Post on 03-Apr-2018
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Smith papyrus 2600 – 2200 BC grease-honey-lint as wound dressing
Sumerian clay tablet c. 2000 BC various prescriptions
Ebers papyrus c. 2000 BC 300 prescriptions
Aristotle 350 BC sore eyes, wounds
Dioscorides c. 1 AD sores, ulcers, throat & eye infections
Dioscorides (c.50 AD) - an early herbalist
Dioscorides wrote of honey being good for: • sunburn • spots on the face
He also wrote that honey heals inflammation
of the throat and tonsils
Honey has been used for infected
wounds throughout all ages –
displaced by penicillin in 1940s
It is being “rediscovered” now that the ‘antibiotic era’ is coming to an end
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THE TENNESSEAN Apr. 28, 2012 MRSA is one of the more prevalent, potentially deadly, germs spread in gyms and locker rooms. MRSA (methicillin-resistant Staphylococcus aureus) is a type of Staph bacteria found on the skin and in the nose that is resistant to antibiotics. More than 90,000 Americans get potentially deadly MRSA infections every year and more than 18,000 die each year from this deadly disease.
Aristotle (350 BC), discussing differences in honeys, referred to pale honey being good as a salve for sore eyes and wounds
Aristotle (350 BC) Historia Animalium
Dioscorides (c.50 AD) stated that:
"Attick Hony is the best… That which is best… a pale yellow, not liquid…is good for all rotten & hollow ulcers.“
Gunther (1934) The Greek Herbal of Dioscorides
The potency of the anti-bacterial activity of honey can vary 100-fold
In present-day
folk medicine,
specific honeys
are known to be
the best to use
as medicines
NZ folk knowledge: manuka honey is best
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All honey: glucose gluconic acid
+ + oxygen hydrogen peroxide
glucose oxidase
All honey: glucose gluconic acid
+ + oxygen hydrogen peroxide
glucose oxidase
Was there something else in manuka honey?
Tested honey solutions with
catalase added to destroy hydrogen
peroxide
Manuka honey is unique – it still has full antibacterial activity with catalase added
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Honey does not produce hydrogen peroxide unless it is diluted
It continues to do so only for about 24 – 48 hours after it is diluted
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A standard antiseptic, phenol, is used for comparison
0
10
20
30
40
50
60
70
0-5 6-10 11-15 16-20 21-25 26-30 31-35Activity (equivalent % phenol)
Num
ber
of s
ampl
es
Non-peroxide activity of samples of manuka honey
Reasons for the variation:
• different varieties of manuka
• blending with other nectars
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2 months after heart surgery MRSA could not be cleared
8 days after using honey: MRSA cleared Wound closed 10 days later
Sores from menigitis infected with antibiotic-resistant bacteria, not cleared for 8 months
Diabetic ulcer not responding to treatment or
antibiotics
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Standards for medical honey: • Foreign matter <50 µm • Microbiology <50 cfu/g
(before sterilisation) • Free from antibiotic residues • Free from agricultural chemicals • Traceability to hive
Composition of honey: • ~18% water • 80% sugars (fructose 39%,
glucose 33%, others 8%) • 0.2% protein • gluconic acid (pH 3.2 - 4.5) • traces of vitamins & minerals • antioxidants
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The high osmolarity from the sugar content of honey stops the growth of microorganisms
– but some, especially Staph. aureus, can grow when honey gets diluted by wound fluid
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Neutrophils squirm out from gaps in the walls of capillaries. They and macrophages capture and engulf bacteria by phagocytosis to destroy them
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Dormant protein-digesting enzymes in wound tissues are activated by oxidation by H2O2
The over-active enzymes digest the
matrix and tissue growth factors
The cytokines and cell growth factors produced by leukocytes stimulate growth of fibroblasts, epithelial cells and vascular cells (angiogenesis)
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With matrix Matrix destroyed
The matrix in a healing wound is essential for cell attachment for
migration and multiplication
Attachment stimulates fibroblasts to
move along the strands of the matrix
It also stimulates them to multiply Epithelial cells migrate across the matrix
(using fibronectin-integrin contact)
Bacteria in wound
Inflammatory response
Exudation of serum
Good nutrition for bacteria
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MIC values for species of bacteria for manuka honey with near median levels of antibacterial activity:
Staphylococcus aureus from infected wounds: 2%–3% (v/v) honey
Cooper R A et al. (1999) J. Royal Soc. Medicine 92: 283-285 Pseudomonas from infected wounds: 5.5%–8.7% (v/v) honey
Cooper, R. A.; Molan, P. C. (1999) J. Wound Care 8: 161-164 MRSA from infected wounds: 2.7–3.0% (v/v) honey VRE from hospital surfaces: 3.8–5.0% (v/v) honey
Cooper, Molan & Harding (2002) J. Applied Microbiology 93: 857-863
β-Haemolytic streptococci from wounds: 4.5%–9.7% (v/v) honey Cooper R A et al. (2000) First World Congress on Wound Healing: Melbourne
Coagulase-negative Staphylococci isolates: 3–3.5% (v/v) honey French, V.M. et al. (2004) J. Antimicrob. Chemo. 56: 228-231
5 isolates of Acinetobacter baumannii
MIC No. of isolates Manuka honey 6% 2
7% 1 8% 1
>8% 1 Pasture honey >7% 5
Unpublished work conducted with the Central Public Health Laboratory, Colindale, London
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4 isolates of Stenotrophomonas maltophilia
MIC No. of isolates Manuka honey 3% 3
4% 1 Pasture honey <4% 1
5% 1 6% 2
Unpublished work conducted with the Central Public Health Laboratory, Colindale, London
MIC values for clinical isolates for Medihoney:
20 strains MRSA 4%
28 strains nMRSA 4%
20 strains VRE 6-8%
30 strains Ps. aeruginosa 6-8%
11 strains Acinetobacter 6-8%
28 strains ESBL 6-8% (10 E. coli, 12 Klebsiella, 6 Enterobacter)
George N (2004) Australian Infection Control Conference: Hobart
Alandejani, T. et al. (2009). Effectiveness of honey on Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Otolaryngology–Head and Neck Surgery 141(1): 114-118
Maddocks, S. E. et al. (2012). Manuka honey inhibits the
development of Streptococcus pyogenes biofilms and causes reduced expression of two fibronectin binding proteins. Microbiology 158: 781-790
Merckoll, P. et al. (2009). Bacteria, biofilm and honey: A study of
the effects of honey on 'planktonic' and biofilm-embedded chronic wound bacteria. Scandinavian Journal of Infectious Diseases 41(5): 341-347
Okhiria, O. A. et al. (2009). Honey modulates biofilms of
Pseudomonas aeruginosa in a time and dose dependent manner. Journal of ApiProduct and ApiMedical Science 1(1): 6-10
Honey has other advantages for wound
treatment besides antibacterial activity
• moist healing environment
• autolytic debriding action
• anti-inflammatory action
• stimulates cell growth
Wounds heal 50% faster if a moist environment is maintained
Winter, GD & Scales JT 1963 Nature 197: 91-92
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So why are wounds often kept dry? Bacteria thrive in moist conditions
The osmotic action of honey draws out fluid
The osmotic action of honey draws out fluid
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Like a Vac, draws out nutrifying fresh serum
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A moist environment can also cause maceration of skin around the wound
Slough harbours bacteria ��inflammatory response
Debridement is needed to remove harboured bacteria
Slough harbours bacteria ��inflammatory response
Streptokinase is expensive
Maggots are problematical
Moist autolysis �� bacterial growth
Published evidence is:
• honey works faster than autolytic debridement
• honey compares well with surgical debridement
• honey stops slough forming on fresh wounds
Molan P. C. (2009) ‘Debridement of wounds with honey’ Journal of Wound Technology 5: 12-7
3 days after using honey dressings
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Proposed mechanism of action:
• Slough is attached by a fibrin clot which is digested by a protease
• Is there activation of plasmin, which digests only fibrin, not matrix?
Conclusions from the study: • A mechanism for the debriding action
of honey has been found
• This activity varies in potency between different batches of honey
• The debriding activity of honey dressings can now be standardised
Anti-inflammatory effect of honey on wounds • observed clinically (reported in many papers):
visibly reduces inflammation reduces oedema, exudation and pain
• observed histologically: fewer neutrophils present in: biopsy samples from burns 5 animal studies with no infection present
Reviewed in: Molan, P. C. (2002)
Ostomy/Wound Management 48: 28
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6 RCTs have been published on using honey on burns, demonstrating its effectiveness in reducing inflammation
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Chapter 2 Characterising THP-1
55
It can be seen that all three treatments gave a significant increase in
phagocytosis with the treatments giving significantly different degrees of
activation of phagocytosis from each other. The effect of PMA was
approximately twice that of Vit-D3 and of LPS was a further three times greater.
Figure 2.12. Time lapse photographs under a fluorescent microscope of an LPS-activated macrophage (100 ng/ml LPS for 1 day) phagocytising a FITC-labelled latex particle. The whole event took approximately 25 seconds. As the cell moves, other particles already phagocytosed become visible (400 x magnification).
Time-lapse photography of phago-cytosis of fluorescent latex beads
The effect of manuka honey on phagocytosis with zymosan (yeast cell wall fragments)
The effect of 0.25% various honeys on phagocytosis (The error bars show the standard deviation)
!
The anti-inflammatory activity was not correlated with the rating of antibacterial activity of the honeys
The inflammatory component of honey
has been identified as Apalbumin-1
The
effe
ct o
f 0.2
5% v
ario
us h
oney
s on
pha
gocy
tosi
s (T
he e
rror
bar
s sh
ow th
e st
anda
rd d
evia
tion)
!
The
anti-
infla
mm
ator
y ac
tivity
was
not
cor
rela
ted
with
the
ratin
g of
ant
ibac
teria
l act
ivity
of t
he h
oney
s
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Apalbumin-1 is a bee protein –
so why is manuka honey more active?
and why some batches more than others?
The special antibacterial activity of
manuka honey is due to MGO
MGO reacts with Apalbumin-1 to make
it more potently anti-inflammatory
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Fibroblasts are stimulated by hydrogen peroxide
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Sutures removed 10 days post-op.
2 weeks post-op.)
4 weeks post-op.
12 weeks post-op.
Several studies with experimentally inflicted wounds have demonstrated that honey hastens the healing process.
Case studies have shown ‘kick-starting’ of healing in recalcitrant wounds
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Studies with leukocytes in culture have shown that honey stimulates the production of cytokines
31 days of honey
dressings
From C. Goldberg MD, UCSD From C. Goldberg MD, UCSD
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No oxygenation: xanthine oxidase enzyme formed
Re-oxygenation: xanthine oxidase
O2 → H2O2 tissue damage
inflammation