344
Views
39
CrossRef citations to date
0
Altmetric
Reviews

Emerging drugs for the treatment of diabetic ulcers

, MD, , DPM & , MD MSc DSc
Pages 207-217 | Published online: 21 May 2013

Bibliography

  • Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999;22:382–7
  • Apelqvist J, Bakker K, van Houtum WH, et al. International consensus and practical guidelines on the management and the prevention of the diabetic foot. International working group on the diabetic foot. Diabetes Metab Res Rev 2000;16(Suppl 1):S84–92
  • Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 1994;130:489–93
  • Panuncialman J, Falanga V. The science of wound bed preparation. Surg Clin North Am 2009;89:611–26
  • Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic ulcer study group. J Am Coll Surg 1996;183:61–4
  • Falanga V. Wound healing and its impairment in the diabetic foot. Lancet 2005;366:1736–43
  • Falanga V, Sabolinski M. A bilayered living skin construct (apligraf) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen 1999;7:201–7
  • Armstrong DG, Nguyen HC, Lavery LA, et al. Off-loading the diabetic foot wound: a randomized clinical trial. Diabetes Care 2001;24:1019–22
  • Birke JA FB, Krieger LA, Sliman K. The effectiveness of an accommodative dressing in offloading pressure over areas of previous metatarsal head ulceration. Wounds 2003;15:33–9
  • Field FK, Kerstein MD. Overview of wound healing in a moist environment. Am J Surg 1994;167:2S–6S
  • Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-bb (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase iii randomized placebo-controlled double-blind study. Diabetes Care 1998;21:822–7
  • Veves A, Falanga V, Armstrong DG, Sabolinski ML. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001;24:290–5
  • Gentzkow GD, Iwasaki SD, Hershon KS, et al. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care 1996;19:350–4
  • Muhart M, McFalls S, Kirsner RS, et al. Behavior of tissue-engineered skin: a comparison of a living skin equivalent, autograft, and occlusive dressing in human donor sites. Arch Dermatol 1999;135:913–18
  • Mueller MJ, Sinacore DR, Hastings MK, et al. Effect of achilles tendon lengthening on neuropathic plantar ulcers. A randomized clinical trial. J Bone Joint Surg Am 2003;85-A:1436–45
  • Morykwas MJ, Faler BJ, Pearce DJ, Argenta LC. Effects of varying levels of subatmospheric pressure on the rate of granulation tissue formation in experimental wounds in swine. Ann Plast Surg 2001;47:547–51
  • Nather A, Chionh SB, Han AY, et al. Effectiveness of vacuum-assisted closure (vac) therapy in the healing of chronic diabetic foot ulcers. Ann Acad Med Singapore 2010;39:353–8
  • Eginton MT, Brown KR, Seabrook GR, et al. A prospective randomized evaluation of negative-pressure wound dressings for diabetic foot wounds. Ann Vasc Surg 2003;17:645–9
  • Armstrong DG, Lavery LA. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 2005;366:1704–10
  • Ubbink DT, Westerbos SJ, Evans D, et al. Topical negative pressure for treating chronic wounds. Cochrane Database Syst Rev 2008;CD001898
  • Wang C, Schwaitzberg S, Berliner E, et al. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg 2003;138:272–9. discussion 280
  • Knighton DR, Halliday B, Hunt TK. Oxygen as an antibiotic. A comparison of the effects of inspired oxygen concentration and antibiotic administration on in vivo bacterial clearance. Arch Surg 1986;121:191–5
  • Hunt TK, Pai MP. The effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet 1972;135:561–7
  • Londahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care 2010;33:998–1003
  • Wang FS, Wang CJ, Chen YJ, et al. Ras induction of superoxide activates erk-dependent angiogenic transcription factor hif-1alpha and vegf-a expression in shock wave-stimulated osteoblasts. J Biol Chem 2004;279:10331–7
  • Stojadinovic A, Elster EA, Anam K, et al. Angiogenic response to extracorporeal shock wave treatment in murine skin isografts. Angiogenesis 2008;11:369–80
  • Oi K, Fukumoto Y, Ito K, et al. Extracorporeal shock wave therapy ameliorates hindlimb ischemia in rabbits. Tohoku J Exp Med 2008;214:151–8
  • Saggini R, Figus A, Troccola A, et al. Extracorporeal shock wave therapy for management of chronic ulcers in the lower extremities. Ultrasound Med Biol 2008;34:1261–71
  • Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in u.S. Adults. The third national health and nutrition examination survey, 1988-1994. Diabetes Care 1998;21:518–24
  • Honeycutt AA, Boyle JP, Broglio KR, et al. A dynamic markov model for forecasting diabetes prevalence in the united states through 2050. Health Care Manag Sci 2003;6:155–64
  • Margolis DJ, Malay DS, Hoffstad OJ, et al. Economic burden of diabetic foot ulcers and amputations: data points #3. Data points publication series Agency for Healthcare Research and Quality (US); Rockville (MD): 2011
  • Sivan-Loukianova E, Awad OA, Stepanovic V, et al. Cd34+ blood cells accelerate vascularization and healing of diabetic mouse skin wounds. J Vasc Res 2003;40:368–77
  • Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type ii diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002;106:2781–6
  • Bauer SM, Goldstein LJ, Bauer RJ, et al. The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia. J Vasc Surg 2006;43:134–41
  • Lee JA, Conejero JA, Mason JM, et al. Lentiviral transfection with the pdgf-b gene improves diabetic wound healing. Plast Reconstr Surg 2005;116:532–8
  • Lee PY, Chesnoy S, Huang L. Electroporatic delivery of tgf-beta1 gene works synergistically with electric therapy to enhance diabetic wound healing in db/db mice. J Invest Dermatol 2004;123:791–8
  • Saaristo A, Tammela T, Farkkila A, et al. Vascular endothelial growth factor-c accelerates diabetic wound healing. Am J Pathol 2006;169:1080–7
  • Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005;353:999–1007
  • Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002;8:403–9
  • Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–5
  • Kaushal S, Amiel GE, Guleserian KJ, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 2001;7:1035–40
  • Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000;97:3422–7
  • Majka SM, Jackson KA, Kienstra KA, et al. Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest 2003;111:71–9
  • Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999;5:434–8
  • Grant MB, May WS, Caballero S, et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 2002;8:607–12
  • Otani A, Kinder K, Ewalt K, et al. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 2002;8:1004–10
  • Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001;7:1194–201
  • Frangioni JV, Beahm PH, Shifrin V, et al. The nontransmembrane tyrosine phosphatase ptp-1b localizes to the endoplasmic reticulum via its 35 amino acid c-terminal sequence. Cell 1992;68:545–60
  • Dube N, Tremblay ML. Involvement of the small protein tyrosine phosphatases tc-ptp and ptp1b in signal transduction and diseases: from diabetes, obesity to cell cycle, and cancer. Biochim Biophys Acta 2005;1754:108–17
  • Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, et al. Ptp1b regulates leptin signal transduction in vivo. Dev Cell 2002;2:489–95
  • Cheng A, Uetani N, Simoncic PD, et al. Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1b. Dev Cell 2002;2:497–503
  • Gunaratne P, Stoscheck C, Gates RE, et al. Protein tyrosyl phosphatase-1b is expressed by normal human epidermis, keratinocytes, and a-431 cells and dephosphorylates substrates of the epidermal growth factor receptor. J Invest Dermatol 1994;103:701–6
  • Sreejayan N, Lin Y, Hassid A. No attenuates insulin signaling and motility in aortic smooth muscle cells via protein tyrosine phosphatase 1b-mediated mechanism. Arterioscler Thromb Vasc Biol 2002;22:1086–92
  • Trop S, Tremblay ML, Bourdeau A. Modulation of bone marrow-derived endothelial progenitor cell activity by protein tyrosine phosphatases. Trends Cardiovasc Med 2008;18:180–6
  • Nakamura Y, Patrushev N, Inomata H, et al. Role of protein tyrosine phosphatase 1b in vascular endothelial growth factor signaling and cell-cell adhesions in endothelial cells. Circ Res 2008;102:1182–91
  • Stenzinger A, Schreiner D, Pfeiffer T, et al. Epidermal growth factor-, transforming growth factor-beta-, retinoic acid- and 1,25-dihydroxyvitamin d3-regulated expression of the novel protein ptpip51 in keratinocytes. Cells Tissues Organs 2006;184:76–87
  • Pu Q, Chang Y, Zhang C, et al. Chronic insulin treatment suppresses ptp1b function, induces increased pdgf signaling, and amplifies neointima formation in the balloon-injured rat artery. Am J Physiol Heart Circ Physiol 2009;296:H132–9
  • Lanahan AA, Hermans K, Claes F, et al. Vegf receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell 2010;18:713–24
  • Oshikawa J, Urao N, Kim HW, et al. Extracellular sod-derived h2o2 promotes vegf signaling in caveolae/lipid rafts and post-ischemic angiogenesis in mice. PLoS ONE 2010;5:e10189
  • Chang Y, Ceacareanu B, Zhuang D, et al. Counter-regulatory function of protein tyrosine phosphatase 1b in platelet-derived growth factor- or fibroblast growth factor-induced motility and proliferation of cultured smooth muscle cells and in neointima formation. Arterioscler Thromb Vasc Biol 2006;26:501–7
  • Kakazu A, Sharma G, Bazan HE. Association of protein tyrosine phosphatases (ptps)-1b with c-met receptor and modulation of corneal epithelial wound healing. Invest Ophthalmol Vis Sci 2008;49:2927–35
  • El Sayegh TY, Kapus A, McCulloch CA. Beyond the epithelium: cadherin function in fibrous connective tissues. FEBS Lett 2007;581:167–74
  • Quattrini C, Jeziorska M, Malik RA. Small fiber neuropathy in diabetes: clinical consequence and assessment. Int J Low Extrem Wounds 2004;3:16–21
  • Nakamura M, Kawahara M, Morishige N, et al. Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance p-derived peptide (fglm-nh2) and insulin-like growth factor-1. Diabetologia 2003;46:839–42
  • Movafagh S, Hobson JP, Spiegel S, et al. Neuropeptide y induces migration, proliferation, and tube formation of endothelial cells bimodally via y1, y2, and y5 receptors. FASEB J 2006;20:1924–6
  • Ekstrand AJ, Cao R, Bjorndahl M, et al. Deletion of neuropeptide y (npy) 2 receptor in mice results in blockage of npy-induced angiogenesis and delayed wound healing. Proc Natl Acad Sci USA 2003;100:6033–8
  • Kuo LE, Abe K, Zukowska Z. Stress, npy and vascular remodeling: implications for stress-related diseases. Peptides 2007;28:435–40
  • Delgado AV, McManus AT, Chambers JP. Exogenous administration of substance p enhances wound healing in a novel skin-injury model. Exp Biol Med (Maywood) 2005;230:271–80
  • Zukowska Z, Grant DS, Lee EW. Neuropeptide y: a novel mechanism for ischemic angiogenesis. Trends Cardiovasc Med 2003;13:86–92
  • Hokfelt T, Kellerth JO, Nilsson G, Pernow B. Substance p: localization in the central nervous system and in some primary sensory neurons. Science 1975;190:889–90
  • Harrison S, Geppetti P. Substance p. Int J Biochem Cell Biol 2001;33:555–76
  • Khawaja AM, Rogers DF. Tachykinins: receptor to effector. Int J Biochem Cell Biol 1996;28:721–38
  • Pernow B. Substance p. Pharmacol Rev 1983;35:85–141
  • Lindberger M, Schroder HD, Schultzberg M, et al. Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. J Neurol Sci 1989;93:289–96
  • Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Rose W, et al. Neuropeptide y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circ Res 1998;83:187–95
  • Wallengren J, Badendick K, Sundler F, et al. Innervation of the skin of the forearm in diabetic patients: Relation to nerve function. Acta Derm Venereol 1995;75:37–42
  • Toda M, Suzuki T, Hosono K, et al. Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis. Biomed Pharmacother 2008;62:352–9
  • Oltman CL, Davidson EP, Coppey LJ, et al. Treatment of zucker diabetic fatty rats with ave7688 improves vascular and neural dysfunction. Diabetes Obes Metab 2009;11:223–33
  • Hatanaka E, Monteagudo PT, Marrocos MS, Campa A. Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes. Clin Exp Immunol 2006;146:443–7
  • Fisman EZ, Adler Y, Tenenbaum A. Biomarkers in cardiovascular diabetology: interleukins and matrixins. Adv Cardiol 2008;45:44–64
  • Mastej K, Adamiec R. Neutrophil surface expression of cd11b and cd62l in diabetic microangiopathy. Acta Diabetol 2008;45:183–90
  • Stegenga ME, van der Crabben SN, Dessing MC, et al. Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans. Diabet Med 2008;25:157–64
  • Oncul O, Yildiz S, Gurer US, et al. Effect of the function of polymorphonuclear leukocytes and interleukin-1 beta on wound healing in patients with diabetic foot infections. J Infect 2007;54:250–6
  • Ochoa O, Torres FM, Shireman PK. Chemokines and diabetic wound healing. Vascular 2007;15:350–5
  • Dinh T, Tecilazich F, Kafanas A, et al. Mechanisms involved in the development and healing of diabetic foot ulceration. Diabetes 2012;61:2937–47
  • Caballero AE, Arora S, Saouaf R, et al. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes 1999;48:1856–62
  • Veves A, Akbari CM, Primavera J, et al. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes 1998;47:457–63
  • Menzoian JO, LaMorte WW, Paniszyn CC, et al. Symptomatology and anatomic patterns of peripheral vascular disease: differing impact of smoking and diabetes. Ann Vasc Surg 1989;3:224–8
  • Arora S, Pomposelli F, LoGerfo FW, Veves A. Cutaneous microcirculation in the neuropathic diabetic foot improves significantly but not completely after successful lower extremity revascularization. J Vasc Surg 2002;35:501–5
  • Boska M. Estimating the atp cost of force production in the human gastrocnemius/soleus muscle group using 31p mrs and 1h mri. NMR Biomed 1991;4:173–81
  • Greenman RL, Panasyuk S, Wang X, et al. Early changes in the skin microcirculation and muscle metabolism of the diabetic foot. Lancet 2005;366:1711–17
  • Greenman RL, Rakow-Penner R. Evaluation of the rf field uniformity of a double-tuned 31p/1h birdcage rf coil for spin-echo mri/mrs of the diabetic foot. J Magn Reson Imaging 2005;22:427–32
  • Pomposelli FB, Kansal N, Hamdan AD, et al. A decade of experience with dorsalis pedis artery bypass: analysis of outcome in more than 1000 cases. J Vasc Surg 2003;37:307–15
  • Greenman RL. Quantification of the 31p metabolite concentration in human skeletal muscle from rare image intensity. Magn Reson Med 2004;52:1036–42
  • Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic ulcer study group. J Vasc Surg 1995;21:71–8. discussion 79-81
  • Villela DL, Santos VL. Evidence on the use of platelet-rich plasma for diabetic ulcer: a systematic review. Growth factors 2010;28:111–16
  • Saad Setta H, Elshahat A, Elsherbiny K, et al. Platelet-rich plasma versus platelet-poor plasma in the management of chronic diabetic foot ulcers: a comparative study. Int Wound J 2011;8:307–12
  • Balingit PP, Armstrong DG, Reyzelman AM, et al. Norleu3-a(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial. Wound Repair Regen 2012;20:482–90
  • Bowen-Pope DF, Malpass TW, Foster DM, Ross R. Platelet-derived growth factor in vivo: levels, activity, and rate of clearance. Blood 1984;64:458–69
  • Lazarous DF, Shou M, Scheinowitz M, et al. Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury. Circulation 1996;94:1074–82

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.