Arthritis inflammatory

While the obvious value of in vivo animal models is clear, there also are instances—especially in cases of inflammatory arthritis, behavior, and tumor growth—where they have failed to be predictive of useful clinical activity in humans [51], For example, leukotriene (LTB4) antagonists showed activity in animal models of inflammatory arthritis yet failed to be useful in rheumatoid arthritis [52]. Similarly, dopamine D4 antagonists showed activity in animal behavior models previously predictive of dopamine D2 antagonists in schizophrenia. However, testing of dopamine D4 antagonists showed no efficacy in humans [53]. 

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

Gout is the most common inflammatory arthritis in the United States and western Europe. The annual incidence is approximately 62 cases per 100,000 persons in the United States. The incidence increases with age and appears to be rising probably because of a larger number of patients with risk factors for gout. 

Gout A group of disorders of purine metabolism, manifested by various combinations of hyperuricemia recurrent acute inflammatory arthritis induced by crystals of monosodium urate monohydrate tophaceous deposits of monosodium urate monohydrate crystals in and around the joints of the extremities, which may lead to crippling destruction of joints and uric acid urolithiasis. 

Leung BP, Conacher M, Hunter D, Mclnnes IB, Liew FY, Brewer JM. A novel dendritic cell-induced model of erosive inflammatory arthritis distinct roles for dendritic cells in T cell activation and induction of local inflammation. J Immunol 2002 169(12) 7071-7077. 

Kyburz D, Corr M. The KRN mouse model of inflammatory arthritis. Springer Semin Immunopathol 2003 25(l) 79-90. 

John S, Smith S, Morrison JF, et al. Genetic variation in CCR5 does not predict clinical outcome in inflammatory arthritis. Arthritis Rheum 2003 48(12) 3615—3616. 

Lande R, Giacomini E, Serafini B, et al. Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis. J Immunol 2004 173(4) 2815-2824. 

Most 8-selective PI3K inhibitors are derived from IC87114 26, which has an IC50 of 130 nM against PI3K8 and >100-fold selectivity over the a, (3, and y isoforms [99,100], and showed oral efficacy in a neutrophil-driven model of inflammatory arthritis [101]. 

Secondary OA is associated with a known cause such as rheumatoid arthritis or another inflammatory arthritis, trauma, metabolic or endocrine disorders, and congenital factors. 

Psoriatic arthritis is a distinct clinical entity in which both psoriatic lesions and inflammatory arthritis-like symptoms occur. Distal interphalangeal joints and adjacent nails are most commonly involved, but knees, elbows, wrists, and ankles may also be affected. 

Alvaro-Gracia, J. M., Zvaifler, N. J., Brown, C. B., Kaushansky, K., Firestein, G. S. (1991). Cytokines in chronic inflammatory arthritis VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-a J. Immunol 146,3365-71. 

Sulfasalazine anti-inflammatory (arthritis, inflammatory bowel disease) [18,441-445]... 

Rhenmatoid arthritis (RA) is a chronic systemic inflammatory arthritis that occurs in abont 1% of the population worldwide. Untreated, RA is associated with joint destruction, disability, and increased mortality (1). Early detection and therapy with disease-modifying antirheumatic drags (DMARDs) is critical in preventing these seqnelae of RA. With the recent advent of biologic DMARDs, which are effective bnt expensive therapies for RA, there has been a focns on developing methods that... 

Hyperuricemia-associated medical problems are clinical manifestations of gout by recurrent attacks of inflammatory arthritis, chronic tophaceous gout, uric acid urolithiasis, renal impairment, end stage renal disease and early mortality. These manifestations... 

Viral arthritis is rather common and usually selflimited within a few weeks. The most common pathophysiological mechanism is not a direct virus invasion in the synovium but deposition of immune complexes. Viral infections frequently involve multiple joints and produce inflammation without suppuration. The typical clinical presentation is a peripheral and symmetrical polyarthritis, undistin-guishable from other inflammatory arthritis. Virtually all viruses can cause arthritis. There is no specific treatment and simple symptomatic measures are sufficient. 

Anti-arthritic effect. Oral administration of AJA, a cannabinoid acid devoid of psychoactivity, reduced joint tissue damage in rats with adjuvant arthritis. Peripheral blood monocytes (PBM) and synovial fluid monocytes (SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AJA (0-30 mM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for messenger RNA (mRNA), and supernatants were collected for cytokine assay. Addition of AJA to PBM and SFM in vitro reduced both steady-state levels of interleukin-ly (IL-ly) mRNA and secretion of IL-ly in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 mM AJA (p < 0.05 vs untreated controls, n = 7). AJA did not influence tumor necrosis factor-a (TNF-a) gene expression in or secretion from PBM . 

St. John s wort has been used to treat a wide range of ailments for more than 2000 years, and is said to have been prescribed by Hippocrates himself. Apart from depression, St. John s wort is being promoted or used as a treatment for attention-deficit hyperactivity disorder (ADHD), anxiety, stress, obsessive-compulsive disorder, sleep problems, nocturnal enuresis, bacterial and viral infections such as HIV-AIDS, respiratory conditions, peptic ulceration, inflammatory arthritis, cancer, and skin wounds (Rey and Walter, 1998 Walter et ah, 2000). It is also said to increase libido, an application dating from the Middle Ages (Fletcher, 1996). No empirical evidence is currently available to support any of these uses. 

The glucocorticoids also have powerful anti-inflammatory effects and when first introduced were considered to be the ultimate answer to the treatment of inflammatory arthritis. Although there are increasing data that low-dose corticosteroids have disease-modifying properties,... 

Arnason BG Long-term experience with interferon beta-lb (Betaferon) in multiple sclerosis. J Neurol 2005 252(Suppl 3) iii28. Brown MA Antibody treatments of inflammatory arthritis. Curr Med Chem 2005 12 2943. [PMID 16378497]... 

N.A. Triterpene glycosides, actein, tannins, cimicifugoside, isoflavones, isoferulic acid, salicylic acid, resin.99-100 103 119-120 Promote menstrual flow, antirheumatic, expectorant, sedative. Treat inflammatory arthritis, high blood pressure, whooping cough, and asthma. 

Egan PJ, Lawlor KE, Alexander PS, Wicks IP. 2003. Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J Clin Inv. 111 915-924. 

Wong PKK, Egan PJ, Croker BA, Donnell KO, et al. 2004. SOCS3 negatively regulates innate and adaptive immune mechanism in acute IL-1 -dependent inflammatory arthritis. J Clin Inv. 116 1571-1581. 

Satsuma S, Scudamore RA, Cooke TDV, et al. 1993. Toxicity of complement for chrondytes. A possible source of cartilage degradation in inflammatory arthritis. Rheumatol Int 13 71-75. 

Ballara S, Taylor PC, Reusch P, Marme D, Feldmann M, Maini RN, et al. Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum 2001 44 2055-2064. 

Frankhn J, Lunt M, Bunn D, Symmons D, Silman A. Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory arthritis. Ann Rheumat Dis 2006 65 617-22. 

The most common types of arthritis in the UK are osteoarthritis (UK prevalence 23%) and rheumatoid arthritis (1%). The less common t3 es of inflammatory arthritis include juvenile idiopathic arthritis spondylarthritis (ankylosing spondylitis, Reiter s syndrome, psoriatic arthritis, arthritis associated with inflammatory bowel disecise) and reactive arthritis associated with infection. Joint pains (arthralgia) are common in many other diseases, for example the connective tissue diseases (systemic lupus erythematosus, scleroderma), endocrine conditions (hypo-and h5 erthyroidism) and malignancies, but in these, joint inflammation and damage do not usually occur. 

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