Follica - Good News!
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michael barry
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http://hairloss.about.com/od/preventing ... nerals.htm
................."an excess of selenium can be toxic, leading to the loss of hair, nails, and teeth".
See what I mean about frustration in researching baldness. You stop one thing, it just causes another.
................."an excess of selenium can be toxic, leading to the loss of hair, nails, and teeth".
See what I mean about frustration in researching baldness. You stop one thing, it just causes another.
harold
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Yeah. The more I looked into the anecdotal "evidence" the more talk there seemed to be of people saying head and shoulders caused significant hair loss. Its just people talking and people tend to ascribe hair loss to pretty much anything.....but still if you thought something was gonna help, and help a lot then you might not expect that.
Actually my mistake as Head and Shoulders is mostly pyrithione zinc. Then again a lot of brands use selenium nowadys.....perhaps its not so "damning" as i first thought.
hh
Actually my mistake as Head and Shoulders is mostly pyrithione zinc. Then again a lot of brands use selenium nowadys.....perhaps its not so "damning" as i first thought.
hh
michael barry
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I have read through the experimental section of the patent application.
I feel like I must be missing something guys.
All it looks like is this:
They use dermabrasion after using NAIR on it (whch gets mouse fur all in the same cycle)
They suppress WNT signalling for 9 days (by simply using DKK-1)
They dont suture or put band aids on the wound, and just let it heal naturally.
De Noveau hairs form
If that is all there is to this, one could simply take green tea extract capsules about twice a day for nine days after sandpapering their scalp. I was thinking some induction of WNT was necessary by using a drug was necessary somewhere in this (like using lithium chloride), but I sure dont see where they discuss it. The only external thing I see them doing is applying dkk-1 to INHIBIT wnt signalling for nine days after wouding so the new hairs are pigmented and not white. To get white hairs only, it looks like just wounding and letting the skin naturally heal (which might include not getting the scalp wet or putting any kind of bandage on it for at least a 7 days as thats when the researches noted that they noted newish hair-like structures had formed and were growing) might be necessary.
Harold,
Do you see where they are pulling something different in the experiments that what Ive roughly described above?
My only concern with the human hairs in the experiments being formed was the fact that we dont know the androgen levels in the immunodeficient mice that the human skin was grafted ontop of. It still may be necessary to inhibit DHT for these hairs to continue beyond the first phase, or even if they would form with adult levels of DHT. I hope not, but I'd still consider it something of a concenr.
I feel like I must be missing something guys.
All it looks like is this:
They use dermabrasion after using NAIR on it (whch gets mouse fur all in the same cycle)
They suppress WNT signalling for 9 days (by simply using DKK-1)
They dont suture or put band aids on the wound, and just let it heal naturally.
De Noveau hairs form
If that is all there is to this, one could simply take green tea extract capsules about twice a day for nine days after sandpapering their scalp. I was thinking some induction of WNT was necessary by using a drug was necessary somewhere in this (like using lithium chloride), but I sure dont see where they discuss it. The only external thing I see them doing is applying dkk-1 to INHIBIT wnt signalling for nine days after wouding so the new hairs are pigmented and not white. To get white hairs only, it looks like just wounding and letting the skin naturally heal (which might include not getting the scalp wet or putting any kind of bandage on it for at least a 7 days as thats when the researches noted that they noted newish hair-like structures had formed and were growing) might be necessary.
Harold,
Do you see where they are pulling something different in the experiments that what Ive roughly described above?
My only concern with the human hairs in the experiments being formed was the fact that we dont know the androgen levels in the immunodeficient mice that the human skin was grafted ontop of. It still may be necessary to inhibit DHT for these hairs to continue beyond the first phase, or even if they would form with adult levels of DHT. I hope not, but I'd still consider it something of a concenr.
I've succeeded in creating/reawakening a few hair follicles just goofing off with some needling & sandpaper on a small spot. Some hairs were even fully dark colored.
But a few random hairs are not a dense normal-looking layer of hairs that will grow many inches long like my original hair. I certainly can't imagine producing anything that's "cosmetically significant" with these methods.
If there's any worth to this, then those small chemical changes & inhibitions described must be causing a MAJOR change in how the skin heals.
But a few random hairs are not a dense normal-looking layer of hairs that will grow many inches long like my original hair. I certainly can't imagine producing anything that's "cosmetically significant" with these methods.
If there's any worth to this, then those small chemical changes & inhibitions described must be causing a MAJOR change in how the skin heals.
Barry, must the surpressing of WNT-signaling be through topical means or can it be through internal too?
My guess is that it should be through external/topical.
However, there seems to be an undeniably interesting mechanism, the surpression of WNT + dermabrision.
And since the experiment as depicted above through Barrys Algorithm does not seem to include any danger one should rather easily be able to attempt it?
I hope Costarelis and his gang are really onto something here.
My guess is that it should be through external/topical.
However, there seems to be an undeniably interesting mechanism, the surpression of WNT + dermabrision.
And since the experiment as depicted above through Barrys Algorithm does not seem to include any danger one should rather easily be able to attempt it?
I hope Costarelis and his gang are really onto something here.
harold
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I dont know michael are we talking about this patent
http://www.wipo.int/pctdb/en/wo.jsp?wo= ... SPLAY=DESC
I see a lot of places where they are talking about adding something to promote the stem cell to become a hair follicle rather than skin cells. Lithium is mentioned:
[00071 ] In another embodiment, the present invention provides a use of (a) a ?-catenin protein;
etc
this one caught my attention:
the fact that they are talking about tgf-beta 1 and antagonists says they are leavig their options open at least...
hh
http://www.wipo.int/pctdb/en/wo.jsp?wo= ... SPLAY=DESC
I see a lot of places where they are talking about adding something to promote the stem cell to become a hair follicle rather than skin cells. Lithium is mentioned:
[00071 ] In another embodiment, the present invention provides a use of (a) a ?-catenin protein;
etc
this one caught my attention:
the fact that they are talking about tgf-beta 1 and antagonists says they are leavig their options open at least...
hh
harold
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Dont know if this is new but i guess its related.
http://www.wipo.int/pctdb/en/wo.jsp?WO= ... LAY=STATUS
From 2004 - looks like PGD2 analogues were being looked at for getting rid of unwanted hair.
hh
http://www.wipo.int/pctdb/en/wo.jsp?WO= ... LAY=STATUS
From 2004 - looks like PGD2 analogues were being looked at for getting rid of unwanted hair.
hh
harold
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michael barry said:
Could be a good one.
Ibuprofen hits pretty much everything across the board including the "good for hair" PGE2.
http://en.wikipedia.org/wiki/Image:Eico ... thesis.svg
Ibuprofen and aspirin work at inhibiting COX-1 and COX-2.
still might be worth something if PGD2 does more damge than PGE2 does good. But if PGE2 is essential.....
At any rate this was interesting
J Invest Dermatol. 2003 Oct;121(4):661-8.Click here to read Links
Expression of cyclooxygenase isozymes during morphogenesis and cycling of pelage hair follicles in mouse skin: precocious onset of the first catagen phase and alopecia upon cyclooxygenase-2 overexpression.
Müller-Decker K, Leder C, Neumann M, Neufang G, Bayerl C, Schweizer J, Marks F, Fürstenberger G.
Section of Eicosanoids and Epithelial Tumor Development, Deutsches Krebsforschungszentrum, Heidelberg, Germany. K.Mueller-Decker@dkfz.de
Cyclooxygenase (COX)-1 and -2 catalyze the key reaction in prostaglandin biosynthesis. Whereas COX-1 is found in most tissues, COX-2, with a few exceptions, is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions. In many neoplastic epithelia, COX-2 is constitutively overexpressed. Here we show that COX isozymes are spatiotemporally expressed during morphogenesis of dorsal skin epithelium of NMRI mice. COX-1 and COX-2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT-PCR, northern blot, and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production. Being barely detectable in interfollicular epidermis and resting hair follicles of adult mice, COX-2 protein appeared in embryonic skin first in epidermal precursor cells and later on in the basal cells and the peridermal layer of the stratified epidermis. In the course of pelage hair follicle morphogenesis, COX-2 remained expressed in the basal interfollicular compartment and, in addition, became apparent in elongated hair germs and hair pegs and later on in the outer root sheath cells of the distal and proximal hair follicles as well as in basal sebaceous gland cells. During the subsequent synchronous phases of hair cycling, COX-2 expression declined in catagen, was barely detectable in telogen, and was reinduced in the basal outer root sheath and basal sebaceous gland cells of anagen hair follicles. COX-1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing, neonatal, and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles. Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX-1-positive. Transgenic overexpression of COX-2 under the control of a keratin 5 promoter in basal cells of the interfollicular and follicular epidermis induced a precocious entry into the first catagen stage of postnatal hair follicle cycling and a subsequent disturbance of hair follicle phasing. Furthermore, transgenic mice developed an alopecia. Inhibition of transgenic COX-2 activity by feeding the specific COX-2 inhibitor valdecoxib suppressed the development of alopecia, indicating that COX-2-mediated prostaglandin synthesis is involved in hair follicle biology.
So "wiping out" PGE2 activity (presumably) didn't seem to hurt as much as wiping out PGD2 presumably helped.
On the flip side guys have been all over this for years on hairsite and other places looking at the inflammation angle. I never really followed it but i am sure stuff like this has prob been done before. Maybe someone wants to hit the archives.
Interesting.
Latanaprost DOES NOT inhibit prostaglandin D2, but does "get" three or so of the other prostaglandins.
Not all prostaglandins are apparently bad for hair, but they do control alot of functions. They can make smooth muscles contract or relax, and control alot of inflammatory processes apparently on whether or not an area is to be inflammed. I dont care what they do, I just want to f*** with what ever one suppresses hair growth.
[/quote:1a3wu3c0]
They are amazingly diverse in their effects on different tissues.
Yeah that in browser pdf thing is awful. And you cant save it if its longer than 50 pages.
I dont know exactly what the timing is and it sounds like that is something that Cotsarelis et al want to mess around with now but yeah it seems like there is a time for wnt and a time for no wnt.
Yeah its interesting stuff. I guess the patent was filed first and then the publications will come out. Priorities
hh
michael barry
Senior Member
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Ive now been able to read the experimental section of the patent.
1)The steps were pretty much easy. They wounded the sking through dermabrasion with a felt-wheeled instrument. There was no blood.
2)They block wnt expression (they used DKK-1, ecgc from green tea and curcumin also block wnt) for nine days during the re-epilithializaition period
3)They add wnt protiens thereafter.
Thats it.
Lithium chloride mimics wnt-in the skin (hint) for after day nine
They tried this with HUMAN SKIN grafted onto the backs of immuno deficient mice. If they didn not block wnt for the first nine days, they got hair with no pigment (white hair). If they blocked wnt with dkk-1, they'd get dark hair. They had hair at day 25 and 50-something. The importance of having hair at both days was that it showed that the human hair cycled normally and didn't go into a rest phase like mouse hair would at that time apparently. It really was human hair with color
Im going to cut and paste example three from the patent:
Here is the human skin experiment (Experiment 7)
I wonder if ginger can be made into a topical. It would seem that using nizoral a couple of times a week with a topical Prostaglandin D2 inhibitor would be very beneficial. There would still be DKK-1, TGF beta, TNF-alpha, and PKC to be concerened with.
Harold might have a different assessment, but if Prostaglandin D2 ALONE could keep mouse hair from re-entering anangen at day fifity and its expressed 4.4 times as much in bald scalp..........................I think it might surpass PKC and TNF-alpha in importance in the balding process and perhaps be one of the prime movers in the T-cell response to hair in the first place. We know that DKK-1 and TGF-beta are made by the dermal papilla proper though....................so they would seemingly come before the prostaglandins. Im wondering if prostaglandins can actually stand in for androgens at the receptor site though. I seem to remember reading that they could stand in for some steroid hormones in the correct circumstances.................Its interesting stuff. He's obviously (costarialis and his team) have found a few things useful.
Its also nice to actually discuss a finding with people who are willing to actually look into it. At other places, its seemingly just dismissed as "another mouse result" with no-one willing to look at the chemicals involved in the process and how they are mirrored in human alopecia.
1)The steps were pretty much easy. They wounded the sking through dermabrasion with a felt-wheeled instrument. There was no blood.
2)They block wnt expression (they used DKK-1, ecgc from green tea and curcumin also block wnt) for nine days during the re-epilithializaition period
3)They add wnt protiens thereafter.
Thats it.
Lithium chloride mimics wnt-in the skin (hint) for after day nine
They tried this with HUMAN SKIN grafted onto the backs of immuno deficient mice. If they didn not block wnt for the first nine days, they got hair with no pigment (white hair). If they blocked wnt with dkk-1, they'd get dark hair. They had hair at day 25 and 50-something. The importance of having hair at both days was that it showed that the human hair cycled normally and didn't go into a rest phase like mouse hair would at that time apparently. It really was human hair with color
Im going to cut and paste example three from the patent:
Here is the human skin experiment (Experiment 7)
I wonder if ginger can be made into a topical. It would seem that using nizoral a couple of times a week with a topical Prostaglandin D2 inhibitor would be very beneficial. There would still be DKK-1, TGF beta, TNF-alpha, and PKC to be concerened with.
Harold might have a different assessment, but if Prostaglandin D2 ALONE could keep mouse hair from re-entering anangen at day fifity and its expressed 4.4 times as much in bald scalp..........................I think it might surpass PKC and TNF-alpha in importance in the balding process and perhaps be one of the prime movers in the T-cell response to hair in the first place. We know that DKK-1 and TGF-beta are made by the dermal papilla proper though....................so they would seemingly come before the prostaglandins. Im wondering if prostaglandins can actually stand in for androgens at the receptor site though. I seem to remember reading that they could stand in for some steroid hormones in the correct circumstances.................Its interesting stuff. He's obviously (costarialis and his team) have found a few things useful.
Its also nice to actually discuss a finding with people who are willing to actually look into it. At other places, its seemingly just dismissed as "another mouse result" with no-one willing to look at the chemicals involved in the process and how they are mirrored in human alopecia.
Funny, I often put ginger in my green tea to drink because I really like the taste. It should be able to be made into a topical
if you mix it up with a mixer after peeling the outer layers off and then pour it down in the nizoral-bottle with some green tea extractions?
The dermabrasion should be only 5mm.
if you mix it up with a mixer after peeling the outer layers off and then pour it down in the nizoral-bottle with some green tea extractions?
The dermabrasion should be only 5mm.
As someone else pointed out this procedure has similarities with the CURIS-program that was evaluated as too risky by the investors, this worries me a bit, I wonder how similar they really are.
What toxicities might they be speaking about?
A comparison can be done by someone who knows this kind of stuff, I'm clueless except that WNT seems to refer to
proteins of some sort. Or am I correct when I say that the CURIS-program was about using the Hedgehog signaling pathway to make hair whilst the Follica-approach is about closing the WNT-signaling-pathway for 9 days after dermabrision to make hair?
http://en.wikipedia.org/wiki/Hedgehog_% ... gnaling%29
http://en.wikipedia.org/wiki/Wnt_signaling_pathway
What toxicities might they be speaking about?
A comparison can be done by someone who knows this kind of stuff, I'm clueless except that WNT seems to refer to
proteins of some sort. Or am I correct when I say that the CURIS-program was about using the Hedgehog signaling pathway to make hair whilst the Follica-approach is about closing the WNT-signaling-pathway for 9 days after dermabrision to make hair?
http://en.wikipedia.org/wiki/Hedgehog_% ... gnaling%29
http://en.wikipedia.org/wiki/Wnt_signaling_pathway
michael barry
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The wnt pathway was actually obstructed for nine days (to get pigmented hair instead of white hair) after the dermabrasion by using dkk-1. Follica wants to us an-already in use and FDA approved drug to suppress wnt for the first nine days, however.
After the first nine days post-dermabrasion (or laser resurfacing, which they have discussed using), they will apply wnt-protiens to the skin with a carrier vehicle to get it through the dermis. Apparently they can do this with another FDA approved indication already in use, or so they claim. New hairs were supposedly visible before 30 days, so the wnt protiens would not be applied for very long.
Hedgehog, wnt, and beta-catenin are all pathways that come up in hair indications over the years. Wnt is something that can be blocked with green tea and curcumin also.
After the first nine days post-dermabrasion (or laser resurfacing, which they have discussed using), they will apply wnt-protiens to the skin with a carrier vehicle to get it through the dermis. Apparently they can do this with another FDA approved indication already in use, or so they claim. New hairs were supposedly visible before 30 days, so the wnt protiens would not be applied for very long.
Hedgehog, wnt, and beta-catenin are all pathways that come up in hair indications over the years. Wnt is something that can be blocked with green tea and curcumin also.
harold
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On the prostaglandin front - those same mice I mentioned earlier that overexpressed cox-2 andlosthair follicles and had sebaceous gland overddevelopment were looked at by Cotsarelis in his patent centred on PGD2 and compared to human balding areas.
The first part in bold shows these mice had not just hair loss but miniaturized hair follicles as well as sebaceous gland hyperplasia which sounds a hell of a lot like balding skin. You can see the same stuff reported in the studies where this line of mice were first developed.
I think the second part in bold is interesting because it shows that PGD2 seems to be a stronger growth inhibitor than PGE2 is a growth promoter. I think this is important because knocking out a whole bunch of prostaglandin production is probably a lot easier for us than selectively knocking out PGD2.
Heres some more stuff from humans. Cant remember if I already posted some of this stuff - its becoming a bit of a blur....
Wow - hair regrowth is still inhibited almost 2 months after the last application of PGd2 as Michael mentioned.
An average increase of PGD2 expression of 11.6 between balding and non-balding areas. And as Bryan will appreciate they controlled for the expression of genes elevated by UV light to make sure that the gene expression did not reflect the fact that balding areas get much more UV exposure.
At any rate atm I am on a topical of lithium carbonate and ibuprofen. Ibuprofen inhibits both COX-1 and COX-2 and should knock down production of both hairpromoting and hair inhibiting prostaglandins but what the hell. I have to say my scalp has felt a lot less itchy the last few days and after the first application I noticed a distinct absence in the pain/discomfort where my crown rubbed against the pillow as i sleep. I guess I hadnt realised how bad that had been since quitting finasteride. On the other hand that doesnt mean its gonna do squat for stopping hairloss. But maybe if nothing else I can lose hair a littl more comfortably. Will see how it goes.
hh
The first part in bold shows these mice had not just hair loss but miniaturized hair follicles as well as sebaceous gland hyperplasia which sounds a hell of a lot like balding skin. You can see the same stuff reported in the studies where this line of mice were first developed.
I think the second part in bold is interesting because it shows that PGD2 seems to be a stronger growth inhibitor than PGE2 is a growth promoter. I think this is important because knocking out a whole bunch of prostaglandin production is probably a lot easier for us than selectively knocking out PGD2.
Heres some more stuff from humans. Cant remember if I already posted some of this stuff - its becoming a bit of a blur....
Wow - hair regrowth is still inhibited almost 2 months after the last application of PGd2 as Michael mentioned.
An average increase of PGD2 expression of 11.6 between balding and non-balding areas. And as Bryan will appreciate they controlled for the expression of genes elevated by UV light to make sure that the gene expression did not reflect the fact that balding areas get much more UV exposure.
At any rate atm I am on a topical of lithium carbonate and ibuprofen. Ibuprofen inhibits both COX-1 and COX-2 and should knock down production of both hairpromoting and hair inhibiting prostaglandins but what the hell. I have to say my scalp has felt a lot less itchy the last few days and after the first application I noticed a distinct absence in the pain/discomfort where my crown rubbed against the pillow as i sleep. I guess I hadnt realised how bad that had been since quitting finasteride. On the other hand that doesnt mean its gonna do squat for stopping hairloss. But maybe if nothing else I can lose hair a littl more comfortably. Will see how it goes.
hh