Biomedical subjects

D Hollander

Publications and source records attributed to D Hollander.

At least 217 records · Page 12Linked to original sources

PubMed1977

Vitamin K2 colonic and ileal in vivo absorption: bile, fatty acids, and pH effects on transport.

Colonic and ileal absorption of vitamin K2 ([2-methyl-3H]menaquinone-9) was investigated in the conscious rat. When the absorption rate was plotted against the perfusate concentration, a linear relationship was found between these two parameters in the ileum and colon. The absorption rate of menaquinone by the ileum was increased as the bile salt concentration, degree of unsaturation of the added long-chain fatty acids, hydrogen ion concentration, and perfusate flow rates were increased. Colonic menaquinone absorption decreased as the bile salt concentration was increased. Menaquinone colonic absoprtion increased as the pH decreased, but no change was noted as the perfusion rate was increased. The present experimental observations in vivo, coupled with prior observations in vitro, indicate that absorption of menaquinone by the ileum and colon occurs by a passive diffusion process that is modified by variations in the perfusate bile salt concentration, the presence of unsaturated fatty acids, and the perfusate pH. The present observations indicate that the mammalian colon and terminal ileum can provide a constant source of vitamin K to aid hemostasis despite episodic lack of dietary vitamin K.

Absorption↗

PubMed1977

Intestinal absorption of alpha-tocopherol in the unanesthetized rat. The influence of luminal constituents on the absorptive process.

3H-alpha-tocopherol intestinal absorption was studied in the unanesthetized rat. The rate of alpha-tocopherol absorption remained linear over a wide range of concentrations (4 nM to 400 micrometer). Increasing the sodium taurocholate concentration in the micellar infusate up to 15 mM did not increase the rate of absorption of the vitamin. Addition of long-chain fatty acids to the micellar infusate decreased the absorption rate of the vitamin (p less than 0.05). The decrease was most significant (p less than 0.01) following the addition of the polyunsaturated linolenic (C18:3) acid. Increasing the hydrogen ion concentration in the perfusate increased the absorption rate of alpha-tocopherol. The present experiments in vivo support the conclusions drawn from in vitro uptake experiments which indicated that alpha-tocopherol is absorbed by a passive diffusion process. These experiments indicate that micellar expansion with polyunsaturated fatty acids interferes with the absorption of alpha-tocopherol and may result in deficiency of the vitamin.

Animals↗

PubMed1976

Inhibition of nocturnal acid secretion in duodenal ulcer patients by an H-2 histamine antagonist-cimetidine. A controlled double-blind investigation.

A new H-2-receptor antagonist, cimetidine, was tested as to its ability to suppress overnight gastric acid secretion in 8 male duodenal ulcer patients. In a double-blind controlled investigation, each volunteer was studied during four consecutive nights. In randomized order they received either 100, 200, or 300 mg of cimetidine or a placebo. No untoward clinical orlaboratory effects of the drug were found. Single-dose oral administration of 300 mg cimetidine caused a significant (P less than 0.05) inhibition of overnight gastric acid secretion for an 8-hr period, with the intragastric pH staying between 3.5-6.0. Cimetidine, because of its potent gastric acid inhibitory effect, may become an important therapeutic agent in the management of peptic ulcer disease.

Administration, Oral↗

PubMed1976

Mechanism and site of small intestinal uptake of vitamin D3 in pharmacological concentrations.

The site and mechanism of initial uptake of 1,2-3H vitamin D3 pharmacological concentrations was investigated using everted rat small bowel sacs incubated in a micellar medium. The mean +/- SE uptake rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 6.7 +/- 0.26, 7.8 +/- 0.54, and 3.3 +/- 0.20 nmole/min/100 mg tissue, respectively. Incubation with the addition of 10(-3) M 2,4-dinitrophenol, or 10(-3) M KCN, or under nitrogen atmosphere did not change (P greater than 0.05) the above rates of absorption. Incremental increases in the concentration of vitamin D in the incubation medium up to 1200 muM resulted in a linear increase in the uptake rate indicating lack of saturation kinetics. In all the above experiments, greater rate of uptake of the vitamin occurred in the proximal and medial small bowel than the distal small bowel (P less than 0.01). The above experiments indicate that vitamin D3 in this range of concentrations is taken up by enterocytes by a nonsaturable passive diffusion mechanism showing no evidence for carrier mediation. The rate of intestinal uptake is highest in the proximal and medial segments of the small bowel.

Animals↗

PubMed1976

Factors affecting the absorption of vitamin K-1 in vitro.

Factors which might affect the absorption of vitamin K of dietary origin were investigated using everted small bowel sacs. Increasing the bile salt concentration to 20 mM or the addition of long chain fatty acids, monoolein, or lecithin all resulted in significant (P less than 0-05) decrease in the absorption rate of the vitamin. The addition of 2-5 mM short and medium chain fatty acids did not change the absorption rate of vitamin K-1 (P greater than 0-05). The absorption rate of vitamin K-1 appears to be modified by the presence of compounds in the incubation medium which either alter the partition of the vitamin between the micelle and the cell membrane or which change the permeation characteristics of the compound through the unstirred water layer or modify the physical characteristics of the cell membrane itself. It is possible that some of the above factors modify the absorption of lipid soluble compounds in general.

Butyrates↗

PubMed1976

Colonic absorption of bacterially synthesized vitamin K2 in the rat.

Colonic absorption of bacterially synthesized vitamin K2 ([3H]menaquinone-9) was studied with everted rat colonic sacs in vitro. The mean +/- SE rate of absorption of the vitamin by the colon was 20 +/- 1.45 pmol/min per 100 mg tissue at 300 nM mucosal concentration of the vitamin. The rate of absorption did not change (P greater than 0.10) with the addition of 2,4-dinitrophenol, Na azide, or KCN to the mucosal incubation medium. No evidence for transmural transport of the vitamin was detectable. When the concentration of the vitamin was increased in a stepwise fashion up to 900 nM, the absorption rate remained linear with respect to the mucosal fluid concentration (r = 0.98). Autoradiography indicated that the vitamin accumulated in the mucosal and submucosal layers of the large bowel. Absorption of the vitamin by the large bowel takes place via a passive, nonsaturable process that shows no evidence of energy dependence or carrier mediation. It was concluded that vitamin K2 (bacterial origin) is absorbable by the rat colon in amounts sufficient to meet the daily requirement of the animal and may explain the lack of bleeding problems in the face of episodic lack of dietary vitamin K.

Animals↗

PubMed1976

Vitamin K2 absorption by rat everted small intestinal sacs.

Small intestinal absorption of vitamin K2 was investigated in vitro. Experiments with increasing concentrations of the vitamin up to 900 nM revealed linerity between the concentration and the rate of absorption (r = 0.99). Addition of metabolic uncouplers and inhibitors such as 2,4-dinitrophenol, sodium azide, and potassium cyanide did not decrease the rate of absorption of the vitamin (P less than 0.05). Absorption rate of the vitamin increased when taurocholate was replaced by a nonionic detergent, Pluronic F-68. The addition of butyric and octanoic acids to the incubation solution caused an increase in the absorption rate of vitamin K2. No change in the absorption of the vitamin occurred in the presence of oleic and linoleic acid. Addition to vitamins K1 and K3 to the incubation solution did not change the rate of vitamin K2 absorption. These findings suggest that vitamin K2 is absorbed by the small bowel by a passive noncarrier-mediated diffusion process. The rate of diffusion varied when the lipid and bile salt composition of the incubation solution was modified. Distal intestinal absorption of vitamin K from bacterial sources coupled with colonic absorption of the vitamin may be the major constant source of vitamin K in mammals.

Animals↗

PubMed1975

Mechanism and site of small intestinal absorption of alpha-tocopherol in the rat.

The site and mechanism of alpha-[5-methyl-3-H]tocopherol absorption was investigated using everted rat small bowel sacs incubated in a micellar medium. Mean plus or minus SE absorption rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 2.2 plus or minus 0.17, 3.4 plus or minus 0.21, and 2.0 plus or minus 0.04 nmoles per min per 100 mg, respectively. Addition of 2,4-dinitrophenol, sodium azide, or potassium cyanide to the incubation medium in separate experiments did not change the rate of absorption (P greater than 0.10). Stepwise increase in incubation solution tocopherol concentration up to 1200 muM resulted in a linear increase in the absorption rate. In all of the above described experiments the rate of absorption of the vitamin by the medial portion of the small bowel was significantly (P smaller than 0.01) higher than the rate of absorption of the vitamin by the proximal and distal small bowel segments. No transmural transport of the vitamin into the serosal compartment took place. Autoradiographic examination of the tissue after incubation disclosed accumulation of the vitamin in the submucosal lymphatic spaces. Alpha-Tocopherol absorption by the rat small bowel appears to be a passive diffusion process taking place at the highest rate in the medial portion of the small bowel.

Animals↗

PubMed1974