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Thread: Drugs with anti-inflammatory properties may help scoliosis?

  1. #31
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    unbelievable find

    Ballet Mom

    HOLY MACKERAL!!!!!

    Could you recap what happened to your daughter's curve after she started accutane and antibiotics? Please contact the researchers in La Jolla and tell them your story.

    Administration of RA maternally to RA-deficient mouse embryos restores normal axial turning and normal spinal column development
    Vitamin A deficiency may (or may not) be the cause of Scoliosis, but maybe Retinoids can treat it. Wow, those are some amazing links.

    It's my understanding that Dr. Moreau is working on medicine to treat Scoliosis. I'm not sure what his approach is.

    I believe at least two other teams of scientists are experimenting with Tamoxifen (a breast cancer drug) to create a treatment for Scoliosis.
    The Effect of Calmodulin Antagonists on Experimental Scoliosis: A Pinealectomized Chicken Model
    Last edited by Dingo; 08-16-2010 at 03:14 PM.

  2. #32
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    Quote Originally Posted by Dingo View Post
    Ballet Mom

    HOLY MACKERAL!!!!!

    Could you recap what happened to your daughter's curve after she started accutane and antibiotics? Please contact the researchers in La Jolla and tell them your story.

    Vitamin A deficiency may (or may not) be the cause of Scoliosis, but maybe Retinoids can treat it. Wow, those are some amazing links.
    Yes, I will definitely include these researchers in the letter I write...anyone I can find interested in scoliosis and retinoid research.

    It seems somehow very fitting that these researchers are in La Jolla...that's where Dr. Vert Mooney (and perhaps skevimc?) of your torso rotational exercise studies had his facilities.

  3. #33
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    effect on Scoliosis

    Ballet Mom

    Could you recap your experience with antibiotics and Accutane for us?

  4. #34
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    Quote Originally Posted by Dingo View Post
    Ballet Mom

    Could you recap your experience with antibiotics and Accutane for us?
    Oh, sorry Dingo. I thought you were asking if I could recap what happened for the researchers in La Jolla!

    I won't be able to get to it tonight...but I'll try sometime tomorrow.

  5. #35
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    Okay, here's a quick recap of my daughter's interesting experience with antibiotics and isotretinoin. It's going to be really quick though because I am really on the fly this week and most of the information can be found in the archives here if someone really wanted the information.

    During my daughter's treatment for scoliosis (which consisted of wearing a Charleston Bending Brace at night and when she outgrew that, a custom-made night-time brace similar to a Providence), she had developed a serious case of acne. She was started on antibiotics after trying the prescription topical arsenal for quite some time.

    I noticed that when she had been switched to Solodyn, which is an extended release formula of Minocycline, after about three months of use, she had an x-ray taken at her regular orthopedic check. I noticed at the time that her compensatory curve had diminished in size. I don't remember how much, and I don't have time to check with the x-rays...but I think I mentioned it in the archives...but it was quite noticeable. She stopped taking the Solodyn at three months because it didn't work anymore for her and I believe her curve reverted by the next x-ray.

    What's especially interesting about this and the tie-in with isotretinoin is that I was just now looking to pull up an article that I read at that time that said something to the effect that Solodyn was a many times more powerful anti-inflammatory than regular Minocycline for some reason...even though it's just an extended release version. I couldn't find it but I did pull up this information about Minocycline in general (Sound familiar to the retinoids studies? I think so!!!) :

    Minocycline and other tetracycline derivatives have neuroprotective effects unrelated to their antimicrobial properties. Minocycline has the greatest permeability of all tetracyclines through the blood-brain barrier and is well suited for treatment of CNS disorders.

    Minocycline can reduce neuronal death after excitotoxicity and ionizing radiation in culture6-7 and in animal models of stroke7-9, Parkinson's disease10-11, Huntington's disease12, and amyotrophic lateral sclerosis13. The neuroprotective effects of minocycline have been attributed both to reduced inflammation and a direct effect on neuronal survival.
    http://www.emedexpert.com/facts/minocycline-facts.shtml

    Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against progression of a group of neurodegenerative disorders including multiple sclerosis (MS), rheumatoid arthritis (RA), amyotrophic lateral sclerosis (ALS), Huntington's disease, and Parkinsons disease.[14][15][16][17]

    In the Journal of the American Medical Association (JAMA), Chris Zink, Janice Clements, and colleagues from Johns Hopkins University reported that minocycline may exhibit neuroprotective action against AIDS Dementia Complex by inhibiting macrophage inflammation and HIV replication in the brain and cerebrospinal fluid.[18] Minocycline may suppress viral replication by reducing T cell activation.[19] The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase,[20] an inflammatory enzyme associated with brain aging, and the antibiotic is being studied for use in Alzheimer's disease patients.[21] Minocycline may also exert neuroprotective effects independent of its anti-inflammatory properties.[22] Minocycline also has been used as a "last ditch" treatment for toxoplasmosis in AIDS patients. Minocycline is neuroprotective in mouse models of amyotrophic lateral sclerosis (ALS) and Huntington's disease and has been recently shown to stabilize the course of Huntington's disease in humans over a 2-year period.

    As an anti-inflammatory, minocycline inhibits apoptosis (cell death) via attenuation of TNF-alpha, downregulating pro-inflammatory cytokine output. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which results in the decreased ability of T cells to contact microglia which impairs cytokine production in T cell-microglia signal transduction .[23] Minocycline also inhibits microglial activation, through blockade of NF-kappa B nuclear translocation.
    http://www.ask.com/wiki/Minocycline

    Anyhow, nothing worked for her acne, so the day before Christmas she started on isotretinoin (Accutane). She developed complications including breathing and weakness difficulties in ballet and her white blood cell count decreased dramatically and she contracted RSV from her pediatrician during her low immune state (he told us this) and others I won't mention. This was due to being placed on a dose double the amount she should have been for her weight, even though she didn't have chest or back acne which would have allowed for a slightly upped dosage.

    I took her off the isotretinoin for five weeks and she proceeded again at half the dose with a new dermatologist and finished the course in June without additional side effects.

    At her June orthopedic appt, her lower curve had basically gone away. There's a slight "curve" but basically, her x-ray now looks like one major structural curve instead of two curves.

    My daughter is now significantly improved in ballet from December and continues to improve greatly. She had been very unstable and unable to lift her legs high in her extensions or her arabesques or penchees. In her June performance, I was shocked how much she had improved because I had stopped watching her because it had become too hard for me to watch.

    Coincidence? I certainly don't think so. I really think these drugs that are able to permeate the blood-brain barrier really positively affected her scoliosis. I think the retinoids are especially a class that needs to be researched especially from that study that I linked that states: "These studies thus provide evidence that a loss of RA (Retinoic Acid) synthesis during gestation causes spinal column birth defects, but that normal development can be restored by supplying an exogenous source of RA." The retinoids seem to have great potential to be a possible treatment of scoliosis.

    Also, my daughter's rotation has improved throughout the course of her treatment. Is it due to ballet and stretching? Or due to the drugs she's been taking? I don't know..but the reduction in the amount of rotation has been impressive and therefore the reduction in deformity has been pretty dramatic, I think.

    Anyhow, hope that helps. I really hope my daughter's experience causes someone to be interested in researching the retinoids as a possible treatment for scoliosis.
    Last edited by Ballet Mom; 08-17-2010 at 11:48 PM.

  6. #36
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    Ballet Mom -

    I think it is wonderful that you are writing to Dr. Collins at NIH about this. It does not seem like such a coincidence to me - and it will be good to hear what he may say about this. As a sidebar - I've had cause to be on antibiotics, and when I was ... my back always felt much better. A curious thing.

  7. #37
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    Quote Originally Posted by skevimc View Post
    The MMP-3 thing is kind of neat. I'd like to track that down a bit more.

    <snip>

    In fact, an increase in IL-6 has also been shown after exercise. It's thought that the rise in IL-6 levels trigger the response of several anti-inflammatory cytokines as well as various growth factors.
    I was thinking of what you had to say here while reading some information found at: http://www.schroth-skoliosebehandlun..._scoliosis.php

    Looking at the picture attached along with the text:

    The greater the spinal deviations from the body's centerline, the longer the
    corresponding muscles become and thus lose their thickness (diameter) and elasticity, and become slack and finally inactive. They lose their holding function.

    The structural changes described above are only possible because the muscles permit them to take place. The muscles shorten or lengthen depending on which direction the trunk shifts and twists. That is, the lateral and posterior torso shifts can only occur when the corresponding structural muscles yield and lengthen.

    Makes me wonder - could the body with scoliosis be in a constant state of "exercise" in the attempt to try and hold the spine straight in even the simplest of daily activities - causing readings similar to those without scoliosis following exercise?

  8. #38
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    Talking More Notes for the file

    Quote Originally Posted by Dingo View Post
    I have to admit that on a technical level this is way over my head. But theoretically speaking it makes perfect sense.

    For example a gene that protects the body from the flu virus may make it more susceptible to a cold virus.

    In this case genes may increase the secretion of inflammatory cytokines. This may protect the body from some diseases but increase the likelihood of other diseases like Scoliosis. In certain environments that may be a smart trade off because the Scoliosis trigger is uncommon or rare. That's how nature works.

    If scientists could determine what the environmental trigger was they could probably eliminate it with a vaccine or some other measure.

    Dingo - just some more "finds" for the file ... man, it never ends!

    Susceptibility of host
    Most humans are not easily infected. Organisms usually cause infections in people who are weak, sick, malnourished, have cancer, are diabetic or are immuno-suppressed. Individuals who have a suppressed immune system are quickly over powered by the organisms. The majority of chronic or persistent infections occur in individuals who have poor defense mechanism(s).

    Occult infection
    An occult infection is medical terminology for a "hidden" infection, that is, one which presents no symptoms. Dr. Fran Giampietro discovered this type, and coined the term "occult infection" in the late 1930s. Another word for an infection with no symptoms is "asymptomatic" http://en.wikipedia.org/wiki/Infection


    • Infections during pregnancy. * Infectious diseases caused by viruses, such as toxoplasmosis, rubella (German measles), cytomegalovirus, and herpes, can infect the womb and placenta.* Researchers currently think that maternal infection leads to elevated levels of immune system cells called cytokines that circulate in the brain and blood of the fetus.* Cytokines respond to infection by triggering inflammation.* Inflammation may then go on to cause central nervous system damage in an unborn baby.* Maternal fever during pregnancy or delivery can also set off this kind of inflammatory response. http://www.ninds.nih.gov/disorders/c...bral_palsy.htm

    • Inflammation may be considered a homeostatic response designed to destroy or inactivate invading pathogens, remove waste and debris, and permit restoration of normal function, either through resolution or repair. Tissue structure is normal after resolution, whereas repair leads to a functional, but morphologically altered, organ. In acute inflammation, tissue damage is followed by resolution, whereas in chronic inflammation, damage and repair continue concurrently. The initial inflammatory response is usually acute, and may or may not evolve into chronic inflammation. However, chronic inflammation is not always preceded by an acute phase. Although usually beneficial to the organism, inflammation itself may lead to tissue damage, resulting in escalation of chronic inflammation. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC128891/

    • Cytokines are immune system modulators produced by cells throughout the body. Cytokines communicate with your brain, sounding the alarm when they detect an intruder. A subclass of cytokines called leukotrienes (or interleukins) ensures that the immune response is checked before it destroys outlying healthy cells and tissue. Importantly, they call off the inflammatory response. If you have overactive leukotrienes, your body can lose control of the process white blood cells begin to digest healthy tissue, causing excessive damage and scarring, a common symptom in many autoimmune disorders. http://www.womentowomen.com/inflamma...yhormones.aspx

  9. #39
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    Quote Originally Posted by mamamax View Post
    I was thinking of what you had to say here while reading some information found at: http://www.schroth-skoliosebehandlun..._scoliosis.php

    Looking at the picture attached along with the text:

    The greater the spinal deviations from the body's centerline, the longer the
    corresponding muscles become and thus lose their thickness (diameter) and elasticity, and become slack and finally inactive. They lose their holding function.

    The structural changes described above are only possible because the muscles permit them to take place. The muscles shorten or lengthen depending on which direction the trunk shifts and twists. That is, the lateral and posterior torso shifts can only occur when the corresponding structural muscles yield and lengthen.

    Makes me wonder - could the body with scoliosis be in a constant state of "exercise" in the attempt to try and hold the spine straight in even the simplest of daily activities - causing readings similar to those without scoliosis following exercise?
    I'd need to think about that a bit more. My initial thoughts and one thing I think is wrong with the figure/rationale is that they are claiming that the concave side muscles are stronger and the convex are trying to keep up by constantly resisting. This was a common dogma for along time and still might be. I personally do not believe this to be the case and think the rotational studies support my views. Although I admit that trunk rotations are a very complex interaction of a large number of muscles so a definitive answer to this will be hard.

    Regardless, I do agree with the idea that certain muscles become atrophied and the only reason for this is that the muscles aren't being worked, i.e. the muscle is healthy it just isn't firing for some reason. And generally it is correct that if the joint is making a movement, then the appropriate muscles are firing. However, I think the spine has a lot of muscular redundancy so the assumption that the correct muscles are firing might not be accurate.

  10. #40
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    strength asymmetry

    Skevimc

    My initial thoughts and one thing I think is wrong with the figure/rationale is that they are claiming that the concave side muscles are stronger and the convex are trying to keep up by constantly resisting. This was a common dogma for along time and still might be. I personally do not believe this to be the case and think the rotational studies support my views.
    I know this is a complicated problem so maybe I don't understand (always possible). But didn't your study find a difference in rotational strength?

    Trunk rotational strength asymmetry in adolescents with idiopathic scoliosis: an observational study

    Conclusion: This preliminary study measured trunk rotational strength in a group of adolescent healthy females and a group of adolescent idiopathic scoliosis females. Scoliosis patients were significantly weaker when rotating towards the concavity of the spinal curve in the neutral position and when pre-rotated 18 and 36 toward the concavity and then contracting towards the concavity, i.e. away from neutral, termed "low force". In contrast, the healthy group did not show weakness in the low force arc. In addition, low force arc trunk strengths on the concave side in scoliotic individuals were also significantly lower than those on the left side in the healthy subjects. These finding may help future researchers develop effective new approaches for the management of idiopathic scoliosis.
    Last edited by Dingo; 08-19-2010 at 09:21 AM.

  11. #41
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    Quote Originally Posted by mamamax View Post

    [INDENT][INDENT][INDENT][LIST][*]Infections during pregnancy. * Infectious diseases caused by viruses, such as toxoplasmosis, rubella (German measles), cytomegalovirus, and herpes, can infect the womb and placenta.* Researchers currently think that maternal infection leads to elevated levels of immune system cells called cytokines that circulate in the brain and blood of the fetus.* Cytokines respond to infection by triggering inflammation.* Inflammation may then go on to cause central nervous system damage in an unborn baby.* Maternal fever during pregnancy or delivery can also set off this kind of inflammatory response.
    I have always been worried that my son was negatively affected by the terrible infection I had when I was pregnant with him...obviously not one of these horribly damaging infections that you have listed...but enough to explain a lot about my son...

    Quote Originally Posted by mamamax View Post
    [*]Cytokines are immune system modulators produced by cells throughout the body. Cytokines communicate with your brain, sounding the alarm when they detect an intruder. A subclass of cytokines called leukotrienes (or interleukins) ensures that the immune response is checked before it destroys outlying healthy cells and tissue. Importantly, they call off the inflammatory response. If you have overactive leukotrienes, your body can lose control of the process white blood cells begin to digest healthy tissue, causing excessive damage and scarring, a common symptom in many autoimmune disorders.
    From my reading this appears to be a hot, hot field of research. Hope they come out with some amazing finds that could help a lot of people.

  12. #42
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    links

    Once again some great links Mamamax

    Ballet Mom
    I have always been worried that my son was negatively affected by the terrible infection I had when I was pregnant with him...obviously not one of these horribly damaging infections that you have listed...but enough to explain a lot about my son...
    If your kid is healthy don't sweat it.

    However it's certainly true that infection during pregnancy can lead to serious mental or physical illness.

    Herpes Virus Link To Preterm Birth And High Blood Pressure During Pregnancy

    Their work demonstrates, for the first time, that exposure to viral infection -- especially viruses of the herpes group -- may be associated with pregnancy-induced hypertensive disease (pre-eclampsia) and also with pre-term birth. The research discovered the presence of viral nucleic acid in heel-prick blood samples from 1326 newborn babies, taken over a 10-year period. More than 400 of these babies were diagnosed with cerebral palsy.

  13. #43
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    Quote Originally Posted by Dingo View Post
    Skevimc



    I know this is a complicated problem so maybe I don't understand (always possible). But didn't your study find a difference in rotational strength?

    Trunk rotational strength asymmetry in adolescents with idiopathic scoliosis: an observational study
    Yes, we found a significant rotational strength asymmetry. In the observational study the difference was significant but in the training study there was no significant difference. However, the patients in the two studies overlap by about 90%. So there were some people in the observational study that did not strength train and there were a few patients that were not included in the observational study. Despite the study flaws, we feel pretty confident in the asymmetry findings.

    The weakness is when the patient is rotating in the direction of the concavity while in the neutral position and when pre-rotated towards the concavity.

    Layman's terms. For a right T curve. You are weaker when trying to twist to the left than when you twist to the right.

    It's a tab bit more complicated, but that's the basic idea. The issue is whether or not the muscles on the concave side are the cause for the weakness. A trunk rotation is an extremely complicated coordination of muscle activity. It's even further complicated by the idea that the primary movers for a rotation don't directly influence the spine, i.e. they influence indirectly via the rib cage or fascia. Therefore, any muscle weakness directly on the spine would only have minimal rotational force OR would be primarily involved with stabilization/antagonistic contractions.

    One very rough way to think about it is, if you have two people (A and B) in a line one behind the other facing one direction and person A is holding a balloon against a wall and person B is going to try to pop the balloon by pushing against A which will push the balloon against the wall and pop it. No matter how strong B is, if A is not strong enough to withstand the force required, the balloon will not pop (assuming arms must remain rigid).

    So with rotations, the force exerted is certainly dependent on the primary movers (person B). But it is also dependent on the strength of the stabilizers (person A). You see other orthopedic conditions resulting from this such as shoulder or ankle instability. Even low back pain can be a result of this. This is somewhat theoretical and is a very difficult thing to measure or confirm.

    It is also made even more complicated when you factor in different lengths and angles of muscles (the biomechanics). Ian Stokes has published some very nice computer modeling on this. He modeled a rotation of lumbar curve. And based only on the altered biomechanics of the muscles showed a weakness towards the concavity. (I hope I'm remembering that result correctly).

  14. #44
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    I've been missing out here lately! Good find Mamamax!

    The nucleus pulposus of scoliotic discs respond to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines
    http://scoliosisjournal.com/content/4/S1/O1

    http://en.wikipedia.org/wiki/Carcinogens
    Cooking food at high temperatures, for example grilling or barbecuing meats, can lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzo[a]pyrene).

    Barbecuing meat was popular back when Hippocrates discovered scoliosis.... Just wondering "if" this might be the naturally occurring carcinogen at blame?

    Hamburger anyone?
    Ed
    49 yr old male, now 60, the new 55...
    Pre surgery curves C12,T70,L70
    ALIF/PLIF T2-Pelvis 01/29/08, 01/31/08 7" pelvic anchors BMP
    Dr Brett Menmuir St Marys Hospital Reno,Nevada

    Bending and twisting pics after full fusion
    http://www.scoliosis.org/forum/showt...on.&highlight=

    My x-rays
    http://www.scoliosis.org/forum/attac...2&d=1228779214

    http://www.scoliosis.org/forum/attac...3&d=1228779258

  15. #45
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    is this the same thing?

    skevimc

    Very interesting. I didn't realize that the muscles around the spine weren't doing all of the work during a rotation. But is a rotation still the best way to engage those muscles?

    Does this study from 2006 measure the same problem discovered in the rotational studies but in a different manner? For instance one policeman may use a radar gun while the other uses a lasar but both are trying to determine how fast a car is speeding.

    Geometric and electromyographic assessments in the evaluation of curve progression in idiopathic scoliosis.

    METHODS: The changes in radiographic geometric and EMG variables between the first presentation and consecutive 4-6-month follow-up periods were analyzed in 105 patients with idiopathic scoliosis. Statistical analyses were performed to elucidate in more detail how spinal geometry evolves during curve progression.

    RESULTS: Curve severity was associated with remaining growth potential expressed as an increasing spinal growth velocity (SGV). With increasing SGV, an enhanced EMG activity at the lower part on the convex side of the curve expressed as EMG ratio was found. High EMG ratio was associated with increased axial rotation and diminished kyphosis before the rapid increase in Cobb angle. Lateral deviation, wedge angle, and axial rotation all increased during periods of progression. Changes in tilt angle and lordosis were not associated with curve progression.

    CONCLUSIONS: In the natural history of idiopathic scoliosis, SGV and EMG ratio at the lower end vertebra are prominent risk factors of curve progression. The asymmetric muscle activity is associated with increased axial rotation, which in its turn is associated with increasing Cobb angle and diminishing kyphosis. The combination of these variables provides insight in the physiologic and 3-dimensional biomechanical evolution of the natural history of curve progression in idiopathic scoliosis.

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