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Trodusquemine Reverse Plaque - Group Buy Share Data

arterial plaque trodusquemine msi-1436 cardiovascular disease coronary arteries carotid arteries calcification mouse study cancer diabetes

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#61 zorba990

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Posted 11 September 2018 - 10:45 PM

Well, I'd certainly like to see it commercially available without having to wait a decade to get it through the FDA. Whatever it takes.

The FDA has become such an impediment to medical technology development.


I would vote for supplement. Wouldn't want to see this go the way of gcMaf

#62 YOLF

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Posted 12 September 2018 - 02:40 AM

I would vote for supplement. Wouldn't want to see this go the way of gcMaf

So you're saying that GcMAF has applications regardless of whether some of its studies were flawed and retracted and that this could happen to Trodusquemine if we tried to develop it as an Rx? 

 

I think once Trodusquemine was approved as a new ingredient, if it even needs that, it wouldn't matter if something happened to remove it from Rx status, it would always be available as a supplement unless there were safety concerns. For the Rx portion we'd have to redefine how it is to be applied clinically assuming it still useful in light of the new information or understanding. 



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#63 zorba990

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Posted 12 September 2018 - 02:54 AM

So you're saying that GcMAF has applications regardless of whether some of its studies were flawed and retracted and that this could happen to Trodusquemine if we tried to develop it as an Rx?

I think once Trodusquemine was approved as a new ingredient, if it even needs that, it wouldn't matter if something happened to remove it from Rx status, it would always be available as a supplement unless there were safety concerns. For the Rx portion we'd have to redefine how it is to be applied clinically assuming it still useful in light of the new information or understanding.


Wow. No.
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#64 docmaas

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Posted 12 September 2018 - 05:38 AM

I found this today.  Appears to date back to the initial discovery.  https://www.scienced...20801075128.htm

 

This paragraph gave me pause:  "The researchers initially thought that MSI-1436 could be an effective treatment for HIV because it stopped the reproduction of the virus in the lab. However, when the researchers tested it in animals they discovered that it caused them to stop eating and therefore could not be used safely as an HIV treatment. It was then that the researchers realized its potential as an anti-obesity treatment."

 

Was this just with animals infected with HIV or it is that strong of an appetite suppressant in general?  Sounds like it would be useful in a fairly acute manner.  

 

Mike



#65 Daniel Cooper

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Posted 12 September 2018 - 01:49 PM

Keep in mind the following:

 

1.) Loss of appetite, loss of weight/wasting is a hallmark of HIV/AIDS.

 

2.) Treatment of HIV/AIDS with trodusquemine would likely require long term/continuous dosing.  Clearly appetite suppression is not desirable for those with this disease on a long term basis.

 

3.) Trodusquemine does cause appetite suppression, which is why it was investigated as a treatment for obesity.

 

4.) Treatment of atherosclerosis with trodusquemine would likely only require a limited short term dosing.

 

5.) We do have a short term human trial (4 days) were 4 out of 7 subjects reported appetite suppression.

 

6.) Humans are not rodents.  We can be alert for this effect and to some extent force ourselves to eat more should it become an issue, or discontinue dosing.

 

I'm not personally overly concerned about this aspect of trodusquemine, in fact if you could stand to lose a few pounds it might be a useful side effect.

 

 


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#66 mikey

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Posted 12 September 2018 - 08:33 PM

So you're saying that GcMAF has applications regardless of whether some of its studies were flawed and retracted and that this could happen to Trodusquemine if we tried to develop it as an Rx? 

 

I think once Trodusquemine was approved as a new ingredient, if it even needs that, it wouldn't matter if something happened to remove it from Rx status, it would always be available as a supplement unless there were safety concerns. For the Rx portion we'd have to redefine how it is to be applied clinically assuming it still useful in light of the new information or understanding. 

 

Having functioned professionally in the dietary supplement industry for over 40 years I can attest that the Dietary Supplement Health and Education Act of 1994 provides that if an ingredient is found in nature it is automatically a food supplement, not requiring approval unless it presents dangers to the public.

 

Attempting to get drug qualification for TD would require perhaps hundreds of millions of dollars. While we would like doctors to prescribe it, Niagen (NR) is doing quite well without doctors prescribing it.

 

Also, if we attempt to get TD "in the stream" of conventional American medicine we will likely suffer all the roadblocks that others have noted on these forums. The AMA, FDA, etc... have the opposite of a healthy interest in such things as nicotinamide riboside and trodusquemine. These "ingredients" are not profitable the way that patented drugs are and challenge conventional medical therapies and the billions of dollars that they generate.

 

The path of least resistance for TD is to do our own research on it and perhaps a dedicated group brings it to market as a dietary supplement and hopes that Big Pharma doesn't figure out a way to cut us off.

Aside from this comment, I am excited. I will post more in a moment about the critical issue of dosing. 


Edited by mikey, 12 September 2018 - 08:35 PM.

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#67 YOLF

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Posted 12 September 2018 - 09:20 PM

Well, I'm still in for developing another supplement, but I don't think it would cost us hundreds of millions of dollars. I think it can be done with less money and with crowdfunding. We don't have to compensate our study group, and in fact, they would be paying to take part in the trial and to have an ownership in the profits of development. With a double blind trial, falsifying results as a patient would be just as bad for the data as if it didn't work, so as long as we explain that, our results would still be every bit as good as those done by a pharmaceutical company and we'd be setting a precedent for decentralized trials. Plus, in the process of crowdfunding, we'd already be marketing our drugs to the public.



#68 Daniel Cooper

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Posted 12 September 2018 - 09:22 PM

I don't think Mikey was saying it would cost hundreds of millions of dollars to develop trodusquemine as a supplement, just the opposite in fact. As a drug yes (FDA trials are expensive).  

 

 

 

 

 

 



#69 mikey

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Posted 12 September 2018 - 09:45 PM

Keep in mind the following:

 

1.) Loss of appetite, loss of weight/wasting is a hallmark of HIV/AIDS.

 

2.) Treatment of HIV/AIDS with trodusquemine would likely require long term/continuous dosing.  Clearly appetite suppression is not desirable for those with this disease on a long term basis.

 

3.) Trodusquemine does cause appetite suppression, which is why it was investigated as a treatment for obesity.

 

4.) Treatment of atherosclerosis with trodusquemine would likely only require a limited short term dosing.

 

5.) We do have a short term human trial (4 days) were 4 out of 7 subjects reported appetite suppression.

 

6.) Humans are not rodents.  We can be alert for this effect and to some extent force ourselves to eat more should it become an issue, or discontinue dosing.

 

I'm not personally overly concerned about this aspect of trodusquemine, in fact if you could stand to lose a few pounds it might be a useful side effect.

All good points, Daniel.
Considerations
1. I spent 5 years as Director of Research for a non-profit and wrote a book about it. HIV-related appetite loss was most usually addressed with a prescription for Marinol, which is a capsule of pure synthetic delta-9-THC. Medical marijuana, the entire natural plant with all of its components, works better than Marinol, so this provides one answer to appetite loss.
2. Some plain old pot, vaporized, so as to not ingest the tar, which amounts to 50% more than tobacco in the smoke of MJ, is preferred.

4. The mouse study showed that one exposure was desirable. "Therefore, the robust phosphorylation of aortic AMPKα1 observed in response to a single injection, and to some extent chronic global PTP1B inhibition with trodusquemine, and the associated protection and reversal of atherosclerotic plaque area, suggest that PTP1B inhibition may be protective through an AMPKα1-driven mechanism. It is important to note that at the time of culling, single dose and chronic drug-treated mice had 4- and 6-weeks washout of drug, respectively, this two-week difference may explain why chronic treatment did not exhibit phosphorylation of AMPKα1 or Akt to the same extent as those given a single injection.

What more could one want than a more optimal response from one exposure?!?

 

6. I could stand to lose a few pounds to get back to my "fighting" weight, so this sounds like a benefit to me.
 



#70 mikey

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Posted 12 September 2018 - 09:50 PM

Well, I'm still in for developing another supplement, but I don't think it would cost us hundreds of millions of dollars. I think it can be done with less money and with crowdfunding. We don't have to compensate our study group, and in fact, they would be paying to take part in the trial and to have an ownership in the profits of development. With a double blind trial, falsifying results as a patient would be just as bad for the data as if it didn't work, so as long as we explain that, our results would still be every bit as good as those done by a pharmaceutical company and we'd be setting a precedent for decentralized trials. Plus, in the process of crowdfunding, we'd already be marketing our drugs to the public.

 

Good creative thinking and what is proposed could set a precedent that would encourage more such events while discouraging the Big Pharma/FDA/Medical cartel from trying to stop us.


I don't think Mikey was saying it would cost hundreds of millions of dollars to develop trodusquemine as a supplement, just the opposite in fact. As a drug yes (FDA trials are expensive).  

 

Correct.



#71 YOLF

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Posted 12 September 2018 - 11:26 PM

I don't think Mikey was saying it would cost hundreds of millions of dollars to develop trodusquemine as a supplement, just the opposite in fact. As a drug yes (FDA trials are expensive).  

I didn't think that he was, I thought he was saying that developing Trodusquemine as a drug would be expensive. In my mind, paying a little bit more for it but getting insurance to pay for life extension is a game changer that the industry needs for the mission of achieving indefinite lives. 



#72 ryukenden

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Posted 13 September 2018 - 07:30 AM

I believe there is some risk that the unplugged fatty deposits might end up in other vital organs such as brain, lung causing stroke or pulmonary embolism?

#73 Daniel Cooper

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Posted 13 September 2018 - 02:07 PM

I believe there is some risk that the unplugged fatty deposits might end up in other vital organs such as brain, lung causing stroke or pulmonary embolism?

 

 

I suppose if you think of this like a solvent "dissolving" fatty buildups that might be a concern.  But, that almost certainly isn't how this stuff works.

 

Arterial plaques are mainly composed of fat engorged marcrophages which have become pathological and are called "foam cells" because of their foam like appearance under the microscope.

 

Some of the things that we think will reverse arterial plaques (like cyclodextrin for instance) appear to work by resetting these foam cells back to their non-pathological state where they then consume and dispose of these fatty deposits.  

 

Now, how does trodusquemine work?  The proposed mechanism is PTP1B inhibition.  That seems like a useful mechanism for a long term effect.  Frankly, I have trouble buying that as the mechanism for something at is said to have an effect from a single dose so I suspect that isn't the only mechanism in play.  To get that kind of "one shot" effect I would suspect something along the lines of a similar macrophage reprogramming which I do not believe would carry a huge risk of dislodging a plaque.

 

Trodusquemine has been through a couple of human trials.  Limited in number of subjects but human trials none the less. Some of those trials have been in diabetic patients which are pretty much guaranteed to have some amount of cardiovascular disease.  And, so far they haven't induced a stroke or heart attack.  As I said, these are relatively small trials but this isn't completely uncharted territory.

 

Every drug and supplement carries a risk.  Even FDA approved drugs. People have to make their assessment of the risk decide for themselves if they want to take it.  



#74 mikey

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Posted 13 September 2018 - 02:57 PM

I believe there is some risk that the unplugged fatty deposits might end up in other vital organs such as brain, lung causing stroke or pulmonary embolism?

 

A human safety study already resolved this type of safety concern, which is why the human breast cancer study was approved and in process until the sponsor went belly-up because of a lack of funding, after seeing that profiting from TD would not produce enough profits to satisfy normal corporation profit demands. (This is one reason that many potentially valuable drugs never make it to market.)

 

The human safety study is attached.



#75 Bzork

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Posted 14 September 2018 - 08:10 PM

I am interested participating in a group buy.

#76 mikey

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Posted 15 September 2018 - 03:17 AM

I am interested participating in a group buy.

 

This makes 14 today, folks. Thank you, Bzork.

 

DOSING
As to dosing, below is what appears to be a good starting point.

 

Note that this first applies to mice given TD intraperitoneal (injected in the abdomen), which was then adjusted for a human equivalent dose (HED).

 

I have not received a reply from Darren who said in another forum that  TD was "orally available," which most of us want. Determining how the intraperitoneal dose for mice in an HED for humans converts to oral use is still a question.

 

While I have not heard back from Darren I did find a study that likely provides some enlightenment. It is a study of DPM-100, an analog of TD.

A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models.

I have requested the full text from an author on ResearchGate. If I don't get a rapid response I will purchase the full text

As to dosing, quoting from Jules Clement Nguedia Assob, University of Buea:

"There are two conversions to perform. I think you should first convert the dose in Body surface area (BSA) in humans to body weight dose. i.e.: 3700 mg/sq.m (3700/37) is equivalent to 100 mg/kg for humans. 

Divide this value by 12 (the conversion factor from humans to mice) that is 100/12.  This will give you the body-weight dose corresponding to mice = 8.33 mg/kg. Freireich, EJ, et al. Quantitative comparison of toxicity of anticancer agents in mouse, rat, dog, monkey, and man. Cancer Chemother Rep.1966;50(4):219-244.

If we view the mouse study that showed one exposure reversing atherosclerosis we can begin to arrive at what might be a potential oral and SubQ dose of Trodusquemine.

 

"After 8 weeks HFD, a further 20 mice were injected with a single dose of 10mg/kg Trodusquemine and designated

accordingly..."

Thus, if I were injected IV with Trodusquemine, at my body weight of 200 pounds (90.0 kg), a single dose might be 90.9 kg x 8.33 mg = 0.757 grams. Golly, that is a whopping dose. It seems like it would only be OK if it was done in a two-hour IV drip, as was indicated for the human breast cancer study that was terminated. However, the doctor that would do that for me is retired.

SubQ administration of that large amount sounds scary or at the very least, quite irritating. I expect the worse and that I would get some terrible reaction, putting that much of the majority of substances SubQ anywhere.

Or, if considered for oral administration, we need to determine what Darren said would apply in a post where he said that Trodusquemine was orally available. I messaged Darren on LongeCity but have not received a response, so I found the study hyperlinked above when I searched for “oral dose for Trodusquemine.”

 

Please chip in your thoughts. This study does give us something to go on.

If I don't receive the full text by Saturday PM, I will order it.


 



#77 roscotx

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Posted 15 September 2018 - 03:05 PM

I am in as well.

 

roscotx



#78 zorba990

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Posted 15 September 2018 - 04:20 PM

This makes 14 today, folks. Thank you, Bzork.

DOSING
As to dosing, below is what appears to be a good starting point.

Note that this first applies to mice given TD intraperitoneal (injected in the abdomen), which was then adjusted for a human equivalent dose (HED).

I have not received a reply from Darren who said in another forum that TD was "orally available," which most of us want. Determining how the intraperitoneal dose for mice in an HED for humans converts to oral use is still a question.

While I have not heard back from Darren I did find a study that likely provides some enlightenment. It is a study of DPM-100, an analog of TD.

A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models.

I have requested the full text from an author on ResearchGate. If I don't get a rapid response I will purchase the full text
As to dosing, quoting from Jules Clement Nguedia Assob, University of Buea:
"There are two conversions to perform. I think you should first convert the dose in Body surface area (BSA) in humans to body weight dose. i.e.: 3700 mg/sq.m (3700/37) is equivalent to 100 mg/kg for humans.

Divide this value by 12 (the conversion factor from humans to mice) that is 100/12. This will give you the body-weight dose corresponding to mice = 8.33 mg/kg. Freireich, EJ, et al. Quantitative comparison of toxicity of anticancer agents in mouse, rat, dog, monkey, and man. Cancer Chemother Rep.1966;50(4):219-244.

If we view the mouse study that showed one exposure reversing atherosclerosis we can begin to arrive at what might be a potential oral and SubQ dose of Trodusquemine.


"After 8 weeks HFD, a further 20 mice were injected with a single dose of 10mg/kg Trodusquemine and designated
accordingly..."

Thus, if I were injected IV with Trodusquemine, at my body weight of 200 pounds (90.0 kg), a single dose might be 90.9 kg x 8.33 mg = 0.757 grams. Golly, that is a whopping dose. It seems like it would only be OK if it was done in a two-hour IV drip, as was indicated for the human breast cancer study that was terminated. However, the doctor that would do that for me is retired.

SubQ administration of that large amount sounds scary or at the very least, quite irritating. I expect the worse and that I would get some terrible reaction, putting that much of the majority of substances SubQ anywhere.

Or, if considered for oral administration, we need to determine what Darren said would apply in a post where he said that Trodusquemine was orally available. I messaged Darren on LongeCity but have not received a response, so I found the study hyperlinked above when I searched for “oral dose for Trodusquemine.”


Please chip in your thoughts. This study does give us something to go on.

If I don't receive the full text by Saturday PM, I will order it.



Since when is 757mg a whopping dose? Am I misreading here?

#79 mikey

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Posted 15 September 2018 - 05:26 PM

"Since when is 757mg a whopping dose? Am I misreading here?" 

Just attempting to place a dissolved 757 SubQ (so that with a diluent its mass would seem like it would create a huge lump SubQ, with irritation and a potentially strong immune reaction.

 

When I had testosterone pellets (TP) placed in my glute to address my low production of testosterone I experienced a strong irritation in that site and strong enough immune reaction that an old staph infection, which my immune system had contained and kept dormant (compartmentalized) woke up and expressed pus, two times, from my elbow.

The immune dysfunction caused by the new immune system having to "deal" with the mass of T pellets in my butt caused a systemic immune burden. My immune system had been focused on the large mass of (foreign materials) as T pellets,  so the dormant infection was able to express with less available immune agents. Too many fights at once and the "army" could do both jobs well.

 

I assume that most people are attracted to that notion that only using it TD one time could effective, based on the mouse study.

 

I am wary of such invasive procedures putting a lof material in one locus. This is likely why the breast cancer study that ran out of money was to administer TD in a two-hour drip. 757 mg over two hours would likely not cause the kinds of problems that a 757 mg depot would cause, whether IV, IM, Subq, whatever.

 

I will work to find a logical oral dose and invite help. People can do whatever they want but I'm going to be as conservative as possible.

 

(If I had a doctor to do a 2-hour IV of 757 mg, I would do it.)

 

Let's determine what a potential oral dose is and everyone can do as they wish, of course.

 

(Also I suggest considering that SubQ in fat tissues has less potential to cause infections than IM.)
 

Also important we will need to know the conversion to an oral dose which I logically would not absorb as well, therefore more than 757 mg would need to be taken.

I am eager to read the results about the oral bioavailability of TD's analog, DPM-1001, shown in A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models.

I will order the full text now.


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#80 mikey

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Posted 15 September 2018 - 05:56 PM

I further ordered "Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine"

 

The library is offline until Wednesday, so expect full texts of these two oral dosing studies about Wednesday or Thursday.



#81 Daniel Cooper

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Posted 15 September 2018 - 07:25 PM

Here you go Mikey -

 

A potent, selective and orally bioavailable inhibitor of the protein tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models

 

 

 

 



#82 Daniel Cooper

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Posted 15 September 2018 - 07:28 PM

I further ordered "Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine"

 

The library is offline until Wednesday, so expect full texts of these two oral dosing studies about Wednesday or Thursday.

 

And this one:

 

Multistep Inhibition of αSynuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine

 

 


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#83 bladedmind

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Posted 15 September 2018 - 10:46 PM

Thanks to all for thinking this through.  if there is a goup buy I'd appreciate taking part in it. 



#84 mikey

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Posted 16 September 2018 - 08:20 PM

Thanks to all for thinking this through.  if there is a goup buy I'd appreciate taking part in it. 

 

You're in. This makes 15, folks.



#85 mikey

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Posted 16 September 2018 - 08:28 PM

I further ordered "Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine"

 

The library is offline until Wednesday, so expect full texts of these two oral dosing studies about Wednesday or Thursday.

 

Ah. The patent (attached) has some detailed dosing instructions for IV, subq, nasal and oral use. Section 8 has the following:

Note the patent's stated dose equals less than the dose-effectiveness study on mice.

 

Let's note that a patent is going to give round high and low number so that they can enforce their patent right if anyone comes up with a similar formula or use or use for the ingredient. So, we might consider that the breast cancer number are more likely where are to devise or human oral and subq dosing.

 

The following dosage ranges are exemplary. Suitable dosages for intravenous administration are generally about 20 micrograms to 40 milligrams of active compound per kilogram body weight. This would  

Suitable dosage ranges for
intranasal administration are generally about 0.01 mg/kg body weight to 1 mg/kg body weight. Suitable dosage ranges for topical administration are generally at least about 0.01% by weight.

Suitable dosages for oral administration are generally about 500 micrograms to 800 milligrams per kilogram body weight, and preferably about 1-200 mg/kg body weight. Suppositories generally contain, as the active ingredient, 0.5 to 10% by weight of the aminosterol active ingredient. Oral formulations preferably contain 10% to 95% active ingredient.

So, doing this equation at 800 mg/kg = 72.72 x 90.0 kg (for myself x the HED for mice) = 0.757grams.  x  0.135 grams or 135 mg to for humans yields 

https://www.ncbi.nlm...les/PMC4804402/

 


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#86 Rocket

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Posted 17 September 2018 - 12:09 AM

You're in. This makes 15, folks.


16 as long as meatsauce isn't organizing things.
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#87 docmaas

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Posted 17 September 2018 - 01:12 AM

Not sure if I committed or not but count me in.

 

Mike


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#88 Beetlejuice

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Posted 17 September 2018 - 02:05 PM

You're in. This makes 15, folks.


Hope you’re counting me in that
Beetlejuice

#89 OP2040

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Posted 17 September 2018 - 06:28 PM

Count me in (as another potential).  My reservations are price and dosing.  I hate the idea of IV, and even subQ at this point.  But even if oral is proven to be OK, I would like to know for sure that it is both OK, and effective.  I did read a lot of these studies in the past, but filed them away for that very reason.  Kudos on whipping up some enthusiasm :-D

 

 



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#90 Orinoco

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Posted 17 September 2018 - 10:26 PM

So 17 members now? Seems enough to get this going. 

 

Sorry if this had been mentioned already; but did we know of a supplier yet?







Also tagged with one or more of these keywords: arterial plaque, trodusquemine, msi-1436, cardiovascular disease, coronary arteries, carotid arteries, calcification, mouse study, cancer, diabetes

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