Biomedical subjects

D Hollander

Publications and source records attributed to D Hollander.

At least 145 records · Page 8Linked to original sources

PubMed1986

Acute gastric mucosal injury: pathogenesis and therapy.

Our knowledge concerning the pathogenesis and treatment of acute gastric mucosal injury is rapidly expanding. The gastric mucosa maintains its integrity despite exposure to hydrochloric acid, pepsin, bile, and potentially damaging ingested substances. The balance between gastric mucosal injury and repair is a dynamic process involving multiple complex mechanisms. Clinically, when this process breaks down, acute gastric musocal injury results. Therapy of this disorder has included the use of antisecretory drugs and antacids, while more recent research efforts are exploring the use of cytoprotective agents.

Acute Disease↗

PubMed1986

Transport of butyric acid in vascularly perfused anuran small intestine: importance of pH and anion transport.

Butyric acid transport was studied in the isolated, vascularly perfused frog small intestine. At luminal butyric acid concentrations of 5-50 mM, absorption was a nonlinear function of the luminal concentration, whereas the relationship of absorption to concentration remained linear at 0-1,000 microM. The most important factor regulating the rate and direction of butyric acid transport was the pH. We used unidirectional flux analysis to determine net transport across the epithelium while the pH of the luminal or vascular compartments was changed. We found a four- to fivefold decrease in butyric acid transport into the portal circulation as the lumen pH was increased from 6.0 to 8.0. The pH of the vascular perfusate influenced the vascular-to-lumen transport of butyric acid in the same proportions. The second important regulatory factor of butyric acid transport was the 4,4'-diisothiocyananostilbene-2,2'-disulfonic acid (DIDS)-sensitive anion transport protein. DIDS added to the lumen at 10(-6) M decreased butyric acid transport by approximately 40% at pH 7.4. DIDS also inhibited butyric acid transport when added to the vascular perfusate or when transport was measured in a vascular-to-lumen direction. We suggest that, at the relatively low pH of the proximal small intestine, butyric acid becomes protonated and lipophilic and is mainly transported directly through the cell membrane. At the more alkaline pH of the distal small intestine butyric acid is in the ionized form and transport by the DIDS-sensitive anion transport protein may predominate.

3-O-Methylglucose↗

PubMed1986

Protection against alcohol-induced gastric mucosal injury by aluminum-containing compounds--sucralfate, antacids, and aluminum sulfate.

Previously, we demonstrated that both antacids and sucralfate can protect the gastric mucosa against alcohol injury. Since these compounds contain aluminum, we studied whether other aluminum compounds have cytoprotective properties as well. Fasted rats were pretreated intragastrically with A) 0.9% NaCl, B) sucralfate, C) aluminum-magnesium antacid gel, D) Al2(SO4)3, E) Al(OH)3, and 1 h later they received 2 ml 100% ethanol by gavage. The stomach was removed and assessed for injury 3 h after ethanol administration. Control (group A) rats had 39 +/- 3% gross mucosal injury, which was reduced to 5 +/- 1% with sucralfate, 7 +/- 1% with Al2(SO4)3, 12 +/- 2% with Al(OH)3, and 16 +/- 2% with aluminum-magnesium antacid gel pretreatment. Microscopic surface epithelial injury and submucosal edema were seen in all five groups, while deep mucosal necrosis was largely prevented by pretreatment in groups B to E. These findings indicate that aluminum in a wide variety of molecular forms can protect the gastric mucosa against alcohol injury.

Alum Compounds↗

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↗

PubMed1986

Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor.

The cause of Crohn's disease is unknown, although alterations in intestinal permeability may play a primary role. Because we were interested in permeability changes that occur before the onset of intestinal inflammation, we took advantage of the known genetic predisposition to this disease and studied not only patients with Crohn's disease, but their clinically unaffected relatives as well. Intestinal permeability was assessed using the marker polyethylene glycol-400 ingested with a standard meal. We found that 17 normal volunteers absorbed 215 +/- 29.6 mg (mean +/- SE), whereas 11 patients with Crohn's disease absorbed 514 +/- 94.7 mg and their 32 healthy relatives absorbed 566 +/- 62.4 mg. The twofold increase in permeability of patients and their relatives (p less than 0.005 compared with controls) indicates that the intestinal defect in the ability to exclude larger sized molecules is not secondary to clinically recognized intestinal inflammation, but is a primary defect that may be an etiologic factor in this disease.

Adolescent↗

PubMed1986

Selective impairment of nutrient absorption from intestines with chronic venous hypertension.

Malnutrition is frequently associated with advanced cirrhosis. To investigate the role of portal hypertension in nutritional impairment, we developed an animal model to isolate and characterize the effects of chronic intestinal venous hypertension on intestinal nutrient absorption. We performed mesenteric arteriovenous anastomosis combined with portal vein banding in rats. Hepatic architecture and excretory function (bile flow and bile salt output) were unaltered, while severe and persistent intestinal venous hypertension was produced. We then measured in vivo absorption rates of three test nutrients (vitamin D3, valine, and tryptophan) and water. Vitamin D3 absorption was significantly impaired by intestinal congestion, while amino acid absorption was unaffected. Splanchnic hypertensive rats absorbed less water than controls. We conclude that chronic intestinal venous hypertension alone selectively impairs nutrient absorption.

Animals↗

PubMed1986

Is arachidonic acid protected gastric mucosa more resistant to rechallenge with a second dose of ethanol?

In our previous studies we found that pretreatment with arachidonic acid protects the gastric mucosa against ethanol-induced injury. In the present experiments we studied whether: gastric mucosa protected with arachidonic acid against ethanol injury is more resistant to a subsequent second ethanol injury, and whether a second ethanol dose produces further damage of the nonprotected damaged gastric mucosa in a control group. We found that: rechallenge with a second ethanol dose increases the extent of gastric mucosal necrosis in control rats; once protected (with arachidonic acid) the gastric mucosa is more resistant to subsequent ethanol rechallenge but some deep necrosis occurs and restoration of the surface epithelium is somewhat impaired when compared to the initial injury and repair. Thus, pretreatment of the gastric mucosa with a prostaglandin precursor dietary essential fatty acid confers excellent protection against alcohol damage with some residual protective activity against a subsequent rechallenge with alcohol.

Animals↗

PubMed1986

Liquid-chromatographic method for estimating urinary sugars: applicability to studies of intestinal permeability.

Sugars of exogenous origin excreted in the urine can be rapidly quantified by "high-pressure" liquid chromatography. A simple extraction with an ion-exchange resin is used to prepare the sample for analysis. Aliquots (20 microL) are chromatographed on a cation-exchange column at 85 degrees C, with water as the mobile phase. Sugars are detected with a refractive index detector. Lactulose, rhamnose, and mannitol all give discrete peaks and a linear response up to 5 g/L, with analytical recoveries from urine of 80, 62, and 80%, respectively. Precision is good, the CVs for lactulose, rhamnose, and mannitol being 2.9, 4.0, and 5.6%, respectively. The only endogenous compound consistently present in the chromatograms is urea, which does not interfere. However, glucosuria, if present, could interfere with the lactulose estimation. This method may be a simple, labor-saving means of quantifying urinary sugars in the clinical laboratory.

Carbohydrates↗

PubMed1986

New liquid-chromatographic method for measuring polyethylene glycol in urine.

The various Mr fractions of polyethylene glycol (PEG) in human urine are quantified by "high-pressure" liquid chromatography. A simple preparation step involving lyophilization and chloroform extraction of the sample is required. Aliquots (10 microL) are chromatographed isocratically in equivolume mixtures of methanol and water on a column of styrene divinylbenzene and the refractive index of the effluent is measured. The results vary linearly with the concentrations of standards up to at least 10 g/L, and the six major fractions are clearly identifiable in injected samples containing 2 g or more of total PEG per liter. As little as 4 g/L can be precisely quantified, but for assessing the individual fractions, we recommend a minimum sample concentration of 7 g/L. Analytical recovery of PEG added to urine controls was 90%. Urines collected during 6 h from 11 human subjects after each had ingested 5.6 g of PEG showed no interference from endogenous compounds. We find this method to be a simple, labor-saving means of quantifying urinary PEG in the clinical laboratory.

Adult↗

PubMed1985

Comparison of antacid, sucralfate, cimetidine, and ranitidine in protection of the gastric mucosa against ethanol injury.

The abilities of antacid (Mylanta II), sucralfate, cimetidine, and ranitidine to protect the gastric mucosa against ethanol-induced necrosis were compared in a standardized, experimental rat model. Fasted rats received pretreatment with either saline, Mylanta II, 500 mg/kg of sucralfate, 50 mg/kg of cimetidine, or 50 mg/kg of ranitidine. This was followed one hour later by intragastric administration of 2 ml of 100 percent ethanol. Gastric mucosal injury was assessed four hours after administration of ethanol by quantitation of gross mucosal necrosis, assessment of mucosal histology, and determination of intragastric blood and protein concentrations. Pretreatment with Mylanta II or sucralfate significantly reduced ethanol-induced gastric mucosal necrosis. The protective effect of sucralfate was six to 10 times greater than that of Mylanta II. H2-receptor antagonists increased ethanol-induced gastric mucosal necrosis.

Aluminum↗

PubMed1985

Does aging affect the intestinal transport of riboflavin?

Riboflavin deficiency has been reported in older individuals. The cause of this deficiency is not know but could include a decrease in the intestinal absorptive capacity for riboflavin. Therefore, we examined the intestinal absorption of riboflavin in young (3 month) and old (26 month) rats. We used in vitro jejunal everted sacs. The kinetic parameters of riboflavin absorption disclosed apparent Km of 0.37 and 0.43 microM and Vmax of 37 and 38 pmole/g initial tissue wet wt/20 min in young and old rats, respectively. These data do not demonstrate an aging associated change in the intestinal transport capacity for riboflavin. If these results are extrapolated to man, it would mean that the deficiency of riboflavin found in the elderly is not due to its intestinal malabsorption. Therefore, other mechanisms must be sought to account for the deficiency of riboflavin seen in the elderly.

Aging↗

PubMed1985

Colonic absorption of 1,2-dimethyl hydrazine (DMH) in the rat.

1,2-Dimethyl hydrazine (DMH) is absorbed in the colon by passive diffusion in the 0.1-5.0 mM concentration range. Absorption of DMH is enhanced by both conjugated and unconjugated bile acids. The presence of hydroxy-fatty acids in the colon markedly increased DMH absorption while fatty acids of different chain length did not influence absorption.

1,2-Dimethylhydrazine↗

PubMed1985

Prostaglandin protection of the gastric mucosa against alcohol injury--a dynamic time-related process. Role of the mucosal proliferative zone.

The aim of the present study was first to resolve controversies regarding the extent of prostaglandin protection ("cytoprotection") of the gastric mucosa against injury produced by 100% ethanol and second to determine time sequence and histologic, ultrastructural, and functional features of this protection. Fasted rats received intragastrically (A) 0.9% NaCl alone as a control, (B) 5 micrograms/kg of 16,16-dimethyl prostaglandin E2 dissolved in 0.9% NaCl, and (C) 100 micrograms/kg of 16,16-dimethyl prostaglandin E2 dissolved in 0.9% NaCl. Thirty minutes later, 2 ml of 100% ethanol was instilled. The gastric mucosa was assessed macroscopically, by quantitative histology, and by scanning and transmission electron microscopy for [3H]thymidine uptake, mitotic activity, ion fluxes, and gastric potential difference determined at several time intervals (between 10 min and 16 h) after ethanol administration. Between 10 min and 16 h after ethanol administration macroscopic necrosis involved 27% +/- 3% to 41% +/- 4% of the mucosal area in controls (group A), but necrosis was prevented in groups receiving 16,16-dimethyl prostaglandin E2 (groups B and C). In the control group, histology and electron microscopy showed extensive disruption of the surface epithelium and deep necrosis (greater than 0.2 mm) involving greater than 46% +/- 4% of the mucosa between 15 min and 16 h after ethanol administration. Deep necrotic lesions were completely prevented by either dose of 16,16-dimethyl prostaglandin E2 (groups B and C). The mucosal proliferative zone was severely damaged in controls (68% +/- 5%) within the first hour after ethanol administration, whereas 16,16-dimethyl prostaglandin E2 protected the zone from damage (less than 5% +/- 1%). Neither dose of 16,16-dimethyl prostaglandin E2 prevented the occurrence of initial (at 15-30 min) morphologic and functional disruption of the surface epithelium after ethanol administration. However, initial disruption of the surface epithelium by 16,16-dimethyl prostaglandin E2 (groups B and C) was followed by migration of cells from the mucosal proliferative zone; the result was prompt restoration of the surface epithelium and resumption of its barrier and transport functions.

16,16-Dimethylprostaglandin E2↗

PubMed1985

Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat. Macroscopic, histologic, ultrastructural, and functional time sequence analysis.

Histologic or ultrastructural evidence of the ability of sucralfate to protect the gastric mucosa against ethanol injury is lacking. Therefore we analyzed morphologic and functional changes in the mucosa of 120 rats receiving, intragastrically, 2 ml of either sucralfate 500 mg/kg body wt or a control solution and 1 h later 2 ml of 100% ethanol. At 15 min, 1, 4, 6, and 24 h after ethanol instillation, mucosal changes were assessed by macroscopic examination, quantitative histology, scanning electron microscopy, recordings of gastric potential difference, and measurements of volume, pH, and electrolytes in the gastric contents. Between 15 min and 24 h after ethanol instillation, macroscopic necrotic lesions in controls involved greater than 33% of mucosal area and in the sucralfate-treated group less than 4% (p less than 0.001 for each period). In controls, ethanol instillation produced surface epithelial cell disruption and deep (greater than 0.2 mm) mucosal necrosis involving greater than 55% +/- 3% of the mucosal length. In sucralfate-pretreated animals, disruption of the surface epithelium was present at 15 min, 1 h, and 4 h after ethanol instillation, but deep necrotic lesions were virtually absent (0%-2%; p less than 0.001 vs. controls) during the entire study period. The surface epithelium was mostly reestablished by 6 h after ethanol instillation in the sucralfate group but not in the controls. We concluded that sucralfate protects the gastric mucosa against ethanol-induced injury by preventing deep mucosal necrosis and as a consequence the mucosal proliferative zone cells rapidly restitute mucosal integrity.

Aluminum↗

PubMed1985

Impaired intestinal absorption of riboflavin in experimental uremia.

Increased plasma and red blood cell concentrations of riboflavin have been reported in uremia. The possible role of altered intestinal absorption of riboflavin in the genesis of this abnormality is not known. For this reason we examined the intestinal absorption of riboflavin in rats made uremic by subtotal nephrectomy and sham-operated (control) rats in vivo using the recycling perfusion technique and in vitro using the everted-sac technique. Paradoxically, the results showed a significant impairment of intestinal absorption of riboflavin in vivo in uremic rats compared to the control group. However, no significant difference was observed in riboflavin transport in vitro. We conclude that the intestinal absorption of riboflavin is decreased in experimental uremia and cannot account for the reported increase in its plasma and red blood cell concentrations.

Animals↗

PubMed1985

Aging-associated increase in intestinal absorption of macromolecules.

The intestinal permeability of aging rats to various molecular weight species of polyethylene glycol 400 (PEG 400) was studied. Animals received a bolus of PEG 400 by oral gavage and urine was collected for 6 h to assess its rate of absorption. Quantitation by gas liquid chromatography revealed that total urinary excretion of PEG 400 increased with aging. 34-week-old rats excreted 34.3% of the administrated dose while 43.6% was excreted in the urine by rats 133 weeks of age. This effect was more pronounced with the higher molecular weight PEG since excretion of the lower molecular weight PEG 282 decreased by 10.5% while PEG 634 excretion increased by 11.4% with aging. The increased permeability of the intestinal tract to higher molecular weight species of PEG may indicate that the intestinal protective barrier to the absorption of potentially harmful environmental substances may be less efficient in aging animals. If similar findings are found in aging humans, they may indicate increased potential for absorption of large antigenic or carcinogenic compounds from the intestinal lumen.

Aging↗

PubMed1985

Development maturation of riboflavin intestinal transport in the rat.

The intestinal transport of riboflavin in the immature intestine of the suckling rat (14 day old) and its subsequent maturation in weanling (22 day old) and adult (90 day old) rats were investigated using the intestinal everted sac technique. The mucosal-to-serosal transport of 0.5 microM riboflavin was linear with time for 30-min incubation and occurred at a rate of 4.6, 3.6, and 1.6 pmol/g initial tissue wet wt/min in suckling, weanling, and adult rats, respectively. The transport of 0.5 microM riboflavin was higher in the jejunum than the ileum in all age groups. The transport system of riboflavin in all age groups was saturable, energy-, temperature-, and Na+-dependent. Kinetic parameters of the transport process were different. Apparent Kt of the transport process was the same in suckling and weanling rats (0.12 and 0.11 microM, respectively) but tripled in adult rats (0.35 microM). On the other hand, a progressive decrease in Vmax from 166 to 122 to 54 pmol/g initial tissue wet weight/30 min was observed in the suckling, weanling, and adult rats, respectively. The present study demonstrates that the characteristics of the transport process of riboflavin is similar in suckling, weanling, and adult rats and occurs by an energy-, temperature-, and Na+-dependent carrier-mediated process. However, the affinity and the activity (or the number) of the transport carriers of riboflavin decrease with maturation.

Age Factors↗

PubMed1985

Pure human pancreatic juice directly enhances uptake of cobalamin by guinea pig ileum in vivo.

Although pancreatic enzymes clearly degrade R binder, a nonintrinsic factor binder, the full scope of the pancreatic role in cobalamin absorption remains the subject of debate. Therefore the direct effect of pure human pancreatic juice (PPJ) on ileal cobalamin absorption in the absence of intrinsic factor was studied. PPJ significantly enhanced cobalamin uptake in guinea pig ileal loop perfused in vivo. It did not do so in the jejunum. This PPJ activity in the ileum was further stimulated by enteropeptidase and inhibited by aprotinin. The intestinal mucosa remained intact during our study by morphologic and inulin clearance criteria and behaved normally with respect to intrinsic factor and nonintrinsic factor binders. Since no intrinsic factor was present in the perfusate, PPJ must directly enhance cobalamin uptake by the ileum, perhaps promoting cobalamin attachment to receptor sites for subsequent transport by intrinsic factor. PPJ thus seems to affect cobalamin absorption at several levels. Previous studies have established its interaction with luminal R binders and with bile. The findings now indicate that pancreatic juice may have an additional, more direct role in promoting cobalamin absorption in the ileum.

Animals↗