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PubMed1993

Intestinal absorption and malnutrition in patients with the acquired immunodeficiency syndrome (AIDS).

The relation of small intestinal dysfunction and malnutrition (body composition and serum index parameters of nutrition) was investigated in 36 male patients with AIDS. Mucosal absorptive capacity was assessed by the 25 g D-xylose test. D-xylose absorption (2 h - serum profile and 5 h - urine) classified 17 patients as having impaired and 19 patients as having normal absorption. In both groups body weight, body mass index as well as body composition analysis indicated malnutrition when compared to healthy male controls (n = 340) or asymptomatic HIV-infected patients (n = 26). Patients with abnormal D-xylose test had more severe malnutrition indicated by a lower body cell mass (17.7 +/- 5.4 vs. 22.5 +/- 4.5 kg; p < 0.01) and an increased ratio of extracellular mass to body cell mass (1.99 +/- 0.82 vs. 1.45 +/- 0.46 p < 0.01). Total serum protein, albumin, cholinesterase activity, cholesterol and LDL were significantly diminished in AIDS-patients with abnormal D-xylose test compared to those with normal D-xylose absorption. Intestinal dysfunction indicated by decreased D-xylose Intestinal dysfunction indicated by decreased D-xylose absorption thus represents an important feature of malnutrition and wasting, and patients with abnormal D-xylose absorption have more profound impairment of body composition, visceral proteins and lipids reflecting malnutrition than patients with unaffected intestinal absorption.

AIDS-Related Opportunistic Infections↗
PubMed1990

Intestinal absorption of vitamin E in experimental renal failure.

We studied intestinal absorption of vitamin E in rats with experimental renal failure (RF) and in sham-operated normal and pair-fed controls using in vivo perfusion and in vitro everted sacs. The in vivo absorption rates per unit of intestine length were significantly reduced in RF and pair-fed groups. Expression of data per unit of intestine weight gave normal values in the pair-fed but depressed values in the RF animals. Vitamin E uptake in vitro was significantly increased in RF animals, suggesting enhanced permeability. We conclude: (i) vitamin E absorption in vivo is impaired in experimental RF; (ii) this is in part due to reduced nutrient intake; and (iii) disparity between in vivo and in vitro results suggests the presence of some inhibitory influence(s) in intact animals with RF.

Acute Kidney Injury↗
PubMed1979

Interaction of cations and chelators with the intestinal absorption of tetracycline.

The influence of certain compounds on intestinal absorption of tetracycline was tested, using two different in vivo techniques: a) Disappearence of the drug from perfused intestinal segments of the rabbit; b) Measuring urinary excretion in the rat after oral dosage. Ca2+ and Fe2+ ions both reduced the permeation rate of tetracycline by about 30%. In presence of Ca2+ and salicylate ions, leading to ion-pair formation with the antibiotic, intestinal uptake was significantly increased in comparison to experiments where only calcium was present. A more pronounced increase was observed with EDTA. Phosphate ions had different effects on the uptake of the antibiotic in both experimental techniques. Possible mechanisms are discussed.

Animals↗
PubMed1994

Relationship between the suppressive actions on intestinal absorption and on cGMP production for the natriuretic peptide family in dogs.

1. The aim of this study was to investigate whether the suppressive effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) on net intestinal absorption were related to guanosine 3',5'-cyclic monophosphate (cGMP) production in the intestine. 2. We measured the plasma cGMP concentration of the arterial, jejunal and ileal venous blood after intravenous infusions of natriuretic peptides (97 pmol/kg per min for 30 min) in anaesthetized dogs. 3. The infusion of ANP increased cGMP concentration of the aortic blood by 49.9 +/- 9.0 (pmol/mL), BNP by 71.8 +/- 12.3 and CNP by 5.5 +/- 1.3. The increases in cGMP after ANP and BNP were larger than after CNP. The infusion of ANP increased jejunal arteriovenous differences in cGMP concentration by 69.9 +/- 3.5 (pmol/mL) and ileal arteriovenous differences by 8.7 +/- 3.2. In BNP infusion, the jejunal and ileal arteriovenous differences in cGMP concentration tended to increase by 15.6 +/- 5.8 (pmol/mL) and by 14.8 +/- 6.6 but neither were significant. CNP infusion did not change the jejunal and ileal arteriovenous differences in cGMP concentration. 4. These results suggest that, while the actions of ANP on intestinal absorption may be mediated by cGMP, those of BNP and CNP are not.

Animals↗
PubMed1979

[Evaluation of intestinal absorption of calcium by means of double-isotope methods and oral administration of the tracer].

The percent intestinal absorption of calcium was measured in normal volunteers and in patients with idiopathic hypercalciuria employing the deconvolution method, the ratio of the two administered isotopes at equilibrium and the percent of dose present in plasma 2 hr after oral administration of the tracer. Comparison of results obtained showed that the technique based on the ratio between the two radioisotopes overestimates intestinal absorption by about 9% with respect to values calculated with the deconvolution method, but gives results comparable to those determined by oral administration of the isotope. The percent dose of the tracer 2 h after i.v. administration is closely correlated with the size of the miscible calcium pool. A less significant correlation exists between the size of the pool and percent of the dose 2 h after oral administration.

Administration, Oral↗
PubMed1999

Theoretical calculation and prediction of intestinal absorption of drugs in humans using MolSurf parametrization and PLS statistics.

A method for modeling and prediction of the intestinal absorption of drugs in humans using theoretically computed molecular descriptors and multivariate statistics has been investigated using 20 diverse drug-like compounds. The program MolSurf was used to compute theoretical molecular descriptors related to physicochemical properties such as lipophilicity, polarity, polarizability and hydrogen bonding. The multivariate Partial Least Squares Projections to Latent Structures (PLS) method was used to delineate the relationship between the intestinal absorption of drugs in humans and the theoretically computed molecular descriptors.Good statistical models were derived. Properties associated with hydrogen bonding had the largest impact on absorption and should be kept to a minimum to promote high absorption. High charge-transfer properties and the presence of surface electrons, i.e. valence electrons, which are not tightly bonded to the molecule, were also found to promote high absorption.

Computer Simulation↗
PubMed2000

The rhamnogalacturonan-II dimer decreases intestinal absorption and tissue accumulation of lead in rats.

The rhamnogalacturonan-II dimer (dRG-II) forms strong complexes in vitro with lead (Pb) and other selected cations. We examined the in vivo bioavailability of Pb complexed with dRG-II and the effect of unleaded dRG-II on the intestinal absorption and tissue retention of Pb in rats. Forty male Wistar rats were divided into four groups. Each group consumed a purified control diet for 3 wk or the same diet supplemented with: i) 3 mg of Pb/kg, ii) 0.5 g of leaded dRG-II/kg, or iii) 0.5 g of leaded dRG-II/kg and 4.5 g of unleaded dRG-II/kg. The leaded dRG-II provided approximately 3 mg of Pb/kg of diet. A chemical balance study was conducted during the last 5 d of the 3-wk study, and blood and organs were sampled for Pb and mineral analyses. The apparent intestinal absorptions of Pb were 62.3, 15.2, 11.8 and -0.1%, and Pb balances were 1.9, 9.6, 5.6 and -0.2 microg/d for the control and the three experimental groups, respectively. The Pb complexed with dRG-II was less available than Pb acetate, as reflected by significantly lower blood and tissue Pb levels. The addition of unleaded dRG-II decreased the intestinal absorption and the tissue retention of Pb significantly. We further found that the apparent absorption and status of magnesium, zinc and iron were unaffected by Pb treatment or dRG-II addition. We conclude that dRG-II may be useful in decreasing toxicity related to chronic Pb exposure. Human studies will be necessary however, to further evaluate the clinical utility of this beneficial effect.

Analysis of Variance↗
PubMed1990

Immunolocalization of transferrin and transferrin receptor in mouse small intestinal absorptive cells.

The mechanisms by which the duodenal mucosa absorbs iron are unknown. Insorption into absorptive cells of luminal iron bound to transferrin via receptor-mediated endocytosis has been hypothesized, but transferrin and transferrin receptor are absent in apical microvillous brush borders of small bowel biopsies taken from fasted patients and normal volunteers. We hypothesized that a normal iron-containing diet might induce the transient appearance of transferrin and transferrin receptor in apical brush borders of small intestinal absorptive cells in a normal mouse that was provided iron-containing chow until the moment of sacrifice. Light and electron microscopic immunolocalization of transferrin and transferrin receptor in proximal small intestinal absorptive cells was limited to basolateral membranes and coated pits of cells predominantly in the crypts and basal regions of the villi. Transferrin and transferrin receptor were not detected in apical microvillous brush border membranes of these enterocytes. In parallel immunolocalization protocols designed to show the ability to immunodetect other antigens at these locations, maltase and proteoglycan were demonstrated in apical microvillous brush border membranes and in basolateral membranes, respectively, in absorptive cells of small intestinal villous tip, base, and crypt regions. Furthermore, transferrin and transferrin receptor were immunolocalized in hepatocyte sinusoidal microvillus membranes. We conclude that food does not induce the appearance of immunodetectable transferrin and transferrin receptor in the apical microvilli of small intestinal absorptive cells and, therefore, that these iron transport proteins are not involved in the apical microvillous membrane transport of luminal dietary iron.

Animals↗
PubMed1978

Effect of diester and diether phosphatidylcholine on intestinal absorption of neutral and acidic sterols.

The effects of nondigestible diether phosphatidylcholine on intestinal absorption of cholesterol and dihydroxy and trihydroxy conjugated bile salts were studied in bile fistula rats using radioactive substrates. No inhibition of absorption of either dihydroxy or trihydroxy bile salts was observed. Nondigestible phospholipid did, however, significantly inhibit cholesterol absorption. Under control conditions with natural phosphatidylcholine in the intestinal perfusate, absorption of cholesterol was significantly greater when infused with taurocholate (TC) as compared to results obtained after infusion with taurochenodeoxycholate (TCD). Studies were repeated using radioactive rat liver phosphatidylcholine to determine whether the observed decrease in cholesterol absorption could be correlated with a decrease in digestion and absorption of rat liver phosphatidylcholine. No evidence was found for decreased absorption of this phospholipid when given with TCD. It is concluded that less cholesterol is absorbed in the presence of TCD as compared to TC, but the mechanism for this remains unexplained.

Animals↗
PubMed1982

[Impaired intestinal absorption of thyroid hormone in a case of Hashimoto's disease with anti-T3 and anti-T4 antibody].

A 28 year old woman with Hashimoto's disease was treated with desiccated thyroid and triiodothyronine (T3). She improved steadily during the first 2 to 3 months and thyroidal function tests turned to normal. Then, in spite of continuing treatment, her serum T4 level decreased gradually and she became fatigued. A serum T3 radioimmunoassay manifested an interference pattern suggested anti-T3 antibody in her serum. Ethanol-extracted serum T3 and T4 levels were low in spite of ingestion of desiccated thyroid or synthetic T3 and T4, suggesting intestinal malabsorption of T3 and T4. Antibodies against T3 and T4 were identified in her serum; affinity constants were 1.16 X 10(10) and 8.73 X 10(8) l/mol respectively. After treatment with synthetic T3 and/or T4 for 20 months, the titer of anti-T3 and anti-T4 antibodies decreased, and impaired intestinal absorption of thyroid hormone improved. Then, after desiccated thyroid treatment was reinstituted, the anti-T3 antibody titer again increased and intestinal absorption of thyroid hormone decreased. These results suggest the oral immunization against thyroid hormones. There was associated impairment in intestinal absorption of thyroid hormone presumably secondary to the anti-T3 and anti-T4 antibodies.

Adult↗
PubMed1998

Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis.

The intestinal absorption of an intact oligopeptide was investigated in rats using a synthetic cationic peptide, 001-C8 (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH2). The peptide was coupled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) to prepare a fluorescence-labeled derivative 001-C8-NBD (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH-NBD) for the purpose of quantification. The degradation half-life of 001-C8-NBD in jejunal homogenate (1 mg/mL) was 99.5 min, which was significantly longer than that of natural leucine enkephalin (1.14 min). The absorption of 001-C8-NBD was evaluated by the vascular-perfusion method. Intact 001-C8-NBD appeared in the blood time-dependently and the absorption volume at 30 min (2.75 +/- 0.14 microL/cm intestine) was significantly larger than that of [3H]PEG 900 (0.88 +/- 0.13 microL/cm intestine), of which membrane permeability is very low. The absorption of 001-C8-NBD was greatly reduced by an adsorptive-mediated endocytosis inhibitor, protamine (10 mM). No inhibition of the absorption of [3H]PEG 900 by protamine was observed. The intestinal absorption was also measured by an in vivo loop method. The absorption clearance of 001-C8-NBD measured by this method (0.083 +/- 0.008 microL/min/cm intestine) was comparable to that obtained by the vascular perfusion method (0.092 +/- 0.005 microL/min/cm intestine). All of these data suggested that 001-C8-NBD was absorbed as the intact oligopeptide in the intestine in vivo. Adsorptive-mediated transcytosis is suggested to have enormous potential as an oral delivery system for peptide and/or protein drugs.

Animals↗
PubMed1979

The effect of the anticonvulsants phenobarbital and diphenylhydantoin on intestinal absorption of calcium.

The effect of anticonvulsant drugs (phenobarbital and diphenylhydantoin) on the metabolic balance of calcium and on its intestinal absorption, as measured by an in situ intraluminal perfusion method, was studied in rats. The administration of these drugs produced: (a) an increase of the fecal excretion of calcium,. (b) a decrease of the intestinal absorption of calcium (45Ca). Both effects were more intense in rats treated with phenobarbital. There is evidence to suggest that the anticonvulsant drugs affect the intestinal mechanism of active transport of calcium.

Animals↗
PubMed1988

Analysis of sequential events in intestinal absorption of folylpolyglutamate.

Although it is clear that the intestinal absorption of folylpolyglutamates is associated with hydrolysis to monoglutamyl folate, the precise sequence and relative velocity of the events involved in this absorption are not fully elucidated. In the present study, we used biosynthetic, radiolabeled folylpolyglutamates purified by affinity chromatography to analyze the relationship of hydrolysis and transport in rat jejunal loops in vivo. Absorption was best described by a series of first-order processes: luminal hydrolysis to monoglutamyl folate followed by tissue uptake of the product. The rate of hydrolysis in vivo was twice as high as the rate of transport. The latter value was identical to that measured for folic acid administered separately. The relevance of this sequential model was confirmed by data obtained using inhibitors of the individual steps in absorption of "natural" folate. Heparin and sulfasalazine were both effective in decreasing absorption. The former affected hydrolysis solely, whereas the latter acted as a competitive inhibitor of transport of monoglutamyl folate. These studies confirm that hydrolysis is obligatory and that the product is subsequently taken up by a transport process, common to monoglutamyl folates, that is the rate-determining step in transepithelial absorption.

Animals↗
PubMed1996

Relationship between structure and intestinal absorption of bile acids with a steroid or side-chain modification.

UNLABELLED: A structure-activity relationship for bile acid (BA) intestinal absorption is known to exist. To better understand the BA structural requirements for optimal BA intestinal absorption, rabbit ileal perfusion studies were performed. Unconjugated BA: Ursodeoxycholic (UDCA) and ursocholic acid (UCA) with methyl (6MUDCA and 6MUCA) or fluoro group (6FUDCA and 6FUCA) in the 6 position and UCA with a methyl group in 23 position (23MUCA) were compared with unconjugated UDCA, UCA, deoxycholic (DCA), chenodeoxycholic (CDCA), hyocholic (HCA), and hyodeoxycholic (HDCA) acid. BA lipophilicity was evaluated by their octanol-water partition coefficient. Conjugated BA: Taurine-conjugated UDCA and UCA with a methyl group in the 23 position (T23MUDCA and T23MUCA) were compared with the corresponding taurine-conjugated natural analogs. An analog of glycine-conjugated UDCA with the C24 amide bond replaced by a -CO-CH2- in the 24 position (24PUDCA) was studied and results were compared with the natural form (GUDCA). Unconjugated BA absorption was dose dependent (i.e., passive) and followed their lipophilicity: DCA > 6MUDCA > CDCA > HDCA > UDCA > HCA > 6FUDCA > 6MUCA > 6FUCA > UCA. Conjugated BA absorption was active, and Vmax was in the following order: TCA > TUDCA > TUCA > T23MUCA > T23MUDCA > 24PUDCA > GUDCA. 24PUDCA transport was also active and higher than GUDCA. CONCLUSION: Passive transport is dependent on BA lipophilicity. Conjugated BAs are actively transported, and the presence of a 23-C methyl group does not improve transport when compared with the natural analogs. The substitution of the C24 amide bond with a -CO-CH2-still affords interaction of the BA with the intestinal transport carrier.

Animals↗