Inflammation synovial fluid

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. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

Glycoproteins similar to the IDGFs are found in mammals and may constitute a novel class of cytokines, some of which are important in inflammation. The best characterized is the human glycoprotein HC gp-39 (= YKL40 16-23% identical to IDGFs), which accumulates in the synovial fluid of rheumatoid arthritis... 

A. indica L. Indian Aristolochia, also known as Indian birthwort, ishvara (Sanskrit), or adagam (Tamil), is a bitter climber native to India. The medicinal material consists of the rhizome, which is to resolve inflammation (India), counteract insect poison, and as an antipyretic (Philippines and Vietnam). The rhizome contains aristolochic acid, which inhibits in vitro and dose-dependent phospholipid hydrolysis by the human synovial fluid phospholipase A2, snake venom phospholipase A2, porcine pancreatic phospholipase A2, and human platelet phospholipase A2 (2). 

Vishwanath BS, Fawzy AA, Franson R, et al. Edema-inducing activity of phospholipase A2 purified from human synovial fluid and inhibition by aristolochic acid. Inflammation 1988 12 549-561. 

Local inflammatory changes occur in the joint capsule and synovium. The synovium becomes infiltrated with T cells, and immune complexes appear. Crystals or cartilage shards in synovial fluid may contribute to inflammation. There are also increased levels of interleukin-1, prostaglandin E2, tumor necrosis factor-a, and nitric oxide in synovial fluid. Inflammatory changes result in effusions and synovial thickening. 

Tumor Necrosis Factor There are two types of tumor necrosis factor TNF-a and TNF- 8. Of the two, TNF-a has been studied in more detail. TNF-a is a 157 amino acid polypeptide. It is a mediator of immune regulation, including the activation of macrophages and induction of the proliferation of T cells. Another TNF-a function is its cytotoxic effects on a number of tumor cells. Recent research, however, concentrates on its property in the stimulation of inflammation, particularly in the case of rheumatoid arthritis. Clinical trials are being conducted with drugs to block TNF-a with anti-TNF-a monoclonal antibodies. These antibodies target the excessive levels of TNF-a in the synovial fluid of joints and provide relief to sufferers of rheumatoid arthritis (Exhibit 4.10). 

Anakinra is a nonglycosylated form of the human IL-1 receptor antagonist (IL-lra). It is produced in a recombinant Escherichia coli expression system and has an additional methionine residue at its amino terminus. In rheumatoid arthritis patients, the amount of naturally occurring IL-lra in the synovial fluid is not sufhcient to counteract the high levels of locally produced IL-1. Anakinra acts as a competitive antagonist of the type 1 IL-1 receptor and decreases the pain and inflammation produced by IL-1. It is administered as a daily subcutaneous injection. 

Drug concentrations in pleural fluid, peritoneal fluid, synovial fluid, aqueous humor, and vitreous humor approach two-thirds of the serum concentration when local inflammation is present. Meningeal and am-niotic fluid penetration, with or without local inflammation, is uniformly poor. Measurement of serum, urine, or cerebrospinal fluid drug levels has not been used clinically. 

McCord, J. M. Free radicals acid inflammation Protection of synovial fluid by superoxide dismutase. Science 185, 529 (1974)... 

Nitric oxide has a role in both acute and chronic inflammation. NOS-3 is involved in the vasodilation associated with acute inflammation. In experimental models of acute inflammation, inhibitors of NOS-3 have a dose-dependent protective effect, suggesting that nitric oxide promotes edema and vascular permeability. Nitric oxide has a detrimental effect in chronic models of arthritis dietary L-arginine supplementation exacerbates arthritis whereas protection is seen with NOS-2 inhibitors. Psoriasis lesions, airway epithelium in asthma, and inflammatory bowel lesions in humans all demonstrate elevated levels of nitric oxide and NOS-2. Synovial fluid from patients with arthritis contains increased oxidation products of nitric oxide, particularly peroxynitrite. 

K8. Kaur, H., and Halliwell, B., Evidence for nitric oxide-mediated oxidative damage in chronic inflammation Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett. 350, 9-12(1994). 

Women suffer far more frequently than men. Clinically, there is arthralgia of varying intensity and symptoms of chronic proliferative inflammation of the synovial fluid in the diseased joints. Systemic manifestations can be recognized on the basis of haematological, neurological, pulmonary, renal, cardiovascular and hepatic symptoms. Laboratory parameters show marked inflammatory criteria (s. tab. 38.2) as well as a rise in y-globulins and immunoglobulins M and G. The rheumatoid factor is often detectable, (s. p. 118) Alkaline phosphatase may be elevated. (lOO)... 

Inflammation of the synovial joints in rheumatoid arthritis includes this change in the synovial fluid. 

Site of therapeutic action (if different from plasma circulation) local protein expression and transport rates between the site and blood circulation (e.g., a target in brain will see very small fraction of injected dose due to poor mAb brain penetration, and synovial fluid may have higher concentration of a target inflammation factor than plasma in rheumatoid arthritis)... 

The H NMR spectra of the synovial fluid of a female patient with seronegative erosive rheumatoid arthritis and of another female patient with sarcoidosis and independent inflammatory osteoarthritis were followed over the course of several months and standard clinical tests were performed on paired blood serum samples taken at the same time. It was found that the synovial fluid levels of triglyceride CH3, CHj and CH, glycoprotein N-acetyl signals and creatinine all correlated well with one another, and with standard clinical measures of inflammation. The correlation of disease state with creatinine level is of particular interest, and the altered triglyceride composition and concentration in osteoarthritis were suggested as potential markers for the disease in synovial fluid. ... 

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