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T Mach

Publications and source records attributed to T Mach.

At least 55 records · Page 3Linked to original sources
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

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

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

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↗
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↗
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↗
PubMed1981

Ethanol induced duodenal lesions in man. Protective effect of prostaglandin.

This study aimed: 1. to investigate quantitatively mucosal changes in the human duodenum after ethanol instillation, 2. to determine the effect of 16,16 dimethyl prostaglandin E2 (dmPGE2) pretreatment on these changes. In 11 healthy subjects were instilled into the postbulbar duodenum solutions of normal saline or dmPGE2 and 15 minutes later 20 ml 40% ethanol. Mucosal changes were evaluated endoscopically and histologically. Thirty minutes after ethanol and saline, hemorrhagic changes involved the entire mucosa (endoscopic lesion index: 4.8 +/- 0.2) and all histological specimens showed erosions. Pretreatment with dmPGE2 significantly prevented ethanol-induced mucosal changes (endoscopic lesion index: 2.17 +/- 0.17 p less than 0.01) and mucosal biopsies did not show erosions outside endoscopically abnormal areas. In conclusion, direct instillation of ethanol induced consistent damage to duodenal mucosa in man. This damage was significantly reduced by dmPGE2 pretreatment.

Adult↗
PubMed1981

Prostaglandin protection of carbon tetrachloride-induced liver cell necrosis in the rat.

We studied whether 16,16--dimethyl prostaglandin E2 (dmPGE2) may prevent acute liver damage induced by carbon tetrachloride (CCl4) in the rat. One hundred thirty male rats were divided into the following groups: (1) controls, (2) rats given CCl4 6670 mg/kg body wt subcutaneously, (3) rats pretreated with 5 micrograms/kg dmPGE2 given subcutaneously 30 min before, and 8 and 24 h after CCl4 administration, and (4) animals given dmPGE2 only as in group 3. Liver damage was assessed by biochemical studies (SGPT, serum alkaline phosphatase, and bilirubin) and by histology. In rats receiving CCl4 alone, SGPT activities were significantly elevated to 1024 +/- 82 U/L, 1270 +/- 120 U/L, 386 +/- 48 U/L and 208 +/- 20 U/L at 24, 48, 96, and 120 h after CCl4 respectively. In animals pretreated with dmPGE2 before CCl4, SGPT activities were 201 +/- 24 U/L, 55 +/- 4.6 U/L, 28 +/- 4 U/L, and 24 +/- 4 U/L at 24, 48, 96, and 120 h after CCl4, respectively (p less than 0.01, versus animals receiving CCl4 only). Histologically, livers of rats treated with CCl4 alone showed severe centrilobular necrosis at 24 and 48 h. Livers of animals pretreated with dmPGE2 before CCl4 did not show necrosis. It is concluded that dmPGE2 protects the liver against cell necrosis induced by CCl4 in the rat.

16,16-Dimethylprostaglandin E2↗
PubMed1980

Cytoprotective effect of 16, 16' dimethyl prostaglandin E2 and some drugs on an acute galactosamine induced liver damage in rat.

Present experiment was aimed to study whether 16, 16' dimethylprostaglandin E2 (dmPGE2), Hepatofalk (HF), or Orotofalk (OF) may prevent an acute liver damage induced in rats with D-galactosamine (GalN). Fifty male rats were divided into 5 groups: 1. controls, 2. rats receiving GalN 750 mg/kg b. w. intraperitoneally, 3. animals pretreated with 5 microgram/kg dmPGE2 given subcutaneously 24 hours prior to, 30 min prior to and 6 hours after GalN. Rats of group 4 received HF 0,8 ml/kg intramuscularly and group 5 OF 0,3 caps/kg intragastrically 24 hours prior to, 30 min prior to and 6 hours after GalN. Animals were sacrificed 24 hours after GalN injection. Histological, histochemical and ultrastructural studies of the liver were performed. In rats receiving GalN alone (group 2) typical severe liver damage consisting of acidophilic necrosis of hepatocytes, periportal and intralobular inflammatory infiltration, hypertrophy and hyperplasia of Browicz-Kupffer cells has been observed. Histochemical investigations showed in this group fatty degeneration and a decrease in glycogen content in hepatocytes, irregular distribution of lysosomes, numerous cytolysosomes and uneven decrease in lysosomal enzymes activity (acid phosphatase and beta-glucuronidase). Ultrastructural studies revealed depletion in glycogen, fat droplets, hypertrophy of smooth endoplasmic reticulum and numerous autophagic vacuoles. Some of these vacuoles or residual bodies were dropping out into intercellular space. Focal accumulation of lamellar cytomembranes as well as condensation of heterochromatin in nuclei were also observed. Pretreatment of animals with dmPGE2 (group 3), HF (group 4) or OF (group 5) prior to GalN prevented liver cell necrosis. Histological, histochemical and ultrastructural picture of the liver was in these groups close to normal. Only very slight hypertrophy and hyperplasia of Browicz-Kupffer cells, was seen as well as depletion of glycogen and hypertrophy of smooth endoplasmic reticulum in hepatocytes. We conclude dmPGE2, HF and OF offered impressive cytoprotection against GalN induced liver damage in rat.

16,16-Dimethylprostaglandin E2↗