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"Science" behind copper peptides

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Josee
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Fri Apr 30, 2010 7:07 am      Reply with quote
Keliu wrote:
DarkMoon wrote:
All the scientific research quoted seems to still have to do with wound healing? Where does that apply to wrinkles, sagging, hyperpigmentation ect.?
My understanding, please correct me if I am wrong is that there is no real evidence that these would be considered wounds? The CP's may not behave at all the same on uninjured, intact skin as they do on broken, wounded skin? Smile


I don't think anyone would consider a wrinkle a wound. However, if CPs are supposed to stimulate cell renewal to create new skin then surely this would be beneficial for wrinkles as well as for wounds.


Actually there are a lot of processes during wound healing that are good for wound healing but not good outside of that situation.

For e.g. copper peptides stimulate MMPs. MMPs degrade collagen. In wound healing, this is actually good. When we injure ourselves, there's such a HUGE response to make collagen that it's done fast in disorganized arrays and also overdone. Hence we get scars. So a compound with MMPs activity is good because it might help degrade collagen and prevent the massive deposit.

But outside of wound healing, for anti-wrinking purposes for example, you want to keep your collagen, not degrade it so something with MMPs activity is something we want to avoid.

Also there are compounds good for healing (e.g. honey) that do nothing for wrinkles.

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Fri Apr 30, 2010 7:56 am      Reply with quote
I found an interesting paragraph in a Dr. Obagi's dermatology textbook that states that dermal damage can not be corrected via AHAs and BHAs, and that only procedures that truly reach the dermal level (chemical peels, lasers, etc.) can correct such problems. And who would argue with Dr. Obagi's expertise as one of the best dermatologists in the world?

So that basically proves Josee's point that scars, etc. below the epidermis do NOT migrate up. I'll add the quote later after I get out of my meeting.

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Fri Apr 30, 2010 8:04 am      Reply with quote
So why do people's scars improve/fill in/disappear with the use of CP and exfoliators then?
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Fri Apr 30, 2010 8:20 am      Reply with quote
Josee wrote:
Quote:

Actually there are a lot of processes during wound healing that are good for wound healing but not good outside of that situation.

For e.g. copper peptides stimulate MMPs. MMPs degrade collagen. In wound healing, this is actually good. When we injure ourselves, there's such a HUGE response to make collagen that it's done fast in disorganized arrays and also overdone. Hence we get scars. So a compound with MMPs activity is good because it might help degrade collagen and prevent the massive deposit.

But outside of wound healing, for anti-wrinking purposes for example, you want to keep your collagen, not degrade it so something with MMPs activity is something we want to avoid.

Also there are compounds good for healing (e.g. honey) that do nothing for wrinkles.


Actually the above thought regarding CPs & MMP's is inaccurrate & incomplete.

And comparing CPs to honey???

............................................
From Dr. Pickart:
...........................................
Quote:
1. CPs increase collagen in normal skin

Effects of topical creams containing vitamin C, a copper-binding peptide
cream and melatonin compared with tretinoin on the ultrastructure of
normal skin - A pilot clinical, histologic, and ultrastructural study.
Abdulghani A.A.; Sherr A.; Shirin S.; Solodkina G.; Tapia E.M.;
Wolf.GottliebA.B.; Dermatology, UMDNJ, Robert Wood Johnson Medical
School; Disease Management and Clinical Outcomes, 1998, 1:136-141.

A clinical study which compared the effect on the skin's production of
collagen after using creams containing copper-peptides, vitamin C, or
retinoic acid (retin-A) Twenty volunteers applied the various creams to
their thighs daily for one month. New collagen production was determined
by studying skin biopsy samples using immunohistological techniques.
The study found, that after one month, copper-peptides had the most
significant effect on collagen production. Significant increases in
collagen production were found in 70% of the persons treated with
copper-peptide creams, 50% of the persons treated with the vitamin C
cream, and 40% of the persons treated with retinoic acid.

2. Other studies on skin

2.1 A Clinical Evaluation of a Copper-Peptide Containing Liquid
Foundation and Cream Concealer Designed for Improving Skin Condition.
Appa Y, Barkovic S, Finkey M B, Neutrogena Corporation, Los Angeles,
CA, Stephens, T, TJ Stephens & Associates, Inc, Dallas, TX Abstract
P66, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing liquid foundation tested on skin appearance, skin
elasticity and epidermal thickness in an 8 week study. GHK-Cu containing
liquid foundation improved skin appearance, and increased skin
elasticity and epidermal thickness.

2.2 The Effect of Tripeptide to Copper Ratio in Two Copper Peptide
Creams on Photoaged Facial Skin. Leyden J, University of Pennsylvania,
Philadelphia, PA, Grove, G, KGL, Inc/Skin Study Center, Broomall, PA;
Barkovic S, Appa Y, Neutrogena Corporation, Los Angeles, CA; Abstract
P67, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing creams tested for reducing visible signs of aging and
increasing skin density. GHK-Cu containing creams reduced visible signs
of aging, decreased photodamage, and increased skin density in 8 weeks
on facial skin.

2.3 Skin Care Benefits of Copper Peptide Containing Facial Cream. Leyden
J, University of Pennsylvania, Philadelphia, PA Stephens T, Thomas J
Stephens & Associates, Inc, Dallas, TX; Finkey MB, Barkovic S,
Neutrogena Corporation, Los Angeles, CA; Abstract P68, American Academy
of Dermatology Meeting, February 2002

GHK-Cu containing creams tested for effect on wrinkles, fine line, skin
elasticity, skin density, and thickness. Placebo-controlled study, 71
females, 12 weeks. GHK-Cu containing creams reduced wrinkles and fine
lines while increasing skin elasticity, skin density, and thickness.

2.4 Skin Care Benefits of Copper Peptide Containing Eye Creams. Leyden
J, University of Pennsylvania, Philadelphia, PA; Stephens T, Thomas J
Stephens & Associates, Inc, Dallas, TX; Finkey MB, Barkovic S,
Neutrogena Corporation, Los Angeles, CA; Abstract P69, American Academy
of Dermatology Meeting, February 2002

GHK-Cu containing eye creams tested on wrinkles, fine lines and eye
appearance in placebo controlled study, 41 females, 12 weeks. In a
second placebo controlled, 3 week, half face study, GHK-Cu was
significantly better than a vitamin K cream. GHK-Cu containing eye
creams reduced wrinkles and fine lines while improving eye appearance in
placebo-controlled study. GHK-Cu was significantly better than a
vitamin K cream.

2.5 Copper Peptide and Skin, M.B. Finkley, Y. Appa, S. Bhandarkar,
Cosmeceuticals and Active Cosmetic, 2nd Edition (ISBN: 0-8247-4239-7),
2005, pp 549-563

A series of placebo-controlled studies found GHK-Cu skin creams to:
1. Tighten loose skin and improve elasticity
2. Improve skin density and firmness
3. Reduce fine lines and deep wrinkles 4. Improve skin clarity
5. Reduce photodamage and mottled hyperpigmentation
6. Strongly increase keratinocyte proliferation in women of 50 year old
range

2.6 GHK-Cu reduced overall metalloproteinase activity. This activity is
a result of the level of proteinases and anti-protease proteins. In
wound studies, GHK-Cu actually reduced the level of activity. Remodeling
of skin is the process of removing older skin and damage, then new cells
and proteins are produced. Skin cannot be rebuilt without removing old
proteins.

Copper peptides increase the production of MMPs and anti-proteases that
block MMP actions. So the actual MMP activity depends on the balance of
these two types of proteins. The only direct test of copper peptides and
MMP activity is from a study in rats this idea was from a study in rats
that found that the copper peptides actually decreased the activity of
MMPs.

Vet Surg. 2003 Nov-Dec;32(6):515-23.
The effect of topical tripeptide-copper complex on healing of ischemic
open wounds.

Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak AM, Swaim SF,
Vangilder J, Lee-Ambrose L, Martin FG.
Department of Small Animal Clinical Sciences, University of Florida
College of Veterinary Medicine, and the School of Medicine Institute for
Wound Research, Gainesville, FL 32610, USA.
OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine
tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation,
Redmond, WA) on healing in ischemic open wounds.
STUDY DESIGN: Experimental study. SAMPLE POPULATION: Twenty-four adult
male Sprague-Dawley rats. METHODS: Rats were divided into 3 groups:
topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and no
treatment (control). Six-mm-diameter, full-thickness wounds were created
within an ischemic bipedicle skin flap on the dorsum of each rat. Each
day, for 13 days, wound margins were traced, and the TCC and TCC vehicle
groups were treated topically. Tracings were scanned, and wound
perimeter and area were calculated. On days 6, 10, and 13, selected
wounds were biopsied and analyzed for tumor necrosis factor alpha
(TNF-alpha) and matrix metalloproteinases (MMP) 2 and 9.
RESULTS: A significant decrease in wound area was seen in the TCC
group, but not the vehicle group, when compared with the control group
on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC
vehicle on days 3 and 9. On day 13, initial wound area had decreased by
64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the
control group. On days 6, 10, and 13, TCC-treated wounds contained
significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than
control wounds.
CONCLUSION: Topical TCC resulted in accelerated wound healing in
ischemic open wounds.
CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of
ischemic open wounds in rats and may have an application for the
treatment of chronic wounds in other species. Clinical evaluation of
topical TCC is warranted.
bethany
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Fri Apr 30, 2010 9:02 am      Reply with quote
bethany wrote:
I found an interesting paragraph in a Dr. Obagi's dermatology textbook that states that dermal damage can not be corrected via AHAs and BHAs, and that only procedures that truly reach the dermal level (chemical peels, lasers, etc.) can correct such problems. And who would argue with Dr. Obagi's expertise as one of the best dermatologists in the world?

So that basically proves Josee's point that scars, etc. below the epidermis do NOT migrate up. I'll add the quote later after I get out of my meeting.



Here is the quote I mentioned...Dr. Obagi's book in general confirmed for me that the dermis must be reached (and a new epidermis rebuilt as a result of that) in order to repair issues...they do not just exfoliate up and out.

Of course topicals proven to reach the dermis (like Retin A) can cause new collagen and elastin to develop, and make it LOOK like the scar is gone, but anything in the dermis is staying in the dermis...unless you have a major procedure and eradicate the part of the dermis with the issue.

Image

http://books.google.com/books?id=H2fnydnNRiUC&printsec=frontcover&dq=obagi+restoration+rejuvenation&source=bl&ots=WHiEq-35_i&sig=4No1Tx22ltj3Sd5xpuEpHZ8L8UA&hl=en&ei=6f3aS4fCJ5PS8QS6-c1j&sa=X&oi=book_result&ct=result&resnum=3&ved=0CCMQ6AEwAg#v=onepage&q&f=false

I do own this book, and it's unfortunate that more of it is not available online. I wouldn't suggest people buy it though...way too pricy!

http://www.amazon.com/Obagi-Skin-Health-Restoration-Rejuvenation/dp/0387984690

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Fri Apr 30, 2010 9:06 am      Reply with quote
moosejavian wrote:
So why do people's scars improve/fill in/disappear with the use of CP and exfoliators then?


It would have to be due to development of collagen/elastin...not because of exfoliation.

And keep in mind that most people with scars are also needling and have done significant peels (TCA, higher % glycolic, etc.) at some point, all of which which also generate collagen.

Of course CPs may help with that collagen generation. My only point is that scars do not exfoliate up and out as people keep saying.

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Fri Apr 30, 2010 11:50 am      Reply with quote
Star Model wrote:
I asked Dr. Pickart about histological pictures.

From Dr. Pickart:

There are many histological pictures in the article that is referenced on www.skinbiology.com/copperpeptideregeneration.html.

Copper Peptide and Skin, M.B. Finkley, Y. Appa, S. Bhandarkar, Cosmeceuticals and Active Cosmetic, 2nd Edition (ISBN: 0-8247-4239-7),
2005, pp 549-563. Any good medical library will have the book. The paper describes:

A series of placebo-controlled studies found GHK-Cu skin creams to:
1. Tighten loose skin and improve elasticity
2. Improve skin density and firmness
3. Reduce fine lines and deep wrinkles 4. Improve skin clarity
5. Reduce photodamage and mottled hyperpigmentation
6. Strongly increase keratinocyte proliferation in women of 50 year old range.



I looked at the available images on the SkinBiology link provided . I am interested in the ultrasound images provided of the 59 year old woman pre- and post- copper peptide usage.

First of all, does anyone know exactly where these images come from? There are no credits provided by the website for these images. Originally I thought they were from either the Neutrogena studies or possibly the book chapter by Finkley et al, but the SkinBiology link includes them under the heading "SRCPs - Skin Remodeling Remodeling Copper Peptides" and says the following:

The application of SRCPs to the skin's surface creates an environment that helps the skin tighten its barrier and increase its collagen and elastin density. The photo on the left is an ultrasound scan of the skin of a women aged 59 before treatment with the a cream containing SRCPs. On the right is the same skin after one month of treatment with the complexes. The white-yellow colored areas are the ultrasonic reflection from skin areas that are more dense because of closer cellular binding and increased amounts of collagen and elastin. This is an effect that is opposite to the usual thinning and loosening of skin during aging.

These images are included elsewhere on the SkinBiology websites with slightly different descriptions. The caption for the first image states "An ultrasound scan of a woman age 59 before treatment with a cream containing Skin Remodeling Copper Peptides" and the second image says "After one month of treatment with SRCPs. White-yellow coloured areas are the Ultrasonic reflection from skin areas that are more dense due to closer cellular binding and increased amounts of collagen and elastin".

Can anyone explain exactly what these images represent? I am not sure if I am looking at the epidermis, dermis or both. Does anyone know if the ultrasound scan are taken from EXACTLY the same area of the skin? The only thing I know for sure is there is a larger concentration of yellow-white in the second image but I do not know exactly what caused this ... was it the copper "peptide" itself, or something else in the cream. Overall, it appears to me that the second image is thinner/more compact than the initial image, but I am not sure what that means (since the caption says increased collagen and elastin).

I was also able to locate further ultrasound images on another website which you can view here:

http://www.wrinkle-free-skin-tips.com/copper-peptides.html

I do not know if this is the same subject (both subjects are a 59 year old woman) but these images are supposedly for GHK-Cu. I could not find them on the SkinBiology website (I may have overlooked them). I have been able to find them reprinted elsewhere on the Internet though.

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Fri Apr 30, 2010 11:53 am      Reply with quote
The similarity between wounds, or rather scars, and wrinkles is that they are both made from a larger than normal type of collagen. The contention is that CPs help to slowly encourage the body to replace this collagen with the healthy, normal sized type of collagen molecule, and also help to develop more healthy collagen at the site.
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Fri Apr 30, 2010 11:53 am      Reply with quote
Star Model wrote:

But outside of wound healing, for anti-wrinking purposes for example, you want to keep your collagen, not degrade it so something with MMPs activity is something we want to avoid.

Also there are compounds good for healing (e.g. honey) that do nothing for wrinkles.

Actually the above thought regarding CPs & MMP's is inaccurrate & incomplete.

And comparing CPs to honey???


We have already spoken about these papers. It would really be good if we brought new papers/evidence so as not to leep repeating ourselves.

And I was not comparing CPs to honey... I just really like honey and keep trying all kinds of different ones.

Star Model wrote:

CPs increase collagen in normal skin

Effects of topical creams containing vitamin C, a copper-binding peptide
cream and melatonin compared with tretinoin on the ultrastructure of
normal skin - A pilot clinical, histologic, and ultrastructural study.
Abdulghani A.A.; Sherr A.; Shirin S.; Solodkina G.; Tapia E.M.;
Wolf.GottliebA.B.; Dermatology, UMDNJ, Robert Wood Johnson Medical
School; Disease Management and Clinical Outcomes, 1998, 1:136-141.

A clinical study which compared the effect on the skin's production of
collagen after using creams containing copper-peptides, vitamin C, or
retinoic acid (retin-A) Twenty volunteers applied the various creams to
their thighs daily for one month. New collagen production was determined
by studying skin biopsy samples using immunohistological techniques.
The study found, that after one month, copper-peptides had the most
significant effect on collagen production. Significant increases in
collagen production were found in 70% of the persons treated with
copper-peptide creams, 50% of the persons treated with the vitamin C
cream, and 40% of the persons treated with retinoic acid.


Again, this paper is not being properly reported.

The study is not randomized. The study did not do any statistical analysis to check for statistical significance so it's impossible for them to report significance. They also did not compare which produced more. If you see the picture they posted on the paper though, the one with tretinoin has obviously more staining. In addition, they did not measure collagen but pro-collagen so we don't know how these creams can influence collagen generation and how much of that procollagen actually became collagen.

In fact, this is what Dr. Maibach has to say about this paper: "Abdulghani et al. revealed its enhanced but insignificant anti-ageing effects when compared with tretinoin, Vitamin C and melatonin. "

In addition, they measured Ki67 which is a measure of keratinocyte proliferation (which some would say it's a sign of skin regeneration). Only tretinoin showed a significant increase in Ki67

They also measured dermal CD3+ (sign of inflammation). Only tretinoin and Vitamin C decreased CD3+

Star Model wrote:

2. Other studies on skin

2.1 A Clinical Evaluation of a Copper-Peptide Containing Liquid
Foundation and Cream Concealer Designed for Improving Skin Condition.
Appa Y, Barkovic S, Finkey M B, Neutrogena Corporation, Los Angeles,
CA, Stephens, T, TJ Stephens & Associates, Inc, Dallas, TX Abstract
P66, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing liquid foundation tested on skin appearance, skin
elasticity and epidermal thickness in an 8 week study. GHK-Cu containing
liquid foundation improved skin appearance, and increased skin
elasticity and epidermal thickness.


They (suspiciously and conveniently) did not do a comparison with placebo so for all we know the foundation thing did not show any difference with a placebo cream.

The study was fully funded by Neutrogena and conveniently was never published in a peer-reviewed journal. The study was not blinded


Star Model wrote:

2.2 The Effect of Tripeptide to Copper Ratio in Two Copper Peptide
Creams on Photoaged Facial Skin. Leyden J, University of Pennsylvania,
Philadelphia, PA, Grove, G, KGL, Inc/Skin Study Center, Broomall, PA;
Barkovic S, Appa Y, Neutrogena Corporation, Los Angeles, CA; Abstract
P67, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing creams tested for reducing visible signs of aging and
increasing skin density. GHK-Cu containing creams reduced visible signs
of aging, decreased photodamage, and increased skin density in 8 weeks
on facial skin.


Again this study is unpublished and fully funded by Neutrogena. It was not blinded and it was not randomized. There is no comparison with placebo (there are lots of studies where placebo creams improve the condition of the skin) so for all we know, these creams are no better than placebo. In addition, they do not say that the results were statistically significant which probably means they were not (people DO say if they're significant because it's a good thing).

Star Model wrote:

2.3 Skin Care Benefits of Copper Peptide Containing Facial Cream. Leyden
J, University of Pennsylvania, Philadelphia, PA Stephens T, Thomas J
Stephens & Associates, Inc, Dallas, TX; Finkey MB, Barkovic S,
Neutrogena Corporation, Los Angeles, CA; Abstract P68, American Academy
of Dermatology Meeting, February 2002

GHK-Cu containing creams tested for effect on wrinkles, fine line, skin
elasticity, skin density, and thickness. Placebo-controlled study, 71
females, 12 weeks. GHK-Cu containing creams reduced wrinkles and fine
lines while increasing skin elasticity, skin density, and thickness.


In this placebo-controlled study (which is also unpublished and fully funded by Neutrogena), even though the subjects were followed for 12 weeks, the authors report a significant difference between the GHK-Cu cream and placebo only until the 4th week!

Star Model wrote:

2.4 Skin Care Benefits of Copper Peptide Containing Eye Creams. Leyden
J, University of Pennsylvania, Philadelphia, PA; Stephens T, Thomas J
Stephens & Associates, Inc, Dallas, TX; Finkey MB, Barkovic S,
Neutrogena Corporation, Los Angeles, CA; Abstract P69, American Academy
of Dermatology Meeting, February 2002

GHK-Cu containing eye creams tested on wrinkles, fine lines and eye
appearance in placebo controlled study, 41 females, 12 weeks. In a
second placebo controlled, 3 week, half face study, GHK-Cu was
significantly better than a vitamin K cream. GHK-Cu containing eye
creams reduced wrinkles and fine lines while improving eye appearance in
placebo-controlled study. GHK-Cu was significantly better than a
vitamin K cream.


I think Dr. Pickart is confusing this paper with something else. There is no placebo-controlled thing in this study. And the 41 females were not controlled for anything. The 41 females just applied cream and there is no comparison with placebo.

This is another unpublished study fully funded by Neutrogena.

There is a comparison with vitamin K cream in this study, for 3 weeks. We don't know how many people were enrolled for this. After the 3 weeks, the paper says that GHK-Cu was better for tolerance and efficacy... what that "efficacy" is? God knows. These pharmaceutical companies do have a creative way of reporting their studies!


Star Model wrote:

2.5 Copper Peptide and Skin, M.B. Finkley, Y. Appa, S. Bhandarkar,
Cosmeceuticals and Active Cosmetic, 2nd Edition (ISBN: 0-8247-4239-7),
2005, pp 549-563

A series of placebo-controlled studies found GHK-Cu skin creams to:
1. Tighten loose skin and improve elasticity
2. Improve skin density and firmness
3. Reduce fine lines and deep wrinkles 4. Improve skin clarity
5. Reduce photodamage and mottled hyperpigmentation
6. Strongly increase keratinocyte proliferation in women of 50 year old
range


These are not studies. These are the SAME Neutrogena people commenting on their studies. And they're not published in a peer-reviewed journal.

Star Model wrote:

Cosmeceuticals and Active Cosmetic
2.6 GHK-Cu reduced overall metalloproteinase activity. This activity is
a result of the level of proteinases and anti-protease proteins. In
wound studies, GHK-Cu actually reduced the level of activity. Remodeling
of skin is the process of removing older skin and damage, then new cells
and proteins are produced. Skin cannot be rebuilt without removing old
proteins.


This conclusion cannot be derived from the papers. As I have said before, yes, the GHK-Cu stimulates MMPs and TIMPs but we don't know the overall balance in human wounds and even less in unwounded skin. So since this is unknown, I'd rather use something that has no MMP activity or that it's absolutely known to increase collagen production in vivo in unwounded skin.


Star Model wrote:
The only direct test of copper peptides and
MMP activity is from a study in rats this idea was from a study in rats
that found that the copper peptides actually decreased the activity of
MMPs.


Not according to the available literature.


Star Model wrote:

Vet Surg. 2003 Nov-Dec;32(6):515-23.
The effect of topical tripeptide-copper complex on healing of ischemic
open wounds.

Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak AM, Swaim SF,
Vangilder J, Lee-Ambrose L, Martin FG.
Department of Small Animal Clinical Sciences, University of Florida
College of Veterinary Medicine, and the School of Medicine Institute for
Wound Research, Gainesville, FL 32610, USA.
OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine
tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation,
Redmond, WA) on healing in ischemic open wounds.
STUDY DESIGN: Experimental study. SAMPLE POPULATION: Twenty-four adult
male Sprague-Dawley rats. METHODS: Rats were divided into 3 groups:
topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and no
treatment (control). Six-mm-diameter, full-thickness wounds were created
within an ischemic bipedicle skin flap on the dorsum of each rat. Each
day, for 13 days, wound margins were traced, and the TCC and TCC vehicle
groups were treated topically. Tracings were scanned, and wound
perimeter and area were calculated. On days 6, 10, and 13, selected
wounds were biopsied and analyzed for tumor necrosis factor alpha
(TNF-alpha) and matrix metalloproteinases (MMP) 2 and 9.
RESULTS: A significant decrease in wound area was seen in the TCC
group, but not the vehicle group, when compared with the control group
on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC
vehicle on days 3 and 9. On day 13, initial wound area had decreased by
64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the
control group. On days 6, 10, and 13, TCC-treated wounds contained
significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than
control wounds.
CONCLUSION: Topical TCC resulted in accelerated wound healing in
ischemic open wounds.
CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of
ischemic open wounds in rats and may have an application for the
treatment of chronic wounds in other species. Clinical evaluation of
topical TCC is warranted.



In this study rats were followed for 13 days.

In regards with the wound area, the GHK-Cu was significantly better than placebo only on days[b][/b][/u] 3 and 9 Confused So in the end... it was no better than placebo overall.

In regards with MMP yes, there was a difference in MMP2 and MMP9 but not in pro-MMP2.

However, this study only followed the rats for 13 days and the authors acknowledge an increase in MMP activity in day 18:

"A stimulatory effect of TCC on MMPs and connective tissue accumulation occurred in rat wounds but not until day 18 of treatment."

In addition, there are 2 more papers that showed increase on MMP with GHK-Cu:

- J Invest Dermatol. 1999 Jun;112(6):957-64.
- Life Sci. 2000 Sep 22;67(1Cool:2257-65.

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Fri Apr 30, 2010 12:30 pm      Reply with quote
alexes wrote:
The similarity between wounds, or rather scars, and wrinkles is that they are both made from a larger than normal type of collagen. The contention is that CPs help to slowly encourage the body to replace this collagen with the healthy, normal sized type of collagen molecule, and also help to develop more healthy collagen at the site.


No it's actually different.

Wrinkles are "produced" due to collagen (and elastin) degradation (i.e. collagen loss). Scars are produced due to collagen overproduction.

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Fri Apr 30, 2010 12:35 pm      Reply with quote
bethany wrote:
moosejavian wrote:
So why do people's scars improve/fill in/disappear with the use of CP and exfoliators then?


It would have to be due to development of collagen/elastin...not because of exfoliation.

And keep in mind that most people with scars are also needling and have done significant peels (TCA, higher % glycolic, etc.) at some point, all of which which also generate collagen.

Of course CPs may help with that collagen generation. My only point is that scars do not exfoliate up and out as people keep saying.



I think even with very mild exfoliation the appearance of skin can improve because exfoliation helps with the "plumping" effect.

Also I was reading recently (so don't quote me on this!) that even mild exfoliation (that doesn't really really reach the dermis) may increase collagen production because of cytokine production. When we exfoliate lightly, there's a little bit of inflammation that happens. That tiny inflammation would still help the release of certain cytokines that would then increase collagen production.

Now with medium depth peels people do reach the upper reticular dermis so there the mechanism for collagen production seems more clear.

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Fri Apr 30, 2010 1:06 pm      Reply with quote
Josee wrote:
bethany wrote:
moosejavian wrote:
So why do people's scars improve/fill in/disappear with the use of CP and exfoliators then?


It would have to be due to development of collagen/elastin...not because of exfoliation.

And keep in mind that most people with scars are also needling and have done significant peels (TCA, higher % glycolic, etc.) at some point, all of which which also generate collagen.

Of course CPs may help with that collagen generation. My only point is that scars do not exfoliate up and out as people keep saying.



I think even with very mild exfoliation the appearance of skin can improve because exfoliation helps with the "plumping" effect.

Also I was reading recently (so don't quote me on this!) that even mild exfoliation (that doesn't really really reach the dermis) may increase collagen production because of cytokine production. When we exfoliate lightly, there's a little bit of inflammation that happens. That tiny inflammation would still help the release of certain cytokines that would then increase collagen production.

Now with medium depth peels people do reach the upper reticular dermis so there the mechanism for collagen production seems more clear.


So all of this means that the exfoliators definitely contribute to the collagen generation, and can be directly associated with a portion of any results seen when used in tandem with CPs, yes?

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Fri Apr 30, 2010 7:06 pm      Reply with quote
Josee
Wrinkles are caused by a loss of collagen, however the collagen that remains in the damaged area (usually due to sun damage)changes from healthy, normal collagen to a larger, less viable type. This is shared with the collagen found in scars. It is this type of collagen molecule that CPs are supposed to help the body replace with healthier newer collagen.
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Sat May 01, 2010 7:26 am      Reply with quote
The BF and I are avid users of many skincare products (favorite now being CP's) and the evidence I like is the one I see as we sit in bright sun and visibly notice the firm, more youthful skin. Today I really noticed it on the BF. It was a big AHA - and I told him so. Next stop CP's for the eye area.

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Sat May 01, 2010 8:59 am      Reply with quote
impressive, Sister!

Alexes (or anyone else wo may know):

So is the function of the CP's, then, to break down the non-viable collagen in wrinkles so that healthy new collagen can form? In other words, do the CP's just break down old non-viable collagen making way for healthy collagen (aided by massage, exfoliating acids, dry brushing, dermarolling,etc.)or does it also play a role in building new collagen in the wrinkle area?

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Sat May 01, 2010 2:00 pm      Reply with quote
bethany wrote:
Josee wrote:
bethany wrote:
moosejavian wrote:
So why do people's scars improve/fill in/disappear with the use of CP and exfoliators then?


It would have to be due to development of collagen/elastin...not because of exfoliation.

And keep in mind that most people with scars are also needling and have done significant peels (TCA, higher % glycolic, etc.) at some point, all of which which also generate collagen.

Of course CPs may help with that collagen generation. My only point is that scars do not exfoliate up and out as people keep saying.



I think even with very mild exfoliation the appearance of skin can improve because exfoliation helps with the "plumping" effect.

Also I was reading recently (so don't quote me on this!) that even mild exfoliation (that doesn't really really reach the dermis) may increase collagen production because of cytokine production. When we exfoliate lightly, there's a little bit of inflammation that happens. That tiny inflammation would still help the release of certain cytokines that would then increase collagen production.

Now with medium depth peels people do reach the upper reticular dermis so there the mechanism for collagen production seems more clear.


So all of this means that the exfoliators definitely contribute to the collagen generation, and can be directly associated with a portion of any results seen when used in tandem with CPs, yes?


Yes I would think so. I'm going to try to find the paper and just post at least the reference and abstract so it's more clear because I can't remember which cell exactly produced the cytokines Very Happy

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Sat May 01, 2010 2:13 pm      Reply with quote
alexes wrote:
Josee
Wrinkles are caused by a loss of collagen, however the collagen that remains in the damaged area (usually due to sun damage)changes from healthy, normal collagen to a larger, less viable type. This is shared with the collagen found in scars. It is this type of collagen molecule that CPs are supposed to help the body replace with healthier newer collagen.


No alexes, that's just not how it works. Collagen degrades and any collagen aggregation is insignificant in photoaging. If you want to know more about what happens with the skin and collage in photoaging, please read this:
Am J Pathol. 2009 Feb;174(2):401-13

I can provide you with the full paper if you need it.


During wound healing, there's this HUGE RUSH of all kinds of cytokines, growth factors, etc, etc. Thus there is the big stimulus for fibroblast to proliferate, deposit more collagen, for keratinocytes to proliferate, etc, etc. This stimulus is so potent that it causes collagen to be deposited in excess and in a disorganized way. So if you put something that stimulates the MMPs then it's a good thing because you will prevent collagen from depositing like crazy and creating a scar. Even if something activates MMPs, the stimulus to produce collagen is so big that still collagen will be produced.


Now during photoaging, basically UV rays activate the transcription of certain genes who in turn at the end of the chain activate MMPs. It is because of the MMPs that our collagen degrades. When it degrades it just degrades. The collagen that's degraded does not form aggregates. So in the end, you have an overall loss of collagen. So you definitely DO NOT want to stimulate any MMP activity. Even if there were some aggregates produced during the photodamage you DO NOT want to get rid of them because non-optimal collagen is better than no collagen. Wrinkles are not created by non-optimal collagen, it's lack of collagen that creates it. Think about ablative laser treatments. The type of collagen aggregates they generate is similar to the one generated by a wound (i.e. it forms aggregates) but because it is a "controlled" wound, the effect at the end of the day is less wrinkles and firmer skin.

As an illustration, take the case of isotretioin. Isotretinoin in low doses is being used for photoaging. Among the effects of isotretinion is the inhibition of MMPs. So after using isotretinoin for a certain amount of time, dermal collagen increases.

However, doing peels while on isotretinoin is contraindicated. Why is that? Because (due to the fact that it inhibits MMPs) there is an increased risk of scarring.

So as you can see, wound healing and photoaging are 2 distinct processes and something that can be good for wound healing can be bad for photoaging and vice versa.

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Sat May 01, 2010 2:30 pm      Reply with quote
Josee wrote:

No alexes, that's just not how it works. Collagen degrades and any collagen aggregation is insignificant in photoaging. If you want to know more about what happens with the skin and collage in photoaging, please read this:
Am J Pathol. 2009 Feb;174(2):401-13

I can provide you with the full paper if you need it.




http://www.ncbi.nlm.nih.gov/pubmed/19147830

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630545/?tool=pubmed

Another article worth reading on Photoaging:

http://archderm.highwire.org/cgi/content/full/138/11/1462

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Sat May 01, 2010 6:37 pm      Reply with quote
Josee
I repeat - while wrinkles are caused by a loss of collagen, the collagen that remains is damaged. This is usually due to DNA damage from the sun
http://www.telemedicine.org/sundam/sundam2.4.1.html
I did not say wrinkles were not caused by loss of collagen, but that the extra large collagen particle is shared between wrinkles and scars. Please read my posts properly before you decided to respond. Other wise this whole discussion makes about as much sense as taking dermatological advise from a gynecologist.
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Sat May 01, 2010 7:54 pm      Reply with quote
Imperfect repair of the dermal damage impairs the functional and structural integrity of the extracellular matrix. Repeated sun exposure causes accumulation of dermal damage that eventually results in characteristic wrinkling of photodamaged skin.


Above is quoted from article Lacy posted. Validates Alexes post. I knew what she meant.

FYI Josee: Others opinions are worthwhile also.

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Sat May 01, 2010 8:14 pm      Reply with quote
alexes wrote:
Josee
I repeat - while wrinkles are caused by a loss of collagen, the collagen that remains is damaged. This is usually due to DNA damage from the sun
http://www.telemedicine.org/sundam/sundam2.4.1.html
I did not say wrinkles were not caused by loss of collagen, but that the extra large collagen particle is shared between wrinkles and scars. Please read my posts properly before you decided to respond. Other wise this whole discussion makes about as much sense as taking dermatological advise from a gynecologist.


First of all, I would suggest you check other sources since the article you are reading has very old references from the 80s and early 90s. Lots has been understood and much of what thought to be a product of DNA "damage" is actually activation of certain genes (there's still DNA damage though).
It's amazing how the gene-molecular sequence is much more understood nowadays.

So a couple of things that don't seem clear from your post.

DNA damage is DIFFERENT than collagen degradation. DNA is in the cells and DNA damage usually results in the death of a cell.
Collagen is a protein and it does not have DNA.

Secondly, the link you posted says nothing about collagen.

Thirdly, when collagen is broken down by the MMPs it is broken down. It does not form extra-large anything. If anything... it's smaller particles! This happens both in wounds and in photoaging.

The extra large collagen is not a product of damage but a product of a very strong stimulus of collagen to aggregate that then instead of having a nice arrangement you have large aggregates. One of the biggest culprits of this is TGF b1. TGF b1 is increased in wound healing. In one in vitro study I think CPs were shown to decrease TGF b1 in a wound model which is one of the reasons people claim it's good for wound healing. However, in absence of wounds, having a little TGF promoting collagen synthesis is not bad. In fact, one of the effects of UV rays in fibroblasts (besides the activation of MMPs) is a reduction in the expression of TGF b1. So again, while this is good for wound healing... not so good for photoaging.

Now

Again, I suggest you read the links that were provided on photoaging to understand how the process works, which were written by specialists on that field so you should like that Smile

In fact, you might be interested in reading the following paper:

The effect of narrowband ultraviolet B on the expression of matrix metalloproteinase-1, transforming growth factor-beta1 and type I collagen in human skin fibroblasts.Br J Dermatol. 2007 May;156(5):951-6.

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Sat May 01, 2010 8:16 pm      Reply with quote
sister sweets wrote:
Imperfect repair of the dermal damage impairs the functional and structural integrity of the extracellular matrix. Repeated sun exposure causes accumulation of dermal damage that eventually results in characteristic wrinkling of photodamaged skin.


Above is quoted from article Lacy posted. Validates Alexes post. I knew what she meant.



Again, dermal damage is not accumulation of extra large collagen, it is degradation of collagen. What I said is exactly what Lacy's articles said. If there is any collagen aggregation it is insignificant.

I can be wrong, it would not be the first or the last time. I know what I read but I can't possibly read every single article. So if someone finds a recent article saying that somehow due to photoaging these layers of extra large collagen accumulate and affect the skin's appearance then I'll be more than grateful for the dermatology lesson.

The fact that I respond to people's posts and ideas is the clearest indication that I consider them worthwhile. If I did not deem them worthwhile I would not spend time typing.

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Sat May 01, 2010 8:26 pm      Reply with quote
Not to take this off topic but how is isotretinoin (which you mentioned earlier was contraindicated with peels) different than tretinoin. I'm on obagi now and once on maintenance, want to do some peels. I will still be using the tretinoin during maintenance.
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Sat May 01, 2010 8:47 pm      Reply with quote
Josee wrote:
sister sweets wrote:
Imperfect repair of the dermal damage impairs the functional and structural integrity of the extracellular matrix. Repeated sun exposure causes accumulation of dermal damage that eventually results in characteristic wrinkling of photodamaged skin.


Above is quoted from article Lacy posted. Validates Alexes post. I knew what she meant.



Again, dermal damage is not accumulation of extra large collagen, it is degradation of collagen. What I said is exactly what Lacy's articles said. If there is any collagen aggregation it is insignificant.



For what it's worth, I concur with Josee; damage to the dermis from UV exposure results in the degradation of collagen. I provided the link for the article Josee referenced and then added my own link for the second article because both articles fully support her explanations. The links I provided do NOT validate the statements made by Alexes.

I read the link provided by Alexes 3 times (all 3 pages). I saw no reference to collagen, let alone extra large collagen particles.

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Sat May 01, 2010 8:48 pm      Reply with quote
its_kristy wrote:
Not to take this off topic but how is isotretinoin (which you mentioned earlier was contraindicated with peels) different than tretinoin. I'm on obagi now and once on maintenance, want to do some peels. I will still be using the tretinoin during maintenance.


Kristy, isotretinoin is also known as Accutane and is oral.
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