Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The leukotrienes (LTs) are a novel group of biologically active mediators derived from arachidonic acid via lipoxygenase enzymes. LTB4 is a potent chemotactic agent for polymorphonuclear leukocytes and in vivo may mediate inflammatory reactions by inducing leukocyte recruitment by mediating indirectly vascular permeability charges and by modulating pain responses. LTC4 and LTD4 collectively account for the biological activity known as slow-reacting substance of anaphylaxis and are potent smooth muscle contracting agents. They may mediate inflammatory reactions by producing changes in blood flow and increases in vascular permeability. Evidence for LT involvement in a number of pathological conditions including diseases such as asthma, psoriasis, ulcerative colitis, and gout is now accumulating.
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PMID:Leukotrienes: their formation and role as inflammatory mediators. 298 30

It is widely accepted that oxygen radicals and other activated oxygen species are potent mediators or modulators of acute and chronic inflammation. They are common products of cellular metabolism, where their concentrations are controlled by different protective mechanisms such as superoxide dismutase, catalase etc. In addition to their destructive effects on various macromolecules, oxygen radicals or their products are beneficial e.g., in killing bacteria. Oxygen radicals are also closely related to arachidonic acid metabolism, prostanoids (cyclo-oxygenase pathway) and leukotrienes (lipoxygenase pathway) as well as to lipid peroxidation in general. Also, the classical mediators of inflammation, histamine and bradykinin, may be connected with the release of oxygen radicals. In addition to the earlier described inhibition of formation of prostanoids, non-steroidal anti-inflammatory drugs can inhibit production of free radicals or scavenge those already formed. Antirheumatic penicillamine and allopurinol used in the treatment of gout also act on oxygen radicals. New anti-inflammatory compounds with antioxidant properties will be developed in the near future.
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PMID:Free radicals and anti-inflammatory drugs. 301 36

High levels of reactive oxygen species (ROS) are generated by phagocytes involved in host defence and inflammation. Thus, it appears highly desirable to learn more about the potential of antirheumatic drugs to scavenge ROS or to inhibit their enzymatic generation. Amplified chemiluminescence (CL) allows detection of O-2 using lucigenin (LgCL) or H2O2 using luminol (LuCL). A total of 43 compounds have been tested quantitatively in vitro (10(-6) to 10(-4) mol/l) with respect to three test parameters; varying cell-activity, and incubation-time employing two different phagocyte populations (neutrophils/macrophages). The most active compounds with LgCL were the known radical scavengers nordihydroguaiaretic acid (NDGA), N-propyl gallate, superoxide dismutase and chloroquine, the non-steroidal anti-inflammatory drugs (NSAID) benzydamine, timegadine, carprofen, enolicam, the known lipoxygenase inhibitors (e.g. CBS 1108/1114, BW 755C) and glucosaminoglucan polysulfate. Inactive in this system were corticosteroids (prednisolone, dexamethasone) most of the tested NSAID (N = 16/20), most disease modifying drugs (D-penicillamine, levamisole, gold-TM) and the anti-gout drugs (sulfinpyrazone, allopurinol, colchicine). Therefore amplified CL with lucigenin appears to be a rapid, kinetic, reproducible means of pharmacological profiling in vitro new anti-inflammatory drugs for radical scavenger activity.
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PMID:The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers. 303 4

An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.
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PMID:Persisting eicosanoid pathways in rheumatic diseases. 2451 15