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PubMed2006

Effects of hyaluronan on nitric oxide levels and superoxide dismutase activities in synovial fluid in knee osteoarthritis.

The aim of the present study was to evaluate the effects of hyaluronan (HA) on nitric oxide (NO) levels and superoxide dismutase (SOD) enzyme activities in synovial fluid (SF) in the treatment of patients with knee osteoarthritis (OA). SF samples were aspirated from OA patients before the commencement of the treatment (n=23) and 6 weeks after they were treated with HA products. NO levels and SOD activities were compared between the pre- and post-treatment of OA patients and of the control group (n=10). SF NO levels were significantly higher in patients with OA before the commencement of the treatment compared with the post-treatment (p<0.001) and the control groups. The SF SOD activity of patients before the commencement of the treatment was lower than the values in the controls and post-treatment (p<0.001). There is no significant correlation between SF NO and SOD levels and the radiographic changes of the OA knee according to Kellgren-Lawrence grading (p>0.05). Also, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) pain scores and physical function scores were gradually improved. These findings made us think that SF NO was a potent mediator in cartilage damage in OA, whereas SOD was an antioxidant mediator in the same process. Exogenous HA injections might reduce the NO levels and increase SOD activities in synovial fluid. These effects also do not seem to be dependent on the radiographic grading of the OA knee. More comprehensive studies are needed to clarify a possible clinical significance of this topic, and we suggest that this is an important area for further research into new treatment options.

Aged↗
PubMed1983

Clinical, microscopical and biochemical investigation of synovial fluid from temporomandibular joints.

The aim of this study was to investigate the relationship between pain and tenderness to palpation of the temporomandibular joint (TMJ), radiographic changes of the joint and signs of inflammation in the synovial fluid. Saline was injected into and aspirated from the TMJ of 29 patients with painful and tender TM joints and from five individuals with healthy joints. In another two patients synovial fluid could be aspirated without saline. The aspirated fluid was analyzed for inflammatory cells and for plasma proteins. A clinical examination of the stomatognathic system and a radiographic examination of the TMJ were performed before the aspiration. Besides tenderness to palpation of the TMJ, pain on mandibular movement and tenderness to palpation of the masticatory muscles were common. Erosion of the cortical outline of the joint surfaces was the most common radiographic finding. Inflammatory cells were present in the fluid of three patients but in none of the healthy individuals. Plasma proteins of inflammatory type could be detected in the fluid from seven of the patients. The results show that radiographic, cellular or biochemical signs of inflammation can frequently be found in the TMJ of patients with longstanding pain and tenderness of this joint.

Adolescent↗
PubMed1996

The effects of the phospholipase A2 inhibitor, manoalide, on cartilage degradation, stromelysin expression, and synovial fluid cell count induced by intraarticular injection of human recombinant interleukin-1 alpha in the rabbit.

OBJECTIVE: To evaluate the effects of the phospholipase A2 (PLA2) inhibitor manoalide on cartilage degradation, stromelysin expression, and inflammatory cell accumulation in rabbits treated intraarticularly with recombinant human interleukin-1 alpha (rHuIL-1 alpha). METHODS: Rabbits were given an intraarticular injection of rHuIL-1 alpha. At various time points over a 24-hour period, the rabbits were euthanized and the articular space was lavaged with sterile PBS. The proteoglycan content of the lavage fluid was measured using a dimethylmethylene blue assay. PLA2 activity and differential cell counts were also measured. The femur was removed and cartilage proteoglycan content determined. In some experiments, levels of synovial stromelysin messenger RNA (mRNA) were assessed. Manoalide or vehicle was administered 30 minutes before the rHuIL-1 alpha injection. RESULTS: The rHuIL-1 alpha-induced arthritic response is characterized by significant accumulation of inflammatory cells, loss of proteoglycan from the condylar cartilage, and induction of mRNA for stromelysin. PLA2 activity was also elevated in synovial fluids from rHuIL-1 alpha-injected joints. Pretreatment with manoalide (0.3 mg/joint) significantly inhibited PLA2 activity in the synovial fluid, prevented the loss of proteoglycan from the condylar cartilage, and reduced proteoglycan levels in lavage fluids. However, manoalide either had no effect on, or stimulated, cell accumulation. To assess the relationship between the induction of PLA2 and stromelysin, levels of stromelysin mRNA were measured in synovial tissue from manoalide- and vehicle-treated joints. Stromelysin message levels were significantly suppressed in a dose-dependent manner. CONCLUSION: These studies demonstrate that manoalide is a potent inhibitor of inflammation and cartilage catabolism, and suggest that PLA2 is involved in the pathophysiology of rHuIL-1 alpha-induced arthritis in rabbits.

Animals↗
PubMed1998

Comparison of the boundary-lubricating ability of bovine synovial fluid, lubricin, and Healon.

Purified human umbilical hyaluronate and a commercial preparation of rooster comb hyaluronate (Healon) intended for intra-articular viscosupplementation did not demonstrate the same degree of boundary-lubricating ability as bovine synovial fluid or its purified lubricating mucin, lubricin (p < 0.01). Boundary lubrication was measured in vitro in an arthrotripsometer oscillating natural latex against polished glass under a load of 0.35 MPa with an entraining velocity of 0.37 mm/s. The two hyaluronate solutions possessed the same hyaluronate concentration as synovial fluid, but Healon was 4.5 times more viscous. Present practice of viscosupplementation therapy for degenerative joint disease is limited and fails to implicate the important role of synovial mucin. Boundary lubrication provided by synovial mucin, independent of its viscosity, is not replicated by hyaluronate hydrogels.

Animals↗
PubMed2000

Osteolytic indicators found in total knee arthroplasty synovial fluid aspirates.

Interleukin-1beta and tartrate resistant acid phosphatase concentrations in synovial fluid aspirates were examined to determine if they could be used as indicators of increased synovial inflammation and an osteolytic reaction in patients having total knee arthroplasty. Synovial aspirates were obtained from seven patients with severely osteoarthritic knees that were scheduled for primary total knee arthroplasty and from 20 patients with knees scheduled for total knee arthroplasty revision. Eleven of the revision cases involved titanium alloy prostheses and nine involved cobalt chrome alloy prostheses. The interleukin-1beta and tartrate resistant acid phosphatase concentrations were obtained and compared between the group having primary total knee arthroplasty and the group having revision total knee arthroplasty. The knees having revision surgery had higher concentrations of interleukin-1beta and tartrate resistant acid phosphatase than did the knees having primary total knee arthroplasty. These results indicate a greater inflammatory and osteolytic response in knees having revision surgery. Although the osteoarthritic knees and the knees needing revision surgery in this study are considered to have an inflammatory state, it was only after total knee arthroplasty when particulate wear debris would be present that appreciable concentrations of interleukin-1beta and tartrate resistant acid phosphatase were produced.

Acid Phosphatase↗
PubMed1982

Characterisation of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other joint diseases by monoclonal antibodies (OKT series) and acid alpha-naphthyl esterase staining.

Mononuclear cell preparations from peripheral blood (PBL) and synovial fluid (SFL) of 27 Patients with rheumatoid diseases (15 patients with definite rheumatoid arthritis (RA), 10 with other inflammatory joint diseases (OJD), 1 with sarcoid arthritis (SA) and 1 with traumatic arthritis (TA) were examined for lymphocyte subpopulations determined by monoclonal antibodies of the OKT series and by the dot-like, acid alpha-naphthyl esterase staining (ANAE) activity. In patients with classic, active RA, blood T cells carrying the OKT8+ (suppressor/killer) phenotype were significantly reduced leading to an elevated OKT4/OKT8 ratio of 4.1 +/- 0.4 compared with 2.1 +/- 0.1 in healthy controls. In 10 patients with OJD this diminution of OKT8+ cells in peripheral blood was less pronounced or absent. As regards SFL subpopulations, patients with RA and OJD exhibited a similar distribution pattern with an elevation of OKT8+, Ia+ and ANAE negative cells and a similar OKT4/OKT8 ratio of 1.5 +/- 0.3 and 1.6 +/- 0.4, respectively. Similar results were also obtained in the only patient with TA, whereas the patient with SA and one RA patient with relapse after surgical synovectomy exhibited high OKT4/OKT8 ratios, both in synovial fluid and peripheral blood. Neither the OKT markers nor the dot-like ANAE staining pattern were significantly correlated to parameters of systemic or local disease activity as estimated by erythrocyte sedimentation rate and a local disease activity index.

Adolescent↗
PubMed1980

Synovial fluid beta 2 microglobulin and hydroxyproline fractions in rheumatoid arthritis and nonautoimmune arthropathies.

Fourteen patients with classical and definite seropositive rheumatoid arthritis (RA), 5 patients with microcrystalline arthritis, and 7 patients with osteoarthrosis were studied with respect to markers of newly synthesised collagen (synovial NDOH pro levels); markers of connective tissue resorption (synovial DOH pro and NBH levels); markers of lymphoid tissue activity (synovial and plasma beta 2m levels). Higher amounts of NDOH pro in RA synovial fluid are compatible with the hypothesis of a local connective tissue production as suggested by Uitto et al. on basis of a higher protocollagen proline hydroxylase activity in RA synovial tissue. DOH pro and NBH do not differ significantly in synovial fluid from RA or gouty patients, but the correlations between these forms of OH pro and, respectively, synovial lymphocytes and polymorphonuclear leucocytes are indicative of different processes of connective tissue remodelling in the 2 conditions. Synovial beta 2m levels are a direct function of total synovial lymphocyte counts independently of the type of arthropathy being explored. The ratio of synovial to plasma beta 2m is systematically above unity in RA patients only.

Arthritis, Rheumatoid↗
PubMed1990

Polyamine oxidase activity in rheumatoid arthritis synovial fluid.

Oxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity.

Arthritis, Rheumatoid↗
PubMed1994

Protein-G binding material from synovial fluid of rheumatoid arthritis patients induces unorthodox autoantibodies (IgG1 rheumatoid factor) in NZB, NZW and (NZB x NZW)F1 mice.

Our previous studies have demonstrated that injection of rheumatoid arthritis (RA) synovial fluid (SF) induces a marked increase mainly of IgG1 antibody-producing cells in autoimmune disease prone (NZB x NZW)F1 mice but not in CBA mice. In the present study, the in vivo effect of RA-SF on autoantibody production was tested in different strains of mice. Injection of RA-SF induced the production of unorthodox autoantibodies (IgG1 rheumatoid factor, RF) in young (NZB x NZW)F1 mice as well as in their parental strains NZB and NZW, but not in normal mice (CBA) or in mice with severe combined immunodeficiency, indicating that the response is not caused by a conventional immune response against RA-SF material. IgG1 RF production was rapidly induced and reached high levels already on day 7 and lasted for more than 90 days. The induction of IgG1 RF was not the result of polyclonal activation, since RA-SF did not stimulate the production of other antibodies, such as autoantibodies against double-stranded DNA, bromelain-treated mouse red blood cells, myosin, transferrin, cytochrome c, thyroglobulin or myoglobin or antibodies reactive with the hapten TNP. To elucidate the identity of the active substance in RA-SF, responsible for IgG1 RF production, bound and unbound material of RA-SF, eluted from a protein-G column was injected into (NZB x NZW)F1 mice. Only the protein-G binding material was active, indicating that the effect is mediated by autoantibodies or immune complexes in the synovial fluid. Further studies demonstrated that identical concentrations of protein obtained from a pool of normal human IgG or SF from seronegative RA and non-RA arthritides patients did not contain the same activity.

Animals↗
PubMed1976

Exfoliative cytology interpretation of synovial fluid in joint disease.

Criteria for the specific diagnoses of the several arthritides, on the basis of exfoliative cytology examination of fluids aspirated from diseased joints, were derived from examinations of 126 specimens of synovial fluid. They were screened cytologically and wholly on the basis of the cytological findings were classified into seven groups: rheumatoid arthritis, osteoarthritis, traumatic arthritis, gouty arthritis, Reiter's syndrome, pigmented villonodualr synovitis, and septic arthritis. The cytological features of each group appeared relatively constant and reproducible. Subsequent comparison of the clinical and cytological diagnoses showed excellent correlation.

Arthritis↗
PubMed1999

Relationship of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover: analyses of synovial fluid from patients with osteoarthritis.

OBJECTIVE: To determine the relationship between matrix metalloproteinases (MMPs), their inhibitors, and the turnover of matrix molecules in articular cartilage from patients with osteoarthritis (OA). METHODS: Synovial fluid samples were collected from the knees of 54 patients with OA. Radiographic evaluations and magnetic resonance imaging were performed on the knees of 34 OA patients to classify the stage of the disease. Biochemical analyses and immunoassays were used to measure the concentrations of MMP-1, MMP-3, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, the disaccharide of hyaluronic acid, the proteoglycan glycosaminoglycan disaccharides of chondroitin 4-sulfate (delta di-CS4) and chondroitin 6-sulfate (delta di-CS6), the 846 epitope on chondroitin sulfate of cartilage proteoglycan aggrecan (putative biosynthetic marker), the keratan sulfate (KS) epitope of aggrecan (putative degradation marker), and the C-propeptide of cartilage type II procollagen (CPII) (biosynthetic marker). RESULTS: The concentration of TIMP-1 was directly correlated with the levels of MMP-1 and MMP-3 (both were also correlated with each other), confirming earlier results. There was an inverse correlation between the delta di-CS6:delta di-CS4 ratio and the concentration of MMP-3. The level of delta di-CS6 was correlated with that of the KS epitope, and to a lesser degree, with that of the 846 epitope (the latter was also correlated with the level of delta di-CS4). The concentration of TIMP-1 correlated with that of the 846 epitope, whereas TIMP-2 levels correlated with those of CPII. There were significantly lower concentrations of delta di-CS6, delta di-CS4, the 846 epitope, and CPII in synovial fluid from patients with late-stage OA. CONCLUSION: These observations suggest a link between proteolysis and inhibitor concentrations in OA cartilage. Production of TIMPs appears to be individually linked to the synthesis of specific cartilage molecules. The reduction in the amount of cartilage-matrix structural components suggests that there is a measurable loss of cartilage in the late stages of the disease, as suggested previously. The resultant composition of the cartilage suggests that the loss may primarily involve "resident" molecules originally present in healthy cartilage.

Aged↗
PubMed1991

Elevation of a gamma delta T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis.

We examined the levels of TcR delta 1+ T cells (total gamma delta T cell) and delta TCS1+ (gamma delta T cell subset) T cells in the peripheral blood (PB) and synovial fluid (SF) of 16 patients with rheumatoid arthritis (RA) and compared them to the levels in PB of patients with Felty's syndrome (FS) and 21 healthy control subjects (NML). Synovial fluid from eight patients with seronegative spondyloarthropathies (SSA) was also examined. The results demonstrated elevated levels of the delta TCS1+ subset in the PB of RA and FS patients relative to NML (P less than 0.05). No such differences were observed in the levels of PB TcR delta 1+ T cells. The results did not appear to reflect a non-specific inflammatory response since delta TCS1 T cells were elevated in the SF of RA patients relative to SSA SF and NML PB. delta TCS1 T cells in SSA PB and SSA SF were comparable to NML PB. TcR delta 1+ T cells levels in RA SF were higher than SSA SF levels but were comparable to those of NML PB. Taken together, the results support a pathogenic role for delta TCS1+ T cells in RA.

Antibodies, Monoclonal↗
PubMedDate not supplied

Serum and synovial fluid inhibitors of antibody-mediated lymphocytotoxicity in rheumatoid arthritis and systemic lupus erythematosus.

Many sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) inhibit lymphocyte-dependent antibody cytotoxicity (LDAC). RA synovial fluids also inhibit LDAC. RA serum inhibition was present in high molecular weight and 5S serum fractions, whereas in SLE it was confined to 7S fractions. A correlation between rheumatoid factor activity and LDAC inhibition was noted, and there was some evidence for inhibition of SLE serum acting on effector cells. Inhibition in RA synovial fluid was found in both high molecular weight and very low molecular weight fractions (less than 4S.)

Adult↗
PubMed1999

Synovial fluid markers in osteoarthritis.

Exploration of the mechanisms responsible for breakdown and repair of articular cartilage in osteoarthritis has promoted interest in the potential use of cartilage-derived molecules as markers of cartilage metabolism in this disease. Many of the macromolecules detectable in synovial fluid have been evaluated as possible surrogate markers of the severity or activity of disease processes. Measurements of the synovial fluid concentration of any marker without due consideration of the fate of the molecule in the joint cavity are likely to be misleading and insufficient to cement a relationship between marker concentration and the severity of articular pathology.

Animals↗
PubMed1992

Synovial fluid analysis of two groups of proteoglycan epitopes distinguishes early and late cartilage lesions.

OBJECTIVE: To investigate whether fragmentation of proteoglycans in arthritis results in domains that have different levels of release from cartilage at different stages of the disease. METHODS: Two regions of the proteoglycan, the hyaluronan-binding region and the glycosaminoglycan-rich region of the core protein, were measured, by immunoassay, in knee joint synovial fluids of patients with rheumatoid arthritis or reactive arthritis. RESULTS: Synovial fluid concentrations of the glycosaminoglycan-rich region were highest in rheumatoid arthritis patients who had little cartilage damage as determined by radiography, whereas release of the hyaluronan-binding region predominated in patients with advanced cartilage destruction. In reactive arthritis, release of the glycosaminoglycan-rich region predominated. CONCLUSION: These findings indicate that the hyaluronan-binding region is initially retained in the tissue during the development of cartilage destruction. The combined analysis of these markers offers a new avenue for assessment of the degree of cartilage damage in arthritis.

Adult↗
PubMed2003

Gelatinase activity in synovial fluid and synovium obtained from healthy and osteoarthritic joints of dogs.

OBJECTIVE: To determine matrix metalloproteinase (MMP) activity in synovial fluid (SF) obtained from the joints of dogs with degenerative joint disease (DJD) secondary to various underlying conditions. SAMPLE POPULATION: 35 samples of SF obtained from 18 clinically normal (control) dogs and 34 samples of SF obtained from 17 dogs with DJD; dogs with DJD were from 2 populations (client-owned dogs and research dogs that had DJD secondary to the lysosomal storage disease mucopolysaccharidosis VII). PROCEDURE: MMP activity in samples of SF was semiquantitatively examined by use of gelatin or casein zymography. Western blot analysis was performed by use of antibodies for MMP-2 and MMP-9. In addition, in situ MMP activity was observed in sections of synovial membrane obtained from healthy and osteoarthritic joints. RESULTS: Samples of SF from osteoarthritic joints had higher MMP-2 activity and dramatically increased MMP-9 activity, compared with values for healthy joints. Substrate-overlay analyses indicated minimal gelatin-degrading activity in synoviocytes obtained from control dogs, whereas greater activity was seen in osteoarthritic synoviocytes, with additional activity in the underlying tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Higher MMP-2 activity and dramatic increases in MMP-9 activity were associated with the osteoarthritic state, even though MMP-2 activity was detected in healthy joints. This study expands information on MMP production in SF of osteoarthritic joints in other species and documents the similarity of MMP activity patterns regardless of the cause of DJD.

Animals↗
PubMed1994

[The test of the synovial fluid in microcrystalline joint diseases].

The search for crystals in the synovial fluid must be carried out promptly and is very helpful in the diagnosis of microcrystalline arthropathy. If at light microscopy the fluid is negative for crystals and negative or weakly positive for alizarin red, and if the diagnosis is nevertheless suspected, analysis of the centrifuged fluid sediment facilitates the identification of crystals and increases the specificity of alizarin red (the specific stain for crystals) in the identification of apatite crystal deposits. Electronmicroscopy can the be used to confirm the presence or absence of crystals.

Apatites↗