• 1

    Singh N, Armstrong DG, Lipsky BA: Preventing foot ulcers in patients with diabetes. JAMA 293: 217, 2005.

  • 2

    Ramsey SD, Newton K, Blough D, et al.: Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 22: 382, 1999.

  • 3

    Dinh T, Tecilazich F, Kafanas A, et al.: Mechanisms involved in the development and healing of diabetic foot ulceration. Diabetes 61: 2937, 2012.

  • 4

    Tellechea A, Kafanas A, Leal EC, et al.: Increased skin inflammation and blood vessel density in human and experimental diabetes. Int J Low Extrem Wounds 12: 4, 2013.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Leal EC, Carvalho E, Tellechea A, et al.: Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype. Am J Pathol 185: 1638, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Wulff BC, Wilgus TA: Mast cell activity in the healing wound: more than meets the eye? Exp Dermatol 22: 507, 2013.

  • 7

    Sismanopoulos N, Delivanis D-A, Alysandratos K-D, et al.: Mast cells in allergic and inflammatory diseases. Curr Pharm Des 18: 2261, 2012.

  • 8

    Theoharides TC, Alysandratos K-D, Angelidou A, et al.: Mast cells and inflammation. Biochim Biophys Acta 1822: 21, 2012.

  • 9

    Komi DEA, Khomtchouk K, Santa Maria PL: A review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clin Rev Allergy Immunol 58: 298, 2020.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Nishikori Y, Shiota N, Okunishi H: The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice. Arch Dermatol Res 306: 823, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Tellechea A, Leal EC, Kafanas A, et al.: Mast cells regulate wound healing in diabetes. Diabetes 65: 2006, 2016.

  • 12

    Tellechea A, Bai S, Dangwal S, et al.: Topical application of a mast cell stabilizer improves impaired diabetic wound healing. J Invest Dermatol 140: 901, 2020.

  • 13

    Fathabadie FF, Bayat M, Amini A, et al.: Effects of pulsed infra-red low level-laser irradiation on mast cells number and degranulation in open skin wound healing of healthy and streptozotocin-induced diabetic rats. J Cosmet Laser Ther 15: 294, 2013.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Bagheri M, Amini A, Abdollahifar M-A, et al.: Effects of photobiomodulation on degranulation and number of mast cells and wound strength in skin wound healing of streptozotocin-induced diabetic Rats. Photomed Laser Surg 36: 415, 2018.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Petrosino S, Puigdemont A, Della Valle MF, et al.: Adelmidrol increases the endogenous concentrations of palmitoylethanolamide in canine keratinocytes and down-regulates an inflammatory reaction in an in vitro model of contact allergic dermatitis. Vet J 207: 85, 2016.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Cerrato S, Brazis P, Della Valle MF, et al.: Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs. Vet J 191: 377, 2012.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Petrosino S, Iuvone T, Di Marzo V: N-palmitoyl-ethanolamine: biochemistry and new therapeutic opportunities. Biochimie 92: 724, 2010.

  • 18

    Kendall AC, Nicolaou A: Bioactive lipid mediators in skin inflammation and immunity. Prog Lipid Res 52: 141, 2013.

  • 19

    Abramo F, Salluzzi D, Leotta R, et al.: Mast cell morphometry and densitometry in experimental skin wounds treated with a gel containing adelmidrol: a placebo controlled study. Wounds 20: 149, 2008.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Abramo F, Noli C, Giorgi M, et al.: Elastic fibres and mast cells in canine open skin wounds treated with an aliamide-based gel: a morphometric study. Vet Dermatol; p 354; 2005.

    • Search Google Scholar
    • Export Citation
  • 21

    Mantis P, Lloyd D, Pfeiffer D, et al.: Assessment of the effect of an aliamide-containing topical gel by evaluation of the reduction of wound volume measured by high resolution ultrasound biomicroscopy. Wounds 19: 113, 2007.

    • Search Google Scholar
    • Export Citation
  • 22

    Zimmerman DC, Coudron CA: Identification of traumatin, a wound hormone, as 12-oxo-trans-10-dodecenoic acid. Plant Physiol 63: 536, 1979.

  • 23

    Vick BA, Zimmerman DC: Lipoxygenase and hydroperoxide lyase in germinating watermelon seedlings. Plant Physiol 57: 780, 1976.

  • 24

    Gardner HW: 9-Hydroxy-traumatin, a new metabolite of the lipoxygenase pathway. Lipids 33: 745, 1998.

  • 25

    Miyamoto I, Uchida Y, Shinomiya T, et al.: Effects of cosmetics containing bioactive substances on skin. J Soc Cosmet Chem Japan 22: 254, 1989.

    • Search Google Scholar
    • Export Citation
  • 26

    Trypuc´ AJ, Pankiewicz W, Czerpak R: Traumatic Acid Reduces Oxidative Stress and Enhances Collagen Biosynthesis in Cultured Human Skin Fibroblast. Lipids 51: 10211035, 2016.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Lavery LA, Armstrong DG, Harkless LB: Classification of diabetic foot wounds. J Foot Ankle Surg 35: 528, 1996.

  • 28

    AMD: Documento di consenso: trattamento dell’arteriopatia periferica nel diabetico. Il Giornale di AMD 16: 72, 2013.

  • 29

    Bakker k, Apelqvist J, Lipsky B, et al.: The 2015 IWGDF guidance documents on prevention and management of foot problems in diabetes: development of an evidence-based global consensus. Diabetes Metab Res Rev 32: 2, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Sheehan P, Jones P, Caselli A, et al.: Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care 26: 1879, 2003.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Sheehan P, Jones P, Giurini JM, et al.: Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Plast Reconstr Surg 117: 239S, 2006.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Siracusa R, Impellizzeri D, Cordaro M, et al.: Topical application of adelmidrol + trans-traumatic acid enhances skin wound healing in a streptozotocin-induced diabetic mouse model. Front Pharmacol 9: 871, 2018.

    • Crossref
    • Search Google Scholar
    • Export Citation

Effect of a Topical Gel Based on Adelmidrol + Trans-Traumatic Acid in the Treatment of Diabetic Foot Ulcers: An Open-Label Study

View More View Less
  • 1 Division of Endocrinology, Diabetes, and Metabolism, Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Restricted access

Background: Diabetic foot ulceration is a severe complication of diabetes characterized by chronic inflammation and impaired wound healing. This study aimed to evaluate the effect of a medical device gel based on adelmidrol + trans-traumatic acid in the healing process of diabetic foot ulcers.

Methods: Thirty-seven diabetic patients with foot ulcers of mild/moderate grade were treated with the gel daily for 4 weeks on the affected area. The following parameters were evaluated at baseline and weekly: 1) wound area, measured by drawing a map of the ulcer and then calculated with photo editing software tools, and 2) clinical appearance of the ulcer, assessed by recording the presence/absence of dry/wet necrosis, infection, fibrin, neoepithelium, exudate, redness, and granulation tissue.

Results: Topical treatment led to progressive healing of diabetic foot ulcers with a significant reduction of the wound area and an improvement in the clinical appearance of the ulcers. No treatment-related adverse events were observed.

Conclusions: The results of this open-label study show the potential benefits of adelmidrol + trans-traumatic acid topical administration to promote reepithelialization of diabetic foot ulcers. Further studies are needed to confirm the observed results.

Corresponding author: Ilaria Teobaldi, DPM, Division of Endocrinology, Diabetes, and Metabolism, Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Aristide Stefani, 1, Verona, 37126 Italy. (E-mail: ilaria.teobaldi@aovr.veneto.it)