René Menguy

Role of inhibition of gastric mucous secretion in the phenomenon of gastric mucosal injury by indomethacin

SummaryThe purpose of this study was to clarify the mechanism by which the therapeutic use of indomethacin is sometimes complicated by peptic ulceration. Mucous secretions from gastric-antral pouches of 5 dogs were collected before, during, and after the daily administration of 5 mg./kg. of indomethacin. This drug decreased the rate of mucous secretion and lowered the concentration of carbohydrate, particularly sialic acid andl-fucose, in the mucosubstance. Peptic ulcers appeared in 3 animals during the administration of indomethacin. The data suggest that gastric mucosal injury by indomethacin may be due to altered mucosal defense mechanisms.

Influence of Phenylbutazone on Gastric Secretion of Mucus.

Summary This study was undertaken in an attempt to clarify the mechanism by which the therapeutic use of phenylbutazone sometimes causes gastric mucosal injury in the form of hemorrhage, erosions or frank ulcerations. Mucoid secretions from gastricantral pouches of dogs were studied before, during and after the oral administration of phenylbutazone in doses of 100 mg/kg of body weight. This drug decreased the rate of mucus secretions and the carbohydrate to protein ratio in non-dialyzable mucosubstance. The data suggest that gastric mucosal injury by phenylbutazone may be due to altered mucosal defense mechanisms.

Human Salivary Glycosidases

Summary The activity of several glycosidases—neuraminidase, α-galactosidase, β-galactosidase, α-glucosidase, β-glucosidase, β-N-acetylglucosaminidase, α-mannosidase, β-glucuronidase, and α-L-fucosidase—was assayed in whole, parotid, and submaxillary–sublingual human saliva as well as in mixed cultures of oral microflora. All of these enzymes were present in whole saliva and, with the exception of α-mannosidase, were also present in mixed broth cultures of oral organisms from the same subjects. Only α-L-fucosidase and β-N-acetylglucosaminidase were found in sterile parotid and submaxillary–sublingual saliva. The latter had peaks of optimal pH activity that differed from those of the corresponding bacterial enzymes recovered from the same subject. Since salivary glycosidases can degrade salivary mucins they may be capable, under certain conditions, of attacking the surface layer of mucus in the stomach.

REGULATION OF SECRETION OF MUCUS FROM THE GASTRIC ANTRUM

Gastric secretion of mucus was studied in dogs by collecting secretions from vagally‐denervated or ‐innervated gastric antral pouches. Mucous secretions were studied for volume and for concentration of nitrogen, hexsoses, hexsosamines, L‐fucose and sialic acid concentrations in dialyzed, lyophilized mucosubstance. Gastric mucosal content of mucus of rats was measured by analyzing the concentration of hexsosamine and sialic acid in freeze‐dried gastric mucosal scrapings. Vagal stimulation of the gastric antrum and administration of cholinomime‐tic agents had no detectable influence on either the volume or the biochemical composition of antral mucus. Insulin‐induced hypoglycemia appeared to depress the secretion of mucus. Adrenergic stimulation was without influence. Serotonin had a strong stimulatory effect on the volume of mucus secretion but did not alter its biochemical composition. Cortisone had a profound inhibitory influence on the secretion of mucus and altered its biochemical composition by decreasing the concentration of sialic acid. Parathyroid extract was found to increase gastric mucosal content of mucus in rats.

Role of gastric acid in aspirin-induced erosive gastritis.

Summary The purpose of this study was to determine whether preexisting atrophic gastritis and high intragastric pH render the gastric mucosa more or less susceptible to the ulcerogenic effects of parenteral aspirin. Radiation-induced gastric atrophy was used to produce achlorhydria in rats. Properly shielded rats received 1750 rads to the eviscerated stomach. Paired controls were subjected to a sham procedure. By comparison with the paired controls, all the irradiated rats became achlorhydric. When challenged with aspirin given parenterally (600 mg/kg/day in 4 divided doses over 2 consecutive days), the average number of gastric erosions in the sham irradiated control animals was 10, while the average number of erosions in the irradiated animals was 0.25. The data suggest that gastric HCl plays an important role in the phenomenon of gastric mucosal injury by parenterally administered aspirin.

Source of sialogastrone, a gastric inhibitory substance in human saliva

SummaryHuman saliva contains a substance that inhibits gastric secretion when administered intravenously to dogs or rats. The purpose of this study was to determine which one of the salivary glands elaborates this substance. Individual samples of whole, parotid, submaxillary, and sublingual saliva were collected from normal human subjects. The amount of inhibitory substance in each sample of saliva was estimated by its inhibitory action on the 4-hr, gastric secretion of pylorus-ligated rats. Of the secretions from the 3 principal salivary glands, that from the sublingual glands had the greatest inhibitory effect on gastric secretion of rats. It is proposed that the gastric inhibitory substance present in saliva be called sialogastrone.

Glycosidases in Canine Pancreatic Secretion

Summary Several glycosidases present in extracts of pancreatic tissue have been found in pancreatic juice. The corresponding enzyme systems in pancreatic juice and pancreatic tissue extract have identical pH optima and similar curves of pH activity. Velocity-substrate relationships of β-glucosaminidase, β-galactosaminidase, α-D-mannosidase, and α-L-fucosidase in pancreatic juice have been estimated.

Role of the Liver in the Glycoprotein Mobilizing Property of Parathyroid Extract.

Summary Studies were carried out to determine the action of hepatectomy on the glycoprotein action of PTE as well as on PTE-induced renal calcification and deposition of glycoprotein. Our data showed that in hepatectomized rats, PTE no longer caused an elevation in serum glycoproteins. However, hepatectomy did not alter the formation of glycoprotein tubular casts produced by PTE administration. The data suggest that the liver is the major source of the elevated serum glycoproteins found in rats receiving PTE. In addition, it is possible that PTE may have a direct stimulating action on biosynthesis of glycoprotein by the kidney.

Do corticosteroids cause peptic ulcer? Another point of view.

I N THE .X, IARtm tSSCE Of the AMERICAN JOURNAL OF DmESTlVE DISEASES, Dr. Allan 1L Cooke reviewed the evidence for and against tile thesis that therapeutic administration o[ corticosteroids causes peptic ulcer. He concluded that corticosteroids in low doses do not cause peptic ulceration, and that it is uncertain whether the administration of these compounds in large doses to patients with rheumatoid arthritis causes peptic ulceration with a frequency greater titan that seen in patients not treated with corticosteroids. Since the introduction of corticosteroids into the medical armamentarium, many clinicians using these compounds for ttle treatment of rheumatoid arthritis have observed that treatment is often complicated by the development of a peptic ulcer de novo or by the exacerbation of a previously existing ulcer. For many clinicians this Phenomenon has remained more a clinical impression than a scientifically documentated [act. However, several prospective studies have allowed their authors to conclude that large doses of these compounds increase the liability of the treated patients to pept.ic ulceration beyond the incidence of spontaneous ulcer disease. Dr. Cooke contends that snch conclusions are not justified because of the absence of radiologic studies of the upper digestive tract prior to cortlcosteroid therapy. I would be the first to agree with Dr. Cooke that clinicians should-strive to replace clinical impressions with scientifically documentated facts. However, I believe that Dr. Cooke may have become overly rigid in his approach to the problem. The prospective study of Kammerer t remains the one most often quoted in the literature. In this study, 31% of 117 patients with rheumatoid arthritis who were treated with corticosteroids and subjected to periodic X-ray examinations of the upper gastrointestinal tract over a 12-month period developed peptic ulcers. By contrast, only 9% of a group of patients with rheumatoid arthritis but not receiving steroids were found to have peptic ulcers when subjected to the ~me pattern of X-ray examinations. Dr. Cooke has taken the

Influence of Secretin-Cholecystokinin and Secretin-Pentagastrin on Pancreatic Secretion of Glycosidases

Discussion and Summary We had previously described the presence in canine pancreatic juice of several glycosidase enzyme systems. The present data indicate that the outputs of β-glucosaminidase, β-galactosaminidase, α-mannosidase, and α-fucosidase in pancreatic juice increase in response to pancreatic hormonal stimulation to the same degree as those of trypsinogen and amylase. This suggests that these glycosidase enzyme systems may belong to the physiologic complement of enzyme protein in pancreatic juice. It is, of course, important to recognize that the ability of a glycosidase to remove a glycosyl group from a synthetic substrate, which forms the basis of our enzyme assay, does not prove that the enzyme can release the same group from a naturally occurring large molecular substrate. However, the suggestion of a physiologic role for at least one of these enzymes, β-N-acetylglucosaminidase, is strengthened by our finding (to be reported) that this enzyme releases N-acetylglucosamine from ovomucoid.