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Klimas London presentation, CD26/DPPIV impaired in CFS - retroviral involvement?

Discussion in 'XMRV Research and Replication Studies' started by natasa778, May 25, 2010.

  1. Esther12

    Esther12 Senior Member

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    Always excellent to have people looking into things thoroughly. Dampen away.
     
  2. natasa778

    natasa778 Senior Member

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    JT1024, nancy did mention perforin, as in a 'another marker, surrogate for measuring NK cell function'...
     
  3. Karin

    Karin

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    I personally think that while theories and studies are good, nothing replaces a simple diet trial. There is so much we don't know and don't understand yet. Anecdotally many kids with autism benefit from GFCF, so I think it is worth a try. I believe in planning for it, than going 100% for it cold-turkey, to really see if it's doing something. If it brings big improvements, great. if not, then you can move on to something else. Just my opinion.
     
  4. subtr4ct

    subtr4ct Senior Member

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    Any more details? Porphyrins are a complicated subject, and another contentious issue in autism research.

    Edit: Oh -- I see that perforin is a protein related to immune cells. So much that I don't know... Any way that biomedical effects can run across near-homonyms? :Retro smile:
     
  5. natasa778

    natasa778 Senior Member

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    that is the crux of it! all those studies to prove or disprove that the diet works are such a colossal tragic waste of money. short term ones do not prove anything (like the much publicised recent one looking at what, 14 kids, for a month... a joke) and long term ones are tragic in a way that kids who could be benefiting are given 'placebo' for months/years, and those that don't needed it are kept on it for years.

    such a waste, those studies are next in line of uselessness, right after "autism susceptibility gene studies", those looking at serotonin transporters or similar. criminal waste of money.
     
  6. Athene

    Athene ihateticks.me

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    In case anyone is interested, this explains the gluteomorphin and caseomorphin research project done at the University of Sunderland

    http://www.espa-research.org.uk//urine.html

    They've been analysing urine samples for years, have done thousands, and have found consistent results. The link explains some of the requirements for reliable results in detecting these unstable organic compounds. The wee needs to be very fresh and stored with a preservative for a max of 24 hours. This may be where the other research project failed.

    If you live in the UK you can get your wee tested by them for these gluten and dairy derived compounds - it's not expensive. Follow link for details.

    For anyone interested in trying GFCF, there is a lot of info on this site.
     
  7. leaves

    leaves Senior Member

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    I have been gfcf ( except for goat products) for several years now and it has helped me immensely: much more relaxed and less locked in. I'm xmrv and I suspect my mum too. she's now also gf for some time and is doing much better.
     
  8. Gemini

    Gemini Senior Member

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    Frank,

    Thanks for the gluten/casein information.

    Do you know if there's a list of proline-rich foods (besides those containing gluten & casein)?

    Gemini
     
  9. natasa778

    natasa778 Senior Member

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    http://articles.mercola.com/sites/ar...in-autism.aspx

    The concept of opiate-like peptides affecting children with ASD was led by Shattock29-30, Reichelt31-32, and others33-34 through examination of urinary metabolites containing peptides from gluten and casein. The opiate antagonist naltrexone proved unsuccessful in controlled trials (this is only partially true, the trials of FULL dose naltrexone showed very positive results in a subset...) with dietary removal of gluten and casein yielding anecdotal positive results. Association with ASD and serotonin was scrutinized in intricate detail40-43 but not clarified until Matson44 (1996,unpublished data) isolated bufotinines, methylated serotonin compounds, in the serum of children with ASD.

    Matson found that these compounds literally are created by the patient evoking hallucinogenic symptoms finding that children with ASD overmethylate. Friedman45 (stated in public forum) noted through tandem mass spec analysis in 1998 that aberrant peptides originally derived from casein/gluten as well as Clostridium created hallucinogenic effects initially linking casein ingestion to cellular surface immune response, specifically CD26, which is crucial to clearing of beta-casomorphin. Friedman continued his research (study submitted for publication) linking the effect of opiates from gluten, casein, and particular species of Clostridium upon the suppression the enzyme Dipeptidyl Peptidase-DPP4 or CD26 ultimately impacting the liver, kidney, small intestine and blood brain barrier where this enzyme predominates.

    The role of CD26 is primarily one of T cell activation and the cleavage of peptides at the location of proline and alanine thereby breaking down aberrant peptides or inactivation of neuropeptides. Friedman has noted the amino acid sequencing of peptides in the urine of children containing alanine and proline in the D- rather than the L- position whereby CD26 cleavage of these isomers would be 1000 fold over peptides containing alanine and proline in the L-position. The research of Friedman and Matson link endogenous polypeptides to autistic behaviors (hallucinogenic in nature), with Matson's research oriented to serum rather than urinary metabolites, and indicating that the endogenous creation of bufotinines are related to bizarre behavior patterns.

    Treatment protocols have not yet been established, but clinicians must consider that of tremendous concern in children with ASD is the very passage of peptides through the blood brain barrier, electrolyte instability, allergic manifestation, GI disturbance and intestinal permeability46 as all are indicative of a loss of cell membrane integrity. Bauman47 and Minshew48-49 have clearly identified aberrations in neurons and membrane phospholipids in ASD patients. Certainly the removal of casein and gluten may be of tremendous benefit, but the very mechanism of metabolic entropy, immune dysregulation and loss of cell membrane integrity must be addressed to sustain the health of multiple body systems ... (thanks for this R!)
     
  10. Rosemary

    Rosemary Senior Member

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    http://www.thecrystaltarot.com/articles/nutrition-articles/autism-alternative

    Autism, an extreme challenge to integrative medicine.
    Alternative Medicine Review, Dec, 2002 by Parris M. Kidd

    Peptide Abnormalities (6)

    Peptides (small polymers of amino acids) act as regulatory or signal molecules, affecting a variety of neurotransmitter systems that regulate behavior. Certain peptides can be abnormally elevated in the urine of ASD subjects. (73) For example, as previously mentioned, high urinary levels of the dipeptides anserine and carnosine generally indicate poor digestive function.

    Certain food-derived peptides have endorphin-like effects on the dopamine neurotransmitter system, and to differing extents also the cholinergic, serotonergic, noradrenergic, and GABAergic systems. In 1979, Panksepp suggested incompletely digested peptides with opioid activity could be causative in autism. (74) Thus began the “opioid excess” theory of autism alluded to in part I of this review. In 1981, Reichelt and colleagues reported abnormal peptides with opioid activity in the urine of 22 of 25 autistics studied. (73) Gillberg later found excessive levels of endorphin-like substances, later coined exorphins, in the CSF of autistics. (75)

    Dietary exorphins are peptides produced from incomplete digestion of casein or gluten foods–casomorphins, gluteomorphins, and gliadomorphins (4)–all with powerful endorphinopiate activity in the brain. Effective digestive breakdown of these substances normally relies on only one, highly specialized peptidase enzyme called dipeptidyl-peptidase IV (DPPIV). Congenital weakness in DPPIV function was linked to autism by Stubbs in 1982. (76) The DPPIV enzyme is also highly sensitive to mercury and organophosphate xenobiotics. (6) This metabolic weakness may be a cause of ASD by enhancing absorption of exorphins, leading to adverse reactions in the brain and to immune dysregulation. (68)

    In 1990 Shattock et al reviewed the various mechanisms by which opioid peptides may initiate perceptual impairment, stereotypic behaviors, self injury, and other autistic behavior. (77) They discussed how the blockade of dopamine receptors by opioids can result in spillage of dopamine into the CSF, or into the urine predominantly as homovanillic acid. High CSF and/or urine HVA is a frequent finding in subgroups of ASD children, and is an indicator of possible CNS insufficiency of dopamine. (77)

    To decrease the possibility of abnormal peptide production from foods, protein digestion can be improved by supplementing with digestive enzymes and betaine hydrochloride (HCl). (48) Since enzyme supplementation does not guarantee inhibition of exorphin production from casein and gluten foods, a strict casein and gluten-free diet should still be considered.


    Correcting Gastrointestinal Abnormalities


    Many ASD individuals have GI abnormalities (see part I of this review). Maldigestion and malabsorption are common and combine with dysbiosis that commonly results from repeated antibiotic treatment. Chronic inflammation of the GI tract afflicts at least half of ASD subjects sampled, whether or not symptoms manifest. (78) Melmed et al reported that a study of 385 autistic people found 46 percent had chronic diarrhea, constipation, or other GI symptoms. (79) Horvath et al reported on 36 ASD children with chronic diarrhea, gas, abdominal discomfort and distension. (80) More than two-thirds had GI inflammation, associated with impaired digestive enzyme activity.

    In 2002, Wakefield’s group published a provocative overview of a pattern designated autistic enterocolitis, (26) featuring motility disorder combined with inflammation. They reported impressive improvement from the use of 5-aminosalicylates and a limited diet, including casein and gluten elimination, to decrease inflammation. The dysmotility could be due to exorphin actions directly on the GI tract. They discussed a scenario in which exorphins, such as gluteomorphin or gliadomorphin from wheat and beta-casomorphin from milk, escape digestion by the DPPIV enzyme due to gut damage. These substances can either be absorbed, reach the bloodstream, and travel to the CNS; or act locally to directly impair the intestinal wall motility.

    Integrative practitioners have worked closely with laboratories to develop comprehensive assessments of GI abnormalities. (20,68) One result of this effort is the comprehensive digestive and stool analysis (CDSA) that includes tests for digestive function (undigested food, for example), metabolic function (particularly short-chain fatty acids that reflect probiotic activity), microbiology (from bacterial culture), mycology (presence and types of yeasts and other fungi), and parasitology. The Biomedical Assessment manual from DAN! lists laboratories that offer CDSAs. (20)

    Frequent findings in autism are discussed below, together with some of the corrective approaches suggested by Baker and Pangborn in the DAN! assessment manual. (6) For a more comprehensive list of options this manual should be consulted directly.

    Bolte (81) suggested the possibility of a sub-acute, chronic tetanus infection of the gut as an underlying cause of autism in some individuals. Clostridium tetani is a ubiquitous anaerobic bacterium that is opportunistic in the gut and produces a potent neurotoxin. This toxin can move from the intestine to the brain via the vagus nerve. Antibiotic treatment should be accompanied by high-potency probiotic replacement.
     
  11. Rosemary

    Rosemary Senior Member

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    Digestive breakdown of the small peptides from casein and wheat mostly relies on just one enzyme, the dipeptidyl-peptidase IV (DPPIV). Congenital weakness in DPPIV function is linked to autism,3 and the enzyme is highly sensitive to mercury and organophosphate xenobiotics.

    Recently, Brudnak, Rimland, and collaborators designed a sophisticated digestive enzyme supplement aimed at supporting DPPIV activity. Their pilot study with 22 subjects documented wide-ranging symptom improvements of between 50-90%.23

    *****The supplement included galactose, as a food source for the “probiotic” bacteria of the intestinal tract. These symbionts such as lactobacilli and the bifidobacteria, produce DPPIV and are able to fully digest exorphins. This innovation has particular clinical promise since there are normally far more probiotic cells housed in the human intestines (over 1011) than there are cells in the intestinal lining.*****

    Brudnak and collaborators also discussed the potential for repleting probiotics in the intestines, using multiple species on a rotating or “pulsed” basis.23 Altogether, a new four-pronged GI approach is emerging, of combining food restriction with potent enzyme supplementation, probiotic substrate support, and probiotic supplementation. This approach represents the current best effort to restore GI function and epithelial lining integrity, thereby to protect the brain against damage from food-derived molecules.

    3. Kidd PM. Autism, an extreme challenge to integrative medicine. Part 1. The knowledge base. Altern Med Rev 2002;7:292-316.23.

    23.Brudnak MA, Rimland B, Kerry RE, et al. Enzyme-based therapy for autism spectrum disorders – is it worth another look? Med Hypotheses 2002;58:422-428.

    http://www.dockidd.com/articals/autism.htm
     
  12. Athene

    Athene ihateticks.me

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  13. Gemini

    Gemini Senior Member

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  14. Frank

    Frank Senior Member

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    Rosemary the same kind of supplement exisits in norway from a company called neurozym, it's called probiozym.
     
  15. JT1024

    JT1024 Senior Member

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    DPP-IV Forte Capsules

    Looks like all the things I like are proline rich...

    Just found this.....perhaps another supplement to consider..

    http://www.ourkidsasd.com/products/enymes/168|DPP-IV Forte™-Kirkman Labs

    Kirkman Labs
    DPP-IV Forte Capsules

    (A Dipeptidyl peptidase IV (DPP-IV) Analog for Comprehensive Digestion of Protein Peptides) DPP-IV FORTE (featuring a Dipeptidyl peptidase IV analog) is one of the most exciting nutritional enzyme supplements available from Kirkman Laboratories. This digestive enzyme can be supplemented alone or in combination with other nutritional enzymes to support the digestive process.

    This unique enzyme specifically breaks apart proline-containing peptides (casomorphin, gluteomorphin and gliadomorphin), which are generally known to come from dairy products and cereal grains. The DPP-IV enzyme assists digestion of these peptides, which are generally resistant to being completely broken down by other enzymes.

    WHAT IS DPP-IV? Dipeptidyl peptidase (DPP-IV) is a protein that has multiple functions in the body. It is known under different names depending on where it is found. When DPP-IV is on the surface of the T-cell (lymphocyte), it is called CD26, and supports immune function. When this enzyme is found on and imbedded on the epithelial brush boarder mucosal membrane of the intestinal tract lining it is known as DPP-IV. The importance of DPP-IV is that it has primary function in breaking down casein and side chain activity in breaking down gluten. Thus the use of a DPP-IV containing enzyme will support the digestion of casein-containing milk products as well as the protein in gluten-containing grains.

    Guaranteed:
    SCD-legal
    wheat-free
    gluten-free
    milk-free
    casein-free
    soy-free
    yeast-free
    sugar-free
    starch-free
    egg-free
    MSG-free
    no artificial sweeteners
    no colors or flavors
    stearate-free
    preservative-free
    salicylate-free
    no common allergens

    Quantity: 60 capsules
    Price: $15.00
     
  16. Karin

    Karin

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    Thanks. We have already been using Kirman's DPPIV enzymes for three years, but always with food. We are gluten-free, soy-free and casein-free, but use those anyways. However, we've never tried using those on an empty stomach, which would ensure that the DPP-IV would go in the body. If there is a lack of DPP-IV resulting in autonomic nervous issues, I am thinking this could help? I'll try it on myself.

    I too was eating a diet consisting of 90% gluten and casein (pasta, bread, cereals, milk, cheese, yogurt, ...), at breakfast, lunch, dinner, snacks. That's all I've been eating for 35+ years. Three years ago I went GFCFSF overnight cold-turkey. Like I said earlier, horrible widthdrawal. No wonder, if these peptides act on our nervous system, going off them is going to be like going off opioid-based drugs. But then I saw so many benefits that three years later I am still GFCFSF. I discovered so many great things to eat.
     
  17. Gemini

    Gemini Senior Member

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    Karin,

    I'd be very interested in your reaction to taking the capsules on an empty stomach.
    Please keep us posted.

    Gemini
     
  18. Athene

    Athene ihateticks.me

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    I'm also trying this experiment - DPP-IV capsules on empty stomach, with a GFCF diet.
    I started 3 days ago so it's early to comment but I'll see how it goes.
     
  19. Rosemary

    Rosemary Senior Member

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  20. Karin

    Karin

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    Gemini, I will post on this list. It might be a couple weeks before I try though, I'll have to work up the courage. I tried enzymes on an empty stomach for my son a couple years ago, combos of multiple enzymes (that the manufacturer claimed were fine on an empty stomach), and got very bad results, with high fevers, very, very sick. Ever since then I have been very careful to give enzymes only with food. If there is inflamation in the digestive track, biofilms and other nasties, active enzymes in the mix can be explosive. However, just DPP-IV and nothing else would be a very different situation, I would think, and I would try on myself first. But anyways, I'll need to plan it and work up the courage...
     

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