Synovial Fluids

The technique of obtaining synovial fluid for examination is caEed arthrocentesis. Synovial fluid is withdrawn from joints to aid characterization of the type of arthritis and to differentiate noninflammatory effusions from inflammatory fluids. NormaEy, oiEy a very smaE amount of fluid is present in any joint, but this volume is usually very much increased in the presence of inflammatory conditions. Arthrocentesis should be performed by a physician using sterile procedures, and the technique must be modified from joint to joint 

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A new generation of antiinflammatory agents having immunosuppressive activity has been developed. The appearance of preclinical and clinical reports suggest that these are near entry to the pharmaceutical market. For example, tenidap (CP-66,248) (12) has been demonstrated to inhibit IL-1 production from human peripheral blood monocytes in culture (55). Clinically, IL-1 in synovial fluids of arthritic patients was reduced following treatment with tenidap. Patients with rheumatoid or osteoarthritis, when treated with tenidap, showed clinical improvement (57,58). In addition to its immunological effects, tenidap also has an antiinflammatory profile similar to the classical NSAIDs (59). Other synthetic inhibitors of IL-1 production are SKF 86002 (20) andE-5110 (21) (55). 

Joints are stmcturaHy unique. They permit bodily movement and are bound together by fibrous tissues known as ligaments. Most larger joints are encapsulated in a bursa sac and surrounded by synovial fluid which lubricates the joint continuously to reduce friction. The skeleton is constmcted of various types of moveable joints. Some joints allow for no movement, such as those connecting the bones of the skull. Other joints permit only limited movement. For example, the joints of the spine allow limited movement in several directions. Most joints have a greater range of motion than the joints of the skull and spine. 

A bursa, a sac filled with fluid located around a principal joint, is lined with a synovial membrane and contains synovial fluid. This fluid minimizes friction between the tendon and the bone, or between tendon and ligament. Repeated small stresses and ovemse can cause the bursa in the shoulder, hip, knee, or ankle to swell. This swelling and irritation is referred to as bursitis. Some patients experience bursitis in association with tendonitis. Bursitis can usually be reheved by rest and in some cases by using antiinflammatory medications. Some orthopedic surgeons also inject the bursa with additional medication to reduce the inflammation. 

Gelenk-. articular, -basalt, m. flexible basalt. -flussTgkeit, /. synovial fluid. 

II A-F Snake venom, synovial fluid, pancreas, testis, spleen, brain, heart, uterus 13-17 6-8... 

In rheumatoid arthritis the damage that is found in joints may also be a result of the inactivation of a-1-PI due to the oxidation of an essential methionine(s) residue in this protein. It has been found that a-l-PI purified from the synovial fluid of patients with rheumatoid arthritis contained four Met(O) residues and was not able to form a binary complex with elastase89. It is probable that the presence of the Met(Oj residues in a-l-PI from these patients results from a high level of oxidants produced by neutrophils in the inflammed joint. 

Fingerprinting the Hyaluronic Acid Component of Normal and Pathological Synovial Fluids, S. A. Barker, S. H. I. Bayyuk, J. S. Brimacombe, C. F. Hawkins, and M. Stacey, Clin. Chim. Acta, 8 (1963) 902-909. 

Pope, R.M., Lovis, R.M., Gupta, R.S. (1992). Activation of synovial fluid T lymphocytes by 60 kD heat shock proteins in patients with inflammatory synovitis. Arthritis Rheum. 35,43-48. 

Hyaluronic acid consists of an unbranched chain of repeating disaccharide units containing GlcUA and GlcNAc. Hyaluronic acid is present in bacteria and is widely distributed among various animals and tissues, including synovial fluid, the vitreous body of the eye, cartilage, and loose connective tissues. 

HA GIcNAc, GlcUA Nil No firm evidence Synovial fluid, vitreous humor, loose connective tissue... 

Cartilage is an avascular tissue and obtains most of its nutrients from synovial fluid. It exhibits slow but continuous turnover. Various proteases (eg, collage-nases and stromalysin) synthesized by chondrocytes can... 

Figure 1.1 A typical e.s.r. spectrum of knee-joint synovial fluid obtained from a patient with rheumatoid arthritis. The signals detectable have g values that correspond to the nitrosylhaemoglobin adduct (gi = 2.083, 02 = 2.040 and gs = 2.003).

Alpha-l-antiprotease (ai-AP) limits tissue damage arising from the actions of the leucocyte protease, elastase (Carrell and Travis, 1985), and there is much evidence available for the oxidative inactivation of this protein by oxygen-derived free-radical species and hypochlorous acid/hypochlorite anion (HOCl/OCP). The mechanism of this inactivation appears to involve the oxidation of a critical methionine residue (Met-358) to its corresponding sulphoxide and methionine sulphoxide has been detected in ai-AP samples isolated from the lungs of cigarette smokers (Carp et al., 1982) and rheumatoid synovial fluids (Wong and Travis, 1980). 

Figure 1.2 High-fleld (aliphatic) region of 500 MHz H Hahn spin-echo NMR spectra of (a) a typical inflammatory synovial fluid sample (b) as (a) but following 7-radiolysis (5.00 kGy). Typical spectra are shown. A, acetate-CHs ...

Typical spectra obtained are shown in Fig. 1.2. Moreover, substantial radiolytically-mediated elevations in the concentration of serum formate, arising from the oxidation of carbohydrates present by OH radical, were also detectable. In addition to the above modifications, 7-radiolysis of inflammatory knee-joint synovial fluid generated an oligosaccharide species of low molecular mass derived from the radiolytic fragmentation of hyaluronate as outlined in the previous section dealing with oxidative damage to carbohydrates. The... 

Figure 1.4 High-field (aliphatic) regions of 500 MHz single-pulse H-NMR spectra of an inflammatory synovial fluid ultrafiltrate sample obtained before (a) and after equilibration (b) with 2.00 x 10 mol/dm H2O2 at ambient temperature for a period of 24 h. Typical spectra are shown. For abbreviations, see Fig. 1.2 with acac,...

Figure 1.7 Typical zero-order and corresponding second-derivative electronic absorption spectra of ethanol-reconstituted lipid/chloroform extracts of autoxidized model polyunsaturated fatty-acid compounds and inflammatory synovial fluid obtained after (1) reduction with NaBH4 and (2) dehydration with alcoholic H2S04- (a) Methyl linoleate subsequent to autoxidation in air at ambient temperature for a period of 72 h (—), or exposure to a Fenton reaction system containing EDTA (5.75 x 10 mol/dm ), H2O2 (1.14 X 10 mol/dm ) and Fe(ll) (5.75 x IO mol/dm ) as an aqueous suspension (—) (b) as (a) but with methyl linolenate (c) untreated rheumatoid knee-joint synovial fluid.

Chapman, M.L., Rubin, B.R and Gracy, RW. (1989). Increased carbonyl content of proteins in synovial fluid from patients with rheumatoid arthritis. J. Rheumatol. 16, 15-18. 

Grootveld, M., Henderson, E.B., Farrell, A.J., Blake, D.R, Parkes, H.G. and Haycock, P. (1991). Oxidative damage to hyaluronate and gjucose in synovial fluid during exercise of the inflamed rheumatoid joint detection of abnormal low-molecular-mass metabolites by proton NMR spectroscopy. Biochem. J. 273, 459-467. 

Gutteridge, J.M.C. (1987). Bleomycin-detectable iron in knee-joint synovial fluid from arthritic patients and its relationship to the extracellular activities of caeruloplasmin, transferrin and lactoferrin. Biochem. J. 245, 415-421. 

Kofoed, J.A. and Barcelo, A.C. (1978). The synovial fluid hyaluronic acid in rheumatoid arthritis. Experimentia 34, 1545. 

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