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Fibrosis and inflammation *key* to Topical success


#1

Im becoming even more convinced that using agents to help with Fibrosis and inflammation will be the key to Topical success:

This just published study features the integral role that both inflammation and fibrosis play in AGA. It implies that the role played by inflammation and fibrosis is more central to hair loss than the hormonal initiators, namely DHT and Androstenedione.

Androgenetic alopecia in males: a histopathological and ultrastructural study

J Cosmet Dermatol. 2009 Jun;8(2):83-91.

Androgenetic alopecia in males: a histopathological and ultrastructural study.
El-Domyati M, Attia S, Saleh F, Abdel-Wahab H.

Department of Dermatology, Faculty of Medicine, Al-Minya University, Al-Minya,
Egypt

Background Androgenetic alopecia is a common cosmetic hair disorder, resulting from interplay of genetic, endocrine, and aging factors leading to a patterned follicular miniaturization. Microinflammation seems to be a potential active player in this process. Aims To study the histopathological and ultrastructural changes occurring in male androgenetic alopecia (AGA). Patients/methods Fifty-five subjects were included in this study (40 with AGA and 15 as normal age-matched controls). Skin biopsies from frontal bald area and occipital hairy area were subjected to histopathological examination, immunohistochemical staining for collagen I and ultrastructural study. Results The frontal bald area of patients showed highly significant increase in telogen hairs and decrease in anagen/telogen ratio and terminal/vellus hair ratio (P < 0.001). Perifollicular inflammation was almost a constant feature in early cases and showed a significant inverse correlation with perifollicular fibrosis (P = 0.048), which was more marked with thickening of the follicular sheath in advanced cases. Conclusion Follicular microinflammation plays an integral role in the pathogenesis of AGA in early cases. Over time, thickening of perifollicular sheath takes place due to increased deposition of collagen, resulting in marked perifollicular fibrosis, and sometimes ends by complete destruction of the affected follicles in advanced cases.

Regards
Pete


#2

Simply from anecdotal evidence collected on this board, its pretty obvious that inflammation is a factor. This study confirms this, but it doesn’t say much about whether or not its a cause or an effect. I know nothing about steroids except that they can’t be taken chronically, but it would be interesting to see what a topical steroidal cream would do. Are there any safe anti-inflamitories that can be taken daily? I don’t know of any.


#3

» Simply from anecdotal evidence collected on this board, its pretty obvious
» that inflammation is a factor. This study confirms this, but it doesn’t
» say much about whether or not its a cause or an effect. I know nothing
» about steroids except that they can’t be taken chronically, but it would be
» interesting to see what a topical steroidal cream would do. Are there any
» safe anti-inflamitories that can be taken daily? I don’t know of any.

Piroctone Olamine has been shown to beneficial.

There are undoubtedly other factors :

1)inflammation
2)fibrosis
3)SOD levels
4)bloodflow
5)cellular health

Regards
Pete


#4

» » Simply from anecdotal evidence collected on this board, its pretty
» obvious
» » that inflammation is a factor. This study confirms this, but it
» doesn’t
» » say much about whether or not its a cause or an effect. I know nothing
» » about steroids except that they can’t be taken chronically, but it would
» be
» » interesting to see what a topical steroidal cream would do. Are there
» any
» » safe anti-inflamitories that can be taken daily? I don’t know of any.
»
»
»
» Piroctone Olamine has been shown to beneficial.
»
» There are undoubtedly other factors :
»
» 1)inflammation
» 2)fibrosis
» 3)SOD levels
» 4)bloodflow
» 5)cellular health
»
»
»
»
» Regards
» Pete

In the end, I think AA will be proven to be an auto-imune disorder, which is too bad, as there’s not much that can be done about those sort of things (at least not in our useful lifetime). One will either have to suppress DHT (which really only slows the inevitable), or grow completely new follicles through HM or some other technique.


#5

» » » Simply from anecdotal evidence collected on this board, its pretty
» » obvious
» » » that inflammation is a factor. This study confirms this, but it
» » doesn’t
» » » say much about whether or not its a cause or an effect. I know
» nothing
» » » about steroids except that they can’t be taken chronically, but it
» would
» » be
» » » interesting to see what a topical steroidal cream would do. Are
» there
» » any
» » » safe anti-inflamitories that can be taken daily? I don’t know of
» any.
» »
» »
» »
» » Piroctone Olamine has been shown to beneficial.
» »
» » There are undoubtedly other factors :
» »
» » 1)inflammation
» » 2)fibrosis
» » 3)SOD levels
» » 4)bloodflow
» » 5)cellular health
» »
» »
» »
» »
» » Regards
» » Pete
»
» In the end, I think AA will be proven to be an auto-imune disorder, which
» is too bad, as there’s not much that can be done about those sort of things
» (at least not in our useful lifetime). One will either have to suppress
» DHT (which really only slows the inevitable), or grow completely new
» follicles through HM or some other technique.

Are you talking about Alopecia Areata?

We may find other clues to successful treatments for MPB when we look into interlinks into health issues ie. the relationship between MPB and heart problems.

Regards
Pete


#6

» » » » Simply from anecdotal evidence collected on this board, its pretty
» » » obvious
» » » » that inflammation is a factor. This study confirms this, but it
» » » doesn’t
» » » » say much about whether or not its a cause or an effect. I know
» » nothing
» » » » about steroids except that they can’t be taken chronically, but it
» » would
» » » be
» » » » interesting to see what a topical steroidal cream would do. Are
» » there
» » » any
» » » » safe anti-inflamitories that can be taken daily? I don’t know of
» » any.
» » »
» » »
» » »
» » » Piroctone Olamine has been shown to beneficial.
» » »
» » » There are undoubtedly other factors :
» » »
» » » 1)inflammation
» » » 2)fibrosis
» » » 3)SOD levels
» » » 4)bloodflow
» » » 5)cellular health
» » »
» » »
» » »
» » »
» » » Regards
» » » Pete
» »
» » In the end, I think AA will be proven to be an auto-imune disorder,
» which
» » is too bad, as there’s not much that can be done about those sort of
» things
» » (at least not in our useful lifetime). One will either have to
» suppress
» » DHT (which really only slows the inevitable), or grow completely new
» » follicles through HM or some other technique.
»
»
» Are you talking about Alopecia Areata?
»
»
» We may find other clues to successful treatments for MPB when we look into
» interlinks into health issues ie. the relationship between MPB and heart
» problems.
»
»
»
»
»
»
» Regards
» Pete

What do you mean by fibrosis

when you search google it comes up with pulmonary fibrosis, cystic fibrosis, etc


#7

»
» What do you mean by fibrosis
»
» when you search google it comes up with pulmonary fibrosis, cystic
» fibrosis, etc

http://www.keratin.com/ac/baldnessbiology/collagenbuildup/001collagenbuildupcausesbaldness.shtml

Although some of these ideas could have some merit. It could be the case that we are becoming over technical with them.

This issue could be helped simply with daily Scalp massages with anti inflammatory shampoo / Essential oils (used in the Scottish Alopecia Study) .

Regards
Pete


#8

» Are you talking about Alopecia Areata?

No, he meant androgenetic alopecia, but it’s already known that it isn’t an autoimmune disorder.


#9

» » Are you talking about Alopecia Areata?
»
» No, he meant androgenetic alopecia, but it’s already known that it isn’t
» an autoimmune disorder.

No MPB isnt an auto immune disorder as such. The shrinkage/changes probably caused by DHT triggers a relentless immune response which needs to be calmed inorder to stabilise things.

Regards
Pete


#10

» » » » Simply from anecdotal evidence collected on this board, its pretty
» » » obvious
» » » » that inflammation is a factor. This study confirms this, but it
» » » doesn’t
» » » » say much about whether or not its a cause or an effect. I know
» » nothing
» » » » about steroids except that they can’t be taken chronically, but it
» » would
» » » be
» » » » interesting to see what a topical steroidal cream would do. Are
» » there
» » » any
» » » » safe anti-inflamitories that can be taken daily? I don’t know of
» » any.
» » »
» » »
» » »
» » » Piroctone Olamine has been shown to beneficial.
» » »
» » » There are undoubtedly other factors :
» » »
» » » 1)inflammation
» » » 2)fibrosis
» » » 3)SOD levels
» » » 4)bloodflow
» » » 5)cellular health
» » »
» » »
» » »
» » »
» » » Regards
» » » Pete
» »
» » In the end, I think AA will be proven to be an auto-imune disorder,
» which
» » is too bad, as there’s not much that can be done about those sort of
» things
» » (at least not in our useful lifetime). One will either have to
» suppress
» » DHT (which really only slows the inevitable), or grow completely new
» » follicles through HM or some other technique.
»
»
» Are you talking about Alopecia Areata?
»
»
» We may find other clues to successful treatments for MPB when we look into
» interlinks into health issues ie. the relationship between MPB and heart
» problems.
»
»
»
»
»
»
» Regards
» Pete

For your own interest it seems that it is possible to improve heart health via:

1)relaxation, stress response
2)diet/lifestyle, detoxing, mitochondria supps

Regards
Pete


#11

Hideo Uno detailed that stumptailed macaque balding exhibited no inflammation vs. human balding which often (BUT NOT ALWAYS) does. Macaques dont see collagenous streamers appear under their follicles either, they just miniaturized and stay in telogen. Macaques also have a better response to drugs like finasteride and minoxidil.

In short, our immune system “gets involved”, inflames the follicle, and as a result of the chronic inflammation, collageous deposition forms underneath and around the follicle’s root sheath, boxing it in somewhat*

*note: Researcher and owner of keratinDOTcom Kevin McElwee has noted that healthy hairs can secrete enzymes that will eat right through collagenous deposition and grow just fine. Frontal transplants in long-bald men prove this to be so.

So WHY is the immune system inflaming the follicle?

1)Could it be that too many negative growth factors like tgf-beta 1, tgf-beta 2, pkc, thrombospondin, fiberblast growth factor five, DKK-1, or another un-named one are in one mini-organ inciting an immune response?

  1. Could any particular growth factor associated with inflammation and fibrosis (tgf-beta) being secreted too much by the papilla be the reason?

  2. Could it be any particular androgen-inducible gene that is upregged in MPB hair “too much” get the immune system interested that is upstream of the release of growth factors?

4)Could dead keratinocytes in the infrainfundiblulim (the hole in the dermis where the hair follicle exists the skin), because of the apoptosis of keratinocytes caused by DKK-1 (DKK-1 has been shown to cause apoptosis in Kertainocyte cells) be the reason. WE DO KNOW FOR A FACT THAT THE FIRST INFLAMMATION SEEN IN Androgenic Alopecia is at the infrainfundibulim…in the uppermost portion of the hair follicle where the dead kt cells would be.

  1. any particular microbial that perhaps flourishes in a dying hair follicle causing an immune response

  2. long term DNA damage in hair cells from AGA, inciting an immuno-response to the damaged DNA?

That about covers the usual suspects that get discussed. I lean toward either number 6 or number 4 myself. Frankly I wonder about androgen-inducible genes. If we could just inhibit one or two of them in particular topically…would the whole thing be different? I also wonder about DKK-1. If that could be inhibited topically, would the keratinocytes not undergo apoptosis…thus leaving some dead cells in the dermis as they emerge onto the skin, perhaps inviting an immuno response so that bacteria or whatnot does not colonize the area? If I had to guess…I’d guess that dead keratinocyte cells in the infrainfundibulum would be the cause of the immuno response and attendant inflammation, and this is the reason that collagenous deposition happens a little later. But I dont know for sure of course, but it does make sense. The FIRST INFLAMMATION in androgenic baldness is seen at the infrainfundibulum, the opening in the dermis where the hair posits on the skin…right where those KT cells would be undergoeing apoptosis while still “in” the body. It makes sense in light of that. Where the first inflammation is, is where we will find our immuno-culprit in my opinion. DKK-1 is the second or third most upregged gene in AGA.

Its probably being looked into. I could of course be 100% wrong about that, but thats my “leading contender” anyway.


#12

» Hideo Uno detailed that stumptailed macaque balding exhibited no
» inflammation vs. human balding which often (BUT NOT ALWAYS) does. Macaques
» dont see collagenous streamers appear under their follicles either, they
» just miniaturized and stay in telogen. Macaques also have a better response
» to drugs like finasteride and minoxidil.
»
»
» In short, our immune system “gets involved”, inflames the follicle, and as
» a result of the chronic inflammation, collageous deposition forms
» underneath and around the follicle’s root sheath, boxing it in somewhat*
»
»
» *note: Researcher and owner of keratinDOTcom Kevin McElwee has noted that
» healthy hairs can secrete enzymes that will eat right through collagenous
» deposition and grow just fine. Frontal transplants in long-bald men prove
» this to be so.
»
»
»
»
» So WHY is the immune system inflaming the follicle?
»
»
» 1)Could it be that too many negative growth factors like tgf-beta 1,
» tgf-beta 2, pkc, thrombospondin, fiberblast growth factor five, DKK-1, or
» another un-named one are in one mini-organ inciting an immune response?
»
»
» 2) Could any particular growth factor associated with inflammation and
» fibrosis (tgf-beta) being secreted too much by the papilla be the reason?
»
»
» 3) Could it be any particular androgen-inducible gene that is upregged in
» MPB hair “too much” get the immune system interested that is upstream of
» the release of growth factors?
»
»
» 4)Could dead keratinocytes in the infrainfundiblulim (the
» hole in the dermis where the hair follicle exists the skin), because of the
» apoptosis of keratinocytes caused by DKK-1 (DKK-1 has been shown to cause
» apoptosis in Kertainocyte cells) be the reason. WE DO KNOW FOR A FACT THAT
» THE FIRST INFLAMMATION SEEN IN Androgenic Alopecia is at the
» infrainfundibulim…in the uppermost portion of the hair follicle where
» the dead kt cells would be.
»
»
» 5) any particular microbial that perhaps flourishes in a dying hair
» follicle causing an immune response
»
»
»
» 6) long term DNA damage in hair cells from AGA, inciting an
» immuno-response to the damaged DNA?
»
»
»
»
»
» That about covers the usual suspects that get discussed. I lean toward
» either number 6 or number 4 myself. Frankly I wonder about
» androgen-inducible genes. If we could just inhibit one or two of them in
» particular topically…would the whole thing be different? I also
» wonder about DKK-1. If that could be inhibited topically, would the
» keratinocytes not undergo apoptosis…thus leaving some dead cells in the
» dermis as they emerge onto the skin, perhaps inviting an immuno response so
» that bacteria or whatnot does not colonize the area?
» If I had to guess…I’d guess that dead
» keratinocyte cells in the infrainfundibulum would be the cause of the
» immuno response and attendant inflammation, and this is the reason that
» collagenous deposition happens a little later. But I dont
» know for sure of course, but it does make sense. The FIRST
» INFLAMMATION in androgenic baldness is seen at the infrainfundibulum, the
» opening in the dermis where the hair posits on the skin…right where
» those KT cells would be undergoeing apoptosis while still “in” the body. It
» makes sense in light of that. Where the first inflammation is, is where we
» will find our immuno-culprit in my opinion. DKK-1 is the second or third
» most upregged gene in AGA.
»
» Its probably being looked into. I could of course be 100% wrong about
» that, but thats my “leading contender” anyway.

I have a hunch that scalp tension may need to addressed via some agents topically also.

Regards
Pete


#13

There are millions of men on earth who are dying with thick NW#1 and NW#2 heads of hair, and they are not immune to MPB. They are not free of the problems of androgen-sensitive hair follicles or inflammation effects. Their balding genes are simply just calling for a slower balding process than ours, and that’s all it took for them to live their whole lives free of our affliction.

We don’t need to “cure” MPB just to be able to live like they do.

We need some kind of realistic practical treatment option for the later stages of the problem. That’s all.


#14

» There are millions of men on earth who are dying with thick NW#1 and NW#2
» heads of hair, and they are not immune to MPB. They are not free of the
» problems of androgen-sensitive hair follicles or inflammation effects.
» Their balding genes are simply just calling for a slower balding process
» than ours, and that’s all it took for them to live their whole lives free
» of our affliction.
»
»
»
» We don’t need to “cure” MPB just to be able to live like they do.
»
» We need some kind of realistic practical treatment option for the later
» stages of the problem. That’s all.

A little off topic here, but Cal don’t you think Sebum plays a major roll in hair loss as well? If we tried to eliminate sebum from our scalp I think it just may be more benificial than finasteride itself.


#15

Well, not exactly.

Sebum is an indicator of androgens in the skin. But it’s not a precursor/causative thing. Just physically removing sebum from the scalp (frequent shampooing, etc) will not meaningfully reduce androgen levels.

But things that reduce the production of androgens will also reduce the production of sebum. So the level of sebem production provides sort of a dipstick reading for the level of androgen production.


#16

» Well, not exactly.
»
»
» Sebum is an indicator of androgens in the skin. But it’s not a
» precursor/causative thing. Just physically removing sebum from the scalp
» (frequent shampooing, etc) will not meaningfully reduce androgen levels.
»
» But things that reduce the production of androgens will also reduce the
» production of sebum. So the level of sebem production provides sort of a
» dipstick reading for the level of androgen production.

You may find that by taking Pantothenic acid will reduce the oiliness.

Regards
Pete


#17

».
»
»
» You may find that by taking Pantothenic acid will reduce the oiliness.
»
»
»
»
» Regards
» Pete

Panthotenic acid is in a bunch of shampoos for just this reason. People who have low levels of panthotenic acid oft have bad acne according to some research.


#18

I literally can’t overstate the impact that Pantothenic acid has made in curing my acne. My body acne went from chronic & unfixable to completely gone.

I’m convinced there has been some MPB improvement with it too. I wish I had known about this stuff since puberty.


#19

» I literally can’t overstate the impact that Pantothenic acid has made in
» curing my acne. My body acne went from chronic & unfixable to completely
» gone.
»
»
» I’m convinced there has been some MPB improvement with it too. I wish I
» had known about this stuff since puberty.

Cal where is it found and how did you use it for your body acne?!? I’ve literally spent hundreds of dollars (seriously) on products for my shoulder and back acne to no avail. Right now I’m using doctor prescribed Clindasol Cream which isnt making the slightest difference. And this crap cost me $150 to a 2 month supply!!!


#20

» I literally can’t overstate the impact that Pantothenic acid has made in
» curing my acne. My body acne went from chronic & unfixable to completely
» gone.
»
»
» I’m convinced there has been some MPB improvement with it too. I wish I
» had known about this stuff since puberty.

Topically - an Azelaic acid based cream may also be useful.

Regards
Pete