title: Different molecular forms of basic fibroblast growth factor (bFGF) accelerate duodenal ulcer healing in rats.
abstract: Basic fibroblast growth factor is an angiogenic polypeptide that exhibits potent antiulcer activity without decreasing gastric acid or pepsin secretion. In this study, we investigated the effect of three acid-stable derivatives of human recombinant bFGF (hrbFGF) on the healing of chronic duodenal ulcer in rats. In Sprague-Dawley female rats, duodenal ulcers were induced by cysteamine-HCl. After laparotomy, rats were randomized to create six groups with homogeneously severe ulcers (perforated or penetrated into the liver or pancreas) and treated by gavage twice a day for 3 weeks with a) vehicle, b) cimetidine (10 mg/100 g), c) Ser78,96-hrbFGF (bioequivalent to rbFGF-CS23), d) CMC-hrbFGF, a carboxymethyl cysteine derivative of hrbFGF or e) PEG-hrbFGF, a polyethylene glycol derivative of hrbFGF. The peptides were administered at 100 ng/100 g. Autopsy was performed on the 21st day, and the ulcer size was measured. The ulcer sizes (mm2) were reduced from 10.3 +/- 1.8 in controls to 4.8 +/- 1.4* after cimetidine treatment and to 5.0 +/- 2.4, 4.2 +/- 1.1* and 0.5 +/- 0.2**, respectively, after administration of aforementioned hrbFGF derivatives (*P < .05; **P < .01 vs. vehicle group), which also significantly enhanced angiogenesis in the ulcer bed.
  
  
  CONCLUSIONS
  1) Oral administration of novel derivatives of hrbFGF accelerated the healing of cysteamine-induced chronic duodenal ulcer. 2) The PEG-hrbFGF derivative was more active than the other hrbFGF analogs. 3) The naturally occurring bFGF provides a good prototype to design new locally acting antiulcer drugs.
authors.affiliation: Chemical Pathology Research Division, Brigham & Women's Hospital, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kusstatscher
authors.forename: Z
authors.initials: Z
authors.lastname: Sandor
authors.forename: S
authors.initials: S
authors.lastname: Szabo
authors.forename: A
authors.initials: A
authors.lastname: Seddon
authors.forename: P
authors.initials: P
authors.lastname: Böhlen
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004355:Drug Stability; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D008853:Microscopy; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D002927:Cimetidine