Rheumatoid Membrane

Rheumatoid arthritis represents a chronic inflammatory disease of the joints. About 1% of the population in Germany suffers from this disease. Primarily the synovial membranes of the jounts are affected, however, the disease can also reach other organs such as the pleura, pericardium organ and skin blood vessels. The inflamed... 

Winyard, P.G., Tatzber, F., Esterbauer, H., Kus, M.L., Blake, D.R. and Morris, C.J. (1993). Presence of foam cells containing oxidised low density lipoprotein in the synovial membrane from patients with rheumatoid arthritis. Ann. Rheum. Dis. 52, 677-680. 

Articulated joints between bones, for example at the knee, are covered in a capsule enclosing a space, which contains synovial fluid. The lining of the capsule is composed by the synovial membrane it is this synovium that becomes inflamed in rheumatoid arthritis (RA). Secretions produced by inflammatory cells (lymphocytes, macrophages... 

Rheumatoid arthritis (RA) is an inflammatory disease of the synovium which results in erosion, deformity and finally the destruction of joints. Inflammation of the joints is associated with a villous hypertrophy of the synovial membrane, which on microscopy shows proliferation of the lining layer with an inflammatory infiltrate. There is extensive expression of HLA-... 

Idiopathic thrombocytopenic purpura Membranous glomerulonephritis Polymyalgia rheumatica Polymyositis Psoriatic arthropathies Rheumatoid arthritis Systemic lupus erythematosus Ulcerative colitis Uveitis... 

TNF-a affects cellular function via activation of specific membrane-bound TNF receptors (TNFR1( TNFR2). Three drugs interfering with TNF-a. have been approved for the treatment of rheumatoid arthritis and other rheumatic diseases (Figure 36-4). 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

K10. Kinsella, T. D., Baum, J., and Ziff, M., Immunofluorescent demonstration of an IgG-pllC complex in synovial lining cells of rheumatoid synovial membrane. Clin. Exp. Immunol. 4, 265-271 (1969). 

Arthritis Arthritis is the general term for chronic pain in the joints the fingers, wrists, elbows, shoulders, knees, ankles, and feet. There are two types of arthritis— rheumatoid arthritis, which results from an inflammation of the thin membranes that line the joints, and the more common osteoarthritis, which results from a... 

The pharmacology of these drugs, which are also used in the treatment of malaria, is presented on p. 351. The mechanism of their anti-inflammatory activity is uncertain. Besides inhibiting nucleic acid synthesis, they are known to stabilize lysosomal membranes and trap free radicals. In treating inflammatory disorders, they are reserved for rheumatoid arthritis that has been unresponsive to the NSAIDs or else they are used in conjunction with an NSAID, which allows a lower dose of chloroquine or hydroxychloroquine to be administered. These drugs have been shown to slow progression of erosive bone lesions and may induce remission. They do cause serious adverse effects (see p. 351). 

Differential diagnoses of peripheral neuropathy were entertained. Laboratory tests revealed that serum parameters for electrolytes and proteins were all within the normal range. Urine porphyrinogen and porphobilinogen levels were normal. Tests were negative for serum rheumatoid factor and antinuclear antibodies, the latter used in detection of connective tissue diseases such as systemic lupus erythematosus and polyarteritis nodosa that could present with features of peripheral neuropathy. Nerve conduction studies of the radial, ulnar, and median nerves revealed delayed conduction. Biopsies of the ulnar and radial nerves showed loss of nerve fibers and sudanophilic (indicating lipid) deposits in the Schwann cells of the neurons. Similarly, the yellowish plaques of the pharynx showed abundant macrophages filled with sudanophilic material. These deposits were not membrane-bound. 

Fig. 2.8. Factors controlling the production of free radicals in cells and tissues (Rice-Gvans, 1990a). Free radicals may be generated in cells and tissues through increased radical input mediated by the disruption of internal processes or by external influences, or as a consequence of decreased protective capacity. Increased radical input may arise through excessive leukocyte activation, disrupted mitochondrial electron transport or altered arachidonic acid metabolism. Delocalization or redistribution of transition metal ion complexes may also induce oxidative stress, for example, microbleeding in the brain, in the eye, in the rheumatoid joint. In addition, reduced activities or levels of protectant enzymes, destruction or suppressed production of nucleotide coenzymes, reduced levels of antioxidants, abnormal glutathione metabolism, or leakage of antioxidants through damaged membranes, can all contribute to oxidative stress.

Oxidised LDL in the artery wall initiates a series of reactions designed to repair the damage it causes. Initial damage triggers an inflammatory response. Monocytes enter the artery waU from the bloodstream, with platelets adhering to the area of insult. This may be promoted by induction of factors such as vascular ceU adhesion molecule 1 (VCAM-1), a cell-surface sialoglycoprotein that is expressed by cytokine-activated endothelium. This membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of atherosclerosis and rheumatoid arthritis. 

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