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Biomedical subjects

D Hollander

Publications and source records attributed to D Hollander.

At least 127 records · Page 7Linked 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

Effects of dietary fatty acid saturation on serum and tissue cholesterol concentrations and fecal sterol excretion: a chronic metabolic study in the rat.

We studied the effect of the degree of fatty acid saturation on cholesterol metabolism in rats fed either a low cholesterol-low fat diet (control group), high cholesterol-low fat diet (Chol group), high cholesterol-high saturated fat diet (Chol-SF) or high cholesterol-high PUF diet (Chol-PUF). The highest serum cholesterol levels were found in the Chol-SF group. No significant difference in serum cholesterol was found between the Chol and Chol-PUF groups. The Chol-PUF group showed the greatest accumulation of cholesterol in the liver. There was no significant difference in fecal excretion of acidic sterols, cholesterol and coprostanol between the Chol-PUF and Chol-SF groups. We conclude that in chronic feeding experiments in rats: a) high dietary cholesterol intake results in hypercholesterolemia; b) the hypercholesterolemia is accentuated by high dietary SF but is unaffected by PUF; c) addition of PUF to high cholesterol diet leads to massive cholesterol accumulation in the liver which can partly account for the apparent hypocholesterolemic effect of PUF relative to SF; and d) differences in serum and tissue cholesterol levels between SF and PUF supplemented groups are unlikely to be due to their effects on fecal sterol excretion.

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

Aging-associated increase in intestinal permeability to polyethylene glycol 900.

Effect of aging on the intestinal permeability to medium size [3H]polyethylene glycol (PEG 900) was examined in vivo by gavage and in vitro in intestinal everted sacs of rats ranging in age from 5 to 102 weeks. Rats were gavaged with PEG 900 solution and urinary recovery of PEG 900 was measured for 6 hr in order to assess its absorption. Young rats, 5-15 weeks of age, absorbed 1-1.3% of administered PEG 900. In contrast, rats 35-102 weeks of age absorbed 1.8-2.4% of administered PEG 900 (P less than 0.05 vs younger animals). The increased absorption of PEG 900 with aging is due to changes in intestinal permeability since the total uptake (serosal appearance + tissue uptake) of PEG 900 by jejunum, ileum, and colonic everted sacs was significantly higher (P less than 0.05) in older rats (100 weeks) than young rats (9 1/2 weeks), while urinary excretion of PEG 900 following intravenous injection was the same in the two age groups. These studies indicate that aging rats have diminished capacity to exclude larger size molecules from penetrating the intestinal mucosa. The diminished barrier functions of the small intestine with aging may allow antigenic or mutagenic compounds to reach the systemic circulation.

Aging↗
PubMed1987

Intestinal permeability changes in rodents: a possible mechanism for degraded carrageenan-induced colitis.

Rats and guinea-pigs were treated with degraded carrageenan (50 g/litre in the drinking-water) and their intestinal permeability was studied at weekly intervals over the last 4 wk of the test period by determining the recovery of orally administered tracer doses of [3H]polyethylene glycol (PEG-900) or D-[3H]mannitol in 16-hr urine collections. A freely diffusible dye, Azure A, was administered simultaneously to compensate for non-intestinal factors that could modify renal excretion. Animals were killed after a total treatment period of 5 months for rats and 6 wk for guinea-pigs. After 3 wk of carrageenan treatment, excretion of PEG-900 (expressed as a ratio of the Azure A excretion) in guinea-pigs showed a statistically significant increase over that in the control group. At autopsy, the caeca showed numerous macroscopically visible erosions of the entire mucosal surface and histological examination showed ulcerations largely in the mucosa with abscesses in the crypts. Although no such histological changes were seen in the intestines of the treated rats, even after 5 months, a statistically significant increase in PEG-900 excretion was again found compared with the control group. This increase did not occur when deoxycholate was administered with the carrageenan solution. No effect of carrageenan treatment on mucosal permeability to D-[3H]mannitol was demonstrated in either species. The results suggest that degraded carrageenan-induced colitis could be a result of increased intestinal permeability, since ingestion of this polysaccharide by rats increased PEG-900 absorption without causing mucosal damage.

Animals↗
PubMed1987

A comparison of intestinal permeability between humans and three common laboratory animals.

Intestinal permeability of humans and three species of experimental animals was assessed by the oral administration of the three non-metabolizable sugars: lactulose, rhamnose and mannitol and collecting all the urine produced in a specified time. The total percentage recovery of the permeability markers was determined by high performance liquid chromatographic assays of urinary aliquots. The permeability of the human gut to mannitol was substantially greater than that of rats, guinea pigs, or hamsters (18-, 6- and 29-fold increases, respectively). The permeability to lactulose in humans was somewhat less than that found in guinea pigs (P less than 0.05), but three times greater than that found in rats or hamsters (P less than 0.001). Human rhamnose permeability was substantially greater than that of rats, guinea pigs or hamsters (6-, 2.5-, and 7-fold increases, respectively). The results suggest that the permeability of the human gut to probe molecules is considerably different from that of three common laboratory rodents, but is closest to that of guinea pigs. Possible species differences in the physiological factors which control permeability are discussed.

Adult↗
PubMed1987

Toxic effect on the rat small intestine of chronic administration of asbestos in drinking water.

Sprague-Dawley rats were given a 0.5 g/l Chrysotile asbestos solution in their drinking water (approximately 7 mg/day ingested) for 1.5 years and compared to control rats of the same age. During this time there were no differences in weight or appearance of the asbestos-treated rats in comparison to controls maintained under the same conditions. However, when in vivo intestinal permeability studies were performed using a gavage/urinary collection technique, some significant changes were noted. The recovery of lactulose in the urine of asbestos-treated rats was 0.66 +/- 0.07%, significantly less than that of the controls (1.01 +/- 0.08, P less than 0.005). The recovery of mannitol was similarly decreased (2.2 +/- 0.28 vs. 3.0 +/- 0.17, P less than 0.02), but that of rhamnose was unchanged. Creatinine clearance studies indicated that there was no impairment of kidney function in the asbestos-treated group and polarized light microscopy did not reveal any asbestos fibers in sections of the small bowel. The results suggest that the chronic exposure of rats to asbestos fibers in the drinking water results in a decreased ability of the intestine to absorb some non-metabolizable sugars.

Animals↗
PubMed1987

Thalamic abscess: a stereotactically treatable lesion.

A 69-year-old man developed abdominal pain, fever, shaking chills and acute hemiplegia. Computed tomography (CT) scanning demonstrated a hematoma within a thalamic space-occupying lesion having the radiological characteristics of a malignant glioma. Low-grade fever and leukocytosis persisted and follow-up CT scanning showed ring enhancement of the thalamic lesion and ependymitis suggesting a cerebral abscess. Stereotactic aspiration achieved drainage of the abscess and relief of mass effect and provided pus from which a causative organism was identified and treated with appropriate antibiotics. Contrast-enhanced CT scan should be obtained in cases of hemorrhage within mass lesions and tissue diagnosis should be achieved even in deep brain regions, as this can be accomplished safely using stereotactic techniques.

Aged↗
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

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

Inhibitory effect of bile salts on the enterohepatic circulation of methotrexate in the unanesthetized rat: inhibition of methotrexate intestinal absorption.

The effect of conjugated and unconjugated bile salts on the intestinal absorption of methotrexate (MTX) in the unanesthetized rat was investigated using a recycling perfusion technique. We initially determined the general characteristics of MTX absorption in vivo. Absorption of low (0.5 microM) and high (6 microM) concentrations of MTX was linear with time for 60 min perfusion and occurred at rates of 0.2 and 1.65 nmol/100 cm dry length/min, respectively. Absorption of 0.5 microM MTX was pH-dependent and increased with decreasing perfusate pH. Absorption of MTX involves two processes: (1) a saturable process with a Kt of 0.98 microM, and (2) a nonsaturable diffusion process. The unconjugated deoxycholate and the conjugated taurocholate inhibited the intestinal absorption of 1 microM MTX in a concentration-dependent manner. The inhibitory effect of bile salts was reversible, and was not due to damage to the intestinal mucosa. The structural analogues folic acid and 5-methyltetrahydrofolate and the organic anions rose bengal and sulfobormophthalein were also inhibitory to MTX absorption. This study demonstrates that a variety of organic anions inhibit MTX intestinal absorption. The possible therapeutic importance of this observation is discussed.

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↗