Search PubMed⌕ Search

Biomedical subjects

A Tarnawski

Publications and source records attributed to A Tarnawski.

At least 91 records · Page 5Linked to original sources
PubMed1988

Microvascular endothelium--a major target for alcohol injury of the human gastric mucosa. Histochemical and ultrastructural study.

In healthy volunteers, we studied the effect in intragastric administration of 100 ml 40% alcohol or isotonic saline on the ultrastructure of gastric oxyntic mucosa with emphasis on gastric mucosal microvasculature. We found that a single dose of 40% alcohol produces exfoliation of the surface epithelium, damage to the mucosal microvessels, extravasation of red blood cells and plasma from disrupted microvessels, and extensive edema of superficial lamina propria. The ultrastructural changes were seen as early as 5 min after alcohol administration and occurred in the mucosal areas where glandular cells did not show necrotic changes. Alcohol-induced injury was localized predominantly to interfoveolar mucosal areas and only occasionally extended to the neck areas. This study demonstrates that the mucosal microvasculature is a primary target for alcohol-induced injury of the human gastric mucosa.

Adult↗
PubMed1988

Histochemistry and ultrastructure of gastric submucosal vasculature in portal hypertensive rats.

We studied histochemical and ultrastructural characteristics of the gastric submucosal blood vessels in portal hypertensive (PHT) rats. PHT was induced by two-stage ligation of the portal vein. Control rats were sham operated (SO). On the fifth day after surgery portal vein blood pressure was measured and rats were killed under nembutal anesthaesia. Gastric specimens were obtained for histological, histochemical and ultrastructural assessment. PHT rats showed thickening and increased cellularity of submucosal vessels including increase in number and size of endothelial cells. All these mesenchymal cells were vimentin-positive. Thickening of vascular wall in submucosal vessels was also observed ultrastructurally together with prominent elaboration of luminal surface of endothelial cells. These changes were not observed in SO rats. All changes in PHT rats reflect vasculopathic involvement of gastric wall in portal hypertension.

Animals↗
PubMed1988

The portal hypertensive gastric mucosa: histologic, ultrastructural, and functional analysis after aspirin-induced damage.

We assessed macroscopic, histologic, ultrastructural, and functional features of aspirin-induced gastric mucosal injury in portal hypertensive and sham-operated rats. Portal hypertension was produced by staged portal vein ligation. Four hours after intragastric acidified aspirin administration, intraluminal pH in portal hypertensive rats was 6.6 +/- 0.2 and 4.3 +/- 0.5 in sham-operated controls (p less than 0.01). Gross mucosal damage was significantly greater in portal hypertensive rats compared with controls (18 +/- 2 versus 7 +/- 1% of total mucosal area). Histologic deep necrosis involved 22 +/- 2% of mucosal section lengths in portal hypertensive rats compared with 7 +/- 1% in sham-operated rats (p less than 0.01). In portal hypertensive rats, histologic and ultrastructural evaluation demonstrated capillary endothelial abnormalities, arterialization of submucosal veins, and markedly greater severity of microvascular damage than in sham-operated controls. Neutralized aspirin (pH, 7.0) did not produce any significant damage detectable grossly, histologically, or by transmission electron microscopy in portal hypertensive rats. We conclude that acid-dependent aspirin-induced gastric mucosal damage is significantly increased in portal hypertension.

Animals↗
PubMed1987

Efficacy of sucralfate and cimetidine in protection of the human gastric mucosa against alcohol injury.

In order to study whether sucralfate or cimetidine may protect human gastric mucosa against alcohol injury, 28 healthy volunteers were pretreated with either: (1) placebo 1 g; (2) cimetidine (Tagamet) 300 mg; or (3) sucralfate (Carafate) 1 g. One hour later, 100 ml of 40 percent ethanol was sprayed directly on the gastric mucosa of the greater curvature during an endoscopic examination. Gastric mucosal changes were assessed by endoscopic appearance (according to grading scale) and by histology. In placebo-pretreated subjects, alcohol produced prominent mucosal damage (endoscopic score, 3.9 +/- 0.3, histologic score, 4.0 +/- 1.1 at 30 minutes). Cimetidine alkalinized gastric pH but did not prevent alcohol-induced damage (endoscopic score, 4.0 +/- 0.6; histologic score, 3.8 +/- 1.1, at 30 minutes). Sucralfate reduced endoscopic and histologic features of alcohol injury (endoscopic score, 1.8 +/- 0.6; histologic score, 1.8 +/- 1.1, at 30 minutes) without affecting gastric luminal pH. Reduction of alcohol-induced injury of the human gastric mucosa by sucralfate but not cimetidine demonstrates that effective protection of the gastric mucosa can be achieved without neutralization or inhibition of gastric acid secretion and points out another clinical application for sucralfate.

Adolescent↗
PubMed1987

Prostaglandin protects against taurocholate-induced damage to rat gastric mucosal cell culture.

Prostaglandins protect gastric mucosa against noxious agents, but it is unknown whether this protection includes a direct action on the cells themselves, this action is limited to damaging agents that inhibit prostaglandin synthesis, or cellular cyclic adenosine monophosphate is the mediator. The present study tested these questions in cultured gastric mucous epithelial cells. The effect of 16,16-dimethyl prostaglandin E2 on cellular cyclic adenosine monophosphate level and the effect of 16,16-dimethyl prostaglandin E2, dibutyryl cyclic adenosine monophosphate, and isobutyl methyl xanthine on taurocholate-induced damage to cultured rat gastric mucosal cells was determined. As parameters of cell damage, the trypan blue dye exclusion test and 51Cr-release were employed. Taurocholate significantly increased 51Cr-release in a dose-dependent manner and decreased the number of viable cells. 16,16-Dimethyl prostaglandin E2 (1.0 microM) diminished the cell damage caused by 10 mM taurocholate (p less than 0.01) and increased cyclic adenosine monophosphate levels. Prostaglandin F2 alpha but not prostaglandin I2 was also cytoprotective. Addition of dibutyryl cyclic adenosine monophosphate (1.0 mM) and isobutyl methyl xanthine while significantly increasing cyclic adenosine monophosphate levels did not significantly reduce taurocholate-induced cell damage. Thus, in vitro 16,16-dimethyl prostaglandin E2 directly protects gastric mucous cells against taurocholate-induced injury, direct prostaglandin cytoprotection is not limited to damaging agents that inhibit prostaglandin synthesis, and cyclic adenosine monophosphate levels do not correlate with gastric mucosal cell damage and may not be involved in the direct protective effect of prostaglandins.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Cytoprotective drugs. Focus on essential fatty acids and sucralfate.

Cytoprotection has been defined as an ability of prostaglandins to prevent gastric mucosal injury produced by a variety of ulcerogenic and necrotizing agents without inhibition of gastric acid secretion or without neutralizing intragastric acidity. Since the first demonstration of cytoprotection by prostaglandins many other agents have been claimed to be cytoprotective. Essential fatty acids: arachidonic and linoleic, licorice products, sucralfate, antacids and sulfhydryl compounds all possess cytoprotective properties. All of these compounds are able to prevent or reduce gastric mucosal necrosis produced by absolute ethanol, a necrotizing agent which injures mucosa independently of the luminal pH. Gastric mucosal protection by essential fatty acids is mediated by their conversion by the gastric mucosa to protective prostaglandins. Sucralfate and antacids are also cytoprotective compounds which stimulate release of endogenous prostaglandins from the gastric mucosa.

Animals↗
PubMed1987

Effect of sucralfate on the normal human gastric mucosa. Endoscopic, histologic, and ultrastructural assessment.

Twelve healthy volunteers were given a single sucralfate tablet (1 gm) orally. For 60 min after ingestion they were examined endoscopically for the localization and disintegration of the tablet in the stomach, and biopsies were taken to determine the effect of sucralfate on the histology and ultrastructure of the normal gastric mucosa. After ingestion, the sucralfate tablet had disintegrated and firmly adhered to a relatively small mucosal area of the greater curvature covering 5 +/- 2 and 7 +/- 2 cm2 at 15 and 30 minutes, and 9 +/- 3 cm2 at 60 minutes after drug ingestion. Histologic and ultrastructural examination of the mucosa in direct contact with sucralfate revealed distinct changes in the surface epithelial cells: mucus release, vacuolization, and exfoliation of some of the cells. Endoscopy offers a unique opportunity for the study of gastroduodenal effects and disposition of orally administered drugs.

Adult↗
PubMed1987

16,16-Dimethyl prostaglandin E2 reduced chenodeoxycholate-induced small intestinal mucosal injury in the rat.

To determine whether prostaglandin may protect the small intestinal mucosa against bile acid-induced injury, we perfused in vivo rat jejunal segments with 5 mmol/L chenodeoxycholate with and without topical pretreatment with 2.6 mumol/L (1 microgram/ml) 16,16-dimethyl prostaglandin E2. Mucosal injury by chenodeoxycholate and its time sequence was assessed by using mannitol absorption and quantitative histology after 5, 15, 30, and 45 minutes of chenodeoxycholate perfusion. Forty-five-minute perfusion with chenodeoxycholate increased mannitol absorption from 0 to 0.9 nmol/min/cm, whereas prostaglandin pretreatment reduced this increase threefold (P less than 0.001). The increase in mannitol absorption coincided with progressive denudation of epithelial cells from intestinal villi. After 45 minutes exposure to chenodeoxycholate, an average of 50 micron of the cross-sectional surface of the villi tips was denuded of epithelial cells compared with only 25 micron denuded with prostaglandin pretreatment (P less than 0.01). These data indicate that topical administration of 16,16-dimethyl prostaglandin E2 reduces both the functional and morphologic small intestinal mucosal injury caused by chenodeoxycholate.

16,16-Dimethylprostaglandin E2↗
PubMed1987

The mechanism of protective, therapeutic and prophylactic actions of sucralfate.

Sucralfate, a non-systemic drug, speeds the healing of peptic ulcers, prevents their recurrence and prevents stress ulcerations in critically ill patients. In animal experiments sucralfate protects the gastric mucosa against damage produced by ulcerogenic and necrotizing agents. Sucralfate does not inhibit gastric acid secretion and has a minimal neutralizing capacity. The basis for the acute protective action of sucralfate is its effect on the normal gastric mucosa enhancing the natural defensive mechanisms, stimulating mucus, bicarbonate and prostaglandin release and mucosal cell renewal. Therapeutic action of sucralfate is most likely the result of A) local action on ulcerated areas of the mucosa by formation of a protective barrier reducing pepsin and H+injury; B) binding of pepsin and bile acids; and C) trophic effect on the entire mucosa which facilitates healing and re-epithelialization. Long term prophylactic efficacy of sucralfate is probably due to its chronic trophic action on the gastric mucosa. Quantitive and qualitative increase in the surface epithelial and proliferative zone cells enhance the defensive capabilities of the mucosa increasing mucus, bicarbonate, and prostaglandin release and cell renewal.

Animals↗
PubMed1987

Protection of the gastric mucosa by linoleic acid--a nutrient essential fatty acid.

We studied whether linoleic acid, a precursor for arachidonic acid and prostaglandins, could protect the gastric mucosa against ethanol-induced injury. Fasted male rats received intragastric pretreatment with 1 ml of one of: a) solubilizer; b) solubilized linoleic acid (74 mg); or c) solubilized oleic acid (74 mg) (a nonessential fatty acid). One hour later, 2 ml 100% ethanol was given intragastrically. Three hours after ethanol administration, the gastric mucosa was assessed for gross necrosis and for histologic changes. Three hours after ethanol administration in solubilizer, pretreated-group gross mucosal necrosis involved 35 +/- 3% of total mucosal area, while deep histologic necrosis involved 52 +/- 4% of the mucosal strip length. Pretreatment with linoleic acid (but not oleic acid) significantly reduced gross histologic necrosis, to 2.3 +/- 0.5%, and deep histologic necrosis to 4 +/- 2% (both p less than 0.001 versus solubilizer group). The protective action of linoleic acid was significantly reduced (greater than 10-fold) by pretreatment with indomethacin (prostaglandins synthetase inhibitor), suggesting prostaglandins as mediators of protection. The present study showed that effective protection of the gastric mucosa against ethanol injury can be achieved by intragastric administration of linoleic acid, a dietary essential fatty acid.

Animals↗
PubMed1987

Alcohol injury to the normal human gastric mucosa: endoscopic, histologic and functional assessment.

In 15 healthy volunteers, we studied the effect of intragastric administration of 100 ml 40% alcohol (in 10 experimental subjects) or isotonic saline (in 5 control subjects) on endoscopic appearance of the gastric mucosa, mucosal histology, luminal pH, and gastric mucosal potential difference. We found that a single dose of 40% alcohol produces rapid endoscopic changes (congestion and focal hemorrhagic lesions) and prominent histologic changes (exfoliation of the surface epithelium, edema of the lamina propria and hemorrhagic lesions associated with mucosal microvascular damage). The histologic changes were seen as early as 5 minutes after alcohol administration and occurred coincidentally with functional changes, which consisted of a sudden increase in luminal pH and a drop in the mucosal potential difference. The present study correlates the time sequence of the endoscopic, histological, and functional changes of the gastric mucosa following acute alcohol injury in normal human volunteers. This study confirms that many of the previous observations in animal models are also seen in normal human volunteers.

Adult↗
PubMed1986

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats.

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly reduced portal pressures (24 +/- 1 vs 32 +/- 1 cm saline), macroscopic mucosal damage (24 +/- 1 vs 39 +/- 4% of mucosa), and histologic deep necrosis (36 +/- 2 vs 61 +/- 4% of mucosal length). Increased dosage of propranolol to 4 mg did not produce any further reduction of portal pressure or mucosal damage. Central venous and systemic arterial pressures were not significantly altered by propranolol. The extent of mucosal damage correlated with levels of portal pressure (P less than 0.01) in portal hypertensive rats. Sham-operated normotensive rats had less macroscopic mucosal damage (26 +/- 4%) than portal hypertensive rats, and propranolol did not affect the extent of ethanol-induced damage or portal pressures in these animals. We conclude: (1) Propranolol is effective in reducing extent of ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in sham-operated controls; (2) this effect correlates with reduction of portal pressure; and (3) our study supports the clinical impression that reducing portal pressure may be one approach for the prevention and therapy of gastric mucosal damage in portal hypertension.

Animals↗
PubMed1986

Does sucralfate affect the normal gastric mucosa? Histologic, ultrastructural, and functional assessment in the rat.

Although the action of sucralfate on ulcerated mucosa has been demonstrated, its effect on the histology, ultrastructure, and function of normal gastric mucosa is unknown. We investigated the effect of acute administration of sucralfate on the gastric mucosal history, ultrastructure, mucosal potential difference, and luminal release of prostaglandin E2. At 15 min, 1 h, and 3 h after intragastric instillation of sucralfate, whitish incrustations of the drug were firmly adhering to the glandular mucosa. Mucosal histology after sucralfate administration demonstrated the following: disruption and exfoliation of some of the surface epithelial cells, mucosal hyperemia, prominent release of mucus from the surface epithelial cells, and edema of lamina propria and submucosa. These changes were most prominent in the areas where sucralfate was in contact with the mucosal surface. Scanning and transmission electron microscopy confirmed the above changes. Sucralfate produced a drop in gastric mucosal potential difference and a significant increase in luminal release of prostaglandin E2. Sucralfate produces distinct morphologic and functional changes in the normal gastric mucosa, which may account for its preventive and therapeutic efficacy.

Aluminum↗
PubMed1986

Protection against alcohol-induced gastric mucosal injury by aluminum-containing compounds--sucralfate, antacids, and aluminum sulfate.

Previously, we demonstrated that both antacids and sucralfate can protect the gastric mucosa against alcohol injury. Since these compounds contain aluminum, we studied whether other aluminum compounds have cytoprotective properties as well. Fasted rats were pretreated intragastrically with A) 0.9% NaCl, B) sucralfate, C) aluminum-magnesium antacid gel, D) Al2(SO4)3, E) Al(OH)3, and 1 h later they received 2 ml 100% ethanol by gavage. The stomach was removed and assessed for injury 3 h after ethanol administration. Control (group A) rats had 39 +/- 3% gross mucosal injury, which was reduced to 5 +/- 1% with sucralfate, 7 +/- 1% with Al2(SO4)3, 12 +/- 2% with Al(OH)3, and 16 +/- 2% with aluminum-magnesium antacid gel pretreatment. Microscopic surface epithelial injury and submucosal edema were seen in all five groups, while deep mucosal necrosis was largely prevented by pretreatment in groups B to E. These findings indicate that aluminum in a wide variety of molecular forms can protect the gastric mucosa against alcohol injury.

Alum Compounds↗
PubMed1986

Prostaglandin protection of the human gastric mucosa against alcohol-induced injury. Endoscopic, histologic, and functional assessment.

UNLABELLED: We studied whether pretreatment with prostaglandin (16,16-dimethyl (dm) prostaglandin E2) may protect the human gastric mucosa against alcohol-induced injury. Healthy volunteers received (via an endoscope) intragastric pretreatment with either: A) placebo or B) 16,16 dm prostaglandin E2, 1 microgram/kg, and 15 min later 40 ml 60% alcohol was sprayed directly on gastric mucosa. STUDIES: endoscopic appearance of the gastric mucosa was evaluated and scored (scale 0-5) by two investigators, gastric mucosal potential difference (PD) was continuously recorded, and mucosal biopsies were obtained at 30 min after alcohol for histologic examination. Alcohol instillation in subjects pretreated with placebo (group A) produced within 30 min prominent endoscopic hemorrhagic lesions (grade 4.8 +/- 0.2). Histologic examination showed exfoliation of the surface epithelium, extensive edema of lamina propria, and deep hemorrhagic necrotic lesions in 86% +/- 10 of specimens. These morphologic changes coincided with a sudden drop in gastric PD of 42 mV. Prostaglandin pretreatment (group B) significantly reduced alcohol-induced endoscopically visible lesions (grade 3.1 +/- 0.2, P less than 0.01 vs group A). Histologically, prostaglandins reduced deep hemorrhagic erosions (4.5-fold reduction) and subepithelial hemorrhages, but did not prevent exfoliation of the surface epithelium and gastric PD drop. Thus, prostaglandin administration to human volunteers effectively reduced alcohol injury to the gastric mucosa.

16,16-Dimethylprostaglandin E2↗
PubMed1986

Is arachidonic acid protected gastric mucosa more resistant to rechallenge with a second dose of ethanol?

In our previous studies we found that pretreatment with arachidonic acid protects the gastric mucosa against ethanol-induced injury. In the present experiments we studied whether: gastric mucosa protected with arachidonic acid against ethanol injury is more resistant to a subsequent second ethanol injury, and whether a second ethanol dose produces further damage of the nonprotected damaged gastric mucosa in a control group. We found that: rechallenge with a second ethanol dose increases the extent of gastric mucosal necrosis in control rats; once protected (with arachidonic acid) the gastric mucosa is more resistant to subsequent ethanol rechallenge but some deep necrosis occurs and restoration of the surface epithelium is somewhat impaired when compared to the initial injury and repair. Thus, pretreatment of the gastric mucosa with a prostaglandin precursor dietary essential fatty acid confers excellent protection against alcohol damage with some residual protective activity against a subsequent rechallenge with alcohol.

Animals↗