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Biomedical subjects

A Tarnawski

Publications and source records attributed to A Tarnawski.

At least 109 records · Page 6Linked to original sources
PubMed1985

Comparison of antacid, sucralfate, cimetidine, and ranitidine in protection of the gastric mucosa against ethanol injury.

The abilities of antacid (Mylanta II), sucralfate, cimetidine, and ranitidine to protect the gastric mucosa against ethanol-induced necrosis were compared in a standardized, experimental rat model. Fasted rats received pretreatment with either saline, Mylanta II, 500 mg/kg of sucralfate, 50 mg/kg of cimetidine, or 50 mg/kg of ranitidine. This was followed one hour later by intragastric administration of 2 ml of 100 percent ethanol. Gastric mucosal injury was assessed four hours after administration of ethanol by quantitation of gross mucosal necrosis, assessment of mucosal histology, and determination of intragastric blood and protein concentrations. Pretreatment with Mylanta II or sucralfate significantly reduced ethanol-induced gastric mucosal necrosis. The protective effect of sucralfate was six to 10 times greater than that of Mylanta II. H2-receptor antagonists increased ethanol-induced gastric mucosal necrosis.

Aluminum↗
PubMed1985

Prostaglandin protection of the gastric mucosa against alcohol injury--a dynamic time-related process. Role of the mucosal proliferative zone.

The aim of the present study was first to resolve controversies regarding the extent of prostaglandin protection ("cytoprotection") of the gastric mucosa against injury produced by 100% ethanol and second to determine time sequence and histologic, ultrastructural, and functional features of this protection. Fasted rats received intragastrically (A) 0.9% NaCl alone as a control, (B) 5 micrograms/kg of 16,16-dimethyl prostaglandin E2 dissolved in 0.9% NaCl, and (C) 100 micrograms/kg of 16,16-dimethyl prostaglandin E2 dissolved in 0.9% NaCl. Thirty minutes later, 2 ml of 100% ethanol was instilled. The gastric mucosa was assessed macroscopically, by quantitative histology, and by scanning and transmission electron microscopy for [3H]thymidine uptake, mitotic activity, ion fluxes, and gastric potential difference determined at several time intervals (between 10 min and 16 h) after ethanol administration. Between 10 min and 16 h after ethanol administration macroscopic necrosis involved 27% +/- 3% to 41% +/- 4% of the mucosal area in controls (group A), but necrosis was prevented in groups receiving 16,16-dimethyl prostaglandin E2 (groups B and C). In the control group, histology and electron microscopy showed extensive disruption of the surface epithelium and deep necrosis (greater than 0.2 mm) involving greater than 46% +/- 4% of the mucosa between 15 min and 16 h after ethanol administration. Deep necrotic lesions were completely prevented by either dose of 16,16-dimethyl prostaglandin E2 (groups B and C). The mucosal proliferative zone was severely damaged in controls (68% +/- 5%) within the first hour after ethanol administration, whereas 16,16-dimethyl prostaglandin E2 protected the zone from damage (less than 5% +/- 1%). Neither dose of 16,16-dimethyl prostaglandin E2 prevented the occurrence of initial (at 15-30 min) morphologic and functional disruption of the surface epithelium after ethanol administration. However, initial disruption of the surface epithelium by 16,16-dimethyl prostaglandin E2 (groups B and C) was followed by migration of cells from the mucosal proliferative zone; the result was prompt restoration of the surface epithelium and resumption of its barrier and transport functions.

16,16-Dimethylprostaglandin E2↗
PubMed1985

Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat. Macroscopic, histologic, ultrastructural, and functional time sequence analysis.

Histologic or ultrastructural evidence of the ability of sucralfate to protect the gastric mucosa against ethanol injury is lacking. Therefore we analyzed morphologic and functional changes in the mucosa of 120 rats receiving, intragastrically, 2 ml of either sucralfate 500 mg/kg body wt or a control solution and 1 h later 2 ml of 100% ethanol. At 15 min, 1, 4, 6, and 24 h after ethanol instillation, mucosal changes were assessed by macroscopic examination, quantitative histology, scanning electron microscopy, recordings of gastric potential difference, and measurements of volume, pH, and electrolytes in the gastric contents. Between 15 min and 24 h after ethanol instillation, macroscopic necrotic lesions in controls involved greater than 33% of mucosal area and in the sucralfate-treated group less than 4% (p less than 0.001 for each period). In controls, ethanol instillation produced surface epithelial cell disruption and deep (greater than 0.2 mm) mucosal necrosis involving greater than 55% +/- 3% of the mucosal length. In sucralfate-pretreated animals, disruption of the surface epithelium was present at 15 min, 1 h, and 4 h after ethanol instillation, but deep necrotic lesions were virtually absent (0%-2%; p less than 0.001 vs. controls) during the entire study period. The surface epithelium was mostly reestablished by 6 h after ethanol instillation in the sucralfate group but not in the controls. We concluded that sucralfate protects the gastric mucosa against ethanol-induced injury by preventing deep mucosal necrosis and as a consequence the mucosal proliferative zone cells rapidly restitute mucosal integrity.

Aluminum↗
PubMed1984

Bile acid-induced gastric mucosal injury: significance of portal hypertension and mucosal capillary permeability.

Rats with portal vein occlusion (PVO) were studied to determine severity of taurocholate-induced gastric mucosal injury during portal hypertension and following its resolution by collaterals. During the portal hypertensive state, after intragastric taurocholate, PVO rats compared with sham-operated controls had significantly greater macroscopic damage (14 +/- 1 vs 3 +/- 1% of total mucosa) and histologic deep necrosis (25 +/- 4 vs 3 +/- 1% of mucosal length). Gastric mucosal capillary permeability was also significantly greater in PVO rats, as assessed by increased appearance of intravenous Evans blue dye in gastric wall and contents. After 21 days of PVO portal pressures returned to normal. At this time taurocholate-induced gastric mucosal damage and capillary leak became similar in PVO and sham-operated rats. It is concluded that the portal hypertensive state alone predisposes to severe gastric mucosal damage and capillary leak.

Animals↗
PubMed1984

Effect of 16,16 dimethyl prostaglandin E2 on aspirin induced damage to rat gastric epithelial cells in tissue culture.

Prostaglandins (PGs) protect gastric mucosa against damage produced by acetylsalicylic acid (ASA). Whether this effect of prostaglandins is truly cytoprotective and whether cAMP plays an important role in this effect is uncertain. We studied the effect of: (1) 16,16 dimethyl prostaglandin E2 (dmPGE2), isobutylmethyl xanthine (IMX), and dibutyryl cAMP (DBcAMP) on ASA-induced damage to monolayer cultures of rat gastric mucosa composed primarily of mucus cells; (2) dmPGE2 on ASA absorption into the cultured cells. Cell damage was quantitated by 51Cr-release and trypan blue staining. Ten millimoles ASA significantly increased 51Cr-release (indicating cell damage) at pH 5.0, but not at pH 7.4. DmPGE2 significantly reduced ASA-induced increase of 51Cr-release. Isobutylmethyl xanthine did not change the rate of 51Cr-release caused by ASA plus dmPGE2. Dibutyryl cAMP did not significantly alter 51Cr-release caused by ASA. A dose response study of ASA damage showed close correlation between 51Cr-release and trypan blue staining (r = 0.93). Dimethyl prostaglandin E2 did not affect 14C-ASA incorporation by the cells at either pH 7.4 or pH 5.0. We conclude that: (1) dmPGE2 exerts a cytoprotective effect on cultured rat gastric cells; (2) cAMP does not play an important role in such cytoprotection; (3) this protection is not because of interference with ASA absorption by prostaglandin.

1-Methyl-3-isobutylxanthine↗
PubMed1984

The gastric mucosa in portal hypertension: effects of topical bile acid.

Clinical observations suggest that patients with portal hypertension are more prone to erosive gastritis. To test this hypothesis we investigated gastric mucosa of rats with portal hypertension (produced by staged portal vein occlusion) and sham-operated controls before and after intragastric taurocholate. Portal pressure was 36 +/- 3 cm saline in portal hypertensive rats compared with 16 +/- 2 cm in controls (P less than 0.01). Before taurocholate no macroscopic or histologic spontaneous mucosal damage was present, but portal hypertensive rats had extensive submucosal edema. Three hours after intragastric taurocholate (2 ml, 80 mM in 0.1 N HCl), macroscopic injury comprised 13.7 +/- 1.1% of mucosal surface in portal hypertensive rats compared with 3.6 +/- 0.6% in controls (P less than 0.01) confirmed also by histologic morphometry. H+ back-diffusion was 402 +/- 40 microEq/h in portal hypertensive rats and 217 +/- 30 microEq/h in controls (P less than 0.01). We conclude taurocholate induced gastric mucosal injury is enhanced by portal hypertension. Greater H+ back-diffusion in portal hypertensive rats suggests increased mucosal permeability contributed by submucosal edema. We confirm quantitatively in an experimental model that portal hypertension predisposes to gastric mucosal injury.

Animals↗
PubMed1984

Sucralfate protection of the gastric mucosa against ethanol-induced injury: a prostaglandin-mediated process?

We studied whether sucralfate's protection of the gastric mucosa against ethanol induced injury in the rat is prostaglandin mediated. Rats received intragastric pretreatment: i) saline, ii) sucralfate, and iii) indomethacin-sucralfate. One hour later gastric contents were obtained for measurements of prostaglandin E2 and 2 ml of 100% ethanol were instilled. Rats were sacrificed 1 h later. The gastric mucosa was assessed: a) macroscopically by planimetry, b) by quantitative histology, and c) by measurements of gastric volume, pH and sodium. We found that sucralfate significantly increased gastric luminal release of prostaglandin E2. The increase was completely abolished by indomethacin pretreatment. Sucralfate protected the gastric mucosa against ethanol injury reducing macroscopic and histologic necrosis. Indomethacin (prostaglandin synthetase inhibitor) given 2 h prior to sucralfate markedly abolished its protective action against ethanol induced necrosis by 70%. These findings indicate that prostaglandins mediate some of the protective action of sucralfate. Sucralfate appears to have additional protective action which is prostaglandin independent.

Aluminum↗
PubMed1983

A monolayer culture of human gastric epithelial cells.

Our aim was to develop a fibroblast-free monolayer culture of human gastric mucosal cells, using the specimens obtained by routine endoscopic biopsy. Human gastric mucosa obtained from normal volunteers by endoscopic biopsy was dissociated from collagenase and hyaluronidase. Dissociated cells were cultured in supplemented Coon's modified Ham's F-12 medium. Within 24 hr of inoculation, the cells were attached to the culture dishes. This was followed by cellular outgrowth. On phase-contrast microscopy, all cells had epithelial characteristics and fibroblasts were not observed. Ninety percent of cells contained periodic acid Schiff reaction-positive mucous granules after diastase digestion consistent with mucous epithelial cells. Two percent of the cells gave a strong reaction for succinic dehydrogenase activity (parietal cells). Immunohistochemical staining for pepsinogen in cultured cells was negative. On EM, microvilli-like projections, junctional complexes, Golgi apparatus, and mucous granules were apparent in the majority of cells. Mitotic figures were observed by day 3 with Giemsa staining. Autoradiographically, these cells were able to incorporate [3H]TdR into the nuclei. Cells were capable of synthesizing DNA, and this function was inhibited by cycloheximide. Cells could be cultured for up to two weeks without fibroblast contamination. A method of primary monolayer culture of human gastric mucosa obtained by a routine endoscopic biopsy has been successfully developed.

Adult↗
PubMed1983

Portal hypertension and gastric mucosal injury in rats. Effects of alcohol.

The present study was performed primarily in order to determine whether gastric mucosa of rats with portal hypertension has different functional and histologic features when compared with controls, and second to quantitate and compare morphologic and functional changes after exposure to topical ethanol. Portal hypertension was produced by staged portal venous occlusion, and in these animals portal pressure was 32 +/- 2 cm saline compared with 18 +/- 2 cm in sham-operated controls (p less than 0.005). Before ethanol, portal hypertensive rats compared with controls had significantly higher luminal pH (2.9 +/- 0.3 vs. 1.9 +/- 0.1), increased H+ back-diffusion (loss of 138 +/- 10 vs. 57 +/- 16 microEq H+/h), lower potential difference (8 +/- 1 mV lower than controls), and extensive submucosal edema (submucosal thickness 325 +/- 25 vs. 138 +/- 18 micrometers). After 3 h of exposure to 2 ml intragastric absolute ethanol, the area of macroscopic hemorrhagic mucosal injury was significantly greater in portal hypertensive rats than in controls (34.0 +/- 8.7% vs. 7.6 +/- 2.1%), confirmed histologically by the greater number of deep hemorrhagic necrotic lesions and extent of mucosal length involved. Furthermore, after ethanol, portal hypertensive rats compared with controls had significantly increased gastric volume (14.4 +/- 1.5 vs. 8.3 +/- 0.6 ml), Na+ (86.6 +/- 8.0 vs. 64.6 +/- 8.0 mEq/L), pH (7.1 +/- 0.3 vs. 4.3 +/- 0.4), H+ back-diffusion (loss of 309 +/- 41 vs. 207 +/- 33 microEq H+/h), and protein and blood loss (100% increases over controls). These results indicate that gastric mucosa of portal hypertensive rats has distinctive functional and histologic abnormalities that can explain its increased susceptibility to erosive injury after ethanol. This study quantitatively confirms in an animal model the clinical observations that portal hypertension may predispose to severe gastric mucosal injury.

Action Potentials↗
PubMed1983

Arachidonic acid protection of gastric mucosa against alcohol injury: sequential analysis of morphologic and functional changes.

We have shown previously that arachidonic acid (AA) prevents gastric mucosal injury by ethanol (ETOH). The present study was designed to determine the sequence of morphological and functional changes in the gastric mucosa during ETOH-induced injury and AA-promoted protection. Fasted male rats received intragastrically 1 ml of vehicle (PL) or 1 ml of 120 mM AA followed 1 hr later by 2 ml of absolute ETOH. Mucosal changes were assessed at 10, 15, and 30 min and 1, 2, 3, 6, and 15 hr after ETOH: (1) macroscopically, histologically, and by scanning EM; and (2) by determinations of (a) mitotic activity and 3H-thymidine incorporation in vivo, (b) gastric volume, pH, and electrolytes, and (c) gastric PD. Macroscopic necrotic changes were present in PL-but not AA-pretreated animals throughout the 15 hr after ETOH. Histological examination and scanning EM showed desquamation of the surface epithelium at 10 min to 2 hr and deep necrotic lesions throughout the 15 hr after ETOH in PL-pretreated animals. In AA-pretreated rats, deep necrotic lesions did not occur, but desquamation of the surface epithelium was seen during the initial 30 min after ETOH. A continuous layer of the surface epithelium was restored within 3 hr after ETOH in AA group, with resumption of the transport and barrier functions. The main feature of AA protection of gastric mucosa against ETOH injury is preservation of the mucosal proliferative zone.

Animals↗
PubMed1983

Ultrastructure of colonic endocrine cells in ulcerative colitis.

Endoscopic specimens of colonic mucosa from 40 ulcerative colitis patients were investigated. Specimens were taken from both sexes patients, aged 16-74 (means = 41 years). An average number of 5 biopsies was examined in each patient taken 10, 20, 40, 50 and 80 cm from rectum. Material was divided into 3 groups: 1. histologically confirmed ulcerative colitis (CU), 2. clinical diagnosis of CU in remission-histologically non specific inflammation, 3. functional disorders of the large bowel-histologically normal colonic mucosa. The latter was a control group. Biopsies were fixed in glutaraldehyde, postfixed in osmium tetroxide. Ultrastructural examination was performed on Epon sections in Tesla BS-500 electron microscope operating at 60 kV. A Lausanne classification of endocrine cells was used in the study. The most common were EC cells, followed by PP, D1 and L respectively. In the first group of patients damaged endocrine cells were more commonly observed. These destructive changes were: vacuolisation of cytoplasm, degranulation and discharge of endocrine granules into intercellular space and degradation of the entire cells.

Adolescent↗
PubMed1982

Effect of pentagastrin on parietal cell ultrastructure in glucagon-pretreated subjects.

The effect on parietal cells of glucagon given prior to pentagastrin is unknown. Fifteen healthy volunteers were studied during constant intravenous infusion of pentagastrin (2 micrograms/kg body weight/hr) and during pentagastrin infusion initiated 20 min after intravenous injection of 2 mg glucagon. Three types of studies were performed: Gastric mucosal biopsies were obtained with a Quinton instrument. Electron micrographs of 320 parietal cells were analyzed by the Loud quantitative method, and intragastric pH (pH probe), or gastric potential difference (PD) were recorded continuously. Pentagastrin infusion produced a significant increase in canalicular and simultaneous reduction of tubulovesicular membrane area of parietal cells. Glucagon pretreatment did not inhibit canalicular and tubulovesicular membrane reaction to pentagastrin; unexpectedly this reaction was significantly greater when compared to that after pentagastrin alone. Initiation of pentagastrin infusion in subjects pretreated with glucagon produced a greater absolute value drop in gastric PD (23 +/- 2 mV) and an earlier drop in intragastric pH (3 min) than in subjects receiving pentagastrin infusion alone (13 +/- 1 mV and 10 min, respectively). In conclusion, at the doses studied, glucagon pretreatment increases parietal cell canalicular reaction to pentagastrin.

Adult↗
PubMed1982

Arachidonic acid protection of rat gastric mucosa against ethanol injury.

AA, an essential dietary fatty acid, is a precursor for synthesis of prostaglandins. The ability of prostaglandins to protect the gastric mucosa against ethanol injury prompted us to investigate the possibility of AA providing similar protection in the rat. AA or its solubilizer were instilled intragastrically 60 min prior to absolute ethanol. The gastric lining was examined at 3 and 15 hr after the administration of ethanol. The extent of damage was assessed both macroscopically and histologically. AA administration 30 or 60 min prior to ethanol ingestion protected the gastric mucosa against macroscopic and histological damage for 3 to 15 hr. The intragastric concentration of prostaglandin E2 was 5,000 to 13,000 times higher in the animals pretreated with AA than in the controls. The protective action of AA was markedly diminished by indomethacin pretreatment. Intrajejunal administration of AA did not protect the gastric mucosa. These experiments demonstrate that a dietary constitutent--arachidonic acid--can protect the gastric mucosa against alcohol injury by inducing the synthesis of prostaglandins by the gastric mucosa.

Animals↗