PubMed Health⌕ Search

Biomedical subjects

D Hollander

Publications and source records attributed to D Hollander.

At least 91 records · Page 5Linked to original sources
PubMed1991

Is the small intestinal epithelium truly "tight" to inulin permeation?

In this study, we evaluated the "leakiness" of intestinal epithelium through examination of small intestinal absorption of inulin in vivo by perfusing rat jejunum with 10 microM inulin. In physiological conditions, we found significant absorption of inulin at a rate of 44.6 nmol.100 cm-1.h-1 or absorption of 14.7%.100 cm-1.h-1 of the amount perfused. Increasing water flux by changing the luminal osmolarity resulted in linear (y = 31.1 + 2.4x, r = 0.97) increase in absorption of inulin, indicating a significant convective component of inulin absorption. There was large permeation of inulin at net water secretion and at zero net water fluxes (31.1 nmol.100 cm-1.h-1), indicating significant absorption of inulin by diffusive movement as well. The small intestinal tissue retention of inulin occurred rapidly within the first 15 min of perfusion, and the total tissue retention remained unchanged thereafter at approximately 10.8 nmol/100 cm. 16,16-Dimethylprostaglandin E2 decreased water flux, whereas cyclooxygenase inhibitors, indomethacin and acetylsalicylate, increased water flux. Inulin absorption closely paralleled changes in water flux induced by these agents. Taurocholate also caused parallel decrease in water and inulin absorption. Varying the resistance of unstirred water layer with changing luminal flow rate, the addition of mucolytic agent acetylcysteine, or alterations of luminal pH did not affect water or inulin absorption. We conclude that inulin permeates the small intestinal epithelium in significant amounts under normal physiological conditions, presumably through the paracellular pathways utilizing aqueous channels.

16,16-Dimethylprostaglandin E2↗
PubMed1991

Eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan: muscle biopsy findings in 4 patients.

Muscle biopsies of 4 patients with the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan showed lymphocytic infiltrates with occasional eosinophils largely restricted to interstitial fibrous tissue and perivascular areas. There was inflammation and fibrosis of muscle spindle capsules in 3 patients. In the 2 sickest patients, there was profound muscle atrophy, affecting both muscle fiber types.

Adult↗
PubMed1990

Polyethylene glycol 400 penetration of the colonic epithelial barrier of the rat.

Permeability changes of polyethylene glycol 400 have been seen in patients with inflammatory bowel diseases. Because the colon can be involved in inflammatory bowel disease, the mechanisms, kinetics, and influence of intraluminal factors on polyethylene glycol 400 permeation of perfused colonic segments of rats were studied. The absorption rate of polyethylene glycol 400 was linearly related to its luminal concentration (r = 0.94), suggesting that passive diffusion is a significant mechanism involved in polyethylene glycol 400 absorption. Changing the perfusate pH from 6.0 to 7.5 did not affect water absorption or polyethylene glycol 400 permeation. Increasing luminal osmolarity significantly decreased water and polyethylene glycol 400 absorption (P less than 0.01). The relationship between polyethylene glycol 400 and water absorption at different luminal osmolarities was linear (r = 0.97). At luminal osmolarity of 0.3 osm/L, 14.3% of polyethylene glycol 400 absorption was mediated by passive diffusion and 85.7% was mediated by convection. The solvent drag reflection coefficient for polyethylene glycol 400 in the colon was 0.03. Taurocholic acid (10 mmol/L) and chenodeoxycholic acid (5 mmol/L) decreased polyethylene glycol 400 and water absorption (P less than 0.01). Addition of 1 micrograms/mL of 16,16-dimethyl prostaglandin E2, 2 mmol/L of dibutyryladenosine-3',5'-cyclic monophosphate, or 10 mmol/L of aminophylline significantly decreased water and polyethylene glycol 400 absorption (P less than 0.01). These studies demonstrate that polyethylene glycol 400 permeation of the colon is mediated by both passive diffusion and solvent drag. Convective absorption is the major mechanism of polyethylene glycol 400 permeation of the colon. Polyethylene glycol 400 permeation is modified by bile acids, prostaglandins, and cyclic nucleotides through changes in water flux.

16,16-Dimethylprostaglandin E2↗
PubMed1990

PEG 400, a hydrophilic molecular probe for measuring intestinal permeability.

There is a widely held misconception that low-molecular-weight polyethylene glycols are "highly lipophilic" permeability probes and therefore are transported across lipid cell membranes. The relative lipophilicity of polyethylene glycols 400 and 600 were examined by determining their partition coefficients (Kd) in water and organic solvents of increasing relative polarity. The Kd of polyethylene glycol 414 between hexane and water was 0.000015, indicating that there are only 1.5 parts of polyethylene glycol 414 in hexane for 100,000 parts of polyethylene glycol 414 in water. When the Kd was determined in organic solvents with increasing relative polarity or "water character", there was a linear increase in Kd. The relative urinary recovery of individual molecular weight fractions of polyethylene glycol 400 in normal volunteers was analyzed. After oral ingestion, there was a progressive decrease in relative urinary recovery of increasing molecular weight fractions of polyethylene glycol 400 suggesting that increase in the molecular size limited polyethylene glycol intestinal permeability. There was excellent correlation between the relative urinary recovery and the hydrophilicity of the intravenously administered polyethylene glycol 400 fractions. It is concluded that polyethylene glycols 400 and 600 are strongly hydrophilic. Since partitioning of polyethylene glycol into lipid phase is negligible in lipid/water mixtures, they are unlikely to be transported via lipid pathways. The intestinal permeability of polyethylene glycols are governed by their molecular size, and once in circulation their urinary excretion appears to be governed in part by their plasma or water solubility.

Adult↗
PubMed1990

Intestinal absorption of arachidonic acid in experimental azotemia.

The effect of renal failure (RF) on intestinal absorption of dietary fatty acids is not known. We studied the intestinal absorption of arachidonic acid (AA) in rats with experimental short-term (2 weeks post-subtotal nephrectomy) and long-term (5-6 weeks post-subtotal nephrectomy) RF. The results were compared with those obtained in sham-operated animals on liberal food intake (NL) and in those pair-fed (PF) with the respective RF groups. In vivo perfusion and in vitro incubation experiments were performed at a wide range of AA concentrations. The rates of AA transport determined both in vivo and in vitro were significantly lower in the short-term RF group than those found in the NL controls and the PF animals who showed comparable values. In contrast animals with long-term RF exhibited an increased rate of AA transport as compared with the respective controls. The observed changes in the transport rates appeared to parallel directional changes in mucosal mass which was reduced in animals with short-term RF and restored in those with long-term RF.

Animals↗
PubMed1990

Influence of aging on vitamin A transport into the lymphatic circulation.

Vitamin A is a lipid soluble essential dietary micronutrient. Because aging individuals have elevated serum levels of vitamin A, we tested the intestinal absorptive capacity of the vitamin in aging rats by measuring the appearance rate of vitamin A in the lymphatic circulation as a measure of intestinal absorption. We infused the vitamin in a physiological concentration of 350 nM into the proximal jejunum of groups of Sprague-Dawley rats 2 to 23 months of age. Lymph was collected for 6 h and vitamin A radioactivity was measured. Lymph flow rate over 24 h ranged from 16 +/- 3.1 ml in the oldest to 21.5 +/- 2.4 ml in the youngest animals. Vitamin A transport into lymph was highest at 23 months of age, reaching 7869 +/- 154 pmol/6 h as compared to 6732 +/- 106 pmol/h at 2 months (p less than .01). The increase in vitamin A absorption with aging represented an increase from 35.6% of the infused vitamin at 2 months to 41.6% at 23 months of age. Because of the cumulative storage of vitamin A in the liver this increase in absorption and lymphatic appearance is of nutritional and metabolic significance. Increased lymphatic appearance of the vitamin could explain its higher absorption and serum levels in aging individuals.

Aging↗
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

Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids. Influence of non-steroidal anti-inflammatory drugs.

Polyethylene glycol 400 (PEG 400) is a clinically useful intestinal permeability probe whose rate of intestinal permeation is influenced in part by solvent drag. As mucosal prostanoids are increased in inflammatory bowel disease and affect water transport we examined the possible relationship between prostaglandin E2 (PGE2) and the inhibitors of endogenous prostaglandins--the non-steroidal anti-inflammatory drugs (NSAIDS)--on PEG 400 absorption in vivo using segmental perfusion of rat small intestine. We found that the addition of exogenous PGE2 in concentrations of 0.5, 1.0, and 1.5 micrograms/ml significantly (p less than 0.01) decreased PEG 400 and water absorption. Addition of 5 mmol/l of the cyclooxygenase inhibitors acetylsalicylic acid (ASA) or indomethacin in concentrations 2.5 or 5.0 mmol/l to the perfusate significantly (p less than 0.01) increased PEG 400 and water absorption. The simultaneous addition of 1.0 micrograms/ml of exogenous PGE2 to the perfusate with 5 mmol/l of ASA or with 2.5 mmol/l of indomethacin reversed the increase of PEG 400 and water transport (p less than 0.01). There were no differences in PEG 400 and water absorption when PGE2 was given alone or in combination with ASA or indomethacin. This study suggests that endogenous or exogenous prostanoids play an important role in the regulation of PEG 400 permeation. PGE2 and NSAIDS modify PEG 400 permeation in parallel with changes in water transport indicating that their effect on permeability is through changes in solvent drag. These findings provide a mechanism which might explain the increase in PEG 400 intestinal permeability in Crohn's disease patients and the increase in intestinal permeability found in patients receiving NSAIDS.

16,16-Dimethylprostaglandin E2↗
PubMed1990

Uptake of biotin by native Xenopus laevis oocytes.

The present study examined biotin uptake by Xenopus laevis oocytes in vitro. Uptake of low (0.03 microM) and high (10 microM) concentrations of biotin was linear with time for up to 4 h of incubation and occurred with little initial binding to oocytes. Uptake of biotin was dependent on extracellular Na+ concentration [Na+]o and was severely inhibited when Na+ was replaced by other monovalent cations [choline, tetraethylammonia, Li+, and tris(hydroxymethyl)aminomethane]. The initial rate of biotin uptake was saturable as a function of concentration with an apparent Michaelis constant of 3.9 +/- 0.5 microM and maximum velocity of 1,559 +/- 70 fmol.oocyte-1.h-1. Addition to the incubation medium of biotin structural analogues desthiobiotin and thioctic acid caused significant and concentration-dependent inhibition in the uptake of [3H]biotin. This inhibition was found to be competitive in nature with inhibition constant values of 9 and 17.5 microM. In contrast, neither the structural analogue biocytin nor biotin methyl ester (compounds in which the carboxyl group of the valeric acid moiety is blocked) showed any effect on the uptake of [3H]biotin. Biotin uptake was significantly blocked by the metabolic inhibitors dinitrophenol, cyanide, and azide and by incubation at 4 degrees C. Also, the sulfhydryl group blocker p-(chloromercuri)phenylsulfonate caused significant inhibition in biotin uptake. These results demonstrate that Xenopus oocytes possess an uptake system for biotin in its cell membrane that is Na+, energy, and temperature dependent. These characteristics of biotin uptake are similar to those reported in mammalian cells. It is suggested that Xenopus oocytes might be a useful in vitro model system to study the details of the mechanisms and regulation of biotin movement across biological membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Characterization of structural xenobiotic modifications in proteins by high sensitivity tandem mass spectrometry. Human hemoglobin treated in vitro with styrene 7,8-oxide.

Alkylation of DNA by xenobiotic agents, or their electrophilic metabolites, is believed to be the major initiating process that may result ultimately in carcinogenesis. The study of hemoglobin alkylated in vivo by chemical carcinogens has previously been proposed as an indicator for DNA alkylation. Xenobiotically modified proteins, however, are not readily amenable to conventional methods for amino acid sequencing. Tandem mass spectrometry allows unambiguous structural elucidation of chemically modified proteins. Styrene is a widely used chemical in the plastics industry and its major metabolite, styrene 7,8-oxide, is both mutagenic and carcinogenic in rodents. Human hemoglobin was modified in vitro with styrene 7,8-oxide and digested with trypsin. Tryptic peptides from unmodified hemoglobin were isolated by high performance liquid chromatography, and their molecular weights were determined by liquid secondary ion mass spectrometry. This allowed confirmation of the known sequence of the protein and provided a reference for the identification of modified peptides. High performance tandem mass spectrometry of modified peptides allowed unambiguous assignment of specific residues modified. The externally accessible histidines were found to be the dominant sites for alkylation at high modification levels of the protein.

Alkylation↗
PubMed1989

Pathways of gastrointestinal protection and repair: mechanisms of action of sucralfate.

Protection, i.e., prevention of major lesions and the mechanisms of repair/healing of major tissue loss in the gastrointestinal mucosa, are multifactorial processes. Conceptually, it is useful to categorize the components and mechanisms of gastroprotection and distinguish between: (1) Preservation of existing cells either by enhanced resistance of cells or by decreased exposure to damaging agents that can be achieved by maintenance of proper blood flow, vascular permeability, motility, mucus and bicarbonate secretion. If these mechanisms fail and tissue necrosis ensues, (2) replacement of lost tissue is achievable by either the original cells (e.g., epithelia), by cell migration (restitution) and proliferation (regeneration), and/or by connective tissue repair (e.g., fibroblasts, collagen) through cell proliferation and production of extracellular matrix. For acute gastroprotection ("cytoprotection"), maintenance of blood flow in the upper mucosa and epithelial restitution are listed as key mechanisms. For the long-term safeguarding of the mucosa, proper mucus and bicarbonate secretion, as well as ability to respond by cell proliferation, are the proposed key mechanisms of mucosal defense. The mechanisms of action of sucralfate are also multifactorial. The acute gastroprotection by sucralfate is a prostaglandin- and sulfhydryl-sensitive process: after early protection of microvasculature and maintenance of blood flow, along with direct or indirect preservation of the proliferative zone, rapid restitution repairs the initial epithelial defect. The mechanisms of accelerated healing by sucralfate of chronic ulcers include enhanced mucus and bicarbonate secretion, increased ability of mucus to maintain pH gradient, stimulated binding of epidermal growth factor and other growth factors, and maintained or enhanced blood flow resulting in increased cell proliferation leading to granulation tissue formation and re-epithelialization. The slight direct antipeptic and bile-acid binding property of sucralfate might also contribute to its ability to accelerate ulcer healing.

Animals↗