TSA (Trichostatin A) mystatin inhibitor

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    TSA (Trichostatin A) mystatin inhibitor


    In the May issue of MD TSA commercially known as Trichostatin A is said to markedly increase follistatin which is a internal myostatin blocker. Patrick Arnold states that a 220 lbs man would need around 60mg of this compound a day. I did a search and was able to find the Trichostatin on a couple of research chem. site for $84.00 for 1mg, $352 for 5mg and $616.00 for 10mg (expensive but interresting).


    Darron Bryant

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    $ 111000 for 1 month cycle.
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    This would be a good project for LMD!!
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    Quote Originally Posted by Darron Bryant View Post
    In the May issue of MD TSA commercially known as Trichostatin A is said to markedly increase follistatin which is a internal myostatin blocker. Patrick Arnold states that a 220 lbs man would need around 60mg of this compound a day. I did a search and was able to find the Trichostatin on a couple of research chem. site for $84.00 for 1mg, $352 for 5mg and $616.00 for 10mg (expensive but interresting).


    Darron Bryant
    u sure it was /mcg not /mg?? just checking cause i would really like to check this out
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    SCIENTISTS SHOW DRUG CAN COUNTERACT MUSCULAR DYSTROPHY IN MICE

    Scientists at the National Institute of Arthritis and Musculoskeletal and
    Skin Diseases (NIAMS) and other institutions have demonstrated for the
    first time that a single drug can rebuild damaged muscle in two strains of
    mice that develop diseases comparable to two human forms of muscular
    dystrophy. This advance, which is reported online in "Nature Medicine", is
    the latest from a research collaboration that began several years ago by
    the teams of Vittorio Sartorelli, M.D., at NIAMS and Pier Lorenzo Puri,
    M.D., Ph.D., now at Dulbecco Telethon Institute (DTI) in Rome, Italy and
    The Burnham Institute in La Jolla, Calif.

    The scientists tested trichostatin A (TSA), an inhibitor of the enzyme
    deacetylase, in two mouse models of muscular dystrophy (MD): one that
    naturally develops a disease similar to Duchenne muscular dystrophy in
    humans, the other genetically altered to develop a form of dystrophy
    similar to the human limb-girdle muscular dystrophy. At 45 to 90 days of
    age, the muscles of the MD mice showed much fibrous tissue and
    infiltration of inflammatory cells. Unlike healthy mice, the mice with MD
    were unable to either run on a treadmill or swim. MD mice given TSA daily
    for two to three months, however, were virtually indistinguishable from
    healthy mice, and biophysical studies showed virtually no difference
    between the muscle strength of the mice with MD given the deacetylase
    inhibitor and healthy mice.

    "This is the first example of using a drug to counteract muscular
    dystrophy in mouse models," says Dr. Sartorelli. Yet he points out that
    the drug is only promoting muscle regeneration - it is not curing the
    defect that causes muscle deterioration. Further studies are needed to
    determine how long the drug works and if it works in larger animals with
    bigger muscles, such as dogs, before such drugs can be tested in people.

    The finding has its roots in several of the group's earlier advances, the
    first of which was reported in 2002 in the "Proceedings of the National
    Academy of Sciences"1. The scientists found that treating muscle cells
    with deacetylase inhibitors caused the cells to grow larger and
    differentiate better, says Dr. Sartorelli, the group leader of the Muscle
    Gene Expression Group in NIAMS' Laboratory of Muscle Biology. The next
    advance, published two years later in the journal "Developmental Cell"2,
    was the discovery that the inhibitor worked by changing gene expression,
    causing some genes to be upregulated, or make more protein, and others to
    be downregulated, or make less protein. Among the genes positively
    regulated by the inhibitors was a gene for a key protein called
    follistatin.

    "It was known that follistatin had a role in muscle development, so by
    understanding normal muscle development we knew that follistatin would
    block the activity of another protein called myostatin," says Dr.
    Sartorelli. "If you block myostatin, you get big muscles."

    One way of inactivating myostatin is to upregulate follistatin. Basically,
    what follistatin does is to prevent myostatin from working, says Dr.
    Sartorelli. When his group treated the cells with deacetylase inhibitors,
    they saw that the cells became large and that follistatin was
    overexpressed. However, when the group treated the cells with the
    inhibitors and then used other agents to block follistatin, the cells
    didn't become bigger, showing that one of the most important pathways the
    inhibitors use to create bigger muscles involves the activation of
    follistatin. "If you didn't have follistatin anymore, these drugs didn't
    work," he says.

    Moreover, Drs. Sartorelli's and Puri's groups were able to show that in
    normal animals, follistatin is upregulated when muscle is damaged. When
    the researchers induced muscle damage and then gave the inhibitors,
    follistatin was even more expressed, as were two proteins that reflect
    increased muscle regeneration.

    Other Italian groups contributed to the present study, including the
    Istituto Dermatologico dell' Immacolata of Rome; the Department of
    Experimental Medicine, Human Physiology Unit, University of Pavia; and the
    Laboratory of Vascular Biology and Genetic Therapy, Centro Cardiologico
    Monzino, Milan.

    This study was supported in part by the Intramural Research Program of the
    National Institute of Arthritis and Musculoskeletal and Skin Diseases of
    the National Institutes of Health. Other support was provided by Telethon
    (Italy), the Muscular Dystrophy Association and the Parent Project
    Organization (Italy).

    The mission of the National Institute of Arthritis and Musculoskeletal and
    Skin Diseases (NIAMS), a part of the Department of Health and Human
    Services' National Institutes of Health, is to support research into the
    causes, treatment, and prevention of arthritis and musculoskeletal and
    skin diseases; the training of basic and clinical scientists to carry out
    this research; and the dissemination of information on research progress
    in these diseases. For more information about NIAMS, call the information
    Clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the
    NIAMS Web site at

    <http://www.niams.nih.gov>

    The National Institutes of Health (NIH) -- "The Nation's Medical Research
    Agency" -- includes 27 Institutes and Centers and is a component of the
    U.S. Department of Health and Human Services. It is the primary federal
    agency for conducting and supporting basic, clinical and translational
    medical research, and it investigates the causes, treatments, and cures
    for both common and rare diseases. For more information about NIH and its
    programs, visit

    <http://www.nih.gov>
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    Any data on the specificity of this effect to skeletal muscle though?
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    I'm a bit skeptical that these results can be replicated in humans..... Don't get me wrong though because im all for new Beast Makers....hope this pans out in humans. It also sounds promising for people who suffer from MD.
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    Quote Originally Posted by BMW View Post
    u sure it was /mcg not /mg?? just checking cause i would really like to check this out
    its milligram unfortunately

    i would imagine its possible that this stuff could be manufactured cheaply enough if some company would have the incentive to invest in the research and development

    however this is an endeavor far beyond the technical and financial capabilities of a supplement company. I suppose a chinese pharmaceutical manufacturer could pull it off though
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    Quote Originally Posted by CDB View Post
    Any data on the specificity of this effect to skeletal muscle though?
    this works through the myostatin pathway. although myostatin inhibition has been theorized to cross react with cardiac muscle, it is my understanding that in-vivo research has not shown this to be a major concern
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    Sodium butyrate may have similar effects via histone hyperacetylation. It is also cheap and well tolerated orally.
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    Quote Originally Posted by Jack Smack View Post
    Sodium butyrate may have similar effects via histone hyperacetylation. It is also cheap and well tolerated orally.
    i think you are talking about sodium phenylbutyrate, not sodium butyrate

    its not cheap and its also supposed to give a pretty ****ed up smell to people that use it

    it also depletes glutamine among other not so desirable things.

    i looked into it and came to the conclusion it was not a good idea, but if anyone scores some and tries it i would like to know the results.

    BTW, it can be made cheaply from gamma-butyrolactone (GBL). GBL used to be cheap and readily available but now is a controlled substance of course cuz its a GHB analog

    bTW, it can be made
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    Quote Originally Posted by Patrick Arnold View Post
    i think you are talking about sodium phenylbutyrate, not sodium butyrate

    its not cheap and its also supposed to give a pretty ****ed up smell to people that use it

    it also depletes glutamine among other not so desirable things.

    i looked into it and came to the conclusion it was not a good idea, but if anyone scores some and tries it i would like to know the results.

    BTW, it can be made cheaply from gamma-butyrolactone (GBL). GBL used to be cheap and readily available but now is a controlled substance of course cuz its a GHB analog

    bTW, it can be made



    No Sir, I am indeed speaking of Sodium butyrate, NOT Sodium phenylbutyrate.

    I just grabbed the below because it was the first of many, many studies concerning NaBu and TSA (I really wasn't concerned with the study it self or the outcome). I just wanted to illustrate that NaBu does hypoeracetylate histone and that it is often studied with TSA.

    I realise NaBu is a shot gun approach to a specific problem, but it may be the best cheap and readily available dietary supplement that we currently have to try and raise follistatin through modification of histone acetylation.



    Effects of the histone deacetylases inhibitors sodium butyrate and trichostatin A on the inhibition of gap junctional intercellular communication by H2O2- and 12-O-tetradecanoylphorbol-13-acetate in rat liver epithelial cells.



    Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, San 56-1, Sillim-dong, Gwanakgu, Seoul 151-742, South Korea.

    The histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) and sodium butyrate (NaBu) are considered as potent therapeutic agents for cancer treatment presenting therapeutic benefits with less risk of side effects. The microbial metabolite, TSA is a potent reversible and highly specific inhibitor of mammalian histone deacetylases. NaBu causes hyperacetylation of core histones with effects similar to TSA but it is not a specific inhibitor of HDACs. The gap junction is a channel in the plasma membrane of most cell types which allows direct communication (gap junctional intercellular communication; GJIC) of small molecules and ions. Modulation of GJIC is a known cellular event associated with tumor promotion. The effects of NaBu and TSA on the H(2)O(2)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced GJIC inhibition of WB cells and the mechanisms involved in the process were assessed. TSA and NaBu exerted differential preventive effects on the H(2)O(2) and TPA-induced inhibition of GJIC as well as hyperphosphorylation of connexin43 (Cx43) in WB-F344 rat liver epithelial cells (WB cells). NaBu prevented the TPA-induced GJIC inhibition via ERK1/2 inactivation whilst TSA restored the H(2)O(2)-induced GJIC inhibition and Cx43 hyperphosphorylation by preventing p38 MAP kinase. The inhibition of tyrosine phosphorylation and down-regulation of src protein observed may also contribute to Connexin 43 dephosphorylation and GJIC restoration by TSA and NaBu partly through depletion of src protein pool. Thus, TSA and NaBu exert differential effects on chemically induced GJIC inhibition via modulation of MAP kinases and partly, tyrosine kinases.
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    Quote Originally Posted by Jack Smack View Post
    No Sir, I am indeed speaking of Sodium butyrate, NOT Sodium phenylbutyrate.

    I just grabbed the below because it was the first of many, many studies concerning NaBu and TSA (I really wasn't concerned with the study it self or the outcome). I just wanted to illustrate that NaBu does hypoeracetylate histone and that it is often studied with TSA.

    I realise NaBu is a shot gun approach to a specific problem, but it may be the best cheap and readily available dietary supplement that we currently have to try and raise follistatin through modification of histone acetylation.

    I am guessing that you would need to consume alot of sodium butyrate to acheive the desired effect (the doses of sodium phenylbutyrate are already high and i am assuming that this is stronger than butyrate).

    If you are familiar with the smell of butyric acid (rancid butter) then you can see what the likely problems with this stuff would be. You would stink incredibly badly
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    PA- Can't remember where I read it, I wrote it down, but somewhere somebody was talking about how you were going to release some info on an antibiotic that inhibits myostatin, something about G148/geneticin? Are you still planning on doing that?

    Also are you ever planning on doing anything with that carrageenan product you wrote about a while ago?

    Thanks.
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    Quote Originally Posted by Speedbacker View Post
    PA- Can't remember where I read it, I wrote it down, but somewhere somebody was talking about how you were going to release some info on an antibiotic that inhibits myostatin, something about G148/geneticin? Are you still planning on doing that?

    Also are you ever planning on doing anything with that carrageenan product you wrote about a while ago?

    Thanks.
    this thread is about the antibiotic. i had written about it in md

    someone else is thinking about the carrgeenan product. he may release it
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    Quote Originally Posted by Patrick Arnold View Post
    this thread is about the antibiotic. i had written about it in md
    LOL, completely missed that. Thanks
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    Quote Originally Posted by Patrick Arnold View Post
    someone else is thinking about the carrgeenan product. he may release it
    Thanks for your response. Whoever it is, hopefully he does release it.
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    Quote Originally Posted by Speedbacker View Post
    Thanks for your response. Whoever it is, hopefully he does release it.
    if anyone knows of a place that will do sterile filling of vials let me know and i will pass the info. on to him

    it will help expedite this

    i don't think its a good idea for me to have any part of manufacturing it otherwise i would do it for him
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    Quote Originally Posted by Patrick Arnold View Post
    if anyone knows of a place that will do sterile filling of vials let me know and i will pass the info. on to him

    it will help expedite this

    i don't think its a good idea for me to have any part of manufacturing it otherwise i would do it for him
    PA- Would this work?

    cGMP Sterile Filling Facility - GMP Sterile Fill Drug Filling
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    Quote Originally Posted by Speedbacker View Post
    i dunno. maybe.

    thanks for caring
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    Quote Originally Posted by Patrick Arnold View Post
    i dunno. maybe.

    thanks for caring
    Well, ****, if that product works anything like how you wrote in your article a while ago on musclegurus, then i'll do anything to speed up the process!
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    Pat - I interned at a little chemical company that used butyric anhydride in one of it's plants to make pharm. coatings. (Basically react the anhydride with cellulose - wood chips - in a CSTR.)

    I worked across the street - and dear GOD did that place smell awful. Forget rancid butter - it was week old moldy baby sh*t.

    The operators that worked in that plant came home smelling like it. Worst was playing basketball with one of them - when he'd sweat that crap would start seeping out of his pores.




    Anyway - yeah anything butyric is BAAAAAAAAAAAAAAAAD.
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    Quote Originally Posted by Speedbacker View Post
    Well, ****, if that product works anything like how you wrote in your article a while ago on musclegurus, then i'll do anything to speed up the process!
    lately i have pondered the potential of longR3IGF-1 mixed with this stuff.

    the carrageenan solution is over 99% water so the stuff should mix and be fine. the carrageenan solution hangs on to water and keeps it from diffusing out really quickly, so i can see the possibility of it keeping the IGF-1 in the muscle longer. which of course would lead to much greater potential for interaction with IGF-1 receptors there
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    Quote Originally Posted by jmh80 View Post
    Pat - I interned at a little chemical company that used butyric anhydride in one of it's plants to make pharm. coatings. (Basically react the anhydride with cellulose - wood chips - in a CSTR.)

    I worked across the street - and dear GOD did that place smell awful. Forget rancid butter - it was week old moldy baby sh*t.

    The operators that worked in that plant came home smelling like it. Worst was playing basketball with one of them - when he'd sweat that crap would start seeping out of his pores.




    Anyway - yeah anything butyric is BAAAAAAAAAAAAAAAAD.

    the guy that used to be our production manager worked at a plant that worked with buytric acid before he got a job with us. he said that it would linger and linger and was impossible to get rid of. he had to endure being treated like a pariah anywhere he went (gym, supermarket, etc)

    yes it is one of the strongest and most vile stenches i know of
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    Quote Originally Posted by Patrick Arnold View Post
    lately i have pondered the potential of longR3IGF-1 mixed with this stuff.

    the carrageenan solution is over 99% water so the stuff should mix and be fine. the carrageenan solution hangs on to water and keeps it from diffusing out really quickly, so i can see the possibility of it keeping the IGF-1 in the muscle longer. which of course would lead to much greater potential for interaction with IGF-1 receptors there
    That would be nice! PA, is there really any chance that somebody will produce the carrageenan product? I know you said that somebody was looking at it, but what are the chances? I am greatly interested in your IGF-1 LR3 idea, with the carrageenan solution.
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    Quote Originally Posted by Speedbacker View Post
    That would be nice! PA, is there really any chance that somebody will produce the carrageenan product? I know you said that somebody was looking at it, but what are the chances? I am greatly interested in your IGF-1 LR3 idea, with the carrageenan solution.
    yeah the guy wants to do it. just needs the ability to do it, either with his own equipment (which he would have to buy) or outsourced
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    Quote Originally Posted by Patrick Arnold View Post
    the guy that used to be our production manager worked at a plant that worked with buytric acid before he got a job with us. he said that it would linger and linger and was impossible to get rid of. he had to endure being treated like a pariah anywhere he went (gym, supermarket, etc)

    yes it is one of the strongest and most vile stenches i know of
    Chemstry - pretty remarkable, ain't it? (Add one more CH3 and you get vile from propanoic acid....)
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    Quote Originally Posted by jmh80 View Post
    Chemstry - pretty remarkable, ain't it? (Add one more CH3 and you get vile from propanoic acid....)
    subtract

    prop = 3, but=4
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    Yeah - that's what I meant: add one C to prop to get vile (but).
  

  
 

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