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D Hollander

Publications and source records attributed to D Hollander.

At least 109 records · Page 6Linked to original sources
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

Lymphatic and portal absorption of vitamin E in aging rats.

We studied the intestinal absorption and lymphatic versus portal distribution of vitamin E and its metabolites in vivo in young (4 month), "middle-aged" (14 month), and old (24 month) male Sprague-Dawley rats. Twenty-four hours after its surgical preparation, the rat's jejunum was infused with a physiological micellar solution containing 200 nM alpha-tocopherol. Its transport rate into lymph and bile as well as its accumulation in liver and intestinal tissues was measured. Lymphatic transport of vitamin E increased from 92 to 269 pmol/5 hr and bile appearance of vitamin E and its polar metabolites increased from 230 to 298 pmol/5 hr as rats aged. Tissue accumulation of the vitamin in the small intestine and liver increased significantly with aging (P less than 0.05). Total absorption of the vitamin and its intestinal metabolites increased from 5912 pmol/5 hr in young rats to 16,467 pmol/5 hr in old rats (P less than 0.01). Absorption expressed as a percentage of infused alpha-tocopherol increased from 19.7% at 4 months to 54.9% at 24 months. These studies demonstrate an aging-associated increase in the total amount of vitamin E absorbed and a shift from portal to lymphatic transport. These changes may represent a salutary adaptive increase in the systemic availability of vitamin E with aging.

Absorption↗
PubMed1989

Mechanisms of linoleic acid uptake by rabbit small intestinal brush border membrane vesicles.

We examined the initial transport of a long-chain unsaturated fatty acid, linoleic acid, by brush border membrane vesicles isolated from rabbit small intestine. This preparation allowed us to examine the transport of linoleic acid across the brush border membrane without the effect of the unstirred water layer or cytosol binding proteins. Linoleic acid was solubilized in a 2 mM taurocholate solution which did not compromise the functional integrity of the vesicles. Linoleic acid uptake in the range of 1 to 100 microM followed passive diffusion kinetics. Time course study showed that linoleic acid uptake reached maximal levels during the initial 15 seconds. Although the amount of linoleic acid accumulated in the vesicles diminished over the next 30 minutes, the molar quantity was still twentyfold higher than that of D-glucose (6.5 vs 0.33 nmol/mg protein). Uptake of D-glucose by the vesicles demonstrated typical osmotic responsiveness. We found no osmotic effect on linoleic acid uptake. Hypotonic lysis of membrane vesicles loaded with linoleic acid released 40% of the fatty acid. We concluded that a major portion of the accumulated fatty acid was bound to or incorporated into the membrane itself while ca. 40% did traverse the membrane and accumulated in the intravesicular space as nonmicellar aggregates. The known inhibitors of anion transport, diisothiocyanatostilbene and isothiocyanatostilbene did not change the transport of linoleic acid. We conclude that, in the absence of an unstirred layer or cytosol proteins, linoleic acid transport at up to 100 microM concentration is passive with rapid accumulation both by the cell membrane and the lumen of vesicles.

Animals↗
PubMed1989

Intestinal permeability in patients with Crohn's disease and their healthy relatives.

The healthy relatives of patients with Crohn's disease were previously found to have increased intestinal permeability to polyethylene glycol 400. To determine whether the abnormal permeability is uniquely detectable by polyethylene glycol 400, we studied the intestinal permeability of three new probes (lactulose, rhamnose, and mannitol) in 25 patients with Crohn's disease, 41 of their healthy relatives, and 29 normal controls without a family history of inflammatory bowel disease. Patients with Crohn's disease had increased lactulose permeability when compared with relatives or controls. Lactulose absorption by patients with Crohn's disease was 0.41% +/- 0.07% (mean +/- SE), whereas that of their relatives and unrelated controls was 0.28% +/- 0.03% and 0.26% +/- 0.03%, respectively. There was no significant difference between the relatives and controls, but both groups differed from the patients (p less than 0.05 and p less than 0.025, respectively). The patients' lactulose/rhamnose ratio was 70.5% +/- 9.2% vs. 37.2% +/- 3.3% in relatives and 40.6% +/- 5.7% in unrelated controls (p less than 0.0005 and p less than 0.0025, respectively). The two intermediate-sized probes, rhamnose and mannitol, did not detect permeability differences among the three groups. The inability of lactulose, rhamnose, or mannitol to detect permeability abnormalities in healthy relatives of patients with Crohn's disease suggests that these probes penetrate the intestinal barrier by routes or mechanisms that are different from those of polyethylene glycol 400. Lactulose, in particular, detects permeability changes in patients with intestinal inflammation, and polyethylene glycol 400 is able to detect permeability changes in the health relatives of our patients. These data indicate that permeability may be abnormal as a secondary result of inflammation, or as a result of a primary genetic abnormality.

Adult↗
PubMed1989

Mechanisms of polyethylene glycol 400 permeability of perfused rat intestine.

Abnormal permeability to polyethylene glycol 400 (PEG 400) has been demonstrated in various disorders with defective intestinal barrier functions. To understand the basic mechanisms of PEG 400 permeability, we compared PEG 400 permeation in different segments of the intestine and studied the kinetics and influence of intraluminal factors on PEG 400 absorption in vivo in perfused intestinal segments of the rat. The permeation rate of PEG 400 was dependent on the luminal concentration (y = 12.99x + 3.5; r = 0.97), indicating that passive movement is the mechanism involved in PEG 400 absorption. Changing the perfusate pH from 6 to 7.4 or modifying the unstirred water layer resistance by changing luminal flow rate did not affect PEG 400 absorption. When luminal osmolarity was varied from 0.225 to 0.6 osmol/L, higher osmolarity decreased both water and PEG 400 absorption (p greater than 0.01). The relationship between PEG 400 and water absorption at different osmolarities was linear (y = 0.9x + 5.7; r = 0.98). At a luminal osmolarity of 0.3 osmol/L 43% of PEG 400 permeation was mediated by passive diffusion and 57% was mediated by solvent drag. Increasing water absorption by decreasing luminal osmolarity resulted in proportional increase of PEG 400 permeation through solvent drag or convection. The solvent drag reflection coefficient (sigma f) for PEG 400 permeation of the jejunum was 0.1. Taurocholic acid (10 mM) alone or with oleic acid (2.5 mM) did not affect PEG 400 absorption. Permeabilities of 1 mM PEG 400 and water were similar in jejunum and ileum but were markedly increased in the colon (p greater than 0.01). These studies demonstrate that PEG 400 is absorbed by both passive diffusion and by solvent drag, with the latter accounting for a greater fraction of the absorptive drive under normal conditions. Polyethylene glycol 400 uses aqueous pathways for its permeation across the intestinal epithelium.

Animals↗
PubMed1989

Intestinal mucosal permeability and rheumatological diseases.

Rheumatological disorders frequently have gastrointestinal manifestations and, conversely, intestinal disorders frequently have rheumatological manifestations. The possibility of altered intestinal permeability in arthritic patients may provide the bridge needed to link the two organ systems. The normal intestine absorbs nutrients and excludes the remaining material. If the intestine were less discriminating or 'leaky' then material normally excluded would be able to cross the intestinal mucosa into the lamina propria. An inflammatory response to these antigens, be they dietary, bacterial, or viral in origin, could produce either local or systemic disease. This would depend upon the type of immunological response and the cross-reactivity between the host's antigens and the absorbed antigens. This theory could account for the postulated relationship between intestinal abnormalities and the pathogenesis of some forms of arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
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

Effect of experimental azotemia on intestinal transport of butyric acid.

Earlier studies have revealed an impairment of jejunal absorption of long chain fatty acids in experimental uremia. We investigated the intestinal absorption of butyric acid which is a short chain fatty acid in experimental renal failure (RF). Sprague-Dawley rats were randomized into the RF group which had subtotal nephrectomy, a sham-operated control group, and a pair-fed group. In vivo recirculating perfusion (n = 5) and in vitro everted sac incubation (n = 8) were employed. The in vitro experiments were repeated substituting the serosal buffer by either predialysis or postdialysis sera from uremic individuals, or normal serum (n = 10). The rate of in vivo butyric acid absorption was significantly lower while the in vitro absorption was significantly higher in the RF group than those observed in the sham-operated and pair-fed groups which showed comparable values. The normality of butyric acid absorption in the pair-fed animals despite comparable weight loss with the RF group tends to exclude anorexia and weight loss as a cause of altered butyric acid transport in RF animals. The disparity between the in vivo and in vitro data is suggestive of an inhibitory influence of uremic environment which is present in vivo and absent in vitro. This viewpoint was corroborated by the observed fall in butyric acid absorption by sacs containing predialysis uremic serum as compared with those containing normal or postdialysis sera. The latter further suggests that the inhibitory factor(s) is dialyzable.

Animals↗
PubMed1989

Polyethylene glycol 900 permeability of rat intestinal and colonic segments in vivo and brush border membrane vesicles in vitro.

Increased intestinal absorption of medium-sized aqueous probes has been found in patients with a variety of disorders. We studied the physiologic control mechanisms, intestinal regions, and effects of lumenal factors on the intestinal absorption of polyethylene glycol (PEG) 900 in the rat in vivo and in rabbit brush border membrane vesicles (BBMVs). The kinetics of PEG 900 intestinal absorption were compatible with simple passive diffusion. Because transport across BBMVs was minimal, we concluded that transport of PEG 900 is mostly through the paracellular tight junctions. Absorption was highest in the midcolon (104.3 +/- 9.5 mumol/100 mg protein per hour vs 9.1 +/- 1.2 mumol/100 mg protein per hour in the jejunum). Absorption was decreased by higher lumenal osmolarity (greater than 400 mOsm/L) after the additions of 2.5 to 5.0 mmol/L chenodeoxycholate or 2.5 mmol/L lysolecithin, or at higher lumenal flow rates (greater than 1 ml/minute), higher lumenal pressure (7.5 cm H2O),or higher lumenal pH (8.0). Lipid solubility of PEG 900 was less than 0.00079%. Under all experimental conditions, PEG net absorption followed changes in water transport. When water transport changed from absorption to secretion, PEG absorption decreased. When water absorption increased, PEG 900 absorption increased in parallel. We conclude that PEG 900 is absorbed by passive diffusion that is modulated by solvent drag and is maximal in the midcolon. Transport directly across cell membranes is mimimal, but overall PEG 900 permeability is closely linked to water absorption by solvent drag and takes place primarily through the paracellular junctions. We propose that these features and mechanisms of PEG 900 transport make PEG 900 a suitable probe molecule for studying intestinal permeability changes.

Animals↗
PubMed1988

Mechanisms of carrageenan injury of IEC18 small intestinal epithelial cell monolayers.

Hydrolyzed carrageenan is used to induce ileocecal inflammation in laboratory animals. We used ileal epithelial cell monolayer cultures (IEC18) to study the cellular and paracellular injurious effects of hydrolyzed carrageenan via an examination of its effects on deoxyribonucleic acid synthesis, chromium release, and cell morphology. Phase-contrast microscopy showed that carrageenan-treated cells initially contracted and pulled away from neighboring cells. Cell and viability counts illustrated that hydrolyzed carrageenan retarded cell growth and eventually caused cell death. [3H]Thymidine incorporation revealed that hydrolyzed carrageenan at a concentration of 0.25 g/L inhibited deoxyribonucleic acid synthesis by 20% during a 5-h labeling period in 1-wk-old confluent monolayers. Chromium 51 release assay demonstrated that a 22-h exposure to 0.75 g/L of hydrolyzed carrageenan induced the release of 30% of the 51Cr trapped in 1-wk-old confluent monolayers. Scanning electron microscopy showed that the disruption of cellular junctions occurred before cell membrane injury. When we treated the monolayers with drugs commonly used for the treatment of inflammatory bowel disease, including prednisolone, 5-aminosalicylic acid, metronidazole, and 6-mercaptopurine, we were not able to demonstrate a reduction in carrageenan-induced cell injury; however, catalase at 1 mg/ml decreased carrageenan cytotoxicity. These studies demonstrate that hydrolyzed carrageenan produces intestinal epithelial injury in a time- and dose-dependent fashion. Morphologic injury starts at the site of cell junctions and eventually affects cell membrane integrity. Drugs commonly used to treat inflammatory bowel disease do not inhibit carrageenan injury in this cell model system, although catalase does decrease injury.

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↗
PubMed1988

The mechanisms of intestinal absorption of the carcinogen MNNG (N-methyl-N'-nitro-N-nitrosoguanidine).

We studied the characteristics and mechanisms of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) intestinal absorption and the interaction between bile acids and fatty acids and MNNG absorption rate in vivo in male Sprague-Dawley rats. We perfused a segment of the proximal small bowel with a physiological solution containing MNNG to assess its basic kinetics and the influence of some physiological and dietary factors on carcinogen absorption. We found that MNNG was absorbed by simple passive diffusion. Transport of MNNG was the highest at pH 6.0. The addition of the bile salt, taurocholate by itself, greatly increased MNNG absorption, while the addition of the long-chain unsaturated fatty acids, oleic and linoleic, decreased the rate of absorption of MNNG. The phospholipid lecithin addition to the perfusate did not change the rate of MNNG absorption. Induction of dietary vitamin A deficiency (serum vitamin A level decreased from 40.9 to 13.7 micrograms/dl) did not change the absorption rate of MNNG. These studies demonstrate that bile acids, dietary fatty acids, and the pH of the intestinal content can modify the rate of absorption of this carcinogen by the small intestine. Since initial intestinal absorption determines serum levels and subsequent reabsorption and enterohepatic cycling determines long-term lumenal levels, serum levels, and total body content, factors which modify the rate of intestinal absorption of MNNG could also modify its carcinogenicity.

Animals↗