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The mechanism by which lack of gastric acid causes hypergastrinaemia was investigated in seven patients with pernicious anaemia. Perfusion of gastric juice from the fasting patients (adjusted to pH 7.0) into the stomachs of conscious rats caused a significant rise in plasma gastrin (median 14 [range 2-20] pmol/l to 27 [12-65] pmol/l; p less than 0.01), whereas perfusion of bicarbonate buffer (18 [13-23] pmol/l to 20 [9-25] pmol/l) or gastric juice from a duodenal ulcer patient (also pH 7.0; 13 [3-30] pmol/l to 17 [9-27] pmol/l) had no significant effect. During gastric lavage at pH 7.0 the median plasma gastrin concentration of the pernicious anaemia patients fell from 320 (63-1760) pmol/l to 125 (46-760) pmol/l (p less than 0.03).

While there are several reports of prostaglandins of the E series being associated with increased mucosal mass in the stomach, their effects on the small intestine are less well documented. A microdissection-based technique was used to measure proliferation and crypt size in the duodenum, jejunum and ileum of dogs given the prostaglandin analogue misoprostol. Six test and six control animals were given an oral dose of 300 micrograms kg-1 day-1 of misoprostol for 11 weeks, a dose-duration combination chosen to optimize the development of gastric hyperplasia. Misoprostol increased both the area of the crypts (P less than 0.001) and the number of mitoses per crypt (P = 0.002) throughout the small intestine. The technique also demonstrated a significant gradient in crypt size and in crypt area from the duodenum to the ileum. There was no statistical interaction between misoprostol and the site studied, suggesting that this trophic effect was systemic or systemically mediated.

Intestinal epithelial morphology, crypt cell production and absorptive function were investigated in 9 groups of rats, aged from 3 to 121 weeks. Absorption per unit length of intestine peaked in the first weeks of life and this was associated with increased villus size, crypt length and absorption per mg tissue weight. Absorption per gut continued to increase throughout life, which could be attributed to a similar increase in intestinal length and weight per cm, despite a decreased absorption per mg in the adult animals. Crypt-villus ratio increased rapidly between 6 and 8 weeks, but then appeared to reach a plateau. Crypt cell production started off at high rate in all sites and then decreased in the young adult. While there was some evidence for a small, non-significant, increase in proliferation in the very old rats, there was no evidence of the marked elevation reported by some workers.

Four groups of intravenously maintained rats were infused with 0, 5, 20 or 80 micrograms/rat/day of peptide tyrosine tyrosine (PYY) for 3 days. After 3 days the rats were injected with 1 mg/kg of vincristine in order to arrest cells entering metaphase and were killed 2 h later. The gastrointestinal tract was removed, weighed and fixed. Samples of small intestine and colon were stained, microdissected and the mean number of metaphases per crypt determined. No significant effect on intestinal tissue mass or the 2-hour collection of metaphases was observed. It is concluded that PYY is not trophic to the gastrointestinal tract.

Prostaglandins of the E series increase stomach mucosal mass by inducing hyperplasia, which could be the result either of increased cell production or of decreased cell loss. This report describes an investigation of the effect of the prostaglandin E1 analogue, misoprostol, on cell migration and transit. 3H-thymidine was used to label those cells synthesizing deoxyribonucleic acid in dogs that had been given an oral dose of 300 micrograms/kg per day misoprostol for 11 weeks. The animals were killed at timed intervals, and tissue from the gastric fundus was prepared for autoradiography. The distribution of labeled cells at various times after labeling was used to follow the movement of the wave of label and to calculate median cell migration rates and transit times. The migration rate of cells toward the gastric lumen was significantly increased from 1.4 +/- 0.3 to 3.6 +/- 0.6 cell positions per day in the misoprostol-treated group (p less than 0.001); however, the gland length (from the most basal mucous neck cell to the luminal surface) was also increased (from 52.1 +/- 1.1 to 74.0 +/- 1.6; p less than 0.001), thus there was no significant difference in the (transit) time taken for cells to reach the top of the gland (control, 17.5 +/- 9.8 days; test, 12.2 +/- 7.1 days).

Increased mucosal mass is associated with prostaglandin administration, raising the question as to whether this is the consequence of increased cell production or decreased cell loss. 3H-thymidine was injected into 30 test dogs given 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol, orally for 11 weeks, and into 30 dogs which had been given the vehicle alone. Six test and 6 control dogs were killed 1 h after thymidine labelling, and the remainder were killed subsequently at timed intervals to determine cell migration rates and transit times. Misoprostol significantly increased the stomach weight, but nonetheless did not significantly increase the labelling index, nevertheless, the number of labelled cells per gland was significantly increased, which was a consequence of the increased gland length. When the data was expressed as a gland cell production rate significant increases were thus observed. The migration rate of cells toward the gastric lumen increased one and a half times in the misoprostol-treated group; however, as the gland length also significantly increased, there was no significant difference in the transit time. It must be concluded that the hyperplasia associated with exogenous prostaglandins is the consequence of increased cell production, not decreased cell loss, and that previous reports to the contrary are the result of failure to allow for concomitant changes in the denominator of proliferative indices.

Dogs were given an oral dose of 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol for 11 weeks. The relative areas of the main components of the fundus and antrum per unit area of serosa were quantified. While the volume occupied by the muscle layers did not change, there was an increase in mucosal volume in both sites. The relative volume fraction of the main mucosal cell types was then determined by a point counting technique. Misoprostol very highly significantly increased the fraction of mucosal volume occupied by surface mucus cells, and also significantly decreased the volume fraction of the parietal cells.

Recombinant urogastrone (human epidermal growth factor) was infused into rats in which intestinal cell proliferation was reduced to a steady state basal level by feeding them intravenously. Urogastrone elevated the augmented metaphase index and weight of all sections of the gastrointestinal tract in a dose-related manner. Infusion of urogastrone at a dose which has a minimal effect on gastric acid secretion significantly increased crypt cell production and tissue weights throughout the gastrointestinal tract. Intravenous urogastrone was also effective in restoring cell proliferation after the intestine had become hypoproliferative. Urogastrone administered luminally had no significant effect on either intestinal weight, crypt cell production rate, or metaphase collection.

The quantification of mucosal DNA as a measure of epithelial cellularity has been criticized because it would include the non-epithelial cell populations present in the mucosa. The weight, DNA content and tritiated thymidine uptake of Peyer's patches and the remaining mucosa were measured and compared. Although the Peyer's patches only contribute 2.5% to the weight of the small intestine, they contained 12% of the DNA and 7% of the tritiated thymidine which would be found in a mucosal scrape.