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[Synovial fluid over the centuries].

This review deals with the most meaningful historical topics on the study of synovial fluid, by starting from the Greco-Roman Medicine, up to Paracelsus (1493-1541), who introduced the term "synovia" to name the intra-articular humour. Afterwards, some till now unreported historical sources are recorded, e.g., a short text by the Italian XVIII century physician Giambattista Contoli ("Breve Instruzione sopre il Glutine, ò Colla., 1699"). Then, in keeping with some recent researches, a brief history of arthrocentesis is outlined, by considering the first procedures, which should have been performed in Mexico, during the precolonial period. Moreover, the first chemical analysis of synovial fluid, as carried out by the French chemist Jean-Louis Margueron (1792), and the first modern study on the synovial membrane by Marie-François-Xavier Bichat (1800) are explained. Finally, some XIX century investigations concerning the synovial pharmacodynamics, in particular an Italian one based on the elimination of certain chemical substances through the synovial membrane, are discussed.

History, 15th Century↗
PubMed1988

Increased macrophage division in the synovial fluid of goats infected with caprine arthritis-encephalitis virus.

Macrophages are a major component of the arthritic lesions induced by the lentivirus caprine arthritis-encephalitis virus (CAEV). Using autoradiography and the appearance of mitotic figures to detect dividing macrophages, we found that 2.1% +/- 0.2% of synovial fluid macrophages from uninfected goats are dividing and that after infection with CAEV the percentage increases three- to sixfold. The enhanced macrophage division was not associated with increased dividing of blood monoblasts. The amount of macrophage division correlated with two measures of arthritis: joint swelling and the number of synovial fluid macrophages. Induction of an immune response in the joints of CAEV-infected goats increased the number of dividing macrophages. The synovial fluid of infected animals was mitogenic for macrophages from infected animals in amounts that correlated with the amount of macrophage division occurring in the joints. Activated lymphocytes produced nondialyzable lymphokines mitogenic for macrophages from CAEV-infected goats but not from uninfected goats. These results suggest that in situ macrophage division contributes to the lesions induced by CAEV and that infection leads to greater responsiveness of macrophages to mitogenic factors produced by lymphocytes.

Animals↗
PubMed2006

Arthrogenic lameness of the fetlock: synovial fluid markers of inflammation and cartilage turnover in relation to clinical joint pain.

REASONS FOR PERFORMING THE STUDY: Joint pain is one of the most common causes of lameness in the horse but its pathogenesis is poorly understood. OBJECTIVES: To investigate which synovial fluid markers may be related to the presence of clinically detectable joint pain in the horse. METHODS: Concentrations of structural (CPII, C2C, GAG) and inflammatory markers (PGE2, LTB4, CysLTs, bradykinin and substance P) were measured in fetlock joint fluid from 22 horses in which lameness was localised to the fetlock region by perineural anaesthesia. Levels of these markers were then compared in horses that responded (n = 15) to those that did not (n = 7) to subsequent intra-articular anaesthesia (IAA). RESULTS: Of all markers analysed, only substance P levels were significantly higher (P = 0.0358) in synovial fluid of horses that showed a positive response to IAA compared to those with a negative response to IAA. Notably, while PGE2 levels were found to be elevated in all 22 lame horses compared to sound controls (P = 0.0025), they were not related to the response to IAA. CONCLUSIONS: While levels of PGE2 are elevated in synovial fluid of lame horses that respond to perineural anaesthesia, only substance P is related to joint pain as detected by the response to intra-articular anaesthesia. POTENTIAL RELEVANCE: Substance P is associated with clinically detectable joint pain in the horse. Elevated levels of PGE2 in fetlock-lame horses, regardless of their response to IAA, indicate that either this mediator does not reflect intra-articular pain or that IAA might have limitations in differentiating between intra- and peri-articular sources of pain. Either way, a negative response to IAA may not exclude intra-articular pathology.

Animals↗
PubMed2002

Inducible nitric oxide synthase is expressed in synovial fluid granulocytes.

The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 +/- 78 versus 176 +/- 65 micro mol/l, P = 0.008), whereas a slight increase in l-citrulline (33 +/- 11 versus 26 +/- 9 micro mol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 +/- 20.7 versus 8.6 +/- 6.5 micro mol/l, P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.

Adult↗
PubMed1997

Synovial fluid interleukin 6, tumor necrosis factor, and nitric oxide values in dogs with osteoarthritis secondary to cranial cruciate ligament rupture.

OBJECTIVE: To measure and compare values of interleukin 6 (IL-6), tumor necrosis factor (TNF), and nitric oxide (NO) metabolites in synovial fluid from canine joints with osteoarthritis (OA) secondary to naturally acquired cranial cruciate ligament (CCL) rupture and experimental CCL transection. ANIMALS: 57 dogs (clinical group) with OA secondary to CCL rupture; 5 dogs (experimental group) with OA secondary to CCL transection; 19 control dogs with normal joints. PROCEDURE: Joints were radiographed and graded for seventy of OA. Synovial fluid was collected from dogs: at surgery from the clinical group, at 90 days after surgery from the experimental group, and at necropsy from the control group. Activities of IL-6 and TNF, as well as concentration of the NO metabolites (NO2-/NO3-) were measured, and results were reported as mean +/- SEM. RESULTS: IL-6 activity in dogs of the clinical (290 +/- 40 U/ml) and experimental (494 +/- 165 U/ml) groups was greater than that in control dogs (6 +/- 1.6 U/ml; P < 0.05). The TNF values in dogs of the clinical (3.0 +/- 0.5 pg/ml) and experimental (2.0 +/- 0.9 pg/ml) groups were lower than those in control dogs (8.6 +/- 2.3 pg/ml; P < 0.05). The IL-6 values were negatively associated with radiographic score of OA and were positively associated with age (R2 = 26.5%, P < 0.05). CONCLUSION: Dogs with OA secondary to naturally acquired CCL rupture and experimental CCL transection had significantly different alterations in synovial fluid IL-6 and TNF values. The decrease in IL-6 activity with advancing OA was independent of the increase in IL-6 activity with aging. CLINICAL RELEVANCE: IL-6 and TNF may be involved in pathogenesis of OA secondary to naturally acquired and experimentally induced CCL rupture.

Age Factors↗
PubMed1999

The role of N-acetylcysteine in protecting synovial fluid biomolecules against radiolytically-mediated oxidative damage: a high field proton NMR study.

High field proton (1H) NMR spectroscopy has been employed to evaluate the abilities of the antioxidant thiol drug N-acetylcysteine and exogenous cysteine to protect metabolites present in intact inflammatory synovial fluid samples against oxidative damage arising from gamma-radiolysis (5.00 kGy) in the presence of atmospheric O2. Although oxidation of urate to allantoin by radiolytically-generated *OH radical was readily circumventable by pre-treatment of synovial fluids with N-acetylcysteine (1.00 or 3.00 x 10(-3) mol x dm(-3)) or cysteine (1.00, 2.00 or 5.00 x 10(-3) mol x dm(-3)), both thiols offered only a limited protective capacity with respect to hyaluronate depolymerisation and the production of formate from carbohydrates in general. Radiolytic products generated from the added thiols (predominantly their corresponding disulphides) were simultaneously detectable in 1H Hahn spin-echo spectra of gamma-irradiated synovial fluids, permitting a quantitative evaluation of the radioprotective capacity of these agents. It is concluded that the multicomponent analytical ability of high field 1H NMR spectroscopy provides much useful molecular information regarding mechanisms associated with the radioprotectant actions of thiols in intact biofluids.

Acetylcysteine↗
PubMed1979

[Immunsuppressive factors in sera and synovial fluids of patients with rheumatoid arthritis (author's transl)].

Serum inhibitory factors (SIF) have been demonstrated in several infectious diseases and autoimmune disorders. Most likely, they are caused by an immune reaction, and their persistence indicates a chronic course. Sera and synovial fluids of 31 patients with rheumatoid arthritis and of 33 patients with arthrosis were therefore studied, in order to determine whether immunosuppressive factors exist only in inflammatory diseases and whether their titers correlate with the activity of the disease. PHA-induced stimulation of normal peripheral blood lymphocytes, measured as 3H thymidine uptake, in the presence of patients' serum, was related to lymphocyte stimulation observed in the presence of control sera. Using the MIF-agarose assay, the effect of sera and synovial fluids on the tuberculin-induced migration inhibition was also studied. Sera of 27 of 31 patients with rheumatoid arthritis inhibited mitogen-induced normal lymphocyte thymidine uptake and abolsihed migration inhibition, probably by blocking MIF-production. High titers appeared to predict an unfavourable course. In contrast, sera of all 33 patients with degenerative joint disease failed to exert these effects. Synovial fluids of all patients, irrespective of the nature of the underlying joint disease, did not affect lymphocyte stimulation or leukocyte migration. Other factors, such as immune complexes, cytotoxic antibodies, or drug metabolites could be excluded as potential causes of the observed effects exerted by rheumatoid arthritis sera. These results indicate that the presence of serum factors inhibiting PHA-induced lymphocyte stimulation and leukocyte migration inhibition, respectively, may be used as a diagnostic tool in the differential diagnosis of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Nucleosides and bases in synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

1. Nucleosides and bases in physiological fluids result from metabolism of nucleic acids and nucleotides and from dietary sources. As nucleotide catabolism increases during tissue injury, nucleosides and bases could serve as useful biochemical markers in arthritis. 2. We have quantified nucleosides and bases in synovial fluid and plasma by high-performance liquid chromatography in order to examine whether nucleotide metabolism is increased in patients with rheumatoid arthritis and osteoarthritis. 3. At least ten u.v.-absorbing compounds were detected in plasma and synovial fluid; only urate, creatinine, hypoxanthine and uridine were present in identifiable and quantifiable amounts. 4. In synovial fluid from patients with rheumatoid arthritis the concentration of hypoxanthine was increased and that of urate decreased compared with osteoarthritis. 5. These data suggest that there is an increase in purine metabolism in the rheumatoid arthritis joint and that hypoxanthine is a potential marker of synovitis.

Adult↗
PubMed1991

Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease.

1. Ten patients with bilateral knee joint effusions were treated topically with a gel containing 1 g diclofenac/100 g (80 mg three times daily). They were randomized to receive diclofenac gel to one knee and a placebo gel preparation to the other knee. 2. Diclofenac was assayed in synovial fluid and blood plasma by GC/ECD as the pentafluorobenzyl-ester derivative. 3. Total concentrations of diclofenac in synovial fluid (day 4) were significantly higher in the diclofenac gel treated knee than in the contralateral placebo treated knee (25.5 +/- 3.6 ng ml-1 vs 21.6 +/- 2 ng ml-1; P less than 0.05). These concentrations were lower than total plasma drug concentrations (40.6 +/- 4.7 ng ml-1, n = 10, P less than 0.01). Unbound concentrations of diclofenac in synovial fluid from either the diclofenac gel treated or the placebo treated knee were not significantly different from each other or from plasma free concentrations (115 +/- 16 and 99 +/- 12 vs 108 +/- 19 pg ml-1). 4. Clinical parameters showed improvement of joint mobility and a small reduction of swelling (circumference) in both knees with time. However, the differences between knees were not significant. 5. We conclude that direct transport of diclofenac from the skin into the ipsilateral knee joint after cutaneous application is minimal. Distribution seems to be predominantly via the blood. Whether the observed improvements of clinical parameters were due to drug effects or to the spontaneous course of the underlying disease cannot be distinguished.

Administration, Topical↗
PubMed2000

Processing of noninflammatory synovial fluids with hyaluronidase for cytospin preparations improves the accuracy of differential counts.

Differential leukocyte counts on noninflammatory synovial fluids (NISF) are not widely reported or used in research, apparently due to technical difficulties related to either high viscosity or low numbers of cells. We describe an evaluation of a technique using hyaluronidase and cytospin preparations to study NISF. Twenty-three consecutive synovial fluids (SF) with less than 2,000 white blood cells (WBC)/mm3 were studied either by the usual smear of a single drop or by adding two drops of hyaluronidase (150 USP units/ml) to 0.25 cc of SF and cytocentrifuging at 800 rpm for 10 min. Both preparations were stained with Wright's stain. Cytospin preparations gave better morphology, and in 22/23 specimens we could count 100 cells on one slide. Smeared preparations gave dark cells and required 2-3 slides to count 100 cells. Differential counts on the cytospin preparations consistently showed higher percentages of monocytes, suggesting that these cells were underdetected and misinterpreted as lymphocytes on the routine smears. Polymorphonuclear leukocytes (PMN) were significantly less frequent (P 0.005) in osteoarthritis (OA) fluids than in the other diseases with NISF. Relatively more PMN may suggest consideration of a diagnosis other than OA. Cytospin preparations of hyaluronidase-treated NISF may open up an important area for investigation of the role of SF cells in less inflammatory diseases.

Centrifugation↗
PubMed1990

Soluble histocompatibility antigens in synovial fluids of patients with rheumatoid arthritis.

Soluble histocompatibility antigens of the class II region have been detected in synovial fluids obtained from patients with rheumatoid arthritis. A capture immunoassay involving two monoclonal antibodies was used; interference by rheumatoid factor, which is a feature of such assays, was overcome by mild pretreatment of fluids with 2-mercaptoethanol. No HLA class II antigen could be detected in matched sera from patients, even when levels were high in synovial fluids. Released HLA-class II material was of high molecular weight (greater than 1000 kD) and was linked to HLA-class I antigen. However, no significant amounts of other common cell surface antigens were detected in the complex, suggesting a preferential release of MHC antigens from cells of the inflamed synovium. Attempts to induce production of similar material from a cell line which expresses HLA class II strongly at the cell surface, by stressing the cells in various ways did not succeed, indicating that release is an active process.

Adult↗
PubMed1984

Relative amounts of chondroitin sulfate and hyaluronic acid in synovial fluid from normal and osteochondrotic swine joints.

Twenty eight nonlame and ten lame pigs were used to study glycosaminoglycans in synovial fluid from normal and osteochondrotic elbow and stifle joints. The results indicated that porcine synovial fluid contains both hyaluronic acid and chondroitin sulfate and that the chondroitin sulfate to hyaluronic acid ratio is similar (P less than 0.05) between normal and osteochondrotic joints.

Animals↗
PubMed1987

Lipid peroxidation and malondialdehyde in the synovial fluid and plasma of patients with rheumatoid arthritis.

The concentration of lipid peroxides in the plasma and synovial fluid of 65 arthritic patients was determined using a new ion-pairing reverse phase HPLC technique. Patients with rheumatoid arthritis receiving only non-steroidal anti-inflammatory drugs, had a significantly higher mean concentration of lipid peroxides in synovial fluid samples (162 +/- 22.0 micrograms/l) than osteoarthritic patients (40.0 +/- 8.0 micrograms/l, p less than 0.0001). Mean concentrations in both groups correlated strongly with the level of beta-glucuronidase activity as a measure of lysosomal enzyme release (r = 0.71, p less than 0.0001). Contrary to previous reports by investigators using less specific methods, we were unable to demonstrate any increase in plasma levels of lipid peroxides in the rheumatoid patient. Treatment of rheumatoid arthritis with D-penicillamine was associated with a significant reduction of lipid peroxide levels (83.2 +/- 11.5 micrograms/ml, p less than 0.002), suggesting that this drug may function as an oxygen radical scavenger in the joint cavity. These results give further support to the concept of oxygen-free radicals playing an important role in the pathogenesis of chronic inflammatory disorders.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Substance P levels in the synovium and synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

Experimental results suggest that substance P (SP) may play an important role in pain and inflammation in rheumatic diseases. Measurements of SP-like immunoreactivity (SPLI) were performed in synovial fluid (SF) and synovial tissue from 40 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). High levels of SPLI were found in the SF of patients with RA compared with OA. Conversely, SPLI content in synovial tissue was higher in OA than in RA, suggesting that there is an active secretory process of SPLI into the SF in RA, thus depleting SPLI stores in the synovium. Our data support the involvement of SP in the perpetuation and exacerbation of inflammation in RA, and may also explain some clinical features of this disease.

Adult↗
PubMed1987

Determination of lysozyme activity by fluorescence polarization in rheumatoid synovial fluids and release of lysozyme from polymorphonuclear leukocytes by chemotactic factors.

A new method for the measurement of lysozyme activity, which is rapid, quantitative and sensitive, was established and applied to clinical material obtained from arthritis patients. The method is based on fluorescence polarization with the use of fluorescein isothiocyanate-labeled peptidoglycan. Using this method, we found that the synovial fluids obtained from rheumatoid arthritis contained more lysozyme activity than similar samples from osteoarthritis patients (P less than 0.001). Furthermore, we found that chemotactic factors and lysozyme-depleted rheumatoid synovial fluids could induce the release of lysozyme from human polymorphonuclear leukocytes in vitro. It is therefore suggested that lysozyme present in rheumatoid synovial fluids may derive in part from polymorphonuclear leukocytes and the action of chemotactic factor(s) within the fluids.

Arthritis, Rheumatoid↗
PubMed2004

Concentrations of moxifloxacin in serum and synovial fluid, and ex vivo bactericidal activity against arthritis-causing pathogens.

Three doses of moxifloxacin 400 mg qd were administered orally to 20 candidates for knee arthroscopy (mean age, 71.2 years). The procedure was scheduled at four different points of time after the last dose: 2, 6, 12, and 24 h. Five patients were studied at each point of time. Drug levels were determined by the bioassay method. Bactericidal activity against four bacterial pathogens (two strains of each) was studied on serum and synovial fluid samples obtained during arthroscopy using the NCCLS guidelines. Mean (+/-S.D.) peak serum and synovial fluid concentrations were 3.46 +/- 0.78 mg/L and 3.42 +/- 0.51 mg/L, respectively. Levels above 1.0 mg/L were detected as long as 24 h. The peak bactericidal titers were (in serum and synovial fluid, respectively) 1:18.3 and 1:32 against Staphylococcus aureus, 1:18.3 and 1:22.6 against Streptococcus pyogenes, 1:45.2 and 1:64.0 against Klebsiella pneumoniae, and 1:2.3 and 1:1.7 against Pseudomonas aeruginosa. Bactericidal titers >1:2 were documented against the first three pathogens up to 24 h after dosing. On the basis of its pharmacokinetic and pharmacodynamic characteristics, moxifloxacin seems to be an excellent candidate for the treatment of joint infections, except those caused by P. aeruginosa.

Administration, Oral↗
PubMed1986

Purification of a soluble phospholipase A2 from synovial fluid in rheumatoid arthritis.

A soluble phospholipase A2 (PLA2) was purified 4,500-fold from human rheumatoid synovial fluid. Preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis yielded two bands of PLA2 activity of molecular weights 15,000 and 17,000 and pl 4.2-5.0. Purified PLA2 had absolute 2-acyl specificity, and hydrolyzed phosphatidylcholine with optimal activity at pH 7.5-8.0 and phosphatidylethanolamine with optimal activity at pH 7.0. Human synovial fluid PLA2 did not cross-react with anti-human pancreatic PLA2, as tested by radioimmunoassay.

Arthritis, Rheumatoid↗
PubMed1987

[Detection of low molecular weight trypsin inhibitors in small samples of cartilage, cartilage extracts and synovial fluid by gel diffusion].

The radial diffusion assay is a very useful method for detection of low amounts of proteinase inhibitors in biological materials. The determination of low molecular weight (LMW) inhibitors in the presence of high molecular weight inhibitors is possible by the combination of radial diffusion and ultrafiltration. Using this method LMW trypsin inhibitors could be demonstrated in human articular cartilage, but not in human synovial fluid. In cow, pig and sheep a LMW trypsin inhibitor could be found in both the articular cartilage and in the synovial fluid. On the other hand, a LMW trypsin inhibitor could not be found neither in the canine cartilage nor in the canine synovial fluid. The method allows also the direct determination of LMW trypsin inhibitors in cartilage extracts in the presence of 4 M guanidinium hydrochloride or 6 M urea. Therefore, the method is recommended for direct determination of LMW inhibitors by column chromatographic separations of inhibitors.

Animals↗