{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:03:01Z","timestamp":1783486981127,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2008,12,16]],"date-time":"2008-12-16T00:00:00Z","timestamp":1229385600000},"content-version":"vor","delay-in-days":2176,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Graves' ophthalmopathy (GO) is a disorder of autoimmune origin caused by a complex interplay of endogenous and environmental factors. After recognition of one or more antigens shared by thyroid and orbit, activated T lymphocytes infiltrating the orbit trigger a cascade of events leading to production of cytokines, growth factors and oxygen reactive species. Proliferation of adipocytes and fibroblasts then follows, with an increased synthesis of glycosaminoglycans (GAG), which attract water and cause edema of orbital structures and venous congestion. Proliferation of orbital fibroblasts and adipocytes, both in the retroocular tissue and in the perimysium of extraocular muscles, are among the most important events leading to the increased volume of orbital structures (fibroadipose tissue and extraocular muscles). The contribution of oxygen reactive species to the changes occurring in the orbit is underscored by in vitro studies. Superoxide radical stimulates orbital fibroblasts to proliferate and to produce GAG. Furthermore, hydrogen peroxide induces expression of HLA\u2010DR and heat shock protein\u201072, involved in antigen recognition and T\u2010lymphocyte recruitment. Cigarette smoking, which is probably the most important environmental factor associated with GO occurrence and maintenance, might also act, among other mechanisms, by enhancing generation of oxygen reactive species and reducing antioxidant production. Substances such as nicotinamide, allopurinol and pentoxifylline reduce superoxide\u2010 or hydrogen peroxide\u2010induced proliferation of fibroblasts, GAG production and HLA\u2010DR or HSP\u201072 expression by GO orbital fibroblasts, possibly through scavenging oxygen free radicals. Two small, non\u2010randomized and\/or uncontrolled studies investigated the effects of nicotinamide, allopurinol or pentoxifylline on GO. Favorable results were reported, but data are not fully convincing and the true effectiveness of these agents needs to be verified in randomized, controlled trials enrolling a larger number of patients.It currently seems unlikely that they may find a relevant place in the limited armamentarium available for the management of severe GO.<\/jats:p>","DOI":"10.1002\/biof.5520190308","type":"journal-article","created":{"date-parts":[[2008,12,19]],"date-time":"2008-12-19T01:20:45Z","timestamp":1229649645000},"page":"155-163","source":"Crossref","is-referenced-by-count":68,"title":["Oxidative stress and Graves' ophthalmopathy: <i>In vitro<\/i> studies and therapeutic implications"],"prefix":"10.1002","volume":"19","author":[{"given":"Luigi","family":"Bartalena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Tanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Piantanida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.21.2.168"},{"key":"e_1_2_1_3_2","first-page":"747","article-title":"Graves' ophthalmopathy: current concepts regarding pathogenesis and management","volume":"14","author":"Burch H.B.","year":"1993","journal-title":"Endocr Rev"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(90)90099-5"},{"key":"e_1_2_1_5_2","unstructured":"J.M.McCordandK.Wong Phagocyte\u2010produced free radicals. In Oxygen free radicals and tissue damage Ciba Foundation Symposium Excerpta Medica Amsterdam(1979) 343\u2013351."},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-002-0813-6"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-351X(97)80738-0"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.8.3562"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1155"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.2.446"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1460457"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/105072502761016476"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1994.tb02445.x"},{"key":"e_1_2_1_14_2","first-page":"195","article-title":"The association between cigarette smoking and ocular diseases","volume":"6","author":"Cheng A.C.K.","year":"2000","journal-title":"Hong Kong Med J"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1997.0353"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.1.121"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5922"},{"key":"e_1_2_1_18_2","first-page":"322","article-title":"Pentoxifylline inhibits the proliferation and glycosaminoglycan synthesis of cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial myxoedema","volume":"129","author":"Chang C\u2010C.","year":"1993","journal-title":"Acta Endocrinol (Copenh)"},{"key":"e_1_2_1_19_2","first-page":"2037","article-title":"Stimulation of glycosaminoglycan production in cultured human retroocular fibroblasts","volume":"33","author":"Korducki J.M.","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-72-5-1169"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.1999.9.297"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.74.4.737"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-73-2-307"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1992.tb02907.x"},{"key":"e_1_2_1_25_2","first-page":"330","article-title":"Inhibitory effects of nicotinamide on intercellular adhesion molecule\u20101 expressio on cultured human thyroid cells","volume":"80","author":"Hiromatsu Y.","year":"1993","journal-title":"Immunology"},{"key":"e_1_2_1_26_2","first-page":"173","article-title":"Inhibitory effect of pentoxifylline on HLA\u2010DR expression and glycosaminoglycan synthesis of retrobulbar fibroblasts induced by interferon gamma","volume":"44","author":"Balazs C.","year":"1997","journal-title":"Acta Microbiol Immunol Hung"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978919"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7533326"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00359-7"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.82.6.9995"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbiof.5520190308","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.5520190308","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T16:29:07Z","timestamp":1693412947000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.5520190308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":29,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1002\/biof.5520190308"],"URL":"https:\/\/doi.org\/10.1002\/biof.5520190308","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]}}}