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Sat Jul 14, 2012 10:13 am |
Keliu wrote: |
Yes! Thanks Tiny. This is the part that concerned me:
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This is why we are tending to tell people to be cautious about applying cytokines dermally - you want to make sure they are the right ones, not a bunch of inflammatory cytokines & adipokines. Some women apply their anti-aging products to their d�colletage - which encompasses a fair amount of breast tissue. |
To me, this sounds like if you are applying inflammatory cytokines (which we've been told adipose are) to the area near the breast then you may run into trouble with the C-word. |
Yes, caution, a good word. I am not trying to be black and white about stem cell sources generally speaking. There are many uses for cytokines from adipose sources, especially in tissue transplantation. I didn't do this work, others did, and I have merely reported on it. The one that seems troublesome to many is this statement:
Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates.
Tissue Eng Part A. 2011 Jan;17(1-2):93-106. University of Pittsburgh Cancer Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
The secretome profile of ASC resembled that reported for MSC, but included adipose-associated adipsin and the hormone leptin, shown to promote breast cancer growth. Our data indicate that ASC enhance the growth of active, but not resting tumor cells. Thus, reconstructive therapy utilizing ASC-augmented whole fat should be postponed until there is no evidence of active disease.
Does this mean that ADSC's cause cancer? No. But we know from multiple sources that ADSC's secrete inflammatory cytokines, plus leptin and adipokines that promote growth of active tumors. E.g.
Adipose-derived Stem Cells: Current Findings and Future Perspectives. Discovery Medicine 2012.
Reciprocal interactions between breast tumor cells and stromal cells are mediated by inflammatory cytokines and chemokines, and may affect tumor development and progression. Therefore, the molecular basis of the effects of adipose tissue on the behavior of tumor cells should be carefully examined before the future clinical application of stem cell therapies.
The paradox of pro-inflammatory cytokines in cancer. Dinarello CA.
Cancer Metastasis Rev. 2006 Sep;25(3):307-13.
Cytokines such as IL-1 and TNF are primarily pro-inflammatory. The inflammation induced by these cytokines is reflected in the type of genes they induce. In the pathogenesis of carcinogenesis as well as tumor growth and spread, cytokines such as IL-1 and TNF induce chemokines that attract neutrophils. Neutrophils are key players in the production of reactive oxygen species and carcinogenesis.
These are all the words of other scientists, not me.
As for me, my issue is not with ADC's per se, but with inflammatory cytokines (from any source) applied topically over long periods of time. Go back and read the last 1/3 of this:
http://barefacedtruth.com/2012/07/04/cytokine-stem-cell-%E2%80%9Ctissue-of-origin%E2%80%9D-issues-part-4-an-inflammatory-view/
to get my views stated as clearly as I can.
In the short term, in the early stages of wound healing, there is a role for inflammatory cytokines. That is natural. What is not physiologic is chronic stimulation with inflammatory cytokines, as that can lead to what? Right! Chronic smoldering inflammation. Which leads to what? That's right - diseases of all sorts. (see table in the BFT article). And even if it didn't cause disease - inflammation accelerates aging. Short term gains (neutrophils fill in the wrinkles a bit) long term losses (fibrosis, bad matrix, depletion of SSC's.
Pro-inflammatory cytokine balances applied chronically is my issue. Whatever their source. Yes, I recommend caution. |
_________________ Physician - scientist - curmudgeon. Kind to animals and stem cells. Nonprofit muckraking site: www.barefacedtruth.com. Day job: www.anteage.com |
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Sat Jul 14, 2012 10:25 am |
DrJ wrote: |
Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates.
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Hi Dr J. Glad to see you back at EDS. My stupid question of the day for you! These studies are all speaking about the actual stem cells, not the conditioned media we are applying to the skin, is this correct? Also, these products we are using are cosmetics (versus actual drugs like Retin A), so how deep are these cosmetics actually getting? |
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Sat Jul 14, 2012 11:03 am |
DrJ wrote: |
As for me, my issue is not with ADC's per se, but with inflammatory cytokines (from any source) applied topically over long periods of time. Go back and read the last 1/3 of this:
http://barefacedtruth.com/2012/07/04/cytokine-stem-cell-%E2%80%9Ctissue-of-origin%E2%80%9D-issues-part-4-an-inflammatory-view/
to get my views stated as clearly as I can.
In the short term, in the early stages of wound healing, there is a role for inflammatory cytokines. That is natural. What is not physiologic is chronic stimulation with inflammatory cytokines, as that can lead to what? Right! Chronic smoldering inflammation. Which leads to what? That's right - diseases of all sorts. (see table in the BFT article). And even if it didn't cause disease - inflammation accelerates aging. Short term gains (neutrophils fill in the wrinkles a bit) long term losses (fibrosis, bad matrix, depletion of SSC's.
Pro-inflammatory cytokine balances applied chronically is my issue. Whatever their source. Yes, I recommend caution. |
Perhaps this chronic inflammation from "pro-inflammatory cytokine balances" is the real reason ReLuma users are advised to reduce usage after the initial period of usage. (The recommended schedule is 2X per day for the first 3 months, then 1X per day for the next 3 months, followed by 2-3X per week thereafter). |
_________________ Born 1953; Blonde-Blue; Normal skin |
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Sat Jul 14, 2012 11:51 am |
Lacy53 wrote: |
Perhaps this chronic inflammation from "pro-inflammatory cytokine balances" is the real reason ReLuma users are advised to reduce usage after the initial period of usage. (The recommended schedule is 2X per day for the first 3 months, then 1X per day for the next 3 months, followed by 2-3X per week thereafter). |
Maybe. But after ten years of actual sales/use, and over 100,000 bottles out there, I would think that problems - especially serious problems - would be apparent. Additionally, I would think that skin care professionals having encountered patients with problems related to this product, would be making noise about pulling if off the market. Or at least informing patients not to use it. But I am aware of none of this. Recently there was a poster here on EDS that wrote about being diagnosed with breast cancer after taking a prescription drug for a medical issue (I think maybe it was rheumatoid arthritis). My point is that you tend to hear about this stuff - especially with the Internet. So until an actual person comes forward with something real, I am inclined dismiss this as nothing more than someone using scare tactics to discredit yet another product. |
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Sat Jul 14, 2012 3:52 pm |
rileygirl wrote: |
Hi Dr J. Glad to see you back at EDS. My stupid question of the day for you! These studies are all speaking about the actual stem cells, not the conditioned media we are applying to the skin, is this correct? Also, these products we are using are cosmetics (versus actual drugs like Retin A), so how deep are these cosmetics actually getting? |
This is not a stupid question at all. I also want to make sure we're comparing apples with apples. |
_________________ Born 1950. There's a new cream on the market that gets rid of wrinkles - you smear it on the mirror!! |
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Sat Jul 14, 2012 4:37 pm |
Wouldn't they be classified as drugs instead of cosmetics if they would have an action more than just skin deep? Or have I misread the FDA guidelines?
On the other hand, the report here of someone apparently linking having a period to the use of Cellese would indicate that there is some kind of systemic action. Same goes for the earlier report by dr J. about someone who was having her cheeks getting fuller due to increase of subcutaneous fat. If it works subcutaneously, it's a drug, not a cosmetic. |
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Sat Jul 14, 2012 4:43 pm |
rileygirl wrote: |
DrJ wrote: |
Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates.
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Hi Dr J. Glad to see you back at EDS. My stupid question of the day for you! These studies are all speaking about the actual stem cells, not the conditioned media we are applying to the skin, is this correct? Also, these products we are using are cosmetics (versus actual drugs like Retin A), so how deep are these cosmetics actually getting? |
Hi RG, no stupid questions, answers are another story.
The Zimmerlan paper noted above actually uses conditioned medium, as well as co-culturing techniques. “Culture media were harvested 3 days after initial plating and snap-frozen for analysis of multiple secreted cytokine, chemokine, and growth factors.” It is a sophisticated series of studies. Some excerpts: We developed an in vitro coculture system to measure their recruitment by shortly expanded human ASC, as compared to BM-MSC. … To explore potential mechanisms by which ASC could promote the growth of primary breast cancer cells in culture, we measured the levels of a battery of cytokines, chemokines, and growth factors secreted by low-passage ASC … ASC uniquely secreted adipsin and leptin, suggesting that despite their immunophenotypic similarity to BM-MSC, they are skewed toward a fat-related repertoire of secreted proteins that could account for their differing-abilities to promote the growth of breast cancer tumor cells from clinical isolates.
The same cytokines are secreted by stem cells in culture as in in the body. There are many studies cited in our BFT series that detail the typical cytokines from different cell types, as part of that stem cell’s “secretome”. The way stem cells work in healing and regeneration is primarily through cytokines (often called a paracrine action). The whole basis for stem cell conditioned medium-derived products recognizes this fact. We capture the signals, and use them therapeutically. Other scientists are tuning into this and using cytokines harvested the same way to create treatments for diseases. See http://barefacedtruth.com/2012/07/02/cytokines-in-healing-and-rejuvenation-part-2/ for a discussion of how and why cytokines are farmed from stem cells.
Cytokines are small “signaling” proteins with molecular weights ranging from 8 to 40,000 daltons. So most are pretty small. Absorption has been measured, and does occur. Further, since we are talking “receptor chemistry” it only takes a few molecules to kick a cell into action. Surprisingly potent.
The pattern of cytokines secreted by cells in culture depends on many things. See http://barefacedtruth.com/wp-admin/post.php?post=1380&action=edit for a full discussion of all that. The ones that were being discussed above are inflammatory, including a type of cytokines known as adipokines, a type associated with adipose- derived stem cells.
But our key concerns have to do with inflammation, or pro-aging, not cancer . Inflammaging. Chronic smoldering inflammation, subclinical, no signs or symptoms. Just the paradox of apply something to stave off the signs of aging, but doing so in a way that actually promotes aging. We don’t envision a sudden crop of facial tumors as much as we see skin aging faster. Might not show up for years. Now I’m 59, and suddenly look 65, that sort of thing. People will think it’s bad genes when the inciting events were actually epigenetic and by their own hand. |
_________________ Physician - scientist - curmudgeon. Kind to animals and stem cells. Nonprofit muckraking site: www.barefacedtruth.com. Day job: www.anteage.com |
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Sat Jul 14, 2012 6:10 pm |
Panda1 wrote: |
Lacy53 wrote: |
Perhaps this chronic inflammation from "pro-inflammatory cytokine balances" is the real reason ReLuma users are advised to reduce usage after the initial period of usage. (The recommended schedule is 2X per day for the first 3 months, then 1X per day for the next 3 months, followed by 2-3X per week thereafter). |
Maybe. But after ten years of actual sales/use, and over 100,000 bottles out there, I would think that problems - especially serious problems - would be apparent. Additionally, I would think that skin care professionals having encountered patients with problems related to this product, would be making noise about pulling if off the market. Or at least informing patients not to use it. But I am aware of none of this. Recently there was a poster here on EDS that wrote about being diagnosed with breast cancer after taking a prescription drug for a medical issue (I think maybe it was rheumatoid arthritis). My point is that you tend to hear about this stuff - especially with the Internet. So until an actual person comes forward with something real, I am inclined dismiss this as nothing more than someone using scare tactics to discredit yet another product. |
It pains me to post on here but, that was 10,000.00 in clinical trials.
Panda, the number of units of ReLuma that have been sold are closer to 500,000.
It is all on the ReLuma thread page 10 has the email from Invitrx the manufacturer:
http://www.essentialdayspa.com/forum/viewthread.php?tid=45705&postdays=0&postorder=asc&&start=225 |
_________________ I'LL SEE YOU ON THE DARKSIDE OF THE MOON.... |
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Sat Jul 14, 2012 7:37 pm |
DarkMoon wrote: |
Panda1 wrote: |
Lacy53 wrote: |
Perhaps this chronic inflammation from "pro-inflammatory cytokine balances" is the real reason ReLuma users are advised to reduce usage after the initial period of usage. (The recommended schedule is 2X per day for the first 3 months, then 1X per day for the next 3 months, followed by 2-3X per week thereafter). |
Maybe. But after ten years of actual sales/use, and over 100,000 bottles out there, I would think that problems - especially serious problems - would be apparent. Additionally, I would think that skin care professionals having encountered patients with problems related to this product, would be making noise about pulling if off the market. Or at least informing patients not to use it. But I am aware of none of this. Recently there was a poster here on EDS that wrote about being diagnosed with breast cancer after taking a prescription drug for a medical issue (I think maybe it was rheumatoid arthritis). My point is that you tend to hear about this stuff - especially with the Internet. So until an actual person comes forward with something real, I am inclined dismiss this as nothing more than someone using scare tactics to discredit yet another product. |
It pains me to post on here but, that was 10,000.00 in clinical trials.
Panda, the number of units of ReLuma that have been sold are closer to 500,000.
It is all on the ReLuma thread page 10 has the email from Invitrx the manufacturer:
http://www.essentialdayspa.com/forum/viewthread.php?tid=45705&postdays=0&postorder=asc&&start=225 |
The advancement of this technology took several more years and is just now at a state of advancement that it can be used in a product such as ReLuma. Clinical studies and over 100,000 patients have used ReLuma and a track record of success and efficacy grows each day.
I think this is what your talking about. It say clinical studies AND 100,000 patients have used Reluma. That means they have SOLD the product to 100,000 people NOT that all those people were in clinical studies. I would still like to see those clinical studies if possible. It doesn't say how many people were in the study and the one I saw referenced was a 4 week study. |
_________________ Everything has beauty but not everyone sees it |
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Sat Jul 14, 2012 8:05 pm |
CookieD wrote: |
DarkMoon wrote: |
Panda1 wrote: |
Lacy53 wrote: |
Perhaps this chronic inflammation from "pro-inflammatory cytokine balances" is the real reason ReLuma users are advised to reduce usage after the initial period of usage. (The recommended schedule is 2X per day for the first 3 months, then 1X per day for the next 3 months, followed by 2-3X per week thereafter). |
Maybe. But after ten years of actual sales/use, and over 100,000 bottles out there, I would think that problems - especially serious problems - would be apparent. Additionally, I would think that skin care professionals having encountered patients with problems related to this product, would be making noise about pulling if off the market. Or at least informing patients not to use it. But I am aware of none of this. Recently there was a poster here on EDS that wrote about being diagnosed with breast cancer after taking a prescription drug for a medical issue (I think maybe it was rheumatoid arthritis). My point is that you tend to hear about this stuff - especially with the Internet. So until an actual person comes forward with something real, I am inclined dismiss this as nothing more than someone using scare tactics to discredit yet another product. |
It pains me to post on here but, that was 10,000.00 in clinical trials.
Panda, the number of units of ReLuma that have been sold are closer to 500,000.
It is all on the ReLuma thread page 10 has the email from Invitrx the manufacturer:
http://www.essentialdayspa.com/forum/viewthread.php?tid=45705&postdays=0&postorder=asc&&start=225 |
The advancement of this technology took several more years and is just now at a state of advancement that it can be used in a product such as ReLuma. Clinical studies and over 100,000 patients have used ReLuma and a track record of success and efficacy grows each day.
I think this is what your talking about. It say clinical studies AND 100,000 patients have used Reluma. That means they have SOLD the product to 100,000 people NOT that all those people were in clinical studies. I would still like to see those clinical studies if possible. It doesn't say how many people were in the study and the one I saw referenced was a 4 week study. |
It was to late to edit my entry but I did see this further down the list but I still think it say the same thing as above but wanted to add it just in case.
Yes. ReLuma products have been tested on over 100,000 users and in clinical trials. All products have also been registered with the FDA. It is not a requirement that the FDA approve ReLuma, nor is it required that it be registered. |
_________________ Everything has beauty but not everyone sees it |
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Sat Jul 14, 2012 8:43 pm |
CookieD wrote: |
CookieD wrote: |
DarkMoon wrote: |
Panda1 wrote: |
Lacy53 wrote: |
Perhaps this chronic inflammation from "pro-inflammatory cytokine balances" is the real reason ReLuma users are advised to reduce usage after the initial period of usage. (The recommended schedule is 2X per day for the first 3 months, then 1X per day for the next 3 months, followed by 2-3X per week thereafter). |
Maybe. But after ten years of actual sales/use, and over 100,000 bottles out there, I would think that problems - especially serious problems - would be apparent. Additionally, I would think that skin care professionals having encountered patients with problems related to this product, would be making noise about pulling if off the market. Or at least informing patients not to use it. But I am aware of none of this. Recently there was a poster here on EDS that wrote about being diagnosed with breast cancer after taking a prescription drug for a medical issue (I think maybe it was rheumatoid arthritis). My point is that you tend to hear about this stuff - especially with the Internet. So until an actual person comes forward with something real, I am inclined dismiss this as nothing more than someone using scare tactics to discredit yet another product. |
It pains me to post on here but, that was 10,000.00 in clinical trials.
Panda, the number of units of ReLuma that have been sold are closer to 500,000.
It is all on the ReLuma thread page 10 has the email from Invitrx the manufacturer:
http://www.essentialdayspa.com/forum/viewthread.php?tid=45705&postdays=0&postorder=asc&&start=225 |
The advancement of this technology took several more years and is just now at a state of advancement that it can be used in a product such as ReLuma. Clinical studies and over 100,000 patients have used ReLuma and a track record of success and efficacy grows each day.
I think this is what your talking about. It say clinical studies AND 100,000 patients have used Reluma. That means they have SOLD the product to 100,000 people NOT that all those people were in clinical studies. I would still like to see those clinical studies if possible. It doesn't say how many people were in the study and the one I saw referenced was a 4 week study. |
It was to late to edit my entry but I did see this further down the list but I still think it say the same thing as above but wanted to add it just in case.
Yes. ReLuma products have been tested on over 100,000 users and in clinical trials. All products have also been registered with the FDA. It is not a requirement that the FDA approve ReLuma, nor is it required that it be registered. |
Email From Invitrix:
DarkMoon wrote: |
Response to my email from Invitrx:
Diem Vo diem@invitrx.com
Hi XXXX,
Lacey brings up a very apt concern. I would like to reassure her and others which may have the same feelings towards our skin care line. Our anti-aging serum has been on the market for about 10 years now and sold close to 500,000 units. Our product will not stimulate hair growth in undesirable locations and here's why: Our product's growth factors and cytokines present in the stem cell conditioned media stimulates further cell signalling specific to the target area (ie dermal skin cells when applied topically to the skin). Furthermore, hair growth will only occur where active hair follicles exist such as applying the hair product to the scalp. Our products do all have the same underlying active ingredient and they differ slightly with other ingredients to create our various products in our skin care and hair care line.
If you have further questions, please feel free to contact us.
Thank you,
Diem |
http://www.essentialdayspa.com/forum/viewthread.php?tid=45705&postdays=0&postorder=asc&&start=225[/ |
_________________ I'LL SEE YOU ON THE DARKSIDE OF THE MOON.... |
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Sun Jul 15, 2012 5:29 am |
Dr. J.,
I think its time you took your own advice, and stop this drama, your product is good or its not, it will sell itself or it won't. Stop bashing all these other products, it is really unbecoming, unprofessional and unnecessary. They are not bashing yours, give them the same courtesy.
DrJ wrote: |
missz wrote: |
Dr J,
Yes, we do recommend that the Lifeline Serums be applied twice a day for best results. But how you choose to do that is up to you. You can apply both the AM and PM products as labeled, or apply the PM product twice a day. The encapsulated stem cell extracts are the same--the difference between the two products is that the AM product contains a sunscreen and more anti-oxidants. Depending on your regimen, do what works best for you.
No, the formula is not designed to remain on the surface of the skin. That's a key differentiating factor between Lifeline and some other creams with growth factors and peptides--many of which are too large to penetrate the skin. Lifeline's stem cell extracts are encapsulated in a lipid bi-layer nanosphere that serves several different functions--(1) it preserves the efficacy of the actives, (2) the nano-technology enhances penetration, and (3) the nanospheres don't break open until after they have penetrated the epidermis. |
You are trying too hard. Don't oversell. We ask basic questions and you keep giving us your competitive stance. Not needed. |
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Sun Jul 15, 2012 6:05 am |
Do go away and actually read the thread Tiny, the majority of the time questions about competitive products are being put to DrJ by people like yourself. Why do you and yours read and post on this thread if you think so little of Cellese/ AnteAGE/ DrJ's professional opinion (delete as applicable)? Most peculiar. |
_________________ Sensitivity, forehead pigmentation & elevens, nose & chin clogged pores. Topicals: Aloe vera, squalane, lactic acid, Myfawnie KinNiaNag HG: Weleda calendula, Lanolips, Guinot masque essentiel, Flexitol Naturals, Careprost. Gadgets: Vaughter dermarollers, Lightstim. |
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Sun Jul 15, 2012 6:11 am |
Firefox7275 wrote: |
Do go away and actually read the thread Tiny, the majority of the time questions about competitive products are being put to DrJ by people like yourself. Why do you and yours read and post on this thread if you think so little of Cellese/ AnteAGE/ DrJ's professional opinion (delete as applicable)? Most peculiar. |
Perhaps you can "read" the thread, I have NEVER once said a bad word about this product, perhaps I've questioned the selling tactics, but NEVER the product. |
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Sun Jul 15, 2012 6:53 am |
DrJ wrote: |
But our key concerns have to do with inflammation, or pro-aging, not cancer . Inflammaging. Chronic smoldering inflammation, subclinical, no signs or symptoms. Just the paradox of apply something to stave off the signs of aging, but doing so in a way that actually promotes aging. We don’t envision a sudden crop of facial tumors as much as we see skin aging faster. Might not show up for years. Now I’m 59, and suddenly look 65, that sort of thing. People will think it’s bad genes when the inciting events were actually epigenetic and by their own hand. |
Thanks for the reply, Dr J, and I will go read the links you provided.
Question about the absorption you mentioned that it has been measured and does occur. Does this mean that these products should be considered drugs then? Do you know how much absorption occurred?
As for the inflammaging, I definitely understand that concern. However, isn't that also a concern for a lot of products and not just the conditioned media ones; meaning we just don't really know what any of the ingredients do over the long term, right? I don't know of anything other than tretinoin that has been studied long term and I think the longest for tret was 5 years (I could definitely be wrong on the length of this, but that number sticks in my mind!). |
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Sun Jul 15, 2012 5:12 pm |
DrJ - Just thinking out loud here - but why hasn't cytokine technology (of any description) been embraced by such companies as Procter & Gamble or Johnson & Johnson for use in their OTC wound and burn products? |
_________________ Born 1950. There's a new cream on the market that gets rid of wrinkles - you smear it on the mirror!! |
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Sun Jul 15, 2012 6:29 pm |
rileygirl wrote: |
DrJ wrote: |
But our key concerns have to do with inflammation, or pro-aging, not cancer . Inflammaging. Chronic smoldering inflammation, subclinical, no signs or symptoms. Just the paradox of apply something to stave off the signs of aging, but doing so in a way that actually promotes aging. We don’t envision a sudden crop of facial tumors as much as we see skin aging faster. Might not show up for years. Now I’m 59, and suddenly look 65, that sort of thing. People will think it’s bad genes when the inciting events were actually epigenetic and by their own hand. |
Thanks for the reply, Dr J, and I will go read the links you provided.
Question about the absorption you mentioned that it has been measured and does occur. Does this mean that these products should be considered drugs then? Do you know how much absorption occurred?
As for the inflammaging, I definitely understand that concern. However, isn't that also a concern for a lot of products and not just the conditioned media ones; meaning we just don't really know what any of the ingredients do over the long term, right? I don't know of anything other than tretinoin that has been studied long term and I think the longest for tret was 5 years (I could definitely be wrong on the length of this, but that number sticks in my mind!). |
Hi RG, absorption medically means movement of what is applied topically through the skin through all layers and into the generally circulation to act systemically. Some drug delivery systems are designed to do just that – use the skin as a route for medication. But I have noticed a lot of people misusing the term to mean absorption through the stratum corneum, or though the epidermis to the dermis and or subdermis. Technically, this is called penetration. For a short summary of penetration (and how often you find things that don’t), see http://barefacedtruth.com/2012/06/23/let%E2%80%99s-talk-penetration/.
Now, whether something penetrates or not, or is absorbed or not, has nothing to do with whether it is a drug. Whether a product is a cosmetic or a drug under the law is determined by a product's intended use. The FD&C Act defines drugs, in part, by their intended use, as "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease" and "articles (other than food) intended to affect the structure or any function of the body of man or other animals". Such claims establish the product as a drug because the intended use is to treat or prevent disease or otherwise affect the structure or functions of the human body. A common example is a claim that a product will restore hair growth. That actually automatically defines it as a drug by the FDA. Doesn’t need to get absorbed or work systemically. Interesting, huh?
Now, think about how many active ingredients claim to increase the production of collagen? (how many don’t is a shorter list). One view is that saying so is a structure-function claim, and makes it a drug. Which calls to question – how closely does the FDA really enforce these regulations? As medical director for a large company, I had the opportunity to sit on FDA panels (with my team of pharma lawyers by my side) convened to discuss drugs and approvals. I can tell you straight out - nothing is black and white when it comes down to enforcement, or even monitoring.
Cytokines are very locally acting, but do penetrate into the dermis, with help (e.g. liposomes). Which is good, because that is where the bulk of the matrix important in wrinkles is formed. It’s where the real work of “improving appearance of aging” happens. But while topically applied cytokines can penetrate (with help), they are not well absorbed. Only tiny quantities if any. So, what would happen if cytokines become “absorbed” in the circulation? Not much, as they would be quickly diluted and/or degraded by the cytokines and cytokine regulators already in circulation, so that the prevalent pattern is undisturbed. No measurable change. Which is one thing that differentiates cytokines from man-made molecules. They are natural, and there are systems in place to degrade them. Unless there is an overwhelming amount, of the wrong kind, which is called a cytokine storm. They are purely inflammatory.
In terms of long term consequences of applying topicals, another great question. Again, I am going to put it into a framework of understand just how a particular substance works, and whether it is pro- or anti-inflammatory. Did you know that tretinoin is anti-inflammatory? (e.g. http://www.ncbi.nlm.nih.gov/pubmed/16045694Z). This is part of what assures its long term safety. Now how about Trichloracetic acid (TCA) at 35%. Highly inflammatory (which is how it works) – would you think it wise to put that on your skin every day for years? Probably not.
Hope this answers your questions. As always, they are very relevant to the discussion. |
_________________ Physician - scientist - curmudgeon. Kind to animals and stem cells. Nonprofit muckraking site: www.barefacedtruth.com. Day job: www.anteage.com |
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Sun Jul 15, 2012 6:48 pm |
Keliu wrote: |
DrJ - Just thinking out loud here - but why hasn't cytokine technology (of any description) been embraced by such companies as Procter & Gamble or Johnson & Johnson for use in their OTC wound and burn products? |
Ah, but is has, and this really speaks to safety issues. I know a lot about this (you can guess why). Platelet Derived Growth factor (PDGF) is one of those inflammatory cytokines we have been talking about. It is also the basis for a drug by J&J named Regranex used to treat diabetic foot ulcers. Now in this case it is put directly into wounds, in high concentrations, so lots can get absorbed. Read the news piece below. It says it all.
June 6, 2008 — Diabetes patients who use Regranex gel to treat dangerous foot and leg ulcers may have a fivefold higher risk of dying from cancer, the FDA today warned.
The FDA will ask Regranex maker Ethicon (a division of Johnson & Johnson) to put a “black box” warning label on the drug. The black-box warning is FDA’s highest warning level.
“In announcing this label change, FDA still cautions health care professionals to carefully weigh the risks and benefits of treating patients with Regranex,” Susan Walker, MD, director of the FDA’s Division of Dermatological and Dental Products, says in a news release. “Regranex is not recommended for patients with known malignancies.”
The cancer finding comes from an FDA review of a postmarketing survey that suggested there might be a link between Regranex and cancer.
“FDA has now completed its review of the study and has concluded that the increase in the risk of death from cancer in patients who used three or more tubes of Regranex was five times higher than in those patients who did not use Regranex,” the FDA reports.
Despite this fivefold increase in risk, the finding is based on only four excess cases of cancer, according to an Ethicon news release.
“We remain committed to the safety and efficacy of this product when used according to its label,” Ethicon spokeswoman Jackie Jankewicz tells WebMD.
Regranex is a medicine that is a genetically engineered form of a human cytokine / growth factor that helps wounds heal faster. It is a huge benefit to diabetic patients with slow-healing wounds on their legs or feet that often result in amputation of the affected limb.
Because Regranex makes cells grow faster, there has been concern that it will also make cancer cells grow more quickly. That’s why Ethicon has monitored patients since the drug was approved in December 1997.
There’s no evidence that Regranex causes new cancers, although the follow-up study has not gone on long enough to rule out this possibility. |
_________________ Physician - scientist - curmudgeon. Kind to animals and stem cells. Nonprofit muckraking site: www.barefacedtruth.com. Day job: www.anteage.com |
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Sun Jul 15, 2012 7:04 pm |
Very interesting DrJ - and, again, rather concerning. And I'm presuming that these are adipose cytokines or are PDGF different?? I find all these different growth factors very confusing!
Still, this isn't exactly what I asked - I was asking about over-the-counter products, not prescription.
Are there any OTC preparations containing cytokines for wound healing? |
_________________ Born 1950. There's a new cream on the market that gets rid of wrinkles - you smear it on the mirror!! |
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Sun Jul 15, 2012 7:59 pm |
Keliu wrote: |
Very interesting DrJ - and, again, rather concerning. And I'm presuming that these are adipose cytokines or are PDGF different?? I find all these different growth factors very confusing!
Still, this isn't exactly what I asked - I was asking about over-the-counter products, not prescription.
Are there any OTC preparations containing cytokines for wound healing? |
http://www.cytomedix.com/prp-systems/autologel/
The AutoloGel™ System harnesses the patient’s natural healing processes with the delivery of a platelet rich plasma gel containing growth factors, cytokines and chemokines for cell growth and formation of new tissue. By delivering both fibrin matrix and platelet releasate to the chronic wound bed, the AutoloGel System re-establishes the natural balance the body needs to escape the inflammatory phase so restoring the natural healing process.
The slides on this page sound like they could have been written by me?? |
_________________ Physician - scientist - curmudgeon. Kind to animals and stem cells. Nonprofit muckraking site: www.barefacedtruth.com. Day job: www.anteage.com |
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Sun Jul 15, 2012 11:11 pm |
DrJ wrote: |
Keliu wrote: |
Very interesting DrJ - and, again, rather concerning. And I'm presuming that these are adipose cytokines or are PDGF different?? I find all these different growth factors very confusing!
Still, this isn't exactly what I asked - I was asking about over-the-counter products, not prescription.
Are there any OTC preparations containing cytokines for wound healing? |
http://www.cytomedix.com/prp-systems/autologel/
The AutoloGel� System harnesses the patient�s natural healing processes with the delivery of a platelet rich plasma gel containing growth factors, cytokines and chemokines for cell growth and formation of new tissue. By delivering both fibrin matrix and platelet releasate to the chronic wound bed, the AutoloGel System re-establishes the natural balance the body needs to escape the inflammatory phase so restoring the natural healing process.
The slides on this page sound like they could have been written by me?? |
But this appears to be for use by doctors when combined with a patient's own blood - as in a PRP treatment.
Quote: |
Indications for Use The AutoloGel� System is intended to be used at point-of-care for the safe and rapid preparation of platelet-rich plasma (PRP) gel from a small sample of a patient�s own blood. Under the supervision of a healthcare professional, the PRP gel produced by the AutoloGel� System is suitable for exuding wounds, such as leg ulcers, pressure ulcers, and diabetic ulcers and for the management of mechanically or surgically-debrided wounds. |
http://www.cytomedix.com/prp-systems/autologel/product-description/
So presumably this is being injected and not applied topically like an OTC product. |
_________________ Born 1950. There's a new cream on the market that gets rid of wrinkles - you smear it on the mirror!! |
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Mon Jul 16, 2012 3:27 am |
Be interesting to see if DrJ gives a different answer to me, I believe he has held senior positions in pharmaceutical industry whereas my background is hospital pharmacy ...
Keliu: I would question whether there is a big enough market for an over-the-counter burns cream based on cytokines, particularly given what we have learned about shelf life, price bracket and complexity of manufacture. IME potential profit largely dictates what Big Pharma plough their research and advertising budget into. In the UK at least few people would be willing to pay AnteAGE prices for a burn/ wound cream, they'd want that on NHS prescription (£7.50/ $11). |
_________________ Sensitivity, forehead pigmentation & elevens, nose & chin clogged pores. Topicals: Aloe vera, squalane, lactic acid, Myfawnie KinNiaNag HG: Weleda calendula, Lanolips, Guinot masque essentiel, Flexitol Naturals, Careprost. Gadgets: Vaughter dermarollers, Lightstim. |
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Mon Jul 16, 2012 4:29 am |
Firefox7275 wrote: |
Be interesting to see if DrJ gives a different answer to me, I believe he has held senior positions in pharmaceutical industry whereas my background is hospital pharmacy ...
Keliu: I would question whether there is a big enough market for an over-the-counter burns cream based on cytokines, particularly given what we have learned about shelf life, price bracket and complexity of manufacture. IME potential profit largely dictates what Big Pharma plough their research and advertising budget into. In the UK at least few people would be willing to pay AnteAGE prices for a burn/ wound cream, they'd want that on NHS prescription (�7.50/ $11). |
Given that we are led to believe that stemcell technology is the future of regenerative medicine, I would have thought that the larger companies would be panting at the bit to encorporate this research into wound healing topicals. Both prescription and OTC.
Burns are also an area in which scientists are always trying to come up with a way of regenerating skin growth. It does amaze me that the research for topical cytokine application seems to be mostly in the cosmedic realm. Which makes me wonder how effective it is if it's not being snapped up for wound healing.
Also, on the subject of PRP for anti-aging - doctors seem to be divided on whether this treatment is of real benefit or not. I personally have had a couple of treatments and was totally under-whelmed. It's not a treatment that has taken the anti-aging industry by storm.
With regard to the cost of cytokine topicals. DrJ has already informed us that one single cell can produce millions of cytokines (or something to that effect) - so they are readily available. I'm sure the larger corporations could find the funding for something that is possibly so beneficial for so many people. |
_________________ Born 1950. There's a new cream on the market that gets rid of wrinkles - you smear it on the mirror!! |
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Mon Jul 16, 2012 8:31 am |
Keliu wrote: |
Firefox7275 wrote: |
Be interesting to see if DrJ gives a different answer to me, I believe he has held senior positions in pharmaceutical industry whereas my background is hospital pharmacy ...
Keliu: I would question whether there is a big enough market for an over-the-counter burns cream based on cytokines, particularly given what we have learned about shelf life, price bracket and complexity of manufacture. IME potential profit largely dictates what Big Pharma plough their research and advertising budget into. In the UK at least few people would be willing to pay AnteAGE prices for a burn/ wound cream, they'd want that on NHS prescription (�7.50/ $11). |
Given that we are led to believe that stemcell technology is the future of regenerative medicine, I would have thought that the larger companies would be panting at the bit to encorporate this research into wound healing topicals. Both prescription and OTC. |
I wouldn’t read much into the dearth of current products. The cycles for drug development are very long, expensive, and macroeconomic environmentally sensitive. There are many other market force factors in play as well. Actually if you look around, you will find a lot of companies (large and small) working on such products, several I know of in the UK. You can also look at clinical trials databases, and the patent literature, as leading edge indicators of what will be on the market in the future. Cytokines for various applications are on the “very hot” list in both realms.
Here is Dr.Zemlo opining on research trends (my bold):
Cytokines and growth factors are small, multifunctional proteins that play critical roles in controlling development and in regulating the body’s responses to disease and infection. Among the clinical applications for cytokine and growth factor research are cancer immunotherapy, wound healing, allergy relief, animal health, treatment of autoimmune disorders, anti-viral therapy, obesity, and disease diagnosis. “With all of these potential benefits, it is not surprising that pharmaceutical and biotechnology companies are spending large sums of money to find new ways to analyze and modulate the activities of cytokines and growth factors,” observes Dr. Tamara Zemlo, Director of Scientific and Medical Communications for The Science Advisory Board.
Keliu wrote: |
Burns are also an area in which scientists are always trying to come up with a way of regenerating skin growth. It does amaze me that the research for topical cytokine application seems to be mostly in the cosmedic realm. Which makes me wonder how effective it is if it's not being snapped up for wound healing. |
I don't share your view that the research is going on in the cosmetic realm. I see the opposite - cosmetic products on the market with very little or zero research evident, questionable formulations defying science logic, and no clinical trials. Why spend on research when you can spend on marketing? (I think some in the skin care marketplace have a low view of the intelligence of the buying public, and seem to think that science will just confuse them.)
Keliu wrote: |
Also, on the subject of PRP for anti-aging - doctors seem to be divided on whether this treatment is of real benefit or not. I personally have had a couple of treatments and was totally under-whelmed. It's not a treatment that has taken the anti-aging industry by storm. |
I agree, and believe it reflects the fact that we are still early on that learning curve, and it really is a shotgun approach but sharpshooters are what is needed (select your cytokines carefully).
Keliu wrote: |
With regard to the cost of cytokine topicals. DrJ has already informed us that one single cell can produce millions of cytokines (or something to that effect) - so they are readily available. I'm sure the larger corporations could find the funding for something that is possibly so beneficial for so many people. |
I never said it was inexpensive to create cytokines. There are ways to do it on the cheap, yes. I could probably teach you how to do it at home (not recommended unless your kitchen is class III and your microwave doubles as an incubator). It's cytokine profile manipulation and measurement and efficacy testing,and all the other aspects of research that eat the dollars. That's my perspective (knowing what we spend) - others may have their own. |
_________________ Physician - scientist - curmudgeon. Kind to animals and stem cells. Nonprofit muckraking site: www.barefacedtruth.com. Day job: www.anteage.com |
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Mon Jul 16, 2012 4:07 pm |
DrJ wrote: |
I don't share your view that the research is going on in the cosmetic realm. I see the opposite - cosmetic products on the market with very little or zero research evident, questionable formulations defying science logic, and no clinical trials. Why spend on research when you can spend on marketing? (I think some in the skin care marketplace have a low view of the intelligence of the buying public, and seem to think that science will just confuse them.) |
I'm not saying that research is only going on in the cosmetic realm - I am well aware of all the medical research taking place and the promise it holds for all fields of medicine. But I agree that cosmetic products are reaching the market place with "very little or zero research evident". This is my point: why haven't OTC wound preparations appeared if this technology is so viable? Why is it only appearing in unregulated cosmetics? |
_________________ Born 1950. There's a new cream on the market that gets rid of wrinkles - you smear it on the mirror!! |
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