Inflamed joints

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. 

Reperfusion of the synovial membrane occurs when exercise is stopped and O2 is subsequently reintroduced to the tissue. O2 is a substrate required for xanthine oxidase activity and O2" is generated. Therefore, repeated cycles of rest-exercise-rest in the inflamed joint may provide a continuous flux of destructive ROM. 

This decreased level of catalase does not offer sufficient protection against the extracellular generation of radicals within the inflamed joint (Blake etal., 1981). 

The importance of vitamin E for maintenance of lipid integrity in vivo is emphasized by the fact that it is the only major lipid-soluble chain-breaking antioxidant found within plasma, red cells and tissue cells. Esterbauer etal. (1991) have shown that the oxidation resistance of LDL increases proportionately with a-tocopherol concentration. In patients with RA, synovial fluid concentrations of a-tocopherol are significantly lower relative to paired serum samples (Fairburn et al., 1992). The low level of vitamin E within the inflamed joint implies it is being consumed via its role in terminating lipid peroxidation and this will be discussed further in Section 3.3. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

Merry, P., Grootveld, M., Lunec, J. and Blake, D.R. (1991). Oxidative damage to lipids within the inflamed joint provides evidence of radical-mediated hypoxic reperfasion injury. Am. J. Clin. Nutr. 53, 362s-369s. 

Buckley CD. Michael Mason prize essay 2003. Why do leucocytes accumulate within chronically inflamed joints Rheumatology (Oxford) 2003 42(12) 1433-1444. 

Wedderbum LR, Robinson N, Patel A, Varsani H, Woo P. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum 2000 43(4) 765-774. 

Absorption/Distribution — CSF levels following IV administration are undetectable. Penetration of the drug into inflamed joints, the vitreous body of... 

It is effective for treatment of acute attacks of gout. It has no effect on renal excretion of uric acid. It binds to tubulin, it interferes with function of mitotic spindles, causes depolymerization and disappearance of fibrillar microtubules in granulocytes. In gout, the useful of colchicine is due to the inhibition of the release of glycoproteins from granulocytes in inflamed joint thus preventing precipitation of uric acid crystals and release of lysosomal enzymes. 

Cao D, Vollenhoven RV, Klareskog L, Trollmo C, Malstrom V. 2004. CD 25+CD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis Res Ther. 6 R335-346. 

Horseradish is stated to possess antiseptic, circulatory and digestive stimulant, diuretic, and vulnerary properties. Traditionally, it is used for pulmonary and urinary infection, urinary stones, edematous conditions, and externally as an application for inflamed joints or tissues. 

Bisphosphonates (particularly clodronate) have been shown to have anti-inflammatory effects in animal models of rheumatoid arthritis (RA), as well as in arthritis in humans. In adjuvant- and antigen-induced arthritis in rats, clodronate suppresses the inflammatory articular lesions in the inflamed joints [29], whilst in human RA, clodronate decreases the levels of interleukin (ILJ-1, tumor necrosis factor-alpha (TNFaand /1-microglobulin in the circulation [30]. In vitro, clodronate inhibits cytokine and nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in macrophage-like cells. 

Recently, we have provided evidence that hypoxic reperfusion injury occurs in the inflamed human joint [2,12,13]. Joint movement in patients with RA produces intra-articular pressures in excess of the synovial capillary perfusion pressure. This phenomenon does not occur in normal joints, where the pressure remains subatmospheric throughout a movement cycle. During exercise of the inflamed joint, the intra-articular pressure is transmitted directly to the synovial membrane vasculature, producing occlusion of the superficial synovial capillary bed and ischaemia. Reperfusion of the synovial membrane occurs when exercise is stopped. Recently, electron spin resonance spectroscopy with spin trapping was employed to demonstrate that synovial tissue from a patient with RA generated ROI following a transient hypoxic... 

Recently, we carried out immunohistochemical studies using an antibody directed against oLDL to demonstrate the presence of foam cells and fatty streaks around blood vessels within the sub-intimal lining of rheumatoid synovial tissue [125]. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples, even after correcting for total lipid concentrations [126],... 

Furthermore, either PGD2 or a DPI receptor agonist decreases responses to mechanical stimulation in rats with inflamed joints and the facilitatory effects of PGE2, and the inhibitory effect of PGD2 could have been resulted from the activation of GABAergic inhibitory intemeurons (Eguchi et al., 1999 Minami... 

Alkylosing spondylids is an inflammatory autoimmune reac-dve arthrids wdth a primary end organ target of the intervertebral Joints and the sacroiliac joint at the hip. The characterisdc features are a bowled spine and inflamed joints. Compared wdth 8% of Caucasians as a w hole, 95% of people wdth alkylosing spondylids have the HLA B27 allele. Unlike many autoimmune diseases, alkylosing spondylids is more common in men and has an early onset betw een 20 and 40 m years of age. 

The lower degree of polymerization of hyaluronic acid present in rheumatoid fluids (B3, BIO, B13, B18) undoubtedly impairs the effectiveness of the fluid as a lubricant between joints. Another factor contributing to this may be the lower concentration of hyaluronic acid found in certain rheumatoid effusions. Special viscosity and elastic properties are exhibited by hyaluronic acid in synovial fluid in concentrations in excess of 0.2 g/lOO ml (Bll) the concentration of hyaluronic acid in inflamed joint fluids of rheumatoid arthritis is generally less than this value. In a recent investigation, Hamerman and Sandson (H4) found that, apart from a reduced anomalous viscosity, the hyaluronate-protein complexes of synovial fluid differed from normal and showed increases in both protein content and amounts of basic amino acids. 

Wild sarsaparilla Avalia nudicaulis) has long been an ingredient of soft drinks. Aloe Aloe vera) once provided needles for early phonographs and remains important today as a salve in the treatment of bums and in cosmetics. Meadow saffron or fall crocus Colchicum au-tumnale) was used to treat gout (a painful disease of inflamed Joints), and is still much used in research. Cochic ine is extracted from the plant and used to pre-... 

DMARDs are used to prevent destruction of inflamed joints these drugs are potentially toxic and their use demands careful monitoring. 

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