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Potential negative interaction of Agmatine and other supps

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    Potential negative interaction of Agmatine and other supps


    I've been reading up on Agmatine as I'm currently taking it and looking to buy more.

    I came across some interesting info about possible negative interactions of Agmatine with other substances and wanted know whether it's valid.

    List of ingredients that may not combine well with Agmatine:
    L-Arginine or L-Citrulline - for some neurological effects; cardiovascular interactions not well elucidated.
    Yohimbine or Rauwolscine - Agmatine activates the α2A receptor that these inhibit.
    D-Aspartic Acid - due to reducing signalling via the NMDA receptors.

    Can anyone confirm whether these points are accurate?

    I know that a lot of people combine Agmatine and Citrulline, for example. Don't remember ever reading about any problems.

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    In for answers
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    Quote Originally Posted by doggy_dog View Post

    List of ingredients that may not combine well with Agmatine:
    L-Arginine or L-Citrulline - for some neurological effects; cardiovascular interactions not well elucidated.
    Yohimbine or Rauwolscine - Agmatine activates the α2A receptor that these inhibit.
    D-Aspartic Acid - due to reducing signalling via the NMDA receptors.
    I don't believe there is a huge need for concern with any of those, but the questions come from still not 100% understanding how agmatine produces the vasodilation effect. L-arginine and L-citrulline will also cause vasodilation, but through a different way then agmatine does, so there may be concern about too much of a good thing. Most healthy people have enough homeostatic mechanisms to protect them, but if you're overdoing something from different angles, you can reach a point where you're doing more harm than good. However, reasonable use of these doesn't put us in danger. But that is for the cardiovascular effects which are why a lot of people on this board use them. The neurological effects get more complicated and the concern is more that they could negate each other.

    Yohimbine and Rauwolscine inhibit the a2A receptor, so this would negate agmatine activity there, BUT agmatine doesn't work solely through the a2A receptor and some studies suggest that it doesn't do anything there at all.

    With DAA, again you have possible negating effects so I would simply say to take DAA and agmatine at separate times if this is a concern. In the past I have taken DAA in the morning and agmatine before I train in the evening.
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    OP, where did you see this? Links?

    MAN's Prometheus Rising (RIP) contained both agmatine and daa, and it's one of my favorite products of all time.
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    Quote Originally Posted by mpaquett View Post
    OP, where did you see this? Links? MAN's Prometheus Rising (RIP) contained both agmatine and daa, and it's one of my favorite products of all time.
    Mine too; I leaned up quite a bit and felt "on" during my runs with it. I certainly didn't feel anything negative with the combo of Agmatine and DAA
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    Quote Originally Posted by mpaquett View Post
    OP, where did you see this? Links?

    MAN's Prometheus Rising (RIP) contained both agmatine and daa, and it's one of my favorite products of all time.
    Test Powder as well
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    Ok, so far the feedback has been positive.


    Here is a comprehensive article I came across:

    http://examine.com/supplements/Agmatine/

    I also read a couple of studies but have to find them again.
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    It should be just fine to take DAA and agmatine together. That author was speaking very generally when in reality NMDA receptor subtypes can be very diverse, so it's not always as easy as A+B=C. A lot of studies (if not most) are done in vitro with specific NMDA receptor subtypes and very specific agonists and antagonists.

    Just wanted to clarify before I get accused of bashing anybody's product.
    Last edited by Aleksandar37; 01-07-2014 at 12:08 PM. Reason: clarifying NMDA as NMDA receptor
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    Quote Originally Posted by doggy_dog View Post
    Ok, so far the feedback has been positive.


    Here is a comprehensive article I came across:

    http://examine.com/supplements/Agmatine/

    I also read a couple of studies but have to find them again.
    and here is the problem with "studies" (well at least one of the problems anyway..)
    this guy starts a thread all freaked out on stacking, based on a "hypothetical" series of thoughts with no firm basis of conclusion, and said "study" does not even use oral agmatine at all in any part of the study -- it is all injected

    (to the credit of the author however, at least he points this fact out and also mentions further study is needed on orally ingested ag)

    so much misunderstanding, leading to so much misinformation....
    there is such thing as too much info, in case you didn't know
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    Quote Originally Posted by snagencyV2.0 View Post
    and here is the problem with "studies" (well at least one of the problems anyway..)
    this guy starts a thread all freaked out on stacking, based on a "hypothetical" series of thoughts with no firm basis of conclusion, and said "study" does not even use oral agmatine at all in any part of the study -- it is all injected

    (to the credit of the author however, at least he points this fact out and also mentions further study is needed on orally ingested ag)

    so much misunderstanding, leading to so much misinformation....
    there is such thing as too much info, in case you didn't know
    The OP was never freaking out and asked valid questions out of concern. And there is no such thing as too much information. However, selective use of information to fit one's needs leads to problems.
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    Quote Originally Posted by Aleksandar37 View Post
    The OP was never freaking out and asked valid questions out of concern. And there is no such thing as too much information. However, selective use of information to fit one's needs leads to problems.
    well thanks alex for your own view and understanding of what has transpired in this thread
    so now is it my turn to say "no, he was freaked out" and we go back and forth on the matter?
    wow man..that post was rather needless as much as it was fruitless

    my exaggeration is pointed reference to mad misinformation from ppl who glance thru these threads and read the highlights, without any real understanding of the concept let alone substance of the discussion, and parrot misinformation ignorantly accordingly..and I never said this applied to OP, I simply made a referenced remark to a concern he had, which was not even based on oral ingestion of agmatine to begin with, yet he made reference to in support of these claims he based on his reading (which would lead to some saying he was indeed "freaked out")

    continue on with your trying to shape things to your own personal viewpoint however, sir
    let me know how that works out for you
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    Quote Originally Posted by snagencyV2.0 View Post
    said "study" does not even use oral agmatine at all in any part of the study -- it is all injected


    my exaggeration is pointed reference to mad misinformation from ppl who glance
    Dear "Educator",

    Perhaps if you "glance" again at the article (not a study as you refer to it), you will see that he does indeed cite articles which used oral doses of agmatine. In fact, he uses the word "oral" 33 times, which you must have missed.
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    Quote Originally Posted by Aleksandar37 View Post
    Dear "Educator",

    Perhaps if you "glance" again at the article (not a study as you refer to it), you will see that he does indeed cite articles which used oral doses of agmatine. In fact, he uses the word "oral" 33 times, which you must have missed.
    I did glance at the article again, in which oral ag was not mentioned once, but studies referring to rat injections were cited numerous times

    what article are you looking at?


    Summary (All Essential Benefits/Effects/Facts & Information)


    Agmatine is a biogenic amine that is derived from L-arginine via decarboxylation (removal of a carboxylic acid group), and appears to be stored in neurons and released upon neuronal activation. Due to this and other properties, agmatine is a seen as a neurotransmitter or at least a neuromodulator. It's most relevant and interesting potential uses (research, overall, is preliminary) include the treatment of neuropathic pain, drug addiction, and protecting the brain from toxins and stroke.

    Agmatine is known as a pleiotropic molecule, and has a large amount of direct mechanisms. These include inhibition of NMDA receptors and possibly also nicotinic acetylcholine receptors, and activation of imidazoline receptors; there is possibly activation of α2-adrenergic receptors but this is not 100% clear (some studies suggest that there is no effect). Agmatine also directly inhibits NOS enzymes (aside from iNOS, at concentrations too high to be concerned with) and may also inactivate these enzymes (more biologically relevant), but despite this apparent inhibition of Nitric Oxide metabolism it appears to directly act as a mimetic and circumvent its own inhibition; the result is somewhat of a regulation of nitric oxide in instances where it is improperly elevated. Other direct mechanisms include inhibition of calcium channels (fairly potent, with an IC50 value of 1.2ÁM) and inhibition of serotonin receptor subset 5-HT3.

    Other mechanisms which are not ascertained if they are direct or vicariously through one of the aforementioned ones include activation of PI3K/Akt (found in multiple cell lines) and adenyl cyclase activation (noted in the prefrontal cortex, it is unsure if this is from serotonin or adrenergic receptors). A release of opioids (β-endorphins) has also been confirmed to be secondary to imidazoline receptor activation in the adrenal glands, and Ryanidine receptors are activated (which release intracellular calcium) although it is not sure if this causes or is a result of the nitric oxide interactions.

    Agmatine has a large number of roles and mechanisms in the body. The primary four roles (that seem to be most important) involve positively influencing imidazoline receptors and α2-adrenergic receptors while inhibiting NDMA receptors and NOS enzymes


    In regards to pain, there are mixed effects (as agmatine appears to have a modulatory role) but overall it appears to be analgesic. While agmatine in isolation can augment the perception of pain (by enhancing the signalling through a receptor known as ASIC3 that mediates pain associated with acidity), it appears to release β-endorphin and synergistically enhance the actions of any opioids. Due to the inherent release of a weak opioid and synergism with opioids, agmatine is able to reduce pain and pharmaceutically is synergistic with both morphine and fentanyl (increasing pain killing, reducing tolerance, and reducing addiction).

    The ability of heat to cause pain in rats is normally reduced by cannabinoid signalling (such as Marijuana), and agmatine also appears to provide synergistic pain relief with cannabinoids. Other potential synergisms between agmatine and marijuana are not yet investigated, but it appears that anything through the CB1 receptor is augmented under the influence of agmatine.

    Agmatine has both pro-pain and anti-pain mechanisms (technically speaking), but it appears that due to being very synergistic with established anti-pain pathways that the overall effect of agmatine injections into research animals is one of pain relief. The pain relief is fairly notable as well


    For strokes, there are repeated studies in rats using injections of agmatine (around 100mg/kg) that suggest potent protective effects that near normalization of symptoms after 3-4 days with minor protective effects noted within a few hours. It is thought that this is due to modulating nitric oxide metabolism, as the increase in iNOS seen during stroke (which normally produces too much nitric oxide and damages tissue) is attenuated while the acute suppression of eNOS (which is protective) is preserved. Nitric oxide and its oxidative metabolite known as peroxynitrate are also attenuated, and this is thought to result in less overall damage.

    When cognition and brain edema are tested after a stroke, they appear to be significantly reduced and almost normalized relative to control rodents.

    Although there is no human evidence at this moment in time, agmatine appears to have potent protective properties against strokes


    Another claim of agmatine supplementation are the anti-addictive properties, which appear to exist in rats who become addicted to opioidergic drugs (morphine, fentanyl, and oxycodone) where agmatine injections during drug administration reduce addictive effects. There is also a potential mechanism for agmatine to reduce Nicotine dependence (which needs to be explored further) and currently the only failure has been on cocaine, which is known to be low on a rewards scale in rats; cocaine may require a human study.

    Agmatine may also help with alcohol and opioid drug withdrawal by reducing symptoms thereof.

    Agmatine is potentially anti-addictive, and awaits human studies to confirm what is seen in rodent models


    Overall, agmatine is a highly promising research chemical that will likely be important in the future. It's usage as a common supplement is limited by a lack of human trials at this moment in time, and although there are a few studies using oral ingestion here and there (which confirm that it does appear to be absorbed) the vast majority of studies use injections of agmatine. Future research will need to re-establish all the current observations following oral ingestion (or at least, more pharmacokinetic studies should be conducted including tissue distribution so we can make educated guesses on oral doses).
    please note bottom boldened .. why read further when the summary makes no mention to support any hypothesis of idea that is being put forward here?

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    Quote Originally Posted by snagencyV2.0 View Post
    I did glance at the article again, in which oral ag was not mentioned once, but studies referring to rat injections were cited numerous times

    what article are you looking at?
    And you complain about misinformation? This is tantamount to reading an abstract and claiming to understand the article that follows. Everybody else that actually reads the article will see that several oral studies are cited, despite the claims of "snags".
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    Quote Originally Posted by Aleksandar37 View Post
    And you complain about misinformation? This is tantamount to reading an abstract and claiming to understand the article that follows. Everybody else that actually reads the article will see that several oral studies are cited, despite the claims of "snags".
    before I start paying attention to something, i'll wait until there are more than a few isolated studies "here and there" (as noted) that show inconclusive data ... sorry, I don't play the paranoid, over-worried, live and die by half-ass-study-I-just-read persona very well

    you're more than welcome to continue your own oversight and expertise in that role, alex
    take care, and best to you in 2014


    *as a sidenote, and to no one in particular:
    I swear some of you guys would be soooo much better off if you'd get your nose out of those books, stop worrying about the latest "study", or investigating the latest-greatest-miracle pill on the market, and just go EAT FOOD and go DO WORK, hit the damn weights

    that is all
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    Quote Originally Posted by Aleksandar37 View Post
    it's not always as easy as A+B=C. A
    Umm could maybe I buy a vowel alex or that is pat
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    Quote Originally Posted by snagencyV2.0 View Post
    my exaggeration is pointed reference to mad misinformation from ppl who glance thru these threads and read the highlights, without any real understanding of the concept let alone substance of the discussion, and parrot misinformation ignorantly accordingly..and I never said this applied to OP, I simply made a referenced remark to a concern he had, which was not even based on oral ingestion of agmatine to begin with, yet he made reference to in support of these claims he based on his reading (which would lead to some saying he was indeed "freaked out")
    Aleks already came to my defense about the "freaking out" claim but I just want to re-iterate how incorrect that statement is.
    I wasn't even remotely "freaked out" and was fairly sure that none of these are even an issue.
    I made no "reference in support of these claims". I was simply asking a question.

    I'm also not sure how you were so certain that none of the information provided in that article was based on studies of orally administered Agmatine.
    You only looked at one part. The were over 100 Agmatine studies referenced and some used Agmatine orally.

    Quote Originally Posted by snagencyV2.0 View Post
    *as a sidenote, and to no one in particular:
    I swear some of you guys would be soooo much better off if you'd get your nose out of those books, stop worrying about the latest "study", or investigating the latest-greatest-miracle pill on the market, and just go EAT FOOD and go DO WORK, hit the damn weights
    You do realize you are on a Supplement forum, right?

    All we're doing, is trying to have a civilized discussion about supplements.
    If taking Agmatine together with DAA affects the efficacy of one of the substances, why wouldn't we want to talk about it?
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    Quote Originally Posted by doggy_dog View Post
    You do realize you are on a Supplement forum, right?

    All we're doing, is trying to have a civilized discussion about supplements.
    If taking Agmatine together with DAA affects the efficacy of one of the substances, why wouldn't we want to talk about it?
    He just sent me a charming private message saying that I should have "kept my mouth shut". You'll probably be getting one as well. Thank you for asking questions and my apologies for any part I had in taking away from your thread.
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    Quote Originally Posted by Aleksandar37 View Post
    He just sent me a charming private message saying that I should have "kept my mouth shut". You'll probably be getting one as well. Thank you for asking questions and my apologies for any part I had in taking away from your thread.
    Wow...not exactly the behavior I like to see from any poster, but especially a company rep.

    No apology needed. Thanks for chiming with your thoughts and knowledge.
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    Quote Originally Posted by Aleksandar37 View Post
    He just sent me a charming private message saying that I should have "kept my mouth shut". You'll probably be getting one as well. Thank you for asking questions and my apologies for any part I had in taking away from your thread.
    jesus, you are really pathetic aren't you?
    had I known as much, I never would have bothered taking the man approach, giving you benefit of doubt to work things out in private discussion, and saved my time for better things
    wow

    to OP:
    I won't sit here and relay what are private communications, like some ppl do
    I also had no intention of sending you any PMs, as this does not involve you at all
    but for your own clarification, I simply corrected him on his intentions to "stick up" for you because he thought I was picking on you (which I wasn't), and told him if OP had an issue with my post, he could tell me himself

    it simply did not involve him, at all.. and I still am puzzled over his arrogance that he feels he needs to be protector of all things unjust
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    Quote Originally Posted by doggy_dog View Post
    Aleks already came to my defense about the "freaking out" claim
    correct, as I already noted
    and what praytell gives him the position to do that?
    is he your boyfriend? your daddy?
    how does that get justified?

    you obviously are quite capable of defending yourself

    that is all, carry on
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    Quote Originally Posted by snagencyV2.0 View Post
    correct, as I already noted
    and what praytell gives him the position to do that?
    is he your boyfriend? your daddy?
    how does that get justified?
    Me and him have been dating for 6 months and are quite happy together.

    Or maybe, it was that he wanted to point out a blatantly incorrect and assumptive comment.

    Quote Originally Posted by snagencyV2.0 View Post
    you obviously are quite capable of defending yourself
    Thanks, that's very sweet of you.

    See, I knew you were a nice guy.
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    Quote Originally Posted by doggy_dog View Post
    Me and him have been dating for 6 months and are quite happy together.
    I make no judgements .. being PC is one of my new years resolutions
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    Alex does have a good point and studies do reference orally taken agmatine.

    One thing I dislike is when we, as students, educators or professionals in our field are told to keep our noses out of books. Yet when we get something wrong, we are told we don't know enough (think doctors in other threads).

    We are also here to protect people from potentially hurting themselves in the gym (think patella tracking during a squat or proper form- all of which are born from an in depth understanding of functional anatomy).

    Or in the case of biochem, do you still use trib to boost test? Arginine to increase vasodilation? or has science, and the board members who study it, informed you for the better?

    Some of us like keeping up with studies in order to improve the people around us. I implore you to find one world class athlete who does not have an exercise specialist who helped him get there or someone like cooper who hasnt changed/ isnt changing a company for the better.

    That statement, i feel, is directed at anyone who studies and enjoys studying anything and because of which i take offense, particulary when i have both time to study and workout.
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    Quote Originally Posted by Jiigzz View Post
    I implore you to find one world class athlete who does not have an exercise specialist who helped him get there
    Done.



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    I don't disagree with your statement above at all jigzz - with a certain respective limitation
    I am all for studying, knowledge, furthering the bar of the human body, and of course science cannot be discounted to help in understanding that position as well as a great many other things....

    it is more the excessive action/interest/and, ultimately, "justification" for advice, based on incomplete or even erroneous information, coming from studies that are perhaps poorly constructed, using irrelevant test subjects, or even bias in what the study is trying to prove as end result

    there is common sense, then there is excess stupidity
    that is my .02 -- we are all here to share our own positions/thoughts
    whether anyone else shares my opinions, I could really care less
    peer pressure has long since stopped affecting any part of my life
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    Quote Originally Posted by jimbuick View Post
    Done.

    ASC Pro Strongman and WSM competitor Marshall White. He turned pro at the age of 24 without hiring any one, and just recently started taking diet guidance from Jon Andersen (7 years after getting his pro card).
    Touche.

    But is he world class or just pro?
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    Quote Originally Posted by snagencyV2.0 View Post
    I don't disagree with your statement above at all jigzz - with a certain respective limitation
    I am all for studying, knowledge, furthering the bar of the human body, and of course science cannot be discounted to help in understanding that position as well as a great many other things....

    it is more the excessive action/interest/and, ultimately, "justification" for advice, based on incomplete or even erroneous information, coming from studies that are perhaps poorly constructed, using irrelevant test subjects, or even bias in what the study is trying to prove as end result

    there is common sense, then there is excess stupidity
    that is my .02 -- we are all here to share our own positions/thoughts
    whether anyone else shares my opinions, I could really care less
    peer pressure has long since stopped affecting any part of my life
    I see. Studies do indeed have limitations which is why it is also important those referencing them understand how the studies were constructed and if they are measuring what they claim to be measuring. People need to also be aware of the information as a whole and not just take one study out of a million (examine is indeed fantastic for doing this, but even it is not flawless).

    I only take 'offense' (using that term loosely) as i enjoy studying as much as i enjoy implementing studies in my own routine. If they work, i discuss them with my clients.
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    Quote Originally Posted by Jiigzz View Post

    Touche.

    But is he world class or just pro?
    Anyone who can qualify for WSM where only 25-30 athletes get the chance to compete every year (from all across the world) is world class lol.
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    I know this isn't current topic I'm just learning how to use this. Has anyone ever tried the ursolic acid? If so does it work without sideffects? Where to get it?
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    Quote Originally Posted by Bear1 View Post
    I know this isn't current topic I'm just learning how to use this. Has anyone ever tried the ursolic acid? If so does it work without sideffects? Where to get it?
    Oral is a waste of time due to poor bioavailability, as a topical is where it gets good results. UR spray. Nutra carries a few options
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    Lol at the pissing contests that constantly go on here at AM
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    Quote Originally Posted by JD261985 View Post
    Lol at the pissing contests that constantly go on here at AM
    LOL\//!!!!!!!​///

    GEORGE: All right, I want you to do me a favor.

    ELAINE: What?

    GEORGE: I want you to find out is she likes me.

    ELAINE: Find out if likes you?. What, are you in High School?...George come on can't you just talk to her yourself?

    GEORGE: But she's gonna know that I like her more than she likes me.

    JERRY: You know my parents are coming in and I got some clean up to do , so if you and Potsie are done scheming....
    "To your wife you should kiss try today"-Touey

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    Dumb as owl shyte posting
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    Quote Originally Posted by Piston Honda View Post
    Dumb as owl shyte posting
    honda he thieving my copyrights
    "To your wife you should kiss try today"-Touey

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    [QUOTE="Touey;4307848"] honda he thieving my copyrights[/QUOTE
    Do no go argue with your shadow
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    Quote Originally Posted by Piston Honda View Post
    Do no go argue with your shadow
    no /// it go.. "Does never pay to arguing your shadow"
    "To your wife you should kiss try today"-Touey

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    Quote Originally Posted by Touey View Post
    no /// it go.. "Does never pay to arguing your shadow"


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