Juven Ingredients???!!!
I just got our first box of Juven and started Gus on it - then I read the ingredients! It has aspartame and artificial dyes in it!!!!!!!!!! Do I have to give my kid cancer while trying to preserve his muscles???
What do the rest of you think? Are there any alternatives where I can get the good ingredients, not the bad?
Thanks,
Tonya
What do the rest of you think? Are there any alternatives where I can get the good ingredients, not the bad?
Thanks,
Tonya
Replies to This Discussion
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Permalink Reply by Rhonda on
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Juven is not scientifically proven to stimulate muscle growth. I would stay away from it.
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Permalink Reply by Christine McSherry on
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I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future. - Attachments:
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Permalink Reply by Laurie Paschal on
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I can share our story a bit. Sam started deflazacort in Sept 2005. He started l-arginine about 3 months after that, 3000mg/day. The brand he was using was discontinued last year, so we switched to Juven. He's 7½ and about 48lbs. He currently takes a 1/2 packet of Juven each day, broken into A.M. and P.M. doses. Sam is a very active little boy. He runs circles around me with his energy. He does have things he can't do like ride a normal bike, but he's still playing basketball with "normal" boys his age. We limit him to two non-consecutive quarters per game, but if we didn't he'd go until he collapsed. He also barely has a gowers anymore. Is this all b/c of the meds and supps? I don't know. But in my gut, I think it's made a difference. Do I worry about the additives? Sure, but I've had to pick what I'm comfortable with. That's all each of can do. It's a very personal decision.
Christine said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
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Laurie, gut wrenched - I completely understand, totally ignoring the data - I just don't get...the community needs and warrants information that helps parents decide TODAY actions; such as Juven. Let's get to the data, let's create the data - the data that ultimately changes the outcome TODAY!
Laurie Paschal said:I can share our story a bit. Sam started deflazacort in Sept 2005. He started l-arginine about 3 months after that, 3000mg/day. The brand he was using was discontinued last year, so we switched to Juven. He's 7½ and about 48lbs. He currently takes a 1/2 packet of Juven each day, broken into A.M. and P.M. doses. Sam is a very active little boy. He runs circles around me with his energy. He does have things he can't do like ride a normal bike, but he's still playing basketball with "normal" boys his age. We limit him to two non-consecutive quarters per game, but if we didn't he'd go until he collapsed. He also barely has a gowers anymore. Is this all b/c of the meds and supps? I don't know. But in my gut, I think it's made a difference. Do I worry about the additives? Sure, but I've had to pick what I'm comfortable with. That's all each of can do. It's a very personal decision.
Christine said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
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Permalink Reply by Cheri Gunvalson on
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Christine, thanks for clarifing this for other parents!
Our son Jacob who is now 18 was in a trial for JUVEN and I still have the funtion measurements by his PT, his timed testing improved on JUVEN. One of the most important issues is as Christine stated it is the suppliment tested to contain what it says it has. When you go to GNC and K Mart you never know exactly what you are getting as it is not regulated like the suppliments from pham companies like Abbott. I asked Lee Sweeney years ago if there was a better source of these suppliments which appeard to assist with the NOS complex. Lee said stick with the JUVEN because you can be assured you are getting what you want.
What we need is one stop shopping for pharm grade suppliments for our sons! I really worry that some parents may buy cheaper unregulated suppliments and end up giving thier child a sugar pill or worse yet a possible toxic substance. We need suppliments that have been tested with deflazacort, prednisone and the cardiac meds the boys are on as these suppliments can have synergetic (combined) effects that can be very toxic.
Cheri Gunvalson RN, MSN
Christine McSherry said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
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Permalink Reply by Ofelia Marin on
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Was there a trial with Juven in DMD boys? Who conducted the trial? Have they published the results? Can you give us more details please? I would really like to take a look at that data. Thanks!
Cheri Gunvalson said:Christine, thanks for clarifing this for other parents!
Our son Jacob who is now 18 was in a trial for JUVEN and I still have the funtion measurements by his PT, his timed testing improved on JUVEN. One of the most important issues is as Christine stated it is the suppliment tested to contain what it says it has. When you go to GNC and K Mart you never know exactly what you are getting as it is not regulated like the suppliments from pham companies like Abbott. I asked Lee Sweeney years ago if there was a better source of these suppliments which appeard to assist with the NOS complex. Lee said stick with the JUVEN because you can be assured you are getting what you want.
What we need is one stop shopping for pharm grade suppliments for our sons! I really worry that some parents may buy cheaper unregulated suppliments and end up giving thier child a sugar pill or worse yet a possible toxic substance. We need suppliments that have been tested with deflazacort, prednisone and the cardiac meds the boys are on as these suppliments can have synergetic (combined) effects that can be very toxic.
Cheri Gunvalson RN, MSN
Christine McSherry said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
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Hello Ofelia,
I am not sure if there was a human clinical trial or not...Cheri may have that information, but I will start digging - in the meantime, I can tell you this; L Arginine and corticosteroids increase tetanic force of the muscle fiber, in a dish. We really need to see where it is in an actual human with DMD - there are many stories of boys improving physically and/or not progressing as quickly, while taking the two together - this should be enough to demand a human clinical trial.
- What if a lower dose of corticosteroids combined with L Arginine produces a better result?? Information we NEED to know now because this is an area that we can all implement with our kids TODAY!!!!!!!!
- What is the best source of L Arginine...should it be JUVEN or is it better as just L Arginine alone with the corticosteroid?
- Is there a difference when using Prednisone and Deflazacort with L Arginine?
- What is the safest and best source of L Arginine?
A small cohort of patients, for a 3 month study - would probably answer these questions....so why aren't parents pushing for this? This is something that everyone can do for their son's today-no wait time.
Not to mention that there could be utrophin upregulation with L Arginine as stated in this published article - more reason to run a human clinical trial!!!!!
"Neurobiol Dis. 1999 Dec;6(6):499-507.
Nitric oxide and l-arginine cause an accumulation of utrophin at the sarcolemma: a possible compensation for dystrophin loss in Duchenne muscular dystrophy.
Chaubourt E, Fossier P, Baux G, Leprince C, Israël M, De La Porte S.
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif sur Yvette Cedex, 91198, France.
Duchenne muscular dystrophy (DMD), a severe X-linked recessive disorder which results in progressive muscle degeneration, is due to a lack of dystrophin, a membrane cytoskeletal protein. An approach to treatment is to compensate for dystrophin loss with utrophin, another cytoskeletal protein with over 80% homology with dystrophin. Utrophin is expressed, at the neuromuscular junction, in normal and DMD muscles and there is evidence that it may perform the same cellular functions as dystrophin. So, the identification of molecules or drugs that could up-regulate utrophin is a very important goal for therapy. We show that in adult normal and mdx mice (an animal model of Duchenne myopathy) treated with l-arginine, the substrate of nitric oxide synthase (NOS), a pool of utrophin localized at the membrane appeared and increased, respectively. In normal and mdx myotubes in culture, l-arginine, nitric oxide (NO), or hydroxyurea increased utrophin levels and enhanced its membrane localization. This effect did not occur with d-arginine, showing the involvement of NOS in this process. The NO-induced increase in utrophin was prevented by oxadiazolo-quinoxalin-1-one, an inhibitor of a soluble guanylate cyclase implicated in NO effects. These results open the way to a potential treatment for Duchenne and Becker dystrophies. Copyright 1999 Academic Press."
Ofelia Marin said:Was there a trial with Juven in DMD boys? Who conducted the trial? Have they published the results? Can you give us more details please? I would really like to take a look at that data. Thanks!
Cheri Gunvalson said:Christine, thanks for clarifing this for other parents!
Our son Jacob who is now 18 was in a trial for JUVEN and I still have the funtion measurements by his PT, his timed testing improved on JUVEN. One of the most important issues is as Christine stated it is the suppliment tested to contain what it says it has. When you go to GNC and K Mart you never know exactly what you are getting as it is not regulated like the suppliments from pham companies like Abbott. I asked Lee Sweeney years ago if there was a better source of these suppliments which appeard to assist with the NOS complex. Lee said stick with the JUVEN because you can be assured you are getting what you want.
What we need is one stop shopping for pharm grade suppliments for our sons! I really worry that some parents may buy cheaper unregulated suppliments and end up giving thier child a sugar pill or worse yet a possible toxic substance. We need suppliments that have been tested with deflazacort, prednisone and the cardiac meds the boys are on as these suppliments can have synergetic (combined) effects that can be very toxic.
Cheri Gunvalson RN, MSN
Christine McSherry said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
-
-
The researcher presented at several PPMD conf's, I believe he was from Iowa. Yes it was a trial with DMD boys in 2001. I do not have his name and address anymore, sorry but Pat should have it.
When Jacob was in the trial he had monthly GSCG testing, ie timed gait, stairs, chair and gowers by our PT and then I mailed in the results.
Ofelia Marin said:Was there a trial with Juven in DMD boys? Who conducted the trial? Have they published the results? Can you give us more details please? I would really like to take a look at that data. Thanks!
Cheri Gunvalson said:Christine, thanks for clarifing this for other parents!
Our son Jacob who is now 18 was in a trial for JUVEN and I still have the funtion measurements by his PT, his timed testing improved on JUVEN. One of the most important issues is as Christine stated it is the suppliment tested to contain what it says it has. When you go to GNC and K Mart you never know exactly what you are getting as it is not regulated like the suppliments from pham companies like Abbott. I asked Lee Sweeney years ago if there was a better source of these suppliments which appeard to assist with the NOS complex. Lee said stick with the JUVEN because you can be assured you are getting what you want.
What we need is one stop shopping for pharm grade suppliments for our sons! I really worry that some parents may buy cheaper unregulated suppliments and end up giving thier child a sugar pill or worse yet a possible toxic substance. We need suppliments that have been tested with deflazacort, prednisone and the cardiac meds the boys are on as these suppliments can have synergetic (combined) effects that can be very toxic.
Cheri Gunvalson RN, MSN
Christine McSherry said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
-
-
Hi Chirstine,
Yes, it would be so great to have answers to your questions! I am confident that L-arginine (or other NO donor) + steroids give better results than steroids alone but, as you mentioned, I do not know what NO donor to use and what dose. I did see many papers about improvement of the anti inflammatory effect when the NO donor is used in combination with steroids, also L-arginine is thought to upregulate utrophin. But what dose and brand should be used remains unclear.
Enhanced anti-inflammatory potency of a nitric oxide-releasing prednisolone derivative in the rat.
http://www.ncbi.nlm.nih.gov/pubmed/12839870
Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis
http://cat.inist.fr/?aModele=afficheN&cpsidt=18394434
Christine McSherry said:Hello Ofelia,
I am not sure if there was a human clinical trial or not...Cheri may have that information, but I will start digging - in the meantime, I can tell you this; L Arginine and corticosteroids increase tetanic force of the muscle fiber, in a dish. We really need to see where it is in an actual human with DMD - there are many stories of boys improving physically and/or not progressing as quickly, while taking the two together - this should be enough to demand a human clinical trial.
- What if a lower dose of corticosteroids combined with L Arginine produces a better result?? Information we NEED to know now because this is an area that we can all implement with our kids TODAY!!!!!!!!
- What is the best source of L Arginine...should it be JUVEN or is it better as just L Arginine alone with the corticosteroid?
- Is there a difference when using Prednisone and Deflazacort with L Arginine?
- What is the safest and best source of L Arginine?
A small cohort of patients, for a 3 month study - would probably answer these questions....so why aren't parents pushing for this? This is something that everyone can do for their son's today-no wait time.
Not to mention that there could be utrophin upregulation with L Arginine as stated in this published article - more reason to run a human clinical trial!!!!!
"Neurobiol Dis. 1999 Dec;6(6):499-507.
Nitric oxide and l-arginine cause an accumulation of utrophin at the sarcolemma: a possible compensation for dystrophin loss in Duchenne muscular dystrophy.
Chaubourt E, Fossier P, Baux G, Leprince C, Israël M, De La Porte S.
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif sur Yvette Cedex, 91198, France.
Duchenne muscular dystrophy (DMD), a severe X-linked recessive disorder which results in progressive muscle degeneration, is due to a lack of dystrophin, a membrane cytoskeletal protein. An approach to treatment is to compensate for dystrophin loss with utrophin, another cytoskeletal protein with over 80% homology with dystrophin. Utrophin is expressed, at the neuromuscular junction, in normal and DMD muscles and there is evidence that it may perform the same cellular functions as dystrophin. So, the identification of molecules or drugs that could up-regulate utrophin is a very important goal for therapy. We show that in adult normal and mdx mice (an animal model of Duchenne myopathy) treated with l-arginine, the substrate of nitric oxide synthase (NOS), a pool of utrophin localized at the membrane appeared and increased, respectively. In normal and mdx myotubes in culture, l-arginine, nitric oxide (NO), or hydroxyurea increased utrophin levels and enhanced its membrane localization. This effect did not occur with d-arginine, showing the involvement of NOS in this process. The NO-induced increase in utrophin was prevented by oxadiazolo-quinoxalin-1-one, an inhibitor of a soluble guanylate cyclase implicated in NO effects. These results open the way to a potential treatment for Duchenne and Becker dystrophies. Copyright 1999 Academic Press."
Ofelia Marin said:Was there a trial with Juven in DMD boys? Who conducted the trial? Have they published the results? Can you give us more details please? I would really like to take a look at that data. Thanks!
Cheri Gunvalson said:Christine, thanks for clarifing this for other parents!
Our son Jacob who is now 18 was in a trial for JUVEN and I still have the funtion measurements by his PT, his timed testing improved on JUVEN. One of the most important issues is as Christine stated it is the suppliment tested to contain what it says it has. When you go to GNC and K Mart you never know exactly what you are getting as it is not regulated like the suppliments from pham companies like Abbott. I asked Lee Sweeney years ago if there was a better source of these suppliments which appeard to assist with the NOS complex. Lee said stick with the JUVEN because you can be assured you are getting what you want.
What we need is one stop shopping for pharm grade suppliments for our sons! I really worry that some parents may buy cheaper unregulated suppliments and end up giving thier child a sugar pill or worse yet a possible toxic substance. We need suppliments that have been tested with deflazacort, prednisone and the cardiac meds the boys are on as these suppliments can have synergetic (combined) effects that can be very toxic.
Cheri Gunvalson RN, MSN
Christine McSherry said:I agree with Rhonda, there has been no scientific published data that has shown Juven to “stimulate muscle growth”. That is not to say that Juven may not have a role in treating the DMD population – certainly, there is much that we do know about Juven and much that needs further investigation.
Those diagnosed with B/DMD appear to be living a little longer, maybe slightly healthier than those diagnosed in past generations. Is this due to technology, improved coordinated care, earlier intervention, younger diagnosis, increased consensus of corticosteroid use and/or the use of supplements such as Juven? Maybe for all of the reasons above, for one or for none of the reasons – but the evidence is clear, these young men are living longer – I am not sure if anyone will ever have a definitive answer why.
Here is what we do know about Juven;
Juven is a proprietary blend of ingredients; L Arginine, HMB and Glutamine. In a study recently published; FASEB Journal, June 2009, L – Arginine when combined with a corticosteroid increased the force of the mdx mini muscle fiber (mBams) by 170% (tetanic force), neither compound (L-Arginine or corticosteroids) were able to perform at this capacity independent of each other. Are these two compounds working in synergy to compliment each other, possibly. Myomics would like to repeat this test in 2010 on human DMD muscle fibers using the same technology to measure the tetanic force – subsequently followed by a fatigue and injury assay to further determine long term effects and outcomes.
Over the last ten years, there have been many young men that have followed the regime of Juven (2 packs per day, 14grams of L-Arginine) and a prescribed dose of corticosteroids. Their history and progression doesn’t appear to be well documented – in hindsight, this would be a resourceful and valuable tool to our community when parents are faced with making these decisions.
Juven is distributed and the patent owned by Abbott (http://www.abbott.com/). Juven has proven some success in wound healing and in some other areas, its unique combination of amino acids appear to play a supportive role in maintaining some of the proteins required by our muscles and also used in healing wounds. The side effects are listed as such on their web site;
“Juven does not usually cause side effects. However, any change in the diet can cause temporary GI symptoms, such as diarrhea or constipation. If you have G.I. symptoms, you can reduce them by drinking 4 fluid ounces of Juven 4 times a day, or by adding more water to it. If you have any unusual problems, stop using Juven and talk to your doctor”.
Furthermore, Abbott is a nutritional supplier, a scientific partner and a pharmaceutical grade company that has a proven record to supply a quality and SAFE nutriceutical compound; Juven, to the public. http://www.abbott.com/static/content/document/fact_sheet_qa.pdf
Not all supplement companies carry the same credentials as Abbott. Supplement suppliers/companies are NOT regulated by the FDA (Natural Causes, Dan Hurley, Broadway Books, 2006). After extensive research and testing (12 months worth), even I was astounded that the supplements often times did not contain the ingredients that were listed on the bottle. Interestingly enough, on January 15, 2010 – this recall was issued by the FDA for a muscle enhancer, the manufacturer is being investigated for lacing its ingredients with anabolic steroids - http://www.fda.gov/Safety/Recalls/ucm197824.htm.
The B/DMD community should be very concerned with where they are obtaining their supplements. GNC and other natural health food stores may not be the best source for obtaining clean supplements – this is a big concern when we are giving these potentially contaminated compounds to children, children that may already be compromised by Duchenne.
Juven, L Arginine and corticosteroids are readily available, are currently used off label in Duchenne and would appear to have some safety data already existing. Why not perform a human clinical trial on the effects of L – Arginine in those who are using corticosteroids to provide information on the optimal dose or range of doses of the efficacy, safety and tolerability? Perhaps the Myomics technology will push us to human clinical trials and provide the scientific data needed to make these choices.
A human clinical trial with the above compounds; L Arginine/Corticosteroids should be done to answer these questions. It would require a conservative funding effort, would have less obstacles of new novel compounds that have no history or safety data – it would make the timeline a whole lot shorter AND availability to the compounds almost IMMEDIATE to the community – and lastly, negate much of the red tape of large pharma/bio-tech companies. Hmmmm?
Ultimately, using Juven or not is a personal, family decision that should be discussed with your son’s physician. Purchasing the Juven brand that is distributed by Abbott - at least offers some reassurance that the product is quality and safety assured. Talking to parents of children who have used this regime may also offer insight that has not been documented, but perhaps has proven some small successes in their experiences – lastly, most importantly – let’s push science for the answers to some of the compounds that are right in front of us, let’s not waste any time in finding what can slow down DMD today - and - give our young men a fighting chance for a curative therapy in the future.
-
-
More papers... There are many, these are only some examples...
Nitric oxide reverses prednisolone-induced inactivation of muscle satellite cells
http://www3.interscience.wiley.com/journal/116843244/abstract?CRETR...
Jenna L. Betters, PhD, Jodi H.D. Long, PhD, Kathleen S. Howe, PhD, Randy W. Braith, PhD, Quinlyn A. Soltow, MS, Vitor A. Lira, MS, David S. Criswell, PhD *
Center for Exercise Science, Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida 32611, USA
email: David S. Criswell (dcriswell@hhp.ufl.edu)
*Correspondence to David S. Criswell, Center for Exercise Science, Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida 32611, USA
Funded by:
American Heart Association
Abstract
Long-term corticosteroid therapy causes myopathy and can inhibit regeneration of skeletal muscle. Therefore, we hypothesized that corticosteroid exposure reduces satellite cell activity in skeletal myofibers. Male Swiss-Webster mice were injected daily for 8 weeks with prednisolone (GC) or vehicle (control). Single myofibers were isolated from the gastrocnemius, centrifuged to mechanically activate satellite cells, and maintained in culture for 48 h. Both constitutive nitric oxide synthase (NOS) isoforms were reduced in muscle by GC treatment (nNOS: -30%, eNOS: -34%). Fewer myogenic (myoD+) cells emanated from GC myofibers compared to control (-61%, P < 0.05). Supplementation of culture media with the nitric oxide donor, diethylenetriamine NONOate (DETA-NO; 5-50 M), caused a dose-dependent increase in the number of myoD+ cells arising from both control and GC myofibers (P < 0.05), and 10 and 50 M DETA-NO eliminated the GC-induced deficit in myogenic cells (P > 0.05). Therefore, supplementation of GC myofibers with DETA-NO restores satellite cell activity to control levels. Nitric oxide production could be an important therapeutic target for the prevention of corticosteroid myopathy. Muscle Nerve, 2007
Inhibition of iNOS expression and NO production by anti-inflammatory steroids. Reversal by histone deacetylase inhibitors.
Pulm Pharmacol Ther. 2008;21(2):331-9. Epub 2007 Aug 24.
Hämäläinen M, Lilja R, Kankaanranta H, Moilanen E.
The Immunopharmacology Research Group, University of Tampere Medical School and Tampere University Hospital, Research Unit, Tampere, Finland.
In inflammation, nitric oxide (NO) is produced by inducible nitric oxide synthase (iNOS) induced by bacterial products and cytokines, and NO acts as a regulatory and pro-inflammatory mediator. Glucocorticoids are powerful anti-inflammatory agents that inhibit the expression of iNOS and various other inflammatory factors. Histone deacetylation has been recently described as a novel mechanism how glucocorticoids down-regulate transcriptional activation of some inflammatory genes. The aim of the present study was to investigate the effects of inhibitors of histone deacetylation on the suppressive effects of glucocorticoids on NO production and iNOS expression. Dexamethasone and a dissociated glucocorticoid RU24858 inhibited NO production, and iNOS protein and mRNA expression in macrophages exposed to bacterial lipopolysaccharide (LPS). In the presence of a glucocorticoid receptor (GR) antagonist mifepristone, dexamethasone and RU24858 had no effect on NO production. The role of histone deacetylation in the glucocorticoid effect was studied by using three structurally different inhibitors of histone deacetylases (HDACs): trichostatin A, apicidin and MC1293. HDAC inhibitors reversed the effects of dexamethasone and RU24858 on iNOS expression and NO production. Stably transfected A549/8 cells containing luciferase gene under the control of human iNOS promoter were used in promoter-activity studies. iNOS promoter activity induced by IL-1beta was inhibited by dexamethasone and the inhibitory effect was reversed by HDAC inhibitor trichostatin A. The results suggest that glucocorticoids inhibit iNOS expression and NO production by a GR-mediated and GRE-independent manner through histone deacetylation and transcriptional silencing.
Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis
http://cat.inist.fr/?aModele=afficheN&cpsidt=18394434
Auteur(s) / Author(s)
JIPING DA (1 2) ; LUNI CHEN (1 2) ; HEDENSTIERNA Gbran (3 4) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Medical Sciences, Clinical Physiology, University Hospital, Uppsala University, SUEDE
(2) Air Force General Hospital, Beijing, CHINE
(3) Research Department, Department of Medical Sciences, Clinical Physiology, Uppsala University, SUEDE
(4) Nuclear Medicine Unit, University Hospital, Uppsala, SUEDE
Résumé / Abstract
Objectives: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: A total of 45 anesthetized and mechanically ventilated pigs. Interventions: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. Measurements and Main Results: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-κB and tumor necrosis factor-a. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. Conclusion: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.
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