{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:49:27Z","timestamp":1779097767626,"version":"3.51.4"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec>\n            <jats:title>Summary:<\/jats:title>\n            <jats:p>Objective evidence for the role of inhibition of collagen cross-linking in human scar using a nontoxic topical inhibitor, 1,4-diaminobutane (1,4 DAB), in patients with scars at risk for hypertrophic scar formation is presented. The authors used a concentration of 1,4 DAB of 0.8% (weight\/volume) in a cream base similar to Glaxal Base. Application was once per day at night. The control was treated with cream base alone. In treatment phase studies at 2 months, tissue biopsies were performed and used to determine a therapeutic effect biochemically in paired scars harvested chosen with typical hypertrophic scars at two major treatment centers. Tissue transglutaminase activity revealed a significant reduction of the \u03b5-(\u03b3-glutamyl)lysine cross-links in the treated scars: 7.96 \u00b1 1.51 pmol\/\u00b5mol amino acid versus 14.78 \u00b1 3.52 pmol\/\u00b5mol amino acid. A subset of paired scars (<jats:italic toggle=\"yes\">n<\/jats:italic> = 15) was also analyzed for soluble procollagen type III amino propeptide. The effect was a significant increase in procollagen type III amino propeptide in the scars treated with 1,4 DAB compared with sham-treated scars: 47.75 \u00b1 4.6 \u00b5g\/mg wet weight versus 39.08 \u00b1 6.02 \u00b5g\/mg wet weight, respectively. Levels of tissue 1,4 DAB was found to be twice as high in the presence of the active cream versus in the tissue of the control group. In subsequent prophylaxis studies, the authors treated 44 breast reduction patients prospectively with active cream to one or the other side in a double-blind randomized fashion. Hardness (in grams) measured using a Rex Durometer at 6 and 12 weeks postoperatively along with photographs were analyzed. The mean value \u00b1 SD of 24.98 \u00b1 1.2 g on the active side versus 31.76 \u00b1 1.1 g on the sham side was significantly different (<jats:italic toggle=\"yes\">p<\/jats:italic> &lt; 0.05). The patient scale scores of the Patient and Observer Scar Assessment Scale were also requested by survey in a responding 27-patient subgroup at a minimum 1 year postoperatively, and the differences between the two sides were found to be statistically significant, where the mean on the active side was 14.07 \u00b1 1.34 and the mean on the sham side was 21.41 \u00b1 1 (<jats:italic toggle=\"yes\">p<\/jats:italic> &lt; 0.05). The results are evidence to support the use of this agent in prevention of hypertrophic scars.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CLINICAL QUESTION\/LEVEL OF EVIDENCE:<\/jats:title>\n            <jats:p>Therapeutic, II.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/prs.0000000000006413","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T19:41:46Z","timestamp":1577216506000},"page":"76e-84e","source":"Crossref","is-referenced-by-count":7,"title":["A Preliminary Report of the Biochemical and Clinical Effects of 1,4-Diaminobutane on Prevention of Human Hypertrophic Scars"],"prefix":"10.1097","volume":"145","author":[{"given":"Kenneth N.","family":"Dolynchuk","sequence":"first","affiliation":[{"name":"From the Section of Plastic Surgery, Department of Surgery, University of Manitoba; and the Division of Plastic Surgery, Department of Surgery and Critical Care Medicine, University of Alberta."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward E.","family":"Tredget","sequence":"additional","affiliation":[{"name":"From the Section of Plastic Surgery, Department of Surgery, University of Manitoba; and the Division of Plastic Surgery, Department of Surgery and Critical Care Medicine, University of Alberta."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20231017","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0198-8859(90)90117-8","article-title":"The HLA-DR beta 16 allogenotype constitutes a risk factor for hypertrophic scarring.","volume":"29","author":"Castagnoli","year":"1990","journal-title":"Hum Immunol"},{"key":"R2-20231017","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1046\/j.1524-475X.1996.40105.x","article-title":"Inhibition of tissue transglutaminase and epsilon (gamma-glutamyl) lysine cross-linking in human hypertrophic scar.","volume":"4","author":"Dolynchuk","year":"1996","journal-title":"Wound Repair Regen"},{"key":"R13-20231017","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1097\/01.prs.0000172982.43599.d6","article-title":"Reliable and feasible evaluation of linear scars by Patient and Observer Scar Assessment Scale.","volume":"116","author":"van de Kar","year":"2005","journal-title":"Plast Reconstr Surg"},{"key":"R3-20231017","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/00006534-199601000-00019","article-title":"Topical putrescine (Fibrostat) in treatment of hypertrophic scars: Phase II study.","volume":"97","author":"Dolynchuk","year":"1996","journal-title":"Plast Reconstr Surg"},{"key":"R7-20231017","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/S0021-9258(19)75743-3","article-title":"Identification of a substrate site for liver transglutaminase on the aminopropeptide of type III collagen.","volume":"262","author":"Bowness","year":"1987","journal-title":"J Biol Chem"},{"key":"R8-20231017","first-page":"97","article-title":"The aminoterminal propeptide of type III procollagen and basement membrane components in serum during wound healing in man.","volume":"154","author":"Bensten","year":"1988","journal-title":"Acta Chir Scand"},{"key":"R9-20231017","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0363-5023(10)80136-4","article-title":"Transglutaminase levels in Dupuytren\u2019s disease.","volume":"16","author":"Dolynchuk","year":"1991","journal-title":"J Hand Surg Am"},{"key":"R10-20231017","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/jcp.1041490304","article-title":"Localization of cellular transglutaminase on the extracellular matrix after wounding: Characteristics of the matrix bound enzyme.","volume":"149","author":"Upchurch","year":"1991","journal-title":"J Cell Physiol"},{"key":"R11-20231017","doi-asserted-by":"crossref","first-page":"13768","DOI":"10.1021\/bi00042a007","article-title":"Transglutaminase-catalyzed cross-linking of fibrils of collagen V\/XI in A204 rhabdomyosarcoma cells.","volume":"34","author":"Kleman","year":"1995","journal-title":"Biochemistry"},{"key":"R12-20231017","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.0022-202X.2005.23771.x","article-title":"Hypertrophic scar cells fail to undergo a form of apoptosis specific to contractile collagen: The role of tissue transglutaminase.","volume":"125","author":"Linge","year":"2005","journal-title":"J Invest Dermatol"},{"key":"R6-20231017","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1177\/44.8.8756760","article-title":"Latent transforming growth factor-beta 1 and its binding protein are components of extracellular matrix microfibrils.","volume":"44","author":"Taipale","year":"1996","journal-title":"J Histochem Cytochem"},{"key":"R16-20231017","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1083\/jcb.121.2.439","article-title":"Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells.","volume":"121","author":"Kojima","year":"1993","journal-title":"J Cell Biol"},{"key":"R18-20231017","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1097\/00006534-199810000-00001","article-title":"Transforming growth factor-beta in thermally injured patients with hypertrophic scars: Effects of interferon alpha-2b.","volume":"102","author":"Tredget","year":"1998","journal-title":"Plast Reconstr Surg"},{"key":"R19-20231017","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/BF00455376","article-title":"Collagen polymorphism in pathologic human scars.","volume":"261","author":"Weber","year":"1978","journal-title":"Arch Dermatol Res"},{"key":"R20-20231017","doi-asserted-by":"crossref","first-page":"7016","DOI":"10.1016\/S0021-9258(18)50277-5","article-title":"Inhibiting effect of procollagen peptides on collagen biosynthesis in fibroblast cultures.","volume":"254","author":"Weistner","year":"1979","journal-title":"J Biol Chem"},{"key":"R21-20231017","first-page":"119","article-title":"Searching for the function of tissue transglutaminase: Its possible involvement in the biochemical pathway to programmed cell death.","volume":"231","author":"Fesus","year":"1988","journal-title":"Adv Exp Med Biol"},{"key":"R22-20231017","first-page":"CD003826","article-title":"Silicone gel sheeting for preventing of hypertrophic and keloid scars and for treating existing hypertrophic and keloid scars.","volume":"9","author":"O\u2019Brian","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"R23-20231017","first-page":"347","article-title":"Onion extract and quercetin induce matrix metalloproteinase-1 in vitro and in vivo.","volume":"25","author":"Cho","year":"2010","journal-title":"Int J Mol Med"},{"key":"R24-20231017","first-page":"3575","article-title":"The emerging role of antineoplastic agents in the treatment of keloids and hypertrophic scars: A review.","volume":"64","author":"Shriharani","year":"2010","journal-title":"Ann Plast Surg"}],"container-title":["Plastic &amp; Reconstructive 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