Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn's disease interstitial cystitis and possibly Reiter's syndrome

Ulcerative colitis, Crohn's disease and interstitial cystitis share many co mmon features, the most important of which is a defect in the glycoaminogly can (GAG) defensive barrier. This defect allows penetration of toxins causi ng localized inflammatory response, followed by fibrosis and distant pathol ogical changes, together with a myriad of biochemical and immunological cha nges. The latter has caused confusion as to etiology of the aforementioned disorders. This hypothesis is somewhat supported by the fact that agents su ch as glucosamine and pentosan polysulphate (Elmiron(R)) that replace the G AG layer, improve the conditions. The potential for extrapolation of this h ypothesis to atherosclerosis and arthropathies exists. There is a great danger in modern medical research that if one misses the w ood for the trees, one becomes hopelessly lost in the minutiae of research. At present, it is embarrassing that ulcerative colitis (UC), Crohn's (CR) and interstitial cystitis (IC) are the cause of a great deal of morbidity a nd occasionally mortality, yet after intensive research, the etiology and e ffective treatment eludes us. The research in the past has focused extensiv ely on inflammatory response in the mucosal lining, and biochemical, infect ive and immunological changes in the serum. This has led to a vast array of research pathways that seem at the present time to be totally lost and, mi ght I say, aimless in direction, as a cause for these conditions, that rema in amongst the most imperically treated in modern medicine. Another possible syndrome in this class would be Reiter's, which has many f eatures in common with the above. The basic tenet of a GAG deficiency hypot hesis is that, as shown in Figure 1A, an intact GAG layer provides, firstly , a mechanical and electrostatic defence against penetration of infective a gents, toxins, antigenic protein moieties, etc. and, secondly, the preventi on of extravasation of body fluid components. A degraded GAG layer is the s tart of the disease cascade of the above group of illnesses.