{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:31:53Z","timestamp":1787585513215,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,6,6]],"date-time":"2013-06-06T00:00:00Z","timestamp":1370476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30\u2010CA77598"],"award-info":[{"award-number":["P30\u2010CA77598"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50\u2010CA101955"],"award-info":[{"award-number":["P50\u2010CA101955"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["KL2\u2010RR033182"],"award-info":[{"award-number":["KL2\u2010RR033182"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate clinical and immunohistopathological effects of topical glycyl\u2010histidyl\u2010lysine\u2010copper (GHK\u2010Cu) on in vivo irradiated rat wounds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Animal model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Academic institution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>After dorsal irradiation and a 28\u2010day recovery period, 2 \u00d7 8\u00a0cm cranially based dorsal flaps were created in Sprague\u2010Dawley rats. Twice daily GHK\u2010Cu gel (test) or aquaphilic ointment (control) was applied for 10\u00a0days. Animals were euthanized, digital images of flaps were taken, and harvested tissues were immunohistochemically stained for a vascular endothelium marker, caveolin\u20101, and vascular endothelial growth factor (VEGF). Digital image analysis was used for outcome measures. Unpaired <jats:italic>t<\/jats:italic>\u2010tests were used for statistical analyses; significance of <jats:italic>P<\/jats:italic> &lt;. 01 accounted for multiple comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By digital analysis of clinical images, 13 test and 10 control animals showed mean ischemic areas of 5.0\u00a0cm<jats:sup>2<\/jats:sup> (SD = 0.9) for tests and 3.8\u00a0cm<jats:sup>2<\/jats:sup> (SD = 1.1; <jats:italic>P<\/jats:italic> =. 011) for controls. Whole slide digitized images allowed quantification of caveolin\u20101\u2010stained blood vessels and VEGF expression in fibroblasts at the interface of healing flaps. Caveolin\u20101 analyses showed a mean of 209.0 vessels (SD = 111.1) and a mean vessel luminal area of 525.7 um<jats:sup>2<\/jats:sup> (SD = 191.0) in tests and 207.4 vessels (SD = 109.4; <jats:italic>P<\/jats:italic> =. 973) and 422.8 um<jats:sup>2<\/jats:sup> (SD = 109.7; <jats:italic>P<\/jats:italic> =. 118) in controls. VEGF quantified as the percentage of pixels exceeding a colorimetric threshold, with higher fractions of positive pixels indicating more intense staining, showed a mean intensity score of 0.34 (SD = 0.19) in tests and 0.54 (SD = 0.41; <jats:italic>P<\/jats:italic> =. 169) in controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Irradiated dorsal rat flaps treated with topical GHK\u2010Cu gel demonstrated no difference in flap ischemia, blood vessel number or area, or VEGF expression compared to controls.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599813492644","type":"journal-article","created":{"date-parts":[[2013,6,7]],"date-time":"2013-06-07T00:09:18Z","timestamp":1370563758000},"page":"384-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Topical Copper Tripeptide Complex on Wound Healing in an Irradiated Rat 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