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Celiac Disease

Celiac Disease

Natural treatments for ailments due to allergies to gluten and casein and INTEREST ASSAY OF URINARY PEPTIDES in the immuno-pathological reactions to proteins of cereal.

Introduction

the test ? 

Therapeutic Applications

References

Introduction summary

The pathology most studied and induced by proteins of cereals is Celiac disease [1-3] characterized by defective degradation of proteins in wheat, the passage into the general circulation of gliadin fragments which are binding to tissue transglutaminase, causing a reaction with lymphocyte proliferation of anti-transglutaminase antibodies in the blood and anti-endomysium of isotype IgA.

This pathology is accompanied histologically of atresia of the intestinal villi and is often associated with various neurological disorders : headaches , migraine [4], cerebellar ataxia [5], anemia [6], osteoporosis [6], cancer [6], autoimmune diseases 6], learning disabilities and hyperactivity (ADHD).

It also emerges from the medical scientific literature of other pathologies where gluten may also be implicated with other events than immunological or intestinal and what may be called Silent celiac diseases and characterized by normal intestinal villi, normal blood antibodies or at the upper limit and associated with neurological disorders (depression, hyperactivity, epilepsy [4], dyspraxia, dyslexia, schizophrenia [7, 8] and other psychiatric disorders therapeutic applications ) and / or dermatological (dermatitis herpetiformis, atopic dermatitis, acne, eczema, psoriasis, ...).

The extreme variability of the symptoms observed in patients having a particular sensibility to the proteins of cereal (and\or in proteins of cow's milk) led us to develop an assay by high performance liquid chromatography (HPLC) of urinary peptides as a diagnostic tool and therapeutics monitoring of these patients.

The urinary excretion of oligopeptides, mostly exogenous origin, is indeed in humans, the global reflection of all the various mechanisms involved in the degradation of food proteins in the digestive tract then, after absorption, their fate in the body including the passage of the renal barrier.

It is clear that in the celiac disease, that gliadin fragments pass into the general circulation by altering tight junctions of the intestinal wall [9].

These tight junctions are also associated with adherens junctions and desmosome, involving a range of protein families such as claudins, occludin, cadherins, ZO-1 à 3, [10]...

The whole is very complex, but these tight junctions are also present in other epithelia such as the blood-brain barrier and kidney , there are also in their immediate environment many peptidases of which dipeptidyl-peptidase IV (DPP IV ; EC 3.4.14.5) particularly in the brain [11] but also spread to other organs.

The existence of diverse mechanisms that can modulate the flow of the respective peptides (often of food origin) in the body and potentially interfere with the brain receptors m, d and k  (by analogy with the gluten exorphins B5 [12, 13] and the morphiceptine from casein [14]) allows to explain the great variability of the previously evoked symptoms, and firstly the neurological symptoms, causing changes in behavior depending on the food as it does in schizophrenia [7, 8].

Our experience on over 1700 peptides urinary analysis shows that this biological environment is sufficiently discriminative to extract from it, based on clinical and biological criteria, nearly 600 normal values in a very narrow range of values.

The low values seem to have no physiological or behavioral involvement. When there is accumulation of these peptides (up to a 50-fold increase), we may suggest dietary restriction resulting in most cases to a clinical improvement of the patient.

On the other hand, we were nevertheless able to observe very rare cases of " false negatives " (currently less than 1 %) with normal urinary peptide levels, but these patients, put under food restriction, can nevertheless find a clinical profit and even relapse transiently by differences in diet (among others during holidays) or permanently if they resume a normal diet.

Whatever is the biological result, it finally belongs to the clinician, according to his sagacity and symptoms of his patientto propose him a temporary food restriction (Where hide the gluten and the casein in food) as well as from nutritional advice (particularly for the bowel therapeutic applications) over a period of a several months while following its clinical and biological evolution.

The Test summary

Very few laboratories in the world are authorized to make the search for peptides in urine by HPLC and who have the experience and sufficient hindsight.

We shall quote first the Norwegian Kalle Reichelt [15-17] in Oslo which initiated this research  from the 1980s, but other researchers have subsequently used this technique by applying it in England (Paul Shattock [18]), United States, Japan or Switzerland.

Therapeutic APPLICATIONS 

Obviously, all the therapeutic means to be advised will be developed, so that they present no contraindication to the persons allergic to the gluten, lactose or casein (GCF Gluten Lactose & Casein Free). 

We recommend in the front line of action ... summary

Nutracare 2 capsules a day to treat  the intestinal malabsorption and more generally in all the situations where, after elimination of etiological factors, it is to repair the intestinal epithelium and correct the deficiencies induced.

And according to the etiology ...

For neurological disorders, Betacine 3 capsules a day; its action to reduce homocysteine and increase the natural production of SAMe (S-adenosyl methionine) is appropriate for depression, hyperactivity and epilepsy.

For the regulation of intestinal transit, Fytostin 2 capsules per day, allows a good regulation of the rhythm of saddles, improves intestinal cycle, reduces bloating and intestinal gurgling and cleanses the body by reducing the fermentation.

To regenerate the bacterial flora Proflore, 1 capsule a day, combines three lactic bacteria specially selected for their synergy (Lactobacillus bulgaricus, Bifidobacterium bifidum, Lactobacillus acidophilus)

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REFERENCES

•1.      Yardley JH, Bayless TM, Norton JH, Hendrix TR. Celiac disease. A study of the jejunal epithelium before and after a gluten-free diet. N Engl J Med 267, 1173-9 (1962).

•2.      Lepers S, Couignoux S, Colombel JF, Dubucquoi S. Celiac disease in adults : new aspects. Rev Méd Int 25, 22-34 (2004).

•3.      Israel EJ, Levitsky LL, Anupindi SA, Pitman MB. A 14-year-old boy with recent slowing of growth and delayed puberty. N Engl J Med 352, 393-403 (2005).

•4.      Egger J, Carter CM, Soothill JF, Wilson J. Oligoantigenic diet treatment of children with epilepsy and migraine. J Pediatr 114, 51-8 (1989).

•5.      Bürk K, Bösch S, Müller CA, Melms A, Zühlke C, Stern M, Besenthal I, Skalej M, Ruck P, Ferber S, Klockgether T, Dichgans J. Sporadic cerebellar ataxia associated with gluten sensitivity. Brain 124, 1013-9 (2001).

•6.      Alaedini A, Green PH. Narrative review: celiac disease: understanding a complex autoimmune disorder. Ann Intern Med 142, 289-98 (2005).

•7.      Dohan FC. Cereals and schizophrenia. Data and hypothesis. Acta Psychiatrica Scandinavica 42, 125-52 (1966).

•8.      Dohan FC. The possible pathogenetic effect of cereal grains in schizophrenia. Celiac disease as a model. Acta Neurol 31, 195-205 (1976).

•9.      Schneeberger EE, Lynch RD. The tight junction : a multifunctional complex. Am J Physiol Cell Physiol 286, C1213-C1228 (2004).

•10.  Liu Y, Nusrat A, Schnell FJ, Reaves TA, Walsh S, Pochet M, Parkos CA. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 113, 2363-74 (2000).

•11.  Brownless J, Williams C. Peptidases and peptides at the blood-brain barrier. In : « Metabolism of brain peptides « , ed. by O'Cuinn, CRC Press, London, 159-99 (1995).

•12.  Zioudrou C, Streaty RA, Klee WA. Opioid peptides derived from food proteins. The exorphins. J Biol Chem 254, 2446-9 (1979).

•13.  Fukudome SI, Yoshikawa M. Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett 296, 107-11 (1992).

•14.  Chang KJ, Killian A, Hazum E, Cuatrecasas, Chang JK. Morphiceptin (NH4-Tyr-Pro-Phe-Pro-CONH2): a potent and specific agonist for morphine (?) receptors. Science 212, 75-7 (1981).

•15.  Trygstad O, Foss I, Edminson PD, Johansen JH, Reichelt KL. Humoral control of appetite: a urinary anorexigenic peptide. Chromatographic patterns of urinary peptides in anorexia nervosa. Acta Endocrinol (Copenh.) 89, 196-208 (1978).

•16.  Reichelt KL, Ekrem J, Scott H. Gluten, milk proteins and autism: dietary intervention effects on behavior and peptide secretion. J Appl Nutr 42, 1-11 (1990).

•17.  Knivsberg AM, Reichelt KL, Hoien T, Nodland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci 5, 251-61 (2002).

•18. Shattock P, Lowdon G. Proteins, peptides and autism. Part 2: implications for the education and care of people with autism. Brain Dysfunct 4, 323-34 (1991).

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