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L- MESITRAN IN WOUND HEALING AND CARE

L-Mesitran, is the first range of unique honey-based wound products in Europe, in EU and Non-EU countries to be CE marked and carry FDA approval. L-Mesitran wound care products are produced by Triticum, in Maastricht, The Netherlands. Dr Theo Postmes, a leading pioneering scientist from the University Hospital of Maastricht, demonstrated the important wound healing capacity and quantification facts of honey.


HISTORICAL AND THEOLOGICAL PERSPECTIVE REGARDING WOUND HEALING BY ANCIENT PHYSICIANS. Natural Egyptian Medicine.

  • The Greek physician Hippocrates applied honey to cure skin disorders and Romans cleaned and sanitized wounds with it. At the same time silver, garlic and mustard was also in use.

  • Reference to the use of honey is reflected in translations of the Papyrus Ebers dating back about 1500 BC.
  • Honey has been used for treatment of wounds for more than 4000 years, and the medicinal properties have been known to ancient physicians (also used in cough elixirs).
  • According to Dr Monzur Ahmed, both the holy Qu’ran and Hadith refer to honey as a healer of disease. “ And thy Lord taught the bee to build its cells in hills, on trees and in ( men’s) habitations….. there issues from within their bodies a drink of varying colours, wherein is healing for mankind. Verily in this is a sign for those who give thought”. In addition, the Prophet ( PBUN) said: “ Honey is remedy for every illness and the Qu’ran is a remedy for all illness of the mind, therefore I recommend to you both remedies, the Qu’ran and honey” ( Bukhari).


IMPORTANT SCIENTIFIC LETTER IN THE LANCET 1993 REGARDING USE OF HONEY

Dr Postmes and co-workers of The Netherland’s, reported some important microbiological and quantification findings regarding honey that have stood the test of time.

  • The healing properties of honey relevant to wound healing and care are cleansing, resorption of wound oedema, anti-microbial activity, deodorization, granulation tissue enhancement, improvement of epithelilization.

  • Honey in the bottle is not always sterile.
  • Honey off the shelf can contain clostridial spores and can cause infant botulism. To-day, these potential hazards can be avoided by sterilization processing.
  • Components of different honeys are not constant and often contain residues and antibiotic contaminants such as tetracyclines.
  • Honey should only be used for clinical use from specified-pathogen-free hives (SPF).
  • Honey shows anti-bacterial activity against aerobes and anaerobes including S.aureus, Str.faecalis, Pseudomonas aeruginosa and E. coli to mention a few.
  • Lime tree honey seems better than both fruit tree and acacia-sourced honey.
  • Some honey products bought in the supermarket have no anti-bacterial activity.
  • Sterilization is possible without affecting the antibacterial activity.
  • For clinical use, honey should be sterile and free of residues.


RESEARCH ON HONEY REGARDING WOUND HEALING OUTCOMES: STUDIES FROM NEW ZEALAND ( MOLAN ET AL, SAGEPUB.COM)


  • There have been 17 trials confirming that honey assists wound healing.

  • There have been 16 experimental studies confirming that honey assists wound healing.
  • Case studies show evidence that honey assists wound healing.
  • There is very little published evidence to support use of nanocrystalline silver dressings.
  • Honey has a debriding action (in the wound, inactive plasminogen is converted to active plasmin and this process softens eschars and promotes granulation tissue).
  • Honey stimulates cytokine production by monocytes. This apparently can initiate the tissue repair process as well as the immune response to infection.
  • Honey can increase proliferation of B and T lymphocytes.
  • A publication by White and Molan, 2005 showed the following characteristics of honey treatment:
  1. Honey possesses antimicrobial properties.

  2. Honey application promotes autolytic debridement.
  3. Honey deodorizes malodorous wounds.
  4. Honey stimulates growth of wound tissue.
  5. Honey has anti-inflammatory properties (probably high sugar content and formation of hydrogen peroxide) and can minimize hypertrophic scarring.
  6. Honey promotes moist wound healing.
  7. In a recent publication from the University of Auckland, manuka impregnated honey-dressings rendered wound healing of venous ulcers as effective as standard usual care including compression bandages. ( Br J Surg 2008, 95:175-82)


WOUND HEALING ASSOCIATION OF SOUTHERN AFRICA ( WHASA): WWW.WHASA.ORG : Choice and recommendation of L- Mesitran dressings in the clinic.


Professor Sibbald, of Canada, has emphasized the importance of the DIME classification in wound healing and care:

  • D: debridment.

  • I: infection. Bacterial balance and moisture balance.
  • M: moisture.
  • E: advanced edge effect therapies for wounds with the ability to heal ( Wond Healing South Africa, 2008).

Some refer to the TIME classification ( tissue, infection or inflammation, moisture balance, and edge of wound)- this is a valuable clinical framework based on the assessment and treatment to the barriers of wound healing ( Schultz et al 2003). This was emphasized at the second congress of WHASA, held at the Indaba Hotel, in Johannesburg during May 2008. Professor Donald du Toit , FRCS of Stellenbosch, gave an academic overview on the cell biology, tissue culture, cell phenotypes and mode of action of L-Mesitran in wound healing and care. This referenced the unique biological effects on skin keratinocytes, dermal fibroblasts and adult adipose derived fibroblasts relevant to wound healing and care. L- Mesitran is distributed by Omnimed ( PTY).,LTD in Sandton, Johannesburg. Extensive cell biology research at Stellenbosch have demonstrated the advantages of honey over silver in wound care, based on cell biology technologies.

The characteristics of L- Mesitran fit in perfectly with the DIME or TIME classification, and therefore addresses all the important physiological issues of wound healing and repair cascade. Honey impregnated-dressings are included in the new classification of wound care dressings and will appear in the next edition of the journal.

L- Mesitran Hydro and Border are suitable for acute and chronic superficial wounds such as: bruises, cuts, bedsores, first and second-degree burns and other traumatic wounds, venous and arterial ulcera, diabetes ulcers, donor sites and post-operative wounds. Avoid use in wounds with deep, narrow cavities, in dirty wounds (which first must be cleansed), third-degree burns and fistulae.

L- Mesitran Active is highly effective for minor burns, superficial cuts, lacerations and abrasions and other small wounds. The dressing maintains a moist wound healing environment which fits in nicely with the DIME classification of Whasa.

L- Mesitran Net is suitable for acute and chronic superficial wounds such as: bruises, tears, pressure ulcers, venous and arterial ulcers, diabetes ulcers, donor sites, cuts, superficial burns, postoperative wounds and other traumatic wounds. Avoid heavily infected wounds, deep dirty wounds, third-degree burns and deep narrow cavities. Again, the moist environment supports optimal wound healing. Performance data show that L-Mesitran is non-irritating, non-sensitizing and non-toxic.

L- Mesitran wound gel is also available (i.e. soft: see WWW.L- Mesitran.com).

BIOTECHNOLOGY, TISSUE CULTURE AND CELLBIOLOGY: TISSUE ENGINEERING WITH HONEY–BASED DRESSINGS, FIBROBLASTS AND KERATINOCYTES: CELL RESEARCH AT STELLENBOSCH, IN CAPE TOWN

In vitro research in Cape Town during 2008, by lead cell-biology, surgical-scientist Professor Donald du Toit ( doctoral student from the University of Oxford { Wolfson College} and Stellenbosch University, has uncovered more secrets and TC properties ex vivo, relevant to the use of honey-impregnated dressings in the clinic, and more specifically wound healing and dressings. The Stellenbosch group has shown:

  • Co-culture with honey-based dressings increases proliferation of dermal fibroblasts ex vivo, without signs of cell toxicity.

  • Honey-based dressings co-cultured with Platelet-rich plasma (PRP), that contain platelet derived GF such as TGF, PDGF, EGF and VEGF, stimulates keratinocytes and fibroblasts further and that are relevant to wound healing.
  • Co-culture with honey-based dressings can stimulate spreading and branching of dermal and adult-derived adipose fibroblasts, both of which are critical for wound healing and ulcer closure. Silver-controls tended to have the opposite effect with cell inhibition in TC.
  • Keratinocytes are enhanced in TC by honey-based dressings, and form stabile monolayers compared to silver that most often inhibits and retards keratinocyte proliferation .
  • Honey-based dressings in co-culture enhance cell locomotion of fibroblasts and keratinocytes, ex vivo, both of which cell lines play a critical role in wound healing and contraction relevant to healing by secondary intention.
  • In comparative studies using silver-dressings wound healing cell lines were inhibited in proliferative studies ex vivo.
  • The provisional analysis is that this situation will mimic the wound healing scenario in vivo. There is no reason to suggest otherwise. From these ex vivo studies evaluating the effect of honey-based dressings it is clear that honey has an enhanced and positive effect on the cells without signs of toxicity. All controls, using varying doses of silver-based dressings had just the opposite effect, namely inhibition of keratinocytes and dermal fibroblasts. This suggests, at least in vitro, that L-Mesitran, has superior wound healing properties than equivalent silver dressings available on the market and in use for treatment of wounds. It is the opinion of these cell biologists, that this new evidence, regarding the TC properties of honey, should guide the wound care specialist rather in favour of first-line honey-based wound healing, that may well obviate cauterization and eschar formation commonly seen with the use of topical silver dressings. These, in vitro cell biology studies therefore strongly support the use of L-Mesitran dressings in wound healing and care as apposed to the use of silver-based dressings. These secrets, unlocked regarding the biological properties of honey, do suggest that silver–based dressings and products need re-evaluation by cell biologists, and that silver cannot be accepted, on the currant evidence provided, to be the universal and first-line or maintenance panacea treatment of acute or chronic wounds in the wound clinic and hospital leg ulcer unit.



WOUND HEALING AND DRAWBACKS OF SILVER-BASED AND IMPREGNATED DRESSINGS

  • Nanocrystalline silver released from some commercially available dressings, compared to honey-based dressings, are cell toxic, and sometimes visible as black eschar formation on the wound surface.

  • Silver in TC culture is cytotoxic to fibroblasts and keratinocytes, and therefore potentially inhibitory for wound healing, especially relevant in patients with poor wound healing. This is critically important in the wound clinic, and the cytotoxic effect of silver and silver-based products must be taken into account when deciding on wound dressings ( INIST-CNRS, 2006)
  • Suprahmanyam et al, in a burn-study, showed superior antimicrobial action of honey over sulphadiazine gauze dressings. In that study, burn healing was superior in honey treated subjects compared to silver.
  • Wang et al, from the Royal Australasian College of Medicine, studying wound healing outcome, question the effectiveness of silver dressings in the management of chronic wounds in a community setting.
  • Herman’s of the United States has stated that the antimicrobial efficacy of silver products is often inconclusive or contradictory (Am J Nursing 2006, 106.60-80.)
  • Fong and Wood (2006), of the Burns Service, Royal Perth Hospital West Australia have cautioned against the use of silver–containing bandages on epithelializing and proliferating wounds, because of the in vitro work that shows crystalline silver toxicity to keratinocytes and fibroblasts ( Int J Nanomedicine 2006, 1:441-9). Therefore some burns units in Australia are sensitive to the use of silver-impregnated dressings despite the publications on the antimicrobial spectrum silver properties.


CONCLUSIONS: Natural honey products, and honey impregnated dressings, such as L- Mesitran, for wound healing and care, offer the patient and doctor predictable outcomes. Honey is clearly, preferable to silver, because of the unique ex vivo cell biological characteristics that favour fibroblast and keratinocyte proliferation that play key roles in re-epithelialization.

Figure 1: An experienced medical doctor is often needed to fine tune and oversee dressings and options made by the nurse health-care professional.
Figure 2: A good wound care specialist is needed to treat chronic wounds as the healing is often protracted over many months.
Figure 3: Biotechnology and tissue culture: co-culture with honey- based dressing’s results in measured stimulation and proliferation of dermal fibroblasts; critical building blocks during wound healing.
Figure 4: Tissue engineering ex vivo: honey based-dressings in co-culture stimulate the growth and proliferation of human skin keratinocytes. Postmes, of The Netherland’s, has indicated that hydrogen peroxide is released in the wound by topical honey. Hydrogen peroxide produced by the Fenton reaction is bactericidal and stimulates fibroblast cell proliferation also detected by Cape Town cell biologists.
Figure 5: Tissue culture biology: Co-culture with honey-based dressings ex vivo results in controlled growth stimulation of adult adipose derived fibroblasts.
Figure 6: Honey-based stimulation of fibroblasts monolayer in 2D and 3D culture in TC ex vivo. Note branching, ruffling , filo- and lamellopodia, an indication of good locomotion of the cells ex vivo.
Figure 7: Comparative cell lines, including keratinocytes and dermal fibroblasts are inhibited by co-culture with silver-based dressings ex vivo.
Figure 8: Lower leg varicose ulcer suitable for treatment with L-Mesitran hydrocolloid and suitable compression bandages. We refer to this as ambulant out-patient varicose compression bandage therapy.

 


BOLANDCELL ACADEMIC REFERENCE PUBLICATIONS ON THE USE OF HONEY AND SILVER FOR CHRONIC WOUND HEALING AND CARE


HONEY:

  1. WWW.triticum.org/index

  2. Theo Postmes: The Lancet 341,756-757,1993
  3. Subrahmanyam M et al. Annals of Burns and Fire Disasters 19: 1-3, 2001
  4. Subrahmanyam M. Br J Surg 78: 497-8, 1991
  5. WWW.silverton.com/history.html ( silver wound care dressings).
  6. Hoekstra MJ et al: Br J of Plast Surg ( silver sulfadiazide )
  7. Molan PC. Jnl of Apicultural Res 27: 62, 1988
  8. White JW et al. Biochemica Biophysica Acta 73,37.1963
  9. Postmes T et al. Speeding up the healing of burns with honey. An experimental study with histological assessment of wound biopsies. Chapter in Book.
  10. Molan PC.. The evidence supporting the use of honey as a wound dressing. http://ijl.sagepub.com ( 2006)
  11. Molan PC et al. Nur Times 96:36-7.
  12. Alcaraz A et al: Br J Nurs 11: 859-60, 2002
  13. Trudie Young: Practice Nursing. 16:542-547, 2005
  14. Cooper RA et al. J Burn Care Rehábil 23: 366-70,2002
  15. Dunford CE et al. J Wound Care 13:193-7,2004
  16. Flanagan M. J Wound Care 9:287,2000
  17. Gethin G. J Wound Care 13:275-8, 2004
  18. White R. The benefits of honey in wound management. Nursing Standard 20.10, 57-64, 2005
  19. Al-Waili NS. Clinical Microbiology and Infection 11, 2 ,160-163, 2005
  20. Green AE. Br J Surg 75.12, 1278.1988
  21. Marshall C. Wounds UK. 1,1,10-18, 2005
  22. Molan PC. Ostomy Wound Healing. 48, 11, 28-40. 2002.
  23. Widgrow AD. Wound Healing SA. 5-15, 2008
  24. Naude L. Wound Healing SA. 16-24, 2008
  25. Sibbald RG et al. Wound Healing SA. 29-37, 2008 ( WWW.WOUNDHEALINGSA.CO.ZA)
  26. Weir G. Wound Healing SA. 44-48, 2008
  27. Cutting KF. Ostomy Wound Manage 53.49-54,2007
  28. Jull A et al. Br J Surg 95.175-82, 2008
  29. Misirlioglu A et al. Dermatol Surg 29,168-72, 2003
  30. Van der Weyden EA. Br J Community Nurs Suppl 1: S24, S 26-7, 2005
  31. Hendriques A et al. J Antimicrob Chemother 58: 773-7, 2006
  32. Visavadia BG et al. Br J Maxillofac Surg 46.258, 2008
  33. McIntosch CD et al. J Wound Care 15. 133-6, 2006
  34. Ingle R et al. Wound healing with honey--- a randomized trial. From the University of Limpopo ( Medunsa Campus). S Afr Med J 96.831-5, 2006
  35. Yapucu G et al. J Wound Ostomy Continence Nurs 34.184-90, 2007
  36. Mphande AN et al J Wound Care 16. 317-9, 2007
  37. Vandeputte J et al. Clinical evaluation of L- Mesitran…a honey based wound ointment. Professional Nursing To-day. 11. 26-31, 2007
  38. Du Toit DF et al. Specialist Forum SA, May, 2008. In Press.


SILVER

  1. Kim JS et al. Nanomedicine 3, 95-101, 2007

  2. Meaume S et al. Evaluation of a silver-releasing hydroalginate dressing in chronic wounds with signs of local infection. J Wound Care 14. 411-9, 2005
  3. Walker M et al. Ostomy Wound Manage 53. 32, 2007
  4. Wang J et al. J Wound Care 16. 352-6, 2007
  5. Percival SL et al. Int Wound J 4.186-91, 2007
  6. Hermans MH. Am J Nurs 106.60-8, 2006
  7. Vlachou E et al. Burns 33.979-85, 2007
  8. Hampton S. Br J Community Nurs 12.S24-30, 2007
  9. Percival SL et al. Ostomy Wound Manage 54: 30-40, 2008
  10. Vavassis P et al. J Otolaryngol 37.124-9,2008
  11. IP M et al. J Medical Microbiol 55.59-63, 2006
  12. Fong J et al. INT j Nanomedicine 1, 441-9,2006
  13. Epstein NE. Surg Neurol 68: 483-5, 2007


Posted: 20 May 2008

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