Thickness Of Mucus Gel Layer Research Articles

Effect of 10% ethanol and sofalcone on prostaglandin E2 content, mucus gel thickness, and experimental ulcers in the stomach of developing rats.

We studied the effects of a mild irritant, 10% ethanol, and sofalcone on the gastric mucosal defense mechanisms in newborn rats, comparing the effects to those seen in adult rats. The results indicated (1) that both mucosal prostaglandin E2 (PGE2) content and mucus gel layer thickness increased with age, (2) that sofalcone, but not 10% ethanol, increased mucosal PGE2 content and mucus gel thickness in 1- and 8-week-old rats, (3) that both sofalcone and 10% ethanol decreased mucosal damage induced by 50 or 75% ethanol in both age groups, and (4) that 10% ethanol, but not sofalcone, decreased ethanol-induced mucosal damage in rats pretreated with indomethacin. We concluded that 10% ethanol and sofalcone increase gastric mucosal defence mechanisms in newborn rats as in older rats.

Prostaglandin E2 in gastric mucosa of children with Helicobacter pylori gastritis: relation to thickness of mucus gel layer.

To evaluate the changes in mucus gel layer thickness and prostaglandin E2 (PGE2) content caused by Helicobacter pylori infection in the antral mucosa of children: to assess whether decreased mucus gel thickness is related to PGE2 production. Antral biopsy specimens were taken at endoscopy from 153 children. H pylori gastritis was evident in 45 and normal mucosa in 59. The other 49 children were studied one month after antibiotic treatment that eradicated the infection in 37 of them had been stopped. One antral specimen was immersed in ice-cold saline, put under an inverse microscope with an eyepiece graticule. Mucus gel thickness was measured and then the processed for histological examination; another specimen was weighed and processed for in vitro prostanoid generation. Mucus gel layer thickness was significantly decreased in children with H pylori gastritis (90 (SD) 29) microns v 120 (58) microns in controls, p < 0.01) but returned to control values after H pylori had been eradicated. PGE2 generation was significantly increased in children with H pylori gastritis (1022 (811) ng/g v 641 (473) ng/g in controls, p < 0.01). One month after treatment PGE2 generation significantly decreased in children without infection (880 (534), p < 0.01), but was still high where infection persisted. A significant inverse correlation was found between PGE2 generation and mucus gel layer thickness (p < 0.05). These data suggest that H pylori damages the mucus gel layer, and that the gastric mucosa increases generation of PGE2 in response to back diffusion of acid and pepsin.

Developmental changes in gastric mucus gel thickness: responsiveness to 16,16-dimethyl prostaglandin E2 and mucosal protection in the rat.

The gastric mucosa of newborn rats is sensitive to the damaging effects of acid and ethanol. We measured gastric mucus gel thickness in newborn, suckling, and weaned rats by inversion microscopic observation. The thickness in newborn rats was 52.2 +/- 6.7 microns and increased with age, reaching 96.8 +/- 5.6 microns in 8-wk-old rats (p less than 0.001). Oral administration of 16,16-dimethyl prostaglandin E2 at concentrations of 10 and 100 micrograms/kg body weight increased mucus thickness in 8-wk-old rats but had no effect in 1-wk-old rats. We also assessed the effect of 16,16-dimethyl prostaglandin E2 on the prevention of gastric mucosal damage induced by ethanol. Oral 16,16-dimethyl prostaglandin E2 reduced damage in 8-wk-old rats, but there was no effect in 1-wk-old rats. These data suggest that the susceptibility of newborn rats to gastric mucosal injury may be related to the relative thinness of the gastric mucus gel layer and the failure of prostaglandins to increase the mucus gel layer thickness.

In vitro measurement of the pH gradient and thickness of the duodenal mucus gel layer in rats.

The mucus bicarbonate barrier of the duodenum has lately been reported to be one of the most important defensive factors for the duodenal mucosa. We established an in vitro system for evaluating the mucus bicarbonate barrier in the rat duodenum. Our method allows direct measurement of the pH gradient as well as the thickness of the mucus gel layer of the rat duodenum in vitro. The obtained results suggest that alkali secretion in response to acid-loading as well as the thickness of the duodenal mucus gel layer are greater than those in the stomach.

Role of the Mucus Gel Layer in the Healing of Acetic Acid-induced Gastric Ulcers in Rats

Changes in the pH gradient and thickness of the mucus gel layer in the healing of acetic acid-induced gastric ulcers in rats were investigated. The maximum of the pH gradient and the thickness of mucus gel layer at the edge of ulcers and in the regenerated mucosa were higher, decreased gradually with the healing of the ulcers and finally reached normal values. This indicates that mucus and bicarbonate are secreted actively from the mucosa surrounding an ulcer and that they play an important role in protection of the base of ulcers and in acceleration of the healing of the ulcers.

Gastric mucus gel layer thickness measured by direct light microscopy. An experimental study in the rat.

A method for measuring the thickness of the mucus gel layer present on the gastric mucosa is described. This method enables minimal handling of the mucosal specimens and thereby minimizes the errors connected with tissue handling. Male Sprague-Dawley rats were used. With the rats under general anesthesia, the stomach was excised and opened along the greater curvature, and full-thickness biopsy specimens from the corpus region were obtained by means of a skin biopsy punch. From these specimens a slice of mucosa, 1 mm thick, was rapidly cut out and put into a specially made glass chamber containing 0.9% NaCl. The chamber was sealed with a cover glass. Mucus gel layer thickness could then be measured in a conventional light microscope operated at a primary magnification of x120. This method was tested on two groups of 10 rats. The animals in the control group were given 1 ml of 0.9% NaCl, and the rats in the experimental group were given 1 ml of sodium salicylate, 75 mg/kg, dissolved in saline. After 15 min the animals were anesthetized and specimens prepared for measuring mucus gel layer thickness. In the control group, the mucus gel layer measured 145 microns, whereas in the experimental group it reached a thickness of 305 microns. The method proved to be easy to use, and the effects of pharmacologic substances on the mucus gel layer in the stomach could be investigated.

N-acetyl-cysteine and prostaglandin. Comparable protection against experimental ethanol injury in the stomach independent of mucus thickness.

The role of barrier mucus in mediating the protective effects of 16,16 dimethyl PGE2 (dm PGE2) against ethanol-induced gastric injury, with and without concomitant treatment with N-acetyl-cysteine (NAC), a potent mucolytic agent, was evaluated. Fasted rats were orally administered either saline, 10 micrograms/kg dm PGE2, 20% NAC, or 10 micrograms/kg dm PGE2 plus 20% NAC. In the first study, the rats were killed 15 minutes later and their stomachs were removed and assayed for barrier mucus adherent to the gastric wall using the Alcian blue technique. In the second study, the rats were orally given 2 mL of absolute ethanol (EtOH) after receiving one of these pretreatment regimens, and 5 minutes later they were killed and their stomachs were evaluated histologically by light microscopy for the magnitude of EtOH injury. Although NAC significantly reduced the thickness of barrier mucus by 76% when compared with control animals, it did not adversely affect the ability of dm PGE2 to spare the deep epithelium from injury by EtOH. In fact, NAC was as effective a protective agent as dm PGE2. Neither agent prevented damage to the surface epithelium by EtOH, verifying previous studies regarding the protective effects of prostaglandins. These results indicate that both dm PGE2 and NAC prevent EtOH-induced damage to the deeper layers of the gastric mucosa independent of mucus gel layer thickness, suggesting that other mechanisms than mucus are involved in mediating this protection.

Lack of Correlation Between Mucus Gel Thickness and Gastric Cytoprotection in Rats

The effect of various cytoprotective agents on the thickness of gastric mucus gel layer in rats was studied. It was hypothesized that an increase in the mucus gel layer might be involved in cytoprotection. The results show that this is not the case. Neither prostaglandin E2, 16,16-dimethyl prostaglandin E2, nor mild irritants (20% ethanol, 0.35 M HCl, 20% glucose, 20% mannitol), all given orally, altered the thickness of the mucus gel layer, although these agents were found to be cytoprotective, i.e., inhibiting the formation of gastric mucosal necrotic lesions caused by oral administration of absolute ethanol. The only agents that significantly increased the thickness of the mucus gel layer were a hypertonic solution (4% NaCl) and sodium salicylate. We conclude that if mucus plays a role in cytoprotection, it is not by virtue of an increase in thickness of the gel layer adherent to the gastric mucosa.

A method for measuring changes in tracheal mucus gel layer thickness as an indication of an immediate hypersensitivity response.

A visual method for measuring increase in tracheal mucus gel layer thickness as an indication of an immediate hypersensitivity response, using a Zeiss slitlamp and pachymeter is described. Mucus gel layer thickening is antigen dose dependent. Antigen challenge of nonsensitized rats does not cause significant increases in gel thickness dispelling the notion that changes in the gel layer result from nonspecific irritation. Cromolyn sodium, cimetidine, and FPL-55712 inhibit increases in gel layer thickness following antigen challenge of actively sensitized rats, while atropine, pyrilamine, and methysergide do not.

A simple method for measuring thickness of the mucus gel layer adherent to rat, frog and human gastric mucosa: influence of feeding, prostaglandin, N-acetylcysteine and other agents.

1. A technique has been developed for measuring thickness of the gastric surface mucus gel layer. Mucosal sections (1.6 mm) were cut from frog and rat stomach and human antrum, mounted transversely and viewed by an inverse microscope (x 200 magnification) under dark field illumination or phase contrast. The mucus layer was readily distinguishable and its dimensions could be recorded by means of an eyepiece graticule. 2. Mean mucus gel thickness in rat, frog was 73, 76, 55 and 192 micrometer respectively. However, there was variation in the average thickness of the gel layer between individual mucosae from the same species (up to twofold). Mucus thickness between adjacent regions of the same mucosal section also varied markedly (up to tenfold). 3. Topical administration of 16,16-dimethylprostaglandin E2 by oral intubation caused a significant increase in thickness in both rat and frog at doses of 5 microgram/ml and 0.5 microgram/ml respectively. Feeding and exposure of the mucosa to N-acetylcysteine (10-20%, w/v) produced variable effects whereas pepsin (1 mg/ml) caused a marked reduction in thickness of the surface gel layer in both rat and frog. 4. The technique provides a rapid and simple method for determining gastrointestinal mucus thickness in relation to mucosal morphology. It is ideally suited for studying the control of mucus secretion and effect of drugs.