Need a big favor. S Foote's theory in a nutshell?

[wookster]

Keep working on it, Wookster.

Hint: try explaining what androgens have to do with balding...

It boils down to the cells in the hair follicles and their genetically programmed reaction to androgens. DHT is produced in and/or near the hair follicles via production of 5alpha reductase. Stop 5AR production, remove or block the androgens and stop balding.

Androgens stimulate beard hair follicles to GROW and they stimulate scalp hair follicles on the top of scalp to MINIATURIZE.

Theoretically speaking. :hairy:

 

[wookster]

Some interesting links:

http://www.hairlosshelp.com/pdf/transpl ... _scalp.pdf

Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice...

http://endo.endojournals.org/cgi/content/full/138/1/356

Inhibition of Hair Growth by Testosterone in the Presence of Dermal Papilla Cells from the Frontal Bald Scalp of the Postpubertal Stumptailed Macaque

[...]

Together our data indicate that the inhibitory effect of testosterone on proliferation of epithelial cells is age dependent, and androgen may play an essential role in hair growth either by inducing repressor(s) from dermal papilla cells, which may then inhibit the growth of epithelial cells of the hair follicle, or by inducing growth factor(s) from dermal papilla cells, which, in turn, may trigger the induction of some repressors in epithelial cells, thereby inhibiting the epithelial cell growth. Our animal studies also showed that RU 58841 has a dramatic effect on hair regrowth in the bald frontal scalp of the stumptailed macaque, which may further support our in vitro culture studies showing that antiandrogens can antagonize testosterone-elicited hair growth. In summary, our studies may provide a model for further isolation of androgen-regulated repressor(s)/growth factors, which may help control hair growth and baldness

 

[S Foote.]

How to put my theory across in simple terms? Well i'll try.

First some personal background.

I am now 54, and i started loosing my hair in my late 20's. Transplants were the only option then (early 80's), and i decided to go down that path (wish i hadn't).

I had four scalp reductions followed by grafts to the frontal area and the central scar left by the reductions. The grafts used were four mm "plugs" (common at the time), and the procedures were carried out at a highly reputable clinic here in England, and the initial results were good.

However my long term experience with these transplants caused me to question the reasons for male pattern baldness, given by the current theory.

The current theory is on the surface supported by the very limited data we have concerning hair transplantation, in particular long term studies don't exist, and the results of some in-vitro studies. The conclusion reached is that hair follicles have some kind of built in "difference" that causes a different "direct" growth response to androgens. However there are a number of serious holes in this conclusion as i have argued before.

Now to my theory.

My background is in engineering systems, and i look at things from the view point of the "whole" system. I think this way of looking at androgen related hair loss/growth, answers the questions the current "molecular" theory cannot.


I have argued the details many times before on these forums, but this is it in a "nutshell" as requested.

The amount of hair growth is dependent upon the size of the follicle reached during the anagen enlargement period of the hair cycle. This expansion of a "pocket" (hair follicle) within the dermal tissue has to move the dermal tissue aside. My original thinking was "what if the dermal tissue doesn't want to move"?

All normal cells respond to a growth control called contact inhibition. Cell multiplication can only happen if there is "space" for this. Not much is known about the molecullar pathway of this process, but we know it effects "ALL" normal cells. Cancer cells lose the contact inhibition response, and this is why they can invade the "space" of other tissues.

The point at which contact inhibition is swiched on must involve a particular degree of resistence or pressure. When this degree of resistence is meet by growing cells, the growth is switched off most likely by changes in the expression of the usual growth factors we know effect cell multiplication.

In the case of hair follicle enlargement, there is another factor as well as the natural resistence of the dermal tissue itself. Because the follicle is an expanding "hollow" pocket in the dermal tissue, there can be a pressure difference.

This is the simple analogy of a ordinary party baloon.

If you push your finger into a party balloon to form a pocket, the amount of resistence depends upon the air pressure within the baloon. If your finger action was "switched off" at a given resistence, this point would be reached sooner the higher the pressure in the baloon. The pocket formed would be smaller.

So according to my theory any changes in the tissue fluid "pressure" around follicles, can effect their anagen size through the normal contact inhibition threshold, and even quite small pressure changes can make a difference.

So where do androgens come into this?

The most consistant action of androgens upon hair in people, is they increase hair growth over the larger part of the body, particularly in certain areas. The beard, groin, and armpit areas also are areas with high levels of lymphatic drainage vessels near the surface. Lymphatic vessels play a central role in the control of the local tissue fluid pressures.

So according to my theory androgens, and DHT in particular must be increasing lymphatic drainage of tissue fluid. This reduces the pressure around the local follicles allowing larger anagen follicles and increased hair growth in these areas.

The lymphatic vessels move tissue fluid by regular contractions, the one way valves in the vessels combined with these contractions "pump" tissue fluid away from the area.

The contractions are due to muscle fibers in the vessel walls. Muscle cells have androgen receptors, so it is perfectly possible for androgens to effect these muscle fibers to increase the rate of "pumping".


Such an action of androgens on lymphatic pumping also makes sense in terms of the "performance" effects of male hormones. Increased lymphatic drainage means increased turnover of fluid around cells, increasing nutrient supply and waste removal in tissues, so enhancing the muscle building action of other androgens.

Once you consider what we know about male pattern baldness in terms of DHT related effects on tissue fluid levels, this makes a lot more sense.

Not everyone developes male pattern baldness, and the time period for male pattern baldness can span many years. According to my theory the development of male pattern baldness in an individual depends upon other characteristics related to the blood feed side of a tissue fluid equasion.

Most of the lymphatic vessels of the head are concentrated lower down, including the beard area. The male pattern baldness pattern area at the top of the head is at the end of the system, and fluid draining from here has to pass through the lower vessels. If DHT increases lymphatic drainage the male pattern baldness area is vunerable because of the increase in pumping and the valves closing against flow from the end of the system (male pattern baldness area).

So increasing levels of DHT can cause an opposite effect of reducing tissue fluid drainage from the male pattern baldness area through fluid dynamic effects. This may or may not cause an increase in the local scalp fluid pressure, depending upon an individuals blood feed characteristics. Too much blood feed and the reduced drainage will increase tissue fluid pressures in the male pattern baldness area, smaller follicles through early contact inhibition and male pattern baldness.

This fluid balance shift can happen quickly or slowly of not at all, depending upon the individuals fluid dynamics. When it does cause hair loss, this only happens as follicles go into the anagen phase. Scalp follicles already in full anagen can not cycle again for years, "then" they become effected by the pressure.

This explains why male pattern baldness cannot be directly related to levels of androgens, and the long time periods involved. The current theory has to have every individual follicle expressing different genes to explain male pattern baldness.

Likewise the in-vitro test results support the involvement of a prior in-vivo change in growth gene related activity in male pattern baldness samples. Contact inhibition causing male pattern baldness is going to change the known growth response gene expressions. So of course then TGF beta-1 etc could be differently expressed from these samples in-vitro.

There are other holes in the in-vitro tests that i have argued before.

The only transplanted follicles that survive in the male pattern baldness area, are those that have had a healing process happen very close to them. The modern very small grafts achieve this. The old large grafts lost most of the hair over time until hair only remained around the edges (where the healing happened). This is known as graft "doughnutting", and is well recognised in the transplantation industry.

The well respected researcher Dr Uno reported that the fibrotic formation around long term male pattern baldness follicles, acted as a barrier to follicle enlargement. This is an example of contact inhibition in follicle growth.

In small graft transplantation, large anagen follicles are selected. When these are transplanted the healing produces a fibrotic shell around the graft. So we have a situation as reported by Uno. Only now this is a large fibrotic shell, that acts as a "mold" to preserve this space for future large anagen follicles.

This prevents the pressure in the dermal tissue from pushing dermal cells into the follicle space causing miniaturisation. In the current HM research, there is talk of an extracellular matrix being necessary to ensure proper follicle growth.

I suggest this happens naturaly in transplantation because of the healing, and is why these large follicles can re-cycle properly in the male pattern baldness area.

Also this "fluid pressure action on follicle size simply explains other known factors in male pattern baldness, the current theory cannot without resorting to added unnecessary complication.

The immunology and fibrosis that developes longer term in male pattern baldness, is a recognised effect of higher tissue fluid levels, as in lymphedema.

The proven sweating differences in tissues where DHT grows hair and male pattern baldness tissue, are also easily explained by this mechanism. Sweating reduces significantly in the beard area where DHT grows hair, but significantly increases in the male pattern baldness area.

Sweat is tissue fluid, so reduced fluid in the beard area will reduce sweating capacity, and increased pressure in the male pattern baldness area will increase sweating capacity, simple.

This fluid pressure/contact inhibition mechanism, simply explains all the factors in DHT related hair growth/loss. The current theory requires unknown and complex mechanisms that go against basic scientific principles.

I hope you now understand my theory. I have not used any references here to try to not distract too much, but i have posted the relevant ones before on these forums, and will again if required.

Regards.

S Foote.

 

[youngbaldie]

Yes, now I understand it a lot better. Thanks for taking the time to explain that so well.

I actually hope you are wrong honestly, because it seems like it will be much more complicated to treat in the future if your theory holds true. But then it would explain a lot of problems that we have faced for years in attempting to treat it with the current options available.

Thanks though.

 

[wookster]

:freaked: :freaked: :freaked:

http://dermatology.cdlib.org/122/case_r ... tosti.html

We report 2 adult caucasian males with lipedematous scalp associated with androgenetic alopecia. Patients were studied by dermoscopy and histopathology; they were treated with finasteride 1 mg. In our patients, lipedematous scalp affected the occipital and the vertex areas and pathologically exhibited mild edema and thickening of the adipose subcutaneous layer. At videodermoscopy, lipedematous scalp areas showed linear areas of teleangiectasia within the scalp creases, possibly caused by compression of the superficial blood capillaries by the increased volume of the subcutaneous fat layer within the thickened scalp. Finasteride at a dose of 1 mg per day for 1 year induced mild improvement of androgenetic alopecia in one patient and stabilization of the disease in the other. The lipedematous scalps remain unchanged. Lipedematous scalp is apparently a rare disease even though the condition is probably underdiagnosed.

 

[Bryan]

Wookster, I do so much enjoy these pleasant trips down Memory Lane which you provide to all of us on a regular basis.

You DO know, don't you, that almost all of these studies you cite have already been mentioned and discussed in the past? :wink:

 

[wookster]

Wookster, I do so much enjoy these pleasant trips down Memory Lane which you provide to all of us on a regular basis.

You DO know, don't you, that almost all of these studies you cite have already been mentioned and discussed in the past? :wink:

I did a search and there are only 10 discussions with "lipedematous" in them :hairy:

 

[The Gardener]

If male pattern baldness is caused by poor lymph or sebum drainage, then why don't women suffer male pattern baldness like men do?

 

[powersam]

If male pattern baldness is caused by poor lymph or sebum drainage, then why don't women suffer male pattern baldness like men do?

read footes post above, DHT plays a role in lymphatic draining.

 

[wookster]

If male pattern baldness is caused by poor lymph or sebum drainage, then why don't women suffer male pattern baldness like men do?

How to put my theory across in simple terms? Well i'll try.

First some personal background.

I am now 54, and i started loosing my hair in my late 20's. Transplants were the only option then (early 80's), and i decided to go down that path (wish i hadn't).

I had four scalp reductions followed by grafts to the frontal area and the central scar left by the reductions. The grafts used were four mm "plugs" (common at the time), and the procedures were carried out at a highly reputable clinic here in England, and the initial results were good.

However my long term experience with these transplants caused me to question the reasons for male pattern baldness, given by the current theory.

The current theory is on the surface supported by the very limited data we have concerning hair transplantation, in particular long term studies don't exist, and the results of some in-vitro studies. The conclusion reached is that hair follicles have some kind of built in "difference" that causes a different "direct" growth response to androgens. However there are a number of serious holes in this conclusion as i have argued before.

Now to my theory.

My background is in engineering systems, and i look at things from the view point of the "whole" system. I think this way of looking at androgen related hair loss/growth, answers the questions the current "molecular" theory cannot.


I have argued the details many times before on these forums, but this is it in a "nutshell" as requested.

The amount of hair growth is dependent upon the size of the follicle reached during the anagen enlargement period of the hair cycle. This expansion of a "pocket" (hair follicle) within the dermal tissue has to move the dermal tissue aside. My original thinking was "what if the dermal tissue doesn't want to move"?

All normal cells respond to a growth control called contact inhibition. Cell multiplication can only happen if there is "space" for this. Not much is known about the molecullar pathway of this process, but we know it effects "ALL" normal cells. Cancer cells lose the contact inhibition response, and this is why they can invade the "space" of other tissues.

The point at which contact inhibition is swiched on must involve a particular degree of resistence or pressure. When this degree of resistence is meet by growing cells, the growth is switched off most likely by changes in the expression of the usual growth factors we know effect cell multiplication.

In the case of hair follicle enlargement, there is another factor as well as the natural resistence of the dermal tissue itself. Because the follicle is an expanding "hollow" pocket in the dermal tissue, there can be a pressure difference.

This is the simple analogy of a ordinary party baloon.

If you push your finger into a party balloon to form a pocket, the amount of resistence depends upon the air pressure within the baloon. If your finger action was "switched off" at a given resistence, this point would be reached sooner the higher the pressure in the baloon. The pocket formed would be smaller.

So according to my theory any changes in the tissue fluid "pressure" around follicles, can effect their anagen size through the normal contact inhibition threshold, and even quite small pressure changes can make a difference.

So where do androgens come into this?

The most consistant action of androgens upon hair in people, is they increase hair growth over the larger part of the body, particularly in certain areas. The beard, groin, and armpit areas also are areas with high levels of lymphatic drainage vessels near the surface. Lymphatic vessels play a central role in the control of the local tissue fluid pressures.

So according to my theory androgens, and DHT in particular must be increasing lymphatic drainage of tissue fluid. This reduces the pressure around the local follicles allowing larger anagen follicles and increased hair growth in these areas.

The lymphatic vessels move tissue fluid by regular contractions, the one way valves in the vessels combined with these contractions "pump" tissue fluid away from the area.

The contractions are due to muscle fibers in the vessel walls. Muscle cells have androgen receptors, so it is perfectly possible for androgens to effect these muscle fibers to increase the rate of "pumping".


Such an action of androgens on lymphatic pumping also makes sense in terms of the "performance" effects of male hormones. Increased lymphatic drainage means increased turnover of fluid around cells, increasing nutrient supply and waste removal in tissues, so enhancing the muscle building action of other androgens.

Once you consider what we know about male pattern baldness in terms of DHT related effects on tissue fluid levels, this makes a lot more sense.

Not everyone developes male pattern baldness, and the time period for male pattern baldness can span many years. According to my theory the development of male pattern baldness in an individual depends upon other characteristics related to the blood feed side of a tissue fluid equasion.

Most of the lymphatic vessels of the head are concentrated lower down, including the beard area. The male pattern baldness pattern area at the top of the head is at the end of the system, and fluid draining from here has to pass through the lower vessels. If DHT increases lymphatic drainage the male pattern baldness area is vunerable because of the increase in pumping and the valves closing against flow from the end of the system (male pattern baldness area).

So increasing levels of DHT can cause an opposite effect of reducing tissue fluid drainage from the male pattern baldness area through fluid dynamic effects. This may or may not cause an increase in the local scalp fluid pressure, depending upon an individuals blood feed characteristics. Too much blood feed and the reduced drainage will increase tissue fluid pressures in the male pattern baldness area, smaller follicles through early contact inhibition and male pattern baldness.

This fluid balance shift can happen quickly or slowly of not at all, depending upon the individuals fluid dynamics. When it does cause hair loss, this only happens as follicles go into the anagen phase. Scalp follicles already in full anagen can not cycle again for years, "then" they become effected by the pressure.

This explains why male pattern baldness cannot be directly related to levels of androgens, and the long time periods involved. The current theory has to have every individual follicle expressing different genes to explain male pattern baldness.

Likewise the in-vitro test results support the involvement of a prior in-vivo change in growth gene related activity in male pattern baldness samples. Contact inhibition causing male pattern baldness is going to change the known growth response gene expressions. So of course then TGF beta-1 etc could be differently expressed from these samples in-vitro.

There are other holes in the in-vitro tests that i have argued before.

The only transplanted follicles that survive in the male pattern baldness area, are those that have had a healing process happen very close to them. The modern very small grafts achieve this. The old large grafts lost most of the hair over time until hair only remained around the edges (where the healing happened). This is known as graft "doughnutting", and is well recognised in the transplantation industry.

The well respected researcher Dr Uno reported that the fibrotic formation around long term male pattern baldness follicles, acted as a barrier to follicle enlargement. This is an example of contact inhibition in follicle growth.

In small graft transplantation, large anagen follicles are selected. When these are transplanted the healing produces a fibrotic shell around the graft. So we have a situation as reported by Uno. Only now this is a large fibrotic shell, that acts as a "mold" to preserve this space for future large anagen follicles.

This prevents the pressure in the dermal tissue from pushing dermal cells into the follicle space causing miniaturisation. In the current HM research, there is talk of an extracellular matrix being necessary to ensure proper follicle growth.

I suggest this happens naturaly in transplantation because of the healing, and is why these large follicles can re-cycle properly in the male pattern baldness area.

Also this "fluid pressure action on follicle size simply explains other known factors in male pattern baldness, the current theory cannot without resorting to added unnecessary complication.

The immunology and fibrosis that developes longer term in male pattern baldness, is a recognised effect of higher tissue fluid levels, as in lymphedema.

The proven sweating differences in tissues where DHT grows hair and male pattern baldness tissue, are also easily explained by this mechanism. Sweating reduces significantly in the beard area where DHT grows hair, but significantly increases in the male pattern baldness area.

Sweat is tissue fluid, so reduced fluid in the beard area will reduce sweating capacity, and increased pressure in the male pattern baldness area will increase sweating capacity, simple.

This fluid pressure/contact inhibition mechanism, simply explains all the factors in DHT related hair growth/loss. The current theory requires unknown and complex mechanisms that go against basic scientific principles.

I hope you now understand my theory. I have not used any references here to try to not distract too much, but i have posted the relevant ones before on these forums, and will again if required.

Regards.

S Foote.

 

[zackb]

Stephen,

If your theory is true...then what treatments...herbal or otherwise could we sue to combat scalp edema?

 

[S Foote.]

Stephen,

If your theory is true...then what treatments...herbal or otherwise could we sue to combat scalp edema?

The problem is not going to be easy to solve without more research into the feed side of the equasion in my opinion.

I think my theory is in line with the general things people are finding helpful on these forums. You have to reduce DHT at least in "ALL" the head surface tissue. You have to treat the edema/inflammation in the male pattern baldness area.

At this point i don't make specific recommendations, and would suggest you read up on peoples experiences.

S Foote.

 

[wookster]

This quote appears to agree with Mr. Foote's description of the miniaturization process:

http://www.e-ijd.org/article.asp?issn=0 ... ast=Thomas

When does follicular miniaturization occur in androgenetic alopecia? Its initiation may occur at some stage in early catagen or early anagen, when the dermal papilla is moving up or down the temporary lower follicle and is vulnerable to external forces. It does not occur during established anagen, since anagen hairs maintain the same diameter during each hair cycle, nor in telogen where there is no metabolic activity.

 

[Bryan]

I don't know that anagen hairs maintain the same diameter during each hair cycle. Dr. Proctor has said that they don't necessarily do that.

 

[Armando Jose]

I don't know that anagen hairs maintain the same diameter during each hair cycle. Dr. Proctor has said that they don't necessarily do that.

I'll read any study regarding this aspect. Did have Dr Proctor any reference?

By the way, I think that is more normal that diameter don't change significative in healthy hairs.

Armando

 

[Bryan]

I'll read any study regarding this aspect. Did have Dr Proctor any reference?

I don't think so. I believe he just said that sometimes, individual hairs can be seen to slowly miniaturize along their length because of the balding process, or enlarge in response to treatment.

By the way, I think that is more normal that diameter don't change significative in healthy hairs.

I agree with that. After all, there would be no reason for the diameter of healthy hairs to change significantly! :wink:

 

[Matgallis]

Interesting read.. Damn pumps!


EDIT: I was just thinking about minoxidil and it's effects. I wonder if a combination of enlarged blood vessels in the scalp AND larger drainage areas help increase hair size?

 

[docj077]

Interesting read.. Damn pumps!


EDIT: I was just thinking about minoxidil and it's effects. I wonder if a combination of enlarged blood vessels in the scalp AND larger drainage areas help increase hair size?

Think about how minoxidil works and then think about it's side effects. Minoxidil is a selective arterial vasodilator. It will increase blood flow to areas with which it comes into contact or areas that it penetrates after being absorbed through the skin and moving systemically. One of the greatest side effects of minoxidil is EDEMA. So, how can a drug that causes hypertrichosis also cause edema in tissues that it comes into contact with if edema is the main factor contributing to contact inhibition? If edema is indeed causing contact inhibition and altering cellular signaling (which it doesn't by the way), then how can minoxidil overcome the pro-apoptotic signals enough to truly have any sort of effect in hair loss? If you want to talk about you biochemical interactions that have no basis in science, you've found them.

Besides, minoxidil's likely true mechanism of action in hair loss has nothing to do with selective arterial vasodilation.

I wouldn't focus on "drainage" or anything to do with lymphatics in hair loss. One of the first steps is vessel obliteration (not obstruction) in hair loss. It's difficult to have edema in an area of the scalp if capillary blood flow is altered in the first place.

 

[wookster]

Interesting read.. Damn pumps!


EDIT: I was just thinking about minoxidil and it's effects. I wonder if a combination of enlarged blood vessels in the scalp AND larger drainage areas help increase hair size?

Think about how minoxidil works and then think about it's side effects. Minoxidil is a selective arterial vasodilator. It will increase blood flow to areas with which it comes into contact or areas that it penetrates after being absorbed through the skin and moving systemically. One of the greatest side effects of minoxidil is EDEMA. So, how can a drug that causes hypertrichosis also cause edema in tissues that it comes into contact with if edema is the main factor contributing to contact inhibition? If edema is indeed causing contact inhibition and altering cellular signaling (which it doesn't by the way), then how can minoxidil overcome the pro-apoptotic signals enough to truly have any sort of effect in hair loss? If you want to talk about you biochemical interactions that have no basis in science, you've found them.

Besides, minoxidil's likely true mechanism of action in hair loss has nothing to do with selective arterial vasodilation.

I wouldn't focus on "drainage" or anything to do with lymphatics in hair loss. One of the first steps is vessel obliteration (not obstruction) in hair loss. It's difficult to have edema in an area of the scalp if capillary blood flow is altered in the first place.

http://hyper.ahajournals.org/cgi/content/full/27/3/679

Quote:

"Nitric oxide has a diuretic effect in vivo..."





Minoxidil is an NO agonist according to Proctor

http://www.hairlosshelp.com/qna/Detail. ... ExpertID=1


Quote:

"Minoxidil ( Lonitin ) does not make NO ( "nitric oxide" ) or increase levels of it. As the name implies, miNOxidil contains the nitric oxide chemical structure. It apparently derives its ability both as a blood vessel dialator and as a hair-growth-stimulator from acting as an NO "Agonist". Interestingly, I was the researcher who first discovered and reported this (he says modestly). See http://www.drproctor.com/Archd.htm for the paper.

Again, miNOxidil fakes NO, which is what we pharmacologists mean when we say a drug is an "agonist". It does not produce it."





http://ajpregu.physiology.org/cgi/conte ... 274/3/R790


Quote:

"We conclude that endothelial nitric oxide and prostaglandins are important modulators of lymphatic vasomotion, hence pumping activity of lymph microvessels in vivo."

 

[docj077]

Interesting read.. Damn pumps!


EDIT: I was just thinking about minoxidil and it's effects. I wonder if a combination of enlarged blood vessels in the scalp AND larger drainage areas help increase hair size?

Think about how minoxidil works and then think about it's side effects. Minoxidil is a selective arterial vasodilator. It will increase blood flow to areas with which it comes into contact or areas that it penetrates after being absorbed through the skin and moving systemically. One of the greatest side effects of minoxidil is EDEMA. So, how can a drug that causes hypertrichosis also cause edema in tissues that it comes into contact with if edema is the main factor contributing to contact inhibition? If edema is indeed causing contact inhibition and altering cellular signaling (which it doesn't by the way), then how can minoxidil overcome the pro-apoptotic signals enough to truly have any sort of effect in hair loss? If you want to talk about you biochemical interactions that have no basis in science, you've found them.

Besides, minoxidil's likely true mechanism of action in hair loss has nothing to do with selective arterial vasodilation.

I wouldn't focus on "drainage" or anything to do with lymphatics in hair loss. One of the first steps is vessel obliteration (not obstruction) in hair loss. It's difficult to have edema in an area of the scalp if capillary blood flow is altered in the first place.

http://hyper.ahajournals.org/cgi/content/full/27/3/679

Quote:

"Nitric oxide has a diuretic effect in vivo..."





Minoxidil is an NO agonist according to Proctor

http://www.hairlosshelp.com/qna/Detail. ... ExpertID=1


Quote:

"Minoxidil ( Lonitin ) does not make NO ( "nitric oxide" ) or increase levels of it. As the name implies, miNOxidil contains the nitric oxide chemical structure. It apparently derives its ability both as a blood vessel dialator and as a hair-growth-stimulator from acting as an NO "Agonist". Interestingly, I was the researcher who first discovered and reported this (he says modestly). See http://www.drproctor.com/Archd.htm for the paper.

Again, miNOxidil fakes NO, which is what we pharmacologists mean when we say a drug is an "agonist". It does not produce it."





http://ajpregu.physiology.org/cgi/conte ... 274/3/R790


Quote:

"We conclude that endothelial nitric oxide and prostaglandins are important modulators of lymphatic vasomotion, hence pumping activity of lymph microvessels in vivo."

Minoxidil's ability to serve as a diuretic is definitely in question. In fact, I don't buy it at all. During administration of minoxidil, a diuretic is supposed to be prescribed to go along with it as the decrease in vascular resistance eventually causes salt and water retention. The official FDA stance on Minoxidil is that it has no diuretic properties.

Just because a drug is an agonist that does not mean that it functions in the same manner as the molecule that it mimics. There are partial agonists, so you can not assume that one study demonstrating the pharmacology of one molecule will give you the evidence you need to draw conclusions about another molecule that is far larger and more complex. If you look at the chemical structure of minoxidil, you'll see the NO portion, but that is the portion of the molecule that is initially conjugated with glucoronic acid.

What Dr. Proctor is saying is somewhat correct, but not entirely correct. Minoxidil has far more mechanisms of action in the human hair besides selective arterial vasodilation. It's role as an inhibitory of TGF-beta action makes it a powerful anti-apoptosis drug.


Some "diuretic" you have there...

Warnings

1. Salt and Water Retention: Congestive Heart Failure - concomitant use of an adequate diuretic is required - Minoxidil tablets must usually be administered concomitantly with a diuretic adequate to prevent fluid retention and possible congestive heart failure; a high ceiling (loop) diuretic is almost always required. Body weight should be monitored closely. If Minoxidil is used without a diuretic, retention of several hundred milli-equivalents of salt and corresponding volumes of water can occur within a few days, leading to increased plasma and interstitial fluid volume and local or generalized edema. Diuretic treatment alone, or in combination with restricted salt intake, will usually minimize fluid retention, although reversible edema did develop in approximately 10% of nondialysis patients so treated. Ascites has also been reported. Diuretic effectiveness was limited mostly by disease-related impaired renal function. The condition of patients with pre-existing congestive heart failure occasionally deteriorated in association with fluid retention although because of the fall in blood pressure (reduction of afterload), more than twice as many improved than worsened. Rarely, refractory fluid retention may require discontinuation of Minoxidil. Provided that the patient is under close medical supervision, it may be possible to resolve refractory salt retention by discontinuing Minoxidil for 1 or 2 days and then resuming treatment in conjunction with vigorous diuretic therapy.


So, remind me again. If Minoxidil is a diuretic, then why do you have to give a diuretic with it just to prevent fluid overload and edema?


Lastly, if you read the study on lymphatics that you posted really carefully, you'll notice that your argument is flawed.

ACh causes relaxation of isolated canine thoracic ducts (23) and porcine hepatic lymphatics (10), a response that is mediated by endothelium-derived nitric oxide. In addition, in vivo (4) and in vitro (29) studies have already demonstrated that nitric oxide is released by ACh in small lymphatics. In the present study, in response to ACh, the maximum diameter of lymphatic microvessels increased significantly and there was also a temporary cessation of oscillations in diameter

So, if the vessels are dilating and no longer oscillating due to Ach RELEASING NO, then how is the lymph moving?!? :freaked: :freaked: :freaked:

I put three faces just for you, Wookster.


I don't know who is worse with the interpretation of studies, you or Foote.