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[Primary Neisseria meningitidis arthritis of the knee without meningitis: contribution of synovial fluid culture in blood-culture vial].

INTRODUCTION: Primary meningococcal arthritis is a rare form of meningococcal disease. It occurs as an isolated acute purulent arthritis without meningitis, and presence of Neisseria meningitidis in articular fluid. We report a new case of typical primary meningococcal arthritis. EXEGESIS: A previously healthy 23-year-old female patient was admitted for purpuric lesions of the legs. At admission, conscience was normal and symptoms of meningitis were absent. During the 2nd day of hospitalisation, a warm and painful effusion in the right knee appeared. Aspiration from the right knee yielded a purulent fluid. N. meningitidis was isolated from a blood-culture vial inoculated with the synovial fluid, while blood cultures remained sterile. Anti-biotherapy was initiated as soon as microbiological diagnosis was established. The patient was symptom-free 1 month later. CONCLUSION: We emphasize the fact that agar cultures of the synovial fluid remained sterile, while N. meningitidis grew in a blood-culture vial. We suggest that diagnosis of primary meningococcal arthritis may be underestimated when inappropriate culture media are used.

Adult↗

BINDING OF AN ALPHA GLOBULIN TO HYALURONATEPROTEIN IN PATHOLOGICAL SYNOVIAL FLUIDS.

Rabbits were immunized with hyaluronateprotein isolated from normal or pathological synovial fluids. Immunoelectrophoresis of hyaluroni-dase-digested pathological hyaluronateprotein and its antiserum showed a single precipitin arc extending through both alpha globulin zones. Digested normal hyaluronateprotein formed no lines with either its antiserum or with that to pathological hyaluronateprotein. The antigenic component present in pathological hyaluronateprotein formed a reaction of complete fusion with a serum protein which was identified by immunoelectrophoresis as an alpha globulin.

Alpha-Globulins↗

Pokeweed mitogen-induced secretion of IgG- and IgM-rheumatoid factors by synovial fluid and blood B lymphocytes in rheumatoid arthritis.

Lymphocytes from patients with rheumatoid arthritis (RA) were assayed for their ability to secrete Ig and rheumatoid factors (RF) upon polyclonal activation in vitro. B lymphocytes secreting IgM-RF and IgG-RF were enumerated using hemolytic plaque forming cell (PFC) assays. The sensitivity of RF-PFC formation was similar to that of a reverse PFC assay detecting all cells secreting Ig. Blood mononuclear cells from RA patients generated a median of 12 IgM-RF and 15 IgG-RF-secreting cells/10(6) after 6 days culture with pokeweed mitogen (PWM). Thus a median of approximately 0.5% of IgM- and IgG-secreting cells were identified as RF-PFC. Synovial fluid B lymphocytes co-cultured with autologous blood T lymphocytes in the presence of PWM generated higher numbers of RF-secreting cells; medians of 43 IgM-RF and 441 IgG-RF secreting cells/10(6) were found. Thus, 8-9% of IgM- and IgG-secreting cells from synovial fluid were identified as RF-PFC. In co-cultures containing synovial fluid T cells, PWM-induced RF secretion was low. The data indicate that both blood and SF B cells have the potential for RF secretion.

Antibody Formation↗

Effects of bee venom on protease activities and free radical damages in synovial fluid from type II collagen-induced rheumatoid arthritis rats.

The effect of bee venom acupuncture (BVA) (api-toxin) on the development of type II collagen (CII)-induced arthritis (CIA) in rats has been studied. We have compared the levels of activity of a comprehensive range of cytoplasmic, lysosomal and matrix protease types, together with the levels of free radical-induced protein damage (determined as protein carbonyl derivative) in synovial fluid from CIA-treated, BVA-treated and normal rats. Many protease types showed significantly increased activity in CIA compared with normal rats. BVA (5 and 10 microl/100g) significantly reduced these enzyme activities by some 80% each, but levels of plasma proteases activity (including those enzyme types putatively involved in the immune response, such as dipeptidyl aminopeptidase IV and proline endopeptidase) in CIA, BVA (5 microl/100g)-treated and normal plasma samples were not significantly different. The level of free radical induced damage to synovial fluid proteins was approximately three-fold higher in CIA compared with normal rats. However, BVA (5 microl/100g) significantly decreased the level of reactive oxygen free radical species (ROS) induced oxidative damage to synovial fluid proteins. It was concluded that activation of proteolytic enzymes and free radicals are likely to be of equal potential importance as protein damaging agents in the pathogenesis of rheumatoid arthritis (RA), and the development of novel therapeutic strategies for the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of enzymatic mechanistic types (cysteine, serine, metallo proteinases and peptidases). In conclusion, BVA is considered to be an effective RA modulator, inhibiting protease activities and removing ROS.

Acupuncture↗

Properties of beta-glucuronidase activity in human synovial fluid.

The purpose of the present study was to evaluate the properties of beta-glucuronidase (EC 3.2.1.31) in human synovial fluid. It was shown to have a pH requirement of 5.0 and a KM value of about 8.0 - 10(-3) M using phenolphthalein beta-glucuronide as the substrate. At low substrate concentration an endogenous inhibitor is demonstrable. The inhibition is of the competitive type and is removed by proteolytic digestion of synovial fluid, whereas hyaluronidase digestion and addition either of Triton X-100 or of various salts to the assay mixture, are ineffective. The possibility that the inhibitor is a protein from serum is discussed.

Animals↗

Enantiospecific pharmacokinetics of ketoprofen in plasma and synovial fluid of horses with acute synovitis.

Pharmacokinetic parameters were established for enantiomers of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (KTP) administered as the racemic mixture at a dose of 2.2 mg/kg and as separate enantiomers, each at a dose of 1.1 mg/kg to a group of six horses (five mares and one gelding). A four-period cross-over study in a LPS-induced model of acute synovitis was used. After administration of the racemic mixture S(+)KTP was the predominant enantiomer in plasma as well as in synovial fluid. Unidirectional inversion of R(-) to S(+)KTP was demonstrated but the inversion was less marked than previously reported. It is suggested that this reduction could be because of the influence of the inflammatory reaction on hepatic metabolism. The disposition of KTP enantiomers after administration of the racemic mixture was similar to those observed after administration of S(+) and R(-)KTP. The S(+) and R(-)KTP concentrations in synovial fluid were low and short lasting. After administration of R(-)KTP significant concentrations of the optical antipode were detected in synovial fluid.

Acute Disease↗

N-terminal procollagen peptide and beta 2-microglobulin in synovial fluids from inflammatory and non-inflammatory joint diseases.

The concentrations of NH2-terminal procollagen peptide were determined radioimmunologically in synovial fluids from inflammatory and non-inflammatory joint diseases. The mean concentrations +/- SD were 1.39 +/- 0.77 and 1.13 +/- 0.63 mg/l and, hence, did not reveal significant differences. Compared with serum, peptide levels in synovial fluids are 10(3) times higher. No statistical correlation was found between procollagen peptide levels and the concentrations of beta 2-microglobulin, a suggested parameter of disease activity, and other established indicators (total protein, total and differential cell count) of inflammatory activity.

Arthritis↗

Expression of cytolytic mediators by synovial fluid lymphocytes in rheumatoid arthritis.

To understand the role of cytolytic lymphocytes in the pathogenesis of rheumatoid arthritis, we investigated the expression of lymphocyte cytotoxicity mediators, perforin, and serine esterases, in lymphocytes derived from the synovial fluid of 15 patients with rheumatoid arthritis. Previous work has shown that CD8+ lymphocytes that possess markers of activation appear to be present in rheumatoid arthritis (RA). By means of in situ hybridization techniques and immunohistochemical analysis, the authors show that perforin and two serine esterases (serine esterase 1/Hanukah factor/granzyme A, and serine esterase 2/granzyme B) are expressed by subpopulations of CD8+ and CD56+ lymphocytes obtained from synovial fluid. The presence of these cytotoxic mediators suggests a possible mechanism for tissue damage, and provides evidence implicating cytolytic lymphocytes in the pathogenesis of RA.

Arthritis, Rheumatoid↗

Analysis by high-performance gel permeation chromatography of hyaluronic acid in animal skins and rabbit synovial fluid.

The simultaneous analysis of the molecular weight and concentration of hyaluronic acid in biological samples using high-performance liquid chromatography with two gel permeation columns is described. The elution volumes of various molecular weights of hyaluronic acids were linearily related to the logarithms of their molecular weights up to 600,000. The concentration of hyaluronic acid could be determined in the range from 20 to 100 micrograms/ml, i.e., from 4 to 20 micrograms per 200 microliter injected. The method was applied to the analysis of several animal skin extracts and rabbit synovial fluid. Skin extracts from mouse, rat, guinea-pig and rabbit could be chromatographed without prior isolation and purification. Hyaluronic acids in skin were separated clearly from chondroitin sulphates and their concentrations were determined. The molecular weights were estimated simultaneously to be more than 10(6). Rabbit synovial fluids from intact joints and saline- and carrageenin-treated joints could be chromatographed directly. The chromatograms showed that the concentration of hyaluronic acid in carrageenin-treated synovial fluid is lower than that in saline-treated fluid and the molecular weight distribution is broader. This technique enabled the rapid analysis of hyaluronic acid present at low levels in biological samples.

Animals↗

Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides.

Thirty-five synovial fluid (SF) specimens were examined for the presence of mast cells and for their histamine content. Mast cells were seen in SF cells from 27 of 35 fluids, and histamine was measurable in 19 of 34. There was a strong correlation between mast cell number and histamine content. No consistent relationship was found between either the mast cell number or histamine level and the patients' diagnoses, except that the 2 patients with systemic mastocytosis had markedly elevated values for both SF mast cell number and histamine content. SF mast cells from one of the mastocytosis patients were studied for histamine release; significant amounts of histamine were released upon exposure to anti-human IgE, but not compound 48/80. Thus, mast cells similar to those present in connective tissue are frequently present in SF in numbers which correlate with SF histamine levels. These mast cells contain active proteases and are capable of degranulation. Mast cells were consistently present in large numbers in the SF of patients with systemic mastocytosis, but their numbers were highly variable in fluids of patients with other diseases.

Adult↗

Three-dimensional structures of human phospholipase A2 from pancreas and synovial fluid by model building.

Three-dimensional structures of the enzyme phospholipase A2 (PLA2) from human pancreas and from human synovial fluid were constructed by model building based on high-resolution X-ray crystallographic structures and homology considerations. The structure of the human pancreatic PLA2 was based on the X-ray structure of the highly homologous bovine pancreatic PLA2 (Type I) by amino acid substitution and modification of the C-terminal part followed by geometry relaxation. The structure of the PLA2 from human synovial fluid was constructed from the X-ray structure of PLA2 from Crotalus atrox (Type II) by modification of the calcium binding loop, amino acid substitution, and insertion of two additional amino acid residues followed by geometry relaxation. The structure of the two human PLA2's have been compared and their use as targets for rational design of enzyme inhibitors discussed.

Amino Acid Sequence↗

Synovial fluid chondroitin sulphate epitopes 3B3 and 7D4, and glycosaminoglycan in human knee osteoarthritis after exercise.

OBJECTIVE: Walking exercise alleviates some symptoms, such as pain, in patients with mild to moderate knee osteoarthritis (OA). However, a major concern is that weightbearing exercise on osteoarthritic joints may exacerbate articular cartilage degradation. Loading of proteoglycan depleted articular cartilage in vitro increased expression of the chondroitin sulphate epitope 3B3, suggesting that loading may influence metabolism of osteoarthritic cartilage. This study aimed at evaluating the effects of walking exercise on articular cartilage metabolism in patients with knee OA, as reflected by changes in concentrations of synovial fluid markers. METHODS: Thirty elderly patients with knee OA (Kellgren-Lawrence grades II to IV) were randomly allocated to control (n = 15) and 12 week exercise (n = 15) groups. Synovial fluid obtained from 21 of the patients at time zero and after 12 weeks was examined by enzyme linked immunosorbent assay (ELISA) for the chondroitin sulphate epitopes 3B3 and 7D4, and by a dye binding assay with 1, 9-dimethylmethylene blue for total sulphated glycosaminoglycan (GAG) concentrations. The 3B3/GAG and 7D4/GAG ratios were calculated. RESULTS: No significant changes in concentrations of 3B3, 7D4, GAG, 3B3/GAG, or 7D4/GAG between time zero and 12 weeks were found in either group. However, there were significant declines in 3B3 (p=0. 001), GAG (p=0.007), and the 3B3/GAG ratio (p=0.049) with aging. CONCLUSION: Twelve weeks of walking exercise had no demonstrable adverse effects on articular cartilage metabolism, as reflected by the concentrations of synovial fluid GAG or the chondroitin sulphate epitopes 3B3 and 7D4.

Aged↗

The ordinary light microscope: an appropriate tool for provisional detection and identification of crystals in synovial fluid.

To determine if the ordinary light microscope is a useful tool in the detection and identification of crystals in synovial fluid 63 fluids (13 with monosodium urate (MSU), 14 with calcium pyrophosphate dihydrate (CPPD), one with both types of crystal, and 35 without crystals) were examined blindly by two observers, first with an ordinary light microscope, then with a polarising light microscope. Tentative identification of the crystals by their shape was attempted. The sensitivity of the ordinary light microscope for the detection of crystals was 96.2% and 100%, with specificity of 100% and 97.1% for observers 1 and 2, both with respect to the polarising light microscope. The concordance between observers for the ordinary light microscope was chi = 0.90 (0.897, 0.902) and for the polarising light microscope chi = 0.96 (0.958, 0.961). The specificity for identification of MSU and CPPD crystals by their shape with respect to the polarising light microscope was 92.3% and 85.7% for observers 1 and 2. When a polarising light microscope is not available examination of synovial fluid by an ordinary light microscope may allow a provisional diagnosis; definitive identification of the crystals requires a polarising light microscope.

Crystallization↗

In vivo effects of carprofen, deracoxib, and etodolac on prostanoid production in blood, gastric mucosa, and synovial fluid in dogs with chronic osteoarthritis.

OBJECTIVE: To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis. ANIMALS: 8 dogs with chronic unilateral osteoarthritis of the stifle joint. PROCEDURE: Each dog received carprofen, deracoxib, or etodolac for 10 days with a 30- to 60-day washout period between treatments. On days 0, 3, and 10, prostaglandin (PG) E2 concentrations were measured in lipopolysaccharide-stimulated blood, synovial fluid, and gastric mucosal biopsy specimens; PGE1 concentrations were measured in gastric mucosal biopsy specimens; and thromboxane B2 (TXB2) was evaluated in blood. RESULTS: Carprofen and deracoxib significantly suppressed PGE2 concentrations in blood at days 3 and 10, compared with baseline, whereas etodolac did not. None of the drugs significantly suppressed TXB2 concentrations in blood or gastric PGE1 synthesis at any time point. All 3 drugs significantly decreased gastric synthesis of PGE2 at day 3 but not day 10 of each treatment period. All 3 drugs decreased synovial fluid PGE2 concentrations in the affected and unaffected stifle joints at days 3 and 10. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1-sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets. Etodolac also appears to be COX-1 sparing but may have variable effects on COX-2 depending on the tissue. In gastric mucosa and synovial fluid, there were no significant differences in PG production between compounds at recommended concentrations.

Animals↗

Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) consists of a heterogeneous group of disorders with, for the most part, an unknown immunopathogenesis. Although onset and disease course differ, the subtypes of JIA share the occurrence of chronic inflammation of the joints, with infiltrations of immunocompetent cells that secrete inflammatory mediators. OBJECTIVE: To identify a panel of cytokines specifically related to the inflammatory process in JIA. METHODS: Using a new technology, the multiplex immunoassay, 30 cytokines were measured in plasma of 65 patients with JIA, of which 34 were paired with synovial fluid. These data were compared with plasma of 20 healthy controls and 9 patients with type I diabetes, a chronic inflammatory disease. RESULTS: Patients with JIA had, irrespective of their subclassification, significantly higher levels of tumour necrosis factor alpha, macrophage inhibitory factor (MIF), CCL2, CCL3, CCL11, CCL22 and CXCL9 in plasma than controls. In paired plasma and synovial fluid samples of patients with JIA, significantly higher levels of interleukin (IL)6, IL15, CCL2, CCL3, CXCL8, CXCL9 and CXCL10 were present in synovial fluid. Cluster analysis in all patients with JIA revealed a predominant pro-inflammatory cytokine cluster during active disease and a regulatory/anti-inflammatory-related cytokine cluster during remission. Whether a discrimination profile of various cytokines could help in the determination of disease classification was tested. CONCLUSION: It is suggested that several cytokines (IL18, MIF, CCL2, CCL3, CCL11, CXCL9 and CXCL10) may correspond to the activation status during inflammation in JIA and could be instrumental in monitoring disease activity and outcomes of (new) immunotherapies.

Adolescent↗

Tumor necrosis factor alpha and interleukin 1 beta in synovial fluid of infants and children with suppurative arthritis.

Tumor necrosis factor alpha and interleukin 1 beta concentrations were measured in synovial fluid of 24 infants and children with diagnoses of suppurative arthritis (n = 16) and other kinds of arthritis (n = 8). Large concentrations of tumor necrosis factor alpha (range, 100 to 85,000 pg/mL) were found in 12 (75%) of 16 patients with bacterial infection and in none of the patients with noninfectious origins. Large concentrations of interleukin 1 beta (greater than 200 pg/mL) were found in 15 (94%) of 16 patients with bacterial infection and in none of the other patients. In the latter group, small concentrations of interleukin 1 (range, 40 to 120 pg/mL) were present in 5 (63%) of 8 patients. Serum samples obtained simultaneously were negative for both cytokines. Tumor necrosis factor alpha and interleukin 1 beta concentrations correlated significantly and with leukocyte counts in synovial fluid. We conclude that large concentrations of tumor necrosis factor alpha and interleukin 1 beta are produced locally in patients with suppurative arthritis and they may be potentially useful in differentiating this condition from other kinds of arthritis.

Adolescent↗

Difference in cartilage proteoglycan level in synovial fluid in early rheumatoid arthritis and reactive arthritis.

Cartilage proteoglycans were measured, by the use of an enzyme-linked immunosorbent assay, in synovial fluids obtained from 109 unselected patients attending an outpatient rheumatology clinic because of inflammation of the knee. The content of proteoglycans in synovial fluid was inversely related to the degree of joint destruction shown on X-ray. The proteoglycan concentrations in knee-joint exudates were higher in patients with reactive arthritis than in patients with rheumatoid arthritis having synovitis of corresponding duration and lacking radiological evidence of cartilage destruction. The measurement of proteoglycan levels may therefore be useful in differentiating between the two conditions.

Arthritis↗