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Fetal bile salt metabolism. The intestinal absorption of bile salt.

The intestinal absorption of sodium taurocholate was studied in the near-term fetal and neonatal dog. Absorption rates were measured in vivo in isolated loops of fetal jejunum and ileum. Absorption was also measured in vitro in everted sacs and rings of fetal and neonatal jejunum and ileum. The maximal rates of taurocholate absorption observed after instillation of 1 micronmol taurocholate into closed segments of fetal jejunum and ileum with intact blood supply were not significantly different (P less than 0.2), and equalled 0.282+/-0.026 (mean+/-SEM) and 0.347+/-0.051 micronmol/h per 10-cm segment length jejunum and ileum, respectively. Similarly, the rates of absorption from open segments of jejunum and ileum perfused with 0.4 and 1.0 mM taurocholate were nearly identical (0.232+/-0.040 and 0.255+/-0.039, respectively at 0.4 mM, and 0.470+/-0.065 and 0.431+/-0.013, respectively at 1.0 mm) (P greater than 0.2). At perfusate concentrations of 4.0 mM, moreoever, jejunal absorption exceeded ileal absorption (1.490+/-0.140 and 0.922+/-0.200, respectively (P less than 0.05). As expected, concentration of taurocholate by the mucosa was readily demonstrated in adult ileal, but not in adult jejunal everted rings. In contrast, there were no significant differences in mucosal uptake of taurocholate by fetal jejunal and ileal rings. Fetal ileal mucosal concentrations were not significantly above those in the incubation medium after 1-h exposure of the mucosa to 0.003, 0.03, and 0.3 mM taurocholate. Uptake was proportional to incubation medium concentration over the full range of values. This was also true of tissues from 1-wk-old neonates. However, by 2 wk of age, ileal mucosal concentration of taurocholate was evident and adult levels were attained by 5 wk of age. It is concluded that taurocholate is absorbed by the fetal gut and that ileal absorption is no more efficient than jejunal absorption. Although active glucose transport was demonstrable in both jejunum and ileum, it was not possible to demonstrate an ileal mechanism for active transport of taurocholate in the fetus. Active ileal transport was not demonstrable in the newborn until at least 2 wk after birth.

Age Factors

Type I hyperprolinemia: a study of the intestinal absorption of proline, hydroxyproline, and glycine.

Intestinal absorption of proline, hydroxyproline, and glycine was interpreted by investigation of a type I hyperprolinemia patient and six control subjects. Intestinal perfusion was performed. When proline (Pro), hydroxyproline (OH-Pro), and glycine (Gly) were infused together, an increase in proline concentration did not alter aminoacid uptake in the control subjects; however, in the hyperprolinemia patient, uptake of aminoacids became negliglible (Pro, 17--6 muM/min; OH-Pro, 15--0.3 muM/min; and Gly, 13.5--0 muM/min). When each aminoacid was infused alone at increasing concentrations aminoacid uptake increased in controls; in the hyperprolinemic patient, intestinal absorption was less for glycine and hydroxyproline but aminoacid uptake increased with substrate concentration; however, for proline, the uptake remained constant (1l.5--17 muM/min/20 cm of intestinal test segment) (Table 1). When hydroxyproline was infused with an increased concentration of proline in the hyperprolinemic patient, hydroxyproline uptake first increased (9.8--14.3 muM/min/20 cm) then decreased to its basal value, whereas, in the control subjects, uptake increased without decreasing subsequently.

Biological Transport

Intestinal absorption and losses of copper measured using 65Cu in zinc-deprived men.

The absorption and intestinal losses of endogenous Cu in response to a low Zn diet were studied in five young male subjects using stable 65Cu as an oral tracer. The subjects received a semi-purified formula diet providing 85 mumol (5.6 mg) Zn/d during 15-day baseline and repletion phases and 12 mumol (0.8 mg) Zn/d during an intervening period of 25 days. Thirty-eight mumol (2.4 mg) Cu/d was provided throughout the study. In four of the subjects, the mean +/- SEM luminal disappearance of 65Cu was 37 +/- 4 per cent during the baseline phase and was unaffected by Zn deprivation (32 +/- 7 per cent) or repletion (30 +/- 7 per cent) as were intestinal losses of endogenous Cu [7 +/- 4, 8 +/- 3, 8 +/- 3 mumol/d (0.4 +/- 0.1, 0.5 +/- 0.1, 0.5 +/- 0.1 mg/d) during baseline, Zn deprivation and Zn repletion phases, respectively]. In a fifth subject, who had some evidence of a resolving alcohol-induced hepatitis, the luminal disappearance of 65Cu was 31, 44 and 42 per cent and the intestinal losses of endogenous Cu 11, 2 and 6 mumol/d (0.7, 0.1 and 0.4 mg/d) during the baseline, Zn deprivation and Zn repletion phases respectively. Plasma Cu concentrations, however, fell throughout the study in all the subjects, despite consistently positive Cu balances. There may be subtle effects of a low dietary intake of Zn on Cu metabolism which were not revealed by the methods used in this study.

Adult

Intestinal absorption of 1,25-dihydroxyvitamin D3 in the rat.

Intestinal absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] from in vivo jejunal sacs was studied in rats with thoracic duct and bile duct cannulas. In 6 h 86.5% of the administered 1,25(OH)2D3 was absorbed, but only 7.3% was recovered in thoracic duct lymph. Appearance in plasma of [3H]-1,25(OH)2D3 after intrajejunal administration was identical in rats with and without diverting lymph cannulas, indicating that the 1,25(OH)2D3 is absorbed almost entirely via portal blood. When 1,25(OH)2D3 was instilled into the jejunum in a fat suspension without bile salts rather than a mixed micellar solution, less was recovered in lymph, but total intestinal absorption was unchanged. High-pressure liquid chromatography of a lymph extract demonstrated that 1,25(OH)2D3 was present only as the unchanged secosteroid. In lymph, only 4.1% of the 1,25(OH)2D3 was in the chylomicrons, with the remainder bound to the plasma protein fraction of lymph. Treatment of rats with cycloheximide to block chylomicron synthesis did not decrease absorption of 1,25(OH)2D3. These results indicate that intestinal absorption of 1,25(OH)2D3 is effective and not very dependent on luminal bile salts. Almost all 1,25(OH)2D3 is released from the intestine directly into portal blood and does not require packaging in chylomicrons for transport into intestine lymph.

Animals

[Postoperative intestinal absorption in old age (author's transl)].

The function of intestinal absorption was analysed in elderly patients before and after cholecystectomy by the help of the modified D-xylose-absorption test. A characteristic dependence upon the age for the process of intestinal absorption was demonstrated in the elderly not only preoperatively but also postoperatively. The effective intestinal absorption of D-xylose normalized postoperative by in freshly operated older patients more slowly than in younger ones.

Aged

Nonabsorbable marker and single, random stool samples used for measuring intestinal absorption of macronutrients in infants and children.

To measure intestinal absorption by using a single, random stool sample, polyethylene glycol (PEG), 1 g/d, and a constant diet were given to healthy infants, with a constant PEG-to-macronutrient ratio. After 10 d equilibration, apparent intestinal absorption of macronutrients was estimated from a standard 3-d metabolic balance and compared with that estimated by using the ratio of PEG to macronutrients in a single random sample of feces. Correlation coefficients for this comparison were 0.649, 0.715, and 0.924 for nitrogen, carbohydrate, and fat, respectively. Additionally, apparent intestinal absorptions estimated from two separate consecutive 3-d metabolic-balance studies were compared, showing correlation coefficients of 0.106, 0.653, and 0.463 for nitrogen, carbohydrate, and fat, respectively. The random sample-marker technique appears to be acceptable for measuring apparent absorption of macronutrients and is at least as accurate as a standard 3-d metabolic-balance study.

Child, Preschool

The effect of exercise associated with acute poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption of D-xylose in rats.

The intestinal absorption of D-xylose was studied during acute poisoning of male Wistar rats receiving intragastrically potassium nitrate and sodium nitrite and small intestine perfusion with these compounds. The metabolic parameters, Na+/K(+)-ATPase, alkaline phosphatase, oxygen uptake, and lactic acid level, were assessed in the small intestine mucosa one hour after administration of these compounds. Exercise was demonstrated to reduce the intestinal absorption of D-xylose, to raise the level of lactic acid, and to increase the oxygen uptake by the small intestine mucosa, but caused no changes in the activity of Na+/K(+)-ATPase or alkaline phosphatase. Also, exercise failed to change the direction of the toxic effects of sodium nitrite but increased potassium nitrate toxicity as evidenced by reduced absorption of D-xylose from the intestine despite lack of changes of the enzymes Na+/K(+)-ATPase and alkaline phosphatase in the mucosa.

Alkaline Phosphatase

Passive and carrier-mediated intestinal absorption components of captopril.

The intestinal absorption mechanism of captopril was investigated in fasted rats using a single-pass perfusion method. Captopril and captopril disulfide were analyzed by HPLC. A modified boundary-layer solution was applied to determine the apparent intestinal wall permeabilities (Pw*). The results indicated that captopril is very permeable in the small intestine but not in the colon, and the permeability in the small intestine is both pH and concentration dependent. The estimated parameters for the carrier are: Km*, 6 mM; Jmax*, 12 mM; and Pc*, 2. There is also a significant passive component to captopril absorption in the small intestine. Furthermore, the intestinal permeability of captopril was significantly decreased by the withdrawal of sodium from the perfusate (3 times), and the addition of 85 mM of gly-gly (2.5 times), 15 mM of gly-pro (4 times), dipeptide mixture (4.5 times), 0.5 mM of 2,4-dinitrophenol (4 times), and 10 mM of cephradine (6 times). This is the first demonstration that an angiotensin converting enzyme (ACE) inhibitor is at least in part transported by a carrier-mediated process in the intestine via the peptide carrier system. In addition, the results showed that the peptide carrier system can transport a substrate without a "N" terminal nitrogen atom.

Animals

Intestinal absorption and metabolism of homoursodeoxycholic acid in rats.

Intestinal absorption, hepatic biotransformation and intestinal bacterial modification of the C25 homolog of ursodeoxycholic acid, homoursodeoxycholic acid, and its glycine conjugate, glycohomoursodeoxycholic acid, were studied in rats. Homoursodeoxycholic acid, like ursodeoxycholic acid, was efficiently absorbed from the intestine and rapidly excreted into the bile. Most (greater than 95%) of the absorbed homoursodeoxycholic acid was found to undergo beta-oxidation to form two C23 bile acids, norursodeoxycholic acid and nor-beta-muricholic acid during passage through the liver. Bacterial modification of homoursodeoxycholic acid was very similar to that of ursodeoxycholic acid. In the rat intestinal tract, glycohomoursodexycholic acid was deconjugated to form unconjugated homoursodeoxycholic acid which was then 7 beta-dehydroxylated to form homolithocholic acid.

Animals

Intestinal absorption and metabolism of norcholic acid in rats.

Intestinal absorption and hepatic and intestinal bacterial biotransformations of norcholic acid, the C23 homologue of cholic acid, were studied in the rats. Norcholic acid, like cholic acid, was efficiently absorbed from the intestine and quickly secreted into the bile. Unlike the C24 bile acid, however, which is secreted by rat liver as its taurine conjugate, the C23 bile acid appeared in the bile predominantly as the unconjugated form. conjugated form. Bacterial modification of norcholic acid was similar to but less extensive than that of cholic acid. A considerable part of norcholic acid was left unchanged during its passage through the intestinal tract. A major bacterial metabolite of norcholic acid was the 7-dehydrogenation product, 7-ketonordeoxycholic acid, rather than the 7-dehydroxylation product, nordeoxycholic acid, though the reverse is true for cholic acid.

Animals

Intestinal absorption of choline in rats.

The intestinal absorption of choline, an endogenous quaternary ammonium, from the rat jejunum has been investigated with an in situ ligated loop method and an in vitro everted sac method. Choline was absorbed rapidly from the ligated jejunum and structural analogs inhibited choline absorption competitively. In in vitro experiments, choline was transported from the mucosal fluid to the intracellular fluid against a concentration gradient and the rate of tissue uptake was highly affected by incubation temperature, aerobic condition and the presence of a metabolic inhibitor, 2,4-dinitrophenol. The tissue accumulation of choline was saturable at concentrations below 100 microM and, above this concentration the uptake ratio of choline (medium to tissue) was almost constant. One mM hemicholinium-3, which is well known to inhibit choline uptake by neurons through the choline specific carrier, also significantly inhibited choline uptake, especially at concentrations of choline below 100 microM. The fact that the choline uptake is linear in the presence of hemicholinium-3 shows that choline is partially absorbed by passive diffusion. The difference between the total tissue accumulation and choline uptake by the passive diffusional pathway followed Michaelis-Menten kinetics and the apparent Kt of 47 microM and Vmax of 4.1 nmol/ml intracellular fluid/min were determined by an in vitro everted sac method. These findings suggested that, a lower concentrations, choline was absorbed from the rat intestine mainly by an active transport system.

Animals

Incomplete intestinal absorption of fructose.

Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children with bowel disorders showed incomplete absorption. Seven children were tested again with an equal amount of glucose, and in three of them also of galactose, added to the fructose. The mean maximum breath hydrogen increases were 5 and 10 ppm, respectively, compared with 103 ppm after fructose alone. In one boy several tests were performed with various sugars; fructose was the only sugar incompletely absorbed, and the effect of glucose on fructose absorption was shown to be dependent on the amount added. It is concluded that children have a limited absorptive capacity for fructose. We speculate that the enhancing effect of glucose and galactose on fructose absorption may be due to activation of the fructose carrier. Apple juice in particular contains fructose in excess of glucose and could lead to abdominal symptoms in susceptible children.

Adolescent

Effects of vasoactive intestinal polypeptide on intestinal absorption and blood flow.

1. Intestinal absorption and blood flow in anaesthetized dogs was determined after I.V. infusion of vasoactive intestinal polypeptide (VIP) (1.75-175 ng/min) to determine the contribution of the cardiovascular changes to transport. 2. 22Na and 3H2O were utilized to determine the unidirectional fluxes of Na and H2O from saline perfused through the ileal lumen and the clearances of 3H2O were used to determine total and absorptive site blood flow. 3. Net Na and H2O absorption were reversed to secretion by VIP at 175 ng/min due to a significant decrease in unidirectional absorptive fluxes and smaller increases in secretory fluxes. 4. Arterial pressure and absorptive site blood flow were reduced in proportion to the changes in Na and H2O fluxes. 5. Total and absorptive site blood flow decreased and the blood flow resistances increased. 6. Prior treatment with guanethidine to suppress sympathetic effects did not greatly affect the responses to VIP. Prior treatment with atropine to suppress cholinergic effects inhibited most of the effects of VIP. 7. Absorptive site blood flow was linearly related to absorptive fluxes of Na and H2O but with different slopes for results from atropinized dogs as compared to those from dogs given VIP alone or VIP plus guanethidine. 8. It was concluded that VIP reduces gut absorption through a generalized cardiovascular effect and also through a mechanism which depends on the release of ACh by the gut.

Animals

Intestinal absorption of fluoride preparations.

Gastric intestinal absorption of five different preparations of sodium fluoride was measured by means of ten hour urinary excretion. Best absorption was by nonenteric coated sodium fluoride. All three enteric coated preparations showed poorer absorption, with marked individual variations. Florical, the currently available preparation, showed better absorption than any enteric coated tablets and only slightly less than sodium fluoride alone. For active cochlear otospongiosis two capsules three times a day should be prescribed.

Administration, Oral