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PubMed1984

Metalloproteinases and collagenase inhibitors in rheumatoid synovial fluid.

The levels of metalloproteinases and metalloproteinase inhibitors were measured in rheumatoid synovial fluid. Reliable estimates of total enzyme and inhibitor levels in the synovial fluids were obtained only after hyaluronidase treatment and gel filtration. Three latent metalloproteinases were found which, after activation, degraded collagen, proteoglycan, and gelatin. These enzymes closely resembled the metalloproteinases secreted into connective tissue culture medium. In addition to alpha 2 macroglobulin, an Mr 30,000 collagenase inhibitor was detected which closely resembled the tissue inhibitor of metalloproteinase found in tissue culture medium.

Arthritis, Rheumatoid↗

PubMed2005

Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses.

OBJECTIVE: To examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels. METHODS: Eight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dosing and at 1 and 12 hours after dosing. Glucosamine was assayed by fluorophore-assisted carbohydrate electrophoresis. RESULTS: The maximum concentration of glucosamine in serum reached approximately 300 muM ( approximately 50 microg/ml) following IV dosing and approximately 6 microM (approximately 1 microg/ml) following NG dosing. Synovial fluid concentrations reached 9-15 microM with IV dosing and 0.3-0.7 microM with NG dosing, and remained elevated (range 0.1-0.7 microM) in most animals even at 12 hours after dosing. Following NG dosing, the median serum maximal concentration of 6.1 microM (range 4.38-7.58) was attained between 30 minutes and 4 hours postdose. The mean apparent volume of distribution was 15.4 liters/kg, the mean bioavailability was 5.9%, and the mean elimination half-life was 2.82 hours. CONCLUSION: Clinically relevant dosing of glucosamine HCl in this large monogastric animal model results in serum and synovial fluid concentrations that are at least 500-fold lower than those reported to modify chondrocyte anabolic and catabolic activities in tissue and cell culture experiments. We conclude that the apparent therapeutic benefit of dietary glucosamine on pain and joint space width in humans and animals may be secondary to its effects on nonarticular tissues, such as the intestinal lining, liver, or kidney, since these may be exposed to much high levels of glucosamine following ingestion.

Administration, Oral↗

PubMed1990

Substance P and arthritis: analysis of plasma and synovial fluid levels.

The uncadecapeptide substance P (SP), which is localized in peripheral and central terminals of afferent nerve fibers with polymodal nociceptors, has recently been implicated as having a neurogenic, inflammatory role in experimental arthritis. We used a radioimmunoassay to measure SP levels in plasma and synovial fluid samples from patients with rheumatoid arthritis (RA), osteoarthritis (OA), Reiter's syndrome (RS), and posttraumatic arthritis, as well as in plasma samples from 13 normal subjects. Plasma SP levels in RS patients exceeded levels in RA and OA patients, which in turn exceeded levels in posttrauma patients and in normal subjects. Synovial fluid SP levels exceeded respective plasma levels for all groups, except in RS patients, in whom the plasma level was not significantly different from that in synovial fluid. SP levels in synovial fluid of RA, OA, and RS patients did not differ significantly from each other, but the level in posttrauma patients was higher than in all other groups (P less than 0.005). These studies demonstrate localized intraarticular SP release, and significant plasma/synovial fluid SP concentration gradients in several forms of arthritis.

Arthritis↗

PubMed1998

Proinflammatory cytokines detectable in synovial fluids from patients with temporomandibular disorders.

OBJECTIVE: To measure the levels of the proinflammatory cytokines, interleukin (IL)-1 beta, IL-6, tumor necrosis factor- (TNF) alpha, IL-8, and interferon- (IFN) gamma in synovial fluid samples taken from patients with temporomandibular disorders (TMD). STUDY DESIGN: We studied 6 asymptomatic volunteers and 51 patients with TMD. The IL-1 beta, IL-6, TNF-alpha, IL-8, and IFN-gamma levels in temporomandibular joint synovial fluid were measured using enzyme-linked immunosorbent assay. RESULTS: Measurable level of at least one cytokine in the synovial fluid was found in 40 (64.5%) of 62 joints in the patients: IL-1 beta and IFN-gamma were each detected in 18 (29.0%) of 62 joints; IL-6 in 13 (21.0%) of 62 joints; IL-8 in 11 (19.3%) of 57 joints; and TNF-alpha in only 5 (8.1%) of 62 joints. None of these cytokines was detectable in the synovial fluid in the control group. Furthermore, there was a strong correlation between the detection of IL-1 beta and pain in the joint area. CONCLUSIONS: These data clearly demonstrate increased levels of several proinflammatory cytokines in certain patients with TMD and suggest that these cytokines may play a role in the pathogenesis of synovitis and degenerative changes of the cartilaginous tissue and bone of the temporomandibular joint.

Adolescent↗

PubMed2002

The heterogeneity of the glycosylation of alpha-1-acid glycoprotein between the sera and synovial fluid in rheumatoid arthritis.

Alpha-1-acid glycoprotein (AGP) is a plasma glycoprotein produced by the liver that undergoes increased production and altered glycosylation in several physiological and pathological conditions including rheumatoid arthritis. To date, although present in the synovial fluid of rheumatoid arthritis patients, there has been no evidence for the separate extra-hepatic production of AGP. This study indicates that there could be a localized production of AGP in rheumatoid synovial fluid by demonstrating that the glycosylation patterns of AGP differed between the serum and synovial fluid in the same rheumatoid patient. Serum AGP was largely composed of fucosylated tri- and tetra-antennary oligosaccharide chains while the synovial fluid contained mainly bi-antennary chains that were fucosylated to a lesser extent. This structural heterogeneity of glycosylation resulted in functional diversity; serum but not synovial AGP is able to inhibit binding to the cell adhesion molecule E-selectin through expression of antigen sialyl Lewis X.

Arthritis, Rheumatoid↗

PubMed1991

Determination of chromium, cobalt and molybdenum in synovial fluid by GFAAS.

An artificial knee joint made of a cobalt alloy (Cr 27-38%, Mo 5-7%, others 9%, Co balance) failed in an orthopaedic patient with severe tissue reaction. Samples of synovial fluid and blood were analyzed for cobalt, chromium and molybdenum concentration using graphite furnace atomic absorption spectrophotometry (GFAAS). NIST SRM 909 Human Serum containing 91.3 micrograms/L chromium was used as the Cr Standard. To obtain reliable values for cobalt and molybdenum, three different independent analytical methods were employed to analyze each sample: 1) dilution of the samples with Triton TX-100 solution, followed by GFAAS; 2) microwave decomposition of the samples, followed by GFAAS; 3) classic nitric-perchloric acid decomposition of the samples, followed by GFAAS. The two decomposition methods were used to control the accuracy of the dilution method. The results showed that the non-decomposition method gave comparable results to the decomposition techniques for analysis of synovial fluid and blood. The data revealed that the patient had elevated levels of Co, Cr and Mo in both synovial fluid and blood with the values being 2-3 orders of magnitude higher in the synovial fluid from the affected knee.

Chromium↗

PubMed1986

Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory joint disease.

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.

Adult↗

PubMed1996

Permeation from the synovial fluid as nutritional pathway for the anterior cruciate ligament in rabbits.

The anterior cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from synovial fluid. In order to quantitate the relative importance of these two routes and to compare the anterior cruciate ligament with the medial collateral ligament, we injected [3H]methyl-glucose as a tracer intravenously or directly into the knee in rabbits. Tracer concentrations in plasma, synovial fluid, the anterior cruciate ligament and the medial collateral ligament were analysed by a pharmacokinetic compartment model developed for this study. The contribution of [3H]methyl-glucose permeation from the synovial fluid was calculated at 59.7% in the anterior cruciate ligament and at 18.1% in the medial collateral ligament. We concluded from these results that the nutrition for the medial collateral ligament, which is an extraarticular structure, is provided mainly by its vascular supply. In contrast, synovial fluid permeation is an important transport route for small molecules for the normal anterior cruciate ligament.

Animals↗

PubMed2002

Secretory phospholipases A2 induce cytokine release from blood and synovial fluid monocytes.

Secretory phospholipases A2 (sPLA2) are released in the blood of patients with various inflammatory diseases and exert proinflammatory activities by releasing arachidonic acid (AA), the precursor of eicosanoids. We examined the ability of four sPLA2 to activate blood and synovial fluid monocytes in vitro. Monocytes were purified from blood of healthy donors or from synovial fluid of patients with rheumatoid arthritis by negative immunoselection and by adherence to plastic dishes, respectively. The cells were incubated with group IA, IB, IIA and III sPLA2 and the release of TNF-alpha, IL-6 and IL-12 was determined by ELISA. Group IA, IB and IIA sPLA2 induced a concentration-dependent release of TNF-alpha and IL-6 from blood monocytes. These sPLA2 activated IL-12 production only in monocytes preincubated with IFN-gamma. Group IA and IIA sPLA2 also induced TNF-alpha and IL-6 release from synovial fluid monocytes. TNF-alpha and IL-6 release paralleled an increase in their mRNA expression and was independent from the capacity of sPLA2 to mobilize AA. These results indicate that sPLA2 stimulate cytokine release from blood and synovial fluid monocytes by a mechanism at least partially unrelated to their enzymatic activity. This effect may concur with the generation of AA in the proinflammatory activity of sPLA2 released during inflammatory diseases.

Animals↗

PubMed1995

Diagnostic value of synovial fluid analysis in children with reactive arthritis.

We report on three children with pauciarticular arthritis in whom the clinical picture and serology were compatible with both arthritis reactive to infection with Yersinia or Salmonella and with Lyme arthritis. Results of analysis of synovial fluid by polymerase chain reaction for enterobacterial or borrelial sequences were negative. Immunofluorescence with specific antibodies revealed the presence of amorphous enterobacterial antigens in synovial fluid cells. Since this staining did not reveal enterobacterial morphology, we infected synovial fluid cells of two children with juvenile rheumatoid arthritis in vitro with Yersinia or Salmonella. After 24 h typical rods were observed, but after about 1 week amorphous antigen similar to what had been found in the three patients was seen. In cases of reactive arthritis with ambiguous results of serological testing the diagnosis may be confirmed by demonstration of enterobacterial antigens in synovial fluid.

Adolescent↗

PubMed1975

Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis.

Twenty patients with definite or classical rheumatoid arthritis and chronic knee effusions were each given an oral dose of 4 g benorylate as the 40% suspension. Synovial fluid and plasma samples were obtained up to 9 hours after drug administration and assayed for their salicylate and benorylate content. A mean peak benorylate plasma level of 2.18 +/- 0.19 mug/ml occurred 30 min after drug administration but declined rapidly and benorylate was virtually undetectable in the plasma 90 min later. The mean peak benorylate synovial fluid level of 0.74 +/- 0.21 mug/ml occurred 3 hours after drug administration but the concentration remained steady for at least a further 9 hours. A mean peak plasma salicylate level of 119 +/- 14.2 mug/ml and mean peak synovial fluid salicylate level of 78 +/- 13.6 mug/ml occurred 3 hours after benorylate administration. Both levels declined slowly over some hours. This study shows that benorylate per se readily enters the synovial fluid in patients with rheumatoid arthritis and continues to accumulate there even when undetectable in the plasma. It is possible that the lipophilic nature of the benorylate molecule facilitates its uptake by the inflamed synovial tissue.

Arthritis, Rheumatoid↗

PubMed1994

Soluble interleukin-2 receptor in sera and synovial fluids of rheumatoid patients: correlations with disease activity.

The measurement of serum soluble interleukin-2 receptor (sIL-2R), a sensitive marker of lymphocyte activation, has been proposed as an indicator of disease activity and "outcome" in patients with inflammatory diseases characterized by the activation of immune cells. Serum sIL-2R levels have been reported higher in rheumatoid patients than in controls. Using an enzyme-linked immunoabsorbent assay (ELISA), we evaluated soluble IL-2R levels in the serum of 34 patients with RA and in the synovial fluid of 25 of these patients and we compared it with levels found in the serum of 13 healthy controls. Serum sIL-2R levels were significantly elevated in RA patients compared with the healthy age-matched control group (P < 0.005). The mean level of soluble IL-2R in synovial fluids was significantly higher than the mean sera levels in RA patients (P < 0.0001). Moreover, we examined the correlation between serum and synovial fluid sIL-2R levels and disease activity measures. Serum sIL-2R correlated only with ESR (P < 0.04). The synovial fluid sIL-2R correlated with ESR (P < 0.02) and a visual analogue scale (VAS) pain score (P < 0.04). Both serum and synovial fluid sIL-2R levels correlated with the chronic arthritis systemic index (CASI; P < 0.04 and P < 0.005, respectively). Our data suggested that in RA the measurement of sIL-2R may certainly mirror the degree of chronic inflammation and the continuous activation of the immune cells in the joint, although the role of this molecule in the immune response is still unclear.

Adult↗

PubMed2003

The presence of bacteria in the synovial fluid of the temporomandibular joint and clinical significance: preliminary study.

PURPOSE: The objective of this study was to find any relation between the presence of specific bacterial species in the synovial fluid of the temporomandibular joint (TMJ) and clinical parameters. PATIENTS AND METHODS: We studied 43 patients (male-to-female ratio, 1:1.69; average age, 34.37 +/- 14.55 years). Thirty-three patients had a displaced disc in the TMJ (DD group), and 10 patients did not have a displaced disc of the TMJ or any symptom related to TMJ disorders (NDD group). Clinical examinations were made to determine maximum mouth opening, joint sounds, previous trauma history, systemic disease, and TMJ pain. Six bacterial species that were reported in other studies were chosen to evaluate the presence of bacteria in the TMJ for this study. RESULTS: Mycoplasma genitalium was most frequently detected in synovial fluid (86.0%). Staphylococcus aureus, Mycoplasma fermentans/orale, Actinobacillus actinomycetemcomitans, and Streptococcus mitis were detected in 51.2%, 37.2%, 25.6%, and 7.0% of samples, respectively. beta-Hemolytic Streptococcus was not detected. The prevalence of S aureus was significantly higher in the DD group than in the NDD group (P <.05). The patients who had M. fermentans/orale were 5.40 times more likely to be younger than 30 years than were those without M. fermentans/orale (P <.05). Those with M. genitalium were 5.81 times more likely to be female than were those without M. genitalium (P <.05). CONCLUSION: The presence of S. aureus in TMJ synovial fluid was related to TMJ disorder symptoms and clinical parameters seemed to be influenced by bacterial presence in TMJ synovial fluid.

Adult↗

PubMed1986

Functional capacities of T lymphocyte subsets from synovial fluid and blood in rheumatoid arthritis.

A reverse haemolytic plaque forming cell (PFC) assay was employed to analyse the impact of T suppressor/cytotoxic and T helper cells on B cell function in 10 patients with rheumatoid arthritis (RA). In all cases T8-enriched cells from synovial fluid and blood suppressed the pokeweed mitogen (PWM) induced IgM, IgG, and IgA secretion by autologous lymphocytes to the same degree. The suppression was partly abolished by irradiation of T8-enriched cells. T4-enriched cells from blood increased the PWM induced Ig secretion by autologous blood B cells. In six of 10 patients responses 1.2 to four times higher were obtained with T4-enriched cells from synovial fluid, but in four of 10 patients synovial fluid T4-enriched cells did not increase the PWM responses of blood B cells. T4- and T8-enriched T cells from synovial fluid comprised more Ia+ cells than did T cells from blood (36% v 3% and 43% v 6%). Ia+ T helper and suppressor/cytotoxic cells may modulate in vivo activation of synovial B cells in RA.

Arthritis, Rheumatoid↗

PubMed2000

Hyaluronan in synovial fluid of patients with loose total hip prosthesis. Comparison with hyaluronan in patients with hip osteoarthritis and idiopathic osteonecrosis of femoral head.

The concentration and molecular weight of hyaluronan (HA) in the synovial fluid of the hip joint were determined in 13 patients (aged 62.8 +/- 9.4 years) who had undergone prior total hip arthroplasty(THA), 23 patients (aged 65.0 +/- 8.2 years) with osteoarthritis of the hip joint (OA), and 13 patients (aged 40.2 +/- 2.7 years) with idiopathic osteonecrosis of the femoral head (ION). A sample of synovial fluid was obtained during revision THA because of loosening of the total hip prosthesis for the THA group, and during the first replacement surgery or osteotomy for the OA and ION groups. The concentration of HA in the synovial fluid was 0.64 +/- 0.42 mg/ml in the THA group, 1.07 +/- 0.28 mg/ml in the OA group, and 1.30 +/- 0.56 mg/ml in the ION group. The concentration of HA in the synovial fluid of the THA patients was significantly lower than that of the OA and ION patients (P = 0.0156 vs OA, P = 0.003 vs ION). The molecular weight of HA was 309 +/- 88.3 x 10(4) Da in the THA group, 377 +/- 201 x 10(4) Da in the OA group, and 240 +/- 148 x 10(4) Da in the ION group; these values do not differ significantly (P = 0.259 vs OA, P = 0.174 vs ION). Among the THA patients, there was no relation between the concentration of HA and the age of the patient, length of time since the first operation, or type of prosthesis fixation; there was also no relation between the molecular weight of HA and each of these factors. These results suggest that a pseudosynovial membrane is regenerated after THA, and that it produces HA of the same molecular weight as that in patients with OA and ION, although in smaller quantities.

Adult↗

PubMed1985

[The role of protein and hyaluronic acid in the synovial fluid in animal joint lubrication].

The purpose of this investigation was to study the role of protein and hyaluronic acid of synovial fluid in the animal joint lubrication. The D-fraction (0.2 micron up to 0.8 micron) from the bovine synovial fluid showed the lowest friction coefficient and contained about 20% protein and 70% hyaluronic acid of the synovial fluid. Protein but not hyaluronic acid of this fraction had lubricating ability, and the protein but not hyaluronic acid could support the lubricating film thickness. By electron microscopic observation hyaluronic acid was 2,000A-5,000A formless mass and the protein complex that had lubricating ability was 200A-300A spherical particle. Through these results I presume that hyaluronic acid enclose the spherical protein particles in its network like a cage of the roller-bearing and the particles can rotate freely like rolling elements of the roller-bearing. It was suggested that the roller-bearing mechanism was performed along with elastohydrodynamic lubrication in animal joint.

Animals↗

PubMed2002

Importance of proinflammatory cytokines in synovial fluid from 121 joints with temporomandibular disorders.

The concentrations of cytokines were measured by an ELISA in the synovial fluid from 117 patients with temporomandibular disorders (TMD) and correlated with degenerative changes of the condyle and clinical symptoms.Fifty-seven patients had degenerative changes of the condyle. The fluid from seven healthy volunteers was used as controls. The concentrations of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly higher in the synovial fluid of patients than controls (P<0.05). The concentration of IL-6 was significantly higher in the patients with degenerative changes than in other patients (P<0.05). The detection of IL-8 correlated with the concentrations of IL-6 and TNF-alpha. However, there was no correlation between the concentrations of any cytokines and symptoms. In conclusion, the cytokines in the synovial fluid may participate in the pathogenesis of TMD. In particular, IL-6 is important and may be associated with the development of osteoarthritis.

Adult↗

PubMed1983

[Comparative elimination of pirprofen from the plasma and synovial fluid of the knee. 26 cases].

Twenty-six patients with various inflammatory diseases of the knee were treated with a 400 mg dose of pirprofen orally twice a day for 2 days. On the third day, samples of blood and synovial fluid were taken 3 h and 10 h approximately after a fifth 400 mg dose of the drug. Pirprofen concentrations, as determined by gas-liquid chromatography, were higher in plasma than in synovial fluid during the 2-5 h period post-dosing. They decreased with an elimination half-life of 6 h in plasma as against 41 hours in synovial fluid. This study demonstrates that pirprofen diffuses into the synovial fluid where it remains significantly longer than in plasma.

Adolescent↗