JCDSA  Vol.1 No.4 , December 2011
Dual Treatment Strategy by Venous Ulcers: Pilot Study to Dual-Frequency Ultrasound Application
Abstract: We propose a new dual treatment strategy by venous ulcer, consisting in simultaneous modulation of matrix metalloproteinases (MMPs) and heat shock proteins (HSPs) in the wound. One treatment method which can efficiently modulate both these substances is based on the application of dual-frequency ultrasound (LDM). This strategy was checked in a pilot study on 10 patients with chronic venous ulcers and demonstrated excellent healing rate.
Cite this paper: nullI. Kruglikov and E. Kruglikova, "Dual Treatment Strategy by Venous Ulcers: Pilot Study to Dual-Frequency Ultrasound Application," Journal of Cosmetics, Dermatological Sciences and Applications, Vol. 1 No. 4, 2011, pp. 157-163. doi: 10.4236/jcdsa.2011.14024.

[1]   N. L. Browse and K. G. Burnand, “The Cause of Venous Ulceration,” Lancet, Vol. 2, No. 8292, 1982, pp. 243-245. doi:10.1016/S0140-6736(82)90325-7

[2]   P. D. Smith, P. Thomas, J. H. Scurr and J. A. Dormandy, “Causes of Venous Ulceration: A New Hypothesis,” British Medical Journal, Vol. 296, No. 6638, 1988, pp. 1726- 1727. doi:10.1136/bmj.296.6638.1726

[3]   H. Cook, P. Stephens, K. J. Davies, K. G. Harding and D. W. Thomas, “Defective Extracellular Matrix Reorganization by Chronic Wound Fibroblasts is Associated with Alterations in TIMP-1, TIMP-2, and MMP-2 Activity,” Journal of Investigative Dermatology, Vol. 115, No. 2, 2000, pp. 225-233. doi:10.1046/j.1523-1747.2000.00044.x

[4]   Y. Herouy, “The Role of Matrix Metalloproteinases (MMPs) and Their Inhibitors in Venous Leg Ulcer Healing,” Phlebology, No. 44, 2004, pp. 231-243.

[5]   S. E. Gill and W. C. Parks, “Metalloproteinases and Their Inhibitors: Regulators of Wound Healing,” International Journal of Biochemistry & Cell Biology, Vol. 40, No. 6-7, 2008, pp. 1334-1347. doi:10.1016/j.biocel.2007.10.024

[6]   A. F. Laplante, V. Moulin, F. A. Auger, J. Landry, H. Li, G. Morrow, R. M. Tanguay and L. Germain, “Expression of Heat Shock Proteins in Mouse Skin during Wound Healing,” Journal of Histochemistry & Cytochemistry, Vol. 46, No. 11, 1998, pp. 1291-1301. doi:10.1177/002215549804601109

[7]   M. S. Bitar, T. Farook, B. John and I. M. Francis, “HeatShock Protein 72/73 and Impaired Wound Healing in Diabetic and Hypercortisolemic States,” Surgery, Vol. 125, No. 6, 1999, pp. 594-601. doi:10.1016/S0039-6060(99)70222-9

[8]   A. L. McMurtry, K. Cho, L. J. Young, C. F. Nelson and D. G. Greenhalgh, “Expression of HSP70 in Healing Wounds of Diabetic and Nondiabetic Mice,” Journal of Surgical Research, Vol. 86, No. 1, 1999, pp. 36-41. doi:10.1006/jsre.1999.5700

[9]   M. Atalay, N. Oksala, J. Lappalainen, D. E. Laaksonen, C. K. Sen and S. Roy, “Heat Shock Proteins in Diabetes and Wound Healing,” Current Protein & Peptide Science, Vol. 10, No. 1, 2009, pp. 85-95. doi:10.2174/138920309787315202

[10]   E. A. Rayment, Z. Upton and G. K. Shooter, “Increased Matrix Metalloproteinase-9 (MMP-9) Activity Observed in Chronic Wound Fluid is Related to the Clinical Severity of the Ulcer,” British Journal of Dermatology, Vol. 158, No. 5, 2008, pp. 951-961. doi:10.1111/j.1365-2133.2008.08462.x

[11]   R. Lobmann, A. Ambrosch, G. Schultz, K. Waldmann, S. Schiweck and H. Lehnert, “Expression of Matrix-Metalloproteinases and Their Inhibitors in the Wounds of Diabetic and Non-Diabetic Patients,” Diabetologia, Vol. 45, No. 7, 2002, pp. 1011-1016. doi:10.1007/s00125-002-0868-8

[12]   F. M. Ho, S. H. Liu, W. W. Lin and C. S. Liau, “Opposite Effects of High Glucose on MMP-2 and TIMP-2 in Human Endothelial Cells,” Journal of Cell Biochemistry, Vol. 101, No. 2, 2007, pp. 442-450. doi:10.1002/jcb.21192

[13]   P. Verbeke, J. Fonager, B. F. C. Clark and S. I. S. Rattan, “Heat Shock Response and Ageing: Mechanisms and Applications,” Cell Biololy International, Vol. 25, No. 9, 2001, pp. 845-857. doi:10.1006/cbir.2001.0789

[14]   C. S?ti, A. S. Sreedhar and P. Csermely, “Apoptosis, Necrosis and Cellular Senescence: Chaperone Occupancy as a Potential Switch,” Aging Cell, Vol. 2, No. 1, 2003, pp. 39-45. doi:10.1046/j.1474-9728.2003.00031.x

[15]   S. D. Morris, “Heat Shock Proteins and the Skin,” Clinical & Experimental Dermatology, Vol. 27, No. 3, 2002, pp. 220-224. doi:10.1046/j.1365-2230.2002.01012.x

[16]   M. Oberringer, H. P. Baum, V. Jung, C. Welter, J. Frank, M. Kuhlmann, W. Mutschler and R. G. Hanselmann, “Differential Expression of Heat Shock Protein 70 in Well Healing and Chronik Human Wound Tissue,” Biochemical & Biophysical Research Communications, Vol. 214, No. 3, 1995, pp. 1009-1014. doi:10.1006/bbrc.1995.2386

[17]   J. Chung, A.-K. Nguyen, D. C. Henstridge, A. G. Holmes, M. H. S. Chan, J. L. Mesa, G. I. Lancaster, R. J. Southgate, C. R. Bruce, S. J. Duffy, I. Horvath, R. Mestril, M. J. Watt, P. L. Hooper, B. A. Kingwell, L. Vigh, A. Hevener and M. A. Febbario, “HSP72 Protects against Obesity- Induced Insulin Resistance,” Proceedings of the National Academy of Sciences, Vol. 105, No. 5, 2008, pp. 1739- 1744. doi:10.1073/pnas.0705799105

[18]   M. M. Simon, A. Reikerstorfer, A. Schwarz, C. Krone, T. A. Luger, M. J??ttel? and T. Schwarz, “Heat Shock Protein 70 Overexpression Affects the Response to Ultraviolet Light in Murine Fibroblasts. Evidence for Increased Cell Viability and Suppression of Cytokine Release,” Journal of Clinical Investigation, Vol. 95, No. 3, 1995, pp. 926-933. doi:10.1172/JCI117800

[19]   E. Souil, A. Capon, S. Mordon, A. T. Dinh-Xuan, B. S. Polla and M. Bachelet, “Treatment with 815-nm Diode Laser Induces Long-Lasting Expression of 72-kDa Heat Shock Protein in Normal Rat Skin,” British Journal of Dermatology, Vol. 144, No. 2, 2001, pp. 260-266. doi:10.1046/j.1365-2133.2001.04010.x

[20]   L. Vígh, P. N. Literáti, I. Horváth, Z. T?r?k, G. Balogh, A. Glatz, E. Kovács, I. Boros, P. Ferdinándy, B. Farkas, L. Jaszlits, A. Jednákovits, L. Korányi and B. Maresca, “Bimoclomol: A Nontoxic, Hydroxylamine Derivative with Stress Protein-Inducing Activity and Cytoprotective Effects,” Nature Medicine, Vol. 3, No. 10, 1997, pp. 1150-1154. doi:10.1038/nm1097-1150

[21]   F. Reno, P. Grazianetti, M. Stella, G. Magliacani, C. Pezzuto and M. Cannas, “Release and Activation of Matrix Metalloproteinase-9 during in Vitro Mechanical Com- pression in Hypertrophic Scars,” Archives of Dermatology, Vol. 138, No. 4, 2002, pp. 475-478. doi:10.1001/archderm.138.4.475

[22]   K. Kaarniranta, C. I. Holmberg, M. J. Lammi, J. E. Eriksson, L. Sistonen and H. J. Helminen, “Primary Chondrocytes Resist Hydrostatic Pressure-Induced Stress while Primary Synovial Cells and Fibroblasts Show Modified Hsp70 Response,” Osteoarthritis & Cartilage, Vol. 9, No. 1, 2001, pp. 7-13. doi:10.1053/joca.2000.0354

[23]   C. Uhlemann and U. Wollina, “Wirkungsphysiologische Aspekte des Therapeutischen Ultraschalls in der Wundbehandlung,” Phlebologie, Vol. 32, No. 4, 2003, pp. 81-85.

[24]   M. Weichenthal, P. Mohr, W. Stegman and E. W. Breitbart, “Low-Frequency Ultrasound Treatment of Chronic Venous Ulcers,” Wound Repair & Regeneration, Vol. 5, No. 1, 1997, pp. 18-22. doi:10.1046/j.1524-475X.1997.50107.x

[25]   C. Roche and J. West, “A Controlled Trial Investigating the Effect of Ultrasound on Venous Ulcers Referred from General Practitioners,” Physiotherapy, Vol. 70, No. 12, 1984, pp. 475-477.

[26]   M. J. Callam, D. R. Harper and J. J. Dale, “A Controlled Trial of Weekly Ultrasound Therapy in Chronic Leg Ulceration,” Lancet, Vol. 330, No. 8852, 1987, pp. 204-206. doi:10.1016/S0140-6736(87)90776-8

[27]   T. Lundberg, F. Nordstrum, G. Brodda-Jansen, S. V. Ericsson, J. Kjartansson and U. E. Samuelson, “Pulsed Ultrasound does Not Improve Healing of Venous Ulcers,” Scandinavian Journal of Rehabilitation Medicine, Vol. 22, No. 4, 1990, pp. 195-197.

[28]   J. M. Watson, A. R. Kang’ombe, M. O. Soares, L.-H. Chuang, G. Worthy, J. M. Bland, C. Iglesias, N. Cullum, D. Torgerson and E. A. Nelson, “Use of Weekly, Low Dose, High Frequency Ultrasound for Hard to Heal Venous Leg Ulcers: The VenUS III Randomised Controlled Trial,” British Medical Journal, Vol. 342, 2011, p. d1092. doi:10.1136/bmj.d1092

[29]   J. Hart, “The Use of Ultrasound Therapy in Wound Healing,” Journal of Wound Care, Vol. 7, No. 1, 1998, pp. 25- 28.

[30]   S. R. Park, B. H. Choi and B.-H. Min, “Low-Intensity Ultrasound (LIUS) as an Innovative Tool for Chondrogenesis of Mesenchymal Stem Cells (MSCs),” Organogenesis, Vol. 3, No. 2, 2007, pp. 74-78.

[31]   W. Sontag and I. L. Kruglikov, “Expression of Heat Shock Proteins after Ultrasound Exposure in HL-60 Cells,” Ultrasound in Medicine & Biology, Vol. 35, No. 6, 2009, pp. 1032-1041. doi:10.1016/j.ultrasmedbio.2008.12.011

[32]   I. L. Kruglikov, W. Sontag, “Ultrasound of 10 MHz Frequency as a Novel Strategy for Skin Anti-Aging Therapy,” Medical Hypotheses, Vol. 74, No. 3, 2010, pp. 620- 621. doi:10.1016/j.mehy.2009.10.048