I have referred to the fact that a special size of hyaluronic acid is effective for the purpose of preventing TSA. Here I will write the details.
The above illustration is keratinocytes and hyaluronan particles (blue, round). A keraticocyte has many spikes on its cell surface. Red round one is HAS3 ( hyaluronic acid synthetase 3 ) which produces hyaluronic acid. CD44 is the receptor of hyaluronic acid. Hyaluronan particles are produced from HAS3 by the keratinocyte itself and stimulate CD44 of its own. CD44 signals reach CDC42 and actin filaments ( brown lines ) are constructed. Actin filaments are the frame of the spikes. Without actin filaments the keratinocyte can’t elongate its spikes.
The spike formation is very important because EGF (epidermal growth factor, diamond-shaped light green one) can’t attach to its receptor without spikes. EGF stimulates keratinocyte to lead to cell division and proliferation.
When topical corticosteroids are applied to the skin, HAS3 becomes inactive. There are few hyaluronan particles in the space between keratinocytes. Spike formation of keratinocyte becomes poor and EGF can’t work anymore. It means the epidermis becomes thin (epidermis atrophy ) and the barrier disfunction occurs.
Even if the HAS3 is inactive, external supplementation of HA (HAFi, blue round) can stimulate CD44, elongates spikes and activates the EGF pathway. That is the mechanism by which external application of hyaluronan works.
Not all size of hyaluronic acid has this ability of stimulating keratinocytes. Only around 100 thousand dalton size of hyaluronan works.
Around 100 thousand dalton hyaluronic acid is mystical. It increases in the amnion fluid transitorily.
A fetus before 16 weeks has no skin on it. At the period of around 16 weeks, the skin is created.
Hyaluronan of 100 thousand dalton increases in the amnion fluid only at that time temporarily. It grows the fatus skin and changes the outer cells to the epidermis.
What is the most mystical is that the hyaluronan is produced by the kidney of the fetus itself. It is made in the kidney of the fetus and urinated to the amniotic fluid. A fetus grows its skin by itself.
So external application of 100 thousand dalton hyaluronan is just like soaking damaged skin to the amniotic fluid at the period of 16 weeks. hyaluronan repairs the damaged skin.
I thought it must be useful for TSA or possible TSA patients who use TS. So I began to look for the commercially available hyaluronic acid solution of this size. Soon I found I had thought too lightly. All available cosmetics containing hyaluronic acid adopted only more than 1 million dalton sized one. Molecular size is associated with viscosity. The more the molecular size is, the stronger moisturizing capacity becomes. 100 thousand dalton hyaluronan is less viscous than that of 1 million dalton and no cosmetics company in Japan adopted the former.
I was disappointed but soon I spread my search worldwide. Then I could find three items.
One is of South Africa.
The brand name is Hydrating HA Serum. It seems to be provided to only medical doctors (Maybe people can purchase it in clinics). The price is about ZAR 430.
http://www.mellowlaser.co.za/p/507054/hydrating-ha-serum
Though HAiF is written to be added in the website, the concentration is unknown. I asked to the company by e-mail if I could import it to Japan. The answer was as the following.
Dear Mototsugu
Thank you for your enquiry. Unfortunately Lamelle Research Laboratories does not export products as we do not have an exporters code. Lamelle is in the process of obtaining a code and only then will be able to export products. Please accept my apologies for the inconvenience.
Kind regards
Brand Manager Lamelle Research Laboratories
There seemed to be some governmental regulation which doesn’t exist in Japan.
Another is Avene’s Eluage. Avene is a brand name of Pier Fabre group which has a patent of addition of HAiF to topical steroids.
I found the concentration of HAiF of Eluage by the following article. The concentration is 1 % (half of Barnes’s report). Eluage contains retinalaldehyde also. Retinalaldehyde is also reported useful for suppressing eczema by Prof. Saurat in Geneva university (Dr Barnes’s boss). So I guess they have connections.
http://www.ncbi.nlm.nih.gov/pubmed/21649816
The third one is from United States. The brand name is Bionect.
Bionect seems to be produced according to entirely other concept than Barnes’s HAiF. There is no term of HAiF (50-300 thousand Dalton hyaluronan) on its website. I could identify its molecular weight from the brand name of original material HYALASTINE. The MW is 50-100 thousand dalton and the concentration is 0.2%. The price is about USD 100 per 30g tube.
http://www.google.com/patents/EP0138572B1?cl=en
http://www.goodrx.com/bionect
I could find above three products containing HA of around 100 thousand dalton. But the postage seemed expensive when imported from overseas to Japan. If it was reasonable I could inform it through my Japanese blog to Japanese patients. Patients could import it directly from overseas.But I resigned.
I decided to produce it all by myself. I could find raw material of HA of 50-100 thousand dalton in Kikkoman company website (Brand name is FCS-SU). It is easy to produce 2% aqueous solution from it. So now I am a seller of hyaluronan cosmetics since two months ago.
My hyaluronan solution
I am selling 2% 30 ml at a price of JPN 3,000 and 2% 150ml at JPN 10,000. I think it is enough reasonable. Bionect 0.2% 30ml costs about USD 100. The concentration of mine is ten times thick but one third in price.And what is important is that mine is simple aqueous solution while other products must contain various ingredients as usual cosmetics. Most patients with AD or TSA don’t tolerate usual cosmetics because they contain various stimulants.
Some readers might be disappointed or amazed because now I am promoting my production as a seller. Anyway, please read to the last.
I am proud because I can recommend something for patients now. I couldn’t recommend anything before ten years ago because the mechanism of TSA was entirely unclear. What I could do for my poor patients was guiding the way to withdrawal. That was all. I felt myself powerless.
So I am now proud to introduce the above hyaluronic acid solution to patients.
Another reason why I feel my idea nice is that it might become a small source of income for some patients. When I saw my TSA patients, mostly I didn’t prescribe anything. I used to hand the prescription document written as JPN 10,000 ($ 100 ) by me to the patient.
“I think what you need now must be this one. Go to the pharmacy to exchange this prescription paper with the money.”
Of coarse it is a joke. A cynical joke. But patients smiled. I prescribed smile. I knew any little smile would be more helpful than medication at the hard rebound period.
I also told as the following.
“You should not come to dermatologists too often. It costs expensive. What is the most important during withdrawal is care to money. Patients are likely to become poor when they could get their healthy skin back at last. The side effect of topical steroid is addiction while the side effect of withdrawal is poverty.”
Patients smiled because they thought it was also my joke. But I was serious in fact.
Let’s go back to the subject, I can provide 10 bottles of 2% 30ml at a price of JPN 21,000 and 10 bottles of 2% 150ml at a price of JPN 73,500. I will send them by EMS. Charge list of EMS from Japan to overseas is at the following website.
http://www.post.japanpost.jp/int/charge/list/ems_all_en.html
You first purchase one small hyaluronic acid from me and try to use it. If you become satisfied with it, you can become a provider in your country. It will help your damaged income recover a little. If your skin becomes healthy, it is the strongest promotion material for you.
Clinical studies about this size of hyaluronic acid have rapidly advanced recently. Todd in US reported its usefulness for rosacea.
Efficacy and Tolerability of Low Molecular Weight Hyaluronic Acid Sodium Salt 0.2% Cream in Rosacea. Todd E et al. JDD 2013 Vol.12(6)
Anti-aging effect for normal aged people is also reported as the following in 2011. So you can introduce and recommend my hyaluronic acid lotion to the aged people in your neighborhood.
Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. Pavicic T et al. J Drugs Dermatol. 2011 Sep;10(9):990-1000.
On line shop is open at the following site. http://drfukaya.ocnk.net/
Important:
I must add and insist that my hyaluronic acid doesn’t suppress strong eczema or flare of rebound. It is the most appropriate for possible TSA patients who are using steroids. It decreases the risk of TSA.
After withdrawal from TS (after strong flare storm of rebound) patients’ skin is likely to become dry and very very sensitive for a while. At that period patients can’t use most topical application including even simple white petrolatum. My hyaluronic acid is appropriate at that period. It seems to be possible for such patients to use my hyaluronic acid without irritation. Hyaluronic acid will thicken and strengthen such a sensitive skin to recover.
For young patients including babies it is OK. There is no possible risk.
References
Inhibition of Putative Hyalurosome Platform in Keratinocytes as a Mechanism for Corticosteroid-Induced Epidermal Atrophy.
Barnes L et al, J Invest Dermatol. 2012 Dec 6. doi: 10.1038/jid.2012.439. [Epub ahead of print]
Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism. Kaya G et al, PLoS Med. 2006 Dec;3(12):e493.
Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: In vitro studies of re-epithelialisation in human skin wounds. Nyman E et al, J Plast Surg Hand Surg. 2013 Apr;47(2):89-92.
The Hyaluronan Receptor for Endocytosis (HARE) activates NF-κB mediated gene expression in response to 40-400 kDa, but not smaller or larger, hyaluronan. Pandey MS et al, J Biol Chem. 2013 Mar 24. [Epub ahead of print]
Hyaluronic acid targets CD44 and inhibits Fc epsilonRI signaling involving PKCdelta, Rac1, ROS, and MAPK to exert anti-allergic effect. Kim Y et al, Mol Immunol. 2008 May;45(9):2537-47.
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