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Biomedical subjects

D Hollander

Publications and source records attributed to D Hollander.

At least 199 records · Page 11Linked to original sources

Intestinal absorption of 25-hydroxyvitamin D3 in unanesthetized rat.

We investigated the mechanism and characteristics of 25-hydroxyvitamin D3 (25-OH-D3) absorption in the unanesthetized rat by using a single-pass intestinal perfusion technique. The rate of 25-OH-D3 absorption remained linear for a wide range of concentrations (2-900 nM). Absorption rate of 25-OH-D3 increased as the pH, the bile acid concentration, and thickness of the unstirred water layer were decreased. Absorption did not change after the additions of fatty acids of varied chain lengths and degrees of saturation. In rats with lymph and bile fistulas, 18.5% and 16.3% of the infused radio-activity appeared in the lymph and bile drainage, respectively. These experiments indicate that 25-OH-D3 is absorbed by a passive diffusion mechanism that is influenced by the intestinal pH, bile acid concentration, and thickness of the unstirred water layer, but not by the presence of fatty acids. Approximately equal fractions of the infused hydroxylated vitamin are recovered from the lymphatic and biliary fluids.

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A dual, concentration-dependent absorption mechanism of linoleic acid by rat jejunum in vitro.

Linoleic acid absorption was studied using everted rat jejunal sacs. At low concentrations (42-1260 microM), the relationship between linoleic acid concentration and its absorption rate fitted best to a rectangular hyperbola. At high concentrations (2.5-4.2 mM) the relationship between the two parameters was linear. The separate additions of 2,4-dinitrophenol, cyanide, or azide, or decrease in the incubation temperature from 37 to 20 degrees C did not change the absorption rate of linoleic acid. Absorption rate of linoleic acid at low concentrations increased as the hydrogen ion and taurocholate concentrations were increased or as the unstirred water layer thickness was decreased. Linoleic acid absorption rate was decreased after the additions of lecithin, oleic, linolenic, and arachidonic acids or the substitution of taurocholate with the nonionic surfactant Pluronic F 68. These observations indicate that a concentration-dependent, dual mechanism of transport is operative in linoleic acid absorption. Facilitated diffusion is the predominant mechanism of absorption at low concentrations, while at high concentrations, simple diffusion is predominant. At low concentrations, the absorption rate of linoleic acid is influenced by the pH, surfactant type and concentration, the simultaneous presence of other polyunsaturated fatty acids, and the thickness of the unstirred water layer.

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Diurnal rhythmicity of absorption of a lipid compound (vitamin K-1) in vivo in the rat.

The possibility of rhythmicity in the intestinal absorption of lipids was explored by assessing the absorption of vitamin K-1 by the unanesthetized rat at 6 PM, 12 and 6 AM, and 12 PM. A marked variability in the absorption rate of vitamin K-1 was found throughout the 18-hr period. The highest rates of absorption occurred at midnight (139.8 +/- .22 and 134.4 +/- 9.1 pmol/min/10 cm of jejunum and ileum, respectively). The lowest rates of absorption occurred at 6 AM (54.5 +/- 1 and 81.4 +/- 7.4 pmol/min/10 cm of jejunum and ileum, respectively). Absorption rates at noon were not different from absorption at 6 AM but an initial increase in absorption was noted at 6 PM. Synchronization of the absorptive rate with time is most likely related to the time of feeding and not to changes in the pattern of illumination. The possibility of marked diurnal variability in the absorption rate should be considered in the design and execution of intestinal absorption experiments.

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Arachidonic acid intestinal absorption: mechanism of transport and influence of luminal factors of absorption in vitro.

The mechanism and characteristics of intestinal absorption of arachidonic acid were studied in vitro using everted intestinal sacs of the rat. Arachidonic acid absorption was studied at concentrations of 5 micron to 8.36 mM. The plot of absorption rate vs. concentration fitted best to a rectangular hyperbola at low micron concentrations and to a straight linear relationship in the mM range of concentrations. Metabolic inhibitors and uncouplers did not change absorption in either range of concentrations. The absorption of arachidonic acid increased with thinning of the unstirred water-layer, decrease in the pH, or the substitution of sodium taurocholate by Pluronic F 68 OR Tween 80. Absorption decreased following the equimolar additions of oleic, linoleic, and linolenic acids. Absorption rate did not change when the taurocholate concentration was varied from 5-15 mM or following the additions of butyric or glutamic acids, leucine, lysine, or dextrose. It was concluded that arachidonic acid is absorbed by a concentration-dependent dual mechanism of transport which is not energy dependent. At the low micron range of concentrations, facilitated diffusion is predominant, while at mM concentrations, simple diffusion is the dominant mechanism of absorption. Changes in the intestinal fluid composition, flow rate, and pH can modify the rate of absorption of arachidonic acid.

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Initial cholesterol uptake by everted sacs of rat small intestine: kinetic and thermodynamic aspects.

The kinetics of initial cholesterol uptake by everted rat proximal and distal small intestinal sacs were evaluated in vitro. The mucosal incubation solution consisted of 0.05 mM cholesterol solubilized in 4.8 mM sodium taurocholate micellar solution at pH 7.4 Experiments were performed at temperatures from 26 to 38 C. The rate of cholesterol uptake followed a linear relationship when plotted against time indicating an apparent zero-order kinetics mechanism for initial uptake. An Arrhenius plot of the results of uptake versus temperature remained linear over the entire range of temperatures studied. The large free energy of activation (20 kcal/mole) suggests that an energy barrier for cholesterol uptake exists at the enterocyte luminal cell membrane and may be an important limiting step in cholesterol uptake. It is proposed that a transient association between cholesterol and a component of the enterocyte luminal cell membrane is formed during initial uptake of cholesterol. The transient association may be an activated complex formed with proteins present at or within the luminal enterocyte cell membrane.

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Vitamin D-3 intestinal absorption in vivo: influence of fatty acids, bile salts, and perfusate pH on absorption.

Intestinal absorption of vitamin D-3 in physiological concentrations was studied in the live unanesthetised rat. In both the jejunum and the ileum a linear relationship was found between the absorption rate of the vitamin and its intraluminal concentration. Increasing the sodium taurocholate concentation in the perfusate above 5mM did not change ileal absorption rate but did decrease jejunal absorption rate. The vitamin's rate of absorption was raised by increases in either the hydrogen ion concentration in vivo is mediated by passive diffusion. The rate of absorption of ttion or the perfusate's flow rate. Addition of 2.5 mM fatty acids of varying chain length and degrees of saturation resulted in a decrease in the rate of vitamin D-3 absorption. These experiments indicate that vitamin D-3 absorption in vivo is mediated by passive diffusion. The rate of absorption of the vitamin is influenced by the composition of the perfusate and the thickness of the unstirred layer.

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Effect of luminal constituents on vitamin K1 absorption into thoracic duct lymph.

Lymphatic appearance rate of [3H] phylloquinone was studied in unanesthetized rats with cannulated bile and lymph ducts. A linear relationship (y= -44.9 + 10.2x, r=0.99) was found between the rate of the compound's infusion into the duodenum and its appearance rate in the lymph. Increasing the taurocholate infusate concentrations from 5 to 15 mM increased phylloquinone appearance rate in the lymph from 6.47 +/- 1.82 to 24.14 +/- 1.20 pmol/min (P less than .01). Varying the infusate pH from 4.35 to 8.0 did not change lymphatic appearance rate of vitamin K1 or lymphatic flow rate. Addition of short-chain fatty acid (butyrate) to the infusate enhanced the total absorption of vitamin K1 into the bile and lymph, whereas the addition of polyunsaturated fatty acids inhibited the total absorption of the vitamin. These experiments delineate some factors that modify the extrusion rate of vitamin K1 out of the enterocyte into the lymphatic circulation and add information regarding this phase of the absorptive pathway of lipids.

Absorption↗

beta-carotene intestinal absorption: bile, fatty acid, pH, and flow rate effects on transport.

beta carotene absorption in the unanesthetized rat was investigated by recirculating a micellar perfusate that contained beta-carotene through jejunal and ileal intestinal loops. Radioautography revealed extensive distribution of the provitamin throughout the layers of the small bowel. A linear relationship was found between the concentration of beta-carotene in the perfusate and its rate of absorption at perfusate concentrations of 0.5--11 mM. Increases in the perfusate hydrogen ion concentrations, additions of fatty acids of varied chain lengths and degrees of saturation, and an increase in the perfusate flow rate caused higher rates of beta-carotene absorption. Increase in the perfusate sodium taurocholate concentration above 2.5 microM did not change the absorption rate of beta-carotene. These experiments indicate that beta-carotene absorption takes place by passive diffusion. The process of diffusion can be modulated by intraluminal factors that change the physical characteristics of perfusate or stimulate the intracellular cleavage of carotene to retinal.

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Propranolol as an adjunct to the treatment of schizophrenia.

Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more.

Adult↗

Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport.

Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate.

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Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport.

Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length.

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