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Interleukin-15 (trying to add to my knowledge base here)

weltweite

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Does anyone have any experience with Il-15? I've been trying to study up on it for a while, and managed to find a few studies about what it can do for muscle growth and.. well it naturally peaked my interest.

Everything I've read when searching back to 2000 :eek: on different forums, is that it works, and works well from user experience but doesn't go into much detail over that. (real vague when it comes to the science and real world results oddly..) I've heard it's called "PIQUE" in bodybuilding circles

From what I have read (limited reading with much room for misinterpretation on my part at that) with IGF it supposedly has a 500% synergistic effect. It is effective at stimulating MHC accretion when added after differentiation of myoblasts had occurred. According to one study I'll post, it was beneficial in increasing protein synthesis, and also inhibiting protein degrading effects, while also lowering white adipose tissue. *phew*


However I read people who say it isn't worth it for the price, effects etc. However price is NOT a factor when I'm trying to learn about what something does in general, rather than what it does for ME. I don't have to use the product to learn about it.

From what I have read, dosages go from 20mcg to 100mcg per KG of weight.

Any user feedback/constructive opinions on the science of it would be much appreciated.

It seems IGF before hand, and IL-15 after would have a synergistic effect..

Some info below:
 
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I highlighted in red and blue some things I found interesting:

Interleukin-15 increases myosin accretion in human skeletal myogenic cultures.

Furmanczyk PS, Quinn LS.

University of Washington, School of Medicine, Seattle, WA 98195, USA.

Interleukin-15 (IL-15) has been shown to have anabolic effects on skeletal muscle in rodent studies conducted in vitro and in vivo. The mechanism of IL-15 action on muscle appears to be distinct from that of the well-characterized muscle anabolic factor insulin-like growth factor-I (IGF-I). IL-15 action has not been investigated in a human culture system nor in detail in primary skeletal myogenic cells. The purpose of this study was to compare the effects of IL-15 and IGF-I in primary human skeletal myogenic cells. Accretion of a major myofibrillar protein, myosin heavy chain (MHC), was used as a measure of muscle anabolism. We found that both growth factors induced increases in MHC accretion in primary human skeletal myogenic cultures; however, IL-15 and IGF-I actions were temporally distinct. IL-15 was more effective at stimulating MHC accretion when added to cultures after differentiation of myoblasts had occurred. In contrast, IGF-I was more effective at stimulating MHC accretion when added to cultures prior to differentiation of myoblasts. These results using a human system support recent findings from rodent models which indicate that the primary mode of IGF-I action on skeletal muscle anabolism is through stimulation of myogenic precursor cells, whereas the primary target of IL-15 action is the differentiated muscle fiber. Further, since clinical and experimental studies have shown IGF-I is not effective in preventing skeletal muscle wasting, the distinct mode of action of IL-15 suggests it may be of potential usefulness in the treatment of muscle wasting disorders.





Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders.

Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, Argiles JM.

Division of Gerontology and Geriatric Medicine, University of Washington, Seattle 98195, USA. [email protected]

Interleukin-15 (IL-15) is a novel anabolic factor for skeletal muscle which inhibits muscle wasting associated with cancer (cachexia) in a rat model. To develop a cell culture system in which the mechanism of the anabolic action of IL-15 on skeletal muscle could be examined, the mouse C2 skeletal myogenic cell line was transduced with a retroviral expression vector for IL-15 and compared to sister cells transduced with a control vector. (My note: Would this cause a discrepancy in the test, since this is more Autocrine/paracrine function than systemic due to it being transduced with a retrovirus.. like a study with MGF showed, inspite of there being no receptor for MGF as Dat pointed out) Overexpression of IL-15 induced fivefold higher levels of sarcomeric myosin heavy chain and alpha-actin accumulation in differentiated myotubes. Secreted factors from IL-15-overexpressing myogenic cells, but not from control cells, induced increased myofibrillar protein accumulation in cocultured control myotubes. IL-15 overexpression induced a hypertrophic myotube morphology similar to that described for cultured myotubes which overexpressed the well-characterized anabolic factor insulin-like growth factor-I (IGF-I). However, in contrast to IGF-I, the hypertrophic action of IL-15 on skeletal myogenic cells did not involve stimulation of skeletal myoblast proliferation or differentiation. IL-15 induced myotube hypertrophy at both low and high IGF-I concentrations. Furthermore, in contrast to IGF-I, which stimulated only protein synthesis under these culture conditions, IL-15 both stimulated protein synthesis and inhibited protein degradation in cultured skeletal myotubes. These findings indicate that IL-15 action on skeletal myogenic cells is distinct from that of IGF-I. Due to the ability of IGF-I to stimulate cell division and its association with several forms of cancer, controversy exists concerning the advisability of treating cachexia or age-associated muscle wasting with IGF-I. Administration of IL-15 or modulation of the IL-15 signaling pathway may represent an alternative strategy for maintaining skeletal muscle mass under these conditions.





Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control.

Carbo N, Lopez-Soriano J, Costelli P, Alvarez B, Busquets S, Baccino FM, Quinn LS, Lopez-Soriano FJ, Argiles JM.

Departament de Bioquimica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.

Interleukin (IL)-15 is a cytokine which is highly expressed in skeletal muscle. Cell culture studies have indicated that IL-15 may have an important role in muscle fiber growth and anabolism. However, data concerning the metabolic effects of this cytokine in vivo are lacking. In the present study, IL-15 was administered to adult rats for 7 days. While IL-15 did not cause changes in either muscle mass or muscle protein content, it induced significant changes in the fractional rates of both muscle protein synthesis and degradation, with no net changes in protein accumulation. Additionally, IL-15 administration resulted in a 33% decrease in white adipose tissue mass and a 20% decrease in circulating triacylglycerols; this was associated with a 47% lower hepatic lipogenic rate and a 36% lower plasma VLDL triacylglycerol content. The decrease in white fat induced by IL-15 was in adipose tissue. No changes were observed in the rate of lipolysis as a result of cytokine administration. These findings indicate that IL-15 has significant effects on both protein and lipid metabolism, and suggest that this cytokine may participate in reciprocal regulation of muscle and adipose tissue mass.







Interleukin-15: a novel anabolic cytokine for skeletal muscle.

Quinn LS, Haugk KL, Grabstein KH.

Geriatric Research, Education, and Clinical Center, American Lake VA Medical Center, Tacoma, WA 98493, USA.

Interleukin-15 (IL-15) is a recently discovered growth factor which is highly expressed in skeletal muscle. In order to determine a functional role for IL-15 in skeletal myogenesis, the effects of IL-15 on myoblast proliferation and muscle-specific myosin heavy chain (MHC) expression were analyzed using the mouse C2 skeletal myogenic cell line and primary fetal bovine skeletal myogenic cultures. IL-15 had no effect on [3H]thymidine incorporation, nor on the rate of myoblast differentiation, assessed by anti-MHC immunocytochemical staining, in either type of culture. However, Western blot analyses revealed that IL-15 used at concentrations of 10 or 100 ng/ml increased MHC accumulation five-fold in C2 myoblast cultures and 2.5-fold in primary bovine myogenic cultures. Moreover, C2 myotubes formed in the presence of IL-15 appeared larger than controls. These findings indicate IL-15 can stimulate differentiated myocytes and muscle fibers to accumulate increased amounts of contractile proteins. Well-fused primary bovine myogenic cultures treated with the mitotic inhibitor aphidicolin, then administered IL-15 and/or the anabolic growth factor insulin-like growth factor-I (IGF-I), were analyzed for MHC accumulation using Western blots. IL-15 used at 10 ng/ml doubled MHC accumulation and was as effective as IGF-I used at 10 or 100 ng/ml. IL-15 and IGF-I used together increased MHC accumulation close to five-fold, indicating these two factors can act additively on muscle fibers. These findings indicate IL-15 affects parameters associated with skeletal muscle fiber hypertrophy, and suggest that IL-15 may be a novel anabolic agent to increase skeletal muscle mass.
 
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Very good find. I've been studying this compound for several years now, although you rarely ever read anything about it on the boards.

Effective dosages appear to be cost prohibitive for most yet I know of one anecdotal report that was very positive.

Thanks for sharing the research.

Clarity
 
Very good find. I've been studying this compound for several years now, although you rarely ever read anything about it on the boards.

Effective dosages appear to be cost prohibitive for most yet I know of one anecdotal report that was very positive.

Thanks for sharing the research.

Clarity

Thank you, I've been going thru as many boards as possible to find information. One board in particular from what I hear seems to have more info about it but it's private and not registering new members unfortunately (or maybe just not me lol).

Have you heard dosages along the same lines I had read (20mcg-100mcg per KG) ?

At the 20mcg per kg dose (if that is effective) cost isn't as bad as I had first speculated in relation to what it seems to give in results, if speculation is correct.

May I ask further details on the anecdotal report?

Thanks once again for replying
 
Thank you, I've been going thru as many boards as possible to find information. One board in particular from what I hear seems to have more info about it but it's private and not registering new members unfortunately (or maybe just not me lol).

Have you heard dosages along the same lines I had read (20mcg-100mcg per KG) ?

At the 20mcg per kg dose (if that is effective) cost isn't as bad as I had first speculated in relation to what it seems to give in results, if speculation is correct.

May I ask further details on the anecdotal report?

Thanks once again for replying


The stuff goes for about $200 per 100mcg. I seen studies using 2-10mcg/kg with significant results. Still that $100 a day if your at least 200pnd.
 
Research being done with IL-6 as well for ,muscle loss/stem cells.


Public release date: 8-Jan-2008
[ Print Article | E-mail Article | Close Window ]

Contact: Cathleen Genova
[email protected]
617-397-2802
Cell Press
New insight into factors that drive muscle-building stem cells

A report in the January issue of Cell Metabolism, a publication of Cell Press, provides new evidence explaining how stem cells known as satellite cells contribute to building muscles up in response to exercise. These findings could lead to treatments for reversing or improving the muscle loss that occurs in diseases such as cancer and AIDS as well as in the normal aging process, according to the researchers.

The researchers showed that a transient and local rise in an inflammatory signal, the cytokine known as interleukin-6 (IL-6), is essential for the growth of muscle fibers. The findings offer the first clear mechanism for the stem cells’ incorporation into muscle and the first evidence linking a cytokine to this process, said Pura Muñoz-Cánoves of Universitat Pompeu Fabra in Barcelona, Spain. “As we learn more about how muscles grow in adults, we may uncover new methods for restoring lost muscle mass in the elderly and ill,” she added.

Skeletal muscles are made up of individual myofibers, each with many nuclei containing genetic material. As muscles are made to work harder, they adapt by bulking up each of those individual fibers, the researchers explained, but the mechanisms responsible have largely remained elusive.

Mounting evidence has shown that the growth of myofibers is limited by the need to maintain an equilibrium between the number of nuclei and the fibers’ overall volume. Because mature myofibers are incapable of cell division, new nuclei must be supplied by satellite cells (muscle stem cells). Once activated, satellite cells follow an ordered set of events, including proliferation, migration, and incorporation into the myofiber, leading to its growth.

Now, the researchers have found that IL-6 is an essential regulator in that process. While IL-6 was virtually undetectable in the muscles of control mice, animals whose muscles were made to work harder showed an increase in IL-6 after one day. That cytokine rise was maintained for two weeks before it declined again.

Interestingly, systemically high levels of IL-6 had earlier been implicated in the muscle wasting process, Muñoz-Cánoves noted. “Having excess IL-6 is bad, but its local translation is required for muscle growth.”

The researchers further found that IL-6 was produced both within myofibers and in their associated satellite cells, leading to muscle growth.
In contrast, the muscles of mice lacking IL-6 did not show any significant increase in size after several weeks of overloading. the researchers also showed that IL-6 exerts its effects by inducing the proliferation of satellite cells.

While Muñoz-Cánoves said that the findings are “just the beginning” of a new line of investigation into how adult muscle grows, she added that they might ultimately provide a new avenue for muscle-building therapies.

“Treatments could be designed to compensate for or block the pathways leading to muscle loss,” she said. “In muscles that have already lost mass, you might also be able to stimulate muscle growth.”
 
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J. Anim Sci. 2008. 86:E75-E83. doi:10.2527/jas.2007-0458
© 2008 American Society of Animal Science

Interleukin-15: A muscle-derived cytokine regulating fat-to-lean body composition1,2

L. S. Quinn3

Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle 98195, and Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108

3 Corresponding author: [email protected]

An increasing body of literature links immune and inflammatory factors to modulation of growth and control of fat:lean body composition. Recent progress in understanding the control of body composition has been made through identification of inflammatory cytokines and other factors produced by adipose tissue that affect body composition, often by direct effects on skeletal muscle tissue. Adipose-derived factors such as leptin, tumor necrosis factor-{alpha}, resistin, and adiponectin have been shown to affect muscle metabolism, protein dynamics, or both, by direct actions. This review summarizes recent results that support the existence of a reciprocal muscle-to-fat signaling pathway involving release of the cytokine IL-15 from muscle tissue. Cell culture studies, short-term in vivo studies, and human genotype association studies all support the model that muscle-derived IL-15 can decrease fat deposition and adipocyte metabolism via a muscle-to-fat endocrine pathway. Fat:lean body composition is an important factor determining the efficiency of meat production, as well as the fat content of meat products. Modulation of the IL-15 signaling axis may be a novel mechanism to affect body composition in meat animal production.
 
Thank you, I've been going thru as many boards as possible to find information. One board in particular from what I hear seems to have more info about it but it's private and not registering new members unfortunately (or maybe just not me lol).

Have you heard dosages along the same lines I had read (20mcg-100mcg per KG) ?

At the 20mcg per kg dose (if that is effective) cost isn't as bad as I had first speculated in relation to what it seems to give in results, if speculation is correct.

May I ask further details on the anecdotal report?

Thanks once again for replying

Yeah, I heard the same on dosing.

What I stated earlier is all I know about the anecdotal report but it came from a reliable source.

STEN Labs carries this peptide for $125 per mg which is an absurdly low price. It is normally $1,799 or so per mg from what I have seen online. The owner of STEN, however, swears it is the real deal and says to not let the price fool ya.

Who the fuck knows?

Clarity
 
Yeah, I heard the same on dosing.

What I stated earlier is all I know about the anecdotal report but it came from a reliable source.

STEN Labs carries this peptide for $125 per mg which is an absurdly low price. It is normally $1,799 or so per mg from what I have seen online. The owner of STEN, however, swears it is the real deal and says to not let the price fool ya.

Who the fuck knows?

Clarity


Ya I had noticed that price 2 weeks ago, and was pretty surprised to see that.. Sten wouldn't answer if it should be reconstitued with BW or something else. I guess even for rat research purposes it was still a no-no to ask.. But I did end up noticing interleukins were mixed with BW in studies.

I may look into it. Just hope its not accidentally one of those other dangerous ILs :D

Ill probably do a very low dose with a low dose of IGF-lr3 (currently on 8iu of GH). I'm thinking same pin for such a short period of time wouldn't damage it. (will try it together and in seperate pins (2 weeks of each) to see if there is a difference. I know its not good to mix BW with IGF due to an unwinding issue, but I want to make sure their in the same area.

As you said.. who knows
 
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Ya I had noticed that price 2 weeks ago, and was pretty surprised to see that.. Sten wouldn't answer if it should be reconstitued with BW or something else. I guess even for rat research purposes it was still a no-no to ask.. But I did end up noticing interleukins were mixed with BW in studies.

I may look into it. Just hope its not accidentally one of those other dangerous ILs :D

Ill probably do a very low dose with a low dose of IGF-lr3 (currently on 8iu of GH). I'm thinking same pin for such a short period of time wouldn't damage it. (will try it together and in seperate pins (2 weeks of each) to see if there is a difference. I know its not good to mix BW with IGF due to an unwinding issue, but I want to make sure their in the same area.

As you said.. who knows

"In conclusion, IL-15 mRNA is constitutively expressed in skeletal muscle, and it is responsive to both muscle aging and limb unloading. Our data indicate that aging is a significant stimulus for increased IL-15 mRNA expression..."​

It appears to be increased (not decreased) in aging to fight atrophy. In my limited research a year ago I dismissed it as something that probably is not the THE thing that is missing in aging adults desiring hypertrophy.

I also was very concerned about its ability to stop cell death systemically. This is a double edged sword but is a concern because damaged cells are not eliminated before they can become cancerous.

From the same study *:

"A role for IL-15 in the attenuation of apoptosis is suggested by data showing that exogenous IL-15 protein inhibits death pathway-associated apoptotic signaling. Multisystem apoptosis initiated in mice via treatment with an anti-Fas antibody was suppressed with injection of a long- lasting IL-15-IgG2b fusion protein (9). In addition, IL-15 trans- genic mice are resistant to a lethal dose of Escherichia coli (23). IL-15 administration in control mice also reduces the death rate from a lethal challenge of E. coli. The data further show that administration of IL-15 to isolated peritoneal cells in vitro prevented TNF-alpha-induced apoptosis (23)

The well-characterized cell death pathway initiated by the binding of TNF-alpha to the type I TNFR (i.e., extrinsic apoptotic pathway) can be altered with increases in IL-15 protein. For example, daily injections of IL-15 protein for 7 days in a rodent model of cancer resulted in significant decreases in the gene expression of both the type I and type II TNFR (15). Further- more, incubation of fibroblasts with IL-15 in vitro attenuates apoptosis induced by TNF-alpha 8). The TNF-alpha apoptotic path- way was disrupted when the cytoplasmic signaling molecule TRAF2, which normally mediates the downstream apoptotic signal from the TNFR, was recruited to the cytoplasmic side of the IL-15Ralpha. Interestingly, this recruitment of TRAF2 to IL-15R alpha was only observed when both TNF-alpha and IL-15 protein were present in the culture media (8). Thus IL-15 seems to function, at least in part, to inhibit apoptosis by blocking the signaling downstream of the TNFR. This is relevant in aging muscle because the extrinsic apoptotic pathway is very active in aged skeletal muscle (31). We speculate that the changes in IL-15 mRNA observed in the current study may represent an attempt to counter the pro-apoptotic environment typically observed in aged skeletal muscle."

* - Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy, Emidio E. Pistilli, Parco M. Siu, and Stephen E. Alway, Am J Physiol Cell Physiol 292: C1298–C1304, 2007

I read some of the literature but never took it as far as you so I just don't have any genuine thoughts on it ...not that you want my feeble-assed input anyway.

HEY! I spelled feeble-assed incorrectly and my browser's spell checker highlighted it as spelled wrong. I spelled it "feable-assed". :D

Now would you ever want the opinion of someone who can't even spell feeble-assed?

EDITED
 
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"In conclusion, IL-15 mRNA is constitutively expressed in skeletal muscle, and it is responsive to both muscle aging and limb unloading. Our data indicate that aging is a significant stimulus for increased IL-15 mRNA expression..."​

It appears to be increased (not decreased) in aging to fight atrophy. In my limited research a year ago I dismissed it as something that probably is not the THE thing that is missing in aging adults desiring hypertrophy.

I also was very concerned about its ability to stop cell death systemically. This is a double edged sword but is a concern because damaged cells are not eliminated before they can become cancerous.

From the same study *:

"A role for IL-15 in the attenuation of apoptosis is suggested by data showing that exogenous IL-15 protein inhibits death pathway-associated apoptotic signaling. Multisystem apoptosis initiated in mice via treatment with an anti-Fas antibody was suppressed with injection of a long- lasting IL-15-IgG2b fusion protein (9). In addition, IL-15 trans- genic mice are resistant to a lethal dose of Escherichia coli (23). IL-15 administration in control mice also reduces the death rate from a lethal challenge of E. coli. The data further show that administration of IL-15 to isolated peritoneal cells in vitro prevented TNF-alpha-induced apoptosis (23)

The well-characterized cell death pathway initiated by the binding of TNF-alpha to the type I TNFR (i.e., extrinsic apoptotic pathway) can be altered with increases in IL-15 protein. For example, daily injections of IL-15 protein for 7 days in a rodent model of cancer resulted in significant decreases in the gene expression of both the type I and type II TNFR (15). Further- more, incubation of fibroblasts with IL-15 in vitro attenuates apoptosis induced by TNF-alpha 8). The TNF-alpha apoptotic path- way was disrupted when the cytoplasmic signaling molecule TRAF2, which normally mediates the downstream apoptotic signal from the TNFR, was recruited to the cytoplasmic side of the IL-15Ralpha. Interestingly, this recruitment of TRAF2 to IL-15R alpha was only observed when both TNF-alpha and IL-15 protein were present in the culture media (8). Thus IL-15 seems to function, at least in part, to inhibit apoptosis by blocking the signaling downstream of the TNFR. This is relevant in aging muscle because the extrinsic apoptotic pathway is very active in aged skeletal muscle (31). We speculate that the changes in IL-15 mRNA observed in the current study may represent an attempt to counter the pro-apoptotic environment typically observed in aged skeletal muscle."

* - Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy, Emidio E. Pistilli, Parco M. Siu, and Stephen E. Alway, Am J Physiol Cell Physiol 292: C1298–C1304, 2007

I read some of the literature but never took it as far as you so I just don't have any genuine thoughts on it ...not that you want my feeble-assed input anyway.

HEY! I spelled feeble-assed incorrectly and my browser's spell checker highlighted it as spelled wrong. I spelled it "feable-assed". :D

Now would you ever want the opinion of someone who can't even spell feeble-assed?

Stenlabs has had problems in the past when the owner had a substance abuse problem which seriously effected what his clients ended up receiving or not receiving. Bobaslaw even took a grand out of his pocket and reimbursed people he recommended to Sten to make up for them getting screwed.

But a lot of Stens peptides have always been week. How difficult is it to fuck up GHRP-6? It is just 6 amino acids long and nothing complicated. I have actually watched it being made (well actually the loading of the aminos & reagents and the beginning of the process).

Well don't inject Sten products in your glutes and you won't be so feeble assed :D

That was an interesting study, and I agree, inhibiting cell death is not a good idea.
Now I've gathered IL15 can attach at the IL2 receptor also, so off to do research on IL2 now :eek:

"Until recently, the intracellular molecules activated by the IL-2R at the cell membrane that are responsible for promoting cell cycle progression were obscure. However, early on it was shown that IL-2Rs triggered the expression of cyclin D2 and cyclin D3. Now it is known that the STAT5a/b molecules activated by the IL-2R via the JAK1/3 kinases promote the transcriptional activation of the D cyclins. As well, via the activation of the PI3K pathway, an inhibitor of cyclin-D/CDK activity (p27) is targeted for degradation. Both of these biochemical events, as well as others activated via the IL-2R ultimately promote progression through G1 of the cell cycle and through the G1 restriction point, thereby triggering the onset of DNA synthesis and replication." :food-smi; Now I have to learn what some of these words mean
 
Question:

Is no one concerned that IL's (Interleukin) are primary cytokines in immune cell regulation, proliferation, differentiation?

I know most are interested in the secondary characteristics that may be beneficial to BB, however, the dangers here far outweigh the possible benefits.

abnormal IL-15 levels are responsible for many autoimmune diseases including hashimotos thyroiditis and many autoimmune inflammatory diseases, rheumatoid arthritis for one. In fact, IL-15 blockers are being studied to combat overexpression of IL-15.
This is something that should be a concern when augmenting your immune function in this direction. Not enough info on whether an artificially induced autoimmune response would be quenched once IL-15 is discontinued. BTW, there is no concrete info on dosing and crossing such threshholds so I'd be weary.

Just search for autoimmune and Interleukin or IL-15. Lots of studies and info.

**broken link removed**

http://www.jimmunol.org/cgi/content/full/168/8/4216

http://www.medscape.com/viewarticle/556075_4
 

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