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At least 181 records · Page 10Linked to original sources
PubMed1997

Effects of trecadrine, a beta 3-adrenergic agonist, on intestinal absorption of D-galactose and disaccharidase activities in three physiopathological models.

Impairments in intestinal absorptive and digestive processes have been described in several pathophysiological situations, such as in drug-induced diabetes, obesity and hypercholesterolaemia. Furthermore, there is evidence for the occurrence of beta 3-adrenoceptors in multiple regions of the gastrointestinal tract, but there are no data concerning their possible involvement on jejunal and ileal digestive and absorptive functions. In this work, we have measured the modifications of selective intestinal absorption and disaccharidase activities in alloxan-induced diabetic and in diet-induced obese and hypercholesterolaemic Wistar rats. The action of a beta 3-adrenergic agonist (Trecadrine) with hypoglycaemic and lipolytic properties on those gastrointestinal functions has been studied. Increases in the galactose uptake by intestinal rings and in both sucrase and maltase activities were found in diabetic rats. The results obtained after Trecadrine administration to diabetic rats led to an improvement of the altered values. On the other hand, our data show a decrease in sugar absorption and in disaccharidase activities in both obese and hypercholesterolaemic groups, probably related to the low carbohydrate and high fat content of these diets. An amelioration in sucrase activity was observed after treatment with Trecadrine. Finally, Trecadrine administration to control animals significantly inhibited galactose intestinal absorption, which was independently confirmed by additional in-vitro studies. Overall, these results could be attributed not only to an improvement in the pathophysiological condition (diabetes, obesity and hypercholesterolaemia), but also to a direct effect of the beta 3-adrenergic agonist on the intestinal absorption processes.

Adrenergic beta-Agonists↗
PubMed1986

Intestinal absorption studies in Fasciolopsis buski infection.

The intestinal absorption of carbohydrate, fat, protein and vitamin B12, serum vitamin B12, serum and red cell folate levels were performed in 10 patients harbouring F. buski. No disturbance of carbohydrate, fat and protein absorption was observed but vitamin B12 absorption was found to be slightly lower than normal in 8 out of 10 patients, and serum vitamin B12 was also lower than normal in 4 out of 9 patients. Red cell and serum flolate levels were within the normal limits. Histological study of jejunal biopsy was normal in 7 out of 8 patients.

Adolescent↗
PubMed2000

Chronic nifedipine dosing enhances cephalexin bioavailability and intestinal absorption in conscious rats.

Cephalexin, a beta-lactam antibiotic, is rapidly absorbed via the di-and tripeptide intestinal transporters, as for many peptidomimetic drugs. Acute nifedipine has been shown to increase intestinal absorption of several beta-lactams: amoxicillin and cefixime in humans, and cephalexin in the rat. We showed previously that the nervous system was involved in the increasing effect of nifedipine on cephalexin intestinal absorption in anesthetized rats. The aim of the present study was 2-fold: 1) to investigate whether the effect of nifedipine is maintained in conscious rats, and 2) to determine whether the nifedipine effect will persist during chronic nifedipine administration. Acute and chronic oral administration of nifedipine significantly increased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, respectively), while the distribution and elimination parameters of intra-arterial cephalexin were not affected by acute or chronic nifedipine administration. In conclusion, acute nifedipine effect on intestinal absorption of cephalexin is independent of anesthesia in rats. Since nifedipine could still enhance cephalexin intestinal absorption after a 7-day b.i.d. treatment, it can be envisaged to apply this effect to increase bioavailability of poorly absorbed peptidomimetic drugs in man.

Animals↗
PubMed1986

Inhibitory effect of bile salts on the enterohepatic circulation of methotrexate in the unanesthetized rat: inhibition of methotrexate intestinal absorption.

The effect of conjugated and unconjugated bile salts on the intestinal absorption of methotrexate (MTX) in the unanesthetized rat was investigated using a recycling perfusion technique. We initially determined the general characteristics of MTX absorption in vivo. Absorption of low (0.5 microM) and high (6 microM) concentrations of MTX was linear with time for 60 min perfusion and occurred at rates of 0.2 and 1.65 nmol/100 cm dry length/min, respectively. Absorption of 0.5 microM MTX was pH-dependent and increased with decreasing perfusate pH. Absorption of MTX involves two processes: (1) a saturable process with a Kt of 0.98 microM, and (2) a nonsaturable diffusion process. The unconjugated deoxycholate and the conjugated taurocholate inhibited the intestinal absorption of 1 microM MTX in a concentration-dependent manner. The inhibitory effect of bile salts was reversible, and was not due to damage to the intestinal mucosa. The structural analogues folic acid and 5-methyltetrahydrofolate and the organic anions rose bengal and sulfobormophthalein were also inhibitory to MTX absorption. This study demonstrates that a variety of organic anions inhibit MTX intestinal absorption. The possible therapeutic importance of this observation is discussed.

Animals↗
PubMed1997

Nonlinear intestinal absorption of 5-hydroxytryptamine receptor antagonist caused by absorptive and secretory transporters.

The mechanism of the nonlinear concentration dependence of intestinal absorption of the 5-hydroxytryptamine receptor antagonist azasetron was studied by use of rat in situ intestinal perfusion, as well as an in vitro Ussing-type chamber method mounted with rat intestinal tissue and cultured monolayers of human adenocarcinoma Caco-2 cells. The intestinal absorption rate constant of azasetron evaluated by the Doluisio method increased significantly with increasing concentration of azasetron up to 10 mM in a nonlinear fashion and tended to decrease at higher concentrations. Mucosal-to-serosal directed permeation of [14C]azasetron across rat ileal sheets evaluated by the in vitro Ussing-type chamber method also increased in a nonlinear fashion in a low concentration range, followed by a decrease as the concentration was further increased, whereas serosal-to-mucosal directed permeation decreased in a concentration-dependent manner. Vectorial transport of [14C]azasetron across a Caco-2 cell monolayer was observed, with higher transport in the basolateral-to-apical direction at a trace concentration of azasetron. When the initial uptake rate of azasetron by Caco-2 cells was measured, it was saturable with an apparent half-saturation concentration of 15 mM and was reduced in the presence of several cationic compounds. These observations suggest that azasetron is taken up by a carrier-mediated transport mechanism across the intestinal epithelial cells. When the steady-state uptake of [14C]azasetron was measured, it was increased in the presence of unlabeled azasetron and ondansetron. In addition, the steady-state uptake was enhanced in the presence of a P-glycoprotein inhibitor, cyclosporin A, and by ATP-depletion of the cells, although these treatments had no effect on the initial uptake of [14C]azasetron. Furthermore, the multidrug-resistant cancer cell line K562/ADM that overexpresses P-glycoprotein accumulated azasetron less extensively than did the parental drug-sensitive K562 cells. These results strongly suggest that azasetron is secreted into the intestinal lumen predominantly by P-glycoprotein. We conclude that intestinal transport of azasetron involves specialized transporters in both the absorptive and secretory directions, and the complex nonlinear intestinal absorption characteristics can be ascribed to the participation of multiple transport mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1987

Age influences on intestinal sugar absorption.

Intestinal absorption of sugars show differences depending on animals age. This is demonstrated using in vivo and in vitro techniques. The age dependence relationship is present in animals of different species such as avian, rodents and ruminants. In chicken the intestinal sugar transport increases after hatching and attains its maximum capacity by the first week of life. The D-glucose and D-galactose uptake is greater in young rats, maximum at 21 days, while it decreases thereafter. The total capacity of the small intestine of adult sheep for sugar absorption was approx. 25% of that for lambs less than 1 week of age. The differences observed in intestinal absorption of sugars at different ages could be attributed to differences in sodium and calcium transport. Other authors assume that it is induced by morphological differentiation during intestinal development.

Aging↗
PubMed1984

Guaran effect on rat intestinal absorption. A perfusion study.

Among the components of dietary fiber, the soluble polysaccharides, primarily guaran and pectin, have been found to impair intestinal absorption. Little is known, however, about the mechanism of this effect. The direct action of guaran on small intestinal absorption was evaluated by a single-pass perfusion technique. Guaran in the perfusate (1-7 g/L) inhibited small intestinal absorption of actively transported compounds, such as alpha-methyl-D-glucoside, cycloleucine, and taurocholate, and also of the passively permeating solutes 2-deoxy-D-glucose and urea. Viscosity-related inhibition by guaran was found to depend on the rate of perfusion and was only detectable at perfusion rates below 0.4-0.5 ml/min. Higher perfusion rates abolished and even reversed the inhibitory effect. The observed alterations of absorption rates caused by guaran were completely reversible after switching to a guaran-free perfusate. The concentration-dependent absorption of D-glucose and alpha-methyl-D-glucoside at perfusion rates of 0.4 and 0.2 ml/min, respectively, revealed an increase in the transport constant and essentially unaltered maximal transport capacity in the presence of guaran. Additionally, net water absorption changed to secretion upon addition of guaran. When pectin and carrageenan were used in solutions of comparable viscosity, their effect was similar to that of guaran. The results suggest a general mechanism by which soluble, viscosity-enhancing polysaccharides influence the intestinal absorption of nutrients. The most likely explanation appears to be an increase in the unstirred layer resistance to diffusion. Under our experimental conditions, this occurred at low perfusion rates, but was increasingly counteracted by raising the rate of perfusion.

Animals↗
PubMed1981

Intestinal absorption of aspirin. Influence of pH, taurocholate, ascorbate, and ethanol.

The small intestinal absorption of aspirin at pharmacological concentrations was studied in the unanesthetized rat by using a single-pass perfusion technique. The rate of aspirin absorption remained linear with its concentration (0.5 to 10 mM). Intestinal aspirin absorption increased as the concentration of hydrogen ion, sodium taurocholate, and ascorbic acid in the perfusate increased. Aspirin absorption did not change after ethanol addition. At pH 3.5 or 6.5, intestinal absorption of aspirin was greater than gastric absorption of the compound. Aspirin was not absorbed by the stomach at pH 6.5. These experiments indicate that aspirin can be absorbed to an appreciable extent in its ionized form by the small intestine but not by the stomach.

Animals↗
PubMed1992

[Mucus models for investigation of intestinal absorption mechanisms. 2. Mechanisms of drug interactions with intestinal mucus].

Using in vitro models previously described [1] mucus retention and mucus diffusion of polar and non-polar drugs were measured. It could be shown that drug interaction with pig intestinal mucus was based on non-specific binding. The pH-dependence of retention by mucus does not confirm electrostatic interaction of drugs with mucus but favour drug distribution to hydrophobic areas within the mucus. High lipophilicity and retention by mucus correlate with low diffusion of drugs through mucus.

Chemical Phenomena↗
PubMed1989

[The role of aluminum-induced inhibition of the intestinal absorption of calcium in the pathogenesis of aluminum osteopathy].

The aim of the study was to investigate the effect of aluminium on duodenal calcium absorption, the impairment of which can represent a pathogenic factor in the development of aluminium bone lesions. The authors investigated in the chick the effect of Al(OH)3 administered orally and of AlCl3 administered subcutaneously on the duodenal absorption of 47Ca, on serum concentration of calcium, phosphorous, aluminium and 1,25-dihydroxycholecalciferol and on bone morphology. Oral administration of Al(OH)3 for 8, 15, and 22 days was without any significant change. Subcutaneous administration of Al/Cl/3 for 8 day was associated with a significant increase in serum aluminium and 1,25-dihydroxycholecalciferol levels and with a significant decrease of the duodenal absorption of 47Ca. Decreased intestinal absorption of calcium may play a pathogenic role in the development of aluminium osteopathy. Increased serum 1,25-dihydroxycholecalciferol reflects presumably a compensatory mechanism of the lowered calcium absorption.

Aluminum↗
PubMed2003

Intestinal absorption in health and disease--sugars.

Carbohydrates are mostly digested to glucose, fructose and galactose before absorption by the small intestine. Absorption across the brush border and basolateral membranes of enterocytes is mediated by sodium-dependent and -independent membrane proteins. Glucose and galactose transport across the brush border occurs by a Na(+)/glucose (galactose) co-transporter (SGLT1), whereas passive fructose transport is mediated by a uniporter (GLUT5). The passive exit of all three sugars out of the cell across the basolateral membrane occurs through two uniporters (GLUT2 and GLUT5). Mutations in SGLT1 cause a major defect in glucose and galactose absorption (glucose-galactose Malabsorption), but mutations in GLUT2 do not appear to disrupt glucose and galactose absorption. Studies on GLUT1 null mice and Fanconi-Bickel patients suggest that there is another exit pathway for glucose and galactose that may involve exocytosis. There are no known defects of fructose absorption.

Animals↗
PubMed1992

Improvement of large intestinal absorption of insulin by chemical modification with palmitic acid in rats.

The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 greater than Palins-1 greater than native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.

Animals↗
PubMed1978

Effect of low calcium and low phosphorus diets on the intestinal absorption of phosphate in intact and parathyroidectomized pigs.

The intestinal absorption of phosphate has been studied in conscious pigs, each prepared with a Thiry-Vella loop of jejunum. The feeding of diets low in either calcium or phosphorus caused a significant increase in the efficiency of absorption of phosphate from the solution used to perfuse the jejunal loop in both intact and parathyroidectomized (PTX) pigs. An intravenous infusion of parathyroid hormone (0.22 u. kg-1 h-1) into a PTX pig also enhanced the absorption of phosphate. The increase in the absorption of phosphate when the low phosphorus diet was fed was not caused by an increase in the concentration gradient of phosphate ions between the jejunal lumen and blood. It is concluded that the intestinal absorption of phosphate shows similar changes to those of calcium when diets low in calcium or phosphorus are fed and that parathyroid hormone, although capable of stimulating the absorption of phosphate, is not essential for this adaptation. These effects are probably brought about by changes in the renal production and mucosal uptake of 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D3.

Animals↗
PubMed1997

Intestinal absorption kinetics of amiodarone in rat small intestine.

Amiodarone is a widely used antiarrhythmic agent with highly variable therapeutic effects. These seem to be related, at least in part, to the pharmacokinetics of the drug and particularly to some features of its gastrointestinal absorption process. The drug exhibits physico-chemical properties highly suitable for diffusion across lipophilic absorbing membranes, but its low aqueous solubility can act as the rate limiting step for absorption, making the process erratic and variable. In order to gain an insight into the intestinal absorption mechanism of the drug and detect possible non-linearities, a series of experiments using a classical rat gut in situ preparation were carried out with three amiodarone hydrochloride solutions (10, 75, and 200 micrograms mL-1). A synthetic non-ionic surfactant, polysorbate 80, at supramicellar concentration (2 mM) was used as the drug solubilizer. Amiodarone was assayed in biological samples by HPLC using a rapid, sensitive technique that was validated. The amiodarone first-order absorption rate constants obtained in these conditions were similar. No significant differences between ka values were found. Amiodarone absorption was clearly identified as a passive diffusion process.

Administration, Oral↗
PubMed1970

Intestinal absorption of calcium-47 after treatment with oral oestrogen-gestogens in senile osteoporosis.

Intestinal absorption of radiocalcium was measured in 15 postmenopausal women with osteoporosis before and after six months' treatment with an oral oestrogen-gestogen combination. Comparison with a control group indicated a significant improvement in intestinal absorption after treatment. Though there is no evidence that oestrogens have an anabolic effect on human bone, these results indicate that they affect the intestinal absorption of calcium directly.

Aged↗