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Determination of absorption characteristics of AG337, a novel thymidylate synthase inhibitor, using a perfused rat intestinal model.

The purpose of this study was to determine the intestinal absorption characteristics of AG337, a mechanism-based inhibitor of thymidylate synthase, using a perfused rat intestinal model. Effects of site, pH, temperature, concentration, Na+, and inhibitors on the absorption of AG337 were determined, after the compound was shown to be stable in buffers of various pH, blank perfusate, and intestinal homogenate. The results indicated that absorption of AG337 was temperature-, pH-, Na+-, concentration-, and site-dependent. The best site of absorption is duodenum, where the absorption was 3-10 times (p < 0. 05) higher than absorption at jejunum, ileum, and colon. Among the four pH's studied, the best was at pH 6.5 (p < 0.05). Absorption was 80% lower in the absence of Na+, and 75% lower when the temperature of the perfusate was decreased to 4 degreesC. Permeability of AG337 also decreased about 75% when the concentration was raised to 100 microM. These results suggest that a nutrient carrier may be involved in the transport of AG337. To determine the carrier responsible for the absorption of AG337, its absorption was determined in the presence of various inhibitors at different concentrations. The results indicated that transport of AG337 was inhibited significantly (p < 0.01) by 100 microM of adenine, hypoxanthine, and xanthine. The transport was also inhibited significantly (p < 0.01) by a mixture of 100 microM each of adenine, hypoxanthine, and xanthine, but not by a mixture of 100 microM each of thymine and uracil. A higher concentration of hypoxanthine resulted in increased inhibition. In contrast, prototypical inhibitors of nucleoside transporter, dipyridamole and nitrobenzylthioinosine (NBMPR), did not significantly decrease the transport of AG337. The results also showed that absorption of AG337 had a significant nonsaturable component, with a nonsaturable Pw of 0.8. In conclusion, absorption of AG337 in the rat intestine has been shown to be mainly via a purine base carrier with a significant nonsaturable component.

Animals↗

Stool water content and colonic drug absorption: contrasting effects of lactulose and codeine.

PURPOSE: By varying stool water content using lactulose and codeine, we investigated the influence of luminal water content on the absorption of quinine, a transcellular probe, and 51Cr-EDTA, a paracellular probe, from the distal gut. METHODS: Sixteen volunteers entered a three-way cross-over trial in which absorption of probe markers from a timed-release delivery system was determined following treatment with lactulose 20 mls tds (increasing water content), or codeine 30 gms qds (decreasing water content), and compared with control untreated values. Stool water content was assessed by freeze drying stool samples. Site of release was determined by gamma scintigraphy, and absorption was measured by plasma levels and urinary recovery of the marker probes. RESULTS: Lactulose accelerated ascending colon transit (3.7 +/- 0.8 vs 4.5 +/- 1.4 hrs, p < 0.05), increased stool water content (75 +/- 2 vs 71 +/- 2%, p < 0.01), caused greater dispersion of released material (dispersion score 3.4 +/- 0.3 vs 1.8 +/- 0.2, p < 0.01), and enhanced absorption of the transcellular probe quinine (4.66 +/- 0.78 vs 3.02 +/- 0.63%, p < 0.05) compared to control. Conversely codeine slowed ascending colon transit (8.9 +/- 1.8 hrs), reduced stool water content (61 +/- 2 vs 71.2%, p < 0.05), and tended to diminish absorption (2.60 +/- 0.77 vs 3.02 +/- 0.63%, p = 0.20). Within the ascending colon specifically, there was a significant trend for treatments increasing luminal water content to enhance quinine absorption (medians: codeine = 1.2%, [n = 81 < control = 2.3%, [n = 5] < lactulose = 3.2%, [n = 71, p < 0.01). Delivery site also had an important influence on absorption, with more distal release resulting in less absorption in the control arm (medians: small intestine = 4.4% [n = 5] > ascending colon = 2.3% [n = 5] > transverse colon = 1.5% [n = 6], p < 0.005). CONCLUSIONS: Lactulose accelerates transit, increases stool water content, and enhances drug absorption from the distal gut whilst codeine slows transit, decreases stool water content, and tends to diminish absorption, compared to controls. We conclude that water content may be an important determinant in colonic drug absorption.

Adult↗

Stimulation of sodium chloride absorption from secreting rat colon by short-chain fatty acids.

Inhibition of electroneutral NaCl absorption by cyclic adenosine monophosphate (cAMP) results in fluid malabsorption in cholera. Short-chain fatty acids (SCFA) stimulate electroneutral NaCl absorption from the colon. The present study investigated effects of elevated cAMP on SCFA-stimulated NaCl absorption in rat distal colon. The effect of SCFA on fluxes of 22Na and 36Cl was studied under voltage-clamp conditions, in the presence and absence of secretagogues inducing mucosal cAMP elevation [ie, theophylline, cholera toxin (CT) and forskolin]. The effect of butyrate concentration on Na absorption in CT- and theophylline-treated mucosa was compared with control normal mucosa. cAMP was measured in isolated colonocytes in the presence of secretagogues with and without SCFA using a radioassay method. All secretagogues were noted to inhibit net Na absorption and to induce net Cl secretion. In the presence of SCFA, net Na absorption was normal, and net Cl secretion was partly reversed. The flux data indicated that NaCl absorption from secreting colon was stimulated by SCFA and that Cl secretion was partially inhibited. The effects of SCFA on NaCl absorption were similar regardless of the secretagogue used. The kinetics of butyrate-stimulated Na absorption were altered by theophylline and CT, which decreased Km (6.87 and 7.17, respectively, compared to 10.75 mM for control) and increased Vmax (4.55 and 8.33 compared to 3.45 mM/eq/cm2/hr for control). cAMP production by colonocytes in response to secretory stimuli was significantly reduced (34.4%) by butyrate but not by acetate or propionate. In conclusion, SCFA-stimulated Na absorption is up-regulated by cAMP and may be an absorptive pathway that can be utilized in the therapy of cholera. Effects of butyrate on cAMP generation are also likely to be useful in secretory diarrhea.

Animals↗

Irrigation fluid absorption during transurethral resection of the prostate: spinal vs. general anaesthesia.

BACKGROUND: The absorption of irrigation fluid during transurethral resection of the prostate (TURP) is determined primarily by hydrostatic pressure in the bladder and prostatic venous pressure. In comparison to spontaneously breathing patients, patients undergoing mechanical ventilation with positive pressure have a raised central venous pressure and a reduced venous return, both of which can influence intravascular absorption. The purpose of the prospective study was to compare the effects of general (GA) and spinal anaesthetic (SA) techniques on the perioperative absorption of irrigating fluid in patients undergoing TURP. METHODS: Forty patients undergoing TURP were randomised and assigned either to group GA or SA. Irrigating fluid absorption was traced by adding 1.5% (w/v) ethanol to the irrigating fluid. Perioperative blood ethanol concentration (BEC), haemoglobin concentration, haematocrit, serum sodium concentration and central venous pressure (CVP) were measured at 10-min intervals during TURP and at 30-min intervals while patients were recovering. Absorption routes were indexed by the BEC and changes in serum sodium concentrations. Where the BEC was greater than 0.05 mg.mL-1, absorption of irrigating fluid was assumed. For assessing the volume of irrigating fluid absorbed, the maximum BEC, the absorption rate, the area under the BEC curve (AUC), and the volumes calculated according to the Hahn nomogram (Volin) for each patient were taken into consideration. RESULTS: There were 15 cases of irrigating fluid absorption in patients receiving GA (75%), and 11 in those receiving SA (55%). CVP was significantly lower in spontaneously breathing patients with SA as compared to those with GA (P < 0.05). In patients with irrigating fluid absorption the maximum BEC (P < 0.02), as well as the rate of irrigant fluid absorption (P < 0.01), were significantly higher amongst patients receiving SA. In this group, the calculated area under the curve and the absorbed fluid volumes determined with the nomogram were significantly increased (P < 0.05). CONCLUSION: The absorption of irrigation fluid during the TURP is significantly more marked amongst spontaneously breathing patients with regional anaesthesia in comparison to patients undergoing general anaesthesia with positive pressure ventilation. The markedly lower central venous pressure before the start of irrigation should be considered as a possible cause of this effect.

Absorption↗

Cyclosporine microemulsion (Neoral) absorption profiling and sparse-sample predictors during the first 3 months after renal transplantation.

UNLABELLED: Recent data suggest that optimal cyclosporine (CsA) exposure early post-transplant significantly reduces the risk of acute graft rejection. They indicate that trough level monitoring is inadequate for precise concentration-controlled therapy, and suggest that absorption profiling may offer a superior approach for guiding clinical immunosuppression with Neoral. An international, prospective, multicenter study examined the feasibility, accuracy, precision and clinical utility of cyclosporine microemulsion (Neoral) absorption profiling in de novo renal transplant recipients receiving basiliximab immunoprophylaxis and cyclosporine microemulsion maintenance immunosuppression. The nested pharmacokinetic study reported here was conducted in 4 study centers in which full (11-point) pharmacokinetic profiles were performed on days 3, 7, 14 and 84 post-transplant to examine absorption profile and absorption efficiency, and to determine optimal sparse-sampling pharmacokinetic methods to predict Neoral exposure. Twenty-four patients had complete 12-h pharmacokinetic (PK) data on all 4 sampling days. Area under the time-concentration curve (AUC) over the first 4 h of the 12-h dosage interval (AUC[0-4]) and AUC over the entire 12-h dosage interval (AUC[0-12]) reached 3803 +/- 1033 and 7462 +/- 2120 microg.h/L respectively, by day 3, remained stable throughout the first 2 weeks, and declined to 2310 +/- 698 and 4062 +/- 1158 microg.h/L by day 84 (p < 0.001). AUC[0-4], capturing the drug absorption phase, represented 52% of the AUC[0-12] values across the four PK study days (mean R2 > 0.90). Between-patient variability was highest for C0 and C1 (mean coefficient of variation [c.v.] 36-47%), and lower for C2 (mean c.v. 28%) and subsequent time-points during the dosing interval. Mean relative CsA absorption, measured by dose- and weight-adjusted AUC[0-4] and AUC[0-12], increased significantly over time. The dose- and weight-corrected AUC[0-4h] (DWC.AUC[0-4]) rose by over 100% (p < 0.001) from 753 +/- 202 at day 3 to 905 +/- 232 at day 7, 1080 +/- 330 at day 14 and 1521 +/- 316 by day 84, while the dose-and weight-corrected AUC[0-12h] (DWC.AUC[0-12]) rose by over 80% (p < 0.001) from 1477 +/- 390 microg.h/L/ mg/kg on day 3, to 1721 +/- 426 on day 7, 2086 +/- 478 on day 14 and 2690 +/- 602 on day 84 (p < 0.001). Relative CsA absorption varied over 5-fold between patients at day 3, but patients tended to remain within the same quartiles over time. Sparse-sample modeling identified optimum 3-point, 2-point and 1-point predictors for AUC[0-4] and AUC[0-12]. C2 was the most accurate and robust .1-point predictor for AUC[0-4] (mean R2: 0.80), while C3 was superior for AUC[0-12] (mean R2: 0.75). C0 was not a good predictor of either AUC[0-4] or AUC[0-12] (mean R2: 0.13 and 0.24, respectively). CONCLUSION: Absorption profiling defines the heterogeneity in CsA exposure and relative absorption post-transplant. A 2-h post-dose blood sample is the most consistent, accurate and robust single-point predictor of the absorption phase measured by AUC[0-4] and should replace trough level monitoring for accurate concentration-control of Neoral therapy in the clinical setting. The use of additional samples at 1 and 3h is more complex and costly, but increases prediction accuracy and may be valuable in selected patients with erratic absorption.

Area Under Curve↗

The absorption of dietary phosphorus and calcium in hemodialysis patients.

Absorption of dietary phosphorus plays a critical role in the development of metabolic bone diseases in patients with chronic renal failure. However, phosphorus absorption is difficult to quantitate in dialysis patients because the dialysis treatments complicate metabolic balance studies. Utilizing a recently developed technique which permits measurement of net absorption of dietary constituents after a single meal, we measured phosphorus absorption in dialysis patients. The following observations were made: A.) Following a meal containing approximately 300 mg phosphorus, mean phosphorus absorption in five hemodialysis patients (with severe vitamin D deficiency) was only slightly less than in matched controls (186 +/- 35 vs. 242 +/- 30). B.) After dialysis patients were treated with 1,25(OH)2-D3, phosphorus absorption increased from 186 +/- 35 to 272 +/- 16 mg (P less than 0.025). C.) The effect of three aluminum containing antacids on phosphorus absorption was studied; each slightly reduced the absorption of phosphorus compared to placebo (P less than 0.01), but there was no significant difference between them. D.) Aluminum hydroxide and calcium carbonate each reduced dietary phosphorus absorption to approximately the same extent. Calcium carbonate ingestion was associated with sharply increased calcium absorption. The absorption of dietary phosphorus is influenced only modestly by 1,25(OH)2-D3 and is inhibited to an equal but only modest degree by various aluminum antacids and by calcium carbonate.

Adult↗

Effect of iron status on the intestinal absorption of aluminum: a reappraisal.

Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be mediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, transferrin-dependent pathways and that iron (Fe) deficiency increases the intestinal absorption of Al. However, since no transferrin receptors are expressed on the absorptive surface of small intestinal epithelial cells this notion is doubtful. To further clarify the issue the present study investigated the effect of marked alterations of body Fe stores on the intestinal absorption of Al using three different rat models. (I) Serum Al concentrations and urinary excretion rates of Al were measured in iron-overloaded (Fe+) or iron-deficient (Fe-) rats with either normal (C) or impaired (5/6 nephrectomy) renal function (Nx) employing oral A1 loads in single dose studies. (II) Tissue A1 accumulation as well as serum and urine A1 were determined in respective experimental groups exposed to a prolonged (41 days) dietary Al load. (III) To assess the effect of Fe status on the intestinal absorption of Al directly at the organ level perfusions of in situ rat gut preparations were performed. In the single dose studies administration of Al resulted in similar urinary excretion rates of Al in intact kidney groups (C+Fe-, 229 +/- 85 nmol/5 days; C+Fe+, 240 +/- 59 nmol/5 days) despite marked differences in liver Fe (C+Fe-, 1.34 +/- 0.16 vs. C+Fe+, 55.69 +/- 13.20 mumol/g) and duodenal mucosal Fe (C+Fe-, 0.68 +/- 0.11 vs. C+Fe+, 3.17 +/- 0.82 mumol/g). In addition, mucosal Al concentration 24 hours after the load was not affected by the Fe status (C+Fe-, 37 +/- 16 nmol/g, C+Fe+, 56 +/- 19 nmol/g). Regardless of the Fe status post-load Al excretion was enhanced in Nx rats (Nx+Fe-, 533 +/- 234 nmol/five days, Nx+Fe+, 536 +/- 201 nmol/five days). Irrespective of Fe status a prolonged dietary Al load resulted in a similar increase in tissue Al concentration (nmol/g) in liver (baseline, 159 +/- 22; C+Fe-, 276 +/- 125; C+Fe+, 251 +/- 71; Nx+Fe-, 330 +/- 119; Nx+Fe+, 437 +/- 67) and in bone (baseline, 219 +/- 119; C+Fe-, 433 +/- 174, C+Fe+, 485 +/- 141; Nx+Fe-, 504 +/- 185; Nx+Fe+, 548 +/- 215). The increase in spleen Al was significantly larger in Fe-overloaded rats (baseline, 194 +/- 20; C+Fe+, 511 +/- 129 vs. C+Fe-, 308 +/- 62, P < 0.05; Nx+Fe+, 514 +/- 67 vs. Nx+Fe-, 389 +/- 119, P < 0.05). Brain Al tended to rise in Nx rats only (baseline, 96 +/- 33; Nx+Fe+, 174 +/- 100, Nx+Fe-, 156 +/- 78, P = NS). Analogous results were obtained in in situ intestinal perfusion studies: Fe deficiency and Fe overload both did not affect the time-dependent increase in serum Al in either systemic or portal vein blood. When paracellular intestinal permeability was assessed mannitol absorption was significantly higher in uremic animals as compared to controls. Pharmacological blockade (2 mM kinetin) of the paracellular permeability substantially reduced the time-dependent increase in serum Al in uremic rats but had little effect in control animals, suggesting that even the excess absorption of Al observed in uremia occurs via a paracellular rather than an iron-specific pathway. In conclusion, the findings of the present study provide several lines of evidence against the commonly accepted view that the intestinal absorption of Al occurs via iron-specific pathways. Most likely, this is related to the fact, that neither the absorption of Fe nor the absorption of Al are mediated via transferrin receptors. In addition, the enhanced intestinal absorption of Al observed in uremic rats does also not occur via iron-specific pathways, but seems to due to increased paracellular permeability of the intestine.

Aluminum↗

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury.

BACKGROUND/PURPOSE: This study was designed to explore the efficacy of a synthetic analogue of glucagonlike peptide-2 (GLP-2a) in enhancing mucosal mass and absorptive function in a rat model of intestinal ischemia-reperfusion (I-R) injury. METHODS: Each of 20 Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents over 3 days. Rats were divided into 4 groups (n = 5 per group): (1) normal intestine/saline infusion; (2) 30-minute superior mesenteric artery occlusion/saline infusion, (3) normal intestine/ GLP-2alpha infusion, and (4) 30-minute superior mesenteric artery occlusion/GLP-2alpha infusion. Subsequently, mean mucosal 14C-galactose and 14C-glycine absorption and DNA content were determined for each group. RESULTS: In saline-treated rats, 30 minutes of mesenteric ischemia decreased mean mucosal galactose absorption by 29% (P < .05), glycine absorption by 22% (P = .12), and DNA content by 28% (P < .01) when compared with rats with uninjured intestine. In rats subjected to 30 minutes of intestinal ischemia, GLP-2alpha significantly improved galactose absorption by 46% (P < .05), glycine absorption by 84% (P < .01), and DNA content by 63% (P < .01) when compared with saline-treated control rats. In rats with mesenteric I-R injury treated with GLP-2a, galactose absorption was returned to normal. Glycine absorption and DNA content were increased significantly by 44% (P < .01) and 18% (P < .05), respectively, beyond the baseline for normal intestine. CONCLUSIONS: Thirty minutes of intestinal ischemia followed by immediate reperfusion significantly decreased mucosal mass and absorptive function, validating this rat model of I-R injury. After mesenteric I-R, GLP-2a significantly increased mucosal DNA content and absorption of 14C-galactose and 14C-glycine when compared with untreated control rats. After I-R injury, GLP-2a restored mucosal mass and absorptive function to normal or above-normal levels.

Animals↗

Calcium absorption and achlorhydria.

Defective absorption of calcium has been thought to exist in patients with achlorhydria. I compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement.

Achlorhydria↗

Effects of erythropoietin therapy on iron absorption in chronic renal failure.

The effect of erythropoietin administration on the absorption of dietary and therapeutic iron was examined in patients with anemia of chronic renal failure on maintenance hemodialysis. Absorption from test meals tagged extrinsically with iron 55, iron 59, or both was determined 2 weeks later by using incorporated red blood cell radioactivity and whole body counting. In an initial study of food iron absorption, the effect of initiating erythropoietin therapy was determined by measuring the absorption of heme and nonheme iron before and 2 weeks after the administration of 64 U/kg body weight erythropoietin (range, 46-85 U/kg body weight) three times weekly. Absorption of heme iron increased 1.6-fold from 18.6% to 30.1% (P < .05), and nonheme iron increased 3.7-fold from 1.3% to 4.9% (P < .01) after erythropoietin therapy. In a second study therapeutic iron absorption was evaluated at baseline and after erythropoietin administration (63 U/kg body weight (range, 48-74 U/kg body weight) three times weekly). The absorption of 50 mg of iron as ferrous sulfate increased 2.4-fold from 3.8% to 9.4% (P < .05) when given without food and 4.2-fold from 1.4% to 5.9% (P < .05) when given with food after erythropoietin administration. After adjusting for changes in iron stores with serum ferritin after erythropoietin therapy, the enhanced erythropoiesis associated with erythropoietin therapy increased absorption about 2-fold, which was similar to the response observed previously in normal subjects. In a final study we examined the absorption of therapeutic iron during the steadystate phase of erythropoietin therapy after an erythroid response to erythropoietin had occurred. The absorption of 50 mg of iron was lower than that occurring with the initiation of erythropoietin therapy at 2.2% when given alone and 1.3% when taken with food. We conclude that iron absorption with or without erythropoietin stimulation is unimpaired in patients with chronic renal failure.

Adult↗

A comparison of iron absorption in adults and infants consuming identical infant formulas.

Fe absorption was estimated in adults and infants from the erythrocyte incorporation of Fe isotopes added to infant formula. Fe absorption was measured in adults using radioisotopes, and in infants with a stable-isotope technique. In adults, the geometric mean Fe absorption from a ready-to-feed soya formula with its native phytic acid content was 2.4%. This increased to 6.0% (P < 0.05) after almost complete dephytinization. In infants, mean Fe absorption values were 3.9 and 8.7% respectively from the same products (P < 0.05). In adults, mean Fe absorption from a spray-dried soya formula containing 110 mg ascorbic acid/l was 4.1%, increasing to 5.3% (P < 0.05) when ascorbic acid was doubled to 220 mg/l. In infants, mean Fe absorption values were 5.7 and 9.5% (P < 0.05) from the same products. Mean Fe absorption from a milk-based formula was 6.5% in adults compared with 6.7% in infants. All meals in the adult and infant studies were fed using an identical meal size of 217 g. Increasing the meal size threefold in adults did not change fractional Fe absorption. Mean Fe absorption values for each meal were lower in adults than in infants but the relative inhibitory effect of phytic acid and the enhancing effect of ascorbic acid were similar. We conclude that Fe absorption studies in adults can be used to assess the influence of enhancers and inhibitors of Fe absorption in infant formulas fed to infants. Further studies, however, are required to extend these findings to weaning foods and complete meals.

Adult↗

Calcium and zinc absorption from lactose-containing and lactose-free infant formulas.

BACKGROUND: Calcium absorption is enhanced by the presence of lactose, but the quantitative significance of this effect in infant formulas is uncertain. It is also not known whether lactose affects zinc absorption. OBJECTIVE: We measured the absorption of calcium and zinc from infant formulas by using a multitracer, stable-isotope technique. DESIGN: Eighteen full-term infants (aged 8-12 wk at enrollment) were fed 2 partially hydrolyzed whey-protein-based formulas ad libitum for 2 wk per formula. The carbohydrate source was lactose in one formula and glucose polymers in the other (lactose-free). Infants were studied in a blinded crossover fashion after 2 wk of adaptation to each formula. Isotope absorption studies were conducted with a 4-tracer method in which (70)Zn and (44)Ca were provided orally and (67)Zn and (46)Ca intravenously. Zinc and calcium absorption was measured from the fractional excretion of the oral and intravenous isotopes in urine. RESULTS: Fractional and total calcium absorption was significantly greater from the lactose-containing formula than from the lactose-free formula. For total calcium absorption, the mean difference between formulas was 10.3% (P = 0.002) and 60 mg/d (P = 0.006). For zinc, fractional absorption (32 +/- 11%), total absorption, and intake did not differ significantly between the 2 formulas. CONCLUSIONS: The presence of lactose in a formula based on cow-milk protein increases absorption of calcium but not of zinc. Absorption of calcium from a lactose-free infant formula is, however, adequate to meet the calcium needs of full-term infants when the formula's calcium content is similar to that of lactose-containing, cow-milk-based infant formulas.

Administration, Oral↗

Efficiency of calcium absorption is not compromised in clinically stable prepubertal and pubertal girls with cystic fibrosis.

BACKGROUND: Reduced bone mass is common in both children and adults with cystic fibrosis (CF) and may be a consequence of inadequate calcium absorption. The effect of CF on intestinal calcium absorption and retention has not been described in children. OBJECTIVE: Calcium absorption and urinary losses were characterized in clinically stable girls with CF consuming self-selected diets and following usual pancreatic enzyme regimens. DESIGN: The percentage of calcium absorption was assessed in 23 girls (aged 7-18 y) with CF by using oral ((44)Ca) and intravenous ((42)Ca) stable isotopes. Girls were grouped according to Tanner stage of breast development. True calcium absorption (V(a)) was determined as the product of percentage calcium absorption and average 4-d daily calcium intake. Calcium balance was estimated by subtracting urinary calcium and estimated endogenous fecal losses from the measure of V(a). Analysis of variance was used to compare outcomes among pubertal groups, and regression analysis was used to describe the relations of percentage and total calcium absorption to calcium intake and of urinary calcium to sodium excretion. RESULTS: Percentage calcium absorption was inversely related to calcium intake. Percentage absorption and V(a) were similar to values observed in healthy girls in other studies. Total calcium absorption and estimated calcium balance were significantly greater among girls in early puberty (Tanner stages 2-3) than in prepubertal or late-pubertal girls (P < 0.05). Urinary calcium was positively related to urinary sodium excretion (P = 0.02). CONCLUSION: The efficiency of calcium absorption was not compromised in clinically stable girls with CF.

Absorption↗

Dual-isotope method for determination of human zinc absorption: the use of a test meal of turkey meat.

The percentage of 65Zn taken up (absorbed) from extrinsically labeled turkey meat was calculated from the amounts of 65Zn and a nonabsorbed 51Cr marker present in the body or in a single stool specimen after 1-2 d. 51CrCl3 proved to be a suitable marker for unabsorbed 65Zn and so the early determination of 65Zn absorption was possible. With stool counting, 65Zn absorption data from first stool samples after 1-2 d were accurate as judged by correlation with the amount of 65Zn in the body 7-10 d later (retention); results from subsequent stools gave lower absorption values due to the early excretion of some absorbed 65Zn. The dual-isotope method gave reproducible results when four successive tests of zinc absorption were carried out in a group of six subjects. The average (mean +/- SD) 65Zn absorption from turkey meals containing 31 mumol (2 mg) and 46 mumol (3 mg) of zinc was 39 +/- 8% and 29 +/- 6%, respectively, measured by stool counting; 65Zn absorption and retention correlated well in both studies. A series of different beverages was given in place of water with the turkey meal. Orange juice significantly reduced 65Zn absorption and milk also showed this tendency, but tea, whiskey, wine or beer had no significant effect on the absorption of 65Zn from the turkey meal. In groups of subjects the mean ratio of 65Zn absorption from extrinsically labeled turkey meat on two occasions (1.06) was not significantly different from that of the absorption of extrinsic to intrinsic 65Zn labels (1.16). The dual-isotope technique with either stool or body counting is suitable for the rapid determination of 65Zn absorption from extrinsically labeled turkey within 2 d.

Adult↗

Human calcium absorption from whole-wheat products.

Fractional calcium absorption from wheat products and the influence of co-ingested wheat products on calcium absorption from milk were measured in a series of randomized crossover studies in healthy adult women. The wheat had been intrinsically labeled with 45Ca during growth. In the first study, fractional calcium absorption from leavened whole-wheat bread averaged 0.817 +/- 0.124. By comparison, absorption from milk, ingested at a comparable load in the same women, averaged only 0.589 +/- 0.111. When labeled bread was co-ingested with milk, at the same aggregate load as for bread alone, bread calcium absorption fell to 0.748 +/- 0.103 (P less than 0.05). In a second study, calcium absorption from an extruded cereal prepared from intrinsically labeled wheat bran was compared with milk. Calcium absorption from the cereal (0.223 +/- 0.046) was significantly less than from milk (0.375 +/- 0.072) (P less than 0.001). When the two were co-fed at the same total load, milk calcium absorption fell to 0.258 +/- 0.055 (P less than 0.001). In a third study, the effect of phytate hydrolysis through yeast fermentation and of Maillard browning on calcium absorption was investigated using leavened bread and underbaked and overbaked cookies, each made with intrinsically labeled wheat flour. Calcium absorption from cookies was not affected by the extent of browning and averaged 0.652 +/- 0.087. However, calcium absorption from bread in these same women averaged 0.703 +/- 0.108. This was significantly more than from the cookies (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phosphatidylcholine inhibits and lysophosphatidylcholine enhances the lymphatic absorption of alpha-tocopherol in adult rats.

This study was conducted to compare the effects of enterally infused phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) on the lymphatic absorption of alpha-tocopherol (alphaTP) in male rats. In expt. 1, bile-diverted rats with mesenteric lymph cannulas were infused at 3.0 mL/h for 8 h with a lipid emulsion containing 5.0 micromol alphaTP, 565 micromol 14C-triolein (14C-OA) and 396 micromol Na+-taurocholate with 80 micromol 1,2-dipalmitoyl PC (DPPC) or 1,2-dilinoleoyl PC (DLPC) or without PC (NoPC) in 24 mL phosphate-buffered saline (pH 6.6). In expt. 2, the effects of 1,2-dioleoyl PC (DOPC) and 1-oleoyl-2-hydroxy-PC (lysoPC) on alphaTP and 14C-cholesterol absorption were compared in rats with lymph cannulas. When DPPC or DLPC was infused, the lymphatic absorption of alphaTP was lowered drastically. The cumulative absorptions of alphaTP in rats infused with DPPC and DLPC were 45 and 52%, respectively, of the control values (NoPC). No significant difference was noted between the PC groups. In contrast, the absorption of 14C-OA was increased by 42 to 43% in rats infused with DPPC or DLPC compared with that in NoPC rats. Phospholipid outputs also were significantly higher in DPPC (34.0 +/- 5.5 micromol /8 h) and DLPC (32.4 +/- 2.4 micromol /8 h) rats than in NoPC rats (21.2 +/- 4.2 micromol /8 h). When lysoPC was infused, the absorptions of alphaTP and 14C-cholesterol were increased markedly compared with those for DOPC, with no significant difference in PL output between groups infused with DOPC and lysoPC. These observations provide clear evidence that PC present in a lipid emulsion inhibits alphaTP absorption, whereas it enhances the absorption of fat. The data also demonstrate that lysoPC simultaneously increases the absorption of alphaTP and cholesterol. The findings indicate that luminal PC inhibits the absorption of alphaTP and that hydrolysis of PC is critical to improving the intestinal absorption of the vitamin.

Absorption↗

Intestinal calcium absorption in growing dogs is influenced by calcium intake and age but not by growth rate.

The effects of calcium (Ca) intake (V(I)), age and growth rate on intestinal Ca absorption were studied in growing dogs. Two breeds of dogs differing in their growth rate (67 Great Danes and 23 Miniature Poodles) were raised on diets differing only in their Ca content (range 0.33 to 3.3 g/100 g diet on a dry matter basis). Repetitive Ca balance studies were performed with the aid of (45)Ca from 6 wk (i.e., after weaning) until 6 mo of age. Several models were investigated expressing true Ca absorption (V(a)) as a function of V(I), breed and age. V(a) was directly proportional to a function close to V(I)(0.82) being a continuation of the high Ca needs for mineralization of the growing skeleton. This curvilinear relationship between V(a) and V(I) and the inverse relationship between fractional Ca absorption and V(I) indicated the presence of active and passive Ca absorption in weaned growing dogs. A model in which these two components of Ca absorption can be discerned revealed that active Ca absorption underwent age-dependent changes, whereas passive absorption remained constant and accounted for 53% absorption of the V(I). At low V(I), active absorption contributed to a significant part of the V(a), whereas at excessive V(I) active absorption was negligible and passive absorption was the driving force for causing supra positive Ca balance. Intestinal Ca handling did not differ between breeds with dramatically different mature body size and growth rates.

Aging↗

Absorption of hydrolysed bovine serum albumin from the human jejunum over a 6-hour period.

OBJECTIVE: Quantitative assessment of intestinal absorption of total and single amino acids in a hydrolysed bovine serum albumin solution over a 6-h period. DESIGN: Ten healthy volunteers underwent segmental jejunal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. Prehydrolysed bovine serum albumin served as protein source. In one set of experiments we used a washout phase before the equilibration period to eliminate any contents present in the test segment. In another set we started directly with the equilibration period. Absorption rates of total and single amino acids were measured over a period of 6 h. RESULTS: Absorption rates remained constant throughout this period and there was no significant difference in absorption rates whether a washout phase was used or not. Absorption rates of total amino acids ranged from 6.4 +/- 1.9 (mean +/- SEM) to 10.7 +/- 0.7 g/h and 30 cm, when a washout phase was used. Percentage absorption of the perfusion load per hour was 24 +/- 7% to 40 +/- 2% with a washout phase. Although a highly concentrated perfusion load was used there was a correlation (r = 0.66, P < 0.05) between absolute concentration in the perfusion solution and the amount of individual amino acid absorbed. Individual amino acids showed a wide range of percentage absorption. Percentage absorption of 50% or more of the perfusion load was seen for alanine, phenylalanine, arginine, leucine, methionine and tyrosine. The highest absorption rate was seen for methionine with 86%, the lowest for cysteine with 3%. CONCLUSION: When hydrolysed bovine serum albumin is used, amino acid absorption is constant over a period of 6 h in the human jejunum. A washout phase has no influence on total and single amino acid absorption.

Adult↗