Effect of paracetamol on gastric mucosa.

The effect of paracetamol on the gastric mucosa was examined in seven healthy volunteers. The dose used (2 g instilled in 100 ml isotonic saline) was equivalent to about six tablets taken with water. Biopsy specimens were taken before and 10 and 60 minutes after instillation. The mean incidence of damaged surface cells in the control period was 1.7%. Ten minutes after instillation 3.5% of the surface cells were damaged. This increase was not significant. Light microscopy showed focal cell disruption and infiltration of red blood cells. Scanning electronmicroscopy showed minimal loss of normal cell apices. No erosions were seen on microscopy. Biopsy specimens taken 60 minutes after paracetamol showed similar changes. These findings differ appreciably from the extensive cell damage and microscopic erosions caused by therapeutic doses of 600 mg (two tablets) of aspirin. We conclude that large "analgesic" doses of paracetamol cause minimal ultrastructural changes in normal human gastric mucosa. The continued use of paracetamol in place of aspirin appears to be justified when there is a possibility of gastric mucosal injury.     

Effect of long-term prostacyclin treatment on the gastric mucosa of rat

According to Bálint and Varró, oral administration of prostacyclin (PGI2) resulted in a significant increase of the DNA-content of the gastric mucosa within a short period of time. In the present study, there was no change in the protein content of the gastric mucosa after oral administration of 100 micrograms/kg/day of PGI2 for 80 days, while the DNA-content increased significantly. The RNA/DNA ratio decreased. Histologically a significant increase in the thickness of the gastric mucosa, as well as in the number of parietal and epithelial cells were found. The cell hyperplasia in the corpus mucosa was accompanied by a decreased number of G-cells of the antral mucosa. The increase of parietal cell number and the decrease of G-cell number after long term PGI2 administration might be explained by the divergent effect of treatment on the kinetics of the different cell types in the gastric mucosa.     

Cl- transport by gastric mucosa: cellular Cl- activity and membrane permeability

The mechanism of Cl- secretion in the isolated, resting (i.e. cimetidine-treated) gastric mucosa of Necturus has been investigated with radioisotopic and electrophysiological techniques. Measurement of transepithelial 36Cl- fluxes (mucosal to serosal (M leads to S), Jms Cl-; S leads to M, Jsm Cl-) during control conditions show that at open circuit, when the transepithelial potential difference psi ms = 20 mV (S ground), Jms Cl- = Jsm Cl-, i.e. Jnet Cl- = 0, but during short-circuit current conditions Jnet Cl- = I sc = 2 mu equiv cm-2 h. Experiments with low [Cl-] solutions indicate that Cl- exchange diffusion does not contribute significantly to either Jms Cl- or Jsm Cl-. Double-barrelled, Cl- -selective microelectrodes showed that in open circuit, the cellular (C) chemical potential for Cl-, psi c Cl- = 31 mV (apparent [Cl-] = 29 mM), the electrical potential across the M membrane, psi m = -34 mV (mucosa ground) while that across the S membrane, psi s = -52 mV (serosa ground). During short-circuit current conditions, psi m = psi s = -49 mV and [Cl-]c = 30 mM. The permeability of the M membrane to Cl- (Pm Cl-) was calculated both from the tracer experiments and the electrode measurements by using the constant-field equation. Short-term (45 s) uptake of 36Cl- at [Cl]m = 96 mM during short circuit conditions gave Pm Cl- = 2.6 x 10(-5) cm s-1. Measurement of [Cl-]c by means of the electrodes when [Cl-]m was changed from 96 to 2 mM or from 2 to 96 mM gave Pm Cl- = 2.9-5.7 x 10(-5) cm s-1. Our results indicate that during open circuit conditions Cl- is accumulated across the S membrane into gastric cells in an energy-requiring step, but since Jnet Cl- = 0, Cl- must leak back into the S solution at a rate equal to the entry rate. When the tissue is short-circuited, Cl- secretion occurs (Jnet Cl- = Isc) owing to the same energy-requiring accumulation of Cl- by the cells and a passive (apparently electrodiffusive) movement across the mucosal membrane.     

Effect of diacarb on the carbonic anhydrase activity in the blood and gastric mucosa and pepsinogen concentration in the gastric mucosa of the rat

It was established that the activity of blood and gastric mucosa carboanhydrase increased after the introduction of food irritant (milk) into the stomach, as well as after the subcutaneous injection of histamine. This was accompanied by the increase of pepsinogen content in the gastric mucosa. When introduced into the stomach before the food irritant or histamine, acetazolamide inhibited blood and gastric mucosa carboanhydrase and reduced the content of pepsinogen in the gastric mucosa. Oral administration of acetazolamide for 5 days resulted in a more remarkable inhibition of blood and gastric mucosa carboanhydrase and in a drastically reduced content of pepsinogen in the gastric mucosa. The rate of pepsinogen biosynthesis by the gastric mucosa seems to depend on the activity of carboanhydrase in blood and in the gastric mucosa.     

Effect of ethanol on mucus glycoprotein fatty acyltransferase from gastric mucosa

The enzyme activity that catalyzes the transfer of palmitic acid from palmitoyl coenzyme A to the deacylated intact or deglycosylated gastric mucus glycoprotein was demonstrated in the detergent extracts of the microsomal fraction of antral and body mucosa of the rat stomach. Both types of mucosa exhibited similar acyltransferase activities and acceptor specificities. A 10-14% decrease in the fatty acyltransferase activity was observed with the reduced and S-carboxymethylated mucus glycoprotein, but the proteolytically degraded glycoprotein showed no acceptor capacity. This indicated that the acylation of mucus glycoprotein with fatty acids occurs at its nonglycosylated polypeptide regions and that some of the fatty acids may be linked via thiol esters. Optimum enzyme activity was obtained at pH 7.4 with the detergent Triton X-100, NaF, and dithiothreitol. The apparent Km values for the intact and deglycosylated mucus glycoproteins were 0.45 and 0.89 microM, respectively. The acyltransferase activity of the microsomal enzyme was inhibited by ethanol. With both intact and deglycosylated glycoprotein substrates, the rate of inhibition was proportional to the ethanol concentration up to 0.4 M and was of the competitive type. The K1 values were 0.80 microM for the intact mucus glycoprotein and 1.82 microM for the deglycosylated glycoprotein. Preincubation of the microsomal enzyme with low concentrations of ethanol (up to 0.5 M) did not seem to exert any additional deterrent effect on acyltransferase activity. Higher concentrations of ethanol (1.0 M and above), however, caused substantial reduction in the transferase activity due to denaturation of the enzyme.     

The structure of the gastric mucosa of the llamas (Lama guanocoe and Lama lamae). I. Forestomach]

The mucous membrane of the first and second compartments (ventral regions) as well as of the third compartment of Lama guanacoe and Lama lamae stomach shows tubular glands opening into pits. Below the surface epithelium blood capillaries of the fenestrated type form a regular network, each mesh of which surrounds a gastric pit. From a morphological point of view (thin section and freeze-fracture replicas) the columnar cells of the surface epithelium and those of the pits closest to the capillaries are largely similar to the epithelial cells of the rabbit gallbladder. This similarity suggests that at the level of the columnar cells sodium-dependent water reabsorption occurs. This reabsorption has already been demonstrated in the abovementioned compartments by physiological methods. The surface and foveolae epithelial cells as well as some cells of the tubular glands have a secretory function. Their secretory granules contain mucosubstances, as indicated by light-(PAS- and Alcian blue reactions) and electron microscopic (PA-TCH-Ag-reaction) histochemistry. The secretory granules originate from the Golgi complex which shows a positive histochemical reaction in its innermost sacculi at the electron microscope level. Endocrine cells (s. second part of this investigation) are rare. The mucosal membrane of each muscular lip separating the glandular sacs in the first compartment shows a stratified, not keratinized, squamous epithelium.     

Effect of vitamin A deficiency on the macromolecular permeability of small intestine mucosa in the adult rat

Adult rats with experimental vitamin A deficiency and control animals were intraperitoneally injected with chicken ovalbumin (OA) solution and the entrance of native OA into the blood was assessed 3 hours later by competitive radioimmunoassay. The OA amounts circulating in the blood of control animals averaged (0.39 +/- 0.06) X 10(-4)% of the consumed dose, while in the experimental group it averaged (1.33 +/- 0.42) 10(-4)%. Electron microscopy, using colloid lanthanum hydroxide, has shown vitamin A deficiency to give rise to an abrupt reduction in glycocalix layer, as compared to the control, without increasing erythrocyte membrane permeability for tracer particles. It is concluded that vitamin A deficiency leads to a considerable damage of small intestinal permeability for protein macromolecules.     

Effect of ebrotidine on the density of antral G-cells in the gastric mucosa in the rat

Two groups of male rats were treated orally for 60 days with ebrotidine and cimetidine, used as reference standard, respectively. The dose used of both drugs was 500mg/kg. A third group, used as control, received 10 ml/kg of an aqueous agar suspension. After receiving the last dose, the animals were killed by inhalation of CO₂ in a sealed chamber and the stomachs were removed for histological preparation. The purpose of this study was to count antral G-cells throughout the gastric mucosa by light microscope. A PAP system-associated antigastrin immunohistochemical method was used for cell identification. Cell density, with respect to their location in the gastric mucosa and the treatments given, was calculated using image analysis techniques. The results showed that ebrotidine did not cause any significant differences in the density of the population of these cells compared with the control group, while cimetidine induced a significant proliferation of antral G-cells.