Journal
GASTROENTEROLOGY
Volume 119, Issue 1, Pages 41-50Publisher
W B SAUNDERS CO
DOI: 10.1053/gast.2000.8553
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Funding
- NIDDK NIH HHS [K24-DK02638-01, R01-DK54681-01] Funding Source: Medline
- NINDS NIH HHS [R01-NS39722] Funding Source: Medline
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Background & Aims: The aim of this study was to assess the effects of recombinant human brainderived neurotrophic factor (r-metHuBDNF) and recombinant human neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functions in healthy people and in patients with constipation. Methods: Gastrointestinal and colonic transit was measured by scintigraphy before and after 2 weeks of treatment. Daily diaries documented symptoms over 6 weeks before, during, and after treatment. In a randomized study of healthy subjects, 40 received 100 mu g/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation received 300 mu g/kg r-metHuNT-3 SC thrice weekly. Results: r-met-HuBDNF accelerated overall and proximal colonic emptying (P < 0.05) in health. r-metHuNT-3 accelerated overall colonic transit in health and constipation tall P < 0.05) and gastric and small bower transit (both P < 0.05) in health. r-metHuBDNF tended to increase stool frequency compared with placebo in health (P = 0.09), r-metHuNT-3 increased stool frequency (P = 0.05) and facilitated passage of stool (P < 0.01) in constipated patients. The effects on stool frequency started within 3 days of the beginning of neurotrophin administrations and lasted up to 5 days after treatment ended. r-metHu neurotrophic factors were well tolerated, although half of the participants in the 2 studies developed injection site reactions or paresthesiae. Conclusions: Exogenous neurotrophic factors stimulate human gut motility in health and constipation.
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