Elsevier

Medical Hypotheses

Volume 52, Issue 4, April 1999, Pages 297-301
Medical Hypotheses

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

https://doi.org/10.1054/mehy.1997.0652Get rights and content

Abstract

Summary Ulcerative colitis, Crohn's disease and interstitial cystitis share many common features, the most important of which is a defect in the glycoaminoglycan (GAG) defensive barrier. This defect allows penetration of toxins causing localized inflammatory response, followed by fibrosis and distant pathological changes, together with a myriad of biochemical and immunological changes. The latter has caused confusion as to etiology of the aforementioned disorders. This hypothesis is somewhat supported by the fact that agents such as glucosamine and pentosan polysulphate (Elmiron®) that replace the GAG layer, improve the conditions. The potential for extrapolation of this hypothesis to atherosclerosis and arthropathies exists.

There is a great danger in modern medical research that if one misses the wood 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 and occasionally mortality, yet after intensive research, the etiology and effective treatment eludes us. The research in the past has focused extensively on inflammatory response in the mucosal lining, and biochemical, infective 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, might I say, aimless in direction, as a cause for these conditions, that remain amongst the most imperically treated in modern medicine.

Another possible syndrome in this class would be Reiter's, which has many features in common with the above.

The basic tenet of a GAG deficiency hypothesis is that, as shown in Figure 1A, an intact GAG layer provides, firstly, a mechanical and electrostatic defence against penetration of infective agents, toxins, antigenic protein moieties, etc. and, secondly, the prevention of extravasation of body fluid components. A degraded GAG layer is the start of the disease cascade of the above group of illnesses.

References (32)

  • Burton, A. L. Freeman, H. Method and composition for treatment of lower gastrointestinal tract disorders,...
  • Russell, A. L. Glucosamine may be the catalyst for a shift in paradigm, Med...
  • C.E. Day et al.

    Sulphated polysaccharide inhibition of aortic uptake of low density lipoproteins

    Artery

    (1974)
  • L.M. Morrison et al.

    Glycosaminoglycans and coronary heart disease

    Glycosaminoglycans and Proteoglycans in Physiological and Pathological Processes of Body Systems

    (1982)
  • J.M. Herbert et al.

    In vitro and ex vivo regulation of vascular smooth muscle cell growth and phenotypic modulation by sulphated polysaccharides

    Artery

    (1988)
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