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Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein.

65Zn was used to examine the effects of dietary zinc and protein on true zinc absorption and intestinal excretion of endogenous zinc by an isotope dilution technique in streptozotocin-diabetic and control rats. Four groups each of diabetic and control rats were fed diets containing 20 ppm Zn, 20% egg white protein (HMHP); 20 ppm Zn, 10% egg white protein (HMLP); 10 ppm Zn, 20% egg white protein (LMHP); and 10 ppm Zn, 10% egg white protein (LMLP). Measurement of zinc balance was begun 9 d after an i.m. injection of 65Zn. True zinc absorption and the contribution of endogenous zinc to fecal zinc excretion were calculated from the isotopically labeled and unlabeled zinc in the feces, duodenum and kidney. Results from the isotope dilution study indicated that diabetic rats, but not control rats, absorbed more zinc from 20 ppm zinc diets than from 10ppm zinc diets and that all rats absorbed more zinc from 20% protein diets than from 10% protein diets. Furthermore, all rats excreted more endogenous zinc from their intestines when dietary zinc and protein levels resulted in greater zinc absorption. In diabetic and control rats, consuming equivalent amounts of zinc, the amount of zinc absorbed was not significantly different, but the amount of zinc excreted by the intestine was less in the diabetic rats. Decreased intestinal excretion of endogenous zinc may be a homeostatic response to the increased urinary excretion of endogenous zinc in the diabetic rats and may also lead to the elevated zinc concentrations observed in some organs of the diabetic rats.

Analysis of Variance

Biopharmaceutical studies on hydantoin derivatives. I. Physico-chemical properties of hydantoin derivatives and their intestinal absorption.

The physico-chemical properties of a series of hydantoin derivatives and their intestinal absorption from solution were studied. The introduction of the benzenesulfonyl group at the 1-position of the hydantoin ring greatly affects the physico-chemical properties: the acid dissociation constants were increased 1000-fold and the partition coefficients were increased 100- to 1000-fold in the chloroform/water system and 10- to 100-fold in the n-octanol/water system. The solubilities of 1-benzenesulfonylhydantoin derivatives increased with increasing pH of the solution at pH more than 5, but the solubilities of the 1- unsubstituted hydantoin derivatives were scarcely dependent on the pH of the solution in the pH 1 to 8 region. The intestinal absorption from solution was found to be caused by the passive transport according to the first-order kinetics. The rate constants of absorption of 1-benzenesulfonylhydantoin derivatives were rather large even under the condition where they were 99% ionized in the solution than that of the corresponding 1-unsubstituted hydantoin derivatives which exist mainly as the unionized from under the same condition. The intestinal absorption from a solution and the partitioning to chloroform produced linear free energy relationships to each other for the 1-benzenesulfonylhydatoin derivatives and for the 1-unsubstituted hydantoin derivatives independently. However when the partition coefficients in the n-octanol/water system were applied, the hydroxyl derivatives were found to deviate from linear relationships. On the basis of the results, a suggestion was made on the in vivo behavior and the bioavailability.

Animals

Effect of total colectomy and mucosal proctectomy on intestinal absorptive capacity in dogs.

Changes in intestinal absorptive capacity for water and electrolytes were investigated in dogs after total colectomy and mucosal proctectomy reconstructed with interposing jejunum into the anorectal area. Rate of absorption of water and sodium from the ileum increased significantly at 29 weeks postoperatively. The absorption of water, sodium, and chloride in the jejunum was significantly higher than in the neorectum. The net secretion rate of potassium increased significantly in the ileum and neorectum. The authors suggest that intestinal adaptation achieved after proctocolectomy is enhanced in the jejunum and ileum rather than in the neorectum.

Animals

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

[Postoperative small intestine absorption--principles for enteral nutrition].

The intestinal absorption of nutrients is disturbed to an extent dependent on the degree of trauma in the immediate postoperative period. In a clinical study, the d-xylose absorption was investigated in 3 groups of patients after cholecystectomy. On the day of surgery a significant restriction of the absorption could be observed after intraduodenal administration. After gastric and duodenal administration of d-xylose and simultaneous enteral early nutrition a significant restriction of absorption could be observed on the day surgery was carried out. Optimal conditions for early nutrition can be achieved by combining intraduodenal feeding and a continuous decompression of the stomach. In cases of a gastric drainage an improvement of the postoperative absorptive function can be supported by the results of the nitrogen balance. In 4 pigs (type: country race) the step-by-step normalization of the absorptive kinetics could be demonstrated after catheters were implanted into the portal and subclavian veins.

Adult

Intestinal absorption of calcium and phosphorus.

The intestinal absorption of calcium and phosphorus has received considerable attention in recent years. The evidence has clearly indicated that calcium is absorbed by two processes: active transport and diffusion. Vitamin D appears to affect both processes, and has a significant effect at the brush border of the intestinal cell. Vitamin D also affects the release of calcium from the intestinal cell to the lamina propria. Several proposed models to account for the transmural movement of calcium are discussed. The active transport of phosphate is under the control of vitamin D and is located at the brush border region of the intestinal cell. This transport system, like several others, appears to be sodium-dependent and inhibited by ouabain. In-transit phosphate does not mix with the cellular phosphate pool, implying that phosphate is moving through the cell as a distinct packet or through specialized channels, or possibly a phosphorylated derivative. Emphasized in the presentation is current knowledge of the transport mechanisms and macromolecular changes that potentially account for the stimulatory effect of vitamin D on calcium and phosphate transport.

Adenylyl Cyclases

Control of intestinal absorption by the renin-angiotensin system.

In vivo angiotensin II (ANG II) exerts a dose-dependent dual action upon intestinal absorption. At low doses, ANG II stimulates sodium (Na) and water absorption from all intestinal areas. At high doses, ANG II inhibits absorption. The stimulation of jejunal absorption in response to ANG II is secondary to the release of norepinephrine (NE) from enteric sympathetic nerves. ANG II may act either within the brain or at the sympathetic nerve terminal to liberate NE. In contrast, the inhibition of absorption in response to ANG II is due to enteric prostaglandin production. At the present time it is unclear whether the changes in absorption in response to ANG II in vivo are due to changes in transport processes or secondary to alterations in enteric hemodynamics. ANG II also exerts a dose-dependent dual action on intestinal ion and water absorption in vitro. The mechanisms responsible for changes in absorption in vitro are unknown. However, since enteric sympathetic nerves are severed from their ganglia, it is unlikely that ANG II stimulates absorption in isolated preparations through release of NE. ANG II exerts a major control over intestinal absorption following volume depletion. The hormone controls colonic absorption through release of aldosterone and directly influences jejunal absorption via enteric sympathetic nerves. ANG II may control ileal absorption following volume depletion. All components of the renin-angiotensin system are present within the intestine. Furthermore, ANG II-like immunoreactivity is present within enteric nerves. The role of locally formed ANG II in the control of intestinal absorption has not been studied. Models illustrating the effect of ANG II on intestinal absorption are discussed.

Adrenalectomy

Linoleic acid chyloportal partition and metabolism during its intestinal absorption.

1-14C linoleic acid intestinal absorption and simultaneous biochemical events were followed up on rats under vascular perfusion and on main mesenteric lymphatic duct fistulated rats. 1-14C linoleic acid was introduced in the duodenum alone in doses from 1.2 to 90 mumol or in the presence of oleic acid and monopalmitin (30/30/30 mumol/mumol/mumol). Mesenteric portal venous blood and chyle, respectively, were collected continuously for 1 and 6 h after the infusions. Blood-labeled lipid recovery varied from 4.7 to 2.2% of the 14C linoleic acid infused as the 14C linoleic acid dose infused increased, and dropped to 1.8% with the mixed lipid infusate. Lymph-labeled lipid recovery increased from 25.7 to 31.8% of the 14C linoleic acid infused as the dose infused increased, and rose to 48.1% with the mixed lipid infusate. The oxidation of 1-14C linoleic acid remained low: 0.8-3% of the infused radioactivity. A desaturation and elongation of 14C linoleic acid into 14C arachidonic acid was detected and discussed. We can conclude that the linoleic lymph absorption pathway remained preferential in our experimental conditions, simultaneous to a low rate of oxidation and an eventual ability for the enterocyte to convert this essential fatty acid arachidonic acid.

Animals

Effect of zinc supplements on the intestinal absorption of calcium.

Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca47 and determining plasma levels and urinary and fecal excretions of Ca47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake.

Adult

Intestinal absorption of bile acid glucuronides in rats.

While the intestinal absorption of taurine, glycine, and sulfate conjugates of bile acids has been studied extensively, nothing is known about the absorption of bile acid glucuronides. In the present study, the intestinal phase of the enterohepatic circulation of two bile acid glucuronides was examined. [3 beta-3H]cholic acid 3-O-beta-D-glucuronide or [3 beta-3H]lithocholic acid 3-O-beta-D-glucuronide was perfused through isolated segments of ileum or jejunum with intact blood supply in rats prepared with a biliary fistula. [14C]Taurocholic acid was perfused simultaneously with each glucuronide to compare glucuronide absorption with that of an actively transported bile acid. Intestinal absorption was determined by measuring the rate of secretion of labeled bile acid in bile. The absorption of [3H]cholic acid glucuronide by the ileum and jejunum was one fortieth and one eighth, respectively, that of [14C]taurocholic acid. Comparison of the two glucuronides show that [3H]lithocholic acid glucuronide absorption was 18 and 10 times greater than [3H]cholic acid glucuronide absorption from the jejunum and ileum, respectively. Collectively, the above observations suggest that glucuronidation of bile acids markedly reduces absorption from the small intestine.

Animals

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.

Animals

Site-dependent small intestinal absorption of ranitidine.

The site-dependent, small intestinal absorption characteristics of ranitidine were estimated by the intestinal steady state perfusion technique (triple lumen tubing system) combined with simultaneous measurement of serum concentrations of ranitidine. Ranitidine 150 mg.l-1 was perfused at 10 ml.min-1 for 180 min in different sites of the small intestine between 65-250 cm beyond the teeth. Each of 9 healthy, male volunteers was examined twice, using perfusion sites in different regions of the small intestine to permit intraindividual comparisons. The absorption rates (micrograms.30 cm-1.min-1) calculated from intestinal samples showed distinct site-dependence; the highest rates (medians 160-923 micrograms.30 cm-1.min-1) were found in the most proximal region (duodenojejunal junction), and the most distal perfusion sites (distal jejunum/ileum) showed median rates from 193 to 265 micrograms.30 cm-1.min-1. In both of these regions there was a significant positive correlation between the net intestinal water flux and the movement of ranitidine. Within the mid-jejunum, every subject showed marked secretion of ranitidine into the gut lumen (medians -338 to -124 micrograms.30 cm-1.min-1), and in this region there was no influence of water flux on ranitidine movement. The intraluminal results were confirmed by the corresponding site-dependent areas under the serum concentration-time curves (AUC), which decreased with the distance of the perfusion site from the teeth. After the more distal perfusions individual AUCs amounted to 64-16% of the AUCs obtained after more proximal applications. The results demonstrate the small intestine as the site of a gradient of absorption of ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The effect of luminal pH on large intestinal absorption in ulcerative proctocolitis.

The sensitivity of large intestinal absorption to pH and the absorption of short-chain fatty acids were measured in ulcerative proctocolitis by a dialysis bag method. Lowering luminal pH from 7 to 5.5 significantly reduced absorption of salt and water in proctocolitis, but not in normal controls. Short-chain fatty acid absorption was not affected by inflammation or change in pH when patients with ulcerative proctocolitis were compared with controls.

Adult

Intestinal absorption of copper: effect of sodium.

The mechanisms of copper (Cu) absorption from the small intestinal lumen are poorly understood. In this study we investigated the role of sodium (Na) during the removal of Cu from the lumen of jejunal and ileal segments, using an in situ perfusion procedure in the anesthetized rat. Intestinal absorption of Cu from a 31 microM solution was highest in the presence of an isotonic concentration of NaCl, as compared to solutions containing either glycerol (GRL) or N-methyl-D-glucamine (NMG) as osmotic agents. In the jejunum, mean +/- SEM Cu absorption rates in the presence of the following solutes were: with NaCl, 57.5 +/- 10.5 pmole/min X cm; with GRL, 13.3 +/- 14.7 (P less than 0.05); with NMG, 18.4 +/- 10.1 (P less than 0.05). In the ileum, copper absorption in the presence of NaCl was 64.4 +/- 9.6; with GRL, 24.3 +/- 10.1 (P less than 0.01); with NMG, 15.8 +/- 3.7 (P less than 0.001). Kinetic analysis of the carrier-mediated component of Cu absorption in rat jejunum yielded a Vmax = 47.5 pmole/min X cm and an apparent Kt = 21 microM. The diffusion coefficient was calculated to be 1.4 X 10(-5) cm2/sec. The absorption of Cu was independent of net water absorption, which was highest in the presence of GRL and abolished and reversed into secretion by NMG. The data obtained are indicative of a significant role of Na in the small intestinal transport of Cu, in vivo, although not directly related to unidirectional water fluxes. The cation specificity of Na in this process remains to be elucidated, although the results support earlier studies which postulated that mediated transport may constitute a major component of Cu absorption in the mammalian small intestine.

Absorption

Improvement of bioavailability of poorly absorbed drugs. II. Effect of medium chain glyceride base on the intestinal absorption of cefmetazole sodium in rats and dogs.

The effect of medium chain glyceride (MCG) on the intestinal absorption of cefmetazole sodium (CMZ) was investigated in rats and dogs. In rats, MCG containing glyceryl mono-, di- and tri-caprylate enhanced the intestinal absorption of CMZ after intraduodenal administration, though the promoting effect of MCG was less than that after rectal administration. The promoting effect of MCG was found to be mainly due to glycerylmonocaprylate and dependent on the dosage of MCG. The plasma CMZ levels after intraduodenal administration as MCG solution tended to be slightly higher than those observed after administration as MCG emulsion, though the differences were found to be statistically insignificant. Moreover, the intestinal absorption of CMZ after intraduodenal administration as MCG emulsion was decreased significantly by increasing the amount of water in the emulsion. The promoting effect of MCG in dogs was more clearly demonstrated in the lower intestine than in the upper intestine. Furthermore, the oral bioavailability of pharmaceutical formulations of CMZ was also investigated in dogs. When enteric coated capsules filled with MCG solution were administered to dogs, the bioavailability of CMZ was enhanced significantly.

Animals

Synthesis, intestinal absorption and metabolism of sarcosine conjugated ursodeoxycholic acid.

Sarcosine conjugated ursodeoxycholic acid (SUDC) was synthesized and its intestinal absorption and metabolism were studied in rat and hamster. Intestinal absorption study using bile fistula rat shows that more than 90% of SUDC administered intraduodenally was excreted in the bile within 24 hr. No change of the administered bile acid was seen during the absorption from the intestine, the passage of the liver, and the excretion into the bile. When [24-14C]SUDC and [11,12-3H2]-ursodeoxycholic acid were administered orally to a hamster, more than 95% of both the administered 14C and 3H were recovered from the feces within 6 days. Most (77%) of the fecal 14C-labeled compound was SUDC, whereas 95% of the fecal 3H-labeled compound was unconjugated lithocholic acid. These results indicate that SUDC, unlike taurine or glycine conjugated bile acid, resists bacterial deconjugation and 7-dehydroxylation.

Animals

Determinants of the rate of intestinal absorption of oral cholecystographic contrast agents in the dog jejunum.

Successful opacification of the gallbladder during oral cholecystography depends on adequate absorption of the contrast agent from the intestine. The present studies were undertaken to define the specific characteristics of the intestinal mucosa and the properties of the various contrast agents which determine their rates of intestinal absorption. The polarity of the compounds was established by determining the ratios of their distribution between bulk solvents (benzene and water). In addition, the maximum aqueous solubility of each compound was determined. Using in vivo cannulated segments of dog jejunum, apparent passive permeability coefficients were measured. From these data, the apparent maximal rate of intestinal absorption was calculated. The six cholecystopaques studied differed markedly in polarity as judged by their varying ratios of distribution between benzene and water. The permeability coefficients varied inversely with the polarity of the compounds. However, the incremental changes in the coefficients were considerably less than the corresponding changes observed in the partition ratios. The rates of absorption of the more polar contrast agents (tyropanoate, iopronic acid, and iocetamic acid) were greater than the less polar compounds (iopanoic acid, sodium ipodate, and calcium ipodate) under the conditions in which the resistance of the unstirred water layer is not rate limiting and where bile acid micelles are not present.

Animals