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Resveratrol and Melatonin


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#1 maxwatt

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Posted 22 August 2010 - 02:04 PM


We have been recommending morning administration of resveratrol for higher bioavailability, and because evening administration disrupts sleep cycles via interaction with CLOCK genes interfering with circadian rhythms.

I've been self-experimenting with melatonin to see if this would overcome the effect. I've found that taking 1 mg melatonin, and 400 mg 99% resveratrol at bedtime, allows me to sleep normally without the insomnia resveratrol induces in some people when they use it at night. I cannot measure my blood levels, but morning stiffness has decreased, though I still don't jump out of bed like I did when I was ten.

I also take 400mg resveratrol before breakfast.

This could be a way to increase one's average blood levels of resveratrol to enhance its effect.

----

Mol Nutr Food Res. 2009 Feb 4th

Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers.
Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P.

(Bioavailability higher with morning administration)

PMID: 19194969
-----
Biosci Biotechnol Biochem. 2008 Nov;72(11):3038-40. Epub 2008 Nov 7.
Resveratrol regulates circadian clock genes in Rat-1 fibroblast cells.
Oike H, Kobori M.

National Food Research Institute (NFRI), National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki, Japan. oike@affrc.go.jp
Abstract
Circadian clocks, especially peripheral clocks, can be strongly entrained by daily feedings, but few papers have reported the effects of food components on circadian rhythm. The effects of resveratrol, a natural polyphenol, on circadian clocks of Rat-1 cells were analyzed. A dose of 100 muM resveratrol, which did not show cytotoxicity, regulated the expression of clock genes Per1, Per2, and Bmal1.

PMID: 18997419

Edited by maxwatt, 22 August 2010 - 02:23 PM.


#2 2tender

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Posted 23 August 2010 - 04:51 PM

Melatonin, maybe worthwhile for some people, other people are sensitive to its effects in that it may stimulate auto immune disorders, athletes foot, arthritis, etc. There also appears to be a "hangover" associated with it, as it doesnt seem to clear the system quickly upon waking. It was once a very popular supplement and in the top ten life extenders listed by LEF. Anyone thats considering its use should start at the lowest dose obtainable JMO

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#3 mikeinnaples

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Posted 23 August 2010 - 05:35 PM

Melatonin, maybe worthwhile for some people, other people are sensitive to its effects in that it may stimulate auto immune disorders, athletes foot, arthritis, etc. There also appears to be a "hangover" associated with it, as it doesnt seem to clear the system quickly upon waking. It was once a very popular supplement and in the top ten life extenders listed by LEF. Anyone thats considering its use should start at the lowest dose obtainable JMO


For me ...5mg = hangover, 1mg = no hangover

#4 health_nutty

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Posted 23 August 2010 - 05:42 PM

Melatonin, maybe worthwhile for some people, other people are sensitive to its effects in that it may stimulate auto immune disorders, athletes foot, arthritis, etc. There also appears to be a "hangover" associated with it, as it doesnt seem to clear the system quickly upon waking. It was once a very popular supplement and in the top ten life extenders listed by LEF. Anyone thats considering its use should start at the lowest dose obtainable JMO


For me ...5mg = hangover, 1mg = no hangover


I like the idea of low dose melatonin. With all the light polution it makes sense to supplement what we would natural produce if we had complete darkness in the evening. Even 1mg is higher than what our body would naturally produce. 5mg is much much higher and makes me sleepy in the morning as well. I'm wondering if even 1mg is more that optimal.
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#5 maxwatt

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Posted 23 August 2010 - 07:34 PM

The hangover from too much melatonin is said to because the melanin is not yet metabolized,and is still circulating in your bloodstream, making you groggy. I find too much, and I wake up after two or three hours, wide awake, and stay that way.

1 mg seems to work well for me, and even 1/2 mg works as well, but 1 mg is the smallest tablet I can currently obtain. Source Natural used to make a 0.5n mg pill. I am going to get a tablet-splitter at a drugstore, and try 1/2 and 1/4 mg doses.

#6 2tender

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Posted 23 August 2010 - 09:21 PM

Im sure that LEF makes a 300 mcg capsule at an unbeatable price. I tried it and it was almost just right, meaning, I still experienced morning grogginess only not so much. Idropped it from my regimen though. I have found that lorazepam (low dose) is a cleaner sleep enhancer and that it also inhibits cortisol.

#7 pycnogenol

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Posted 23 August 2010 - 10:36 PM

Im sure that LEF makes a 300 mcg capsule at an unbeatable price. I tried it and it was almost just right, meaning, I still experienced morning grogginess only not so much. I dropped it from my regimen though. I have found that lorazepam (low dose) is a cleaner sleep enhancer and that it also inhibits cortisol.


Interesting. What strength of lorazepam (ativan) are you taking? I take the LEF melatonin (300 mcg) nightly and do not have any grogginess from that amount.

#8 2tender

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Posted 23 August 2010 - 10:57 PM

Im glad to hear it! Im probably a hyper-responder to Melatonin, another supplement of many that I cant take or no longer take. Currently taking no Lorazepam, low dose is the way to go with benzodiazipines and they must be prescribed by a Physician.

Edited by 2tender, 23 August 2010 - 10:58 PM.


#9 pycnogenol

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Posted 23 August 2010 - 11:01 PM

low dose is the way to go with benzodiazipines and they must be prescribed by a Physician.


Or I can just go over to my mom's house where the lorazepam stash is! Doctor, shmocktor. :cool:

Edited by pycnogenol, 23 August 2010 - 11:02 PM.


#10 2tender

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Posted 24 August 2010 - 04:15 AM

Your levity is appreciated. You wouldnt even have to do that, 300 mcg melatonin is probably equivalent to .5 mg t(hats point five) of Lorazepam, in terms of sedation for sleep, perhaps even stronger than that,

#11 maxwatt

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Posted 25 August 2010 - 02:05 AM

Your levity is appreciated. You wouldnt even have to do that, 300 mcg melatonin is probably equivalent to .5 mg t(hats point five) of Lorazepam, in terms of sedation for sleep, perhaps even stronger than that,


The point of using melatonin withnight-time resveratrol is not to induce sleep; it is to prevent disturbance of one's circadian clock. For that, t seems to be working for me. The half life of resveratrol is short, and being able to take it twice a day to maintainhigher levels for longer should help with things like arthritis.

#12 leha

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Posted 25 August 2010 - 08:45 PM

Hello all:

An alternative to taking melatonin that works better for me is to take 5-HTP in the morning. (I take a 50mg oral-dissolving tab). Your body will use the 5-HTP to produce serotonin during the day, but as night approaches, the serotonin gets converted to melatonin on what seems to be an as-needed basis, so you never end up with too much melatonin (or the other problem I was having which was that my body got lazy about producing its own melatonin when I took supps). For me, this has not only helped entrain my clock(s) better, but seems to be making my hair grow faster--hey, why not?

maxwatt, it sounds like you already know that you can entrain your clock by periodic fasting, as well.

I'm still learning about Resveratrol (I guess everyone is), but from light reading in PubMed ( :blink: ) it sounds like it's better absorbed if you take little bits all day long. The mice that have been getting results with low doses are getting it in their drinking water, I believe.

Another thing I figured out by doing some research, and I'm not sure if people here are into getting RSV from foods or not (I'm new here today), is that if you sprout peanuts you can significantly increase the amount of available RSV in them, presumably because the sprouted seed releases whatever stores it has in order to make them available for its own use. Since stress is also known to increase RSV in plants that produce it, I'm guessing you can further up the amount by then stir-frying the sprouted peanuts (how cruel, I know). Since peanuts are also a good source of niacin, and niacin is needed by the body to make NAD+, depending whether you believe in the SIRT1 connection to RSV, this could also be a better way to absorb and utilize the benefits of peanuts. Plus sprouted peanuts taste hella good.

So cool to have found you all!

Leha

#13 2tender

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Posted 25 August 2010 - 11:48 PM

Welcome to the board! I like that , "so cool to have found you all" I have read about the 5-HTP. Are you using Resveratrol as well ? Are you using the premium product? Dose, experiences?



#14 leha

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Posted 26 August 2010 - 12:05 AM

Welcome to the board! I like that , "so cool to have found you all" I have read about the 5-HTP. Are you using Resveratrol as well ? Are you using the premium product? Dose, experiences?


Thank you!

I have just begun to experiment with RSV after reading about it a lot. The most recent articles I've found indicated positive results with low doses for mice, so I thought, okay, I'm going to try this stuff. RSV and CR apparently don't overlap completely in gene expression variations from the norm, so maybe there's some extra benefit there.

As far as which product to use, I'm at a total loss. I was hoping to learn about that here, actually. Do you have a recommendation? I started with Nature's Plus "Extended Release" 125mg, but even that little bit gave me some stomach problems, so I was going to chop them up and have little bits throughout the day, as I might have mentioned above.

#15 2tender

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Posted 26 August 2010 - 03:28 AM

Actually, I think that its better to single dose it. If it is giving you digestion problems that continue, you may be one of the people that cant tolerate emodin (which is in the brand you mention) or Resveratrol itself. The best option is to switch products, opting for the best selling, pre-emulsified, micronized, pure Resveratrol licap available or a micronized, pure, bulk powder that can be mixed with juice first thing in the morning. The powder will allow you to take less or more of a dose according to your preference. Consistent dosing of an amount you feel best at, early in the day of a premium, low emodin content, pure and micronized Resveratrol will allow you to see if its something that is helpful for you. The ad at the top of this page is the leading Resveratrol company in the USA and is considered the best by all his customers. This is where most practical people get their Resveratrol. I hope that helps you .

Edited by 2tender, 26 August 2010 - 03:40 AM.


#16 maxwatt

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Posted 26 August 2010 - 04:07 AM

As 2tender said, emodin in 50% resveratrol extracts causes intestinal problems for many if not most people, and resveratrol itself, even at 99% purity, causes this problem for some people. The severity is dose dependent for those who are sensitive. However, I've found that taking resveratrol on an empty stomach, at least 30 minutes before eating, eases the problem considerably. Some studies have found beter absorption in humans with morning dosing. Higher doses result in higher blood serum levels, which helps overcome the effects of sulfonation which eliminates resveratrol from the body; also, higher serum levels may be important to get some of the anti-cancer effects noted in studies of cells in a medium containing various concentrations of resveratrol.

I would concentrate my resveratrol in a single dose in the morning, but I've been using it to counteract osteo-arthritis, particularly the fingers of my right hand. The extra evening dose is reversing the swelling, but I felt I needed to offeset the effects on circadian rhythm.

Interesting to hear 5-HTP indirectly raises melatonin levels via serotonin neogenesis.

#17 leha

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Posted 26 August 2010 - 05:22 AM

Thank you both for the advice and guidance. I had a feeling emodin might be the problem, but didn't really know how to tell if it was in the one I bought. I'll take it back!

I went to the website referenced in the ad up yonder and learned something I didn't know before, though, which might be a potential problem for me with RSV, or it might be nothing. I'm going to have to proceed with great caution because of this, as I may have some issues around the "P450" system. I'm not sure. I have a totally whacked hypersensitivity reaction to macrolide antibiotics (in any quantity), which all exhibit inhibition of the P450 system, and I see from the supp people that RSV also inhibits a part of that same system. Whether or not the P450 system has anything to do with my reaction is just a total unknown (it doesn't seem likely to me, but raises the question of the mechanism of inhibition). I do NOT want to be rushed to the hospital and put on Prednisone again--that stuff knocked 4 years out of my optimum well-being.

Since I already had some 50% RSV yesterday, I will wait a few days and see if I get any signs of delayed hypersensitivity. Keep your fingers crossed for me!

maxwatt, do check out the notion of using 5-HTP for clock reset. I'll also look around and see if I can figure out where I read about that... I will mention now, though, that the first time I took 5-HTP it made me feel kind of edgy for about an hour. I cut back to half until I got used to it and haven't had that problem since.

#18 2tender

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Posted 26 August 2010 - 06:28 PM

I am of the opinion that supplements and antibiotics, SHOULD NEVER BE COMBINED. Paricularly Resveratrol, as it may cause overt side effects of an antibiotic. Macrolides may have a high side effect profile. How long will you have to take the macrolides and what antibiotic is it? Im quite sure that emodin is the culprit, most people dont understand this. For Resveratrol to be effective and tolerable to take regularly, it absolutely must be micronized and of the highest purity available. JMO

Edited by 2tender, 26 August 2010 - 06:35 PM.


#19 mikeinnaples

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Posted 26 August 2010 - 07:33 PM

Another thing I figured out by doing some research, and I'm not sure if people here are into getting RSV from foods or not (I'm new here today), is that if you sprout peanuts you can significantly increase the amount of available RSV in them, presumably because the sprouted seed releases whatever stores it has in order to make them available for its own use. Since stress is also known to increase RSV in plants that produce it, I'm guessing you can further up the amount by then stir-frying the sprouted peanuts (how cruel, I know). Since peanuts are also a good source of niacin, and niacin is needed by the body to make NAD+, depending whether you believe in the SIRT1 connection to RSV, this could also be a better way to absorb and utilize the benefits of peanuts. Plus sprouted peanuts taste hella good.

So cool to have found you all!

Leha


1. I am not sure the amount of Resv in peanuts is worth anything, unless you eat several pounds of them at a time.

2. Peanuts are horrible for you ;) and would be far worse for you than any benefit you would gain from trace Resv.

3. Hell, if you go that route ...you might as well just drink more wine. That would be the most fun option anyways.

#20 leha

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Posted 26 August 2010 - 09:03 PM

2. Peanuts are horrible for you ;) and would be far worse for you than any benefit you would gain from trace Resv.


Why do you say that? Fat? Allergies? Something I don't know about? Would the same profile that applies to peanut brittle really apply to peanut sprouts, or boiled peanuts (assuming one in non-allergic)?

Regarding quantity, I guess I feel like it hasn't really been proven that a little bit of RSV is useless. Sure, it won't activate SIRT1 in any way so far detected, but RSV modifies over 700 gene transcriptions, even in small doses, and most plants only seem to need a little bit for whatever it is they use it for... Doesn't it seem like the jury is still out on RSV dosage/effect profiles?

Alcohol, on the other hand, has been proven nasty over the long term.

#21 leha

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Posted 26 August 2010 - 09:14 PM

I am of the opinion that supplements and antibiotics, SHOULD NEVER BE COMBINED. Paricularly Resveratrol, as it may cause overt side effects of an antibiotic. Macrolides may have a high side effect profile. How long will you have to take the macrolides and what antibiotic is it? Im quite sure that emodin is the culprit, most people dont understand this. For Resveratrol to be effective and tolerable to take regularly, it absolutely must be micronized and of the highest purity available. JMO


2tender, I agree with you. To clarify, I am not taking macrolides--I am avoiding them, after they almost killed me one time when I did take them. But what I found out (when I didn't get better right away and had a recurring rash long after I stopped the macrolides) is that convetional farming, as practiced in the USA, involves feeding of macrolides to animals in their regular diet, and these antibiotics are unchanged in cooking and processing, and carried over to humans who eat conventionally-produced dairy or meat (or farmed fish). Because my reaction is T cell-mediated, even just trace amounts of macrolides in my food set off a chain reaction. In fact, for years before I knew I had this reaction, I got an unexplained rash from milk products, which I assumed was a milk allergy, so I did not consume any milk products for like, 5 years. Once I understood what was happening to me, I also realized that I could eat organic, or otherwise known antibiotic-free dairy and be fine--yay! (There's always a bright side.)

Anyway, the gist of this is that I am being cautious about RSV now and waiting a few days to make sure that whatever it is in macrolides that makes them inhibit cytochrome P450 pathways has no relation to whatever it is in RSV that elicits the same behavior. Nobody really understands T cell-mediated hypersensitivity reactions, and especially weird, off the map ones like Sweet's Syndrome, which has been incorrectly characterized in the science to date more than it has been correctly characterized on a number of fronts.

That's probably already more than you ever wanted to know about my issue with macrolides, so I'll leave it at that! :wacko:

#22 2tender

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Posted 26 August 2010 - 10:33 PM

Please, theres no need to censor yourself here. This is a board that is based on the sharing of experiences with Resveratrol, your health and related conditions are relative. Im trying to think what typical macrolides are: quinolones, cipro? are those the ones? As mentioned before a bulk powder would be helpful in adjusting your dose. Howeve,r I do understand your sensitivity issues, I think we all have some. Macrolides and other things are in our foods in miniscule amounts, but that doesnt mean that everyone is going to be affected by them. I understand your caution and respect your prudence here. In some cases the P450 inhibition means that "less can be more". regarding the ingestion of anything. I would try the bulk powder from the ad, micronized. Half a scoop would be about 150 mgs, enough for an effect and hopefully not enough to give you any side effects. Thanks for sharing, as it increases our knowledge base here.

#23 leha

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Posted 27 August 2010 - 06:12 PM

Thank you, 2tender, for being so inclusive and interested, as well as helpful. Yes, I absolutely agree--the powder would be the wisest option for me. I have the site bookmarked, and so far have had no side effects from the one dose I took, except the obvious and already explained stomach issues. If RSV were going to do the same thing as the antibiotics, I think I would have had a big rash on my shoulders by now, but I don't (thankfully!).

Macrolides include arithromycin, azithromycin (the one that almost killed me, also known as Zithromax), and tylosin (the one they feed to feed lot animals).

You would not believe how hard they are to avoid when eating in public! I have learned (and anyone on a very restricted diet should know this) that you cannot trust restaurant employees! Some of them lie, for sure, but most of them simply think they know more about what's in the food they're serving than they actually do. This seems especially true in the case of butter, which, because it is a fat, carries a disproportionate load of drugs, toxins, etc. I'll bet there are a whole lot of vegans out there eating butter on a regular basis simply because it's been served to them unwittingly.

#24 2tender

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Posted 28 August 2010 - 04:34 AM

Well, it sounds like Resveratrol isnt agreeing with you and it is probably not best for you to take it or anything, on a daily basis, unless its suggested, by your physician. There is a wonderful search engine on this site, with the comments of some very educated and professional people. If you look for posts by "Maxwatt" here they contain everything about Resveratrol that is currently published..

Edited by 2tender, 28 August 2010 - 04:36 AM.


#25 maxwatt

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Posted 28 August 2010 - 05:34 AM

:blush:

#26 kurt9

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Posted 28 August 2010 - 06:19 AM

I used to take Melatonin, 3 mg per evening. I stopped about a year ago because it was actually keeping me awake. This started a few months after I started taking 250mg of Resveratrol (LEF). I usually sleep fine. So, I don't need the Melatonin anymore.

#27 2tender

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Posted 28 August 2010 - 03:49 PM

:blush:



Okay Maxwatt, I mean anything really pertinent to Resveratrol use that is current. There are many studies that are not even worth reading IMO. For those that use Resveratrol and benefit.

#28 wiserd

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Posted 03 September 2010 - 05:01 AM

2. Peanuts are horrible for you ;) and would be far worse for you than any benefit you would gain from trace Resv.


Why do you say that? Fat? Allergies? Something I don't know about? Would the same profile that applies to peanut brittle really apply to peanut sprouts, or boiled peanuts (assuming one in non-allergic)?

Regarding quantity, I guess I feel like it


If you do eat peanuts, make sure they're from a quality company. Traditional Chinese Medicine regards peanuts as a longevity food. However poor processing or growing practices cause some peanut products to have high aflatoxin content which is just murder on your body. (Also, there was a relatively recent FDA shutdown of the largest peanut product supplier for absolutely noxious processing conditions.)

#29 leha

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Posted 03 September 2010 - 06:37 PM

Thanks, wiserd--I get them from a guy in the city I know I can trust. :cool:

2tender--thanks again, and how ironic that you referred me back to the very person that started this topic!

kurt9--Melatonin had the same effect on me, which is why I switched to 5HTP. That said, I only take 5HTP maybe once a week these days, if that. Basically, I feel I might be running low on melatonin on days when I wake up and don't remember having had any significant dreams. I have always been a big dreamer, so that's a sign to me. One 5HTP and I'm back to dreaming normally for about a week or so, it seems.

That said, I had a weird encounter with the supplement person at my grocery store the other day, and I suspect 5HTP might be involved, because I know she takes a lot of it (several doses a day), and because I know she takes it for depression, and I know all this stuff because I've had several conversations with her, but on this particular occasion I was returning the Resveratrol that didn't work out for me, and my BF had accidentally thrown the receipt away, and this gal practically had a fit when I told her I didn't have the receipt. She said I could have bought it anywhere, and I said something like, well, you know me, though--I come in here all the time. To which she said "I don't know you and I don't remember ever seeing you." Okay, that was weird, but I just said that was fine, and that I would get one of the supervisors to look up the purchase electronically to verify it. I went to do that and the supervisor, who did know me, called the supplement gal over to get her to okay the return and the gal fairly marched over and said "I don't recognize this person..." At which point the sup cut her off and said she did, and the gal said "Fine!" in a pretty huffy tone, and marched back off. It was not the kind of experience you'd expect in your little community grocery store, and the point of this whole story is that I have a hunch this person who is taking 5HTP for depression does not realize that what she actually has in bipolar depression, which one should never take 5HTP for, because it is a risk factor for serotonin syndrome in anyone who has abnormal serotonin levels--which bipolar people often do. I'm pretty sure what I witnessed was an episode of hypomania.

So the moral is, if you think you might be bipolar, or if you take drugs that influence serotonin levels or re-uptake, don't mess with 5HTP unless your doctor says to (and even then, I would get a 2nd opinion).

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#30 leha

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Posted 03 September 2010 - 06:41 PM

Oh, and the other moral: guard your receipts! :ph34r:




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