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Causes of skin aging

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Title: Causes of skin aging


1
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  • ?????
  • ???????

2
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3
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4
Causes of skin aging
menopause
DRYNESS PRURITUS
WRINKLES
LOSS OF FIRMNESS
SPOTS
30 yr/o
40 yr/o
60 yr/o and over
50 yr/o
CAUSE N1
UVA rays
CAUSE N2
Genetic and hormonal aging
Environment Nutrition Lifestyle (smoking,
alcohol) Stress
AND AGGRAVIATING FACTORS
5
Why Does the Skin Age?
6
???????
?? ?? ???/???
? ? ????,?????
? ? ????,??????
? ? ????,????
? ? ???????,????
? ??? ????,???????
? ???? ????,???????
7
??????
  • ???????????????????????????
  • UVA (??320-400nm)
  • UVB (??280-320 nm)
  • UVC (??200-280 nm)

8
UVA
  • ?????,????????????,???????????
  • ?????????

9
UVB
  • ?????????-??
  • ????????,?????????????????

10
UVC
  • ???????????
  • ?????????????
  • ?????? 1,???????????? 2??1900???,??????????????2
    530?????,??????????????60

11
????????
??
??
??
UVC
UVB
UVA
320
400
290
200
? ?
? ? ? ?
? ? ? ?
? ? ?
12
Treatment of Photoaging
13
???????
  • ??????????????????
  • ????????,???????,?????????????????

14
???????
?????
15
Commonly used ingredients in sunscreen
????? ??????
Inorganic Titanium oxide (????) UVAUVB
Inorganic Zinc oxide (???) UVAUVB
Organic PABA (Para-AminoBenzoic Acid) UVB
Organic Padimate O (octyl dimethylPABA) UVB
Organic Cinnamates UVB
Organic Anthranilates UVA UVB
Organic Benzophenones UVA
Organic Parsol 1789 UVA
Organic Mexoryl SX UVA
16
??SPF (Sun Protection Factor) ????
  • ??UVB(??)?????
  • SPF??????????/???????????
  • ?10????,?SPF15 ??????15?150????????150??
  • SPF15??????94?UVBSPF30 ?????97?UVB
  • ??????????????????(2 ?/?2)

17
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18
UVA????
  • PA (UVA????) ????
  • IPD ????????(?????????)
  • PPD (?????????)
  • PAPPD24
  • PAPPD46
  • PAPPD68
  • ?????????????????????370nm????,PPDgt4 ? PA

19
UV Protection Factor (UPF)
  • ????????UV???
  • Good protection (UPF 15-24)
  • 93.3 - 95.9 UV radiation Blocked
  • Very good protection (UPF 25-39)
  • 96.0 - 97.4 UV radiation Blocked
  • Excellent protection (UPF 40-50)
  • 97.5 or more UV radiation Blocked

20
????? (UVI, UV Index)
  • ???????100J/m21 UVI
  • ???????????,???????????
  • 0-2 ???
  • 3-4 ???
  • 5-6 ???
  • 7-9 ???
  • 10-15 ???
  • ??10??,??????10?20??,??????

21
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22
???????
UVI 02 34 56 79 1015
?? ?? ? ?? ? ??
???? 30min? 20min? ??12min
??????? ????? ????? ??? ????? ??? ???? ????? ????? ??? ???? ????? ???? 10001600 ????? ????? ??? ???? ????? ???? 10001600 ?????
23
??????????
  • Hypoallergic (????)
  • Noncomedogenic (??????)
  • Sweatproof (??)
  • Water resistant
  • ?????20??????????
  • Very water resistant
  • ?????80??????????

24
???????
  • ????????????????,??????????????
  • ??????????????

25
????
  • ????????? ????????,
    ???????????
  • ????
  • ? ? ??????(Carnauba wax)?????(Candelilla wax)????
  • ? ? ??????????? ---???????????????
  • ?? ? ????????

26
?????????
  • ???15?30???????,??????????
  • ??????????????????,????????,????????????????????

27
???????
  • ??????
  • ?????????????60???,???????????(water-resistant)???
    ???
  • ???????,????????????????
  • ?????????,???300??,???????8-10?

28
????????
  • ??????????,??????????,????
  • ????
  • ???????????????????
  • ????UVA?UVB

29
?????????????,??????????????????????????
30
????????
  • ?????????
  • ??????,??????????
  • ??????
  • ?????,?????!
  • ????????
  • ??????????,??????
  • ?????????
  • ??????????
  • ??????

31
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32
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33
?????-??
  • ???????????????????
  • ??????????,??????????,????,??????
  • ?????????????????????????
  • ????????????????????????????????????????????????,
    ????????

34
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35
?????-??
  • ??????, ????
  • ???
  • ????????
  • ?????????
  • ????????????
  • ??
  • ???
  • ????

36
?????-????
  • ????
  • ????,?????
  • ????

37
?????
  • ????
  • ????????????
  • ??????
  • ?????????
  • ????
  • ????
  • ??????

38
?????
  • ??????, pH 4.5-6.5?
  • ???
  • ???
  • ?????????????
  • ?????
  • ??
  • ????

39
???????????????? 90
40
????????????
  • ??????????
  • ????????????????????????
  • ??????????????????????????????????????
  • ????????????????????,????????????????????????????
    ,??????????,?????????,??????????????????????
  • ??????????????????,?????????????

41
Pigmentation Pathway
Tyrosine(???)----gt DOPA(??) ---gt DOPA ---gt
Melanin Tyrosinase (?????)
42
Pigmentation Pathway
  • Melanin???????????,???????Tyrosinase
  • Melanin????Melanosome??Melanocyte,???????????
    (Keratinocyte)
  • ????????-Melanocyte ?Keratinocyte??????,?????Epid
    ermal Melanin Unit (???????)
  • ???????Melanocyte???,????Melanin????Melanosome
    ?????

43
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44
Skin Lightening
  • Sunprotection
  • Depigmenting agents
  • Laser

45
Depigmenting agents
  • Work best when melanosis or melanocytosis is
    restricted to the epidermis
  • can be divided into several groups
  • Phenolic compounds
  • Hydroquinone
  • 4-Methoxyphenol
  • 4-Hydroxyanisol
  • Nonphenolic compounds
  • Corticosteroids
  • Tretinoin
  • Azelaic acid
  • N-acetylcysteine
  • L-ascorbyl-2-phosphate
  • Kojic acid
  • Combination formulas
  • Kligman's formula

46
Hydroquinones (????,??)
  • ?????,????????,????????
  • ?????????,???????,????????????
  • ????????????????,?????5?,?????????????,??????????
    ????

47
Hydroquinone
  • Improvement with HQ (monotherapy) is usually
    observed at 4-6 weeks
  • Plateau at approximately 4 months

48
Arbutin???
  • ?????????,??????,?????????????????,??,????????????
    ?

????????
49
Retinoids
  • ????????,????????????????
  • ???A????????????????
  • ???A??A??A??A??A??????????,?????????A?

50
Combination formulas
  • Kligman formula (????? ) in a hydrophilic
    ointment base
  • 5 HQ
  • 0.1 retinoic acid
  • 0.1 dexamethasone
  • Tri-Luma (???) in a cream formulation
  • 0.01 fluocinolone
  • 4 HQ
  • 0.05 tretinoin

51
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52
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53
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54
Kojic Acid (??)
  • ???????????,??????????
  • ????,?????????????,??????,???,????????????????????
    ????
  • a competitive and reversible inhibitor of animal
    and plant polyphenol oxidases, xanthine oxidase,
    and D- and some L-amino acid oxidases.
  • ???????????????(???)
  • Food Chem Toxicol. 2004 Jan42(1)93-105.

55
Azelaic acid (????)
  • ??????,?????????
  • ????????(Azalea)????????,?????????????
  • ????(Pityrosporum ovale)??????????????????????
  • ??tyrosinase??
  • ??????100,????????65

56
Paper Mulberry (??)
  • 5-(3-2,4-dihydroxyphenylpropyl)-3,4-bis
    (3-methyl-2-butenyl)-1,2-benzenediol
  • From paper mulberry root bark
  • Tyrosinase inhibitor
  • Scavenge free radicals
  • The concentration causing 50 inhibition of the
    activity of tyrosinase
  • 0.396 paper mulberry
  • 5.5 for HQ
  • 10.0 for kojic acid
  • 1 paper mulberry extract
  • No irritation or sensitization

57
Thioctic Acid (a-Lipoic Acid, a-??? )
  • Disulfide derivative of octanoic acid
  • ROS scavenger and redox regulator
  • Inhibits tyrosinase activity probably by
    chelating the copper ions

58
Unsaturated Fatty Acids
  • Oleic acid (C181), linoleic acid (C182), and
    a-linolenic acid (C183) suppress pigmentation in
    vitro
  • Linoleic acid accelerates the degradation of
    tyrosinase, inhibiting melanogenesis

59
Glabridin ???? (Licorice extract,????)
  • The active agents liquiritin and isoliquertin
  • Liquiritin induces skin lightening by dispersing
    melanin
  • Inhibited tyrosinase activity of melanocytes
    without cytotoxicity
  • Inhibition of superoxide anion production and
    cyclooxygenase activity
  • UV-Binduced pigmentation and erythema were
    Inhibited by topical application of 0.5
    glabridin
  • 0.4 licorice extract 0.05 betamethasone
    0.05 retinoic acid

60
Aleosin ???
  • From the aloe vera plant
  • Inhibit tyrosinase by competitive inhibition at
    the dihydroxyphenylalanine oxidation site
  • Limited ability to penetrate the skin because of
    its hydrophilic nature

61
???C ???
  • ??????????lysin?proline??????,??procollagen??coll
    agen
  • ?????????????
  • ?????(photoprotection)??UVA?UVB??????
  • ????????????
  • ???????????

62
?????,???C ???????
??????
????
???? ???
???
c
??????? ?????
?????????
??????
63
???C
  • ?????????C?70-75??,?????C??????????????????,??????
    ??????????
  • ????
  • ?????

64
???C????????
?? ???
???C??(??) -
?????
Vit C?
Vit C????
Vit C??liposome
65
Soybean trypsin inhibitor
  • 3 weeks of raw soy milk application
  • Inhibits the activation of protease activated
    receptor-2 pathway (PAR-2) reversible
  • a pathway necessary for keratinocyte phagocytosis
    of melanosomes and melanosome transfer

66
N-acetyl glucosamine
  • Inhibits the glycosylation of tyrosinase
  • 2 N-acetyl glucosamine applied twice daily for 8
    weeks in a cosmeceutical moisturizer showed
    modest pigment lightening
  • NAG 2 niacinamide 4 formulation

67
Tranexamic acid (???)
  • ?????????3
  • ??tyrosinase activity

68
Chamomile ET (?????)
  • ?????????0.5
  • ?????(endothelin)
  • ???

69
Ellagic Acid (???)
  • ?????????0.5
  • ??????
  • ???????????,??????????

70
????
???
????
???
??
??
???
??
71
???????
  • ????(OH)?????????
  • ?-hyroxy acid (AHA)
  • ??? (glycolic acid)
  • ?? (lactic acid)
  • ??? (tartaric acid)
  • ?-hydroxy acid (BHA)
  • ??? (salicylic acid)
  • ?,?-hydroxy acid (ABHA)
  • ??? (malic acid)
  • ??? (citric acid)

72
a-Hydroxy acids
  • Act as chelators (calcium ions), reduce epidermal
    calcium ions
  • cause a loss of calcium ions from the cadherins
    of the desmosomes and adherens junctions?Disruptio
    n of cell adhesion and desquamation
  • Promote cell growth and retard cell
    differentiation
  • Increease type I collagen mRNA and hyaluronic
    acid content in human skin

73
Alpha-hydroxy acids (?? ??????)
  • ????????,?????????,???????
  • AHA????????????????????????
  • ??????????,???????????,?????????
  • ?????????????????,????????????,????????,??????????
    ???????????????????????????

74
???????????
  • ?????????
  • lt3 ?????????,??????????????
  • 3-10???????????????????????????????
  • gt10 ?????,??????????????????????????????????
  • ?????????lt15
  • ????20-70
  • ??????

75
?????????
  • ???????????
  • ?????????????
  • ?????
  • ????????
  • ?????
  • ?????
  • ????

76
Beta-Hydroxy Acids (BHA) (??, salicylic acid)
  • BHA????????????????????
  • ???????????????????????????????
  • ?????????????????????0.2-1.5??,???????????

77
??(Phytic acid, Inositol hexaphosphate, IP6)
  • ???????????????
  • ????????????,??????????????? (phytic acid had
    anti-neoplastic properties in breast, colon,
    liver, leukemia, prostate, sarcomas, and skin
    cancer Complement Ther Med. 2002
    Dec10(4)229-34. )
  • Topical application of IP6 inhibited skin tumor
    development significantly in a dose-dependent
    manner (Nutr Cancer. 20034666-72 )
  • ???????????????????????

78
???????????
79
Retinoids
  • ????????,????????????????
  • ???A????????????????
  • ???A??A??A??A??A??????????,?????????A?

80
Retinoids
  • 0.05 tretinoin and isotretinion improve fine
    and coarse wrinkling and lighten actinic
    lentigins and mottled hyperpigmentation (36-weeks
    period)
  • Compaction of the stratum corneum
  • Epidermal hyperplasia
  • Correction of atypia
  • Dispersion of melanin granules
  • Increased dermal collagen synthesis
  • Angiogenesis

81
Retinoid dermatitisoccur within first month of
treatment
  • Erythema
  • Scaling
  • Pruritus
  • Burning
  • Stining
  • Dryness

82
Kinerase ???
  • Kinerase??????N6-furfuryladenine (Kinetin, ???)
  • 0.1 N6-furfuryladenine?????
  • ??????A?(Retinoids)??,???????
  • ?????,?????????,???Rosacea??????????
  • ????????
  • ???????????,?????

Biochem Biophys Res Commun. 15201(2)665-72,
1994.
83
Antioxidants
  • Limited efficiency of sunscreens
  • No one product provides excellent protection over
    the whole UVA range (320-400 nm)
  • Most people apply sunscreen 0.5 mg/cm2
  • UV-induced DNA damage and immunosuppression are
    still present at suberythemal levels of
    irradiation
  • Components of sunscreens and their photoproducts
    free radicals

84
???C ???
  • ??????????lysin?proline??????,??procollagen??coll
    agen
  • ?????????????
  • ?????(photoprotection)??UVA?UVB??????
  • ????????????
  • ???????????

85
???C
  • ?????????C?70-75??,?????C??????????????????,??????
    ??????????
  • ????
  • ?????

86
Vitamin E (Tocopherols)
  • 90 of tissue Vit Ea- tocopherol
  • Topical a- tocopherol
  • Prevent UV-induced free radical formation
  • Protect endogenous epidermal antioxidants
  • Prevent lipid peroxidation
  • Prevent UV-induced systemic immunisuppresion

87
??? E
  • ????,???????,??????
  • ???E?????????????,?????????????????,??????????????
    ?
  • ???E??????,??????,????????????????????????
  • ??????????????????????

88
  • Cosmetics contain tocopheryl acetate or other
    tocopheryl esters
  • No direct antioxidant properties
  • Not tocopherol precursors owing to the lack of
    adequate esterase in the skin

89
Antioxidants Oral supplements
  • Combination of l-proline, l-lysine, manganese,
    copper, zinc, quercetin, grape seed extract,
    N-acetyl d-glucosamine, and glucosamine sulfate
    was shown to improve wrinkles by 34
  • Combination of vitamin E, vitamin C, carotenoid,
    selenium, and proanthocyanidin led to a
    significant decrease in induction of MMP after UV
    exposure

90
???Q10 (CoQ10)
  • ??Q10 (Coenzyme Q10)???????????????,??????????,???
    ??????(mitochondria)?,?????K??????
  • ?????Q10?????,??????????,????Q10??????,??????????,
    ????????????Q10??????????Q10??????????
  • ??????????????
  • ?????????,???????????????????,?????????????,CoQ10
    ???2?3???,??????

Biofactors. 19999(2-4)371-8.
91
a-Lipoic acid (a-???)
  • An antioxidant and anti-inflammatory agent that
    has been previously shown to reduce the
    production of transcription factors such as NF-?B
    and indirectly affect the gene expression of
    inflammatory cytokines

92
a-Lipoic acid (a-???)
  • One of the most visible roles of lipoic acid is
    as a cofactor in aerobic metabolism, specifically
    the pyruvate dehydrogenase complex.
  • Since the early 1990s lipoic acid has been used
    as a dietary supplement, typically at doses in
    the range of 100200 mg/day.
  • Treatment with 5 a-lipoic acid has led to
    significant improvements in clinical and
    objective measurements of photoaging, including
    laser profilometry

Br J Dermatol 149 841849, 2003
93
Estrogens
  • Oral estrogen use was associated with a
    statistically significant decrease in the risk
    for dry skin and wrinkling
  • Topical estrogen therapy can also lead to
    significant increases in collagen, firmness, and
    elasticity, as well as wrinkle depth measured by
    optical profilometry

Int J Dermatol 35669-74, 1996.
94
Growth factors and cytokines
  • Topical application of a combination of growth
    factors and cytokines has been evaluated in a
    pilot study for its effect on photoaged skin
  • A majority of patients showed clinical
    improvement in at least one facial area and a
    significant change in objective measurements by
    optical profilometry
  • New collagen formation was observed in biopsy
    specimens

95
FROP-3
  • Fucose-rich oligo- and polysaccharide
  • Stimulation of fibroblast proliferation
  • Downregulation of skin matrix degrading enzymes
    as matrix metalloproteinases MMP-2 and MMP-9
  • Free radical scavenging
  • Increase of skin elastin biosynthesis
  • Improvement of collagen fibrillogenesis
  • Increases glycosamino-glycan biosynthesis in
    fibroblast cultures

Skin Research and Technology 2005 11 4752
96
FROP-3
  • In a pilot study examining skin-surface
    microrelief, the pattern of fine wrinkling found
    in skin of any age, a cream containing FROP-3
    showed a 10- to 15-year decrease in apparent age
    after 4 weeks of treatment

97
Emerging Therapies
98
Antioxidants
  • Oral soy isoflavones (?????)
  • can enhance the activity of endogenous
    antioxidant enzymes and protect against
    UV-induced aging
  • ??????????????????????,???0.20.4????????????????
    ?,?????????????12?,??????????????23
    Daidzin(D)?64 Genistin(G)?13 Glycitin?????Daidze
    in(De)?Genistein(Ge)?Glycitein

99
Antioxidants
  • Topical genistein (?????) and N-acetyl cysteines
    (NAC, N-???-L-???? )
  • prevent c-Jun and collagenase up-regulation after
    UV exposure in human skin in vivo
  • an inhibitor of tyrosine kinase activity and may
    inhibit signal transduction induced by UV light

100
Antioxidants
  • Gluconolactone (???????)
  • a polyhydroxy acid
  • capable of chelating metals and may also function
    by scavenging free radicals, thereby protecting
    skin from some of the damaging effects of UV
    radiation
  • a preventive treatment for solar elastosis

101
Antioxidants
  • Green tea polyphenols (GTPs)
  • potent antioxidants
  • Oral administration of GTPs markedly inhibited
    UV-induced expression of MMP in mouse skin.
  • Even in the absence of UV light,
    ()-epigallocatechin-3-gallate, a component of
    green tea, was shown to inhibit the expression of
    various MMPs

102
Silmarin
  • Silymarin????????????(Milk Thistle)????????,??????
    ???
  • 1968?,??????????????? silibinin,
    silidianin?silicristin
  • ????????????,??????,???????????(???????)??????????
    ?????????,????????????
  • ??????????,??????????????,????????E
  • ????????
  • ????????

103
Grape seed
  • Grape seed proanthycyanidin extract (GSPE) are a
    group of biologically active polyphenolic
    bioflavonoids
  • Strong antioxidants (Clin Cancer Res 62921-30,
    2000)
  • GSPE containing 5000 ppm resveratrol Potently
    upregulates oxidant and tumor necrosis
    factor-alpha inducible VEGF expression in human
    keratinocytes (Free Radic Biol Med 3138-42, 2001)

104
Grape seed
  • Topical application of GSPE accelerated wound
    contraction and closure, represents a feasible
    and productive approach to support dermal wound
    healing (Free Radic Biol Med 331089-96 2003)

105
Ginkgo biloba
  • ?????????????,?????????
  • ???????(Gingoflavonglycoside)???????( Super Oxide
    dismutase,??SOD)??

106
  • Ginger extracts
  • Metallothionein (????? )
  • Evening Primrose (???)
  • CoffeeBerry

107
Iron chelators
  • MMP activation is dependent on iron, the iron
    chelator kojic acid was investigated to determine
    its potential preventive effects on photoaging
  • Kojic acid is produced by the fungus Aspergillus
    oryzae and is found in Japanese soy-based
    products

108
Anti-inflammatory agents
  • The protective effects of topical hydrocortisone,
    naproxen, and ibuprofen were examined in the
    hairless mouse.
  • Celecoxib has been shown to reduce inflammation
    caused by short- and long-term UV exposure.

109
Minerals ?(Selenium)
  • ????????????E????????????????????
  • ??????,??????????????,???????????????????
    25mcg,??????????? 200mcg,??????????63????53???46
    ??
  • ???????????????????????????????????????????

110
???? (La Roche-Posay )
  • ?????????????????????????????????? BRGM
    ??,????????? ? ? ????????
  • ? 60 ug/L
  • ???? 30mg/L
  • ???? 396mg/L
  • ? 140mg/L
  • ????  

111
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112
???
  • ???1200?????
  • ???????????????????????,??????,?????,???????,???
    ?
  • ???? ?? ,??????? ,???? ,????
  • ???? ??????????????????????????? ??? ??????
    ??????????? ?????????? ,??????

113
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114
Clinical study
ORIGINAL MEASURES
a
  • CLINICAL MORPHING
  • Video-morphing made on
  • not retouched IN VIVO photos.
  • DERMAL PROTEINS DOSAGE
  • Molecular marking on biopsies

b
T0 T1,5m T3m T4,5m
T6m
Collagens Type I, III, IV, VII
GAG
PG
Elastin
MMP 1 et 9
N.B.based on biopsies from the clinical pivot
study on Active c.the molecular marking focused
on only 2 types of derma proteinscollagens 1
and III. Samples were only taken at T6
months.Results were compared to Active C T6
months against placebo.For Redermic the biopsies
were taken at T0 and at T6 months, which enabled
comparison of T6mths v.s. the control and also
v.s.T0.
115
?????(Idebenone)
  • Idebenone is a synthetic analog of coenzyme Q10.
    This lower molecular weight molecule is presumed
    to penetrate skin more efficiently than its
    parent compound.

116
?????(Idebenone)
117
Tertiary therapies
  • Chemical peels
  • Resurfacing techniques
  • Laser systems

118
????
???
????
???
??
??
???
??
119
Phenol Peeling
120
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121
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122
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123
Radiofrequency technology
  • Produce an electric current that generates heat
    through resistance in the dermis and subcutaneous
    tissue
  • Reflect collagen contraction followed by
    secondary collagen synthesis and remodeling
  • Adverse events erythema, soreness, and
    second-degree burning

124
Botulinum toxins
  • Exotoxin produced by Clostridium botulinum that
    prevents local neuromuscular transmission
  • The toxin facilitates cleavage of synaptosomal
    associated membrane protein (SNAP)-25, which is
    required for exocytosis of acetylcholine, thereby
    inhibiting muscle contraction

125
Botulinum Toxin A Injection
126
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127
Soft tissue augmentation, Filler
  • Autologous lipoaugmentation
  • Bovine collagen
  • An acellular dermal graft derived from human
    cadavers
  • Hyaluronic acid (HA) derivatives
  • A mixture of microspheres of polymethyl-methacryla
    te (20) and bovine collagen (80)

128
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129
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130
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