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Effects of cycle exercise on intestinal absorption in humans.

Intestinal absorption was measured in six trained male cyclists during rest, exercise, and recovery periods with the segmental perfusion technique. Each subject passed a multilumen tube into the duodenojejunum. The experiments consisted of 1) a sequence of 1-h bouts of cycling exercise at 30, 50, and 70% maximal O2 uptake (Vo2max) separated by 1-h rest periods or 2) a 90-min bout at 70% VO2max. The cycling was performed on a constant-load Velodyne trainer. Absorption of water and a 6% carbohydrate-electrolyte (2% glucose, 6% sucrose, 20 meq Na+, 2.6 meq K+) solution (both perfused at 15 ml/min) were compared. The effects of perfusing an isotonic electrolyte solution during mild (30% VO2max) exercise were also studied. Fluid was sampled every 10 min from ports 10 and 50 cm distal to the infusion site. Water flux was determined by differences in polyethylene glycol concentration across the 40-cm test segment. Results showed 1) no difference in water or electrolyte absorption rates among rest, exercise, and recovery periods; 2) no difference in absorption rates among the three exercise intensities or different exercise durations; and 3) significantly greater fluid absorption rates from the carbohydrate-electrolyte (CE) solution than from water. Water flux during rest, exercise, and recovery was about sixfold greater from the CE solution than from the isotonic solution without carbohydrate. We conclude that 1) exercise has no effect on water or solute absorption in the duodenojejunum, 2) fluid absorption occurs significantly faster from a CE solution than from water, and 3) fluid absorption is increased sixfold by addition of carbohydrate to an electrolyte solution.

Adult

Intestinal absorption of drugs. I: The influence of taurocholate on the absorption of dantrolene in the small intestine of the rat.

The influence of sodium taurocholate (1) on the intestinal absorption of the lipophilic drug dantrolene (2) was studied in vivo in a chronically isolated internal loop in the rat. Concentrations of 2 were kept below the saturation concentration in saline. Absorption kinetics of 2 were evaluated on the basis of steady-state blood levels, which develop during single-pass perfusions, and on the basis of the rate of disappearance of the drug from the perfusate during recirculating perfusions. Compound 1 at a concentration of 10 mM in the perfusate induced a twofold reduction of the absorption rate compared with the same concentration of 2 in saline. Pretreatment of the absorptive surface with a 10 mM solution of 1 had no detectable effect on the absorption rate of 2 in saline. After perfusions with 10 mM solutions of 1, the perfusate concentration of proteins, phosphorus, and hexoses in the effluent was increased. The reduction of the absorption rate can be ascribed mainly to a reduction of the thermodynamically active concentration of 2 as calculated from the phase-separation model. In addition, 10 mM 1 seems to temporarily increase the barrier function of the mucous layer.

Animals

Immunological control of drug absorption from the gastrointestinal tract: effect of local anaphylaxis on the intestinal absorption of low molecular weight drugs in the rat.

Intestinal absorption of various drugs was examined by means of in situ recirculation technique during local anaphylaxis. The antibody was determined by passive cutaneous anaphylaxis technique in rats immunized once or three times. The optimal condition of local anaphylaxis was determined by the leakage of Evans Blue. The most significant increase in leaks of the dye was observed by the intraluminal challenge with 400 mg of ovalbumin for 10 min in ovalbumin-immunized rats, and this condition was chosen as the optimal condition of local anaphylaxis. Under this condition, intestinal absorption of caffeine, phenylbutazone, and bromthymol blue (BTB) significantly decreased in ovalbumin-immunized rats compared with the control, whereas no significant effect was noted in the intestinal absorption of salicylic acid, quinine, pralidoxime iodide (2-PAM), tetracycline, and phenol red. In normal rats, no significant decrease was obtained in the intestinal absorption of caffeine, phenylbutazone, and BTB. On the other hand, the decreased absorption of BTB was not found in ovalbumin-immunized rats by the intraluminal challenge with bovine gamma-globulin. Furthermore, there was no significant change in the decreased absorption of BTB between rats immunized once and three times. The most effective condition for decreased BTB absorption was observed by the intraluminal challenge with 200 mg of ovalbumin for 10 min in ovalbumin-immunized rats, which almost correlated with the data of Evans Blue leakage. From these observations, it appears that the mucosal immune responses affect the intestinal absorption of low molecular weight drugs.

Anaphylaxis

Somatostatin and its analogue (D-Trp8,D-Cys14)-somatostatin do not modify intestinal absorption in vivo of carbohydrates in hamster intestine, but they do modify some disaccharidases.

Somatostatin is a widely distributed hormone localized in the central nervous system, pancreas and gastrointestinal tract. We have investigated the possible influence of somatostatin and a synthetic analogue, (D-Trp8,D-Cys14)-somatostatin, on the intestinal absorption 'in vivo' of D(+)-glucose and D(+)-galactose and also the effect on disaccharidase intestinal activities in hamster. Somatostatin, or its analogue, (12 micrograms/100 g body wt) was administered intraperitoneally 4 or 14 h prior to experiments. The results are compared to control animals. Animals treated with somatostatin and the synthetic analogue showed that there were no significant difference from control animals with respect to intestinal absorption of carbohydrates. Somatostatin produced inhibition of brush-border lactase activity in females only, whereas brush-border sucrase was increased 14 h after treatment in males and females, and brush-border maltase was inhibited in females only 4 h after hormone administration.

Animals

Intestinal absorption of aluminium.

The intestinal absorption of aluminium can contribute significantly to systemic exposure to this element. Aluminium can be absorbed not only from oral pharmaceuticals but also from solid food and drinking water. The absorption process is not restricted to patients with kidney disorders; other groups of patients and healthy subjects are not excluded. Details of the absorptive mechanism are mainly obtained from in vitro (everted gut sac) and animal studies (intestinal perfusion) rather than from controlled human studies and case reports. The process of absorption depends on the intraluminal speciation, the intraluminal quantity, the presence of competing (iron, calcium) or complexing (citrate) substances and the intraluminal pH. The condition of the exposed organism with respect to the gut also determines intestinal absorption (iron status, calcium [vitamin D, parathyroid hormone] status, age and kidney function). Various absorption sites and passage routes, both transcellular and paracellular, have been reported, each apparently related to a different aluminium species (hydrated ionic species, aluminium citrate complex etc.). No uniform mechanistic model allowing extrapolation to the clinical situation has yet emerged.

Aluminum

Effects of haemodialysis on fractional intestinal absorption of calcium in uraemia.

Fractional intestinal absorption of calcium was measured in 41 haemodialysed patients 4 hours after an oral dose of 47 Ca. Fractional intestinal calcium absorption was 40.3 +/- 1.9% (SEM) when measured 10 to 12 hours after a haemodialysis session (dialysate calcium concentration: 1.75 mmol/litre). This value was significantly lower (p less than 0.001) than that in 26 healthy controls (56.8 +/- 1.8%) and higher (p less than 0.05) than that of 35 patients with chronic renal failure treated conservatively (34.5 +/- 2.1%). In 17 patients, fractional intestinal calcium absorption was measured just before and just after a dialysis session. Pre-dialysis fractional intestinal calcium absorption (33.7 +/- 3.0%) was not significantly different from fractional intestinal calcium absorption in uraemic patients treated conservatively, while after dialysis fractional intestinal calcium absorption had increased significantly to 42.0 +/- 2.6% (p less than 0.001). It is suggested that the transient increase in fractional intestinal calcium absorption observed after dialysis could be related to dialysis induced volume depletion rather than to a vitamin D-dependent mechanism.

Calcium

New aspects in the study of the mechanism of intestinal absorption of thiamine in rats.

Intestinal absorption of thiamine was studied in rats using such metabolic inhibitors as ouabain, sodium azide and theophylline. These substances changed certain biochemical parameters of the mucosa in the small intestine affecting the level of thiamine transport across the intestinal epithelium. It was found that the intestinal transport of thiamine at lower concentration was an active process depending on the activity of Na, K, Mg-ATPase in the intestinal microvilli, and on the activity of mitochondrial processes. The used metabolic inhibitors increased the intestinal diffusion of thiamine at its higher concentration suggesting that these inhibitors changed membrane permeability by affecting enterocyte homeostasis. At both studied concentrations thiamine was rapidly absorbed from the digestive tract reaching the state of saturation which suggested a carrier character of this transport.

Animals

A review of laboratory tests of intestinal absorption in the tropics.

The intestinal absorptive capacity for xylose and folic acid has frequently been found to be defective in apparently normal asymptomatic residents of the tropics. This suggests the presence among the natives of the tropics of appreciable, yet asymptomatic jejunal functional incompetence which is not seen in the temperate countries. Further, structural abnormalities in the villi which are non-specific occur in varying degrees of severity in the tropics both in health and in disease. These tropical peculiarities raise obvious doubts as to the diagnostic usefulness of these laboratory tests in the evaluation of disorders of absorption in tropical practice. In this review, experiences from the Lagos University Teaching Hospital had shown that the faecal fat analysis for the detection of steatorrhoea is the most dependable single diagnostic and in studies of overt malabsorption in Niageria.

Feces

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