Follica - Good News!

[harold]

Exp Dermatol. 2008 Jan;17(1):63-72. Epub 2007 Nov 13.Click here to read Links
Prostanoid receptors in anagen human hair follicles.
Colombe L, Michelet JF, Bernard BA.

L'Oréal Recherche, Clichy, France.

Prostanoid pathway in hair follicle gained closer attention since trichogenic side-effects on hair growth has been observed concomitantly with prostaglandin F(2alpha) receptor (FP) agonist treatment of intraocular pressure. We thus investigated prostanoid receptor distribution in anagen hair follicle and different cell types from hair and skin. Using RT-PCR, Western blot and immunohistochemistry (IHC), we found that all receptors were present in hair follicle. This data shed new light on an underestimated complex network involved in hair growth control. Indeed most of these receptors showed a wide spectrum of expression in cultured cells and the whole hair follicle. Using IHC, we observed that expression of prostaglandin E(2) receptors (EP(2), EP(3), EP(4)), prostaglandin D(2) receptor (DP(2)), prostanoid thromboxane A(2) receptor (TP) and to a lesser extent EP(1) involved several hair follicle compartments. On the opposite, Prostaglandin I(2) receptor (IP) and DP(1) were more specifically expressed in hair cuticle layer and outer root sheath (ORS) basal layer, respectively. FP expression was essentially restricted to ORS companion layer and dermal papilla (DP). Although extracting a clear functional significance from this intricate network remains open challenge, FP labelling, i.e. could explain the biological effect of PGF(2alpha) on hair regrowth, by directly modulating DP function.

PMID: 18005048 [PubMed - in process]

1: Exp Dermatol. 2007 Sep;16(9):762-9.Click here to read Links
Prostaglandin metabolism in human hair follicle.
Colombe L, Vindrios A, Michelet JF, Bernard BA.

Centre Charles Zviak, L'Oreal Recherche, 90 rue du Général Roguet, Clichy Cedex, France. lcolombe@rd.loreal.com

Prostaglandins regulate a wide number of physiological functions. Recently PGF(2alpha) analogue such as latanoprost was shown to have a real impact on hair regrowth. The aim of this study was to investigate and describe the expression profile in human hair follicle of prostaglandin metabolism key enzymes, i.e. carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 (mPGES-1) and microsomal prostaglandin E synthase-2 (mPGES-2), cytosolic prostaglandin E synthase (cPGES), the aldoketoreductase AKR1C1 and the prostaglandin F synthase AKR1C3. Quantitative RT-PCR on plucked hair follicles revealed some sex-related differences, mPGES-2 and AKR1C3 expression levels being higher in women. Cell and hair follicle compartment specificity was investigated using Western blot, PGE(2) and PGF(2alpha) ELISA assays and immunohistochemistry. Most of the hair cell types were endowed with prostaglandin metabolism machinery and were thus able to produce PGE(2) and/or PGF(2alpha). The epithelial part of the hair bulb was identified by immunohistology and EIA assays as the main source of prostaglandin synthesis and interconversion. All these observations support the concept that prostaglandins might be involved in hair growth and differentiation control.

I dont know which is upstream and which downstream. If PGD2 is as important as the Cotsarelis patent seems to indicate I suspect it is still upstream of the WNT/BMP pathways.
hh

 

[harold]

J Invest Dermatol. 2007 Nov 15 [Epub ahead of print]Click here to read Links
Identification of Histamine Receptors and Reduction of Squalene Levels by an Antihistamine in Sebocytes.
Pelle E, McCarthy J, Seltmann H, Huang X, Mammone T, Zouboulis CC, Maes D.

[1] 1Estee Lauder Research Laboratories, Melville, New York, USA [2] 2Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, New York, USA.

Overproduction of sebum, especially during adolescence, is causally related to acne and inflammation. As a way to reduce sebum and its interference with the process of follicular keratinization in the pilosebaceous unit leading to inflammatory acne lesions, antihistamines were investigated for their effect on sebocytes, the major cell of the sebaceous gland responsible for producing sebum. Reverse transcriptase-PCR analysis and immunofluorescence of an immortalized sebocyte cell line (SZ95) revealed the presence of histamine-1 receptor (H-1 receptor), and thus indicated that histamines and, conversely, antihistamines could potentially modulate sebocyte function directly. When sebocytes were incubated with an H-1 receptor antagonist, diphenhydramine (DPH), at non-cytotoxic doses, a significant decrease in squalene levels, a biomarker for sebum, was observed. As determined by high-performance liquid chromatography, untreated sebocytes contained 6.27 (+/-0.73) nmol squalene per 10(6) cells, whereas for DPH-treated cells, the levels were 2.37 (+/-0.24) and 2.03 (+/-0.97) nmol squalene per 10(6) cells at 50 and 100 muM, respectively. These data were further substantiated by the identification of histamine receptors in human sebaceous glands. In conclusion, our data show the presence of histamine receptors on sebocytes, demonstrate how an antagonist to these receptors modulated cellular function, and may indicate a new paradigm for acne therapy involving an H-1 receptor-mediated pathway.Journal of Investigative Dermatology advance online publication, 15 November 2007; doi:10.1038/sj.jid.5701160.

 

[michael barry]

very interesting stuff Harold.................PGD2 receptors directly on the hair follicles themselves.

 

[harold]

Yeah. One thiong about mast cells is that they have a type of PGD2 synthase (hemapotentic) that is different to the lipocalin type that Cotsarelis says is upregulated in male pattern baldness. So he doesnt think the source of extra PGD2 is mast cell related despite their increased presence in balding scalp. And despite the fact that mast cell degranulation leads to stress induced hair loss. Mast cell degranulation that is inhibited by minoxidil. Its tough to find specific inhibitors of that type of synthase - about the only stuff there is are selenium compounds.
hh

 

[purecontrol]

Pine bark extract seems to inhibit COX-1 and COX-2 according to this:

Original article
Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol)

Angelika Schäfera, Zuzana Chovanováb, Jana Muchováb, Katarína Sumegováb, Anna Liptákováb, Zde?ka ?ura?kováb and Petra Höggera, ,
aInstitut für Pharmazie und Lebensmittelchemie, Bayerische Julius-Maximilians-Universität, Am Hubland, 97074 Würzburg, Germany
bDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, Comenius University, Bratislava, Slovakia
Received 18 July 2005; accepted 5 August 2005. Available online 26 October 2005.



Abstract
There is evidence from several studies that supplementation with French maritime pine bark extract (Pycnogenol®) improves inflammatory symptoms in vivo. However, the molecular pharmacological basis for the observed effects has not been fully uncovered yet. Direct inhibitory effects of plant extracts or components upon cyclooxygenase (COX) activity have been repeatedly reported, but the question remained whether sufficiently high in vivo concentrations of bioactive compounds could be achieved in humans. The purpose of the present study was to determine a possible inhibition of the enzymatic activity of COX-1 and COX-2 by serum samples of human volunteers after intake of French maritime pine bark extract. This methodology considered that the serum samples would contain any bioavailable active principle. Therefore, we obtained blood samples before and after 5 days administration of 200 mg Pycnogenol to five healthy humans. The plasma moderately inhibited both COX-1 and COX-2 activities ex vivo. In a second approach, 10 volunteers received a single dose of 300 mg Pycnogenol. Only 30 min after ingestion of the pine bark extract the serum samples induced a statistically significant increase in the inhibition of both COX-1 (P < 0.02) and COX-2 (P < 0.002). This suggests a strikingly rapid bioavailability of bioeffective compounds after oral intake of the extract. Thus, we provide evidence that Pycnogenol exerts effects by inhibition of eicosanoid generating enzymes which is consistent with reported clinical anti-inflammatory and platelet inhibitory effects in vivo. The next challenge is to identify the active principle(s) that are rapidly bioavailable in human plasma.

Keywords: Cyclooxygenase; Human plasma; Pine bark extract

Ive found info indicating that rosemary and thyme inhibit COX-2, but not COX 1. Honey seems to have a suppressive effect on various prostaglandins as does thyme.



I dont know what they difference between maritime pine bark and cedarwood oil would be though....................



Aspirin was said to be more effective against COX-1 than COX-2 in what I was able to look up.

resveratrol, curcumin, ginger, bromalin, fish oil, quercitin

Rosemary can be a problem as it will raise blood pressure which creates a whole set of new problems.


One of the big pictures here that a lot of people don't get is that high insulin levels and poor glucose disposel causes the majority of inflamation and oxidation. That is why cinnamon is so effective against oxidation and inflamation, it brings glucose and insulin levels down, so does NAC etc

A change in diet and habits is needed

 

[harold]

From the PGD2 patent

EXAMPLE 7: HAIRED SCALP CONTAINS A POPULATION OF CD200H1GH ALPHA-6 30 INTEGRINH1GH CELLS THAT ARE LACKING IN BALD SCALP

[ 00520 ] Haired and bald scalp samples from 5 Androgenetic Alopecia patients were subjected to staining and FACS for alpha-6 integrin and CD200. In each case, haired and bald samples from the same patient were compared. A population of alpha-6 integrinhlgh CD200hlgh cells was found to be present in the haired but not bald samples (Figure 9). These findings demonstrate the existence of a stem cell population that can be transplanted to generate new HF and treat baldness. Further, these findings demonstrate that administration of CD200 and analogues thereof can be used to treat baldness.

I kinda ignored this for a long while cos I wasnt sre what it meant exactly but the below abstracts should help shed some light.

J Invest Dermatol. 2004 Nov;123(5):880-7.Click here to read Links
Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance?
Rosenblum MD, Olasz EB, Yancey KB, Woodliff JE, Lazarova Z, Gerber KA, Truitt RL.

Department of Pediatrics, Medical College of Wisonsin, Milwaukee, Wisconsin, USA.

CD200 (OX-2) is a transmembrane glycoprotein that transmits an immunoregulatory signal through the CD200 receptor (CD200R) to attenuate inflammatory reactions and promote immune tolerance. CD200 expression in the skin has not been described previously. We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive. CD200 expression was accentuated in keratinocytes comprising the outer root sheath of the murine hair follicle (HF). When syngeneic skin grafts were exchanged between gender-matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant perifollicular and intrafollicular inflammation was observed, eventually leading to the destruction of virtually all HF (alopecia) without significant loss of the CD200-negative grafts. Minimal and transient inflammation was observed in WT grafts, which persisted long term with hair. There was a 2-fold increase in graft-infiltrating T cells in CD200-deficient skin at 14 d. Alopecia and skin lesions were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT mice previously grafted with CD200-negative skin, but not from mice grafted with WT skin. Collectively, these results suggest that the expression of CD200 in follicular epithelium attenuates inflammatory reactions and may play a role in maintaining immune tolerance to HF-associated autoantigens.

J Dermatol Sci. 2006 Mar;41(3):165-74. Epub 2006 Jan 4.Click here to read Links
CD200, a "no danger" signal for hair follicles.
Rosenblum MD, Yancey KB, Olasz EB, Truitt RL.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226-4801, USA.

The "danger model" of immune recognition proposes that the immune system does not differentiate between self and non-self when deciding whether to mount a response, but instead, discerns between that which is dangerous or not dangerous to the host. Danger signals incite inflammatory responses, which can lead to the induction of tissue-specific autoimmunity. Immunosuppressive molecules expressed on selected cells have the potential to regulate tissue-specific inflammation, and consequently, autoimmunity. Recent studies have revealed that CD200, a potent immunoregulatory protein, is expressed on Langerhans cells (LCs) and keratinocytes (KCs) in mouse epidermis. CD200 expression is concentrated on KCs comprising the outer root sheath (ORS) of murine hair follicles (HF). Skin deficient in CD200 is highly susceptible to HF-associated inflammation and immune-mediated alopecia. In this concept review, the results of recent studies on CD200 and its inhibitory receptor, CD200R, are summarized and integrated to yield a model whereby CD200-CD200R interaction attenuates perifollicular inflammation, prevents HF-specific autoimmunity and may protect epidermal stem cells from autoimmune destruction. Further elucidation of the CD200-CD200R signaling pathway in cutaneous tissues may advance understanding of how immune homeostasis is established and maintained in the skin.

I also just worked out how to save the 255 page pdf of the patent which will be handy for looking at graphs and figures. Cant believe I didnt figure out how until now...
hh

 

[michael barry]

Harold,

That is extremely interesting. A real difference in balding hairs vs. non-balding hairs. A "find" to be sure.





Pure Control,

When I mentioned the Rosemary, I was suggesting a topical application of that particular substance. Its an "essential oil" that is in alot of old baldness concoctions along with sage, thyme, and cedarwood. You are right about internal inflammation. It ages us in so many ways. Im as guilty as anyone about drinking cokes and liking pasta..................Ive always wondered what the results would be if scientist could find two twins and and raise one on the normal western diet, and have the other eat lean meats, fruits, veggies, and fruit juices. How different would they look at 35, all other things being relatively equal. It would be quite interesting. I'd bet the healthy eater would look five years younger and have a bit more thickness up there on his noggin' myself.

 

[harold]

Harold,

That is extremely interesting. A real difference in balding hairs vs. non-balding hairs. A "find" to be sure.

I guesss its more evidence for the immune/inflammation role in male pattern baldness. Was reading some old papers by Kligman today where he was describing the mast cells and macrophages and so forth that gathered around the miniaturising hair follicle "streamers". One paper by Paus looking at the effect of mast cell degranulation on anagen/telogen transitions found that mice in the control group grew hair around the site of injection for the VEHICLE (NaCl). More early evidence for needling? It was downplayed by the authors who tried to explain it away.
hh

 

[iostream71]

so where are they as far as trials go? it seems like everything they use is already approved and shouldn't take years

 

[bornthisway]

Is this patent relevant? http://www.patentstorm.us/patents/57537 ... ption.html

Many fungicidal compositions are known in the art. But commonly their effectiveness in addressing fungal and/or bacterial infections in humans is quite limited. It appears in most instances that the human body's own immune system actually defends the infected area of the body, thereby reducing the amount of the antibacterial and/or fungicidal substances which pass through the barrier of the immune system and reach the infection. By reducing the free transfer of the disease from the affected area to the healthy areas, the body prevents or reduces the spread of the disease. But this function has the drawback of impeding the transfer of antibiotics and fungicides to affected areas where they may perform their function of killing the infection.

The present inventor has found that by suppressing the immune system, a freer transfer of antibiotics and/or fungicides can be achieved; the more the immune system is suppressed, the more effective the antibiotics and/or fungicides become.

Also, a number of compositions are known which are asserted to promote hair growth in humans. However, such hair growth compositions seem to work by stimulating blood flow and require constant application, suggesting that whatever hair growth results is forced. In other words, these compositions increase blood flow providing more nourishment for hair growth than occurred before the application of the compositions. Further, such compositions offer only limited success and only with a limited class of users.

Accordingly, an object of the present invention is to provide a composition which may be applied to human skin where it will successfully kill bacterial and/or fungal infections, without causing adverse side effects.

A further object of the present invention is to provide a composition which may be applied to human skin, particularly the head, where it will promote the growth of hair.

More details at above link.

 

[Fabio_08]

Wow you people are really smart!

Any chance it can be simplified for me and the others that are completely lost?

Couple of questions i think that everyone wants to no:

a) How does it work?
b) How is it applied
c) Will it regrow a full ehad of hair, or will it be the same as like Rogaine, eg- Some poeple respond to it, others grow some peach fuzz, etc
d) Does it look to be the cure for male pattern baldness?
e) Whats the suggested time before it is used in the public?
f) Does it look like this will be all that is needed to stop male pattern baldness? Or is it simply an improvment on propecia and rogaine with a long way to go before male pattern baldness is concquered?

Thanks in advance

 

[imtooyoungtobald]

Most important question is, will it be DHT resistant? Unless I'm reading it incorrectly, it sounds like they are just regrowing the same type of hair folicles which will in turn suffer the same fate.

 

[symbolx]

The new follicles should be DHT resistant since they are going to gather them from the back of the head where the hairs tend to be resistant. I guess that is not a definite guarantee but it is better than nothing.

 

[Emuler]

The new follicles should be DHT resistant since they are going to gather them from the back of the head where the hairs tend to be resistant. I guess that is not a definite guarantee but it is better than nothing.

I wish it read "The new follicles will be DHT resistant, then only then will it be considered a cure.

 

[sphlanx2006]

Taking into account that the balding process begins a couple of years at least before it is even noticeable, and then it takes another couple of years before your hair is "ugly" that means that most hair have around 4 years of life time before they finally die.

So someone comes up and he says i will give you a full head of hair, all you have to do is come to me once every 4 years and you will have a full head of hair. It is technically not a cure, but there will be a long time until you see a balding guy on the street if this thing WORKS and does not cost as much as a visit to the international space station.

 

[imtooyoungtobald]

How much would something like this cost? If it cost several thousand dollars who the heck could afford that every 4 years? Especially someone like me in their early 20s.

 

[scalpt]

These follicles form differently than the follicles that the scalp forms in the womb.
According to Follica, in embryos the follicles are produced by follicle stem cells. In Follica's research so far, the new follicles are formed by epidermal cells, which don't normally make hair. This is paraphrased from the link below:

http://www.sciencefriday.com/newsbriefs/read/117

I also posted this in another thread.

 

[Fabio_08]

Wow you people are really smart!

Any chance it can be simplified for me and the others that are completely lost?

Couple of questions i think that everyone wants to no:

a) How does it work?
b) How is it applied
c) Will it regrow a full ehad of hair, or will it be the same as like Rogaine, eg- Some poeple respond to it, others grow some peach fuzz, etc
d) Does it look to be the cure for male pattern baldness?
e) Whats the suggested time before it is used in the public?
f) Does it look like this will be all that is needed to stop male pattern baldness? Or is it simply an improvment on propecia and rogaine with a long way to go before male pattern baldness is concquered?

Thanks in advance

 

[first]

I apologize for asking such an obvious question. But if the drugs are visibly through the patent, and the drugs are commonly used and FDA approved. Why can't we do this ourselves right now? While we may not be able to do the proper scaring, shouldn't we be able to do it at least to a lesser degree?

 

[elguapo]

They don't know *for sure* that it will work on humans. I think they will be testing it this year, and will should hear how it went at the end of this year or early next year. We just need to be patient and let the trial/testing take its course.