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PubMed1977

Plasma levels and intestinal absorption of 25-hydroxyvitamin D in patients with small bowel resection.

Plasma levels of 25-hydroxyvitamin D (25-OHD) were found to be significantly reduced in a group of patients with small bowel resection when compared with normal controls. Plasma levels of 25-OHD after an oral dose of 25-hydroxyvitamin D3 (25-ohd3) were also reduced in the patient group. Dietary intake of vitamin D tended to be low in many patients, but seasonal variation of plasma 25-OHD levels indicated normal exposure to sunlight in most of the patients studied. It is suggested that these studies provide some evidence for malabsorption of 25-OHD after small bowel resection, which, it is postulated, may be due to interruption of the enterohepatic circulation of bile acids and of 25-OHD. These factors may contribute towards the low plasma levels of 25-OHD found in the patient group.

Adult↗
PubMed1988

Intestinal absorption enhanced by unsaturated fatty acids: inhibitory effect of sulfhydryl modifiers.

In vitro absorption of carboxyfluorescein was performed with everted colonic segments of rats. Oleic acid solubilized by a nonionic surfactant HCO-60, but not HCO-60 alone, markedly enhanced the permeation of the otherwise poorly permeant carboxyfluorescein through the colonic mucosa. The effect produced by oleic acid was reduced to different extents by pretreating the mucosa with several SH reagents, with N-ethyl-maleimide being the most effective. The inhibitory effect of N-ethylmaleimide was concentration dependent, with more than 5 mM completely blocking the enhancement of transmucosal permeability by oleic acid. The in vitro effect of N-ethylmaleimide in the absorption experiments was also observed in situ. The inhibitory effects of HgCl2 and iodoacetamide were comparable to that of N-ethylmaleimide, whereas PCMPS, an impermeant SH blocker, had no effect on the enhanced permeation. Various other amino-group modifiers had also no effect on the enhancement. On the other hand, the inhibition was accompanied by a significant reduction in the level of non-protein thiols as well as protein SH groups. Diethyl maleate, which reduced only the non-protein SH level, had no pronounced effect on the oleic acid-induced permeability change. These results suggest that the intact SH group of membrane-associated protein is necessary for the enhanced permeation of carboxyfluorescein elicited by oleic acid.

Animals↗
PubMed2000

Detection of impaired intestinal absorption of long-chain fatty acids: validation studies of a novel test in a rat model of fat malabsorption.

BACKGROUND: Classic fat balance studies detect fat malabsorption but do not discriminate between the potential causes of malabsorption, such as impaired intestinal lipolysis or reduced uptake of fatty acids. OBJECTIVE: We aimed to validate a novel test for the specific, sensitive detection of impaired intestinal uptake of long-chain unesterified fatty acids in an appropriate rat model of fat malabsorption. DESIGN: The absorption and appearance in plasma of [(13)C]palmitic acid were determined in control rats and in rats with fat malabsorption due either to chronic bile deficiency (permanent bile diversion) or to oral administration of the lipase inhibitor orlistat (200 mg/kg diet). [(13)C]Palmitic acid results were compared with the percentage absorption of ingested dietary fat determined by fat balance. RESULTS: Between 1 and 6 h after intraduodenal administration, plasma [(13)C]palmitate concentrations in control rats were 4-10-fold higher than in bile-deficient rats (P < 0.05) but were not significantly different between orlistat-supplemented rats and their controls. In control and bile-deficient rats, plasma [(13)C]palmitate concentrations allowed complete discrimination between normal (>92%) and reduced (<92%) fat absorption, whereas the percentage absorption of [(13)C]palmitate over 48 h appeared to be highly correlated with the percentage absorption of ingested dietary fat (r = 0.89, P < 0.001). CONCLUSIONS: The [(13)C]palmitic acid absorption test detects impaired intestinal absorption of long-chain fatty acids selectively and sensitively in a rat model of fat malabsorption due to bile deficiency. Our data strongly support the use of the [(13)C]palmitic acid absorption test for the diagnosis of clinical fat malabsorption syndromes.

Animals↗
PubMed1994

Intestinal absorption of (-)-carbovir in the rat.

(-)-Carbovir (CBV) is a carbocyclic nucleoside analogue with in vitro activity against the human immunodeficiency virus. The sites and mechanism of absorption of (-)-CBV from the rat small intestine were studied in the anesthetized male Sprague-Dawley rat. (-)-CBV was perfused through either duodenal, jejunal, or ileal segments at three concentration levels ranging from 1 to 500 micrograms/mL. The fraction remaining to be absorbed at steady-state and the absorptive clearance were calculated for each experiment. The effect of solvent drag on the absorptive clearance was also investigated. Two-way ANOVA for the absorptive clearance per unit length was not significant for either (-)-CBV concentration or site of perfusion. The fraction remaining to be absorbed at steady-state was found to be 0.804 +/- 0.091 (n = 30). A strong correlation was found between the absorptive clearance and the net water absorptive flux. The mechanism of (-)-CBV absorption across the rat small intestine apparently consists of both passive diffusion and convection.

Analysis of Variance↗
PubMed1959

Effect of bacterial endotoxin on metabolism. II Protein-carbohydrate balance following cortisone. Inhibition of intestinal absorption and adrenal response to ACTH.

Urinary nitrogen excretion over a 17 hour period without food and water was determined for mice poisoned with endotoxin and for control mice with and without the subcutaneous injection of 5 mg. cortisone acetate. Endotoxin did not alter the quantity of nitrogen excreted, compared with that of control mice, but in both groups of animals cortisone increased urinary nitrogen by the same amount. A balance between the quantity of protein catabolized (as estimated by increased urinary nitrogen excretion) and the total carbohydrate stored as a result of cortisone administration was found in fasted and in fed mice but not in endotoxin-poisoned mice. Endotoxin inhibited the motility of the gastrointestinal tract and blocked the absorption of food. Injections of ACTH in normal mice increased protein degradation and carbohydrate synthesis. In endotoxin-poisoned animals, ACTH failed to alter urinary nitrogen excretion and carbohydrate reserves. ACTH increased susceptibility to endotoxin. The number of heat-killed cells of S. typhimurium required to block the increase in urinary nitrogen caused by an injection of ACTH was found to be 10(8). A partial block was found with 5 x 10(7) cells but not with 10(5) cells. Mice infected with S. typhimurium excreted less than the normal amount of urinary nitrogen in response to ACTH 6 to 23 hours postinfection while normal amounts of nitrogen were eliminated 54 to 71 hours postinfection. The number of viable cells in the mice during the earlier period was less than the number of dead cells required to alter the nitrogen output, while the reverse was true during the later period.

Adrenal Cortex↗
PubMed1981

Experimental studies on intestinal absorption following Martin's operation.

Experimental studies were done on rats on compensatory absorptive capacity following Martin's operation for extensive aganglionosis. Experimental aganglionosis was produced in the descending colon of rats by serosal application of 0.1% benzalkonium chloride solution. Wide side-to-side anastomosis was performed between the aganglionic colon and the distal ileum, removing the remaining colon. As to absorptive capacity of water and electrolytes, this experimental intestine was compared, with other intestines, especially control intestine, in which similar side-to-side anastomosis was done between the normal colon and the normal ileum. "Experimental" as well as control intestine showed higher absorptive capacities of water, Na and Cl per unit length than did summed up values of the ileum and the colon per unit length. Postoperative body weight curves showed fairly good increases and appearance of feces showed a fair improvement in the experimental group. Autopsy of experimental intestine revealed marked dilatation of the anastomosed ileum and mucosal hypertrophy of the anastomosed colon. These results suggested a favorable compensatory absorptive capacity following Martin's operation.

Animals↗
PubMed2006

Exploration of linear modelling techniques and their combination with multivariate adaptive regression splines to predict gastro-intestinal absorption of drugs.

In general, linear modelling techniques such as multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS), are used to model QSAR data. This type of data can be very complex and linear modelling techniques often model only a limited part of the information captured in the data. In this study, it was tried to combine linear techniques with the flexible non-linear technique multivariate adaptive regression splines (MARS). Models were built using an MLR model, combined with either a stepwise procedure or a genetic algorithm for variable selection, a PCR model or a PLS model as starting points for the MARS algorithm. The descriptive and predictive power of the models was evaluated in a QSAR context and compared to the performances of the individual linear models and the single MARS model. In general, the combined methods resulted in significant improvements compared to the linear models and can be considered valuable techniques in modelling complex QSAR data. For the used data set the best model was obtained using a combination of PLS and MARS. This combination resulted in a model with a Pearson correlation coefficient of 0.90 and a cross-validation error, evaluated with 10-fold cross-validation of 9.9%, pointing at good descriptive and high predictive properties.

Algorithms↗
PubMed1981

Effects of cytochalasin B and dihydrocytochalasin B on calcium transport by intestinal absorptive cells.

In vivo calcium absorption was studied in normal and rachitic chicks. Cytochalasin B (CB) at a concentration of 25 microgram/ml added to the medium inside the duodenal lumen inhibited calcium absorption (20 min) from 82.5 +/- 1.9% of calcium absorbed in the controls to 59.2 +/- 3% in normal and from 70.0 +/- 2.3% to 47.0 +/- 2.1% in rachitic chicks. In vitro studies by everted ileal sacs of young rabbits also showed an inhibition of active transport of calcium due to CB. Whereas in the controls the ratio of 45Ca concentrations in serosal and mucosal media (60 min) was 7.2 +/- 0.32, the ratios were 5.24 +/- 0.52; 4.40 +/- 0.36; 3.40 +/- 0.42; 5.77 +/- 0.52; 1.38 +/- 0.08; and 1.06 +/- 0.02 in the presence of CB at concentrations of 5, 10 and 25 microgram/ml; colchicine 10(-4)M, Na citrate 0.02M, and heat-devitalized conditions, respectively. 45Ca concentration in the mucosal scrapings was also affected. It showed an increase from controls (15,101 +/- 404 cpm/mg) and correlated with CB concentration: 17,378 +/- 489, 19,015 +/- 1000, and 20,201 +/- 362 at 5, 10, and 25 microgram/ml, respectively. Dihydrocytochalasin B also inhibited active calcium transport and caused an increase in 45Ca concentration in the mucosal scrapings. Correlated electron microscopic studies showed certain changes in the brush border, especially in some actin microfilaments in the terminal web region. It seems that these morphological alterations may be related to transcytoplasmic movement of calcium.

Animals↗
PubMed2005

Cholic acid as key regulator of cholesterol synthesis, intestinal absorption and hepatic storage in mice.

To study the effects of cholic acid (CA) feeding on hepatic cholesterol metabolism, male sterol 12alpha-hydroxylase (CYP8B1) knockout (-/-) mice and wildtype controls (+/+) were fed either a control diet or the same diet supplemented with CA (0.1% or 0.5% w/w) or cholesterol (1% w/w). During feeding of the control diet, cholesterol synthesis was increased in CYP8B1-/- compared to +/+ mice. Both cholesterol and CA feeding down regulated mRNA expression of cholesterogenic genes and hepatic de novo cholesterol synthesis as also reflected by a concomitant decrease in the nuclear factor SREBP-2 precursor protein and increased hepatic free cholesterol levels. Mice with an intact CYP8B1 gene (CYP8B1+/+ and C57Bl/6 mice) accumulated higher concentrations of cholesteryl esters (24- and 25-fold, respectively) in their livers compared to CYP8B1-/- mice (8-fold). Feeding of CA increased intestinal cholesterol absorption in CYP8B1+/+ mice by 23% and in CYP8B1-/- mice by 50%. While plasma cholesterol did not differ between CYP8B1+/+ and -/- mice under control conditions and cholesterol feeding a decrease was seen in CYP8B1-/- but not CYP8B1+/+ mice fed CA. This study indicates that CA is an important determinant for intestinal cholesterol absorption and that the levels of the transcription factor SREBP-2 in the liver are dependent upon the combined effect of CA on intestinal cholesterol absorption and CYP7A1. The possibility is discussed that inhibition of CYP8B1 and thus CA synthesis may be beneficial for the treatment of hyperlipidemic disorders.

Animals↗
PubMed1997

Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site.

Animals↗
PubMed1985

Studies of carnitine metabolism in relation to intestinal absorption.

We studied the postabsorptive fate of L-[3H]carnitine after intraluminal injection into the proximal intestine of anesthetized rats. Carnitine absorption was characterized by slow appearance in the circulation with blood levels still rising 2 h after administration. Absorption via the portal vein was followed by hepatic extraction and appearance in bile with reabsorption of a fraction, thus establishing an enterohepatic circulation. About half of the [3H]carnitine in blood obtained 4 h after administration was free, with the rest largely acetylcarnitine. In contrast the increase in blood carnitine content after intraluminal administration of unlabeled carnitine was almost exclusively limited to the esterified fraction. We hypothesize that release of esterified endogenous or stored carnitine from some other site accounted for the increase in esterified carnitine. The liver may be that site: although about 50% of hepatic [3H]carnitine was in ester form after administration of labeled carnitine, the increase after unlabeled carnitine was primarily in the free fraction, suggesting that a large amount of esterified carnitine had been released. Thus the liver appears to be an important storage and excretory site for exogenous as well as endogenous carnitine, which may be released with an appropriate signal from the intestine.

Acetylcarnitine↗
PubMed1987

[Effect of the nature of carbohydrates in pig diets on the intestinal absorption of volatile fatty acids].

The appearance of nutrients (amino nitrogen and reducing sugars) and microbial metabolites (volatile fatty acids, VFA) was measured quantitatively in five pigs. After ingestion of a semi-synthetic diet (RFL) containing 22% lucerne meal (6% crude fibre), the absorption of reducing sugars (RS) in the small intestine was high (97.8%) and that of VFA low (880 +/- mmoles/24 hrs.). Ingestion of a semi-synthetic diet (RLa) containing 22% lactose and 6% purified cellulose led to lower absorption of RS (85.2%) and a higher absorption of VFA (1,180 +/- mmoles/24 hrs).

Animals↗
PubMed1990

Segmental intestinal absorption of ranitidine: investigative and therapeutic implications.

The absorption of ranitidine from different segments of the intestinal tract was studied in a subject who had an anatomically divided small intestine. The results indicate that the drug is maximally absorbed from the small bowel rather than the stomach. Subsequent animal studies have shown that absorption of ranitidine in dogs is primarily duodenal followed by jejunal and ileal. The lack of gastric absorption, with predominantly small bowel absorption, may have investigational and therapeutic implications in a variety of gastrointestinal diseases.

Animals↗
PubMed2002

Locally and systemically active glucocorticosteroids modify intestinal absorption of sugars in rats.

Glucocorticosteroids enhance digestive and absorptive functions of the intestine of weaning and adult rats. This study was undertaken to assess the influence of treatment of weaning male rats with budesonide (Bud), prednisone (Pred), or control vehicle on the in vitro jejunal and ileal uptake of glucose and fructose. Bud and Pred had no effect on the uptake of d-glucose by sodium glucose transporter-1. In contrast, the uptake of d-fructose by GLUT-5 was similarly increased with Bud and with Pred. The increases in the uptake of fructose were not due to variations in the weight of the intestinal mucosa, food intake, or in GLUT-5 protein or mRNA expression. There were no steroid-associated changes in mRNA expression of c-myc, c-jun, c-fos, proglucagon, or selected cytokines. However, the abundance of ileal ornithine decarboxylase mRNA was increased with Pred. Giving postweaning rats 4 wk of Bud or Pred in doses equivalent to those used in clinical practice increases fructose but not glucose uptake. This enhanced uptake of fructose was likely regulated by posttranslational processes.

Administration, Oral↗
PubMed1983

Intestinal absorption and metabolism of clioquinol in the rat.

Plasma concentrations of clioquinol and its metabolites after single or repeated oral administration of clioquinol, absorption region of clioquinol in gastrointestinal tract, and intestinal metabolism were studied in rats. Plasma concentrations of clioquinol after oral administration of four different doses (20, 100, 200 and 400 mg/kg) were lower than those of the two metabolites, clioquinol glucuronide and sulfate. Mean maximal plasma concentration of unchanged drug was in the range of 1-8 nmol/ml. Clioquinol was absorbed poorly from the stomach and fairly from the small intestine. Bile was an important route for excretion of clioquinol in rats. The mesenteric venous plasma from the closed intestinal loops of both jejunal and ileal regions was analyzed for clioquinol and the metabolites and it was found that clioquinol glucuronide was formed predominantly in both regions. From the results of the present studies, intestinal metabolism of clioquinol can be pointed out as a major factor for difficulty to cause clioquinol intoxication.

Animals↗
PubMed1984

Intestinal absorption mechanism of amino-beta-lactam antibiotics. III. Kinetics of carrier-mediated transport across the rat small intestine in situ.

The transport kinetics of amino-beta-lactam antibiotics was studied by an in situ rat small intestinal recirculating perfusion technique. The disappearance rates of the antibiotics from the perfusing luminal solution followed mixed-type kinetics with saturable and nonsaturable processes. The kinetic parameters were determined. Pharmacokinetic analysis of the time courses of luminal disappearance, tissue accumulation, and blood concentration indicated that the transfer of the antibiotics from the in situ luminal solution to tissue is nearly irreversible. On the assumption that the saturable transport process involves a common carrier for these antibiotics, the predicted extents of mutual inhibition using the in situ kinetic parameters were in good agreement with the experimental values for cephalexin and cephradine. The effects of cephalexin and cefadroxil on the absorption of cyclacillin were also consistent with a common transport mechanism. The dipeptides, carnosine and L-phenylalanylglycine markedly inhibited cyclacillin absorption in a competitive fashion. Furthermore, cyclacillin inhibited the absorption of carnosine. The results indicate that the absorption of amino-beta-lactam antibiotics is closely related with that of dipeptides.

Animals↗
PubMed1994

Calcitonin and insulin in isobutylcyanoacrylate nanocapsules: protection against proteases and effect on intestinal absorption in rats.

One of the major limiting steps for the absorption of peptide drugs from the intestine is proteolytic degradation. To slow this degradation, human calcitonin was trapped in polyacrylamide nanoparticles, and human calcitonin and insulin were encapsulated with polyisobutylcyanoacrylate. Human calcitonin trapped in polyacrylamide nanoparticles showed no delayed release characteristics and thus would not provide protection from proteases. Proteolytic degradation of human calcitonin and insulin in polyisobutylcyanoacrylate nanocapsules was slower than the free peptides in solution. The plasma pharmacokinetic profiles were consistent with increased survival time of the peptides in the intestine, with higher plasma concentrations of the peptides in the later time samples compared with the controls. However, the nanocapsules gave no significant overall enhancement of peptide absorption. This led to the conclusion that the nanocapsules released the peptides into the intestinal lumen, with small amounts then being absorbed but the rest largely degraded.

Acrylic Resins↗
PubMed2006

Altered small intestinal absorptive enzyme activities in leptin-deficient obese mice: influence of bowel resection.

BACKGROUND: Residual bowel increases absorption after massive small bowel resection. Leptin affects intestinal adaptation, carbohydrate, peptide, and lipid handling. Sucrase, peptidase, and acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) are involved in carbohydrate, protein, and lipid absorption. We hypothesized that leptin-deficient obese mice would have altered absorptive enzymes compared with controls before and after small bowel resection. METHODS: Sucrase, peptidase (aminopeptidase N [ApN], dipeptidyl peptidase IV [DPPIV]), and MGAT activities were determined from lean control (C57BL/6J, n = 16) and leptin-deficient (Lep(ob), n = 16) mice small bowel before and after 50% resection. RESULTS: Ileal sucrase activity was greater in obese mice before and after resection. Jejunal ApN and DPPIV activities were lower for obese mice before resection; ileal ApN activity was unaltered after resection for both strains. Resection increased DPPIV activity in both strains. Jejunal MGAT in obese mice decreased postresection. In both strains, ileal MGAT activity decreased after resection, and obese mice had greater activity in remnant ileum. CONCLUSIONS: After small bowel resection, leptin-deficient mice have increased sucrase activity and diminished ileal ApN, DPPIV, and MGAT activity compared with controls. Therefore, we conclude that leptin deficiency alters intestinal enzyme activity in unresected animals and after small bowel resection. Altered handling of carbohydrate, protein, and lipid may contribute to obesity and diabetes in leptin-deficient mice.

Acyltransferases↗