Ethanol-induced gastric mucosal injury: sequential analysis of morphologic and functional changes.
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Action Potentials↗
Biomedical subjects
D Hollander
Publications and source records attributed to D Hollander.
Ultrastructural changes in the gastric mucosal microvessels after ethanol.
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Animals↗
Does the non-absorbable fat, (sucrose polyester), interfere with the intestinal absorption of vitamin A?
Sucrose polyester (SPE) is a synthetic non-absorbable lipid. The effect of SPE on vitamin A absorption was determined by monitoring the disappearance rate of radio-labeled vitamin A from the jejunal perfusate of the rat. The relative distribution of radio-labeled vitamin A between the micellar phase and the perfusate containing SPE was determined. With SPE concentrations of 5, 10 and 20 g/l, vitamin A was concentrated in the SPE phase over the micellar phase by a factor of 4.4, 9.4, 19.8 respectively. Thus, vitamin A favored the SPE phase over the micellar phase in the distribution analysis. In vivo absorption experiments with SPE and non-SPE perfusates showed decreased net vitamin A absorption rates in the presence of SPE by 8.7% Thus, dietary ingestion of SPE results in some impairment of intestinal absorption of vitamin A, and may require vitamin A supplementation.
Animals↗
Absorption of 5-methyltetrahydrofolate in rat jejunum with intact blood and lymphatic vessels.
UNLABELLED: Transport results from in vitro studies may not be applicable to in vivo situations. In this study, we extended our previous in vitro observations regarding the intestinal transport of 5-methyltetrahydrofolate to in vivo studies in the unanesthetized rat and examined the effect of the unstirred water layer on the absorption process. We used a well defined intestinal perfusion technique. Absorption of 0.5 and 5 microM 5-methyltetrahydrofolate proceeded in a linear manner for 40 min of perfusion at 0.31 and 1.74 nmol/100 cm per min, respectively. Absorption of 0.5 microM 5-methyltetrahydrofolate increased with increasing perfusate flow-rate from 0.5 to 2 to 4 ml/min, indicating an unstirred water layer influence on the absorption rate. Absorption of the substrate was saturable with an apparent Kt of 5.7 microM and Vmax of 3.45 nmol/100 cm per min. Absorption was pH-dependent, and was inhibited by structural analogues. In contrast to the in vitro data, addition of glucose (20 mM) to the perfusate was unnecessary for in vivo absorption to proceed. Unconjugated cholic (5 mM) and deoxycholic (1 mM) acids and the organic anion rose bengal (0.1 mM) inhibited the absorption of 0.5 microM 5-methyltetrahydrofolate when added to the perfusate. CONCLUSIONS: the results of previous in vitro studies of 5-methyltetrahydrofolate intestinal transport are applicable to in vivo situations, except that luminal glucose was found to be unnecessary in the latter. The unstirred water layer modulated the absorption of 5-methyltetrahydrofolate, while unconjugated bile acids and rose bengal inhibited it.
Animals↗
Colonic absorption of acetylsalicylic acid in the rat.
Aspirin is absorbed in the colon by passive diffusion to a significant degree in spite of the alkaline pH of the colonic lumen. Aspirin absorption by the colon is enhanced by increasing the hydrogen ion concentration. Butyric acid, by markedly reducing the absorption rate of aspirin, may be partially responsible for the unpredictable absorption of rectally administered aspirin. The addition of glycerol to aspirin preparations does not hinder the absorption of aspirin by the colon.
Animals↗
Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.
The effect of the unconjugated bile acids, cholic, deoxycholic, chenodeoxycholic, and ursodeoxycholic acids, and of the conjugated bile acid taurocholic acid on the mucosal-to-serosal transport and tissue uptake of the naturally occurring folate derivative, 5-methyltetrahydrofolate (5-CH3H4PteGlu) was examined in everted sacs of rat jejunum. Each of the unconjugated bile acids examined inhibited the transport and tissue uptake of 5-CH3H4PteGlu in a concentration dependent manner. At low concentrations (0.01-0.1 mM) of cholic and deoxycholic acids, no structural or functional damage to the intestinal mucosa occurred and the transport of 5-CH3H4PteGlu was inhibited competitively with Ki values of 0.114 mM and 0.055 mM for cholic and deoxycholic acids, respectively. The greater inhibition of 5-CH3H4PteGlu transport by unconjugated bile acids at 1 mM can be attributed to observed structural and functional damage to the intestinal mucosa. The addition of 2 mM lecithin to the mucosal medium failed to prevent the inhibitory effect of 0.1 mM deoxycholic acid on the transport of 0.5 microM 5-CH3H4PteGlu. Compared with the effect of unconjugated bile acids, the conjugated bile acid taurocholic acid (0.01-5 mM) showed no effect on the transport and tissue uptake of 5-CH3H4PteGlu. The results of this study show that intestinal transport and tissue uptake of 5-CH3H4PteGlu are inhibited by unconjugated bile acids in a dose-dependent fashion. The clinical and physiological implications of these observations are discussed.
Animals↗
Intestinal absorption of free oleic acid in the unanesthetized rat: evidence for a saturable component?
The intestinal absorption of free oleic acid at low intraluminal concentrations and the influence of luminal factors on its absorption were studied in the unanesthetized rat. The relationship between oleic acid concentration (30-2500 microM) and its rate of absorptions fitted best to a rectangular hyperbola (y = x/(2.19 + 0.0015x), r = 0.94). Oleic acid's rate of absorption increased as the hydrogen ion and sodium taurocholate concentrations were increased or as the thickness and resistance of the unstirred water layer were diminished or following the addition of lysolecithin. The additions of the artificial detergent Tween-80, or lecithin and linoleic, linolenic and arachidonic acids to the perfusate decreased oleic acid's rate of absorption. It was concluded that oleic acid absorption in this range of concentrations displays apparent saturation kinetics which are due to unstirred layer effects, limited aqueous solubility of oleic acid and possible saturation of cytosol fatty acid binding proteins. Factors which increase oleic acid's protonated concentration or diminish the unstirred layer resistance, enhance its absorption rate, while factors which enhance its micellar solubility or interfere with its transfer out of the cell membrane decrease its overall rate of absorption.
Animals↗
Does aging affect the intestinal transport of 5-methyltetrahydrofolate?
Aging is associated with increased incidence of folate deficiency. The mechanism responsible for the deficiency is not known but could include a decrease in the intestinal absorptive capacity for folates. Therefore, we examined the intestinal absorptive capacity for folate in young and old rats. We assessed the absorption of the natural folate derivative, 5-methyltetrahydrofolate in 3- and 25-month-old rats, using jejunal everted sacs. The kinetic parameters of 5-methyltetrahydrofolate absorption disclosed apparent Kt of 7.7 and 6.54 microM and Vmax of 0.96 and 1.14 nmol/g initial tissue wet weight/30 min in young and old rats, respectively. These data do not demonstrate an aging-associated decrease in the intestinal transport capacity for 5-methyltetrahydrofolate. Therefore the deficiency of folate found in the elderly is unlikely to be due to intestinal malabsorption of folate monoglutamates. Other mechanisms must play a role in the deficiency of folate seen in the elderly.
Aging↗
Aging-associated pancreatic exocrine insufficiency in the unanesthetized rat.
Observations in individuals have suggested that pancreatic functions may be diminished with aging. In order to explore this possibility, we measured pancreatic fluid, protein and amylase output as a function of aging in the rat. Surgical preparations of the rats included external drainage of pancreatic secretions without obstructing normal bile flow and complete diversion of gastric acid out of the duodenum to prevent endogenous secretin release. Pancreatic secretions were collected in the basal state in unanesthetized animals 24 h after surgery. Protein and amylase output were highest at 3 months of age and decreased to less than 20% of maximal values by 27 months of age. For example, amylase output decreased from 4,354 to 105 U/h/kg and protein output fell from 33.5 to 1.7 mg/h/kg between 3 and 27 months of age. Our findings indicate that aging in the rat is associated with diminished pancreatic exocrine functions. Further careful assessment of pancreatic functions in aging individuals is advisable.
Aging↗
Influence of aging on vitamin D absorption and unstirred water layer dimensions in the rat.
Because of the high prevalence of metabolic bone disease in older persons, we investigated the possibility of impaired intestinal absorptive capacity for vitamin D3 in aging animals. Using a single-pass technique, we measured vitamin D absorption and mucosal accumulation in male rats 9 to 101 weeks of age. Intestinal length, water absorption, and vitamin D3 intestinal tissue concentration remained constant after 41 weeks of age. Vitamin D3 absorption increased from 1209 pmol/100 cm/hr at 9 weeks of age to 2114 pmol/100 cm/hr at 41 weeks of age and remained relatively constant thereafter. Because vitamin D3 absorption rate is partly regulated by the dimensions of the unstirred water layer, we assessed the dimensions of the UWL of our aging animals. As the animals aged, the surface area of the UWL increased from 197 to 316 cm2/100 cm, and its resistance decreased from 1.2 to 0.7 min/cm3/100 cm by 41 weeks of age and remained stable thereafter. Inasmuch as the UWL is a major regulatory step in the absorption of vitamin D, its constant dimensions after 41 weeks of age explain the normal absorption of vitamin D3 observed in our aging animals. If these findings are found to be true in humans as well, they would argue against the possibility of vitamin D3 malabsorption as a cause of metabolic bone disease seen in aging individuals.
Aging↗
Intolerance to administered lipids in tumor-bearing animals.
Cancer cachexia is a poorly understood phenomenon that contributes to patient intolerance of operations, radiation, and chemotherapy. Reversal of this dysmetabolic state has been attempted by administration of carbohydrates, proteins, and lipids, with little demonstrated clinical benefit. Identification of elevated serum triglycerides (TG) in two tumor-bearing (TB) animal models and recently reported in humans with cancer may be a part of this dysfunctional state. Because lipids makeup energy repletion in patients receiving TPN, the question of how exogenous lipids affect these TB animals needed to be resolved. Intralipid administered by intravenous or gastrointestinal routes raised serum levels in TB animals to greater than 600 mg/dl, even when their baseline TG levels were comparable to nontumor-bearing control animals. The addition of glucose concomitantly with Intralipid failed to prevent TG levels from rising abruptly. Increased lipolytic activity in TB sera was demonstrated and that was not due solely to hypoglycemia or hypoinsulinemia. Administration of lipids to TB animals results in excessively high serum TG levels that appear to be due, in part, to the demonstrated lipolytic activity in TB animal sera.
Animals↗
Intestinal absorption of vitamin A in experimental uremia.
Intestinal absorption of vitamin A was determined in a group of rats rendered uremic by subtotal nephrectomy. The results were compared with those obtained in a group of sham-operated control animals. Absorption studies were performed by in-vivo perfusion of an isolated loop of the proximal jejunum with intact blood and lymphatic supply. The rate of intestinal absorption of vitamin A, in the uremic groups was nearly identical to that found in the control group. It thus appears that intestinal absorption of vitamin A is not affected by experimental uremia in the rat.
Animals↗
Inhibitory effect of unconjugated bile acids on the enterohepatic circulation of methotrexate.
The effect of unconjugated cholic and deoxycholic acids on intestinal and hepatic transport and bile secretion of methotrexate was studied using everted sacs of rat proximal jejunum and isolated perfused rat liver. Cholic and deoxycholic acids competitively inhibit the mucosal-to-serosal transport of methotrexate (Ki, 0.08 and 0.06 mM, respectively). Cholic and deoxycholic acids also decrease intestinal tissue content of methotrexate in a concentration-dependent manner. Structural and functional damage to the intestinal mucosa does not occur in tissue treated with 0.1 mM and lower concentration of deoxycholic acid as assessed by histological studies, transmural potential difference measurements and the release of the cytoplasmic marker enzyme, lactate dehydrogenase. In the isolated liver, cholic and deoxycholic acids inhibit the uptake, retention and biliary secretion of methotrexate. At 1 mM cholic and deoxycholic acids, 72 and 80% inhibition in liver uptake and 93 and 99% inhibition in bile secretion of 1 microM methotrexate are observed, respectively. These studies demonstrate that unconjugated bile acids inhibit the enterohepatic circulation of methotrexate by impairing its intestinal transport and hepatic uptake and retention and biliary secretion.
Animals↗
Intestinal absorption of 5-methyltetrahydrofolate in experimental uremia.
Folate deficiency and megaloblastic anemia occur in chronic renal failure. However, the possible role of intestinal malabsorption as a cause of the reported deficiency has not been investigated. Therefore, we examined the intestinal absorption of 5-methyltetrahydrofolate in rats made uremic by subtotal nephrectomy using in vivo perfusion technique and in vitro everted sac technique. The results were compared with those obtained in a group of sham-operated rats with normal renal function. The amount of 5-methyltetrahydrofolate absorbed in vivo was significantly lower in the uremic animals as compared to the control group. In contrast, no significant difference was found in the absorption of 5-methyltetrahydrofolate in vitro in the two groups. To mimic the uremic environment, the in vitro studies were repeated using jejunal sacs from normal animals filled with either buffer solution, or sera from uremic patients before and after dialysis. Their results showed a marked suppression of 5-methyltetrahydrofolate absorption with predialysis sera and a significant improvement with post dialysis sera. We conclude that intestinal absorption of 5-methyltetrahydrofolate is impaired in uremia. The results of the in vitro experiments suggest that the observed transport defect is due to some influence of uremic environment rather than to an acquired intrinsic defect of enterocytes in uremia.
Anemia, Megaloblastic↗
Sucralfate protection of the gastric mucosa against ethanol-induced injury: a prostaglandin-mediated process?
We studied whether sucralfate's protection of the gastric mucosa against ethanol induced injury in the rat is prostaglandin mediated. Rats received intragastric pretreatment: i) saline, ii) sucralfate, and iii) indomethacin-sucralfate. One hour later gastric contents were obtained for measurements of prostaglandin E2 and 2 ml of 100% ethanol were instilled. Rats were sacrificed 1 h later. The gastric mucosa was assessed: a) macroscopically by planimetry, b) by quantitative histology, and c) by measurements of gastric volume, pH and sodium. We found that sucralfate significantly increased gastric luminal release of prostaglandin E2. The increase was completely abolished by indomethacin pretreatment. Sucralfate protected the gastric mucosa against ethanol injury reducing macroscopic and histologic necrosis. Indomethacin (prostaglandin synthetase inhibitor) given 2 h prior to sucralfate markedly abolished its protective action against ethanol induced necrosis by 70%. These findings indicate that prostaglandins mediate some of the protective action of sucralfate. Sucralfate appears to have additional protective action which is prostaglandin independent.
Aluminum↗
Does essential fatty acid absorption change with aging?
Linoleic acid, an essential fatty acid, is a prostaglandin precursor. We investigated the maximal capacity of the proximal jejunum and distal ileum to absorb linoleic acid in the unanesthetized rat. Groups of rats 1, 3, 12, and 28 months of age were studied. As the rats aged, their maximal capacity to absorb linoleic acid increased fivefold both in the jejunum and ileum. Since the intestinal wall content of linoleic acid remained relatively constant, age-related changes in mucosal surface area could not account for our observations. A decrease in the unstirred water layer thickness with aging was detected by measuring potential difference changes across the bowel. The total surface area of the unstirred water layer increased some fourfold and its resistance to linoleic acid transfer decreased fivefold with aging. These changes in the dimensions and characteristics of the unstirred water layer with aging may account for the fivefold increase in the maximal capacity of the small bowel to absorb linoleic acid.
Aging↗
Increased intestinal absorption of oleic acid with aging in the rat.
Changes in nutrient absorption could be responsible for some of the disorders associated with aging. Oleic acid is the most common dietary fatty acid. Therefore, we investigated its absorption by the small intestine of aging rats in vivo. We used a single pass intestinal perfusion technique to study absorption in animals between 6 and 138 weeks of age. Rats less than 70 weeks of age absorbed 14,000 to 15,000 nmol of oleic acid per 100 cm/hr. In contrast, rats 94 weeks of age or older, absorbed 22,000 to 23,000 nmol of oleic acid per 100cm/hr. The 61% increase in oleic acid absorption as the rats aged correlated with a decrease in the resistance of the unstirred water layer from 0.8 to 0.5 min/cm3/100cm. Concomitantly, the surface area of the unstirred water layer increased from 97.1 to 141.2 cm2/100cm. The changes in unstirred water layer resistance and surface area explain the observed increase in absorption of oleic acid with aging. The increased surface area and decreased resistance of the unstirred water layer are both conducive to increased intestinal absorption of this lipid nutrient as the animals aged.
Aging↗
Impaired intestinal absorption of vitamin D3 in azotemic rats.
Changes in vitamin D metabolism and their effect on calcium and bone metabolism in uremia have been extensively studied. However, the possible effect of uremia on intestinal absorption of vitamin D has not been investigated. We determined the rate of intestinal absorption of vitamin D3 in uremic and normal rats using a well-defined in vivo perfusion technique under identical experimental conditions. The rate of jejunal absorption of vitamin D3 in uremic animals (5.09 +/- 1.87 pmol/100 cm/h) was significantly less (p less than 0.001) than that found in the control animals (11.5 +/- 1.6 pmol/100 cm/h). While the underlying mechanism(s) of the observed reduction in vitamin D absorption in uremia is not known, its recognition adds another dimension to the previously recognized abnormalities of vitamin D metabolism in uremia.
Animals↗