{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:27:02Z","timestamp":1791322022323,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,10,19]],"date-time":"2001-10-19T00:00:00Z","timestamp":1003449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic venous ulcers are an example of abnormal wound healing showing chronic inflammation which together with the underlying vascular pathology results in delayed healing. Prostaglandins are among the most important mediators of inflammation. They have proinflammatory effects, predominantly by affecting the vasculature. Cyclooxygenase (COX) is the rate\u2010limiting enzyme in prostanoid synthesis. It is present in two isoforms: COX\u20101 (constitutive cyclooxygenase) which is produced in the body to maintain normal haemostatic functions, and COX\u20102 (inducible cyclooxygenase), which is induced during inflammation in response to cytokines. Using immunoenzymatic labelling and western blot analysis, this study has shown that both COX\u20101 and COX\u20102 were up\u2010regulated in chronic venous leg ulcers by comparison with normal human skin. <jats:italic>De novo<\/jats:italic> appearance of COX\u20102 in chronic venous ulcers was demonstrated, which is not seen in normal human skin. The main cellular sources of both COX isoforms are macrophages and endothelial cells. COX\u20102 is also produced by mast cells and fibroblasts. A COX radioimmunoassay showed up\u2010regulation of COX activity in chronic venous ulcers compared with normal skin (<jats:italic>p<\/jats:italic>&lt;0.05). Up\u2010regulation of COX\u20101 in chronic venous leg ulcers could produce prostacyclin, which contributes to angiogenesis. Thus, inhibition of COX\u20101 by non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) could increase the local ischaemia and hypoxia associated with chronic venous ulcers. On the other hand, up\u2010regulation of COX\u20102 is most likely responsible for the persistent inflammation in chronic venous leg ulcers. COX\u20102 selective inhibitors could therefore be effective in the treatment of chronic venous ulcers. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.992","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T12:15:26Z","timestamp":1030277726000},"page":"616-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Expression of cyclooxygenase isoforms in normal human skin and chronic venous ulcers"],"prefix":"10.1002","volume":"195","author":[{"given":"Seham A.","family":"Abd\u2010El\u2010Aleem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W. J.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Appleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Bhowmick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N.","family":"McCollum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grenham W.","family":"Ireland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,10,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/00015555210317"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)90325-7"},{"key":"e_1_2_6_4_2","first-page":"100","article-title":"Pathogenesis of trophic ulcers in varicosity of the lower extremities","volume":"10","author":"Gostishcher KK","year":"1991","journal-title":"Khirurgiya"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.296.6638.1726"},{"key":"e_1_2_6_6_2","first-page":"1085","article-title":"Sequential changes in histological pattern and extracellular matrix deposition during the healing of chronic venous ulcers","volume":"141","author":"Herrick SE","year":"1992","journal-title":"Am J Pathol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.88.6.2510"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/362801a0"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199007053230106"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(74)90381-5"},{"key":"e_1_2_6_11_2","first-page":"179","article-title":"Biochemistry of prostaglandin endoperoxide H synthase\u20101 and synthase\u20102 and their differential susceptibility to nonsteroidal anti\u2010inflammatory drugs","volume":"15","author":"Smith WL","year":"1995","journal-title":"Semin Nepherol"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-3278(95)90039-X"},{"key":"e_1_2_6_13_2","first-page":"21","article-title":"Prostaglandin and protection of gastroduodenal mucosa","volume":"77","author":"Johansson C","year":"1982","journal-title":"Scand J Gastroentrol"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)34105-5"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.7.2692"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.16.7384"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1993.1601"},{"key":"e_1_2_6_18_2","first-page":"6823","article-title":"Molecular cloning of human prostaglandin endoperoxidase synthase type 2 and demonstration of expression in response to cytokines","volume":"264","author":"Jones DA","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116971"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.12.3.7873203"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.12013"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1995.tb01109.x"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00381.x"},{"key":"e_1_2_6_24_2","first-page":"1","volume-title":"Progress in Inflammation Research","author":"Willoughby DA","year":"1999"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/newbio231232a0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2046"},{"key":"e_1_2_6_28_2","first-page":"345","article-title":"Induction of prostaglandin\u2010H synthase\u20102 in rat carrageenan\u2010induced pleurisy and effect of selective COX\u20102 inhibitors","volume":"23","author":"Katori M","year":"1995","journal-title":"Adv Prostaglandin Thromboxane Leukotriene Res"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117060"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1999.5612"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112283"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(80)80762-7"},{"key":"e_1_2_6_33_2","first-page":"31","article-title":"Opposite regulation of prostaglandin E2 synthesis by transforming growth factor beta 1 and interleukin 10 in activated microglial culture","volume":"82","author":"Minghetti L","year":"1998","journal-title":"J Neurorheumatol"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15475.x"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051224"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH654>3.0.CO;2-S"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14441.x"},{"key":"e_1_2_6_38_2","first-page":"287","article-title":"Eicosanoids and inflammation","volume":"16","author":"Higgs GA","year":"1984","journal-title":"Ann Clin Res"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1969.tb08213.x"},{"key":"e_1_2_6_40_2","first-page":"791","volume-title":"Advances in Prostaglandin and Thromboxane Research","author":"Vane JR","year":"1976"},{"key":"e_1_2_6_41_2","first-page":"179","article-title":"Biochemistry of prostaglandin endoperoxidase\u2010H synthase\u20101 and synthase\u20102 and their differential susceptibility to NSAIDs","volume":"15","author":"Smith WL","year":"1995","journal-title":"Semin Neurol"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1400"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.27.6.1124"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00132-5"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.2.193"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041510317"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00019-2"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004030050307"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.1.99"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.992","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.992","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:38:51Z","timestamp":1761050331000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,10,19]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,12]]}},"alternative-id":["10.1002\/path.992"],"URL":"https:\/\/doi.org\/10.1002\/path.992","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,10,19]]},"assertion":[{"value":"2001-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}