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W Forth

Publications and source records attributed to W Forth.

At least 127 records · Page 7Linked to original sources

Absorption of 14C-clanobutin-Na isolated perfused intestinal segments in vitro of rats.

1. The absorption of 14C-labelled 4-[4-chloro-N-(4-methoxyphenyl)-benzamido]-butyric acid (clanobutin) was investigated on isolated perfused jejunal segments of rats in vitro according to the method of Fisher and Parsons and using everted (Wilson and Wiseman) and non-everted sac preparations. 2. Transfer to and content of the mucosal tissue of 14C-clanobutin in isolated perfused jejunal segments is proportional to the concentration administered on the mucosal side in the range of 1-100 mumol/l. 3. The concentration of 14C-clanobutin in the absorbate is 1.5 times higher than in the perfusion fluid. As compared on the basis nmol/ml perfusion fluid versus nmol/g wet weight the concentration of 14C-clanobutin in the tissue is twice that in the perfusion fluid. 4. No detectable metabolic alteration of 14C-clanobutin could be demonstrated during the passage across the jejunal epithelium. 5. The transfer of 14C-clanobutin in everted sac preparations from the mucosal to the serosal side (M leads to S) is about 3.7 times higher than in the reverse direction (S leads to M). 6. In the intestinal tissue the concentration of 14C-clanobutin is 1.7 times higher than that in the incubation medium; this calculation was made on the basis nmol/ml fluid versus nmol/g tissue wet weight. 7. When having administered 14C-clanobutin on both sides, on the serosal side the 14C-clanobutin concentration increases slightly whereas on the mucosal side due to uptake into the intestinal a slight decrease of the 14C-clanobutin concentration was observed.

Animals↗

Absorption of 14C-clanobutin-Na in blood-perfused tied-off jejunal segments in vivo of rats.

1. Absorption, elimination and retention of 14C-clanobutin was investigated on tied-off jejunal segments in situ of rats. 2. 14C-clanobutin completely disappeared from the intestinal lumen within 15-90 min depending on the dose administered (28.8-230.5 micromol/kg). 3. The amount absorbed of 14 C-clanobutin is proportional to the amount administered (28.8-230.5 micromol/kg). 4. The maximum of the accumulation of 14 C-clanobutin in the jejunal tissue is reached within the first 2 min. 5. Within 120 min 40-70% of the 14 C-clanobutin administered are excreted into bile. A concentration gradient bile/blood of nearly up to 300 is established. About 80% of the 14C-clanobutin was converted into (a) metabolite(s). 6. The highest dose of 14C-clanobutin, 230,5 micromol/kg, inhibited the absorption of glucose statistically significantly by about 60% within the first 5 min after administration. After 40 min, however, the amount of glucose adsorbed is not further reduced. The residual fluid as well as the amount of Na+-ions in the jejunal lumen is slightly increased with increasing doses of 14C-clanobutin ( dose: 57.6 and 230.5 micromol/kg), whereas the amount of K+-ions excreted into the intestinal lumen is decreased.

Animals↗

Transfer across mucosal epithelium, tissue content and metabolic fate of 125I-(ipodate-sodium) on isolated everted segments of rat small intestine.

1. Transfer and tissue content of 125I-radioactivity was measured after administration of 125I-(ipodate-sodium) to everted rat jejunal segments. 2. After having administered 10(-5) M 125I-(ipodate-sodium) on both sides of the everted sacs the S/M ratio of the concentration of 125I-radioactivity was 1.5 in jejunal segments and 2.3 in ileal segments. The tissue content was nearly equal for both segments. According to the apparent partition coefficient for ipodate-sodium at pH 7, the 125I-radioactivity is accumulated in the tissue about 10-fold. 3. Lowering of the temperature of the incubation medium from 37 degrees C to 15 degrees C prevents the building up of a concentration gradient between the serosal and the mucosal side on either jejunal and ileal segments whereas the tissue content of 125I-radioactivity was nearly unchanged. 4. With increasing concentrations (1.6--10(-6)--9.6-10(-4) M) of 125I-(ipodate-sodium) administered on the mucosal side the transfer and the tissue content of 125I-radioactivity were decreased. This appears to be a toxic effect since in jejunal segments also the S/M ratio for the concentration of glucose decreases. 5. The analysis of the 125I-radioactivity in the serosal fluid of jejunal segments showed that the bulk of the 125I-radioactivity was present in the aqueous phase and only 33% as the unchanged ipodate-sodium in the organic phase. 10% of the 125I-radioactivity must be attributed to inorganic iodine. The concentration of 125I-(ipodate-sodium) administered in the mucosal fluid only was 3.2-10(-6) M. At lower temperature (7 degrees C) the bulk of the 125I-radioactivity in the serosal fluid was found in the organic phase, i.e. as unchanged ipodate-sodium. 6. After the incubation of the aqueous phase with beta-glucuronidase or NaOH about 97% of the 125I-radioactivity could be extracted into the organic phase. This means that the bulk of the 125I-radioactivity in the aqueous phase is present as a conjugate, e.g. ester glucuronide of the unchanged ipodate. 7. Apparently, the process of the conjugation of ipodate-sodium in the mucosal cells is involved in the transfer of the 125I-radioactivity across the mucosal epithelium.

Animals↗

Inhibition of the intestinal absorption of iron by sodium alginate and guar gum in rats.

Na-alginate as well as guar gum inhibit the absorption of a 59Fe-labelled iron dose (360 nmol) from tied-off jejunal segments of either normal or iron-deficient rats. In order to inhibit the absorption of the iron dose by half as compared with normal rats to which ionized iron was administered 1.2--8 mg of guar gum and 8-30 mg Na-alginate was necessary. In iron-deficient rats the highest dose dose of Na-alginate tested, 100 mg, inhibited the absorption of iron by about 20%; the highest dose of guar gum, 30 mg, inhibited the amount of iron absorbed by about 25%. An artificial diet containing 10% of either guar gum and Na-alginate fed for 3 days inhibited the absorption of iron in normal but not in iron-deficient rats. Also, in these experiments guar gum proved to be more effective than Na-alginate.

Alginates↗

Capacity of the mucosal transfer system and absorption of iron after oral administration in rats.

1. The dose dependence of the iron absorption shows a saturation characteristic if iron (0.25--5 mumoles Fe/kg body weight) is administered in tied-off intestinal segments of normal and iron-deficient rats. 2. If the iron doses (2.1--570 mumoles Fe/kg body weight) are administered by stomach tube only in normal rats a similar dose dependence curve has been obtained as after administration in tied-off intestinal segments. In iron-deficient rats the shape of the dose dependence curve is changed and shows no clear-cut saturation characteristic. 3. The differences of these dose dependence curves are discussed with respect to the differences of the methodological conditions. A saturation type kinetic for absorption cannot be expected under all experimental conditions despite of the existence of a transfer system with limited capacity for the transport of iron.

Animals↗

Pathway of sodium moving from blood to intestinal lumen under the influence of oxyphenisatin and deoxycholate.

The transfer of (51)CrEDTA and inulin--substances which are distributed only in the extracellular space--across the rat colonic mucosa in vivo is increased by oxyphenisatin O (3.5 times 10(-5)M) and deoxycholate D(3 times 10(-3)M). O and D do not change the size of the intra- and extracellular fluid compartments of the mucosa as measured with (51)CrEDTA from the blood side. The sodium and potassium content of the mucosal tissue is not altered. Therefore the calculated intracellular concentrations of sodium and potassium remain constant. The time course of the (22)Na uptake into the mucosal epithelium is not influenced by O and D up to 5 min after i.v. injection. The specific activity of sodium, however, in the luminal fluid increases under the influence of O(twofold) and D(fivefold). The uptake of (22)Na into the mucosal tissue after administration of (22)Nainto the intestinal lumen is not changed in presence of O and D. We conclude that the net transport of sodium and water from blood to lumen under the influence of O and D occurs mainly via the intercellular way.

Animals↗

[Drug-drug interactions (author's transl)].

This short outline of drug-drug interactions does not claim to cover the entire field. The task of this paper is to illustrate the most important principles of drug-drug interactions by paradigms taken from the experience of the practitioner. One consequence of drug-drug interactions is the change in pharmacolinetic parameters important for the therapeutical effect of drugs in the organism. Very often the elucidation of the mechanisms of drug-drug interactions in man is impossible; therefore, for clinical pharmacologists experiments on animals remain the tool in order to gain more knowledge in this field.

Age Factors↗

Iron absorption.

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Anemia, Hypochromic↗