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A comparison of radioactive calcium absorption tests with net calcium absorption.

1. Four different methods of calculating calcium absorption by radioactive calcium procedures have been compared with each other and with net calcium absorption in calcium-balance studies in 100 consecutive studies on 71 patients. 2. All four isotope procedures yielded highly significant correlations with net calcium absorption derived from the balance studies, but there was little to choose between the validity of the double-isotope and single-isotope procedure judged by these criteria. 3. The rate of calcium absorption calculated from one or other isotope procedure correlated better with net calcium absorption than did the fraction of the radioactive calcium absorbed. 4. The measurement of plasma radioactivity 1 h after single-isotope administration, corrected for body weight, proved almost as useful as the more complex procedures but would be expected to underestimate calcium absorption in states of very high bone turnover.

Calcium

Studies on the effects of dietary zinc dose on 65Zn absorption in vivo and on the effects of Zn status on 65Zn absorption and body loss in young rats.

Weanling male rats were maintained on diets containing 5, 10, 20, 40, 80 or 160 mg zinc/kg for 14 d. On day 15 they received 65Zn either by intraperitoneal injection or in a test meal containing 20 mg Zn/kg. After dosing, the rats were again maintained on the diets they had received previously. Whole-body 65Zn retention was measured immediately after dosing and daily for a further 9 d. From regression analysis of the semi-logarithmic plots of 65Zn retention from 0 to 192 h after 65Zn administration, the true extent of 65Zn absorption and the biological half-life (t1/2) of body 65Zn stores were calculated. At the end of the experiment, the rats were killed and the entire small intestines of some rats from each group were rapidly flushed out to remove food and faecal residues, frozen in liquid nitrogen and stored under an atmosphere of N2 at -20 degrees before separation of cytosolic Zn-binding fractions by gel filtration on Sephadex G-75. The results suggest that rats which received diets that were either deficient (5 mg Zn/kg), marginal (10 mg Zn/kg) or adequate (20-80 mg Zn/kg) in Zn achieved homeostatic regulation of body Zn by changes in both the extent of Zn absorption and excretion. However, when Zn supply was excessive, increasing from 80 to 160 mg Zn/kg, no further changes were seen in Zn absorption, and homeostatic control appeared to be effected entirely by changes in rates of body Zn loss. Gel chromatography of intestinal cytosol on Sephadex G-75 revealed that Zn was associated with two major fractions. The first (peak 1) had a molecular weight (MW) greater than 75 kdaltons and the second (peak 2), a MW of approximately 10 kdaltons and was assumed to be metallothionein. There was no obvious relation between the amount of Zn bound to peak 1 and dietary Zn content. In contrast, the amount of Zn recovered in peak 2 increased linearly with increasing dietary Zn content. Comparisons between the effect of dietary Zn content on Zn bound to peak 2 and 65Zn retention may, depending on the range of Zn intakes, indicate possible roles for intestinal metallothionein in the control of Zn absorption or excretion. A study of the effects of dietary dose of 65Zn on the extent of 65Zn absorption in rats of normal Zn status indicated a possible biphasic relation. At low doses (5-40 mg Zn/kg) 65Zn absorption appeared to exhibit a curvilinear response to increasing 65Zn dose, indicating possibly a saturable process.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Food iron absorption in man II. The effect of EDTA on absorption of dietary non-heme iron.

One hundred and eighty iron absorption tests were performed in 45 normal men to determine the effect of EDTA on the absorption of dietary non-heme iron. The addition of 50 mg EDTA to test meals containing 4.1 mg iron reduced absorption by approximately one-half from meals of both high (standard meal) and low (semisynthetic meal) iron availability. Studies employing dual radioiron labels demonstrated complete isotopic exchange of ferric EDTA with dietary non-heme iron. Further studies were carried out to determine the decrease in food iron absorption at varying levels of EDTA. At a 1:1 molar ratio of EDTA to iron, absorption of non-heme iron was reduced to 72% and at a 2:1 molar ratio, to 50% of absorption without EDTA. These levels of EDTA are within the range believed to be present in the United States diet.

Adolescent

Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption.

The ability of various animal proteins to enhance the absorption of dietary nonheme iron was evaluated by performing multiple radioiron absorption measurements in 70 volunteer subjects. Protein equivalent substitutions of nine animal foods were made in two basic test meals. The first was a standard meal of high iron availability (mean absorption, 8.3%) containing beef muscle as the animal protein. The second was a semisynthetic meal of low iron availability (mean absorption, 1.4%) containing ovalbumin as the protein source. Two categories of animal protein were defined. Substitution of beef, lamb, pork, liver, fish, and chicken for the egg ovalbumin in the sannisynthetic meal resulted in a significant, 2-fold to 4-fold increase in iron absorption whereas no increase was observed with milk, cheese, or egg. Reciprocal findings were obtained when these foods were substituted for the beef contained in the standard meal. All sources of animal proteins are not equivalent in their effect on nonheme iron absorption.

Absorption

Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption.

Studies have been conducted on the lymphatic absorption of sitosterol (24 alpha-ethyl cholesterol), stigmasterol (delta 22, 24 alpha-ethyl cholesterol), and fucosterol (24-ethylidine cholesterol) when administered intragastrically to rats. In addition, the effect of each sterol on absorption of endogenous cholesterol has been assessed by including tracer cholesterol in the administered test emulsion. Analysis of 24-h lymph collections by GLC-mass spectrometry demonstrated that all three sterols were poorly absorbed to the extent of only 3 to 4% of the administered dose of 50 mg. In contrast, cholesterol absorption under similar conditions was about 42% of the administered dose. Administration of either sitosterol or stigmasterol resulted in an equally effective inhibition of cholesterol absorption (54%). Under identical conditions fucosterol had no effect on absorption of luminal cholesterol. The data suggest that the mechanism(s) for intestinal discrimination of sterols for absorption may be independent of the mechanism for interference with efficient cholesterol uptake by the intestine.

Absorption

Absorption of low and therapeutic doses of ferric maltol, a novel ferric iron compound, in iron deficient subjects using a single dose iron absorption test.

Ferric maltol is a novel ferric iron compound with potential use as an oral therapy for iron deficiency anaemia. Using a single, low dose iron absorption test we compared absorption of ferric maltol with absorption of ferrous sulphate in 21 iron deficient subjects. Absorption of 10 mg of ferric maltol as either aqueous solution or a single tablet compared favourably with that of an equivalent dose of ferrous sulphate. At a higher, more therapeutic dose of 60 mg elemental iron as tablets, absorption of ferric maltol appeared to be both more rapid and total absorption greater, than that seen with ferrous sulphate. We conclude that iron from ferric maltol, both at low dose and higher, more therapeutic doses, is at least as well absorbed as from ferrous sulphate. Ferric maltol is the first ferric iron formulation to be absorbed to a degree equivalent to that of ferrous iron salts and may represent a viable form of administration for ferric iron in the treatment of iron deficiency anaemia.

Adult

The Journal of clinical Investigation, Volume 41, 1962: iron absorption. IV. The absorption of hemoglobin iron.

The absorption of radioiron in rabbit hemoglobin, hemin, and ferritin has been compared to that of ferrous salt in healthy volunteers and in subjects with iron-deficiency anemia. At a dosage level of 5 mg elemental iron, hemoglobin iron was as well or better absorbed than ferrous salts in the normal subject. Absorption of hemoglobin iron increased less, however, in the iron-depleted or iron-deficient subject. In contrast to the absorption of ferrous salts, that of hemoglobin iron was not decreased by food or by phytate nor increased by ascorbic acid. The absorption of hemin iron was also not decreased by food. Iron absorbed from hemoglobin appeared in the plasma later than that from ferrous salts, but was found to be similarly dialyzable at acid pH with EDTA. These findings suggest that iron in heme complexes is absorbed as a porphyrin complex without conversion to the free ionized form. It is further apparent that there is less effective mucosal regulation of absorption of iron in this form. Finally, the present hypothesis of iron absorption based on the behavior of iron salts is not adequate for all types of food iron.

Absorption

Alcohol and absorption from the small intestine. 1. Impairment of absorption from the small intestine in alcoholics.

An absorption screen was performed in 10 chronic alcoholic patients within a few days of admission due to an acute alcoholic episode. Impaired absorption of d-Xylose was noted in three patients and low leucocyte ascorbic acid and serum folate levels in five. No abnormality was detected in jejunal histology. The absorption of water and electrolytes from the jejunum was studied in these patients using a triple-lumen tube perfusion system. The mean rate of absorption of water in the alcoholic subjects (50-0 +/- 2-3 ml/h) was significantly lower (P less than 0-001) than the mean value in 14 healthy control subjects (205 +/- 15-9 ml/h). A significant reduction of Na+ and Cl-absorption was also demonstrated in the alcoholic subjects. These results indicate that patients with acute-on-chronic alcoholism may have a function impairment of water and electrolyte absorption from the jejunum. This may, in part, account for some of the nutritional deficiencies in such patients and for symptoms such as diarrhoea which may be present.

Adult

Studies on drug absorption from oral cavity. II. Influence of the unstirred water layer on absorption from hamster cheek pouch in vitro and in vivo.

The influence of the unstirred water layer (UWL) adjacent to the membrane surface of the hamster cheek pouch on absorption was studied in vitro and in vivo. The tissue uptake rate of 14C-laurylalcohol was determined in vitro and the value of the effective resistance of UWL (RW) was calculated. RW values were reduced by increasing the stirring rate of the mucosal solution. In vitro permeation of 14C-benzoic acid into the serosal compartment was also increased in the well-stirred condition. Thus, the existence of UWL as an effective diffusion barrier for drug absorption from the hamster cheek pouch was suggested. To clarify the influence of the existence of UWL on the absorption in vivo, the apparatus for luminal stirring was newly devised. When the luminal solution was well-stirred, the absorption of benzoic acid in the lower pH region significantly increased, resulting in the disappearance of the shift of pH-absorption curve for benzoic acid. Furthermore, the luminal stirring increased the absorption rate constant for salicylic acid. From these experimental results, it is suggested that UWL plays a part of barriers against drug permeation in the hamster cheek pouch.

Administration, Buccal

Studies on drug absorption from oral cavity: physicochemical factors affecting absorption from hamster cheek pouch.

A new experimental method using a hamster cheek pouch in vivo for studying absorption processes across the keratinized oral mucous membrane was developed and some characteristics of the oral-mucosal absorption were clarified. A positive correlation between the absorption rate and the lipophilicity was observed in 18 aromatic compounds examined. The absorption of ionizable compounds was poor in the ionized form. These results suggest that the absorption from the keratinized hamster cheek pouch is due to a passive diffusion mechanism and obeys pH-partition hypothesis. The systemic transfer of salicylic acid after intra-cheek-pouch administration could be approximated by the first-order absorption model including a lag time process and the plasma levels found were consistent with this model.

Absorption

Combinative improving effect of increased solubility and the use of absorption enhancers on the rectal absorption of uracil in beagle dogs.

An improvement of the rectal absorption of uracil was examined by the application of absorption enhancers in addition to the increased solubility of uracil. Uracil was ground with additives such as MgO, sodium 2,6-dihydroxybenzoate, human serum albumin or hydroxypropylmethylcellulose acetate succinate. Aqueous, oily and powdery formulations, which consisted of the ground mixtures, nicotinamide, urea and absorption enhancers such as polyoxyethylene (23) cetylether (BC-23) or sodium caprate, were prepared. Uracil solubility in the aqueous formulations was increased about 4-13 times that in the corresponding control formulations. When rectally administered to beagle dogs, marked increases in the plasma uracil level were observed in some of the cases of aqueous and oily formulations. In the powdery formulations and formulations containing macromolecular additives, however, absorption improvements was not observed. The results indicated that an improvement in the absorption of uracil was caused by the combinative improving effect of the increased uracil solubility and the promoting effect of absorption enhancers.

Absorption

Studies on sustained-release suppositories. III. Rectal absorption of morphine in rabbits and prolongation of its absorption by alginic acid addition.

Rectal absorption of morphine from various kinds of suppository bases was investigated. The extent of bioavailability of morphine by rectal administration varied with the bases used (30.5-97.5%), but every value was higher than that in the case of oral administration (13.5%). Witepsol bases were preferable to macrogol base for the rectal absorption of morphine. In particular, Witepsol S-55 or W-35 gave a higher plasma peak level than H-15 or E-75, whereas the difference in the mean residence times obtained from these bases could not be regarded as significant. Sustained-release suppositories of morphine could be prepared simply by mixing alginic acid (Alg) with morphine in a suppository base. Further, prolonged rectal absorption could be obtained by using these sustained-release suppositories, and the absorption rate was controlled by the amount of Alg added. It seems likely that the sustained release was due to the binding of morphine to Alg from the results of partition coefficient and binding ratio measurements in aqueous solution. The rapid initial absorption and the subsequent prolonged absorption of morphine simultaneously obtained from the morphine-Alg suppository may be useful in the clinical context.

Alginates

Effect of intestinal blood flow on absorptive site blood flow and lysine absorption as examined in situ in Holstein calves.

Total blood flow from an intestinal segment (TBF) was altered to determine effects on blood flow at the absorptive site (ASBF) and lysine absorption. Venous blood flow was restricted using a peristaltic pump to 20, 35, 50, 65, and 80% of the initial unrestricted rate. Lysine absorption and ASBF were determined from recovery of 14C and 3H in blood from intestinally perfused [14C]L-lysine and 3H2O, respectively. Fluid flux in the intestinal lumen was estimated from the difference in polyethylene glycol concentrations in luminal infusate and effluent. Restriction of TBF proportionally reduced ASBF, which composed 3 to 6% of TBF. Lysine absorption was reduced linearly during reduction of TBF. Fluid absorption varied among calves but was independent of TBF. Differences between loss of radioactive marker from perfusate and recovery in blood suggested a loss of 3H2O from the intestinal segment that was independent of TBF. Changes in blood flow to the small intestine may affect nutrient absorption in ruminants.

Animals

Estriol: absorption after long-term vaginal treatment and gastrointestinal absorption as influenced by a meal.

This study was designed to evaluate the vaginal absorption of estriol when given as a 21-day treatment. Vaginal absorption was compared with the oral absorption of a known estriol preparation (TriovexR, Leo AB, Sweden). One mg of estriol was administered intravaginally once a day for 21 days to 6 menopausal women. Plasma concentrations of unconjugated estriol were measured by a specific RIA-method at frequent intervals during 24 hours on the first and 21st day of treatment. One month later, 10 mg of estriol was given once orally and plasma estriol concentrations were measured in the same way. At vaginal administration, the absorption of estriol was very effective. When measured on the 21st day, the absorption had declined significantly but was still nearly in the same range as after oral administration of 10 mg of estriol. At oral administration, there was an initial plasma estriol elevation for 3 hours only followed by a second one immediately postprandially. It is concluded that estriol is readily absorbed from the vagina, but the absorption does decline significantly during prolonged treatment. A large single oral dose of estriol provides initially a high plasma estriol concentration but also a second one induced by eating a meal, possibly indicating an enterohepatic recirculation of estriol.

Administration, Oral

Intestinal absorption of alpha-tocopherol in the unanesthetized rat. The influence of luminal constituents on the absorptive process.

3H-alpha-tocopherol intestinal absorption was studied in the unanesthetized rat. The rate of alpha-tocopherol absorption remained linear over a wide range of concentrations (4 nM to 400 micrometer). Increasing the sodium taurocholate concentration in the micellar infusate up to 15 mM did not increase the rate of absorption of the vitamin. Addition of long-chain fatty acids to the micellar infusate decreased the absorption rate of the vitamin (p less than 0.05). The decrease was most significant (p less than 0.01) following the addition of the polyunsaturated linolenic (C18:3) acid. Increasing the hydrogen ion concentration in the perfusate increased the absorption rate of alpha-tocopherol. The present experiments in vivo support the conclusions drawn from in vitro uptake experiments which indicated that alpha-tocopherol is absorbed by a passive diffusion process. These experiments indicate that micellar expansion with polyunsaturated fatty acids interferes with the absorption of alpha-tocopherol and may result in deficiency of the vitamin.

Animals

Absorption of amino acids in different parts of the small intestine in growing pigs. III. Absorption of constituents of protein hydrolysates.

The study was performed on pigs weighing 50-75 kg with temporarily isolated loops of the proximal, middle and distal small intestine. Isolated segments were perfused with enzymic hydrolysates of known amino acids in free form and bound to peptides and proteins. Four hydrolysates were used from: casein I (CI), casein II (CII), soya bean protein (S) and gelatin (G). The absorption of nitrogen from all hydrolysates was least in the proximal small intestine (up to 7 g/m/24 h); there were no significant differences in nitrogen absorption between the other parts. The nitrogen absorption from the hydrolysates varied and was highest for CI and lowest for G. The rates of absorption of various amino acids were different, and were influenced by the proportions and composition of proteins, peptides, and free amino acids in the hydrolysates. However, the rates of absorption of methionine, arginine, leucine and phenylalanine were higher than those of lysine, threonine and histidine irrespective of the hydrolysate source. The peptide fraction of the hydrolysates disappeared from the lumen of the intestine more rapidly than did the amino acid fraction; this suggests that proteases and peptidases in the intestinal mucosa play an important role in the process of amino acid absorption.

Amino Acids

Intestinal strontium absorption: from bioavailability to validation of a simple test representative for intestinal calcium absorption.

Calcium absorption tests have rarely been validated for being representative for absolute bioavailability (true absorption) or for intraindividual variation. Therefore, we investigated the reproducibility of the absolute bioavailability of strontium chloride, a marker for intestinal calcium absorption, in healthy male volunteers (n = 8) by measuring the area under the plasma strontium concentration-time curve after oral and intravenous administration of strontium. Subsequently, we selected a simple test variable as being representative of absolute bioavailability. The mean absolute bioavailability (+/- SD) was 25% +/- 7%. The best test variable appeared to be the fractional absorption at 240 min (Fc240) after oral intake, which demonstrated the highest correlation with absolute bioavailability (r = 0.66). The intraindividual variations of the data for this variable and for the absolute bioavailability are similar to those described for various absorption tests based on the use of calcium isotopes. Thus, the Fc240 of strontium offers the potential of a simple clinical test for use as a measure of intestinal calcium absorption and its modulation.

Adult