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Background: During the healing of gastric ulcers, extensive changes take place in the structure and proportion of the parietal cells in the ulcer margin. We aimed to determine whether these changes are influenced by compounds or by procedures that may promote or delay gastric ulcer healing., Methods: Acetic acid ulcers were produced in the rat gastric corpus; control rats were non-operated or sham-operated. All rats were provided with an osmotic minipump releasing 3H-thymidine for determination of the labelling index (LI). The rats were given omeprazole, gastrin or indomethacin, infected with Helicobacter pylori, or subjected to anterior vagotomy. They were killed after 1, 2, 6 or 13 days, and the ulcer margin and undamaged corpus wall were excised for histology. The proportion of parietal cells was calculated in relation to the total number, and the total volume, of the epithelial cells., Results: The parietal cells averaged 16%-21% of the number and 30%-32% of the volume of the epithelial cells in the unoperated control rats, but considerably less in the ulcer margin. This reduction was partially prevented by indomethacin. In the undamaged, dorsal epithelium the parietal cells increased to 23%-26% of the number, and 41%-47% of the volume, of the epithelial cells, both in the ulcer rats and in the sham-operated rats. The LI of the parietal cells was 6% in the undamaged epithelium of the 13-day ulcer rats, but close to 0% in all other groups examined., Conclusion: Indomethacin prevents much of the loss of parietal cells in the ulcer margin. In the undamaged epithelium of the ulcer rats there is an increased proportion of parietal cells. The new parietal cells are not formed directly from dividing cells, but are probably recruited from existing precursor cells.

Background: Our aim was to infect rats with Helicobacter pylori and to study the effects of the infection on the gastric mucosa in normal and in ulcer-operated rats., Methods: A mouse-adapted H. pylori (cagA-, VacA-) strain was inoculated into 23 rats. Another 20 uninfected rats served as controls. Two months later a gastric ulcer was induced in some rats. The animals were killed 3, 6, or 15 days after the ulcer operation. Tissues were taken for histology and for culture of H. pylori. Serum antibodies were determined., Results: All inoculated rats were infected by H. pylori after 2 months, mainly in the antrum. In these rats a mild to moderate chronic inflammation and a significantly increased frequency of apoptotic cells were observed in the antrum and in the ulcer margin, the ulcer healing was delayed, and the serum level of H. pylori-specific Ig was increased., Conclusions: H. pylori infection in rats was successful and was accompanied by a mild to moderate mucosal inflammation. Gastric ulcer healing was delayed in infected rats, probably due to the inflammation and the increased apoptosis in epithelium.

Background: Helicobacter pylori is associated with peptic ulcer disease. In the present study, the influence of VacA and CagA- H. pylori on gastric ulcer healing was studied in the rat., Methods: Twenty-four rats with acetic-acid-induced gastric ulcer were divided into two groups and given either vehicle (Brucella broth) or H. pylori suspension by gavage every 12 h for 7 days. The animals were killed 1 and 8 days after the last H. pylori gavage (i.e. 10 and 17 days after the induction of the ulcer). One hour before death, 3H-thymidine was given intraperitoneally. Tissue samples from the stomach (including the ulcer area) and the duodenum were processed for determination of labelling index and apoptotic cells., Results: Compared with the vehicle-treated controls, the ulcer area in H. pylori-inoculated rats was significantly larger, the epithelial apoptotic cells in the ulcer margin and intact corpus were more numerous, while the cell proliferation of gastroduodenal epithelium was slightly, but not significantly, increased by H. pylori gavage., Conclusion: Gastric ulcer healing was delayed after the inoculation of VacA- and CagA- H. pylori in the rat, possibly as a result of excess cell loss by apoptosis.

During the healing of experimental gastric ulcers in the oxyntic mucosa, there is a dedifferentiation of the glands in the ulcer margin: previous studies have shown that the parietal cells lose their capacity to produce HCl, and mucous cells replace the zymogen cells. Primarily, we wished to investigate whether or not the glands of the ulcer margin transcribe mRNA for pepsinogen; secondly we also wanted to locate such transcription in other parts of the gastroduodenal epithelium. For this purpose, we first established the baseline for distribution of pepsinogen mRNA in normal rats. We then studied its location in the margin of ulcers in the corpus region after 1-15 days of healing. Formaldehyde-fixed paraffin sections were used for in situ hybridization of mRNA for pepsinogen C, utilizing radioactive riboprobes. The normal gastroduodenal mucosa showed widespread hybridization: the signal was particularly strong in the zymogen cells; weaker signals were obtained from the mucous neck cells, and the cells of the cardiac, antral, and Brunner glands. Specific hybridization was weak or absent in the ulcer margin during the entire period studied. It is concluded that the capacity to produce pepsinogen C is significantly reduced or absent in the gastric ulcer margin during the first 15 days of healing; this should reduce the risks of peptic attack on the delicate scar and margin tissues during ulcer healing.

We investigated if hypergastrinemia exerted any influence on the proliferation of gastroduodenal epithelium during the healing of ulcers in rats. A mucosal ulcer was induced in the corpus region of the stomach in three groups of rats, which were then given vehicle, omeprazole (400 mumol/kg/day), or gastrin-17 (60 nmol/kg/day) for three or six days. A fourth group of unoperated rats served as controls. One hour before killing, [3H]thymidine was injected. The ulcer margin and corresponding control tissues were excised and processed for light microscopic determination of epithelial labeling index (LI), mitotic index, and apoptotic index. LI was also determined in other parts of the gastroduodenal mucosa. Three and six days after the ulcer operation, the LI in the vehicle-treated ulcer rats was significantly increased in the ulcer margin and in the duodenum, in comparison with the intact controls. In the ulcer margin, the mitotic index was significantly increased, in parallel with the LI; the apoptotic index remained at the control level. The LI in the ulcer margin was increased further after administration of omeprazole or gastrin-17, which elevated the plasma gastrin levels by 5-15 times. It is concluded that hypergastrinemia may increase cell proliferation in the ulcer margin, which may accelerate the rate of healing.

The present study was aimed at assessing whether epidermal growth factor (EGF) and its receptors are present in the gastric mucosa during the healing of gastric ulcers. Immunohistochemical, immunochemical and functional studies were performed in rats after induction of ulcers in the oxyntic mucosa. Controls, which included non-operated and sham-operated animals, displayed only rare cells in the bottom of the oxyntic glands showing EGF-like immunoreactivity. Within one day after ulcer induction, a markedly increased number of chief cells in undamaged mucosa showed intense staining. Concomitantly, there was an increased immunoreactivity for EGF receptors in the mucous neck cells. Maximal immunostaining for both compounds was observed at 3 days after ulcer induction; augmented staining was still demonstrable after 3 weeks. RIA revealed significantly increased EGF concentration in the oxyntic mucosa three days after ulcer induction, and at this stage stimulated gastric acid secretion, measured in a parallel group of chronic fistula rats, indicated significant inhibition. The transient increases in EGF-like and EGF receptor immunoreactivities may stimulate gland cell proliferation. The local release of EGF-like substances may also serve to reduce gastric acidity and thereby promote ulcer healing.

The serosa of gastric corpus in adult rats was briefly exposed to 80% acetic acid, and as a result wounds appeared in the subjacent mucosa. The rats were killed 2, 3, 6, 10, 14 or 21 days later, and the wound margins were prepared for light and electron microscopy. The marginal glands became cystically dilated, and the gastric pits increased in depth. Many of the mucous cells at the surface contained large lipid droplets. The zymogen cells lost most of their secretory granules and the bottom of the glands became dominated by mucous cells. The tubulo-vesicles disappeared from the parietal cells, and the volume density of mitochondria was reduced from 34% to 23%. The secretory canaliculi also became smaller than normal. The morphological changes in the epithelial cells were so marked that the secretory capacity might be impaired. Measurements on the surface of the wound margins showed neutral pH in stimulated rats, indicating that the parietal cells had discontinued their secretion of acid.

The regeneration of parietal cells was studied in rat gastric mucosa. For this purpose wounds were produced by cauterization of the corpus mucosa in adult male Sprague-Dawley rats. The animals were killed at 30, 60, 90, 130, and 260 days postoperatively, six at each time. Sham-operated rats, killed at 60 and 260 days, served as controls. Stereologic data were obtained by electron microscopy of 10-20 parietal cells in each animal. At 90 days immature parietal cells appeared in the center of the wound. These cells were characterized by large nuclei, small mitochondrial volume density, and few tubulo-vesicles. With further regeneration the parietal cells became ultrastructurally mature, but their total volume in the mucosa remained subnormal. Also the epithelial cell volume density was lower than normal after 260 days of healing.