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Buccal delivery superior?


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#121 John Barleycorn

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Posted 31 May 2010 - 03:04 AM

Resveratrol and other polyphenols can form a phenolate at high enough pH, but it would be too high (ten-ish, I think) to use biologically.


I saw a quote of a pKa in the high 8's somewhere around here, which I haven't confirmed. This suggests that resveratrol would dissolve in a saturated solution of NaHCO3. Dry that out and you might have a candidate for nasal delivery. The sodium content would be about 10%, which isn't too bad, but it might still be unpleasant. Must try this some time.

Rapid conjugation of polyphenols remains the bugaboo.


I'm wondering whether the jury may have come in a little too soon on that one. Many flavonoids exist as glycosides in nature, and I have heard it speculated that this might actually protect them from the liver (assuming they are not hydrolysed in the gut). Secondly, there are some in vitro studies which suggest that sulphonated flavonoids have enhanced anxiolytic action. Obviously, there is a practical question of whether such substances could make it past the BBB, but maybe that is not such a big deal with resveratrol. I guess it all depends what effects you are chasing, although some folks certainly seem to be reporting central effects.

#122 niner

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Posted 31 May 2010 - 04:44 PM

It also shows the importance of taste and solubility. Resveratrol does have a taste when soluble, and it's strong. That is, if you know how to do it.

And I know how to do it... Yeah, I'm bragging. Yeah, I'm a young published scientist.

No, I don't know how well it works yet, but I know what solvent to use. We'll test it and publish it soon, and we have the patent.

The link to the Lay's Potato Chip article was broken; this is the correct link. So are you saying that if you do to resveratrol whatever it was that Lays is doing to salt, you can get resveratrol to dissolve in water at supra-thermodynamic levels? What are they/you doing, anyway? Inducing a metastable polymorph by some sort of imposed conditions?

Resveratrol plasma levels in humans are limited by phase 2 metabolism rather than absorption. If you speed up absorption, however, you might reduce metabolism by swamping the systems responsible. I don't know how far you can go with this, though. It's interesting that you got a patent without first demonstrating that the method works. The PTO is still underfunded, I take it.

There are a number of scientists on this forum.

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#123 fatboy

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Posted 31 May 2010 - 11:21 PM

It's interesting that you got a patent without first demonstrating that the method works. The PTO is still underfunded, I take it.

Patents only serve as scarecrows. Until they're challenged, they don't mean dick.

#124 Anthony_Loera

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Posted 01 June 2010 - 07:57 PM

Patent pending I take it...

#125 RenegadeSci

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Posted 01 July 2010 - 12:58 AM

I'm going to donate it to a university for study. Sry.

#126 Young Paul

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Posted 06 July 2010 - 12:22 AM

I always hold my res in my mouth as long before swallowing, furthermore I "mix" my Res HPMC PEG combo in my mouth with water just for good measure (as I have said before I feel a little silly doing this and my wife looks at me like I am insane) My original motivation for mouth mixing was that when I used a hand mixer or blender I always had Res liquid left over sticking to the sides and the blender blades so I didnt want to waste any, but I found when I first started the mouth mixing I got a Res energy buzz like when I first started Res or whenever I have increased my dosage.

I even in a PM to Hedgehog when he was thinking of doing more blood level testing asked him to include a test of just Res held in the mouth. I think Maxwatt also mentioned putting Res under his tongue with some of his Alcohol of choice and letting it dissolve and absorb.

I sometimes mix 500mg pure with vodka and swish it around my mouth. I get a buzz, and makes the next 2 weeks of normal capsules seem to work better, as if the original high buccal dose gets stored or something.
BUT....it tastes absolutely disgusting, I almost vomit, it's the worst taste in the world.

#127 stephen_b

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Posted 07 July 2010 - 10:25 PM

I sometimes mix 500mg pure with vodka and swish it around my mouth.
[...]
BUT....it tastes absolutely disgusting, I almost vomit, it's the worst taste in the world.

Really? It tastes very mild to me (using revgenetics 99%).

#128 health_nutty

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Posted 07 July 2010 - 11:38 PM

Pure resveratrol is almost tasteless. Young Paul must have 50% powder.

#129 ArroyoGold

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Posted 13 July 2010 - 08:01 PM

So, in summary, after reading all of the posts here on this topic, what is the general consensus regarding the best delivery system of the best type of Resveratrol for the maximum benefit?

#130 health_nutty

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Posted 13 July 2010 - 10:33 PM

~100mg of 98-99% pure resveratrol powder (micronized is probably even better) with 2 teaspoons of lecithin (put all in the mouth at once). Hold it in your mouth for 10 minutes (buccal delivery) then swallow. It is pretty cost effective and I can feel the effects this way. If I hold it too long (20 minutes), I actually get low grade anxiety (as does another member here).

#131 Antaeus

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Posted 27 September 2010 - 01:26 PM

From the Asensi et al. 2002 article it seems that resveratrol can be absorbed by buccal absorption.
But how do they come to the conclusion that 1 mg (absorbed by buccal absorption) correspond to 250 mg resveratrol taken as a pill ?

I can not see this mentioned anywhere in the article (I got the full article).



Asensi et al. 2002, page 10
Attached File  50ml_Resveratrol_Buccal.jpg   42.22KB   42 downloads

#132 maxwatt

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Posted 27 September 2010 - 02:41 PM

From the Asensi et al. 2002 article it seems that resveratrol can be absorbed by buccal absorption.
But how do they come to the conclusion that 1 mg (absorbed by buccal absorption) correspond to 250 mg resveratrol taken as a pill ?

I can not see this mentioned anywhere in the article (I got the full article).



Asensi et al. 2002, page 10
Attached File  50ml_Resveratrol_Buccal.jpg   42.22KB   42 downloads

50 ml * 23 mcg/ml = 1.2 mg (rounded)
A 1.2 mg dose administered buccally gave a serum level of about 37 microgram (per ml, I assume) within a few seconds. he pek serum level from oral administration is a bit more than than that, though not by much; same order of magnitude. Also the area under the curve (resveratrol concentration over time) I would expect to be much lower with buccal administration. Perhaps this is addressed int he full paper?

I do favor using powder over capsules, and holding the powder in the mouth, but also in taking a larger dose of the powder than 1.2 mg.

#133 RenegadeSci

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Posted 27 September 2010 - 04:49 PM

Someone did the math from one of the bioavalibility studies. Look for walle, or the Phase I done escalation study by bocock, where you're sure to get the references. I believe they showed trace (near 5ng) for 250... lol, it was what was spread on wikipedia. I hadn't thought about it in so long, but it's basically zero with 250mg. It's almost like saying you have "20x" nothing, but sounds impressive.

http://wilmorelabsllc.blogspot.com/

From the Asensi et al. 2002 article it seems that resveratrol can be absorbed by buccal absorption.
But how do they come to the conclusion that 1 mg (absorbed by buccal absorption) correspond to 250 mg resveratrol taken as a pill ?

I can not see this mentioned anywhere in the article (I got the full article).



Asensi et al. 2002, page 10
Attached File  50ml_Resveratrol_Buccal.jpg   42.22KB   42 downloads


Edited by RenegadeSci, 27 September 2010 - 04:51 PM.


#134 Antaeus

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Posted 29 September 2010 - 08:31 AM

Someone did the math from one of the bioavalibility studies. Look for walle, or the Phase I done escalation study by bocock, where you're sure to get the references. I believe they showed trace (near 5ng) for 250... lol, it was what was spread on wikipedia. I hadn't thought about it in so long, but it's basically zero with 250mg. It's almost like saying you have "20x" nothing, but sounds impressive.

http://wilmorelabsllc.blogspot.com/

From the Asensi et al. 2002 article it seems that resveratrol can be absorbed by buccal absorption.
But how do they come to the conclusion that 1 mg (absorbed by buccal absorption) correspond to 250 mg resveratrol taken as a pill ?

I can not see this mentioned anywhere in the article (I got the full article).



Asensi et al. 2002, page 10
Attached File  50ml_Resveratrol_Buccal.jpg   42.22KB   42 downloads


Okay thanks, it seems like I need to compare the data from other studies and not just the Asensi study. These studies may be studies by Walle or Bocock if I understand you correct. Do anyone got the full reference ?

It's strange that everyone just refer to the Asensi et al. 2002 study, but this is not enough.

#135 Young Paul

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Posted 06 February 2011 - 03:46 PM

Then why are people having such success with buccal delivery? I put 110 RESV into some Bacardi 151, swished it in my mouth for 30 minutes. By the end of 30 minutes I was very anxious, very nervous. This has been reported by at least one other member/poster before. Also, the

me too, always.
If I mix it with vodka or baileys, I get a big buzz, super stimulated like 5 redbulls for hours

#136 Young Paul

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Posted 06 February 2011 - 03:50 PM


I always hold my res in my mouth as long before swallowing, furthermore I "mix" my Res HPMC PEG combo in my mouth with water just for good measure (as I have said before I feel a little silly doing this and my wife looks at me like I am insane) My original motivation for mouth mixing was that when I used a hand mixer or blender I always had Res liquid left over sticking to the sides and the blender blades so I didnt want to waste any, but I found when I first started the mouth mixing I got a Res energy buzz like when I first started Res or whenever I have increased my dosage.

I even in a PM to Hedgehog when he was thinking of doing more blood level testing asked him to include a test of just Res held in the mouth. I think Maxwatt also mentioned putting Res under his tongue with some of his Alcohol of choice and letting it dissolve and absorb.

I sometimes mix 500mg pure with vodka and swish it around my mouth. I get a buzz, and makes the next 2 weeks of normal capsules seem to work better, as if the original high buccal dose gets stored or something.
BUT....it tastes absolutely disgusting, I almost vomit, it's the worst taste in the world.

I must now add, that the Res was from a company called Biot...... and the stuff was supposed to be pure but was green and foul smelling crappy substance.

#137 Lufega

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Posted 06 February 2011 - 07:10 PM

Without browsing the entire resveratrol forum, I'm curious, has anyone tried dissolving it in wine ????????

#138 maxwatt

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Posted 06 February 2011 - 10:52 PM

Not enough alcohol in wine at 10 to 15% to dissolve a significant amount of resveratrol. Liquor at 80 proof (40% ethanol) and above, does dissolve it but only up to a point. But just putting the powder in your mouth, under your tongue or in your cheek, works as well as anything. You might want to drink a little liquid with it.

#139 John Barleycorn

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Posted 07 February 2011 - 05:55 AM

But just putting the powder in your mouth, under your tongue or in your cheek, works as well as anything.


One idea I have seen in relation to some other tinctures is the use of a drop or two of menthol to facilitate diffusion across lipid membranes. But, like you say, that could be overkill in the case of resveratrol. This seems to be one of those issues that is substance-specific.

#140 Geoffrey

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Posted 22 February 2011 - 12:41 PM

I must now add, that the Res was from a company called Biot...... and the stuff was supposed to be pure but was green and foul smelling crappy substance.

I do use Biot....'s products (they're just about the only economically viable ones available in Europe), and I can state categorically that you're talking about their 250mg "full spectrum" product, which is not "supposed to be pure", but is a 50% greenish-brown knotweed extract (each capsule is 500mg, containing minimum 250mg of trans-resv). It has a very characteristic knotweed smell/taste, and is absolutely standard for a 50% product. I mix it with yoghurt and I actually like the taste (and I don't react badly to emodin). I also use their 98% trans-resv product (micronized), which is pure-white and doesn't smell/taste of anything (a bit boring, actually!).

I'm interested in trying buccal delivery with both of these and will report back if it seems to make any difference. One thing I do note when I take "too much" (for me) resv (about 1g), is that I get dry/itchy eyes, and a tight feeling at the front of my head, like the beginning of an allergic/hay-fever-type response. This happens to me much more with the pure (white) resv than it does with an equivalent dose of the "full spectrum" product.

#141 keflex

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Posted 23 February 2011 - 10:01 AM

Concerning buccal delivery with alcohol: Is anyone concerned about the carcinogenic effects of swishing alcohol around in the mouth on a daily basis?



#142 maxwatt

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Posted 23 February 2011 - 12:21 PM

Good question. I assume it would be similar to the risk posed by alcohol based mouthwash, which is a known risk. From what I gather from a brief search, the risk is low, except when other risk factors are present: smoking, low folate intake, and lack of fruit in the diet.

I find it is not necessary to use alcohol to administer resveratrol, nor do I believe it enhances buccal delivery. Absent actual tests of blood levels, one cannot say with certainty, but it is unlikiely that ethanol acts as a carrier for a non-polar molecule. Any liquid, including water or alcohol will disperse a powder held in the cheek or under the tongue, and most of it is swallowed.

#143 niner

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Posted 24 February 2011 - 04:48 AM

Absent actual tests of blood levels, one cannot say with certainty, but it is unlikiely that ethanol acts as a carrier for a non-polar molecule. Any liquid, including water or alcohol will disperse a powder held in the cheek or under the tongue, and most of it is swallowed.

But resveratrol is moderately soluble in ethanol, so it should help. Of course, that's 95% ethanol, and I don't think anyone is going to hold that in their mouth. Resveratrol solubility in more palatable alcohol solutions is going to be a lot less, but still a lot higher than water. As I recall, there was blood testing done in the paper that started this buccal delivery craze.

#144 John Barleycorn

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Posted 28 February 2011 - 01:37 AM

but it is unlikiely that ethanol acts as a carrier for a non-polar molecule.


That would suggest the red wine drinkers are barking up the wrong tree? Off the top of my head, I would have thought some sort of alcohol would be the best solvent going for a polyphenol. Hydroxyl attracted to hydroxyl, and all that. However, whether ethanol is the best solvent is another matter.

For those concerned about the alcohol, lecithin as an alternative was previously mentioned.

#145 maxwatt

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Posted 28 February 2011 - 02:04 AM

but it is unlikely that ethanol acts as a carrier for a non-polar molecule.


That would suggest the red wine drinkers are barking up the wrong tree? Off the top of my head, I would have thought some sort of alcohol would be the best solvent going for a polyphenol. Hydroxyl attracted to hydroxyl, and all that. However, whether ethanol is the best solvent is another matter.

For those concerned about the alcohol, lecithin as an alternative was previously mentioned.


FWIW, the amount of resveratrol in red wine is very little, micrograms in a glass typically.

Res. dissolves fairly well in 85 to 95% alcohol; Liquor is typically 40% at 80 proof, and not so much; most people are overly optimistic as to the amount they can dissolve in a drink, and result is often more of a suspension than a solution, and it will settle, all the more os and once it hits the stomach, will precipitate out of solution. Even so, this will result in reduced particle size, and I believe higher availability than taking powder in a capsule. However we were talking about buccal (or sublingual) administration by dissolving in alcohol. Alcohol is absorbed directly by the mucosa, as is a small amount of resveratrol. However I doubt a significant amount gets transported absorbed that way through the membranes fot eh cheeks and mouth that way. Perhaps a bit more than just waiting for powder int he mouth to dissipate, but in terms of blood levels, I doubt the difference is going to be significant. Up to a point, merely taking more of a powder with small particle size, will have much the same result as taking a fancy formulated dispersion in a capsule. Buccal or sublingual may be slightly enhanced by alcohol, but their is still an upper bound determined by mucosal area and absorption per unit area by the mucous membranes. It may be slightly enhanced by alcohol, but even if it doubled you would be hard pressed to get any more into the blood than by taking a slightly higher dose orally. And much of what people think they are taking buccally, is actually slowly dispersed by saliva and swallowed. It would be interesting to measure blood serum levels over time with this method of administration, and compare to blood levels from different preparations. This hasn't been done that I know of.

#146 niner

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Posted 28 February 2011 - 03:04 AM

It would be interesting to measure blood serum levels over time with this method of administration, and compare to blood levels from different preparations. This hasn't been done that I know of.

In the Pharmacology section of the Wikipedia article on Resveratrol, it says:

One way of administering resveratrol in humans appears to be buccal delivery, that is without swallowing, by direct absorption through the inside of the mouth. When one mg of resveratrol in 50 mL solution was retained in the mouth for one min before swallowing, 37 ng/ml of free resveratrol were measured in plasma two minutes later. This level of unchanged resveratrol in blood can only be achieved with 250 mg of resveratrol taken in a pill form.[75]

Reference 75 is the following, which doesn't discuss buccal absorption at all in the abstract, and doesn't deal with humans, which the buccal statement above implies.

Free Radic Biol Med. 2002 Aug 1;33(3):387-98.
Inhibition of cancer growth by resveratrol is related to its low bioavailability.

Asensi M, Medina I, Ortega A, Carretero J, Baño MC, Obrador E, Estrela JM.

Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
Abstract

The relationship between resveratrol (RES) bioavalability and its effect on tumor growth was investigated. Tissue levels of RES were studied after i.v. and oral administration of trans-resveratrol (t-RES) to rabbits, rats, and mice. Half-life of RES in plasma, after i.v. administration of 20 mg t-RES/kg b.wt., was very short (e.g., 14.4 min in rabbits). The highest concentration of RES in plasma, either after i.v. or oral administration (e.g., 2.6 +/- 1.0 microM in mice 2.5 min after receiving 20 mg t-RES/kg orally), was reached within the first 5 min in all animals studied. Extravascular levels (brain, lung, liver, and kidney) of RES, which paralleled those in plasma, were always < 1 nmol/g fresh tissue. RES measured in plasma or tissues was in the trans form (at least 99%). Hepatocytes metabolized t-RES in a dose-dependent fashion (e.g., 43 nmol of t-RES/g x min in the presence of 20 microM tRES), which means that the liver can remove circulating RES very rapidly. In vitro B16 melanoma (B16M) cell proliferation and generation of reactive oxygen species (ROS) was inhibited by t-RES in a concentration-dependent fashion (100% inhibition of tumor growth was found in the presence of 5 microM t-RES). Addition of 10 microM H(2)O(2) to B16M cells, cultured in the presence of 5 microM t-RES, reactivated cell growth. Oral administration of t-RES (20 mg/kg twice per day; or included in the drinking water at 23 mg/l) did not inhibit growth of B16M inoculated into the footpad of mice (solid growth). However, oral administration of t-RES (as above) decreased hepatic metastatic invasion of B16M cells inoculated intrasplenically. The antimetastatic mechanism involves a t-RES (1 microM)-induced inhibition of vascular adhesion molecule 1 (VCAM-1) expression in the hepatic sinusoidal endothelium (HSE), which consequently decreased in vitro B16M cell adhesion to the endothelium via very late activation antigen 4 (VLA-4).

PMID: 12126761

The Pharmacology section of the Wikipedia Resveratrol article is flagged with multiple problems, and I think this buccal absorption report might be one of them. The numbers must have come from somewhere; original research, maybe? I can't completely dismiss buccal absorption of resveratrol from alcoholic solution, since several ImmInst members have reported significant psych effects from that method, but when I try to follow up on the original post of this thread, there seems to be trouble in WikiLand.

#147 maxwatt

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Posted 28 February 2011 - 03:54 AM


The Pharmacology section of the Wikipedia Resveratrol article is flagged with multiple problems, and I think this buccal absorption report might be one of them. The numbers must have come from somewhere; original research, maybe? I can't completely dismiss buccal absorption of resveratrol from alcoholic solution, since several ImmInst members have reported significant psych effects from that method, but when I try to follow up on the original post of this thread, there seems to be trouble in WikiLand.

Might not the psych effects be reproduced by alcohol alone, with no added resveratrol? One absorbs a significant amount of alcohol directly into the blood through the oral mucosa.

#148 niner

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Posted 28 February 2011 - 04:01 AM


The Pharmacology section of the Wikipedia Resveratrol article is flagged with multiple problems, and I think this buccal absorption report might be one of them. The numbers must have come from somewhere; original research, maybe? I can't completely dismiss buccal absorption of resveratrol from alcoholic solution, since several ImmInst members have reported significant psych effects from that method, but when I try to follow up on the original post of this thread, there seems to be trouble in WikiLand.

Might not the psych effects be reproduced by alcohol alone, with no added resveratrol? One absorbs a significant amount of alcohol directly into the blood through the oral mucosa.

It doesn't sound like an alcohol effect; they talk about it being energetic and speedy. Well, I've got some powder and I've got some tequila. I guess it's time for some hands-on science. Maybe tomorrow morning. It's always great to start the day with a shot, and I wouldn't want it to keep me up at night...

#149 maxwatt

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Posted 01 March 2011 - 01:45 AM


The Pharmacology section of the Wikipedia Resveratrol article is flagged with multiple problems, and I think this buccal absorption report might be one of them. The numbers must have come from somewhere; original research, maybe? I can't completely dismiss buccal absorption of resveratrol from alcoholic solution, since several ImmInst members have reported significant psych effects from that method, but when I try to follow up on the original post of this thread, there seems to be trouble in WikiLand.

Might not the psych effects be reproduced by alcohol alone, with no added resveratrol? One absorbs a significant amount of alcohol directly into the blood through the oral mucosa.

It doesn't sound like an alcohol effect; they talk about it being energetic and speedy. Well, I've got some powder and I've got some tequila. I guess it's time for some hands-on science. Maybe tomorrow morning. It's always great to start the day with a shot, and I wouldn't want it to keep me up at night...


A small amount of alcohol makes me feel more energetic and speedy. How others see me, maybe not so much? Anyway, tequilla is notorious for having effects beyond what one might expect from other drinks, so this could be a biased test. How did it go? You might have to repeat with bourbon, then vodka, then scotch….

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#150 PWAIN

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Posted 01 March 2011 - 05:22 AM

Given that it seems that most now feel that large doses of resveratrol are not required and may be harmful, why the continued focus on increasing absorption?




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