Setipiprant

[walrus]

Frankly they don't even mention anything about PGE2. However besides this I can tell you that Minoxidil has shown to do many things which may explain why it works. As upregulating several growth factors, activating b-catenin in DPC, downregulating P53 and P27 and some other things. Again, it's way more complex than you think they are. But what do you know? Not much it seems.

The precise mode of action for Minoxidil on AGA is currently unknown, but there is evidence to believe that it influences prostaglandin levels:

"Minoxidil has effects on prostaglandins. a. In early literature on the mechanism of minoxidil’s effect on reducing blood pressure, it was noted that it has the capacity to increase PGE2, which has been shown to be reduced in AGA (53–55). Although not proven, minoxi- dil’s effects on prostaglandins would be consistent with their aberrant regulation in AGA."

http://onlinelibrary.wiley.com/doi/10.1111/exd.12348/pdf

"Additional evidence that prostaglandins control hair follicle cycling and can be used therapeutically to treat AGA arises from findings on the possible mechanism of the AGA drug minoxidil. Although min- oxidil alters potassium channel kinetics (7), it is also known to increase production of PGE2 (37). Given the decreased amount of PGE2 present in bald scalp versus haired scalp (Fig. 2E), minoxidil may normalize PGE2 levels. Future studies should address whether minoxidil can con- comitantly decrease PGD2 levels and thus normalize multiple prosta- glandin species as a mechanism to improve AGA."

http://stm.sciencemag.org/content/4/126/126ra34

Saying that something is complex, and then belittling another posters knowledge of a subject that no-one knows a great deal about (yourself included) is hardly productive.

[Swooping]

The precise mode of action for Minoxidil on AGA is currently unknown, but there is evidence to believe that it influences prostaglandin levels:

"Minoxidil has effects on prostaglandins. a. In early literature on the mechanism of minoxidil’s effect on reducing blood pressure, it was noted that it has the capacity to increase PGE2, which has been shown to be reduced in AGA (53–55). Although not proven, minoxi- dil’s effects on prostaglandins would be consistent with their aberrant regulation in AGA."

http://onlinelibrary.wiley.com/doi/10.1111/exd.12348/pdf

"Additional evidence that prostaglandins control hair follicle cycling and can be used therapeutically to treat AGA arises from findings on the possible mechanism of the AGA drug minoxidil. Although min- oxidil alters potassium channel kinetics (7), it is also known to increase production of PGE2 (37). Given the decreased amount of PGE2 present in bald scalp versus haired scalp (Fig. 2E), minoxidil may normalize PGE2 levels. Future studies should address whether minoxidil can con- comitantly decrease PGD2 levels and thus normalize multiple prosta- glandin species as a mechanism to improve AGA."

http://stm.sciencemag.org/content/4/126/126ra34

Saying that something is complex, and then belittling another posters knowledge of a subject that no-one knows a great deal about (yourself included) is hardly productive.

Did I ever mention there is no evidence to believe of minoxidil altering PGE2 levels? Where do you see me stating that? I even referred to a study here in relation of minoxidil & PGE2. Did I ever say that I know a great deal or anything about hair follicle biology? Where do you see me stating that?

So what is the purpose of your message? It's totally unrelated rofl. You still don't get the big picture do you? So start learning a bit more so you at least get the basics down. Seek to understand, and don't be ignorant. Or didn't you follow this topic?

Hence look at your quotation;

[QUOTE]Although not proven, minoxi- dil’s effects on prostaglandins would be consistent with their aberrant regulation in AGA."[/QUOTE]

That's how good researchers will talk about such findings. They don't speak in conclusive language when nothing is proven. It's that simple. Scientific method, you know? If you have an opinion that's fine but don't project your opinion as the truth. If you have evidence of tested theories, please provide them?

[eldarlmario]

Did I ever mention there is no evidence to believe of minoxidil altering PGE2 levels? Where do you see me stating that? I even referred to a study here in relation of minoxidil & PGE2. Did I ever say that I know a great deal about hair follicle biology? Where do you see me stating that?

So what is the purpose of your message? It's totally unrelated rofl. You still don't get the big picture do you? So start learning a bit more so you at least get the basics down. Seek to understand, and don't be ignorant. Or didn't you follow this topic?

Hence look your quotation;



That's how elite researchers will talk about such findings. They don't speak in conclusive language when nothing is proven. It's that simple. Scientific method, you know? If you have an opinion that's fine but don't project your opinion as the truth. If you have evidence of tested theories, please provide them?

please dun get yourself angry with trolls. it's obvious he did that intentionally to piss u off

[walrus]

Did I ever say that I know a great deal about hair follicle biology? Where do you see me stating that?

But what do you know? Not much it seems.

I guess this applies to you as well as the other poster you were responding to then?

Did I ever mention there is no evidence of minoxidil altering PGE2 levels? Where do you see me stating that?

You highlight a paper that "Frankly [doesn't] even mention anything about PGE2." in relation to Minoxidil.

I highlight two further papers that do. Such is research.

If you have an opinion that's fine but don't project your opinion as the truth.

Good science is hypothesis driven. That Minoxidil operates by regulating prostaglandin levels, is a testable, evidence-based hypothesis that has been put forward and published in peer-reviewed journals. An opinion is a personal view that requires no proof and cannot objectively be proved 'wrong'.

Scientific method, you know?

Yes bro, I learned all about that during my real-life science PhD---how about you?

[Swooping]

@walrus

I guess this applies to you as well as the other poster you were responding to then?

You highlight a paper that "Frankly [doesn't] even mention anything about PGE2." in relation to Minoxidil.

I highlight two further papers that do. Such is research.

This was more to project a view that perhaps some researchers tend to find some factors more important to mention than others. Fine that you highlight those but that already was clear in this topic. I assume you read the whole topic instead of just hooking in on my last message? I wanted to give a clear picture that we don't know by which mechanism minoxidil exactly does work, again as should be clear in my previous messages.

Good science is hypothesis driven. That Minoxidil operates by regulating prostaglandin levels, is a testable, evidence-based hypothesis that has been put forward and published in peer-reviewed journals. An opinion is a personal view that requires no proof and cannot objectively be proved 'wrong'.

A hypothesis is based on conjecture for which no proof has been found. So it is a testable and evidence based hypothesis of PGE2 in relation to minoxidil? Oh really? Please provide me evidence of in vivo expression of upregulation of PGE2 in any of the hair follicle cell lines after minoxidil application.? I'm curious.

Yes bro, I learned all about that during my real-life science PhD---how about you?

Still studying bio science, but that doesn't even matter. Nice argumentum ab auctoritate though. Kinda like Dr. Hsu right?

[unbalding]

Unbalding my response was to post #107. I explained that the dermal papilla acts as a instructive niche for the progenitors cells in the hair follicle in post #106. In response to post #107 however I explain that he can't make such a statement. First of all you can't say that upregulation of progenitor cells will act as the cure. Cotsarelis would understand this he even mentions this in his study in 2011;



After that study of Cotsarelis we have come to understand that the dermal papilla niche is regulating these progenitors. So if the dermal papilla is altered for instance as shown by other researchers it would automatically lead to a lack of progenitors. This would make the lack of progenitors a secondary event. I hope you understand this so far and everyone else. So to argue that upregulation of progenitors will lead to a cure is ridiculous.

Now he also mentioned that PGD2 down and PGE2 up needs to be done to provide a cure. Well in post #108 (https://www.baldtruthtalk.com/thread...l=1#post219757) I reply. Not with the intention of showing you that PGE2 is carcinogenic. No I reply that the guy is using many compounds that have a lot of effect on downstream pathways.

Look 17b-estradiol tends to grow awesome hair in some people. Can we shout now that 17b-estradiol is a cure now? Hell no. If we look at 17b-estradiol it has much effect on downstream pathways(1);

-P53
-Cyclin D1
-MAPK Pathway
-IGF-1
-SHH
-WNT
-EGFR
-BMP's

And many more. So (some) of these downstream pathways might be attributing to the pro-hair growth effects of 17b-estradiol. Not because 17b-estradiol binds to both estrogen receptors (ERa and ERb) in the hair follicle. Same thing with minoxidil. It grows hair but we don't understand which pathways or what mechanism is responsible for this. If we do know the pathways responsible for it we could perhaps modulate them directly which would possibly provide a far better result. However that could lead to safety concerns obviously but you get the point.

So PGE2 binds to the EP receptors and has many effect on downstream pathways too. So if we go to Garza his study; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982925/. He says that PGE2 has pro-carcinogenic effects and links to two studies. Let's take one of these studies; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759608/. We can see that PGE2 in this study has an effect on

- Cyclin D1
- MAPK pathway
- EGFR
- Other stuff

Hey, do you see some correlations between the two compounds? Now this just acts as an example to explain things but I hope you get the point now. For instance we do know that PGF2A (bimatoprost) grows hair. Does that mean that PGF2A has a big role upstream in the pathway of AGA or acts as a cure? Nope it could have a very small role in the pathology of AGA. Yet it seems to grow hair. That seems strange right? But this can be because using a compound like PGF2A can actually have downstream effect on other pathways that DO have a bigger role upstream in the pathology of AGA.

And I repeat again we don't know what happens after AR activation. I don't concur with the whole prostaglandin hypothesis. I concur with other researchers that master regulatory pathways come into play that decide cell fate decision in the dermal papilla niche. This ultimately leads to an altered dermal papilla niche. We have seen from studies that the dermal papilla regulates hair follicle size. An altered dermal papilla niche would indeed cause a lack of progenitors. I have seen to many correlations and find the evidence of other researchers having it on the right end way way more convincing. Besides that the attention on that hypothesis overall is way more focused than the prostaglandin hypothesis. This is only my opinion. Time will tell eventually.

Hopefully you have gained a bit more insight now. After that reply of my post someone else posted that I was wrong with a total broscience response. So I just reacted to that again. Many things can act as a carcinogen that doesn't mean that they will CAUSE cancer. Read this page and understand for yourself

http://www.cancer.org/cancer/cancercauses/othercarcinogens/generalinformationaboutcarcinogens/known-and-probable-human-carcinogens

Hope that helps unbalding. I wasn't trying to project fear. No, my intention was to explain that some things are far more complex than most think they are. We definitely can't look at someone his temples who grows some intermediate vellus hair by using a whole array of compounds/methods and then make a conclusive statement that this is because of upregulation of PGE2, downregulation of PGD2 and enhancing progenitors or that that will act as a cure. That´s pure broscience.

(1)http://press.endocrine.org/doi/full/...0/er.2006-0020

I am not up to date with the latest research, but I generally agree with you about prostaglandin theory. However, I think it could prove to be very useful as a treatment. I'm just rethinking the idea of putting a half dozen different compounds on my head that may or may not do anything positive, but will almost certainly have side effects. It's one thing to use drugs without a proven safety profile when you know they work, but I'm questioning the risk/reward ratio of drugs that are not proven to work. Then again, I know from experience that RU works only because I took that risk. I am going to try PGE2 for 100 days and evaluate the result. If there is no change after that time, I will drop it.

[Swooping]

I am not up to date with the latest research, but I generally agree with you about prostaglandin theory. However, I think it could prove to be very useful as a treatment. I'm just rethinking the idea of putting a half dozen different compounds on my head that may or may not do anything positive, but will almost certainly have side effects. It's one thing to use drugs without a proven safety profile when you know they work, but I'm questioning the risk/reward ratio of drugs that are not proven to work. Then again, I know from experience that RU works only because I took that risk. I am going to try PGE2 for 100 days and evaluate the result. If there is no change after that time, I will drop it.

I Understand your point. Hope you grow much hair with PGE2 which will serve as cosmetic regrowth/thickening. If you do and others will do, I'll definitely try it too. Good luck!

[breakbot]

please dun get yourself angry with trolls. it's obvious he did that intentionally to piss u off

Eldarlmario are you in love with Swooping or something?
There are studies about green tea, red ginseng etc. Do they work? No i guess.
Everybody can paste a paper and make a hypothesis, fact.

Οh sorry i forgot, you follow only Cotsarelis.
This man is a complete disaster for hairloss research.
I read all your nonsense in your thread, about scoliosis and the correlation with aga. I have to admit it was funny enough. Keep in mind that you don't need calcitriol to upregulate cd200 cells. This is happening through wounding. Good luck with your broscience experiments in your laboratory.

[CurlyBird]

I'm also unable to find seti on Kane's site. I guess people are getting emails only?

[warner8]

we are in the same boat.

I'm wondering if he even sells it at all, i emailed him this week with no response.

I'm also unable to find seti on Kane's site. I guess people are getting emails only?

[JayM]

He's only sending emails. Why don't you just email him. He probably offering to past customers first (email addresses he has) first or something.

[warner8]

is he selling premixed or just powder? if you get the powder, do you know how to use it?

He's only sending emails. Why don't you just email him. He probably offering to past customers first (email addresses he has) first or something.

[Unsure1]

In on this
Wouldn't Seti provide the same blocking mechanisms that OC provides?
Or is the logic here that Seti has undergone more clinical trials and is therefore safer?
I believe adding an internal like sulfasalazine would increase risk due to its effect on the immune system, however I fail to see how various topical methods would cause much effect, although systematic absorption cannot be denied, it is more localised.

[champpy]

I believe kane is selling powder, as i asked about getting 25 grams. But he is def selling seti and said he will have his own groupbuy page running shortly

[Hubris]

I believe kane is selling powder, as i asked about getting 25 grams. But he is def selling seti and said he will have his own groupbuy page running shortly

If any of you guys on the forum manage to get seti, will you please document your results in a similar fashion to Hellouser with RU? I don't have the money to buy seti on the off chance it might work, but if I see that it is working very well for a few people on here, I may be able to justify it to myself.