Rheumatoid arthritis pathophysiology

Khurnana R, Bemey SM (2005) Clinical aspects of rheumatoid arthritis. Pathophysiology. 3 153-165. 

Harris ED. Rheumatoid arthritis pathophysiology and implications for therapy. N Engl J Med 1990 322 1277-89. Depression guidelines... 

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Describe the pathophysiology of rheumatoid arthritis, with emphasis on the specific immunologic components. 

At present, numerous free radical studies related to many pathologies have been carried out. The amount of these studies is really enormous and many of them are too far from the scope of this book. The main topics of this chapter will be confined to the mechanism of free radical formation and oxidative processes under pathophysiological conditions. We will consider the possible role of free radicals in cardiovascular disorders, cancer, anemias, inflammation, diabetes mellitus, rheumatoid arthritis, and some other diseases. Furthermore, the possibilities of antioxidant and chelating therapies will be discussed. 

Pathophysiologically normochromic and normo-cytic anaemia, as occurs in many clinical syndromes exemplified by renal failure, a number of cancers, rheumatoid arthritis and systemic lupus erythematosus, is typical. Initially erythrocytes are of normal size and degree of haemoglobinization. However, persistent impairment of iron supply, especially from mitochondria to globin in the cytoplasm, leads to them becoming hypochromic and microcytic. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

Schuna AA. Rheumatoid arthritis. In DiPiro JT, et al, eds. Pharmacotherapy A Pathophysiologic Approach. 5th ed. New York McGraw-Hill 2002. 

Kannan, K., Ortmann, R. A. and Kimpel, D. (2005) Animal models of rheumatoid arthritis and their relevance to human disease. Pathophysiology 12, 167-181. 

In investigations by the author (1), Chen (2), and Cochran (3), imidazo-, (I), pyrido[2,3-d]pyrimidin-7-ones, (II), and isoquinoline derivatives, (HI), respectively, were prepared, which were effective in treating p38 kinase-mediated disorders by modulating IL-1, IL-6, and IL-8 and TNF-a. These agents were used in treating pathophysiological disorders such as rheumatoid arthritis, fever, and reduction of bone resorption. 

In humans, T-lymphocyte proliferation, which is involved in the pathophysiology of rheumatoid arthritis (RA), was reduced with the administration of 2.4g GLA as borage seed oil, and was associated with increased GLA and DGLA concentrations in plasma cells and monocytes (Rossetti et al., 1997). In an open, uncontrolled study (Pullman-Moar et al., 1990), nine borage seed oil capsules daily were administered for 12 wk to seven patients with active RA, and to seven "normal" patients. DGLA increased in monocytes, and there was a decrease in the production of the inflammatory mediators PGE2, leukotriene B4, and leukotriene C4 by stimulated monocytes. In addition, the DGLA content of the phospholipid bilayer of plasma cells, mononuclear cells, and platelets increased. Six of seven RA patients improved clinically. 

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