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PubMed1988

Synovial fluid lactic acid in acute and chronic pyrophosphate arthropathy and in osteoarthritis.

A comparison of synovial fluid lactate levels has been made in cases of chronic pyrophosphate arthropathy (PA) with and without joint destruction, acute PA and osteoarthritis. No statistically significant difference could be observed between results of chronic PA and osteoarthritis. By contrast, synovial fluid lactate levels were significantly higher in acute PA in comparison with the two other groups. These data suggest that hypoxia is unlikely to play a role in destructive arthropathy commonly found in chronic PA.

Acute Disease↗
PubMed2004

Effects of different hyaluronic acid products on synovial fluid levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee osteoarthritis.

The aim of this study was to evaluate the effects of different hyaluronic acid (HA) forms on synovial fluid levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the treatment of patients with knee osteoarthritis (OA). Forty patients were randomly assigned to 2 groups that were treated with native sodium hyaluronate (group I) or cross-linked hylan G-F 20 (group II). Clinical evaluations and synovial fluid aspirations were performed before the 1st injection (baseline), the 2nd injection (week 1), the 3rd injection (week 2), and at 1 week after the 3rd injection (week 3). Synovial fluid levels of both ICAM-1 and VCAM-1 were significantly reduced at weeks 1 to 3, compared to the baseline values. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index was used for clinical evaluations; the WOMAC pain score and physical function score were progressively improved at weeks 1 to 3 in both groups; the WOMAC stiffness score was significantly improved at week 3 in both groups. No significant differences were noted between the 2 treatment groups in respect to ICAM-1 levels, VCAM-1 levels, WOMAC pain score, stiffness score, or physical function score at any time. The decreased ICAM-1 and VCAM-1 levels after intra-articular HA injection may help to explain the anti-inflammatory effects of HA therapy in knee OA.

Aged↗
PubMed2006

Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis ?

Leptin is an adypocyte derivated peptide hormone that plays a major role in preventing obesity development by the effects at the hypothalamic level. In our study leptin levels of 41 rheumatoid arthritis (RA) patients and 25 healthy subjects as control group were assessed. Synovial fluid from 21 RA patients were collected to detect leptin levels. Synovial fluid and plasma leptin levels were analysed and correlated with RA duration, ESR, CRP, X ray changes (erosive or non-erosive disease) and negative or positive test for rheumatoid factor. There wasn't any significant difference at plasma leptin levels between RA patients (3.91 +/- 6.15) and control group (4.94 +/- 6.44) (p > 0.05). Plasma leptin levels were correlated with body mass index (BMI) in both healthy subjects and RA patients (r = 0.37; p = 0.018). Therefore in RA patients, plasma and synovial fluid leptin levels were not correlated with disease duration, ESR, CRP, negative or positive test for rheumatoid factor and erosive or non-erosive disease (p > 0.05). In conclusion leptin is correlated with BMI both in RA patients and healthy individuals but no considerable relation with disease activity.

Adult↗
PubMed1993

Changes in synovial fluid N-acetyl-beta-glucosaminidase activity in the human temporomandibular joint with dysfunction.

beta-Glycosidases (N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucuronidase) were assayed in temporomandibular joint (TMJ) synovial fluid obtained from 23 patients with closed lock TMJ internal derangement (ID), four with closed-lock TMJ osteoarthritis (OA), and 13 with normal controls (N). Synovial fluid was collected from the upper joint space after injecting 1.5 ml of 1% lidocaine three times. The specific activity of N-acetyl-beta-glucosaminidase increased significantly both with ID (p < 0.01) and with OA (p < 0.001), along with increases in the activity of N-acetyl-beta-galactosaminidase (p < 0.05 with ID and p < 0.01 with OA) and in beta-glucuronidase (p < 0.05 both with ID and OA). The N-acetyl-beta-glucosaminidase activity with OA was also significantly higher (p < 0.001) than with ID. These findings suggest that N-acetyl-beta-glucosaminidase activity in the TMJ synovial fluid reflects the degree of TMJ dysfunction.

Acetylglucosaminidase↗
PubMed1995

Production of PAF-acether by synovial fluid neutrophils in rheumatoid arthritis.

PAF-acether (PAF) is a pro-inflammatory phospholipid molecule potentially involved in the pathogenesis of arthritis. PAF and related metabolites have been isolated in the synovial fluid from patients with arthritis. The aim of this study was to determine fluid and blood in patients with rheumatoid arthritis. Blood neutrophils from normal donors were also studied for their capacity to form PAF. Neutrophils were stimulated with the calcium ionophore A23187 (2 microM) for 1 to 60 min. PAF released in the medium and PAF associated to cells were measured. In synovial fluid neutrophils. PAF production began as soon as 1 min of stimulation (16.1 +/- 6.3 pmol per 1 x 10(6) cells) and reached a maximum at 20 min: 29.2 +/- 2.8 pmol per 1 x 10(6) cells (mean +/- SEM, n = 5). The amount of PAF released in the supernatant increased with the length of stimulation, similar amounts of PAF were produced by blood neutrophils isolated from the joint had a lower capacity to produce PAF than blood neutrophils from the same patients. The present results demonstrate the synthesis and release of PAF by synovial fluid neutrophils. They suggest that neutrophils may be source of PAF locally present in the joint. Newly synthesized PAF could participate in the amplification of the local inflammatory reaction.

Arthritis, Rheumatoid↗
PubMed1991

Retroviral arthritis: phenotypic analysis of cells in the synovial fluid of sheep with inflammatory synovitis associated with visna virus infection.

A phenotypic analysis on synovial fluid cells from the carpal and tarsal joints of sheep with visna virus-induced inflammatory synovitis was performed. The results showed increased representation of cells bearing lymphocyte, macrophage, and dendritic cell markers compared to equivalent synovial fluid cells from normal uninfected age-matched controls. In infected sheep, CD8+ T cells tended to predominate over CD4+ cells, while the numbers of gamma delta T cells varied from being absent in some samples to constituting the major T cell subset in others. B cells were found in relatively smaller numbers. Analysis of the large mononuclear cells showed that they stained with monoclonal antibodies that recognize macrophages and afferent lymph dendritic cells. Major histocompatibility complex (MHC) class II+ macrophage/dendritic cells were found in normal joints, but significantly elevated proportions of such cells were present in the carpal joints of infected sheep. The intensity of MHC class II staining was also significantly elevated in infected animals compared to control animals. A high proportion of these cells also stained for CD1 in both normal and infected animals, but were significantly elevated in number in the carpal joints of infected sheep. The elevated proportion of cells expressing molecules associated with accessary cell function and the increase in the numbers of accessory molecules per cell suggests an enhanced capacity for presenting antigen to a variety of T cell subsets within the joints of infected sheep, which could initiate or perpetuate potentially damaging local synovial inflammatory responses.

Animals↗
PubMedDate not supplied

Synovial fluid changes in induced infectious arthritis in calves.

The objective was to develop an experimental model of septic arthritis in calves and to evaluate the effect of treatment on cytologic and bacteriologic variables of synovial fluid. The right tarsus of 7 healthy Holstein bull calves were inoculated with 10(8) colony-forming units of viable Escherichia coli of a pap-positive strain (day 1). On day 2, joint lavage was performed and antibiotic treatment was instituted. Cytologic examinations, bacterial cultures, and pap factor determinations by polymerase chain reaction (PCR) were performed on synovial fluid samples that were collected daily until day 4, then every 4 days until day 24. Results of physical examination, the severity of lameness, and swelling were recorded. Clinical signs of septic arthritis appeared on day 2 and persisted until day 9 for all calves. Bacterial cultures from all calves were positive for E. coli on day 2, and remained positive until day 3 for 1 calf and until day 4 for 5 calves. In addition, PCR results were positive for all calves, with 6 positive through day 3 and 1 positive through day 4, after which a positive result was again obtained on day 24. Synovial fluid neutrophil counts and white blood cell counts were significantly increased on days 2-4; however, synovial total protein concentrations were increased (P < .05) throughout the experiment in comparison to day 1. Results of all bacterial cultures were negative on day 8, although clinicopathologic signs of inflammation persisted until day 20. This model successfully induced acute septic arthritis in calves. Rapid recovery occurred within 1 week when an appropriate treatment was instituted early in the course of the disease.

Animals↗
PubMedDate not supplied

Lactoferrin and lysozyme levels in synovial fluid: differential indices of articular inflammation and degradation.

Lysozyme and lactoferrin levels were measured in 71 synovial fluids (SF) of patients with traumatic effusions, osteoarthritis, rheumatoid arthritis, pseudogout, septic arthritis, and gout, as well as in 91 synovial fluids graded according to their neutrophil count. Elevated lysozyme levels were found in all the inflammatory arthritides and also in osteoarthritis. Lactoferrin levels were not increased in osteoarthritis but displayed a close correlation to the extent of the inflammatory response as judged by SF neutrophilia. The ratio of lysozyme to lactoferrin decreased progressively with increasing SF neutrophilia. In vitro experiments showed that lactoferrin is released from neutrophils isochronously with lysozyme and beta-glucuronidase. Lactoferrin was not found in hyaline cartilage, a tissue known to contain lysozyme. These results are consistent with belief that SF lysozyme has a major derivation from both cartilage and neutrophils, and that lactoferrin arises only from neutrophils. These findings indicate that the simultaneous measurement of lysozyme and lactoferrin provides a potentially useful index of both joint inflammation and cartilage degradation.

Adult↗
PubMed1997

Substance P level in synovial fluid may predict pain relief after knee replacement.

Substance P is readily detected in the synovial fluid of the knee in which it acts as a powerful inflammatory agent in response to injury and disease. It may be an objective predictor of pain after knee replacement surgery. The level of substance P was measured in the synovial fluid in both knees of 114 patients having unilateral and in 86 patients having bilateral total knee replacement for osteoarthritis. All had severe pain in the knee to be replaced and joint destruction. Substance P was elevated in 73% of replaced knees but not in normal or asymptomatic knees. Good or excellent pain relief was achieved in 97% of patients with an elevated preoperative level of substance P and in 61% of those with a normal preoperative level (p < 0.05 compared with preoperative values).

Aged↗
PubMed2005

Detection and initial characterization of synovial lining fragments in synovial fluid.

OBJECTIVE: Free fragments of synovium have occasionally been seen in synovial fluid but have not been studied systematically. We wished to establish a method for the reliable detection of these fragments in joint and bursa effusions and begin to characterize them by histochemical and immunohistochemical methods. METHODS: Cell smears, wet drop preparations and cytospins were prepared from 39 consecutive joint and bursa effusions. Paraffin cell blocks were prepared from a subset. Analysis encompassed standard and polarized light microscopy, histochemistry, immunohistochemistry and transmission electron microscopy (EM). Synovial biopsy tissue from one different patient was examined for comparison. RESULTS: Tissue fragments were not seen in Wright-stained cell smears and only rarely in wet drop preparations. In contrast, variously sized fragments with the histological appearance of hyperplastic synovial lining were detected in ethanol-fixed, haematoxylin/eosin-stained cytospins from bursitis and all arthropathies studied [17/24 (71%) of non-inflammatory and 12/15 (80%) of inflammatory specimens]. Immunostaining revealed CD68 expression in a subset of cells in a pattern characteristic of hyperplastic synovial lining. Juxtaposed cells with morphological features of macrophage-like and fibroblast-like synoviocytes were seen by EM. CONCLUSIONS: Synovial lining fragments can be detected in effusions from diverse arthropathies and bursitis. They maintain important properties of the synovial lining and can be analysed by immunohistochemistry. They may afford the opportunity to study a relatively pure preparation of synovial lining cells without the need for cell culture, and to evaluate their possible role in augmenting or perpetuating synovitis or joint damage.

Aged↗
PubMed1993

Identification of tissue inhibitor of metalloproteinase-2 (TIMP-2)-progelatinase complex as the third metalloproteinase inhibitor peak in rheumatoid synovial fluid.

The metalloproteinases are a family of enzymes that can degrade all the components of the extracellular matrix. These potent enzymes are often found in proenzyme forms and require activation before the substrate can be digested. To prevent unlimited connective tissue destruction a number of inhibitors exist to limit their activity. In a previous study it was found that metalloproteinases in proenzyme form and metalloproteinase inhibitors were often present in rheumatoid synovial fluids. Two of these inhibitors were identified in rheumatoid synovial fluid as alpha 2 macroglobulin and tissue inhibitor of metalloproteinase (TIMP), the specific metalloproteinase inhibitor. A third inhibitory peak was unidentified. In the study reported here it was shown that this third inhibitor can be purified using gelatin-Sepharose chromatography and consists of TIMP-2 bound to progelatinase (relative molecular weight 72,000) in a similar way to that found in concentrated connective tissue culture medium. The importance of these proteinase inhibitors in synovial fluid is discussed.

Arthritis, Rheumatoid↗
PubMed1999

The increase of parathyroid hormone-related peptide and cytokine levels in synovial fluid of elderly rheumatoid arthritis and osteoarthritis.

We simultaneously measured the concentrations of parathyroid hormone related peptide (PTHrP) and cytokines in synovial fluid (SF) to clarify the relationship between PTHrP and cytokine network in the SF of elderly patients with arthritis. SF was collected from knee joints of five RA patients aged 66+/-11 years old and nine osteoarthritis (OA) patients aged 80+/-9 years old. PTHrP in SF was measured by enzyme-linked immunosorbent assay (ELISA), whereas tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8) in SF were all measured by ELISA. The PTHrP levels in the SF of RA patients (2.56+/-0.89 pmol/l) were significantly (p<0.05) higher than those of OA patients (1.66+/-0.17 pmol/l). TNF-alpha, IL-1beta, IL-2 and IL-6 concentrations in SF of RA were also significantly higher than those in SF of OA (TNF-alpha 22.5+/-14.8 vs 4.8+/-3.0 pg/ml, p<0.01; IL-1beta 11.8+/-11.4 vs 1.4+/-1.3, p<0.05; IL-2 59.9+/-46.6 vs 12.5+/-8.0 pg/ml, p<0.05; IL-6 18424+/-8901 vs 3547+/-2948 pg/ml, p<0.01). The concentrations of IL-4 and IL-8 in SF of RA were similar to those of OA. Immunohistochemical studies revealed the presence of immunoreactive PTHrP in synovial fibroblasts from RA and OA. Among cytokines, only IL-6 was positively correlated with PTHrP levels in SF (r=0.685, p<0.01). In the culture of synovial cells from RA and OA, PTHrP was produced in RA more than OA after phorbol 12-mysistate 13-acetate (TPA) stimulation. These results indicate that PTHrP and cytokines, especially IL-6, might be involved in the inflammatory processes of elderly RA and OA. This is the first study in which PTHrP and cytokine levels were simultaneously examined in synovial fluid of elderly RA and OA.

Aged↗
PubMed1987

Influence of concomitant aspirin or prednisone on methotrexate synovial fluid concentration.

Methotrexate (MTX) is currently being used in the treatment of patients with rheumatoid arthritis. The purpose of this study was to investigate the effect of two classes of drugs, steroids and salicylates, on MTX synovial fluid concentrations. A novel canine model of monoarticular inflammation was used, in which each animal served as its own control with both inflamed and normal knees in the same animal. After the 6-week immunization process, animals in each group received either no drug (control), prednisone or aspirin (low dose and high dose) for 1 week before MTX. On the day of the study, each animal was given i.v. MTX, and serial serum and synovial fluid samples were obtained. Laboratory, histologic and clinical observations supported the presence of monoarticular inflammation. The end-of-infusion synovial MTX concentration in inflamed knees was significantly greater than in normal knees (P less than .05), but, 2 hr after the end of infusion, they were not different. The end-of-infusion ratio of synovial fluid MTX concentration to serum MTX concentration (both total and unbound) was significantly lower in the prednisone group than in the other treatment groups (P less than .05). The end-of-infusion ratio of the MTX synovial concentration in the inflamed knee compared with the normal knee at 2 hr was significantly lower in the prednisone group than in the other three treatment groups (P less than .05). These results have therapeutic implications for the use of MTX in treating rheumatoid arthritis.

Animals↗
PubMed2001

Sequential changes in transforming growth factor (TGF)-beta1 concentration in synovial fluid and mRNA expression of TGF-beta1 receptors in chondrocytes after immobilization of rabbit knees.

We have previously reported that a combination of transforming growth factor (TGF)-beta1 and basic fibroblast growth factor (bFGF) synergistically increases the proliferation of chondrocytes obtained from knee joint immobilized for 7-14 days in male Japanese white rabbits. In the present study, we performed experiments with chondrocytes and syn ovial fluid obtained from rabbit knees immobilized for 0-42 days, to clarify the sequential changes in TGF-beta1 and bFGF concentrations in synovial fluid and the mRNA expression of TGF-beta1 receptor type I (RI) and II (RII) in chondrocytes after immobilization. The combination of TGF-beta1 and bFGF had a synergistic effect on the proliferation of chondrocytes obtained from knee joints immobilized for 7-14 days. The concentration of TGF-beta1 in synovial fluid was significantly higher (up to 3.6-fold) at 7-28 days after immobilization compared with that at 2 days. The mRNA for RI and RII was expressed during the whole immobilization period. The con centration of bFGF was kept at the same level at 2-7 days after immobilization, and gradually decreased thereafter. In the early stages of degenerated cartilage, up to 14 days after immobilization, the concentrations of both TGF-beta1 and bFGF were higher in the synovial fluid and mRNA expression of TGF-beta1 receptors in chondrocytes was kept.

Activin Receptors, Type I↗
PubMed2006

Inhibited apoptosis of synovial fluid lymphocytes in children with juvenile idiopathic arthritis is associated with increased expression of myeloid cell leukemia 1 and XIAP proteins.

OBJECTIVE: Inhibited apoptosis of lymphocytes present in synovial fluid (SFL) and persistently infiltrating synovial tissue may be crucial in the pathogenesis of rheumatoid arthritis (RA). Similarly, this may be the case in juvenile idiopathic arthritis (JIA). Little is known about lymphocyte apoptosis in this disease. Recently, we reported significantly enhanced apoptosis of peripheral blood lymphocytes (JIA-PBL) compared to synovial fluid (JIA-SFL) or healthy lymphocytes, with downregulation of p53 in JIA-SFL. In this study we assessed other possible molecular mechanisms of this phenomenon. METHODS: PBL from 31 children with JIA and 26 healthy children were examined. SFL obtained from 18 patients was also studied. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Expression of several apoptosis-regulating proteins was analyzed, including myeloid cell leukemia 1 (Mcl-1), cross-linked inhibitor of apoptosis (XIAP), FLICE-inhibitory protein (FLIP), or Bcl-xL inhibitors and proapoptotic p53, Bcl-w, Bak, and Bid. RESULTS: We found significant overexpression of Mcl-1 and XIAP in JIA-SFL (p < 0.001 and p < 0.02, respectively). Expression of Mcl-1 and XIAP in SFL correlated inversely with the apoptotic index (p < 0.002 and p < 0.01, respectively). FLIP expression was also distinctly higher in SFL than in JIA-PBL; however, the difference was not statistically significant (p = 0.061). No statistically significant differences were found in the expression of other proteins between SFL and PBL. CONCLUSIONS: This is the first study showing that upregulation of anti-apoptotic Mcl-1 and XIAP proteins, along with downregulation of p53 protein, is correlated with inhibition of JIA-SFL apoptosis.

Adolescent↗
PubMed1993

A high proportion of the V delta 1+ synovial fluid gamma delta T cells in juvenile rheumatoid arthritis patients express the very early activation marker CD69, but carry the high molecular weight isoform of the leucocyte common antigen (CD45RA).

We have previously shown that gamma delta T cells in the synovial compartment of patients with juvenile rheumatoid arthritis (JRA) express activation antigens (CD69 and HLA-DR) and that they are predominantly of the V delta 1 subset. In this study we have analysed the expression of activation antigens (CD69 and HLA-DR) and different isoforms of the leucocyte common antigen (CD45RO and CD45RA) on the V delta 1 and the V delta 2 subsets of gamma delta T cells in paired samples of synovial fluid and peripheral blood of nine patients with JRA, and in the peripheral blood of five children with idiopathic scoliosis. In the synovial fluid of children with JRA, there were significantly more V delta 1+CD69+ and V delta 2+CD69+ cells compared with the peripheral blood of the same patients. In contrast, however, in the synovial fluid the V delta 1 and the V delta 2 subsets differed with respect to the expression of the two isoforms of the leucocyte common antigen. The majority of the V delta 1+ cells expressed the high molecular weight isoform (CD45RA+) while most of the V delta 2+ cells carried the low molecular weight variant (CD45RO+) of this molecule.

Adolescent↗
PubMed1996

Characterization of submicron polyethylene wear debris from synovial-fluid samples of revised knee replacements using a light-scattering technique.

The objectives of this study were to determine whether submicron-sized ultra-high-molecular-weight polyethylene (UHMWPE) wear debris was present in synovial fluid surrounding knee implants, and to report on the utility of a light-scattering technique for the in situ analysis of submicron-sized wear debris. The measured light-scattering coefficients of the implant synovial fluid samples were significantly larger than the coefficients of the control samples (p < 0.0001). The enhanced light scattering was attributed to the presence of submicron UHMWPE particles. This is consistent with light-scattering considerations and a Raman spectroscopy survey of synovial fluid. The mean particle volume fraction of UHMWPE was 1.11 x 10(-5) cm3/mL for the six implant samples, with mean particle diameters in the range of 200-300 nm. The UHMWPE volume fractions were found to differ by a factor of 2 between the osteolytic and nonosteolytic cases. The current findings warrant further work to determine the role of submicron polyethylene debris in the wear mechanisms of biomaterials and in the development of osteolysis following total knee replacement.

Adult↗