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In vivo intestinal absorption of selenate and selenite by rats.

Intestinal absorption of selenate and selenite was investigated in rats by using an in vivo perfusion technique. Different segments of the intestine were perfused with an isotonic solution containing different concentrations of SeO42- or SeO32-. The site of greatest SeO42- absorption was found to be the ileum followed in descending order by the proximal jejunum and large intestine (cecum and colon). Furthermore, SeO42- was absorbed significantly faster from the ileum than SeO32-. The concentration dependence of SeO42- absorption indicates that SeO42- is absorbed by a saturable transport mechanism of the ileal mucosa. Absorption of SeO42- at a concentration of 0.01 mM was not affected by the presence of 1 mM SeO42- in the perfusate. When the SeO42- concentration of the perfusate was increased to 1 mM, the absorptive functions of the ileal epithelium appeared to be generally impaired. It is concluded that selenate is absorbed from the ileum by a carrier-mediated mechanism.

Animals

Effects of silicon, citrate and the fasting state on the intestinal absorption of aluminium in rats.

1. The effect of silicon (Si) contained in drinking water and solid food on the intestinal absorption of aluminium (Al) remains a matter of debate. The present study was designed to readdress this issue in the experimental animal, and to examine concomitantly the effects of citrate and the fasting state, respectively. 2. Three groups of young, non-fasted rats (n = 8 per group) were gavaged by solutions containing 3.8 ng of 26Al, 63 ng of 27Al, and either distilled water (< 0.1 mg/l Si) or commercial mineral water with a medium (6 mg/l) or high (14 mg/l) Si concentration. 3. Two other groups of eight non-fasted rats each received the same distilled water or high-Si gavage solution, respectively, together with a high citrate concentration (62 g/l). In each case the animals had free access to drinking water for 5 days before and 2 days after the gavage, containing the same Si concentration as in the gavage solution. A sixth group of eight rats was gavaged by low-Si, Al and distilled water in the fasted state. 4. The animals were killed 48 h after gavage, and blood, tissue and urine samples were collected for 26Al measurements by accelerator mass spectrometry. 5. We found that the fraction of absorbed 26Al retained in the skeleton (0.025-0.030%) was of the same order of magnitude as the fraction excreted in the 48 h urine (0.035-0.037%). High Si concentrations in the drinking water failed to depress the 26Al fraction absorbed, as estimated on the basis of skeletal accumulation and urinary excretion. 6. The administration of citrate-containing fluid enhanced 26Al absorption 5- to 10-fold (P < 0.005), but again the Si content of drinking water did not interfere. Finally, the intestinal absorption of 26Al was approximately 15 times higher in the fasted than in the non-fasted state. 7. In conclusion, the provision of large amounts of Si in the drinking water failed to modify physiological intestinal Al absorption under basal conditions or after its stimulation by citrate. However, a prolonged fast greatly enhanced Al absorption, compared with the non-fasted state.

Aluminum

The intestinal absorption of dietary folates in health and disease.

Dietary folates exist as pteroylpolyglutamates (PteGlun) that undergo hydrolysis to pteroylmonoglutamate (PteGlu) forms during the process of intestinal absorption. Using the technique of jejunal perfusion of separately labeled folates, our laboratory has demonstrated that hydrolysis of PteGlun occurs on the surface of the jejunum and is a prerequisite for folate absorption. An intestinal brush border pteroylpolyglutamate hydrolase (BB-PPH) has been identified in human and pig jejunum with characteristics that are distinct from those of an intracellular hydrolase (IC-PPH). Functional parallels of BB-PPH with in vivo hydrolysis of PteGlun in human and pig intestine and the clinical responsiveness of BB-PPH to different disease states indicate that this enzyme plays the major physiological role in folate absorption. Folate malabsorption is found in diseases which affect the jejunal mucosa and in response to various drugs. In most of these clinical conditions, folate malabsorption results from suppression of both of the processes of hydrolysis of PteGlun and jejunal uptake of PteGlu. Ongoing studies in miniature pigs are aimed at definition of the sequence of development of folate malabsorption in chronic alcoholism.

Animals

A comparison of the effects of mineral oil, vegetable oil, and sodium sulfate on the intestinal absorption of DDT in rodents.

The effects of mineral oil, vegetable oil, and sodium sulfate on the intestinal absorption of a highly lipid soluble pesticide, DDT, were compared in the rat. Intestinal absorption was evaluated by measuring recovery of DDT and metabolites in feces and the concentration of DDT in adipose tissue following oral administration of DDT and each agent. Vegetable oil was shown to significantly increase absorption of DDT when compared to all other treatments.

Adipose Tissue

Small intestinal absorption of polyethylene glycol 400 to 1,000 in the portacaval shunted rat.

Functional changes of the intestinal barrier that may occur after the creation of a portacaval shunt (PCS) were investigated. After chronic PCS in the rat, the intestinal absorption of and the jejunal permeability to the inert polymer marker polyethylene glycol (PEG) with molecular weight (Mw) ranging from 400 to 1,000 g/mol were investigated. The PEG mixture was orally fed to PCS and sham-operated rats, and urine was collected for 24 hours to obtain the urinary recovery of the different PEG polymers as a measure of intestinal absorption. To study the intestinal permeability, segments from the proximal small intestine were incubated in diffusion chambers with the PEG mixture on the mucosal side, and samples were withdrawn from the serosal side for analysis. The urinary recovery for the PEGs increased (P < .01) while the tissue permeability decreased (P < .001) in the PCS group rats in comparison with Sham-operated rats. The increased absorption in vivo was caused neither by altered renal clearance, nor by changed portal blood pressure. The decreased jejunal permeability in the PCS rats could be explained by a reduction of the mucosal area by shortening of the microvilli. This discrepancy indicates that changes in permeability and absorption may not be parallel during PCS. It is possible that these changes also may be affected by nutritional factors, drug therapy, as well as toxic substances.

Animals

[Intestinal absorption of digoxin in systemic sclerosis (author's transl)].

Gastro-intestinal absorption of digoxin was evaluated in 18 patients with progressive systemic sclerosis. In 8 patients a single-dose crossover study was performed after oral and intravenous administration of 0.5 mg digoxin by comparing the aera under the eight-hour plasma concentration curve. The fraction of the dose absorbed was diminished in 4 patients to less than 55%. There was a significant positive correlation between the extent of digoxin absorption and xylose renal excretion. In addition, steady state digoxin plasma levels and 24-h urinary excretion of digoxin were determined during maintenance therapy in 12 patients. In 6 patients renal excretion of digoxin was clearly less than in normal subjects during chronic dosing of the same digoxin preparation. This finding corresponded well with digoxin plasma levels below the usual therapeutic range in most of the patients. The impaired absorption of digoxin failed to correlate with the extent of the skin manifestation or the time course of the disease while there was massive oesophageal dysfunction in most of these patients. The results suggest that an inadequate therapeutic response to cardiac glycosides in patients suffering from progressive systemic sclerosis is at least partially due to impaired digoxin absorption. Similar problems could occur in therapy of the disease itself due to insufficient enteral absorption of drugs used in treatment of systemic sclerosis.

Administration, Oral

Effect of raw legume diets on intestinal absorption of D-galactose by chick.

The effect of four raw legume diets on the intestinal absorption of D-galactose and oxygen consumption were studied in chick. Field beans (Vicia faba), soybeans (Glycine soja), bitter vetch (Vicia ervilia), and navy beans (Phaseolus vulgaris), were used. The intestinal absorption was determined by both in vivo and in vitro techniques. In vivo, only navy beans and soybeans inhibit intestinal transport of D-galactose, while in vitro all the diets do. Oxygen consumption by intestinal rings increases in chicks fed on bitter vetch diet.

Animal Feed

Intestinal absorption of sugar-coupled somatostatin analogs.

The intestinal absorption of glycosylated somatostatin analogs was compared in rat enterocyte brush border membranes as an in vitro test system and rats as an in situ absorption model. Derivatives of the cyclic octapeptide octreotide with mono-, di-, and trisaccharide residues were used. The uptake of octreotide by the vesicles was inhibited by the glycosylated analogs. The uptake was not inhibited by the bicyclic octapeptide alpha-amanitin, which exhibits structural similarity but is not absorbed in rats. The inhibition of octreotide permeation into the vesicles decreased in the presence of derivatives with an increasing length of the carbohydrate residues. To evaluate, whether the vesicle system is predictable for the in situ situation, the extent of absorption of the peptides was determined after intrajejunal administration. A linear relationship between inhibitory capacity of the octreotide derivatives in the vesicle system and their in situ absorption efficiency was found when blood was taken from a mesenteric vein. However, after sampling from a peripheral vein, deviations from the predicted values were noted. These differences reflected changes in pharmacokinetics (e.g., hepatic elimination) rather than in absorption. In summary, the data indicate that the vesicle system is a useful tool to predict the absorption efficiency of glycosylated somatostatin analogs in situ.

Animals

Intestinal absorption under the influence of vasopressin: studies in unanaesthetised rats.

Experiments were carried out in different segments of the intestine of unanaesthetised rats to assess the effect of vasopressin on intestinal absorptive processes. The following data were observed. (1) Within a physiological range of doses (Aziz, 1969), ADH diminished the net sodium absorption mainly by reducing the unidirectional sodium influx, whereas the behaviour of the efflux was not uniform. (2) The unidirectional volume fluxes showed the same behaviour as did the sodium fluxes. (3) ADH produced an oral-aboral gradient (jejunum greater than ileum greater than colon). (4) ADH did not significantly change the transfer of actively transported sugars; it did influence, however, passively transported substances. (5) During the intravenous application of ADH, a substance was secreted into the perfusion solution which diminished the absorption of volume and electrolytes. (6) Cyclic AMP acted on intestinal absorption in the same way as did ADH. In view of these results two mutually independent transport pathways for sodium and water are supposed, one of which is influenced by ADH or cAMP. Based on a two membrane model, an ADH mechanism is discussed: the permeability of the luminal membrane system is enhanced in the presence of vasopressin.

Animals

Small-intestinal absorption of cadmium and the significance of mucosal metallothionein.

1 Although food intake is among the most important routes of Cd exposure, not many details are known about the intestinal absorption mechanisms of Cd. In this respect Cd is representative of most other nonessential, merely toxic metals. 2 Based on a concept of two distinguishable steps, intestinal absorption of Cd is characterized by high accumulation within the intestinal mucosa and a low rate of diffusive transfer into the organism. 3 After uptake into the mammalian organism, Cd is sequestered into hepatic metallothionein (MT). It is assumed that hepatic Cd-MT then gradually redistributes Cd to the kidney, which is the main target organ for chronic Cd toxicity. 4 When feeding low levels of dietary CdCl2, however, Cd accumulates preferentially in the kidney and to a lesser degree in the liver, a distribution pattern also found after intravenous and peroral administration of the Cd-MT complex itself. As dietary Cd induces intestinal MT, intestinal Cd-MT complexes could be at least partly responsible for the renal accumulation of dietary Cd. 5 For this mechanism, however, serosal release of mucosal Cd-MT is required. In fact, in vitro findings in rats reveal a concentration-dependent release of intestinal MT to the serosal side of the small intestine. These results indicate that endogenous intestinal MT may deliver Cd-MT to other inner organs, thus contributing to the preferential renal accumulation of ingested Cd.

Animals

Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport.

Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length.

Animals

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine.

The intestinal absorption and metabolism of single oral doses of imipramine (ip) have been studied in man by portal catheterization. The concentration of ip and the formed desipramine (dmi) was followed in blood-plasma obtained from the portal and cubital veins. The absorption of ip seemed to be completed 80 min after the administration of the drug. There was no sign of demethylation of ip during the passage across the intestinal wall. Evidence was found of an enterohepatic circulation of both ip and dmi.

Dealkylation

Comparative effects of intestinal absorption of folic acid and methyltetrahydrofolic acid in chronic ethanol-fed rats.

This study concerns in vivo folic acid and methyltetrahydrofolic acid (MTHF) absorption by the whole intestinal surface after 20 weeks of 30% ethanol ingestion in drinking water. The results were compared with control rats fed ad libitum. The total intestinal serosal areas were similar in ethanol-fed and control rats. Significant increases in intestinal length, and decreases in tissue wet and dry weights were found in ethanol-fed rats. Serum folic acid concentrations were significantly less in the animals which had ingested ethanol than in the control rats. Intestinal folic acid absorption was significantly increased at lower substrate concentrations (0.5 and 1 microM), while no difference was observed at 2.5 microM in the ethanol-fed rats. Folic acid absorption relative to tissue wet weight showed significant increases at all tested concentrations in the ethanol-fed rats. Intestinal MTHF absorption showed no significant changes at 0.5 microM MTHF concentration, and an increase was observed in the absorption values at 1 and 2.5 microM concentrations in the ethanol-fed rats. When expressed as tissue wet weight, MTHF absorption values in ethanol-fed rats increased at 1 and 2.5 microM but did not differ at 0.5 microM substrate concentrations. The above results indicate compensatory responses in the folic acid and MTHF intestinal absorption after chronic ethanol ingestion. These effects are observed when the whole intestinal surface is evaluated.

Animals

Acute effects of guar gum on glucose tolerance and intestinal absorption of nutrients in rats.

The mechanism by which non-digestible fibres improve oral glucose tolerance is still unclear. We have studied the effects of guar gum on oral carbohydrate tolerance and intestinal absorption of nutrients in anaesthetized rats. Addition of guar to an intragastric glucose load (1 g/kg) markedly delayed the rise in plasma glucose levels when the concentration of the gum was adequate (10 mg/ml). The insulin response was somewhat less marked, but the differences were not significant. When glucose was introduced directly into the duodenum, the gum only slightly reduced the rise in glucose levels, during the first 15 min. If sucrose (1 g/kg) was infused in the duodenum, acarboseR, an alpha-glucosidase inhibitor, but not guar, slowed the rise in plasma glucose and insulin levels. Intestinal absorption was measured in a tied duodenojejunal loop. Guar decreased active transport of glucose (4 mmol/l) by approximately 20%, but had no significant effect on the passive transport of glucose (100 mmol/l), nor on the absorption of sucrose (40 mmol/l) or leucine (4 mmol/l). At the concentration which improved glucose tolerance (10 mg/ml), but not at lower concentrations, guar gum markedly slowed gastric emptying. These results suggest that guar gum improves tolerance to oral carbohydrates mainly by decreasing the rate of gastric emptying, but inhibition of intestinal absorption may also be involved in the presence of low concentrations of the sugars.

Animals

Early stages of intestinal absorption of specific antibiodies in the newborn. An ultrastructural, cytochemical, and immunological study in the pig, rat, and rabbit.

In mammals, passive immunity is transferred from mother to offspring by transplacental passage or by intestinal absorption. The rabbit receives antibodies exclusively across the placenta, whereas intestinal absorption is the principal source of antibodies for the new-born pig. In the rat, passive immunity is transferred by both pathways. The role of the jejunal absorptive cells was investigated in these three species, by the use of specific immune globulins as tracers of protein absorption. Rabbit anti-peroxidase and anti-ferritin antibodies were injected into the jejunum of newborn pigs, rats, and rabbits, and absorption was studied over the first 2 hr. The specific antibodies were detected in glutaraldehyde-fixed tissues after in vitro treatment with the antigens, and in sera by immunological methods. Intact antibodies are transferred into the circulation of the pig and the rat, but not into that of the rabbit. In the three species, the jejunal absorptive cells take up antibodies by endocytosis. In the pig, the antibodies are transported across the epithelium in vacuoles. In the rabbit, the endocytosis of antibodies triggers a lysosomal response and all absorbed antibodies are trapped in lysosomes. In the rat, both situations are found; there is no evidence of transfer of antibody fragments into the circulation.

Animals

Effect of verapamil on intestinal absorption of calcium in the rat.

The effect of verapamil in vitro, and the in vivo effect of both oral and parenteral verapamil administration on intestinal absorption was tested using everted gut sacs of duodenum, jejunum, distal ileum and proximal colon in rats. In the in vivo study, the effect of verapamil on blood levels of calcium, phosphorus and 1.25(OH)2D3, was investigated and a complete calcium balance was performed. In vitro, verapamil (1.5 mM) inhibited calcium absorption by the duodenum and colon only. Oral verapamil led to a reduction in the blood level of 1.25(OH)2D3. However, both oral and parenteral verapamil had no effect on the intestinal absorption, urinary secretion and consequently on the calcium balance.

Animals