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Effect of palmitoyl-DL-carnitine on the 3H-dihydroergotoxine intestinal absorption in rat.

Using the methods of rat intestine perfusion in situ and kinetics examination in vivo, absorption of 3H-dihydroergotoxine (3HDHE) from the gastrointestinal tract into systemic blood was investigated. The aim of the study was to increase absorption of the ergot alkaloid with palmitoyl-DL-carnitine (5 mg/rat). Low absorption of 3HDHE was demonstrated in contrast to fast and almost complete absorption of the model drug theophylline (5 mg kg-1). In the experiment this was evidenced by in situ continuous measurement of the administered activity (125 micrograms kg-1) into a reservoir. At the end of the experiment (120 min) the plasma activity reached 0.034 +/- 0.014%, retention in the intestine achieved more than 60%, uptake in the brain 0.044 +/- 0.015%, cumulative excretion in bile 1.50 +/- 0.31% of administered activity. Palmitoyl-DL-carnitine did not influenced the percentage of activity in the plasma and did not affect bile excretion, retention in the intestine and uptake in the brain. In the vivo experiment oral administration of 3HDHE into the stomach (222 micrograms kg-1) increased activity in plasma (0.069 +/- 0.020% within 24 h), cumulative excretion in urine was 6.1 +/- 3.6%, retention of the drug in the stomach and intestine 46 +/- 12%, activity of the brain 0.11 +/- 0.02%, in the kidney 0.39 +/- 0.17%, and in the liver 0.80 +/- 0.30%. After palmitoyl-DL-carnitine administration the activity of plasma reached 0.084 +/- 0.022% (NS), retention in gastrointestinal tract 39 +/- 9% (NS), activity in the liver 0.71 +/- 0.17% (NS), and activity in the kidney 0.42 +/- 0.13% (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intestinal absorption of vitamin B12 in patients with chronic pancreatic insufficiency and the effect of human duodenal juice on the intestinal uptake of vitamin B12.

The mean absorption of vitamin B12 (Schilling test) was 13.1 +/- 1.0 (% +/- S.E.M.) in 21 patients with chronic pancreatic insufficiency and 17.6 +/- 1.4 in 13 control patients (p less than 0.01). There was no correlation between pancreatic bicarbonate production after secretion stimulation and vitamin B12 absorption in the patient group (r = 0.117). Human duodenal juice reduced the uptake of 57CoB12-rat intrinsic factor (IF) by perfused rat small intestinal segments in vivo (p less than 0.01) as well as the uptake of 57CoB12-human IF by purified guinea-pig intestinal brush borders in vitro (p less than 0.01). The results confirm reduced absorption of vitamin B12 in chronic pancreatic insufficiency, but the mechanism remains uncertain.

Adolescent↗

Methionine and 2-hydroxy-4-methylthiobutanoic acid are partially converted to nonabsorbed compounds during passage through the small intestine and heat exposure does not affect small intestinal absorption of methionine sources in broiler chicks.

Broiler chicks were fed diets supplemented with DL-methionine or DL-2-hydroxy-4-methyl-thiobutanoic acid. At 4 wk of age the chicks were subdivided into thermoneutral (22 degrees C) and heat-exposed (32 degrees C) groups and maintained under these conditions for 48 h. Highly purified 3H-L-methionine (3H-L-Met) and 3H-L-2-hydroxy-4-methyl-thiobutanoic acid (3H-L-HMB) were used to evaluate treatment effects on the small intestinal passage of sources of supplemental methionine and on the transport of methionine sources across purified small intestinal brush border vesicles. 3H-L-Met was efficiently absorbed in the upper regions of the small intestine; however, 2.5-3.5% of dietary 3H from birds fed 3H-L-Met remained unabsorbed in the distal small intestine. Dietary 3H (15%) initially associated with 3H-L-HMB was not absorbed during passage down the length of the gut. The HPLC analysis indicated that only 10% of the radiolabeled material remaining in the terminal ileum eluted at the time expected for HMB. Partial breakdown of HMB to nonabsorbed, nonmethionine products during passage down the small intestine may contribute to the difference in biopotency of the two sources of supplemental dietary methionine. Heat exposure did not affect in vivo small intestinal passage or in vitro transport of 3H-L-Met and 3H-L-HMB across small intestinal brush border membrane vesicles.

Animals↗

Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters.

Psoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono- and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined using isolated intestinal mucosa as well as Caco-2 cell monolayers, in order to obtain estimates of the fraction of the dose absorbed for these compounds. Relationships between the physicochemical properties of the fumaric acid esters and their biological responses were investigated. The uncharged diester dimethylfumarate displayed a high presystemic metabolic lability in all metabolism models. It also showed the highest permeability in the Caco-2 cell model. However, in permeation experiments with intestinal mucosa in Ussing-type chambers, no undegraded DMF was found on the receiver side, indicating complete metabolism in the intestinal tissue. The intestinal permeability of the monoesters methyl hydrogen fumarate, ethyl hydrogen fumarate, n-propylhydrogen fumarate and n-pentyl hydrogen fumarate increased with an increase in their lipophilicity, however, their presystemic metabolism rates likewise increased with increasing ester chain length. It is concluded that for fumarates, an increase in intestinal permeability of the more lipophilic derivatives is counterbalanced by an increase in first-pass extraction.

Animals↗

Fractional intestinal absorption and retention of calcium measured by whole-body counting. Application of a power function model.

By application of a power function model, fractional intestinal calcium absorption was investigated with a new technique involving whole-body counting after successive oral and intravenous administration of standard doses of 47Ca. The fractional calcium retention 7 days after the oral load of 47Ca was also measured. Fractional calcium retention averaged 30.3% in normal subjects and 11.5% in 11 patients with intestinal malabsorption. In the same groups fractional calcium absorption averaged 46.6% and 16.4%, respectively. Fractional calcium retention and intestinal calcium absorption were significantly correlated to body surface area, and there was a well-defined relation between fractional retention and absorption of calcium...

Adult↗

Toxicity of environmental lead and the influence of intestinal absorption in children.

Exposure to metals, particularly lead, remains a widespread issue that is associated with historical and current industrial practices. Whereas the toxic properties of metals are well described, exposure to metals per se is only one of many factors contributing to elevated blood metal concentrations and their consequent health effects in humans. The absorbed dose of metal is affected by geochemical, biochemical, and physiological parameters that influence the rate and extent of absorption. In children, the interplay among these factors can be of critical importance, especially when biochemical and physiological processes might not have matured to their normal adult status. Such immaturity represents an elevated risk to metal-exposed children because they might be more susceptible to enhanced absorption, especially via the oral route. This review brings together the more recent findings on the physiological mechanisms of metal absorption, especially lead, and examines several models that can be useful in assessing the potential for metal uptake in children.

Biological Availability↗

Mechanism and site of small intestinal absorption of alpha-tocopherol in the rat.

The site and mechanism of alpha-[5-methyl-3-H]tocopherol absorption was investigated using everted rat small bowel sacs incubated in a micellar medium. Mean plus or minus SE absorption rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 2.2 plus or minus 0.17, 3.4 plus or minus 0.21, and 2.0 plus or minus 0.04 nmoles per min per 100 mg, respectively. Addition of 2,4-dinitrophenol, sodium azide, or potassium cyanide to the incubation medium in separate experiments did not change the rate of absorption (P greater than 0.10). Stepwise increase in incubation solution tocopherol concentration up to 1200 muM resulted in a linear increase in the absorption rate. In all of the above described experiments the rate of absorption of the vitamin by the medial portion of the small bowel was significantly (P smaller than 0.01) higher than the rate of absorption of the vitamin by the proximal and distal small bowel segments. No transmural transport of the vitamin into the serosal compartment took place. Autoradiographic examination of the tissue after incubation disclosed accumulation of the vitamin in the submucosal lymphatic spaces. Alpha-Tocopherol absorption by the rat small bowel appears to be a passive diffusion process taking place at the highest rate in the medial portion of the small bowel.

Animals↗

A method for the simultaneous evaluation of exocrine pancreatic function and intestinal absorptive function in dogs.

Exocrine pancreatic function was evaluated in 13 dogs, using the chymotrypsin-labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA). This peptide releases p-aminobenzoic acid (PABA) in the presence of pancreatic chymotrypsin. The amount of PABA in blood or urine after BT-PABA administration then served as an index of pancreatic function. Similarly, a xylose absorption test has been described in the literature to evaluate absorptive function of the small intestine. Here, the pentose sugar d(+)xylose was given orally, and blood xylose concentrations were then measured at intervals. Since both tests were performed in nearly the same way, they were combined into a single test. A solution containing BT-PABA (30 mg/ml) and xylose (100 mg/ml) was administered perorally to dogs with and without pancreatic duct ligation. In the unoperated (control) dogs, peak blood concentrations for PABA occurred between 60 and 120 minutes and xylose concentrations were maximal between 30 and 90 minutes. Pancreatic duct ligation reduced PABA concentrations at 90 minutes to one-sixth of the values in control dogs. Xylose absorption, however, was not altered by pancreatic duct ligation. In this way, digestive and absorptive functions were both evaluated, using a single 90-minute test.

4-Aminobenzoic Acid↗

Measurement of intestinal absorption in mice by a double-label radioisotope perfusion technic.

The use of the standard chemical technic for measuring intestinal glucose absorption was compared with a new double-label radioisotope technic. Glucose absorption and water flux in the mouse small intestine were measured by both methods. The results indicated that the 2 approaches yield almost identical values. The radioisotope technic utilized [14C] polyethylene glycol to measure water flux and [3H] glucose. The technic was found to be reliable, rapid, and applicable to small samples and other substrates. It is particularly suited to absorption studies in small animals such as the mouse, where sample size is limited. The study also showed that the polyethylene glycol recovery rate from the mouse intestine was 97.8%, indicating that it is a valid absorption marker in this species.

Animals↗

Dependence of intestinal absorption in vivo on the unstirred layer.

The appearance rate of butanol, antipyrine, salicylic acid, and urea in the venous blood of rat jejunal loops perfused in vivo is increased up to 64%, if the intraluminal solution is mixed more efficiently by the simultaneous perfusion of air. The enhancement of the absorption can be attributed partly to the enlarged absorbing area but mainly to the reduction of the effective unstirred layer thickness by about 500 micrometers. The unstirred layer reduces the phenylalanine absorption at 0.1 mmol l(-1) but not at 100 mmol l(-1), since at high concentrations a full saturation of the transport system can be achieved in spite of the unstirred layer resistance. The interference of the unstirred layer increases with increasing absorbability of the substances.

Animals↗

Effect of resistant and digestible starch on intestinal absorption of calcium, iron, and zinc in infant pigs.

The first nonmilk foods that are given to infants contain high levels of starch, a fraction of which is resistant to enzyme hydrolysis. Incomplete digestion of starch may interfere with the absorption of certain minerals. A fraction of dietary starch which is resistant to in vitro enzymatic hydrolysis has been termed resistant starch. The aim of this study was to compare the intestinal apparent absorption of calcium, phosphorus, iron, and zinc in the presence of either resistant or digestible starch. Twelve 7-10-d-old piglets were fitted with a T-tube inserted into the intestine approximately 3 m distal to the duodenum. Animals received in random order 200 mL of a test meal of cooked, cooled, high amylose corn starch (16.4% resistant starch), or cooked rice starch (digestible starch) administered by an orogastric tube. Both meals contained the same amount of calcium, phosphorus, iron, and zinc. The test meal also contained tracer amounts of 59Fe and 65Zn, as well as polyethylene glycol 3350, as a nonabsorbable marker. Intestinal apparent absorption of starch was greater the meal with digestible starch (71.0 +/- 17.0%) than after the meal with resistant starch (49.2 +/- 10.3) (p < 0.001). After feeding the meals with resistant and digestible starch, mineral apparent absorption was, respectively: calcium, 40.2 +/- 11.8% versus 28.1 +/- 16.4% (p < 0.05); phosphorus, 73.2 +/- 14.0% versus 67.8 +/- 18% (NS); iron, 24.1 +/- 12.2% versus 12.6 +/- 10.6% (p < 0.01), and zinc, 35.0 +/- 13.0% versus 30.6 +/- 8.22% (NS). In conclusion, a meal containing 16.4% resistant starch resulted in a greater apparent absorption of calcium and iron compared with a completely digestible starch meal. If this finding holds true for the whole bowel, administration of resistant starches could have a positive effect on intestinal calcium and iron absorption.

Animals↗

High rate of intestinal absorption of the phospholipid anlaogue 1-dodecyl 2-[1-14C] octanamido-sn-2-deoxy-glycero-3-phosphocholine in the rat.

The phospholipid analogue with two short fatty chains, 1-dodecyl-2-[1-14C] octanamido-sn-2-deoxy-glycero-3-phosphocholine ([14C] phospholipid analogue), with a non-hydrolyzable bond at position 2 of the glycerol, is an inhibitor of phospholipase A2. It was obtained after chemical synthesis and 0.5 micromol was solubilized in Na+ taurocholate with an equimolar amount of 1-octadecanoyl 2-[3H]eicosatetraenoyl-sn- glycero-3-phosphocholine which is the current substrate of phospholipases A2. Both molecules were introduced into the duodenum of rats in order to follow their captations by intestinal mucosa cells for 30, 60 or 90 min. The [14C] phospholipid analogue was poorly split by phospholipases A2 (pancreatic juice and intracellular enzymes). It disappeared from the intestinal contents (87% of the dose gone in 90 min) as rapidly as the tritiated lecithin (81%) but this was later split by the phospholipases at a higher rate.

Animals↗

Intestinal absorption of biliary and exogenous cholesterol in the rat.

Non-starved rats (fed a cholesterol-free diet prior to the experiments) with common bile fistula were infused intraduodenally with rat bile labelled with [1,2-3H]cholesterol at a constant rate (0.6 ml/h) and a nutritive mixture containing, in particular, olive oil and 1 mumol [4-14C]cholesterol per ml at rates of 1 ml/h (group B) or 2.3 ml/h (group A) for 5 h. Control rats (group C) were prepared as group B rats but the nutritive mixture was free of cholesterol. 1 h after the end of infusions, the animals were killed. Biliary and exogenous cholesterol were absorbed in the upper two-thirds of the small intestine; a large proportion of 3H and 14C radioactivity was present in the mucosa, but cholesterol from exogenous origin went across the mucosa more rapidly than cholesterol from biliary source. These observations suggest the existence of a non-homogeneous luminal mixture of molecules of cholesterol from different sources. The luminal dilution of [3H]- and [14C]sterols by non-labelled sterols increased from the proximal to the distal part of the small intestine. Precursor sterols and coprosterol were present in the stomach contents and in the lumen of caecum, colon and feces.

Animals↗