Rheumatoid arthritis pathology

Human tumor necrosis factor (TNF) (Fig. 1) is a hormone-like proinflammatory peptide belonging to the group of cytokines. It is mainly produced by cells of the immune system in response to infection, inflammation, or cell damage. Disregulated TNF is an important factor in many pathological situations, like sqDsis, rheumatoid arthritis, inflammatory bowel disease (Crohn s disease), and Cachexia. The cytotoxic activity of TNF is of interest in development of new antitumoral strategies. 

In the past number of years a number of studies have shown that in a variety of diseases there is a significant oxidation of Met residues to Met(O) in specific proteins that results in a loss of biological activity. These diseases include cataracts, rheumatoid arthritis, adult respiratory distress syndrome and emphysema. The most convincing evidence that Met(O) in proteins may be involved in the etiology of a pathological condition comes from studies with a-l-PI. It is well accepted that a-l-PI is inactivated upon oxidation of its Met residues. A decreased activity of a-l-PI in lung tissue that would result in an increased elastase activity has been associated with pulmonary emphysema. In patients who have a... 

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. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

Cat K inhibitor therapy may also result in protection against the development of atherosclerosis. Cat K-deficient mice show reduced atherosclerotic lesion number and size on an ApoE receptor-deficient background, compared to wild-type animals [38,39]. Cat K is also associated with increased adiposity in humans [27,28] and may also play a role as a kininase, suggesting a role in blood pressure regulation [40]. Cat K has also been postulated to play a role in the pathology of rheumatoid arthritis [41,42],... 

Figure 8.3. Morphological features of a normal and rheumatoid joint (a) the essential features of a healthy synovial joint (e.g. a knee joint) (b) the pathological features of a joint of a patient with rheumatoid arthritis.

Wasserman V. Development, Characterization, Optimization, and Pharmacokinetic Evaluation of Liposome-Based Piperidine Nitroxide Formulation for Treatment of Pathological Conditions Tumor and Rheumatoid Arthritis. Ph.D. thesis, 2002. 

Generalized/organ specific (lung disease, anemia, decreased blood supply) Cellular hypoxia (cyanide poisoning of electron transport chain in mitochondria) Inflammatory (pathology from abnormal inflammatory response in the body) Autoimmune and/or chronic diseases (systemic lupus erythmatosus, rheumatoid arthritis)... 

Rheumatoid arthritis and osteoarthritis represent the two primary pathologic conditions that affect the joints and periarticular structures. Although the causes underlying these conditions are quite different from one another, both conditions can cause severe pain and deformity in various joints in the body. Likewise, pharmacologic management plays an important role in the treatment of each disorder. Because physical therapists and other rehabilitation specialists often work with patients who have rheumatoid arthritis or osteoarthritis, an understanding of the types of drugs used to treat these diseases is important. 

Disease-modifying agents currently used in treating rheumatoid arthritis are listed in Table 16-3. As the name implies, DMARDs attempt to induce remission by modifying the pathologic process inherent to rheumatoid arthritis. In general, DMARDs inhibit certain aspects of the immune response thought to... 

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