The problem with traditional research

[S Foote.]

The problem with male pattern baldness research.Quantum cat asked me to to sum up my position in previous debates with Bryan Shelton on the forums. I think that given the current dead end we seem to be at in respect of effective treatments for male pattern baldness, i should elaborate here on my objections to the traditional research approach.I think there are two basic problems with traditional research into male pattern baldness, the first being it is just that! There has been no attempt to consider the wider issues, in the context of a proper scientific theory of mammalian hair growth. A scientific theory has to answer all the relevant questions about the evolution and function of hair, not just look at androgen related changes. Once you do this, i suggest the evidence we have in male pattern baldness makes a lot more sense.Secondly, as in all areas of biological research we have the traditional obsession with the genetics. It is only recently that mainstream science has come to realise that this reductionist approach is too restricting, and cannot provide all the answers. There is a long overdue move now towards the systems biology approach, that considers how the structures created by the genetics fit together and interact.As a systems engineer with 45 years experience of building and trouble shooting mechanical/hydraulic systems, this is how i see the issue in male pattern baldness.However the genetics combine to produce biological structures, these structures cannot get around the basic laws of physics. Two things cannot occupy the same space at the same time, and this is a law particularly rellevant to hair follicles. Hair growth is directly related to the size of the hair follicle. Hair follicles are hollow pockets surrounded by dermal tissue. It is not physicaly possible for a hollow pocket to change its size without a significant influence of the surrounding tissue. I have recently published a paper that considers this relationship in terms of evolution. http://www.open-science-repository....mammals-implications-in-human-physiology.htmlThis includes how this relates to the evidence in male pattern baldness, but does not elaborate on the implications for future treatments. I do think this points the way forward for more effective and safe future treatment of male pattern baldness.Importantly, this evolved hair growth control explains why the current research is going nowhere. This is because the issues of genetic changes in follicles and scalp are downstream, and not relevant to the actual cause of male pattern baldness. The follicles are changing size in response to the conditions in the surrounding tissue, as they evolved to do. Trying to change the natural response of follicles as in the HM type research, is proving to be very dificult, because it does not deal with the basic problem. We need to deal with the basic problem and not its downstream effects, if we are to move forward here.

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Sorry, got a problem with forming paragraphs and editing for some reason?

 

[isishearmyplea]

so you are saying research shd be more focused upon what happens around the follicle rather than in it??

 

[Quantum Cat]

thanks for summarising your views. I'm skeptical of a lot of the wild and wacky theories that circulate round these forums, but I've always thought that there are still pieces of the male pattern baldness puzzle missing.

 

[IDW2BB]

Thanks for the thought provoking post S Foote! Are you implying that we can regrow our hair in the balding areas by eliminating tissue pressure from either fluid or fibrosis, thus eliminating contact inhibition? Cots writes that the hair is still there it is just lacking CD34 and CD200 rich progenitors. Garza just agreed with you over on Hairsite that the immunodeficient mouse would allow human Androgenetic Alopecia hair to recover. Bryan disputed that study heavily. It now seems to be a given that it indeed does refute a "direct effect" by androgens. Thanks for your thoughts!

 

[S Foote.]

so you are saying research shd be more focused upon what happens around the follicle rather than in it??

Yes exactly, If we go back to the very early hair transplantation studies, the authors concluded that the effect was either because of a factor within the follicles, or very close around them. But ever since, the research emphasise has been on the internal option. Once you start to consider the external possibilities, things start to fall into place.

 

[Armando Jose]

follicle or pilosebaceous unit?
Withoutt sebaceous gland dont exit hair, it is so?

 

[S Foote.]

Thanks for the thought provoking post S Foote! Are you implying that we can regrow our hair in the balding areas by eliminating tissue pressure from either fluid or fibrosis, thus eliminating contact inhibition? Cots writes that the hair is still there it is just lacking CD34 and CD200 rich progenitors. Garza just agreed with you over on Hairsite that the immunodeficient mouse would allow human Androgenetic Alopecia hair to recover. Bryan disputed that study heavily. It now seems to be a given that it indeed does refute a "direct effect" by androgens. Thanks for your thoughts!

First, I am having problems posting including not being able to form paragraphs. will work at this later. I think that immune-mice study is very important, and people should realise its consequences. As I see the evidence, we are suffering from androgen induced scalp lymphedema, and we have to treat it as such. I think if we can do this. the follicles will sort themselves out. I suggest anyone interested should look at the sites about lymphedema. The similarities with the bald scalp are striking. One of the latest treatments that is proving useful in lymphedema is low level laser treatment. There are things that people can do to help the situation that cost nothing. I need to sort out my posting issues then I will go into these in more detail.

 

[Armando Jose]

Hi Stephen
Have you tried advancing the explanation of the different incidence between men and women?

reading your recent publication in OpenScience I have been astonished to read
"modern human hair growth has no real purpose and is a side effect of something else that does"

I am not agree, but why Modern, not ancient?

- See more at: http://www.open-science-repository....il=arm2003_7@hotmail.com#sthash.xcLFAstO.dpuf


Mr. Foote Honestly, I love your ideas, I like that people seek to solve puzzles, like myself,
I agree with your ideas
"Two things can not occupy the same space at the same time, and this is a law Particularly rellevant to hair follicles. Hair growth is Directly related to the size of the hair follicle. Hair follicles are hollow pockets surrounded by dermal tissue. It is not possible for a hollow physicaly pocket to change its size without a significant Influence of the surrounding tissue"


But why not include fat hair, sebum as an integral part, and very important CHANGING, of the surrounding tissue?


My ideas are complementary to your own,

 

[S Foote.]

Hi Stephen
Have you tried advancing the explanation of the different incidence between men and women?

reading your recent publication in OpenScience I have been astonished to read
"modern human hair growth has no real purpose and is a side effect of something else that does"

I am not agree, but why Modern, not ancient?

Would you like to elaborate then on your opinion of the purpose of modern human hair patterns? If it wasn't for the fact we had the intelligence to cut our long scalp hair or tie it back, we would have had a big problem of survival in our evolution. Developments in evolution should give an advantage. As I argue in my paper this excess growth only makes sense if it is linked to our evolving intelligence, and this side effect didn't matter as we could deal with it.

With respect Armando, I think your sebum idea falls into the same trap as traditional reductionist male pattern baldness research. You are only looking at a small part of the picture. An valid theory has to cover all the bases of its subject matter. In this case we are dealing with mammalian hair growth, related physiology.

Can your theory show a link with hair growth and temperature control, as in the original function of hair as an insulator?

Can it explain the other recognised changes in the bald scalp, like the immunology and sweating changes?

Can it explain why DHT related increases in hair growth have an obvious relationship with local concentrations of lymphatic vessels?

How about the isolated islands of the increased growth that are eyebrows?

I respect you for your original thinking Armando, but you need to address these questions.

Over the weekend I will post in more detail about how I see the mechanism I propose, in future treatments of male pattern baldness.

I should also make it clear that I am not against hair transplantation in the right context, and I think this mechanism can aid in refining transplantation where its applicable. But in their own interest I think the transplantation industry needs to address the issues raised by this mechanism.

If they think they can refute this in a proper scientific way, they should go on the record and do so now. As it stands transplants are being sold on the basis of being genetically different. If this proves to be wrong in the future, they could be left open to possible legal action from anyone with a failed previous procedure.

 

[Armando Jose]

I have not much idea what the purpose of hair in mammals, but I have the impression that our existence would be seriously compromised if there were no pilosebaceous units.
What I have clear that we have become the naked ape, but not a bald monkey. We miniaturized body hair but we have enlarged hair on the head. All hair is not the same, the eyebrows, eyelashes are special and only partly be compared with body hair or scalp.
My theory, as you know, could explain not only the pattern of hair loss, but the difference in incidence between the sexes. For me, the hair on the scalp is the same in men and women. And I have in mind all the processes involved in alopecia, hormones, fibrosis, immunology, blood flow, etc.. What I want to explain are the first processes that occur.
I will carefully read your ideas. Do you think that the DHT is necessary to grow healthy hair, not just the body, but the head?

 

[S Foote.]

I have not much idea what the purpose of hair in mammals, but I have the impression that our existence would be seriously compromised if there were no pilosebaceous units.
What I have clear that we have become the naked ape, but not a bald monkey. We miniaturized body hair but we have enlarged hair on the head. All hair is not the same, the eyebrows, eyelashes are special and only partly be compared with body hair or scalp.
My theory, as you know, could explain not only the pattern of hair loss, but the difference in incidence between the sexes. For me, the hair on the scalp is the same in men and women. And I have in mind all the processes involved in alopecia, hormones, fibrosis, immunology, blood flow, etc.. What I want to explain are the first processes that occur.
I will carefully read your ideas. Do you think that the DHT is necessary to grow healthy hair, not just the body, but the head?

I think you need to go into a lot more detail in support of your idea's Armando. I don't think DHT is necessary to grow hair at all, but it obviously has a major effect on changes in hair growth.

I am posting below about the details of my proposal in male pattern baldness, and the treatment strategy this suggests.

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This is an elaboration in simple terms, upon how this proposed hair adjustment mechanism fits in male pattern baldness. In my following post i will offer my thoughts on current treatments, and the possibilities this mechanism offers for better treatments of male pattern baldness. The proposed mechanism is described here.

http://www.open-science-repository.com/an-evolved-hair-growth-mechanism-in-mammals-implications-in-human-physiology.html

The basic principle is that follicle size is dependent upon the resistence of the surrounding tissue to follicle enlargement, this resistence being modified by changes in local tissue fluid pressures. The recognised molecullar changes in follicles being downstream from this causal action, and not directly rellevant.

When this principle is applied to human androgen related hair growth/loss, it answers the questions according to the scientific requirement of parsimony. Quote "entities should not be multiplied unnecessarily". In this case, an initial action of DHT to increase lymphatic pumping, explains all the downstream effects upon hair growth and related factors. The logic of such an action of androgens on the lymphatics, and how this also explains the associated scalp conditions in male pattern baldness is described in my paper.

Lymphatic vessels drain fluid from tissues by regular contractions. Because the vessels have many one way valves, these contractions move fluid from the tissues to eventualy drain back into the blood circulation. Because of this lymph pumping action, if you wanted to introduce a substance that increased the pumping, this would have to be introduced largely at the extremities of the vessels to balance out over the length of the system.

Any inbalance increasing pumping downstream, would increasingly shut the valves against the flow from the extremities, actually reducing flow in that area. Such opposite effects are common in fluid systems, and this fits with the opposite effect of DHT leading to male pattern baldness in some individuals.

DHT is largely produced near the extremities of lymph vessels, in the dermal tissue. We know DHT is produced from testosterone in hair follicles and sebaceous glands, hair follicles being the largest producer. It stands to reason that there are more DHT producing cells in large hair follicles like scalp follicles. This is how i see the events leading to male pattern baldness.

The rising levels of DHT at puberty increases lymphatic drainage, and increased numbers of these vessels close to hair follicles increases growth through this mechanism. A lot of local DHT is produced by the large scalp follicles, and initially scalp hair growth can increase further. But the amount of the lymph vessels increases lower down, the male pattern baldness area itself is at the extremity of the lymphatics. The increasing DHT feeding into the lower vessels increases drainage here leading to beard growth. The larger follicles of beard growth then add more DHT to the increased lymph vessel pumping lower down. The male pattern baldness area starts to suffer from the back pressure effect, and drainage here reduces increasing risk of lymphedema.

This reduced scalp drainage may or may not lead to male pattern baldness by this mechanism, depending on another related factor. I think the clue to this other factor, is in the recent confirmation that male pattern baldness sufferers are more likely to develope coronary heart disease in later life. The common link would be increased blood pressure feed to the scalp, and perhaps other blood circulation issues.

The fluid balance in tissue depends on a feed and return equation. Reduced lymphatic drainage may not be enough to increase local tissue fluid levels, if the fluid feed is not excessive. The higher the feed pressure, the more likely reduced drainage will lead to increased tissue fluid levels and pressures. I think this is why DHT levels themselves do not equate directly to male pattern baldness in the individual, it's the fluid feed pressure that affects risk of male pattern baldness for a given level of DHT.

How this mechanism of male pattern baldness fits with known and potential treatments, will follow in my next post.

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Following on from my post above, i will discuss traditional treatments for male pattern baldness in the light of this mechanism, and how we might improve the situation.

According to the proposed mechanism, male pattern baldness is caused by DHT induced lymphedema. The recognised effects of lympedema on tissue matches the known conditions in male pattern baldness, as refered to in my paper. The normal obvious swelling of edema does not develope in the scalp, because this is a relatively thin curving tissue that naturaly resists tissue expansion. What this means is a high pressure relative to the degree of tissue expansion, and this is reflected in the recognised scalp tightness in male pattern baldness.

I think the higher scalp fluid level in male pattern baldness also explains how we have been mislead in the diagnoses of the pathway involved. We know that there are higher levels of DHT in the bald area compared to the hairy sides. We also know that every now and then, it is discovered there are also higher levels of other substances in the bald scalp. The latest here being PGD2.

Increased fluid levels in a tissue, will also mean increased levels of anything being transported in that fluid. That dosen't mean these substances are causal in male pattern baldness. Logicaly, the miniaturised follicles in male pattern baldness just cannot produce more DHT than large follicles in hairy areas. I think this is why using topical 5ARI's in the male pattern baldness area does very little, they are being used in the wrong place. The systematic 5ARI's like Propecia work better for this reason, but then you have the side effects.

This mechanism also explains why we get contrary advice on when to start treatments for male pattern baldness. They say with most treatments the sooner the better, but in transplantation the advice is often wait as long as you can for the best results. This fits in very well with this mechanism.

If you are trying to re-enlarge the shrinking follicles, you need to act quickly before the surrounding tissue toughens due to developing fibrosis, also known to be caused by edema. This explains why the longer male pattern baldness goes on, the harder it is to reverse. In transplantation you want fibrosis formation in the scalp. Because this will help stabilise the tissue against further expansion, and form a better protective scaffold around the transplanted follicles.

As i refer to in my paper the common factor in treatments shown to have 'some' effect, is a reduction of fluid levels in the male pattern baldness area. I should add low level lasers to this list, as these have also been demonstrated to reduce fluid levels in lymphedema.

In my opinion, this mechanism also explains why the current research into the HM type procedures, is going nowhere. These are not targeting the problem, in that hair follicles have evolved to adjust their size according to the resistence of the surrounding tissue. Trying to go against the normal tissue growth controls creates a paradox, in that the more effective the procedure, the more likely it will not be licensed for safety reasons. There may be a case for a technology that grows whole large follicles outside of the body. These then being used in conventional transplantation. But i think there is potential for better, safer, and cheaper alternative treatments than this in the future.

They say that the myths and 'old wives tales' about something, often have a grain of truth in them? There has always been the 'poor blood supply to the follicles' notion about male pattern baldness. We get idea's to increase follicle blood supply, hanging upside down, scalp exersises, massage, various electrical devices etc. We know it is not an issue of blood supply to the follicles because of transplantation. However, i think what these things can contribute to is better circulation in the scalp tissue, helping to reduce the fluid levels.

In particular i think a good massage method is very worthwhile. This can help to move excess fluid, and break down fibrosis. Avoid any topical that causes irritation and further inflamation. Use cool water when washing the area, and generally treat the scalp as an edemous tissue.

According to this mechanism we need to target two things to treat male pattern baldness effectively. The DHT induced scalp drainage restriction, and the high pressure scalp blood feed.

The real target for topical 5ARI's is not the male pattern baldness area, but the hairy area's of the scalp and face. This is where the excess DHT is produced that triggers the process of male pattern baldness. I think this is why Nizoral shampoo has been supprising in its effect on male pattern baldness. It is used on the whole scalp, and in effect the face/beard area. It should be possible to produce better 5ARI effective products for this purpose. This better targeting of topicals could make it possible to avoid systematic 5ARI's and their side effects altogether. Topicals for the male pattern baldness area, should be aimed at reducing the inflammation/fibrosis element that hinders the reversal of male pattern baldness, and may help to reverse longer term male pattern baldness.

There is already a surgical procedure that dramaticaly reduces excess blood supply to the scalp. This has been used to good effect in seborrheic alopecia. http://www.ncbi.nlm.nih.gov/pubmed/157397 Note the statement that "the condition of the hair follicle is strikingly improved". It may be argued that this is because of other factors, but such a follicle response to reduced blood feed in the scalp, is in line with the mechanism described here.

This would of course need to be further researched and approved for use in male pattern baldness. But this kind of procedure along with the 5ARI method above, would be the future of more effective male pattern baldness treatment according to the evidence for this proposed mechanism.

 

[IDW2BB]

I am posting below about the details of my proposal in male pattern baldness, and the treatment strategy this suggests.



They say that the myths and 'old wives tales' about something, often have a grain of truth in them? There has always been the 'poor blood supply to the follicles' notion about male pattern baldness. We get idea's to increase follicle blood supply, hanging upside down, scalp exersises, massage, various electrical devices etc. We know it is not an issue of blood supply to the follicles because of transplantation. However, i think what these things can contribute to is better circulation in the scalp tissue, helping to reduce the fluid levels.

In particular i think a good massage method is very worthwhile. This can help to move excess fluid, and break down fibrosis. Avoid any topical that causes irritation and further inflamation. Use cool water when washing the area, and generally treat the scalp as an edemous tissue.

According to this mechanism we need to target two things to treat male pattern baldness effectively. The DHT induced scalp drainage restriction, and the high pressure scalp blood feed.

The real target for topical 5ARI's is not the male pattern baldness area, but the hairy area's of the scalp and face. This is where the excess DHT is produced that triggers the process of male pattern baldness . I think this is why Nizoral shampoo has been supprising in its effect on male pattern baldness. It is used on the whole scalp, and in effect the face/beard area. It should be possible to produce better 5ARI effective products for this purpose. This better targeting of topicals could make it possible to avoid systematic 5ARI's and their side effects altogether. Topicals for the male pattern baldness area, should be aimed at reducing the inflammation/fibrosis element that hinders the reversal of male pattern baldness, and may help to reverse longer term male pattern baldness.

There is already a surgical procedure that dramaticaly reduces excess blood supply to the scalp. This has been used to good effect in seborrheic alopecia. http://www.ncbi.nlm.nih.gov/pubmed/157397 Note the statement that "the condition of the hair follicle is strikingly improved". It may be argued that this is because of other factors, but such a follicle response to reduced blood feed in the scalp, is in line with the mechanism described here.

This would of course need to be further researched and approved for use in male pattern baldness. But this kind of procedure along with the 5ARI method above, would be the future of more effective male pattern baldness treatment according to the evidence for this proposed mechanism.

2 immediate questions S Foote. I don't know how to create paragraphs either so please share how to do this or how I can find out how to do this. The other question I have is, I'm curious as to your thoughts on the use of cb-03-01 for facial acne as a way of helping male pattern baldness? As an androgen blocker, would it not be beneficial based on your mechanism? If so, why would Cosmo have 2 different clinical trials going on regarding acne and Androgenetic Alopecia? Are you familiar with the research regarding it?

 

[S Foote.]

2 immediate questions S Foote. I don't know how to create paragraphs either so please share how to do this or how I can find out how to do this. The other question I have is, I'm curious as to your thoughts on the use of cb-03-01 for facial acne as a way of helping male pattern baldness? As an androgen blocker, would it not be beneficial based on your mechanism? If so, why would Cosmo have 2 different clinical trials going on regarding acne and Androgenetic Alopecia? Are you familiar with the research regarding it?

I changed the settings on my account to one that my browser could handle, been OK since then.

I am not familiar with the research you mention, could you provide a link? The anti androgen would have to be a 5ARI type to help male pattern baldness in my opinion.

 

[Armando Jose]

I am with you Mr Foote, 5AR1 is a clue in male pattern baldness

 

[IDW2BB]

I changed the settings on my account to one that my browser could handle, been OK since then.

I am not familiar with the research you mention, could you provide a link? The anti androgen would have to be a 5ARI type to help male pattern baldness in my opinion.

Thanks for the tip regarding posting!

Regarding CB-03-01, there is a ton of info. out there on it (made by Cosmo Pharmaceuticals) and after rereading your post and reading Armando's post, I think I have figured out my question.

The main thing to know about cb-03-01 in regards to my question, is that it is an androgen blocker. It actually blocks the already formed DHT from binding to the androgen receptor. This action is different from something like finasteride that actually inhibits the DHT from being formed in the first place. I did not read your post correctly when you wrote 5ARI. I took it to mean 5AR Inhibitor and not 5AR type 1. Armando's post clarified that for me.


Your idea is really very interesting. If I understand you correctly, we need to treat the donor area with 5ar type 1 inhibitors in order to help the recipient area. How much further down the head do we need to go in order to influence the hydraulics of the recipient? The face? The neck?

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I actually also want to apologize for using the terms "donor" and "recipient"! I know in your theory that those terms really don't exist, they are just "traditional" terms. Sorry again!

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Another question. Are the macaque subject to the same mechanism you describe? They are the focus of so many androgenetic alopecia studies.

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As an aside......didn't know if you were familiar with this recent research? It is free access.


http://www.ncbi.nlm.nih.gov/pubmed/24049723

Latanoprost Stimulates Ocular Lymphatic Drainage: An In Vivo Nanotracer Study.

Tam AL, Gupta N, Zhang Z, Yücel YH.


Source

Department of Ophthalmology and Vision Sciences, University of Toronto, Canada ; Keenan Research Centre at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.


Abstract


PURPOSE:

Ocular lymphatics have been recently shown to contribute to aqueous humor outflow. It is not yet known whether lymphatic outflow can be stimulated by pharmacological agents. Here we determine whether latanoprost, a prostaglandin F2 alpha analog commonly used to lower IOP to treat glaucoma, increases lymphatic drainage from the eye.

METHODS:

Lymphatic drainage in mice was assessed in vivo, in 11 latanoprost-treated and 11 control animals using hyperspectral imaging at multiple times following quantum dot (QD) injection into the eye. QD signal intensity was also measured in tissue sections using hyperspectral imaging.

RESULTS:

In the latanoprost-treated group, lymphatic drainage rate into the submandibular lymph node was increased compared with controls (1.23 ± 1.06 hours-1 vs. 0.30 ± 0.17 hours-1, mean ± SD, P < 0.02). Total QD signal intensity in the submandibular lymph node was greater in the latanoprost-treated group compared with controls (10.55 ± 1.12 vs. 9.48 ± 1.24, log scale, P < 0.05).

CONCLUSIONS:

This is the first evidence that latanoprost increases lymphatic drainage from the eye. The pharmacological manipulation of this newly identified lymphatic outflow pathway may be relevant to treatments aimed at lowering intraocular pressure in glaucoma.

TRANSLATIONAL RELEVANCE:

This is the first evidence that a prostaglandin drug widely prescribed for glaucoma, enhances lymphatic drainage from the eye. The pharmacological stimulation of this newly identified outflow pathway may be highly relevant to treatments aimed at lowering IOP to prevent blindness from glaucoma.

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Same with this recent research regarding acute inflammation, again, free access:


http://www.ncbi.nlm.nih.gov/pubmed/24086691

Lymphatic Vascular Response to Acute Inflammation.

Lachance PA, Hazen A, Sevick-Muraca EM.


Source

The Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, United States of America ; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.


Abstract


During acute inflammation, functioning lymphatics are believed to reduce edema and to provide a transiting route for immune cells, but the extent at which the dermal lymphatic remodeling impacts lymphatic transport or the factors regulating these changes remains unclear. Herein we quantify the increase in lymphatic endothelial cells (LECs) and examine the expression of pro-angiogenenic and lymphangiogenic factors during acute cutaneous hypersensitivity (CHS). We found that LECs actively proliferate during CHS but that this proliferation does not affect the lymphatic vessel density. Instead, lymphatic remodeling is accompanied by lymphatic vessel leakiness and lower ejection of lymph fluid, which is observed only in the proximal lymphatic vessel draining the inflamed area. LECs and the immune cells release growth factors and cytokines during inflammation, which impact the lymphatic microenvironment and function. We identified that FGF-2, PLGF-2, HGF, EGF, and KC/CXCL17 are differentially expressed within tissues during acute CHS, but both VEGF-C and VEGF-D levels do not significantly change. Our results indicate that VEGF-C and VEGF-D are not the only players and other factors may be responsible for the LECs proliferation and altered lymphatic function in acute CHS

and this excerpt from the same link:

The peripheral lymphatic system drains excess interstitial fluid back to the blood circulation, but also directs the transport of immune cells. Inflammation impacts lymph drainage and the volume of lymph propelled by lymphatic contraction [23,24]. Herein, we demonstrated that the contractility of the lymphatic vessel efferent to the inflamed area is not affected by the inflammation, but that the effectiveness of the lymphatic pumping is reduced as shown by the backflow observed at day 3 post-CHS and the decrease in ejected dye after contraction. Nitric oxide (NO) is known to affect the lymphatic function through changes in local concentration. Liao et al. proposed that iNOS produced by CD11b+ recruited to the inflamed area promote relaxation of the lymphatic vessels which render the contractions incapable of effectively propelling lymph [23]. Studies in isolated lymphatic vessels have shown that large changes in NO level inhibit contractility and that small change in local concentration influences contraction strength [28,29]. These local changes in NO productions are regulated by the shear forces in the vessel to induce the subsequent contractions [30]. In addition, Scallan et al. found that endothelial NO synthase deficient mice have a decrease in contraction amplitude. In our studies, we observed changes in the contraction amplitude or strength localized to the site of inflammation [28]. This effect was not systemic as indicated by the normal transport of the lymph on the counter lateral, untreated sides of treated animals. Our results support the conclusions of Liao et al. by showing that (i) lymph does not exit lymphangions as efficiently at day 3 post-CHS as compared to pre-treatment and that (ii) this effect is seen only in the inflamed side indicating a local, rather than systematic effect. From our data and the work of others, we can hypothesize that in CHS regulation of local levels of NO, vessel dilation, and shear force within the vessel could regulate the lymphatic flow.

 

[Armando Jose]

Interesting topics IDW2BB CB-03 Recipient and donor concepts, macaques, etc
latanoprost induce hairgrowth in eyelashes, maybe/probably throught lymphatic drainage, but eyelashe hair is different to scalp hair

 

[IDW2BB]

Interesting topics IDW2BB CB-03 Recipient and donor concepts, macaques, etc
latanoprost induce hairgrowth in eyelashes, maybe/probably throught lymphatic drainage, but eyelashe hair is different to scalp hair

You are right Armando, eyelash hair is different. Eyelash hair is not affected by androgens in the theory of Androgenetic Alopecia, yet latanoprost and its cousin bimatoprost have been shown to stimulate hair growth. Latanoprost has been used effectively on macaques as well but was looked at through the prism of the "direct theory" or Androgenetic Alopecia. S. Foote is giving us another perspective. I just wonder how closely those "traditional researchers" looked at the lymph system of the macaques? OR the sebaceous glands and sebum of the macaques for that matter!

One thing else I would like to know from S.Foote. Does the galea have any role in tissue pressure of the scalp? one of the unique features of the horseshoe area or the scalp is that it is basically a tendon beneath the skin as opposed to muscle. Does that substructure play any potential role in the tissue pressures S. Foote describes? If the cranial bones are the tectonic plates of the skull would the galea be considered rock/limestone? How does a layer of rock effect hydraulic pressure on the surface area?

 

[Armando Jose]

here is a picture of the galea
http://commons.wikimedia.org/wiki/File:Gray1196.png

http://en.wikipedia.org/wiki/Galea_aponeurotica

 

[S Foote.]

Thanks for the tip regarding posting!

Regarding CB-03-01, there is a ton of info. out there on it (made by Cosmo Pharmaceuticals) and after rereading your post and reading Armando's post, I think I have figured out my question.

The main thing to know about cb-03-01 in regards to my question, is that it is an androgen blocker. It actually blocks the already formed DHT from binding to the androgen receptor. This action is different from something like finasteride that actually inhibits the DHT from being formed in the first place. I did not read your post correctly when you wrote 5ARI. I took it to mean 5AR Inhibitor and not 5AR type 1. Armando's post clarified that for me.


Your idea is really very interesting. If I understand you correctly, we need to treat the donor area with 5ar type 1 inhibitors in order to help the recipient area. How much further down the head do we need to go in order to influence the hydraulics of the recipient? The face? The neck?

- - - Updated - - -

I actually also want to apologize for using the terms "donor" and "recipient"! I know in your theory that those terms really don't exist, they are just "traditional" terms. Sorry again!

- - - Updated - - -

Another question. Are the macaque subject to the same mechanism you describe? They are the focus of so many androgenetic alopecia studies.

- - - Updated - - -

As an aside......didn't know if you were familiar with this recent research? It is free access.


http://www.ncbi.nlm.nih.gov/pubmed/24049723



- - - Updated - - -

Same with this recent research regarding acute inflammation, again, free access:


http://www.ncbi.nlm.nih.gov/pubmed/24086691






and this excerpt from the same link:

Thanks for the lymphatic study info, I will go through these over the weekend. At first glance they seem to fit with my thinking on the immunology effect, that I consider very important in female susceptibility to autoimmune disease.

I think with a topical, it would be more effective to use a 5ARI type 2 inhibitor in this application. Any androgen blocker would according to this mechanism, need to reach the deeper lymphatic's of the face and neck. I think a topical would have a problem here. Reducing the amount of DHT produced in the surface structures by a topical would be easier I think, and a type 2 inhibitor alone should be enough as this produces two thirds of local DHT.

We just need to target the large follicles of the scalp and beard area.

Yes I think the principle is the same in Macaques, also related to the action of androgens. Remember the principles of this growth adjustment mechanism, are natural tissue resistance modified by changing local fluid pressures. This explains the differences In patterns and susceptibility in primates , and modern human hairlessness as I argue in my paper.

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You are right Armando, eyelash hair is different. Eyelash hair is not affected by androgens in the theory of Androgenetic Alopecia, yet latanoprost and its cousin bimatoprost have been shown to stimulate hair growth. Latanoprost has been used effectively on macaques as well but was looked at through the prism of the "direct theory" or Androgenetic Alopecia. S. Foote is giving us another perspective. I just wonder how closely those "traditional researchers" looked at the lymph system of the macaques? OR the sebaceous glands and sebum of the macaques for that matter!

One thing else I would like to know from S.Foote. Does the galea have any role in tissue pressure of the scalp? one of the unique features of the horseshoe area or the scalp is that it is basically a tendon beneath the skin as opposed to muscle. Does that substructure play any potential role in the tissue pressures S. Foote describes? If the cranial bones are the tectonic plates of the skull would the galea be considered rock/limestone? How does a layer of rock effect hydraulic pressure on the surface area?

Yes I do think the Galea does have an effect for the following reason.

Any increase in local tissue fluid pressure, has a natural dispersal to surrounding lower pressure areas This is the basic physics of pressure differences. The Galea is a membrane that hinders this equalisation of pressure from the male pattern baldness area. I see it as another factor that is not causal, but adds to the retention of excess fluid in male pattern baldness.

Armando, you say eyelash hair is different, in what way? In this mechanism, what is important is not the make up of the hair fibre, but the follicle structure. If its a pocket and the production area protrudes into its base, the physics of this mechanism still apply.

Talking about lymphatic layouts, I would love to see the surface lymphatic layout of lions. I am willing to bet this tells a story about the androgen induced male lions mane.

I will read the posted studies, and post again over the weekend.

 

[Armando Jose]

eyelash and eyebrown are specialised hairs, probably inmunes to DHT