Y tophus, although their chemical composition was unknown at that time.
Y tophus, although their chemical composition was unknown at that time. He wrote in 1679 [10]: “I observed the solid matter which to our eyes resembles chalk, and saw to my great astonishmentPage 2 of(page number not for citation purposes)Available online http://arthritis-research.com/content/8/S1/SEarlier, Seegmiller and colleagues [23] had described the relative roles of excessive urate production and impaired excretion in the pathogenesis of hyperuricemia.Treatments for gout through the agesAlthough there is evidence that colchicine, an alkaloid derived from the autumn crocus (Colchicum autumnale), was used as a powerful purgative in ancient Greece more than 2000 years ago [5], its first use as a selective and specific treatment for gout is attributed to the Byzantine Christian physician Alexander of Tralles in the sixth century AD [5]. Although colchicine was useful for the treatment of acute gout, it was recognized from earliest times that it could cause severe gastrointestinal side effects. Because of the great influence of Thomas Sydenham (`the English Hippocrates’), who rejected all medications that were purgatives as being too toxic for use, colchicine was not used for the treatment of gout for about 150 years [5] until its rediscovery in 1763 by Professor Baron Von Stoerk in Vienna [24]. In the modern era, nonsteroidal anti-inflammatory drugs (NSAIDs) are usually the drugs of choice for treating acute gout, whereas selective cyclo-oxygenase-2 inhibitors and intra-articular or systemic corticosteroids are used less frequently to control acute attacks in patients with relative contraindications to Imatinib (Mesylate) cost NSAIDs [25]. Although diet has long been recognized as a major causative factor in the pathogenesis of hyperuricemia and gout, dietary restriction or modification as a means of controlling gout and hyperuricemia has been and continues to be largely neglected. AB Garrod was among the first to suggest that hyperuricemia could be controlled by lowering the intake of purine-rich food [26]. This was confirmed by Haig in a series of clinical experiments he conducted on himself from 1894 to 1897 [27], and more recently in clinical physiological studies on patients given purine-free formula diets [28]. Uricosuric agents, which enhance the renal clearance of urate, were first used at the end of the 19th century [29]. See (1877) [30] was able to induce uricosuria and resolution of tophi in a patient with gout by administering large doses of salicylates. However, salicylates have a bimodal effect on urate excretion; at low doses they reduce urate excretion, whereas at high doses (4? g/day) they are uricosuric [31]. Salicylates were, however, not long used for treating patients with gout because of the toxicity and impracticality of highdose therapy, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27465830 and they were supplanted as uricosuric agents by probenecid [32], sulfinpyrazone [33], and benzbromarone [34]. More recently, the antihypertensive agent losartan (an angiotensin II antagonist) and the lipid-lowering fibrate fenofibrate were shown to have moderate uricosuric effects [35,36], although neither is licensed for the treatment of gout or hyperuricemia. In most mammalian species that express the enzyme urate oxidase (uricase), which converts urate to the more solubleand easily excreted compound allantoin, urate levels are low and gout does not occur. In 1957, London and Hudson published the first report of the use of uricase in two individuals: one with a long history of typical gouty arthrit.