Hair Loss Forum - Inflamation/ PGD-2 and Mast Cell Degranulation?
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Rudy

20.06.2012, 11:35
 

Inflamation/ PGD-2 and Mast Cell Degranulation? (Hair Multiplication & Stem Cells Treatment)

I've been on this site for like 15 years. Dont post hardly ever anymore and just check in once in a while to see if anything new is happening.

It seems there is a lot of stuff about inflammation and its inhibition being talked about.

I've always been interested in Mast Cell Inhibitors like Sodium Chromolyn.

Im hoping some of the brighter folks here can talk about cox-2 inhibition and PGD-2 as it relates to Mast Cell Degranulation. How much is related to the pro inflammatory cytokine cascade produced by mast cell degranulation.

The reason I ask is I am wondering about a Sodium Chromolyn topical as a treatment or adjunct treatment. I had actually experimented for a while putting Nasalcrom on my scalp many years ago but did not follow through long term.

Reason: Expensive ( you can go through the small bottles of nasalcrom pretty quickly applying constantly) and Mast cell inhibitors need to be used 4 times a day to exert their influence. Work best for allergies and other things related to mast cell degranulation after 4-6 weeks. Also it may need to be much higher concentration when used on scalp over larger area as apposed to inhaling it.

Some questions and comments for those that might know. SC is easily absorbed through mucus mebranes and lungs. Does its molecular weight make it a candidate for a topical?

Its been around for ever and has a super safe profile. Again the main issue is its short action.

However Im thinking it should be easy and cheap to get made. Could be added to shampoo/conditioner ( for one application). Then perhaps added to a spritz type topical for another app. Then perhaps to something like an oil or something else that would take longer to dry and have more of a long term effect. Perhaps using an occlusive while sleeping getting 8 or so hours of effect.

I was also thinking if pro inflamatory cytokines were the issue or part of the issue you could add a anti histamine in the topical to mop any of the stuff that escapes if some of the mast cells do pop. Perhaps put the nite time stuff in a base of emu oil with some other known natural anti inflammatory's.

I consume relatively large amounts of tumeric and use a coco butter hand and face product from palmers as a pomade that I work through my hair and onto my scalp. I also take aspirin everyday. I eat alot of wild blueberries ( where i live you can pick pounds for free in a day). They are supposed to be the best anti inflammatory food you can eat and the absolute highest amount of reverestrol (SP?) possible from foods. 2-3 times the amount in commercially grown berries and of course no pesticides ( commercial blueberries have some of the highest pesticide counts of any fruit... organic pesticides can be worse the man made).

My life long itchy scalp, dandruff,scaly scabs, dermatitis is gone. My hairloss is pretty progressed and been in action for over 25 years. The tumeric coco butter blueberry regimen is pretty new so I cant say I am growing my hair back. But it is definately a bit thicker and healthier and my scalp condition is pretty much 100% better. I also have much less body pain in general. Considering I have had a lot of musco skeletal injuries including a torn pec/ shoulder opperation 8 months ago this sais quite a bit I think.

I take no anti andros or minox either.

So I do think alot can be done through diet, spices, aspirin and the coco butter product for scalp. But wondering if adding the SC and perhaps a topical anti histamine to this would be a big/medium/small help or adjunct to re growing/maintaining ones hair. Especially for people in earlier stages.

I think it (SC) would be a worthy thing to experiment with as it should be easy to get (SUPER SAFE AND EFFECTIVE) and many people have tried much scarrier and expensive things. If inflamation is a crucial part of HL and you can stop mast cell degranulation to any degree I cant see how this would not be of use.

Sorry for the long winded post that may a bit allover the place. Would love to hear what people say and ideas for getting SC compounded and such.

Thanks




Rudy is located in [NA] and he is available to meet: NO


Post reply
Rudy

22.06.2012, 20:48

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

» I've been on this site for like 15 years. Dont post hardly ever anymore and
» just check in once in a while to see if anything new is happening.
»
» It seems there is a lot of stuff about inflammation and its inhibition
» being talked about.
»
» I've always been interested in Mast Cell Inhibitors like Sodium Chromolyn.
»
» Im hoping some of the brighter folks here can talk about cox-2 inhibition
» and PGD-2 as it relates to Mast Cell Degranulation. How much is related to
» the pro inflammatory cytokine cascade produced by mast cell degranulation.
»
» The reason I ask is I am wondering about a Sodium Chromolyn topical as a
» treatment or adjunct treatment. I had actually experimented for a while
» putting Nasalcrom on my scalp many years ago but did not follow through
» long term.
»
» Reason: Expensive ( you can go through the small bottles of nasalcrom
» pretty quickly applying constantly) and Mast cell inhibitors need to be
» used 4 times a day to exert their influence. Work best for allergies and
» other things related to mast cell degranulation after 4-6 weeks. Also it
» may need to be much higher concentration when used on scalp over larger
» area as apposed to inhaling it.
»
» Some questions and comments for those that might know. SC is easily
» absorbed through mucus mebranes and lungs. Does its molecular weight make
» it a candidate for a topical?
»
» Its been around for ever and has a super safe profile. Again the main issue
» is its short action.
»
» However Im thinking it should be easy and cheap to get made. Could be added
» to shampoo/conditioner ( for one application). Then perhaps added to a
» spritz type topical for another app. Then perhaps to something like an oil
» or something else that would take longer to dry and have more of a long
» term effect. Perhaps using an occlusive while sleeping getting 8 or so
» hours of effect.
»
» I was also thinking if pro inflamatory cytokines were the issue or part of
» the issue you could add a anti histamine in the topical to mop any of the
» stuff that escapes if some of the mast cells do pop. Perhaps put the nite
» time stuff in a base of emu oil with some other known natural anti
» inflammatory's.
»
» I consume relatively large amounts of tumeric and use a coco butter hand
» and face product from palmers as a pomade that I work through my hair and
» onto my scalp. I also take aspirin everyday. I eat alot of wild blueberries
» ( where i live you can pick pounds for free in a day). They are supposed to
» be the best anti inflammatory food you can eat and the absolute highest
» amount of reverestrol (SP?) possible from foods. 2-3 times the amount in
» commercially grown berries and of course no pesticides ( commercial
» blueberries have some of the highest pesticide counts of any fruit...
» organic pesticides can be worse the man made).
»
» My life long itchy scalp, dandruff,scaly scabs, dermatitis is gone. My
» hairloss is pretty progressed and been in action for over 25 years. The
» tumeric coco butter blueberry regimen is pretty new so I cant say I am
» growing my hair back. But it is definately a bit thicker and healthier and
» my scalp condition is pretty much 100% better. I also have much less body
» pain in general. Considering I have had a lot of musco skeletal injuries
» including a torn pec/ shoulder opperation 8 months ago this sais quite a
» bit I think.
»
» I take no anti andros or minox either.
»
» So I do think alot can be done through diet, spices, aspirin and the coco
» butter product for scalp. But wondering if adding the SC and perhaps a
» topical anti histamine to this would be a big/medium/small help or adjunct
» to re growing/maintaining ones hair. Especially for people in earlier
» stages.
»
» I think it (SC) would be a worthy thing to experiment with as it should be
» easy to get (SUPER SAFE AND EFFECTIVE) and many people have tried much
» scarrier and expensive things. If inflamation is a crucial part of HL and
» you can stop mast cell degranulation to any degree I cant see how this
» would not be of use.
»
» Sorry for the long winded post that may a bit allover the place. Would love
» to hear what people say and ideas for getting SC compounded and such.
»
» Thanks

Ok, so no answers. Did a little research and the 1st line on wikipedia reads

"Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR, as well as CRTH2.[1][2] It is a major prostaglandin produced by mast cells"

Reading a bit about mast cells it seems that mast cells have to be "activated" to release PGD2. So I am assuming this means degranulation. I also assume then if a mast cell stabilizer like SC would/could penetrate the scalp and assert an effect that would result in less PGD2.

Another very interesting thing I read was that mast cells produce PGD2 in response to alcohol. Every darn hair product has alc in it.

So come on guys. This stuff is readily available. Somebody has to have an opinion.

You would have to apply it quite often, but if PGD2 is a major player this is a thing you/we all could try right away.

HL definitely appears like an auto immune response in many ways.

Ive always had a sneaking suspicion a mast cell stabilizer would be helpful in combating hairloss. It would appear if PGD2 is an important mediator I was on to something.

The question is. Will SC stabilize mast cells in the scalp?




Rudy is located in [NA] and he is available to meet: NO


Post reply
gutted

22.06.2012, 21:26

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

here is all the info you need ->

http://www.hairsite.com/hair-loss/forum_entry-id-85302.html




gutted is located in [NA] and he is available to meet: NO


Post reply
action_reaction

22.06.2012, 21:27

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

better question:


why is DHT harmless at 1/3 of its level but once it's at normal it starts inflammation and $hit.... why???




action_reaction is located in [NA] and he is available to meet: NO


Post reply
gutted

22.06.2012, 22:27

@ action_reaction

Inflamation/ PGD-2 and Mast Cell Degranulation?

» better question:
»
»
» why is DHT harmless at 1/3 of its level but once it's at normal it starts
» inflammation and $hit.... why???

loool because its GENETICS why are you questioning this???




gutted is located in [NA] and he is available to meet: NO


Post reply
Rudy

22.06.2012, 23:10

@ gutted

Inflamation/ PGD-2 and Mast Cell Degranulation?

» here is all the info you need ->
»
» http://www.hairsite.com/hair-loss/forum_entry-id-85302.html

Gutted,

Thanks for the response. Lots of info.

What do you think about a Mast cell stabilizer as a topical? Cromolyn sodium or another type?

They can control asthma and allergies which are hyper immune responses.

There was also a study I read where a mast cell stabilizer was applied to wounds in pigs and they did not scar as badly. Excess colagen is an issue with scarring type alopecia as well if im not mistaken (fibrosis).

Systemic stuff would appear to be the strongest way, but mast cell inhibitors work for other things locally so thats where my interest in a topical for scalp that hopefully wont cause nasty side effects like the benaxofen.

Thanks




Rudy is located in [NA] and he is available to meet: NO


Post reply
action_reaction

22.06.2012, 23:36

@ gutted

Inflamation/ PGD-2 and Mast Cell Degranulation?

» loool because its GENETICS why are you questioning this???

bietch I will murder you




action_reaction is located in [NA] and he is available to meet: NO


Post reply
gutted

23.06.2012, 10:35

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

» » here is all the info you need ->
» »
» » http://www.hairsite.com/hair-loss/forum_entry-id-85302.html
»
» Gutted,
»
» Thanks for the response. Lots of info.
»
» What do you think about a Mast cell stabilizer as a topical? Cromolyn
» sodium or another type?
»
» They can control asthma and allergies which are hyper immune responses.
»
» There was also a study I read where a mast cell stabilizer was applied to
» wounds in pigs and they did not scar as badly. Excess colagen is an issue
» with scarring type alopecia as well if im not mistaken (fibrosis).
»
» Systemic stuff would appear to be the strongest way, but mast cell
» inhibitors work for other things locally so thats where my interest in a
» topical for scalp that hopefully wont cause nasty side effects like the
» benaxofen.
»
» Thanks

i dont realy know much about mast cell stabilisers, so cant really comment on that, if it does inhibit pgd2 it could be usefull i guess?

if you think it will work, you should try it out and if you have the time report back here so more people can experiment.

personally my journey is through inhibiting cox 2 and 5 lox.




gutted is located in [NA] and he is available to meet: NO


Post reply
Rudy

23.06.2012, 13:43

@ gutted

Inflamation/ PGD-2 and Mast Cell Degranulation?

» » » here is all the info you need ->
» » »
» » » http://www.hairsite.com/hair-loss/forum_entry-id-85302.html
» »
» » Gutted,
» »
» » Thanks for the response. Lots of info.
» »
» » What do you think about a Mast cell stabilizer as a topical? Cromolyn
» » sodium or another type?
» »
» » They can control asthma and allergies which are hyper immune responses.
» »
» » There was also a study I read where a mast cell stabilizer was applied
» to
» » wounds in pigs and they did not scar as badly. Excess colagen is an
» issue
» » with scarring type alopecia as well if im not mistaken (fibrosis).
» »
» » Systemic stuff would appear to be the strongest way, but mast cell
» » inhibitors work for other things locally so thats where my interest in a
» » topical for scalp that hopefully wont cause nasty side effects like the
» » benaxofen.
» »
» » Thanks
»
» i dont realy know much about mast cell stabilisers, so cant really comment
» on that, if it does inhibit pgd2 it could be usefull i guess?
»
» if you think it will work, you should try it out and if you have the time
» report back here so more people can experiment.
»
» personally my journey is through inhibiting cox 2 and 5 lox.

Thanks again for your response. Mast cell stabilizers definately inhibit pgd2. Mast cells contain all sorts of pro inflammatory cytokines including pgd2. Degranulation basically means the cell explodes or pops and releases all these chemicals like histamine and pgd2. What is cool about mast cell stabilizers is if the mast cell doesnt break you dont need to mop up the inflamation with anti histamines and things like cox 2 inhibitors after the fact. The biggest issue with them is they need to be used 4 times a day ( for nasal stuff). For allergies you need to constantly use them because once the mast cell pops you then need an antihistamine or whatever. Once your in an alergic reaction they dont do anything.

I am on a regimen now where I consume a lot of tumeric which is supposed to be as effective as NSAIDs in reducing inflamation. I take it with black pepper which makes it more bio availible and potentiates it. I also eat a lot of wild blueberries which are supposed to be the best anti inflammatory food you can injest. ( luckily i live where they are very abundant).

I read a little bit about 5 lox but was unfamiliar with it before. What do you do in regards to this? Besides joint health, connective tissue health do you do this as an adjunct to help HL or scalp health.

Thanks again for your response.

Im still hoping for some others to chime in. One thing I did find out is the molecular weight of cromolyn sodium is around 520. I am still wondering if that makes it useful ( will penetrate) to apply to scalp.




Rudy is located in [NA] and he is available to meet: NO


Post reply
gutted

23.06.2012, 19:22

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

» » » » here is all the info you need ->
» » » »
» » » » http://www.hairsite.com/hair-loss/forum_entry-id-85302.html
» » »
» » » Gutted,
» » »
» » » Thanks for the response. Lots of info.
» » »
» » » What do you think about a Mast cell stabilizer as a topical? Cromolyn
» » » sodium or another type?
» » »
» » » They can control asthma and allergies which are hyper immune
» responses.
» » »
» » » There was also a study I read where a mast cell stabilizer was applied
» » to
» » » wounds in pigs and they did not scar as badly. Excess colagen is an
» » issue
» » » with scarring type alopecia as well if im not mistaken (fibrosis).
» » »
» » » Systemic stuff would appear to be the strongest way, but mast cell
» » » inhibitors work for other things locally so thats where my interest in
» a
» » » topical for scalp that hopefully wont cause nasty side effects like
» the
» » » benaxofen.
» » »
» » » Thanks
» »
» » i dont realy know much about mast cell stabilisers, so cant really
» comment
» » on that, if it does inhibit pgd2 it could be usefull i guess?
» »
» » if you think it will work, you should try it out and if you have the
» time
» » report back here so more people can experiment.
» »
» » personally my journey is through inhibiting cox 2 and 5 lox.
»
» Thanks again for your response. Mast cell stabilizers definately inhibit
» pgd2. Mast cells contain all sorts of pro inflammatory cytokines including
» pgd2. Degranulation basically means the cell explodes or pops and releases
» all these chemicals like histamine and pgd2. What is cool about mast cell
» stabilizers is if the mast cell doesnt break you dont need to mop up the
» inflamation with anti histamines and things like cox 2 inhibitors after the
» fact. The biggest issue with them is they need to be used 4 times a day (
» for nasal stuff). For allergies you need to constantly use them because
» once the mast cell pops you then need an antihistamine or whatever. Once
» your in an alergic reaction they dont do anything.
»
» I am on a regimen now where I consume a lot of tumeric which is supposed to
» be as effective as NSAIDs in reducing inflamation. I take it with black
» pepper which makes it more bio availible and potentiates it. I also eat a
» lot of wild blueberries which are supposed to be the best anti inflammatory
» food you can injest. ( luckily i live where they are very abundant).
»
» I read a little bit about 5 lox but was unfamiliar with it before. What do
» you do in regards to this? Besides joint health, connective tissue health
» do you do this as an adjunct to help HL or scalp health.
»
» Thanks again for your response.
»
» Im still hoping for some others to chime in. One thing I did find out is
» the molecular weight of cromolyn sodium is around 520. I am still wondering
» if that makes it useful ( will penetrate) to apply to scalp.

intresting stuff. I hope you get to try it out.
i also take curcumin as a cox 2 blocker. I also read it can inhibit 5 lox too.

here is a patnet by loreal for hair growth by through 5 lox/cox 2 inhibition

-> http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=33&f=G&l=50&co1=AND&d=PTXT&s1=lipoxygenase&s2=%22hair+growth%22&OS=lipoxygenase+AND+%22hair+growth%22&RS=lipoxygenase+AND+%22hair+growth




gutted is located in [NA] and he is available to meet: NO


Post reply
Dogstar

24.06.2012, 18:42

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

I saw this recent interview with Dr Cotsarelis posted on another forum if anyone is interested.



By Abby Van Voorhees, MD, June 01, 2012

In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with George Cotsarelis, MD, about his recent Science Translational Medicine article, “Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia.”


Dr. Van Voorhees: What have we known about androgenetic alopecia (AGA) up until your most recent findings?

Dr. Cotsarelis: We know a lot about AGA from studies a long time ago, in the ’50s, by Dr. James Hamilton. He was the first one to coin the term androgenetic alopecia. He noticed that men who had been castrated before puberty never went bald, and realized that baldness was androgen-dependent. He did some experiments where he gave men who had been castrated testosterone; the ones who had a family history of baldness started to go bald, so that was how he identified the genetic component. He originally called it androchronogenetic alopecia because you needed androgens, time, and genetics. We’ve known it’s androgen-dependent since then.

Next we learned more from studies by Imperato-McGinley, who studied families in the Dominican Republic who were pseudo-hermaphrodites — they were born looking like girls, with female genitals, and then at puberty they virilized, developing musculature, lower voices, and hair, and would actually develop a penis and could be fertile if they had their undescended testes surgically corrected. They were found to have a deficiency of type-2 5- reductase, the enzyme that converts testosterone into dihydrotestosterone. This was when we understood the importance of dihydrotestosterone in the process. Of course that’s what finasteride blocks; Merck developed that drug based on those studies.

Dr. Van Voorhees: What is the mechanism that accounts for the miniaturization of hair?

Dr. Cotsarelis: We know that inhibiting the testosterone pathway slows down the miniaturization of the follicle. Jaworsky, Kligman, and Murphy had a paper 20 years ago showing that half the time there is also inflammation around the hair follicle, which led to some thought that maybe inflammatory cells including mast cells were contributing to hair loss. Studies and case reports of transgender operations where men become women and receive high doses of estrogen show that a scalp that was almost completely bald can have, after castration and high estrogen supplementation, a tremendous amount of hair growth.

The overall feeling is that the follicles can be thought of as being in three states. Either they’re terminal, and they’re large, or they’re miniaturized, and they’re small, and the hair they’re creating is microscopic, or they’re in between, called indeterminate. It’s thought that follicles reach a point where they’re producing a hair so small that at that point the chance of reversing that follicle is small. There seems to be a point of no return with respect to androgen removal; even if you castrate someone who’s bald he won’t regrow all his hair. If you give him estrogen, too, he might.

Dr. Van Voorhees: Do resting stem cells remain in AGA? Do current medications used to treat AGA help us understand this process? What did this research demonstrate about the mechanism of AGA?

Dr. Cotsarelis: About a year ago Luis Garza, MD, did another study in my lab and looked at the stem cells in balding scalps of men undergoing transplants. He got tissue from the donor site and the recipient site and he actually quantitated the number of hair follicle stem cells using flow cytometry, a very accurate cutting-edge technique for quantitating the number of stem cells. And he showed that the percentage of stem cells was very similar in both areas. So the stem cells were still there even in the balding scalp where the follicles were miniaturizing.

However, he did find a population of cells that was markedly diminished in the balding scalp, and those resembled progenitor cells, the immediate progeny of stem cells. At that point we thought there must be either a lack of an activator of the stem cells preventing them from proliferating and doing their job and making hair, or maybe an inhibitor present. Using microarrays of bald and non-bald scalp in the same people, we looked at all 30,000 genes to see whether their expression levels were increased or decreased in the bald scalp. One of the genes that was markedly elevated in the bald scalp was PTGDS, prostaglandin D2 synthase.

We collaborated with Garret FitzGerald, MD, who’s an expert in prostaglandins and has done a lot of work with the COX-2 inhibitor he’s the one who actually showed that the COX-2 inhibitors have dangerous side effects. We gave him tissue from balding and non-bald scalp and he looked at the levels of PGD2 with mass spectrometry and showed that the PGD2 levels were quite high in the bald scalp. That was still just a correlation showing that there were higher levels of the genes and the lipid products in the bald scalp — we didn’t really know functionally whether that meant anything.

So then Luis worked with mouse models to assess the function of PGD2. Luis applied the PGD2 and another breakdown product, PGJ2, topically to the back of a mouse and he showed that hair growth slowed. Next, we collaborated with another group that was good at growing human hair follicles in culture. They showed that PGD2 in the culture media slowed down hair growth. So now we had functional evidence that prostaglandins played a role in hair growth. Luis also looked in the mouse, which has a better-defined hair cycle than humans because all of the hairs tend to be in the same stage whereas humans have mixtures of hair follicles in different stages of growth. In that model we showed that PGD2 started to go up during the end of the growing phase and was highest at catagen, the stage of regression. That, again, was good correlative evidence that PGD2 was inhibiting hair growth and even in a spontaneous hair cycle played a role in controlling hair growth.

There was a mouse that was made in the ’90s by Sue Fisher, who studies skin cancer; it’s a transgenic mouse that makes the COX-2 enzyme in the skin, so you drive COX-2 gene expression with keratin K14 promoters. It’s up higher in the pathway so if you overexpress COX-2 you get increases in PGD2 and also PGE2. E2 and F2 are actually known to promote hair growth — bimatoprost (Latisse) is an F2 analog. We looked at levels of D2 in that mouse, which develops alopecia, and they were sky high. E2 was also higher than the control but D2 levels were much higher. What’s amazing is if you looked at that mouse’s skin histologically the hair follicles were miniaturized and the sebaceous glands were enlarged, just like in androgenetic alopecia.

Finally, in genetic experiments done in collaboration with FitzGerald, we applied D2 to mice that lacked two different receptors that D2 binds to. The DP-1 knockout mouse had suppressed hair growth. The DP-2 (or GPR44) knockout mouse did not have inhibited hair growth.

Dr. Van Voorhees: Does this research open up possible avenues for treatment approaches that have not yet been considered? Are there currently drugs under development which might be utilized?

Dr. Cotsarelis: This work suggested that D2 was working through the GPR44 receptor to inhibit hair growth. It turns out that there are compounds under development by a number of companies to inhibit this receptor. They are being developed for asthma and allergic rhinitis. PGD2 causes bronchoconstriction — when you inhibit its receptor you relax smooth muscle so it helps with lung disorders. No one is developing a topical formulation, but we think if you did, it would be a potential treatment for alopecia.

Dr. Van Voorhees: Do you expect female pattern hair loss to have the same pathologic mechanism?

Dr. Cotsarelis: The only evidence we have is that when you take hair follicles from women, put them in the culture medium, and add D2, it inhibits their hair growth as well. But we haven’t studied women with female pattern hair loss to see if D2 is elevated there as well. The problem is that women who get hair transplants don’t have the donor scalp removed like men do; the grafts go in between existing hair follicles. The role of PGD2 in female pattern hair loss is an important question to address.

Dr. Van Voorhees: Should this allow for reversal of previously lost hairs or do you expect that it will only play a role in retaining hairs that have not yet miniaturized?

Dr. Cotsarelis: We don’t know. Like anything you’d have to test a large number of people to see how they respond. We don’t know if people who are already completely bald will regrow hair. We do know that the stem cells are present in men who are balding so if this is indeed the inhibitor preventing stem cells from making progenitor cells, there’s a possibility this would help there as well.

Dr. Van Voorhees: Why do you think there’s that threshold where miniaturization becomes non-reversible?

Dr. Cotsarelis: That’s an interesting question. There might be other genes downstream of testosterone playing a role. We already know that if you inhibit testosterone that hair doesn’t revert once it’s completely miniaturized. The fate of the hair follicle is determined very early on during development; there’s patterning, that’s why you have follicles responding to androgens on the top of the scalp and in the beard area in completely different ways. Androgen receptors are set up very early in development; I think the more we understand about that patterning the more we’ll likely be able to figure out what’s going on with hair loss.

http://www.aad.org/dermatology-world/monthly-archives/2012/june/can-blocking-pgd2-prevent-androgenetic-alopecia-




Dogstar is located in [NA] and he is available to meet: NO


Post reply
gutted

24.06.2012, 20:31

@ Dogstar

Inflamation/ PGD-2 and Mast Cell Degranulation?

» I saw this recent interview with Dr Cotsarelis posted on another forum if
» anyone is interested.
»
»
»
» By Abby Van Voorhees, MD, June 01, 2012
»
» In this month’s Acta Eruditorum column, Physician Editor Abby S. Van
» Voorhees, MD, talks with George Cotsarelis, MD, about his recent Science
» Translational Medicine article, “Prostaglandin D2 Inhibits Hair Growth and
» Is Elevated in Bald Scalp of Men with Androgenetic Alopecia.”
»
»
» Dr. Van Voorhees: What have we known about androgenetic alopecia
» (AGA) up until your most recent findings?
»
» Dr. Cotsarelis: We know a lot about AGA from studies a long time
» ago, in the ’50s, by Dr. James Hamilton. He was the first one to coin the
» term androgenetic alopecia. He noticed that men who had been castrated
» before puberty never went bald, and realized that baldness was
» androgen-dependent. He did some experiments where he gave men who had been
» castrated testosterone; the ones who had a family history of baldness
» started to go bald, so that was how he identified the genetic component. He
» originally called it androchronogenetic alopecia because you needed
» androgens, time, and genetics. We’ve known it’s androgen-dependent since
» then.
»
» Next we learned more from studies by Imperato-McGinley, who studied
» families in the Dominican Republic who were pseudo-hermaphrodites — they
» were born looking like girls, with female genitals, and then at puberty
» they virilized, developing musculature, lower voices, and hair, and would
» actually develop a penis and could be fertile if they had their undescended
» testes surgically corrected. They were found to have a deficiency of type-2
» 5- reductase, the enzyme that converts testosterone into
» dihydrotestosterone. This was when we understood the importance of
» dihydrotestosterone in the process. Of course that’s what finasteride
» blocks; Merck developed that drug based on those studies.
»
» Dr. Van Voorhees: What is the mechanism that accounts for the
» miniaturization of hair?
»
» Dr. Cotsarelis: We know that inhibiting the testosterone pathway
» slows down the miniaturization of the follicle. Jaworsky, Kligman, and
» Murphy had a paper 20 years ago showing that half the time there is also
» inflammation around the hair follicle, which led to some thought that maybe
» inflammatory cells including mast cells were contributing to hair loss.
» Studies and case reports of transgender operations where men become women
» and receive high doses of estrogen show that a scalp that was almost
» completely bald can have, after castration and high estrogen
» supplementation, a tremendous amount of hair growth.
»
» The overall feeling is that the follicles can be thought of as being in
» three states. Either they’re terminal, and they’re large, or they’re
» miniaturized, and they’re small, and the hair they’re creating is
» microscopic, or they’re in between, called indeterminate. It’s thought that
» follicles reach a point where they’re producing a hair so small that at
» that point the chance of reversing that follicle is small. There seems to
» be a point of no return with respect to androgen removal; even if you
» castrate someone who’s bald he won’t regrow all his hair. If you give him
» estrogen, too, he might.
»
» Dr. Van Voorhees: Do resting stem cells remain in AGA? Do current
» medications used to treat AGA help us understand this process? What did
» this research demonstrate about the mechanism of AGA?
»
» Dr. Cotsarelis: About a year ago Luis Garza, MD, did another study
» in my lab and looked at the stem cells in balding scalps of men undergoing
» transplants. He got tissue from the donor site and the recipient site and
» he actually quantitated the number of hair follicle stem cells using flow
» cytometry, a very accurate cutting-edge technique for quantitating the
» number of stem cells. And he showed that the percentage of stem cells was
» very similar in both areas. So the stem cells were still there even in the
» balding scalp where the follicles were miniaturizing.
»
» However, he did find a population of cells that was markedly diminished in
» the balding scalp, and those resembled progenitor cells, the immediate
» progeny of stem cells. At that point we thought there must be either a lack
» of an activator of the stem cells preventing them from proliferating and
» doing their job and making hair, or maybe an inhibitor present. Using
» microarrays of bald and non-bald scalp in the same people, we looked at all
» 30,000 genes to see whether their expression levels were increased or
» decreased in the bald scalp. One of the genes that was markedly elevated in
» the bald scalp was PTGDS, prostaglandin D2 synthase.
»
» We collaborated with Garret FitzGerald, MD, who’s an expert in
» prostaglandins and has done a lot of work with the COX-2 inhibitor he’s the
» one who actually showed that the COX-2 inhibitors have dangerous side
» effects. We gave him tissue from balding and non-bald scalp and he looked
» at the levels of PGD2 with mass spectrometry and showed that the PGD2
» levels were quite high in the bald scalp. That was still just a correlation
» showing that there were higher levels of the genes and the lipid products
» in the bald scalp — we didn’t really know functionally whether that meant
» anything.
»
» So then Luis worked with mouse models to assess the function of PGD2. Luis
» applied the PGD2 and another breakdown product, PGJ2, topically to the back
» of a mouse and he showed that hair growth slowed. Next, we collaborated
» with another group that was good at growing human hair follicles in
» culture. They showed that PGD2 in the culture media slowed down hair
» growth. So now we had functional evidence that prostaglandins played a role
» in hair growth. Luis also looked in the mouse, which has a better-defined
» hair cycle than humans because all of the hairs tend to be in the same
» stage whereas humans have mixtures of hair follicles in different stages of
» growth. In that model we showed that PGD2 started to go up during the end
» of the growing phase and was highest at catagen, the stage of regression.
» That, again, was good correlative evidence that PGD2 was inhibiting hair
» growth and even in a spontaneous hair cycle played a role in controlling
» hair growth.
»
» There was a mouse that was made in the ’90s by Sue Fisher, who studies skin
» cancer; it’s a transgenic mouse that makes the COX-2 enzyme in the skin, so
» you drive COX-2 gene expression with keratin K14 promoters. It’s up higher
» in the pathway so if you overexpress COX-2 you get increases in PGD2 and
» also PGE2. E2 and F2 are actually known to promote hair growth —
» bimatoprost (Latisse) is an F2 analog. We looked at levels of D2 in that
» mouse, which develops alopecia, and they were sky high. E2 was also higher
» than the control but D2 levels were much higher. What’s amazing is if you
» looked at that mouse’s skin histologically the hair follicles were
» miniaturized and the sebaceous glands were enlarged, just like in
» androgenetic alopecia.
»
» Finally, in genetic experiments done in collaboration with FitzGerald, we
» applied D2 to mice that lacked two different receptors that D2 binds to.
» The DP-1 knockout mouse had suppressed hair growth. The DP-2 (or GPR44)
» knockout mouse did not have inhibited hair growth.
»
» Dr. Van Voorhees: Does this research open up possible avenues for
» treatment approaches that have not yet been considered? Are there currently
» drugs under development which might be utilized?
»
» Dr. Cotsarelis: This work suggested that D2 was working through the
» GPR44 receptor to inhibit hair growth. It turns out that there are
» compounds under development by a number of companies to inhibit this
» receptor. They are being developed for asthma and allergic rhinitis. PGD2
» causes bronchoconstriction — when you inhibit its receptor you relax smooth
» muscle so it helps with lung disorders. No one is developing a topical
» formulation, but we think if you did, it would be a potential treatment for
» alopecia.
»
» Dr. Van Voorhees: Do you expect female pattern hair loss to have the
» same pathologic mechanism?
»
» Dr. Cotsarelis: The only evidence we have is that when you take hair
» follicles from women, put them in the culture medium, and add D2, it
» inhibits their hair growth as well. But we haven’t studied women with
» female pattern hair loss to see if D2 is elevated there as well. The
» problem is that women who get hair transplants don’t have the donor scalp
» removed like men do; the grafts go in between existing hair follicles. The
» role of PGD2 in female pattern hair loss is an important question to
» address.
»
» Dr. Van Voorhees: Should this allow for reversal of previously lost
» hairs or do you expect that it will only play a role in retaining hairs
» that have not yet miniaturized?
»
» Dr. Cotsarelis: We don’t know. Like anything you’d have to test a
» large number of people to see how they respond. We don’t know if people who
» are already completely bald will regrow hair. We do know that the stem
» cells are present in men who are balding so if this is indeed the inhibitor
» preventing stem cells from making progenitor cells, there’s a possibility
» this would help there as well.
»
» Dr. Van Voorhees: Why do you think there’s that threshold where
» miniaturization becomes non-reversible?
»
» Dr. Cotsarelis: That’s an interesting question. There might be other
» genes downstream of testosterone playing a role. We already know that if
» you inhibit testosterone that hair doesn’t revert once it’s completely
» miniaturized. The fate of the hair follicle is determined very early on
» during development; there’s patterning, that’s why you have follicles
» responding to androgens on the top of the scalp and in the beard area in
» completely different ways. Androgen receptors are set up very early in
» development; I think the more we understand about that patterning the more
» we’ll likely be able to figure out what’s going on with hair loss.
»
» http://www.aad.org/dermatology-world/monthly-archives/2012/june/can-blocking-pgd2-prevent-androgenetic-alopecia-

ive read this.

COX 2 has influence on the regeneration of wounds too ;)

the cure to baldness is sucessfully blocking this locally and stimulating the wnt pathway.




gutted is located in [NA] and he is available to meet: NO


Post reply
Rudy

25.06.2012, 14:27

@ Dogstar

Inflamation/ PGD-2 and Mast Cell Degranulation?

» I saw this recent interview with Dr Cotsarelis posted on another forum if
» anyone is interested.
»
»
»
» By Abby Van Voorhees, MD, June 01, 2012
»
» In this month’s Acta Eruditorum column, Physician Editor Abby S. Van
» Voorhees, MD, talks with George Cotsarelis, MD, about his recent Science
» Translational Medicine article, “Prostaglandin D2 Inhibits Hair Growth and
» Is Elevated in Bald Scalp of Men with Androgenetic Alopecia.”
»
»
» Dr. Van Voorhees: What have we known about androgenetic alopecia
» (AGA) up until your most recent findings?
»
» Dr. Cotsarelis: We know a lot about AGA from studies a long time
» ago, in the ’50s, by Dr. James Hamilton. He was the first one to coin the
» term androgenetic alopecia. He noticed that men who had been castrated
» before puberty never went bald, and realized that baldness was
» androgen-dependent. He did some experiments where he gave men who had been
» castrated testosterone; the ones who had a family history of baldness
» started to go bald, so that was how he identified the genetic component. He
» originally called it androchronogenetic alopecia because you needed
» androgens, time, and genetics. We’ve known it’s androgen-dependent since
» then.
»
» Next we learned more from studies by Imperato-McGinley, who studied
» families in the Dominican Republic who were pseudo-hermaphrodites — they
» were born looking like girls, with female genitals, and then at puberty
» they virilized, developing musculature, lower voices, and hair, and would
» actually develop a penis and could be fertile if they had their undescended
» testes surgically corrected. They were found to have a deficiency of type-2
» 5- reductase, the enzyme that converts testosterone into
» dihydrotestosterone. This was when we understood the importance of
» dihydrotestosterone in the process. Of course that’s what finasteride
» blocks; Merck developed that drug based on those studies.
»
» Dr. Van Voorhees: What is the mechanism that accounts for the
» miniaturization of hair?
»
» Dr. Cotsarelis: We know that inhibiting the testosterone pathway
» slows down the miniaturization of the follicle. Jaworsky, Kligman, and
» Murphy had a paper 20 years ago showing that half the time there is also
» inflammation around the hair follicle, which led to some thought that maybe
» inflammatory cells including mast cells were contributing to hair loss.
» Studies and case reports of transgender operations where men become women
» and receive high doses of estrogen show that a scalp that was almost
» completely bald can have, after castration and high estrogen
» supplementation, a tremendous amount of hair growth.
»
» The overall feeling is that the follicles can be thought of as being in
» three states. Either they’re terminal, and they’re large, or they’re
» miniaturized, and they’re small, and the hair they’re creating is
» microscopic, or they’re in between, called indeterminate. It’s thought that
» follicles reach a point where they’re producing a hair so small that at
» that point the chance of reversing that follicle is small. There seems to
» be a point of no return with respect to androgen removal; even if you
» castrate someone who’s bald he won’t regrow all his hair. If you give him
» estrogen, too, he might.
»
» Dr. Van Voorhees: Do resting stem cells remain in AGA? Do current
» medications used to treat AGA help us understand this process? What did
» this research demonstrate about the mechanism of AGA?
»
» Dr. Cotsarelis: About a year ago Luis Garza, MD, did another study
» in my lab and looked at the stem cells in balding scalps of men undergoing
» transplants. He got tissue from the donor site and the recipient site and
» he actually quantitated the number of hair follicle stem cells using flow
» cytometry, a very accurate cutting-edge technique for quantitating the
» number of stem cells. And he showed that the percentage of stem cells was
» very similar in both areas. So the stem cells were still there even in the
» balding scalp where the follicles were miniaturizing.
»
» However, he did find a population of cells that was markedly diminished in
» the balding scalp, and those resembled progenitor cells, the immediate
» progeny of stem cells. At that point we thought there must be either a lack
» of an activator of the stem cells preventing them from proliferating and
» doing their job and making hair, or maybe an inhibitor present. Using
» microarrays of bald and non-bald scalp in the same people, we looked at all
» 30,000 genes to see whether their expression levels were increased or
» decreased in the bald scalp. One of the genes that was markedly elevated in
» the bald scalp was PTGDS, prostaglandin D2 synthase.
»
» We collaborated with Garret FitzGerald, MD, who’s an expert in
» prostaglandins and has done a lot of work with the COX-2 inhibitor he’s the
» one who actually showed that the COX-2 inhibitors have dangerous side
» effects. We gave him tissue from balding and non-bald scalp and he looked
» at the levels of PGD2 with mass spectrometry and showed that the PGD2
» levels were quite high in the bald scalp. That was still just a correlation
» showing that there were higher levels of the genes and the lipid products
» in the bald scalp — we didn’t really know functionally whether that meant
» anything.
»
» So then Luis worked with mouse models to assess the function of PGD2. Luis
» applied the PGD2 and another breakdown product, PGJ2, topically to the back
» of a mouse and he showed that hair growth slowed. Next, we collaborated
» with another group that was good at growing human hair follicles in
» culture. They showed that PGD2 in the culture media slowed down hair
» growth. So now we had functional evidence that prostaglandins played a role
» in hair growth. Luis also looked in the mouse, which has a better-defined
» hair cycle than humans because all of the hairs tend to be in the same
» stage whereas humans have mixtures of hair follicles in different stages of
» growth. In that model we showed that PGD2 started to go up during the end
» of the growing phase and was highest at catagen, the stage of regression.
» That, again, was good correlative evidence that PGD2 was inhibiting hair
» growth and even in a spontaneous hair cycle played a role in controlling
» hair growth.
»
» There was a mouse that was made in the ’90s by Sue Fisher, who studies skin
» cancer; it’s a transgenic mouse that makes the COX-2 enzyme in the skin, so
» you drive COX-2 gene expression with keratin K14 promoters. It’s up higher
» in the pathway so if you overexpress COX-2 you get increases in PGD2 and
» also PGE2. E2 and F2 are actually known to promote hair growth —
» bimatoprost (Latisse) is an F2 analog. We looked at levels of D2 in that
» mouse, which develops alopecia, and they were sky high. E2 was also higher
» than the control but D2 levels were much higher. What’s amazing is if you
» looked at that mouse’s skin histologically the hair follicles were
» miniaturized and the sebaceous glands were enlarged, just like in
» androgenetic alopecia.
»
» Finally, in genetic experiments done in collaboration with FitzGerald, we
» applied D2 to mice that lacked two different receptors that D2 binds to.
» The DP-1 knockout mouse had suppressed hair growth. The DP-2 (or GPR44)
» knockout mouse did not have inhibited hair growth.
»
» Dr. Van Voorhees: Does this research open up possible avenues for
» treatment approaches that have not yet been considered? Are there currently
» drugs under development which might be utilized?
»
» Dr. Cotsarelis: This work suggested that D2 was working through the
» GPR44 receptor to inhibit hair growth. It turns out that there are
» compounds under development by a number of companies to inhibit this
» receptor. They are being developed for asthma and allergic rhinitis. PGD2
» causes bronchoconstriction — when you inhibit its receptor you relax smooth
» muscle so it helps with lung disorders. No one is developing a topical
» formulation, but we think if you did, it would be a potential treatment for
» alopecia.
»
» Dr. Van Voorhees: Do you expect female pattern hair loss to have the
» same pathologic mechanism?
»
» Dr. Cotsarelis: The only evidence we have is that when you take hair
» follicles from women, put them in the culture medium, and add D2, it
» inhibits their hair growth as well. But we haven’t studied women with
» female pattern hair loss to see if D2 is elevated there as well. The
» problem is that women who get hair transplants don’t have the donor scalp
» removed like men do; the grafts go in between existing hair follicles. The
» role of PGD2 in female pattern hair loss is an important question to
» address.
»
» Dr. Van Voorhees: Should this allow for reversal of previously lost
» hairs or do you expect that it will only play a role in retaining hairs
» that have not yet miniaturized?
»
» Dr. Cotsarelis: We don’t know. Like anything you’d have to test a
» large number of people to see how they respond. We don’t know if people who
» are already completely bald will regrow hair. We do know that the stem
» cells are present in men who are balding so if this is indeed the inhibitor
» preventing stem cells from making progenitor cells, there’s a possibility
» this would help there as well.
»
» Dr. Van Voorhees: Why do you think there’s that threshold where
» miniaturization becomes non-reversible?
»
» Dr. Cotsarelis: That’s an interesting question. There might be other
» genes downstream of testosterone playing a role. We already know that if
» you inhibit testosterone that hair doesn’t revert once it’s completely
» miniaturized. The fate of the hair follicle is determined very early on
» during development; there’s patterning, that’s why you have follicles
» responding to androgens on the top of the scalp and in the beard area in
» completely different ways. Androgen receptors are set up very early in
» development; I think the more we understand about that patterning the more
» we’ll likely be able to figure out what’s going on with hair loss.
»
» http://www.aad.org/dermatology-world/monthly-archives/2012/june/can-blocking-pgd2-prevent-androgenetic-alopecia-

Excellent Dogstar!!

That confirms that my hunch about a mast cell inhibitor would have a chance of being helpful.

The wild thing is I watched an HBO special about intersexed people with the 5 AR mutation last nite. They had their testes removed and essentially grew up as sterile females. Just a coincidence, it was mentioned here.

I cant believe a topical has NOT been developed using a mast cell inhibitor. I am also a little surprised that this thread hasn't garnished more attention.

I am still hoping that somebody smarter then me, or at least more eductated and familiarized with chemistry (molecular weights), getting stuff compounded etc. would comment.

Everybody is flipping out about PGD2 inhibition and mast cell stabilzers are known to do this unequivocally.

This may not be a silver bullet but.

1.The chemicals/drugs have been around for a long time and should be easily compounded and I would suspect relatively cheap.

2. They have an established safety profile and treat exactly what the DR here is saying drugs are being developed to do. Although the drugs would down regulate the receptor, if the mast cell doesnt release the PGD2 then one would think there would be less to bind.

3. If this is helpful I would think even if and when a drug that down regulates the receptor is developed that if it didnt down regulate 100% that a mast stell stabilizer would potentiate its action by reducing the amount of availible PGD2.

4. The whole idea here is about reducing inflamation. There are other ways to reduce inflamation and perhaps with a mast cell stabilizer as part of an approach you could significantly reduce the inflamation.

The biggest issue. If the current mast cell stabilizers could be used effectively is that you would have to apply them 4 times a day pretty religiously.

A VERY interesting thing I discovered while researching mast cell's is that one of the things that causes them to degranulate (release PGD2 among other inflammatory agents) is exposure to alcohol. Which tells me that part of the reason so many topicals may not work as well as they should is that some of their benefits must be being negated by the release of PGD2 caused by the alc. Then factor in that nearly all hair products have alc in them. Suggesting ALC free stuff should be a major concern for people with Androgenic HL.

My feeling is that until stuff that is currently in the pipeline to reduce PGD2 is developed and released this approach I have suggested should be tried. At the very least I would expect it to help other treatments work better.

So anybody out there that could help me figure out what type of mast cell stabilizer, what concentration and vehicle to use PLEASE CHIME in.

Anybody who has a line to DR Costaralis or suggestion on getting his opinion would helpful as well.

As a general point. Inflammation is either present in, casual or mediates in someway almost every disease process. I remember reading about this many years ago and now, more and more info comes out about this relating to so many disease's. It seems if you are genetically susceptible to a myriad of diseases or conditions controlling inflammation is a major part of treating/preventing the negative outcome. It makes pretty good sense that people with genetic predisposition to HL would need to control this to have any great amount of success to keep or regenerate the follicles pre disposed.

THANKS AGAIN!! Dogstar. Perhaps that interview will get some more people talking about the possible benefits of stabilizing mast cells in the scalp.

So, come on. A little more chatter on this idea and suggestions on a direction to follow.

Thanks

P.S. It would also seem to me that it would be safer in general if you could have an affect by locally reducing mast cell activity/reducing PGD2 to the scalp. Perhaps a systemic drug might be more effective (perhaps not or even less) but Im almost 100% sure the side effects would be greater.




Rudy is located in [NA] and he is available to meet: NO


Post reply
moawk

Germany,
25.06.2012, 14:52

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

lot of sh1t talking and nothing will get done in 5 years.




moawk is located in GERMANY and he is available to meet: NO

---
1. Predicted the failure of replicel, months in advance.
2. Predicted how their stock would rise/drop even with exact numbers.
3. Predicted the wild claims and crazyness that gc83uk's donor regeneration will cause among the HT industry during this summer. Including rassman's opinion, Dr. Woods special patients and Pro hair clinic photos.
4. Predicted Gho will open up a clinic in asia.
5. No prediction on Histogen. Looks promising if they didn't fake results.
6. Predicted the only viable HM technique other than Gho would surface when hairs are: "generated through the appropriate cell populations" -Team Tokyo 2012


[image]
- Moawk

Advice for patients: If you are considering a hair transplant, only consider Gho's HST and nothing else. First HT treatment in the world that offers: zero scarring, small downtime and donor regrowth.
http://www.hasci.com

Advice for Investors in HM: Invest in Team Tokyo.
http://www.tsuji-lab.com/en/research/organ/hair.html
Ditch replicel, aderans. They are done for and have no future.


Post reply
Rudy

25.06.2012, 15:29

@ moawk

Yeah

» lot of sh1t talking and nothing will get done in 5 years.

Yeah... hmmmmmm.... Ok. Yeah, thats why I am suggesting something that could be used/tested right now. Something that should be readily availible and reasonably cheap and easy to get.

But yeah..... hmmmmmm.... Ok... Thanks for the useful input. Yeah.... hmmmm... Ok Im going to need a report on this by tommorow moawk.

Beyond the Joking and attempt at a goof in the vein of Office Space. I am assuming nobody (pharma company) would or is trying this approach is.

1. Its a newish idea.

2. The current Mast Cell stabilizers are off patent now so they would need a new unique drug to really capitalize.




Rudy is located in [NA] and he is available to meet: NO


Post reply
cal

26.06.2012, 01:55

@ Rudy

Yeah

» » lot of sh1t talking and nothing will get done in 5 years.

If you don't want to discuss the topic then get the fuc off the thread.




cal is located in [NA] and he is available to meet: NO


Post reply
Freddie555

26.06.2012, 03:55

@ cal

Yeah

» If you don't want to discuss the topic then get the fuc off the thread.

I second that. Fuc&kin clueless dumb a$$ morons.

Keep going with your train of thought Rudy. Its something new.

Only thing I can contribute is that there is mixed evidence regarding immuno-supressive drugs doing anything significant for hair loss. Although the odd report does pop up of miraculous hair regrowth - its all testimonial based hearsay unfortunately with no pics.




Freddie555 is located in [NA] and he is available to meet: NO

---
"When true Hair Multiplication comes, it will arise out of the East." - John The Revelator, Feb. 18, 2001


Post reply
Rudy

26.06.2012, 15:12

@ Freddie555

Yeah

» » If you don't want to discuss the topic then get the fuc off the thread.
»
» I second that. Fuc&kin clueless dumb a$$ morons.
»
» Keep going with your train of thought Rudy. Its something new.
»
» Only thing I can contribute is that there is mixed evidence regarding
» immuno-supressive drugs doing anything significant for hair loss. Although
» the odd report does pop up of miraculous hair regrowth - its all
» testimonial based hearsay unfortunately with no pics.

Freddie,

Thanks

Im not all that hip to how Immuno-supressive drugs like cyclosporin work. I do know they are somewhat dangerous systemically and really for serious situations. They generally work by suppressing T-cell function. My dog took it for severe skin allergies. She died prematurely from cancer (coincidence? perhaps but suppressed killer cells is not a good thing for cancer).

Looking at wikipedia I see no reference to prostaglandins or mast cells In reference to cyclosporin. So I think this isnt really a similar approach.

My main Idea is Mast Cell Inhibitors DO suppress the type of prostaglandin people are talking about.

ALSO: One might assume if balding scalp has high levels of PGD2 and inflammation then there is a high rate of mast cell degranulation ( letting loose all its inflammatory agents). Of course the PGD2 may be ending up in the scalp through another mechanism. Most likely it is a local reaction of mast cells causing elevation in the area. Again Im not informed enough to know for sure. Looking at wkipedia I see this

"Prostaglandins are potent but have a short half-life before being inactivated and excreted. Therefore, they send only paracrine (locally active) or autocrine (acting on the same cell from which it is synthesized) signals."

If I understand this correctly. Prostaglandins act locally and are being created in the area and not aggregating in the scalp from somewhere else. I also read that most cells are able to produce Protaglandins. However different prostaglandins do different things. My research and minimal understanding of this subject lead me to believe that Mast cells are the ones most likely to release PGD2. Again being that inflammation is present one would believe that mast cells are degranulating and at least somewhat responsible for the high levels of PGD2.

And if this is the case. Mast cells let off all kinds of inflammatory agents that are probably not very good for hair follicles. We definately know that prolonged inflammation causes all kinds of diseases and conditions.

At the very least I do think controlling inflammation is a part of the puzzle. I would suspect that controlling inflammation would make other treatments more successful. In fact I think without controlling inflammation most treatments on genetically predisposed follicles will always have minor efficacy.

I really just want some people smarter and more knowledgeable then me to help with a direction of how one might pursue this idea.

It would seem a multi pronged approach of reducing cox-2 systemically and perhaps locally and then stabilizing mast cells would certainly be the best approach. I dont completely understand how Bimatoprost works. BUT it seems it is a synthetic prostaglandin that is positive for hairgrowth.

PERHAPS if you down regulate the bad prostaglandin and more Bimatoprost ( the good one) is able to bond it would potentiate the effect. So you apply a mast cell stabilizer then the Bimatoprost. If there are more places not binded with PGD2 the Bimatoprost has greater effect?

AGAIN, I have no real idea. I just wish somebody who understands this stuff better would comment.




Rudy is located in [NA] and he is available to meet: NO


Post reply
TaKeeLa

03.07.2012, 19:59

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

Mast Cell Degranulation... I was researching and ran across this.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0039935;jsessionid=E1D131C577BF494A63CE44C45F94A6AB

Abstract Top
Background and Aims
Psychological stress is a predisposing factor in the onset and exacerbation of important gastrointestinal diseases including irritable bowel syndrome (IBS) and the inflammatory bowel diseases (IBD). The pathophysiology of stress-induced intestinal disturbances is known to be mediated by corticotropin releasing factor (CRF) but the precise signaling pathways remain poorly understood. Utilizing a porcine ex vivo intestinal model, the aim of this study was to investigate the mechanisms by which CRF mediates intestinal epithelial barrier disturbances.

Methodology
Ileum was harvested from 6–8 week-old pigs, mounted on Ussing Chambers, and exposed to CRF in the presence or absence of various pharmacologic inhibitors of CRF-mediated signaling pathways. Mucosal-to-serosal flux of 4 kDa-FITC dextran (FD4) and transepithelial electrical resistance (TER) were recorded as indices of intestinal epithelial barrier function.

Results
Exposure of porcine ileum to 0.05–0.5 µM CRF increased (p<0.05) paracellular flux compared with vehicle controls. CRF treatment had no deleterious effects on ileal TER. The effects of CRF on FD4 flux were inhibited with pre-treatment of tissue with the non-selective CRF1/2 receptor antagonist Astressin B and the mast cell stabilizer sodium cromolyn (10&#8722;4 M). Furthermore, anti-TNF-&#945; neutralizing antibody (p<0.01), protease inhibitors (p<0.01) and the neural blocker tetrodotoxin (TTX) inhibited CRF-mediated intestinal barrier dysfunction.

Conclusion
These data demonstrate that CRF triggers increases in intestinal paracellular permeability via mast cell dependent release of TNF-&#945; and proteases. Furthermore, CRF-mast cell signaling pathways and increases in intestinal permeability require critical input from the enteric nervous system. Therefore, blocking the deleterious effects of CRF may address the enteric signaling of mast cell degranulation, TNF&#945; release, and protease secretion, hallmarks of IBS and IBD.




TaKeeLa is located in [NA] and he is available to meet: NO


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shivers20

03.11.2012, 01:20

@ Rudy

Inflamation/ PGD-2 and Mast Cell Degranulation?

Any news on mast cell Stabilizers?




shivers20 is located in [NA] and he is available to meet: NO


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