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Biomedical subjects

A Tarnawski

Publications and source records attributed to A Tarnawski.

At least 73 records · Page 4Linked to original sources
PubMed1990

Impaired generation of prostaglandins from isolated gastric surface epithelial cells in portal hypertensive rats.

We studied generation of prostaglandins E2 and 6-keto F1a by surface epithelial cell isolated from the gastric mucosa of portal hypertensive and sham-operated rats. Oxygenated cell suspensions containing 80 +/- 3% of surface epithelial cells were incubated for 30 min at 37 degrees C and the concentration of prostaglandin E2 and 6-keto-prostaglandin F1a in medium was measured by radioimmunoassay. Viability of the cells was assessed with Fast green exclusion at baseline and after 30-min and 60-min incubation. Within 30 minutes the surface epithelial cells obtained from portal hypertensive rats generated 22.0 +/- 1.6 (mean +/- SE) pg prostaglandin E2 and 40.7 +/- 4.7 pg 6-keto prostaglandin F1a, per 10(6) cells. These were significantly less than prostaglandin generation by cells obtained from sham-operated rats. The viability of the surface epithelial cells from portal hypertensive rats was also significantly reduced compared with sham-operated rats after 60 minute incubation. Reduced ability of the surface epithelial cells to generate prostaglandins may be one mechanism for increased susceptibility of portal hypertensive gastric mucosa to injury by noxious agents.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study.

It is now generally accepted that Campylobacter pylori is closely associated with peptic ulcer disease and chronic type B gastritis. Whether C. pylori is the direct etiologic cause of either or both of these illnesses remains unclear. Possible pathophysiologic effects of C. pylori are still a matter of debate and conjecture. Utilizing a small group of patients with gastric ulcers and chronic gastritis, we examined the ultrastructural relationship between C. pylori and gastric cells. Forty-eight percent of our gastric ulcer patients and 57% of our chronic gastritis patients had C. pylori in their lower corpus mucosa. Examination with the transmission electron microscope indicated a very close proximation by C. pylori to the surface epithelial cells strongly suggesting adherence. We also describe for the first time the invasion of gastric cells by C. pylori. Although an uncommon occurrence, we had repeated observations of C. pylori invading surface epithelial cells, parietal cells, and chief cells. Most of the intracellular C. pylori were intact but other forms appearing to be degenerating organisms were also seen. We suggest that cell invasion may be one mechanism by which C. pylori causes pathologic changes in the gastric mucosa. These observations may also explain why C. pylori chronically infects gastric cells and frequently recurs after treatment.

Gastric Mucosa↗
PubMed1990

Campylobacter pylori interactions with gastric cell tissue culture.

Many investigators have reported that gastric mucosal biopsies of patients with chronic gastritis and peptic ulcer disease show the presence of Campylobacter pylori in a large majority of cases. Histologic examinations of such tissues indicate a close approximation of C. pylori with gastric surface epithelial cells. A recent report has described both adherence and cell invasion of gastric cells by C. pylori. Using a transmission electron microscope, we have examined the interaction between C. pylori, C. jejuni, and E. coli in vitro with a gastric cancer cell line, Kato III. Our results indicate marked toxicity of E. coli and moderate toxicity of C. jejuni for Kato III cells. C. pylori had only a minor effect on tissue culture viability. C. pylori was found to have a strong association with the Kato III cell membranes and evidence of occasional cell invasion. Both C. jejuni and E. coli showed no attachment or association with the Kato III cells. We interpret these findings as indicating that C. pylori may have a specific adhesion for gastric cells.

Bacterial Adhesion↗
PubMed1990

"Healed" experimental gastric ulcers remain histologically and ultrastructurally abnormal.

The present study was designed to assess histologic and ultrastructural features of gastric mucosa in the areas of grossly healed ulcers (acetic acid-induced gastric ulcers) in rats. The specific question we studied was whether the structure and cellular composition of the gastric mucosa in an area of grossly healed ulcer were fully restored. Eighty Sprague-Dawley rats underwent laparotomy; 100% acetic acid was applied to the lower gastric corpus serosa for 30 s and the abdomen was closed. The stomachs were reopened after 2 weeks or after 2, 3, or 4 months. Standardized gastric wall specimens from the area of grossly healed ulcers were obtained, processed, and evaluated by light microscopy and by transmission electron microscopy. The gastric mucosa of grossly healed ulcers demonstrated re-epithelialization at each study time but the mucosa beneath the surface epithelium displayed prominent histologic and ultrastructural abnormalities. Two different patterns of scar could be distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% reduction vs. normal), with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; or (b) the mucosa displayed ballooning dilatation of gastric glands, reduction in the microvascular network, and poor differentiation of glandular cells. We conclude that (i) the subepithelial mucosa of grossly healed gastric ulcer displays disorganized restoration of glandular and vascular structures and remains histologically and ultrastructurally abnormal; (ii) these abnormalities may interfere with oxygenation, nutrient supply, and with mucosal resistance and defense, and therefore could be the basis for ulcer recurrence.

Acetates↗
PubMed1990

Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats.

The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis.

Acetates↗
PubMed1990

Gastric microvascular endothelium: a major target for aspirin-induced injury and arachidonic acid protection. An ultrastructural analysis in the rat.

Exposure of the gastric mucosa to aspirin results in exfoliation of the surface epithelium and deep mucosal necrosis. We assessed the changes in the mucosal microvessels during aspirin-induced injury and arachidonic acid protection of the gastric mucosa using transmission electron microscopy. Male Sprague-Dawley rats received intragastric pretreatment with either solubilizer (control) or detergent solubilized arachidonic acid (148 mg kg-1). One hour later 1-ml suspension of 200 mg kg-1 body weight acidified aspirin was administered intragastrically. The ultrastructure of mucosal microvasculature was assessed at 15 min and 4 h after aspirin administration both qualitatively and quantitatively by determining the number of necrotic or damaged capillaries in standardized mucosal sections. In addition, mucosal specimens were immunostained with a specific antiserum against vimentin, an endothelial marker, and fluorescence intensity was measured with a Nikon FX microscopic photometric system. In control rats, aspirin produced significant damage to both superficial and deeper microvessels consisting of: rupture of capillary walls, necrosis of endothelial cells, damage to endothelial organelles, deposition of fibrin and adherence of platelets to damaged endothelium. Vimentin fluorescence was reduced three-fold. Microvascular injury preceded the development of deep necrotic lesions. Microvascular damage and deep mucosal necrosis were significantly reduced by arachidonic acid pretreatment. We conclude that gastric mucosal microvessels are the major target for aspirin-induced injury and arachidonic acid protection.

Animals↗
PubMed1990

The protective and therapeutic mechanisms of sucralfate.

Sucralfate is a nonsystemic agent that is effective in protecting the gastroduodenal mucosa against injury. In addition, sucralfate is effective in the healing of acute duodenal and gastric ulceration, the therapy of esophagitis, and the prevention of ulcer recurrence. The mechanisms responsible for sucralfate's successful protective and therapeutic actions include the adsorption of pepsin and bile acids, the stimulation of bicarbonate and mucus secretion, and stimulation of endogenous synthesis of prostaglandins. When sucralfate is given to experimental animals or humans, it stimulates endogenous synthesis and release of prostaglandin E2 and inhibits thromboxane release. Pretreatment of animals with the cyclooxygenase inhibitor indomethacin results in a marked decrease in the protective effect of sucralfate against alcohol injury. Sucralfate also increases epidermal growth factor binding to ulcerated areas and stimulates macrophage activity. In addition, sucralfate stimulates endogenous sulfhydryl compounds. At the microscopic level sucralfate protects the vascular integrity of the mucosa and the mucosal proliferative zone. It also stimulates epithelial cell restitution and stimulates cell proliferation. The administration of sucralfate before acute injury results in decreased depth and extent of injury and in acceleration of healing. Because of sucralfate's ability to stimulate the protective and reparative mechanisms of the gastric and duodenal mucosa, it is an important nonsystemic agent for the therapy and prevention of peptic ulceration.

Animals↗
PubMed1990

Antacids: new perspectives in cytoprotection.

There is increasing evidence that aluminum-containing antacids are able to protect the gastric mucosa against various ulcerogenic and necrotizing agents including 0.6 M HCl, 0.2 M NaOH, and absolute alcohol. Since gastric mucosal necrosis produced by alcohol is independent of luminal acid and cannot be reduced by H2-receptor antagonists, the protective action of antacids is accomplished by mechanism(s) other than acid-neutralizing ability. In addition, since acidified antacids can protect the gastric mucosa even better than an antacid with intact neutralizing capacity, it is clear that such action is independent of acid-neutralizing ability and therefore has all the features of cytoprotection. Whereas the cytoprotective action of antacids in experimental conditions is well established, the mechanisms of antacid-induced mucosal protection are not known. The clinical relevance of antacid-induced protection also requires further elucidation. Antacids have advantages over the H2 blockers in protecting the gastric mucosa against alcohol-induced necrosis and in preventing stress-induced ulcers in critically ill patients. Although more work is needed to clarify the mechanisms of cytoprotective action of antacids, the recent experimental findings gave a new life to and new potential clinical applications for antacids.

Animals↗
PubMed1989

Impaired oxygenation of gastric mucosa in portal hypertension. The basis for increased susceptibility to injury.

Increased susceptibility to mucosal damage is a prominent feature of portal hypertensive gastropathy. Since the portal hypertensive gastric mucosa has extensive microvascular changes, we postulated that the increased sensitivity to mucosal damage could have an ischemic basis. We measured distribution of gastric serosal and mucosal oxygenation in a group of portal hypertensive and sham-operated rats, and then studied the effects of intragastric aspirin. In the basal state, gastric mucosa of portal hypertensive rats had significantly reduced oxygenation compared to controls (24 +/- 5 vs 45 +/- 7 mm Hg PO2, P less than 0.02), while serosal oxygenation was similar between the two groups. Intragastric aspirin produced significantly greater mucosal damage to portal hypertensive rats and mucosal oxygenation was almost one third that of sham-operated controls. Systemic arterial pressures and oxygenation were similar between the two groups. We conclude that there is impairment of gastric mucosal oxygenation and increased mucosal damage by aspirin in portal hypertensive rats compared with sham-operated controls. These results support our hypothesis that the increased sensitivity of the portal hypertensive mucosa to damage is a consequence of impaired mucosal oxygenation.

Animals↗
PubMed1989

Morphologic changes in gastric mucosa of aging rats.

We examined histologic and ultrastructural changes in the gastric mucosa of aging rats. Standardized gastric specimens from Sprague-Dawley rats 3 months of age (young) and 24 months of age (old) were evaluated by qualitative and quantitative histology and transmission electron microscopy. Old rats had the following histologic changes: (1) partial atrophy of the gastric glands and their replacement with hyalinlike connective tissue; (2) cystic dilatation of the gastric glands at the bases with occasional squamous cell metaplasia; and (3) extensive perivascular depositions of PAS-positive material, negative for amyloid. The total mucosal thickness was 484 +/- 100 microns in young rats vs 1122 +/- 240 microns in old rats (P less than 0.01). Electron microscopy demonstrated degenerative changes in parietal and chief cells, hyperplasia of surface and foveolar mucous cells, and prominent accumulation of disorganized collagen fibrils in perivascular connective tissue. This study indicates that the gastric mucosa of aging rats that have not been exposed to damaging agents does show definite histologic and ultrastructural changes.

Aging↗
PubMed1989

Protection of the rat gastric mucosa against aspirin injury by arachidonic acid: a dietary prostaglandin precursor fatty acid.

We studied aspirin-induced injury to the gastric mucosa in control rats pretreated with a solubilizer, pluronic F-68 (PL), and in rats pretreated with solubilized arachidonic acid (AA). Fasted male rats were pretreated intragastrically with 1 ml of either pluronic or AA and 1 h later acidified ASA (1 ml suspension of 200 mg kg-1 body weight) was administered intragastrically. Grossly apparent mucosal lesions developed 1 h after aspirin in pluronic-pretreated rats, but were significantly reduced in AA-pretreated rats. Histology, scanning and transmission electron microscopy demonstrated that AA pretreatment did not prevent aspirin-induced initial damage to the surface epithelium but did significantly reduce extent of aspirin-induced deep mucosal necrosis at 1, 4 and 18 h after aspirin. Initial aspirin-induced surface epithelial damage was rapidly restituted by two distinct types of re-epithelialization - vertical and horizontal. While the vertical type of re-epithelialization has been reported previously as the first stage of mucosal repair following injury by various noxious agents such as concentrated ethanol, the horizontal type of re-epithelialization, which is described for the first time in this paper, seems to be specific for the repair of aspirin-induced gastric mucosal injury. These studies suggest that dietary factors such as essential fatty acids may play a role in gastric mucosal protection against aspirin injury.

Animals↗
PubMed1989

Ability of prostaglandin to reduce ethanol injury to dispersed chief cells from guinea pig stomach.

To determine whether prostaglandin exerts a direct action on individual gastric epithelial cells that protects them from ethanol-induced injury, dispersed chief cells from guinea pig stomach were pretreated with 16,16-dimethyl-prostaglandin E2 (dmPGE2) or placebo before incubation with ethanol or control. Cell injury was assessed in terms of exclusion of Fast Green dye, release of lactate dehydrogenase, alterations of ultrastructure, and pepsinogen secretion stimulated by a variety of secretagogues. Of chief cells 60 +/- 2% were stained by Fast Green if incubated with 10% ethanol for 1 h after pretreatment with placebo, whereas only 38 +/- 1% of cells showed Fast Green staining when pretreated with 2.6 microM dmPGE2 before ethanol exposure. Similarly, 63 +/- 2% of cellular lactate dehydrogenase was released from chief cells pretreated with placebo compared with 36 +/- 4% of lactate dehydrogenase released from cells pretreated with 2.6 microM dmPGE2 (P less than 0.01). The prostaglandin's protective effect persisted throughout a 6-h incubation with ethanol. Scanning and transmission electron micrographs demonstrated disintegration of chief cells pretreated with placebo before ethanol exposure, whereas ultrastructural architecture was relatively preserved among chief cells pretreated with dmPGE2. Preincubation with 8 or 10% ethanol inhibited the subsequent stimulation of pepsinogen secretion caused by carbachol, cholecystokinin, A23187, 12-O-tetradecanoylphorbol 13-acetate, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with dmPGE2 did not reduce the ethanol-induced inhibition of secretion stimulated by any of these secretagogues. These data indicate that dmPGE2 significantly reduces ethanol-induced damage to dispersed chief cells in terms of alterations of membrane permeability and ultrastructure but does not prevent the ethanol-induced impairment of pepsinogen secretion. These findings provide evidence that dmPGE2 exerts a direct but limited protective action on the gastric chief cell, independent of vascular, paracrine, or neural actions.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Protective effect of pentoxifylline on gastric mucosa.

Pentoxifylline (PF) has been shown to increase tissue oxygen tension. This study was performed to determine if PF has a protective effect on the gastric mucosa against alcohol (EtOH)-induced injury. Fasted Sprague-Dawley rats were pretreated with randomized test solution (control, normal saline, or PF, 75 mg/kg) intraperitoneally (ip). At 30 min, 100% EtOH (pH 8.5) was given intragastric. At 90 min, laparotomy was performed and gastric serosal stomach surface oxygen tensions (pO2) were measured. Stomachs were excised and opened and pH was measured. Photographs were taken and sections were obtained for histologic analysis to determine mucosal injury. The PF-pretreated rats had significantly higher serosal pO2 and significantly lower intragastric pH than control animals. There was significantly less gross and histologic mucosal injury in PF-treated animals. We conclude that PF is protective against EtOH gastric mucosal injury. This effect correlates with increased gastric serosal pO2 and is likely due to improved microcirculatory blood flow following PF administration.

Animals↗
PubMed1988

Gastric mucosal blood flow and acid secretion in portal hypertensive rats.

The purpose of this study was to examine gastric mucosal blood flow, measured by hydrogen gas clearance, and acid secretion in portal hypertensive rats. Chronic portal hypertension was induced by a two-stage complete portal vein occlusion procedure. Basal gastric mucosal blood flow was significantly higher in portal hypertensive rats than in sham-operated rats, but there was no difference in basal acid output. In response to administration of pentagastrin, there was the expected rise in both acid secretion and blood flow in sham-operated rats, but in portal hypertensive rats there was a significantly lower increase in acid output and no change in blood flow. In portal hypertensive rats pretreated with indomethacin to inhibit endogenous prostaglandin generation, both basal blood flow and acid secretion--and their response to pentagastrin administration--were the same as in non-indomethacin-treated sham-operated rats. We conclude that in portal hypertensive rats there is an increased gastric mucosal blood flow and an impaired acid output response to pentagastrin stimulation, and these changes appear to be mediated by an increase in endogenous prostaglandin.

Animals↗
PubMed1988

Cellular aspects of alcohol-induced injury and prostaglandin protection of the human gastric mucosa. Focus on the mucosal microvessels.

In healthy volunteers, we studied the cellular target sites of alcohol-induced gastric mucosal injury and prostaglandin-induced protection with special emphasis on the mucosal microvascular ultrastructure. Subjects received pretreatment with saline or 16,16-dimethyl-prostaglandin E2 1 micrograms/kg b.w. and 15 min later 40 ml of 60% alcohol were sprayed on the gastric mucosa through an endoscope. Mucosal biopsies were obtained at 15 and 30 min after alcohol administration for assessment of injury by light and transmission electron microscopy. Alcohol administration to saline-pretreated subjects produced severe damage to gastric mucosal microvascular endothelium. Injury consisted of rupture of the microvessels with formation of intramucosal hemorrhages, platelet aggregation and fibrin deposition, and on occasion total necrosis of the microvessels. In contrast, in the prostaglandin-pretreated group, alcohol-induced damage to the mucosal microvessels and hemorrhages were greatly reduced at both 15 and 30 min after alcohol administration. In separate group of subjects, we investigated the effect of prostaglandin alone (without alcohol) on the gastric mucosal microvessel ultrastructure. We found that prostaglandin produced prominent ultrastructural changes in the capillaries, which may be the basis for its protective action. This study demonstrated that the human gastric mucosal microvasculature is an important target site of alcohol injury and prostaglandin protection. The direct effect of prostaglandin on endothelial ultrastructure may render it more resistant to alcohol injury. While protection of the endothelial cell lining of the mucosal microvasculature represents an example of a broader phenomenon of protective action of prostaglandin on various cells, the crucial strategic role of the microvasculature makes preservation (protection) of its integrity of special importance for the gastric mucosa.

Adult↗
PubMed1988

Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin.

Isolated human gastric glands from surgical specimens were preincubated in an oxygenated medium with placebo or 16,16 dimethyl prostaglandin E2 (dmPGE2) and incubated at 37 degrees C in either medium alone, medium containing 4.43 mM indomethacin or medium containing 8% ethanol. We assessed the viability of gland cells with fast green exclusion, release of lactate dehydrogenase (LDH) into the medium, and ultrastructural damage by scanning and transmission electron microscopy. Both indomethacin and ethanol significantly reduced the viability of placebo-pretreated glands, increased LDH release into the medium, and produced prominent ultrastructural damage. DmPGE2 significantly reduced both indomethacin and ethanol-induced injury, increased the number of viable cells, reduced LDH release, and diminished the extent of ultrastructural damage. These studies indicate that PG protection of gastric mucosal cells has a direct cellular action that is not limited to replacement of depleted endogenous PGs. PG protection in our experiments did not depend on PG's previously described systemic actions, such as protection of the microvessels, preservation of the mucosal blood flow, or stimulation of bicarbonate and mucus secretion.

16,16-Dimethylprostaglandin E2↗