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[Intestinal absorption of calcium gluconate and oseine-mineral complex: an evaluation by conventional analyses].

Calcium (Ca) preparations are widely used in the treatment of osteoporosis, usually as soluble salts. Tolerance might be improved by prescription of slowly dissolved Ca preparations, since Ca is also absorbed distally, even in the colon. In this regard the use of natural forms of Ca might be advantageous, but natural products cannot be labeled reliably for easy evaluation of their absorption. To study the intestinal absorption of an osseino-mineral complex (Ossopan) in comparison with Ca-gluconate, healthy males were investigated by means of conventional blood and urinary measurements before and after ingestion of either substance containing 1.58 g Ca. All subjects were placed on a standard diet 2 days before and during test day. Ca-gluconate (n = 7) evoked a marked and transient rise in plasma ionized calcium; total plasma calcium and urinary calcium followed a parallel course, while plasma and urinary phosphate decreased. After administration of osseino-mineral complex (n = 6), a slow but sustained elevation of plasma ionized calcium was observed while total calcium remained unchanged when corrected by the plasma proteins. Plasma phosphate and proteins increased, as did urinary phosphate. Comparing the 24-hour urine of the test day with that of the previous day, the rise in calcium excretion was slightly greater in the subjects treated by osseino-mineral complex than in those who were given Ca-gluconate, while phosphate excretion increased in the first group and decreased in the second. It is concluded that the bioavailability of Ca in osseino-mineral complex is as good as, if not better than, that of Ca-gluconate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improvement of intestinal absorption of thyrotropin-releasing hormone by chemical modification with lauric acid.

Intestinal absorption of 125I-labelled lauryl thyrotropin-releasing hormone (Lau-TRH), a novel lipophilic derivative of TRH, was examined by rat in-situ closed intestinal loops. At a dose of 1 mumol per rat into the small intestine, a significant increase in percent of dose in plasma radioactivity of Lau-TRH was observed in comparison with that of TRH. A dose-dependent decrease in percent of dose in plasma radioactivity of TRH was noted, suggesting a saturable process of TRH transport. In contrast, the percent of dose in plasma radioactivity of Lau-TRH increased with increasing dose of Lau-TRH. The stability of TRH and Lau-TRH was studied in plasma and rat small intestinal homogenates. Lau-TRH was more stable than TRH in rat plasma. These results suggest that chemical modification of TRH with lauric acid may not only increase the lipophilicity of TRH but also reduce the degradation of TRH, resulting in the increased plasma radioactivity of TRH. On the other hand, Lau-TRH was gradually converted to TRH in the intestinal mucosal homogenate. These findings indicate that chemical modification of TRH with lauric acid might be a useful approach for improving the intestinal absorption of this peptide.

Animals

Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance.

An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account.

Animals

Impaired intestinal absorption of riboflavin in experimental uremia.

Increased plasma and red blood cell concentrations of riboflavin have been reported in uremia. The possible role of altered intestinal absorption of riboflavin in the genesis of this abnormality is not known. For this reason we examined the intestinal absorption of riboflavin in rats made uremic by subtotal nephrectomy and sham-operated (control) rats in vivo using the recycling perfusion technique and in vitro using the everted-sac technique. Paradoxically, the results showed a significant impairment of intestinal absorption of riboflavin in vivo in uremic rats compared to the control group. However, no significant difference was observed in riboflavin transport in vitro. We conclude that the intestinal absorption of riboflavin is decreased in experimental uremia and cannot account for the reported increase in its plasma and red blood cell concentrations.

Animals

Intestinal absorption of aluminum in rats: effect of intraluminal pH and aluminum concentration.

The intestinal absorption of aluminum (Al) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The jejunum-ileum was perfused with media containing 4.63, 9.25 and 18.50 mmol l-1 Al chloride at pH 4.0 and 7.0. Both mucosal retention was not affected by pH but at lower pH more Al was released into the blood. The amount of Al which appeared in the blood was linearly related to the mucosal retention. The Al release into the blood was much less (mumol l-1) than the mucosal retention (mmol l-1). It is concluded that the intestinal absorption of Al is pH- and concentration-dependent.

Aluminum

Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells.

A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of drugs across intestinal epithelium. The cells formed continuous monolayers when grown on permeable filters of polycarbonate. After 10 days in culture, the monolayers had a transmembrane resistance of approximately 260 ohms.cm2 and a cell density of 0.9 x 10(6) cells/cm2. At this time the cells were impermeable to [14C]polyethyleneglycol (MW 4000). These characteristics remained constant for 20 days (i.e., from day 10 to day 30). Six beta-blocking agents with a 2000-fold range of lipophilicity were studied for their transepithelial transport properties. The transport parameters were independent of drug concentration and transport direction. The apparent permeability coefficients ranged from 41.91 +/- 4.31 x 10(-6) cm/s for the most lipophilic drug, propranolol, to 0.203 +/- 0.004 x 10(-6) cm/s for the most hydrophilic drug, atenolol. The transport parameters were compared with those published for rat ileum. The transport rates were similar for four out of five drugs. Atenolol was transported at a slower rate in the Caco-2 model, which may be explained by the fact that the Caco-2 cells form a tighter epithelium than the rat ileal enterocytes. The findings of this paper indicate that Caco-2 cells may be used to model the intestinal absorption of drugs.

Adrenergic beta-Antagonists

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

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

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

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