Imbalance of Stromelysin-1 and Timp-1 Mrna and Protein in the Mucosal Lesions of Children With Inflammatory Bowel Disease

Heuschkel, Robert; Pender, S.; Paintin, M; Arnaud-Battandier, F; Walker, Judith S.; Macdonald, T. O.

doi:10.1097/00005176-199905000-00073

Cited by 2 publications

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“…Therapeutic inhibition of MMPs by their natural antagonists, tissue inhibitors of metalloproteases (TIMPs), has indeed been shown to prevent tissue damage in experimental allergic encephalomyelitis, despite vigorous ongoing inflammation 18 . Active inflammatory bowel disease is characterized by the relative excess of mucosal MMPs over TIMPs, 19 and thus the therapeutic use of TIMPs would appear to be an attractive option for limiting matrix degradation. These inhibitors are now the subject of intense research activity, but are likely to be expensive and unavailable for some years.…”

Section: Introductionmentioning

confidence: 99%

A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease

Salvatore

Heuschkel

Tomlin

et al. 2000

Aliment Pharmacol Ther

143

106

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Background: The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease activity may be effective in treating chronic inflammation. Aim: To report an alternative approach, using the nutriceutical agent N‐acetyl glucosamine (GlcNAc), an amino‐sugar directly incorporated into glycosaminoglycans and glycoproteins, as a substrate for tissue repair mechanisms. Methods: GlcNAc (total daily dose 3–6 g) was administered orally as adjunct therapy to 12 children with severe treatment‐resistant inflammatory bowel disease (10 Crohn’s disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or proctitis resistant to steroids and antibiotics. Where pre‐ and post‐treatment biopsies were available (nine cases), histochemical assessment of epithelial and matrix glycosaminoglycans and GlcNAc residues was made. Findings: Eight of the children given oral GlcNAc showed clear improvement, while four required resection. Of the children with symptomatic Crohn’s stricture, only 3 of 7 have required surgery over a mean follow‐up of > 2.5 years, and endoscopic or radiological improvement was detected in the others. Rectal administration induced remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement, and a significant increase in epithelial and lamina propria glycosaminoglycans and intracellular GlcNAc. Conclusions: GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. It may have the potential to be helpful in stricturing disease. However, controlled trials and an assessment of enteric‐release preparations are required to confirm its efficacy and establish indications for use.

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Section: Introductionmentioning

confidence: 99%

A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease

Salvatore

Heuschkel

Tomlin

et al. 2000

Aliment Pharmacol Ther

143

106

View full text Add to dashboard Cite

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The microbiome landscape in pediatric Crohn’s disease and therapeutic implications

Fetter,

Weigel,

Ott

et al. 2023

Gut Microbes

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Dysbiosis of the gut microbiome and a pathological immune response in intestinal tissues form the basis of Crohn’s disease (CD), which is a debilitating disease with relevant morbidity and mortality. It is increasing in childhood and adolescents, due to western life-style and nutrition and a large set of predisposing genetic factors. Crohn’s disease-associated genetic mutations play an essential role in killing pathogens, altering mucosal barrier function, and protecting the host microbiome, suggesting an important pathogenic link. The intestinal microbiome is highly variable and can be influenced by environmental factors. Changes in microbial composition and a reduction in species diversity have been shown to be central features of disease progression and are therefore the target of therapeutic approaches. In this review, we summarize the current literature on the role of the gut microbiome in childhood, adolescent, and adult CD, current therapeutic options, and their impact on the microbiome.

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Imbalance of Stromelysin-1 and Timp-1 Mrna and Protein in the Mucosal Lesions of Children With Inflammatory Bowel Disease

Cited by 2 publications

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A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease

A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease

The microbiome landscape in pediatric Crohn’s disease and therapeutic implications

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