial fluids by light microscopy: sensitivity and reliability.

Polarised light microscopy of synovial fluid is an established diagnostic technique widely regarded as reliable for the detection of crystals. The threshold concentration of crystals which can be detected has been investigated and the sensitivity and specificity of six observers compared. Various concentrations of laboratory manufactured crystals of monosodium urate monohydrate (MSUM), calcium pyrophosphate dihydrate (CPPD), and basic calcium phosphates (BCP) were added to the synovial fluid. The threshold for reliable identification of MSUM and CPPD was in the range of 10-100 micrograms/ml. False positives were frequent. The mean sensitivity of the six observers for MSUM was 69% and for CPPD was 82%. The mean specificity for MSUM was 97% and for CPPD was 78%. There was much discrepancy in the results of the slides stained with alizarin red S. Thus the value of alizarin red S as a screening test for BCP is questioned. In view of the variable sensitivity and specificity of different observers for MSUM and CPPD and the concentration threshold for reliable crystal identification, greater caution in the interpretation of synovial fluid analysis is advised, and recommendations for increased quality control are supported.

Anthraquinones↗

Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee.

We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4-7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens. Peak total concentrations of 1.73 and 0.86 micrograms.ml-1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively. The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.

Arthritis, Rheumatoid↗

Synovial fluid acid phosphatase in seropositive and seronegative arthritides.

Synovial fluid acid phosphatase was investigated in 82 arthritic patients with hydropsy in a knee joint. 39 of the patients were seropositive and 43 seronegative. 36 of the seropositive group had erosive rheumatoid arthritis. The mean synovial fluid acid phosphatase in the seropositive group, 11.6 U/l (SD +/- 8.4), was significantly higher (p less than 0.001) than in the seronegative group, 6.5 U/l (SD +/- 4.8).

Acid Phosphatase↗

Levels of fibroblast growth factor 2 in synovial fluids in human patients with internal derangement of the temporomandibular joint.

OBJECTIVE: We sought to elucidate the levels of fibroblast growth factor 2 (FGF-2) in synovial fluid taken from internally deranged human temporomandibular joints (TMJs) and to discuss the role of FGF-2 in the pathogenesis of internal derangement. STUDY DESIGN: Through the use of a pumping procedure, diluted synovial fluid was collected from the upper joint compartment of 22 TMJs with evidence of internal derangement (21 patients) and 8 TMJs with no such evidence (5 control subjects). Two of the control subjects were patients who had habitual dislocation, and three were healthy volunteers. The level of FGF-2 in the synovial fluid was assessed by means of an enzyme-linked immunosorbent assay. RESULTS: FGF-2 levels were at detectable levels in 15 of the 22 TMJs (68%) with internal derangement. The mean concentration of FGF-2 was 24 pg/mL. In the control group, FGF-2 levels were detectable in only 1 of 8 joints (13%), for a concentration of 3 pg/mL. The mean concentration of FGF-2 in the synovial fluid was significantly higher in the internal derangement group than in the control group (P =.02). CONCLUSIONS: FGF-2 levels are elevated in the human synovial fluid of TMJs with internal derangement.

Adolescent↗

Measurement of sulphated glycosaminoglycans and proteoglycan fragments in arthritic synovial fluid.

Immunoreactive proteoglycans (iPGs) and sulphated glycosaminoglycans (GAGs) were assayed in synovial fluid obtained from 22 patients with osteoarthritis (OA), 21 with rheumatoid arthritis (RA), 13 with gout, and five with Reiter's syndrome. A strong positive linear correlation was observed between concentrations of sulphated GAGs and iPGs in RA (r = 0.95) and gout (r = 0.94). A linear correlation was also observed in OA (r = 0.65). Patients with gout and Reiter's syndrome had significantly higher concentrations of sulphated GAGs and iPGs than patients with OA or RA. Patients with gout also had significantly higher total quantities of sulphated GAGs and iPGs in the knee joint cavity than patients with OA or RA. In all four diseases similar profiles were observed when comparisons were made between the total quantities and concentrations of sulphated GAGs and iPGs in synovial fluid. These results indicate that the observed differences in concentrations are not simply a function of dilution. The concentrations of sulphated GAGs and iPGs did not correlate closely with the type or number of inflammatory cells in the synovial fluid. Considerable variation was noted in the sulphated GAG/iPG ratios, suggesting that different mechanisms may be contributing to the release of proteoglycans in the diseases studied.

Adult↗