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Intestinal absorption of zinc: sodium-metal-ligand interactions.

The characteristics of zinc small intestinal absorption were investigated with the purpose of clarifying the role of sodium and the possible interaction among certain amino acids, oligopeptides, and zinc with electrolyte and water absorption. A perfusion procedure was used in anesthetized rats. Physiological concentrations of zinc with no ligands, or with twice the zinc levels of either Trp, His, Pro, or a protein hydrolysate (PrH) were pumped through jejunal or ileal segments. PrH was also used at a 10: 1 ratio to zinc. The osmotic solutes were either sodium chloride, glycerol, or NMG at isotonic concentrations. In the absence of LMW ligands, zinc transport appeared to occur only by diffusion, except in the ileum and in the presence of glycerol, where at low zinc concentrations a low affinity mediated transport component could be identified (Kt = 0.67 mM; Vmax = 1,160 pmole/min.cm. Glycerol generally elicited a greater overall zinc absorption rate as well as an enhanced net water uptake than when sodium chloride was the osmotic agent when either Trp, His, or Pro was present. The data indicate that sodium is not a requirement for zinc transport. In the presence of LMW ligands, which may also be from endogenous origin, bulk flow may be a major contributor of zinc translocation across the mammalian small intestinal mucosa.

Amino Acids↗

Immunological control of drug absorption from the gastrointestinal tract: the mechanism whereby intestinal anaphylaxis interferes with the intestinal absorption of bromthymol blue in the rat.

Rats were immunized intraperitoneally with ovalbumin and the disappearance of bromthymol blue (BTB) from the intestinal lumen, its accumulation in the tissue, and its net absorption were examined by means of an in-situ recirculation technique during local anaphylaxis. The disappearance of BTB from the intestinal lumen and its net absorption were significantly reduced, but there was no significant effect on its accumulation in the tissue. The pH value of the luminal solution and the perfusate volume were not influenced by intraluminal challenge with the antigen in ovalbumin-immunized rats. In addition, no significant effect was observed on intestinal permeability to BTB in the in-vitro everted sac technique. The intestinal blood flow, measured by a hydrogen clearance method, was not reduced significantly by the intraluminal exposure to antigen. There was enhanced Evans Blue leakage and mucus release in the perfusate after intraluminal challenge with ovalbumin in ovalbumin-immunized rats, but not in non-immunized rats. A significant increase of BTB binding with macromolecular substances in the perfusate was observed during the local anaphylaxis. These findings suggest that the decreased absorption of BTB is due to the interaction with the macromolecular substances in the perfusate during local anaphylaxis.

Anaphylaxis↗

Inhibition of steady-state intestinal absorption of long-chain triglyceride by medium-chain triglyceride in the unanesthetized rat.

Maximal steady-state intestinal absorption rates in unanesthetized rats for triolein, a long-chain triglyceride, and for trioctanoin, a medium-chain triglyceride, are known to differ. Both these lipids are hydrolyzed in the intestinal lumen but the products of hydrolysis are metabolized differently by the mucosal cell. Intraduodenal infusion of trioctanoin was found to reduce steady-state triolein absorption. Luminal lipolysis was shown not to be rate-controlling. High rates of trioctanoin infusion significantly lowered the pH of the luminal aqueous phase and altered the partition of oleic acid between aqueous and oil phases. Two possible mechanisms for the inhibition of triolein uptake are considered. In the intestinal lumen medium chain lipids might have lowered the activity of oleic acid monomers in the aqueous phase and reduced passive diffusion into mucosal cells. Alternatively, competition between long and medium chain fatty acids for some common receptor during transport into the intestinal mucosal cell may have occurred. Despite significant inhibition of triolein absorption by high levels of trioctanoin, the maximum number of calories absorbed from mixtures of triglycerides exceeded the maxima from either glyceride alone. The optimum proportion of triolein to trioctanoin in lipid infusion mixtures was about 3:4 by weight and the optimum dosages about half maximal for each triglyceride, which represented a caloric intake of 4 kcal/rat per 2 hr. The absorption coefficient for this lipid mixture was about 90%. It is suggested that in patients who have a limited intestinal absorptive capacity dietary fat intake might be doubled with a caloric supplement of medium-chain triglycerides without increase in steatorrhea of long-chain fat.

Animals↗

Intestinal absorption and biomagnification of organic contaminants in fish, wildlife, and humans.

Methods for the regulatory assessment of the bioaccumulation potential of organic chemicals are founded on empirical measurements and mechanistic models of dietary absorption and biomagnification. This study includes a review of the current state of knowledge regarding mechanisms and models of intestinal absorption and biomagnification of organic chemicals in organisms of aquatic and terrestrial food chains and also includes a discussion of the implications of these models for assessing the bioaccumulation potential of organic chemicals. Four mechanistic models, including biomass conversion, digestion or gastrointestinal magnification, micelle-mediated diffusion, and fat-flush diffusion, are evaluated. The models contain many similarities and represent an evolution in understanding of chemical bioaccumulation processes. An important difference between the biomagnification models is whether intestinal absorption of an ingested contaminant occurs solely via passive molecular diffusion through serial resistances or via facilitated diffusion that incorporates an additional advective transport mechanism in parallel (i.e., molecular ferrying within gastrointestinal micelles). This difference has an effect on the selection of physicochemical properties that best anticipate the bioaccumulative potential of commercial chemicals in aquatic and terrestrial food chains. Current regulatory initiatives utilizing Kow threshold criteria to assess chemical bioaccumulation potential are shown to be unable to identify certain bioaccumulative substances in air-breathing animals. We urge further research on dietary absorption and biomagnification of organic chemicals to develop better models for assessing the bioaccumulative nature of organic chemicals.

Absorption↗

[Methods for measuring the intestinal absorption of calcium in humans (author's transl)].

For the determination of intestinal absorption of calcium, the fasting (12 hours) patient receives radioactive labeled calcium (45Ca, more frequently 47Ca) by mouth. After 10, 20, 30, 60, 90, 120, 180 and 240 min, samples of venous blood are taken. The stool is also collected for three days. The determination of radiocalcium in the plasma and in the stool samples is done with a Geiger counter. This oral test provides informative results on numerous aspects of the pathophysiology of intestinal assimilation of calcium. In humans, the duodenum seems to be of the greatest importance for calcium absorption.

Administration, Oral↗

[Carbohydrate substitutes: comparative study of intestinal absorption of fructose, sorbitol and xylitol].

BACKGROUND: The carbohydrate substitutes fructose, sorbitol and xylitol are gaining more and more importance in the production of dietary food. But they can provoke gastrointestinal side-effects. In a randomized double blind study the rate of malabsorption of these sugars was compared and the concomitant symptoms were recorded. SUBJECTS AND METHODS: 25 healthy controls received 25 g of each sugar within 3 consecutive days. The intestinal absorption was determined by H2-exhalation tests and the clinical symptoms were recorded. RESULTS: The rate of malabsorption was 84% for sorbitol, 36% for fructose and 12% for xylitol (p < 0.01 for sorbitol versus fructose and xylitol). 57% of the participants with pathological H2-test after sorbitol and 56% after fructose reported symptoms, while all of the 3 malabsorbers of xylitol were symptomatic. CONCLUSIONS: There is an advantage to administering xylitol and fructose with regard to the intestinal absorption and concomitant symptoms as compared with sorbitol. H2-exhalation tests appear to be a reliable diagnostic tool to detect carbohydrate malabsorption and should find broader application in patients suffering from non-specific abdominal complaints.

Adult↗

Influence of dietary cystine on intestinal absorption and tissue distribution of methionine in the chick.

Studies were conducted on intestinal absorption and tissue distribution of methionine by chicks fed a crystalline amino acid diet containing .2% DL-methionine and .2 or .4% L-cystine or L-cysteine. Chicks fed the higher level of cystine or cysteine had previously been shown to exhibit depressed growth as opposed to chicks fed the lower level of these amino acids. In two experiments, 35S radioactivity of whole plasma and the protein and supernatant fractions were compared among chicks fed the different treatments at 30 or 60 min after oral intubation of L-[35S]-methionine into the crops. When the data were analyzed factorially, a significant level effect was noted for whole plasma and the protein and supernatant fractions, all of which were higher for chicks fed .2% L-cystine than those fed .4% L-cystine. Results with chicks fed the two levels of L-cysteine generally agreed with those of chicks fed L-cystine, although the differences were not as great. The labeled methionine was also added to diets containing .2 or .4% L-cystine of meal-fed chicks. Higher levels of radioactivity were observed in the liver but not in muscle or plasma of chicks fed the lower level of cystine at 7 hr after oral consumption of the isotope. No significant differences in liver, muscle, or plasma radioactivity were noted in a fourth experiment between chicks fed .2 or .4% L-cystine at 24 hr after intraperitoneal injection of L-[35S]-methionine. In vitro studies showed no differences in methionine accumulation by isolated intestinal segments incubated with three levels of cystine.

Animals↗

Characteristics of intestinal absorption and disposition of glycyrrhizin in mice.

As basic studies to apply an intestinal pressure-controlled colon delivery capsule (PCDC) for glycyrrhizin (GZ), the characteristics of intestinal absorption and disposition of GZ were investigated in mice. In the in vivo study, after intravenous (iv) administration of GZ, 10 mg/kg dose, plasma GZ disappeared from the systemic circulation with t(1/2(alpha)) of 0.0063 h, thereafter, it slowly declined with t(1/2(beta)) of 15.23 h. The area under the plasma drug concentration versus time curve (AUC) values of iv (10 mg/kg), intracolonic (50 mg/kg) and intraduodenum (50 mg/kg) administrations were 115.1, 16.7 and 2.7 microgh/mL, respectively. The AUC values of plasma glycyrrhetic acid (GA), a degradation product after intracolonic and intraduodenum administrations were 2.8 and 8.4 microgh/mL, respectively. In the in situ closed loop study, the concentrations of GZ in plasma and liver after intracolonic administration were significantly increased (p<0.05) in comparison with those after intrajejunum or intraileum administration, while the concentration of GA in plasma and liver after intracolonic administration had trends to increase. These observations clearly suggest that the intracolonic administration is a useful way to improve the oral bioavailability of GZ and to enhance its pharmacological efficacy. These pharmacokinetic results of GZ suggest that GZ is a subject drug to be applied for the PCDC system we previously developed. The PCDCs formulation of GZ will enable us to carry GZ to the colon and enhance the oral bioavailability of GZ.

Animals↗

Intestinal absorption of calcium and calcium metabolism in patients with essential hypertension and normal renal function.

Several abnormalities of calcium metabolism have been described in patients with essential hypertension, and they have been linked to the pathogenesis of hypertension. Intestinal calcium absorption has been shown to be decreased in rats with spontaneous hypertension, but it has not been studied in patients with essential hypertension. In these studies we have for the first time measured intestinal absorption of calcium (using oral and intravenous administration of 47Ca), along with other parameters of calcium metabolism, in 14 patients with essential hypertension and normal renal function and in 16 normal subjects. There was no difference in serum total or ionized calcium, serum phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxy-vitamin D(24,25(OH)2D) among hypertensives and normotensives. The urinary excretion of calcium, on the other hand, was greater in hypertensive than in normotensive subjects (195 +/- 33 v 107 +/- 13 mg/24 h, P less than .05). There was also no difference in intestinal absorption of calcium after 2 and 24 h among hypertensives and normotensives. When hypertensive patients were stratified according to plasma renin activity (PRA) we found that patients with low PRA had higher intestinal absorption of calcium at 2 h (23 +/- 2.9 v 18 +/- 0.6%, P less than .05) but not at 24 h. Serum total and ionized calcium, PTH, and 1,25(OH)2D were not different between patients with low and those with normal-high PRA. The major derangement of calcium metabolism in patients with essential hypertension is hypercalciuria. This abnormality is more pronounced in patients with low PRA, and it may lead to increased vitamin D-dependent intestinal absorption of calcium.

Adult↗

Intestinal absorption of trace amounts of aluminium in rats studied with 26aluminium and accelerator mass spectrometry.

1. Until recently studies of intestinal aluminium absorption used pharmacological amounts of stable 27Al. 2. To examine the intestinal absorption of trace amounts of different chemical compounds of aluminium, in the present study we have employed the long half-life isotope of aluminium, 26Al, and accelerator mass spectrometry. Trace amounts of 26Al (2.7-12.1 ng) as the hydroxide, citrate, citrate plus 1 mmol/kg sodium citrate, or maltolate respectively, were administered to four groups of rats (n = 9 per group) by gavage. Blood and urine samples were collected for 5 h and the 26Al content (as a percentage of the administered dose) determined by accelerator mass spectrometry. 3. The 5 h urinary 26Al excretion amounted to 0.1 +/- 0.02, 0.7 +/- 0.2, 5.1 +/- 1.5 and 0.1 +/- 0.1% of administered dose in the four groups respectively. There was a strong positive correlation between peak plasma 26Al (r = 0.98) and urinary 26Al excretion in individual animals (P < 0.001). 4. We conclude that the fractional intestinal absorption of trace oral doses of aluminium hydroxide is at least 0.1% (compared with the previous estimate of 0.01% using large 27Al oral loads). Absorption of aluminium citrate given alone is significantly greater (0.7%) and is further increased to 5% by the accompanying sodium citrate, consistent with an enhancing effect of added citrate upon mucosal aluminium permeability. Aluminium maltolate absorption approximates that of aluminium hydroxide (0.1%).

Aluminum↗

Intestinal absorption of riboflavin, studied by an in situ circulation system using radioactive analogues.

The intestinal absorption of riboflavin was studied using radioactive riboflavin and its analogues 8-demethylriboflavin, 3-methylriboflavin, 5'-deoxyriboflavin, 2'-deoxyriboflavin, 7,8-dimethyl-10-hydroxyethylisoalloxazine, lumiflavin, lumichrome, and riboflavin-5'-monosulfate, which were synthesized with high specific radioactivity. A specific absorption of riboflavin at dietary concentrations was confirmed using an in situ circulation system. The relation between the chemical structure of flavins and the absorption mechanism was studied using this system. The 8-demethylriboflavin, an analogue modified at benzene moiety of the isoalloxazine ring, was absorbed in a similar way to riboflavin, by dual kinetics: by a process specific for riboflavin at dietary concentrations and by simple diffusion (nonspecific absorption) predominating at higher concentrations (over 100 microM). However, 3-methylriboflavin and analogues modified at the ribityl group, including 5'-deoxyriboflavin, were absorbed only via simple diffusion even at dietary concentrations. Many flavins examined, except for 3-isobutylriboflavin, 3-carboxymethylriboflavin, lumichrome, and riboflavin-5'-monosulfate, interfered with the specific absorption of riboflavin. It was concluded from these results that one of the specific absorption processes for riboflavin is a phosphorylation-dephosphorylation process. Four water-soluble vitamins did not interfere with the specific absorption of riboflavin, indicating that these vitamins do not share a common specific absorption pathway with riboflavin.

Animals↗

Effect of gastric emptying rate on the intestinal absorption of chloroquine in rats.

After oral administration, chloroquine caused a dose-related delay in gastric emptying and in its own absorption from the small intestine in rats. Acetyl-beta-methylcholine (0.75 mg/kg i.p.) did not influence the intraperitoneal LD50 value of chloroquine (102 mg/kg) significantly, but reduced oral LD50 from 1,080 to 280 mg/kg. Acetyl-beta-methylcholine increased both the gastric emptying rate and the propulsion motility of the small intestine. As a consequence, the intestinal mucosal surface that had come into contact with the drug was increased in size, resulting in more rapid absorption of chloroquine. Infusion of chloroquine at a rate of 1 mg/min/kg into a mesenteric vein was tolerated by anaesthetized rats for hours. Increasing the dose, however, led to shorter survival times and eventually to death. It is concluded that gastric emptying may play an important role in the rate of intestinal absorption and in the oral toxicity of drugs.

Animals↗

Intestinal absorption following small-bowel resection.

Proximal or distal small-bowel resection was performed on female Wistar rats. Water, glucose, electrolyte, and bile acid absorption from the perfusate was studied in bile-fistula sham-operated rats and in animals 3 months after intestinal resection, using an in-vivo recirculation perfusion system. The jejunum and caecum, but not the colon, showed adaptive increases in intestinal absorption after resection of the ileum, and supranormal bile acid absorption and enhanced glucose, water, and electrolyte absorption were demonstrated in the ileum after jejunal resection. The improvement in diarrhoea observed in some patients after right hemicolectomy may be due to compensatory changes in the residual colon; rectal mucosal thickness becomes significantly increased after right hemicoletomy.

Animals↗

Interactions of cephradine and cefaclor with the intestinal absorption of D-galactose.

Oral cephalosporins are frequently prescribed beta-lactam antibiotics. Although it has been well established that cephalosporins compete with dipeptides for absorption in the intestine, using the same transport mechanism, little is known about the action of the drugs on the absorption of other nutrients. In this work the effect of cephradine and cefaclor on the absorption of D-galactose has been studied. Intestinal sugar uptake was measured in-vitro in pieces of intestine (50 mg) and brush-border membrane vesicles, and in-vivo in intestinal loops. Galactose uptake was inhibited by cephalosporins in a dose-related, time-dependent manner. In-vivo the inhibition appeared when the antibiotics were on the luminal side of the enterocyte and when they reached the gut from the basolateral side. Only the active transport of the sugar was modified; passive transfer did not change in the presence of cephalosporins. In brush-border membrane vesicles, cephradine and cefaclor did not alter sugar uptake in either sodium or potassium gradients. Both antibiotics non-competitively inhibited basolateral Na+,K(+)-ATPase activity. These findings show that cephradine and cefaclor inhibit the active-transport component of galactose absorption because they reduce the activity of the basolateral Na+,K(+)-ATPase.

Animals↗