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Dietary iron absorption in pregnancy - a longitudinal study with repeated measurements of non-haeme iron absorption from whole diet.

In 22 healthy women the non-haeme iron absorption (bone-marrow smears and haematological parameters) was studied at the 12th, the 24th and the 36th week of gestation and two months after delivery. In eight non-pregnant women and in seven pregnant women (at the 36th week of gestation) the absorption of food iron was measured from different types of meals. The iron absorption was measured from radioiron-labelled test meals using a whole-body counter with a very high sensitivity. During pregnancy the non-haeme iron absorption increased continuously from less than 1 % in early pregnancy to almost 15 % in late pregnancy. Calculations indicated that the amount of iron absorbed from the diet covered only about half of the demands. The increasing absorption of food iron during pregnancy seems to be related to the still more increasing demands. However, the very low absorption values in early pregnancy was quite unexpected. The amount of iron absorbed was actually below the basal demands, which means that even in early pregnancy, for reasons unknown, there is a negative iron balance. Further studies are necessary to elucidate the significance of this finding. Two months after delivery the absorption of iron from the diet was increased compared to in non-pregnant women and exceeded the demands at that phase thus indicating that a positive iron balance was achieved.

Adult

On the absorption probabilities and absorption times of finite homogeneous birth-death processes.

This paper provides some formulas for the absorption probabilities, the mean absorption times and the variances of first absorption times in finite homogeneous absorbing birth-death processes. The results are then applied to a genetic model of Moran [1958] for computing the absorption probability densities, the mean absorption times and the variances of first absorption times. Specifically, it is shown that the probability distribution of the first absorption time is the matrix analog of exponential distribution or a mixture of exponential distributions if the transition matrix is diagonable.

Alleles

GI absorption of beta-lactam antibiotics I: kinetic assessment of competing absorption and degradation in GI tract.

An equation was derived for the simultaneous assessment of rate constatns for absorption and nonenzymatic degradation of unstable drugs in in situ absorption experiments. The equation was substantiated by using a variety of beta-lactam antibiotics in the recirculation technique through the rat small intestine. Plots of the apparent first-order rate constant for the disappearance of the drug from the gut lumen versus the reciprocal of the volume of recirculating solution yielded a straight line with a slope equal to the intrinsic absorption rate constant and with an intercept equal to the nonenzymatic degradation rate constant in the GI lumen. The kinetic method for evaluation of the absorption rate constant also was developed for a more complex situation in the GI lumen involving absorption, nonenzymatic degradation, and enzymatic metabolism. The proposed method was confirmed with carbenicillin indanyl, which was metabolized rapidly to carbenicillin by the action of nonspecific esterase in the intestine. In the absence of information of Michaelis--Menten kinetic parameters, the present method is advantageous for evaluation of the intrinsic absorption rate of all unstable drugs.

Animals

Linoleic acid absorption in the unanesthetized rat: mechanism of transport and influence of luminal factors on absorption.

Linoleic acid intestinal absorption was studied in the unanesthetized rat. At low (21-1260 micrometer) intraluminal concentrations, absorption took place by facilitated diffusion; while at high (1.26-2.5 mM) concentrations, simple diffusion was the predominant mechanism of transport. At low concentrations (840 micrometer), the equimolar additions of oleic, linolenic, and arachidonic acids or lecithin inhibited the absorption of linoleic acid. Substitution of potassium for sodium in the buffer solution, substitution of Tween 80 for sodium taurocholate, or decrease in the hydrogen ion concentration all resulted in decreased rate of linoleic acid absorption. Increase in sodium taurocholate concentration, or perfusate flow rate increased linoleic acid's absorption. These experiments demonstrate that linoleic acid is absorbed by a concentration-dependent dual mechanism of transport. The absorption rate is modified by the pH, surfactant type and concentration, the simultaneous presence of other polyunsaturated fatty acids, and the thickness of the unstirred water layer.

Animals

Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow--limited percutaneous absorption.

For most drugs delivered by the transdermal route, percutaneous absorption is limited by the rate of release of the drug from the device or by diffusion across the stratum corneum. However, systemic absorption also requires that the drug be taken up by dermal blood vessels. As part of a bioavailability study of a transdermal delivery system, we observed that a concomitant intravenous infusion of nicotine had a marked effect on the absorption kinetics of transdermal nicotine. Plasma concentrations of nicotine rose less rapidly, reached a lower peak, and peaked at a later time, indicating delayed absorption of transdermal nicotine after intravenous nicotine versus after transdermal nicotine administered alone. Nicotine is known to produce cutaneous vasoconstriction. The likely explanation for our observation is that intravenous nicotine constricts dermal blood vessels, thereby limiting percutaneous absorption. Other vasoconstrictor drugs would be expected to retard the absorption of transdermal nicotine and perhaps other transdermal drugs as well.

Administration, Cutaneous

Absorption of galactose by the rat small intestine in vivo: proximal-distal kinetic gradients and a new method to express absorption per enterocyte.

1. The absorption in vivo of D-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation-perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1-0-6-5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis-Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4-5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3-5 times greater in the jejunum than in the ileum.

Animals

The measurement of calcium absorption and absorption rate with an external arm radioactivity counter.

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2. 2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined. 3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administration of 47CaCL2. 4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.

Absorption

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

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

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

Percutaneous absorption of drugs. IV. Percutaneous absorption of drugs from oily vehicles.

The percutaneous absorption and retention of salicylic acid and carbinoxamine from four oily vehicles (liquid paraffin, oleic acid, hexadecyl alcohol, and isopropyl myristate) were studied by employing a recirculation apparatus. The absorption followed first-order kinetics, with the exception of the initial period. The vehicle that had a strong affinity to the drug showed a poor drug-releasing effect, and poor absorption and retention of drugs by the skin were observed. Higher absorption rate constants were observed for damaged skin than intact skin. The acceleration of absorption because of skin damage, however, was not so great from liquid paraffin as from the aqueous solution. The amount of drugs retained in the damaged skin declined following the initial increase.

Animals

Pharmacokinetic analysis of drug absorption from muscle based on a physiological diffusion model: effect of molecular size on absorption.

In a rabbit hind leg perfusion experiment, the absorption of radiolabeled water and carbohydrates of various molecular sizes from muscle was analyzed using a physiological diffusion model and, also, by statistical moment analysis. The model takes into account diffusion in the interstitial space, transcapillary movement, and removal by the blood circulation and pharmacokinetic parameters representing these processes were computed by curve-fitting. The apparent diffusion coefficients of water and small sugars in the interstitial space (Dm) were proportional to their free diffusion coefficients in water (Df), whereas the diffusion of 14C-inulin was hampered by interstitial structures. The first moments of each absorption process were also determined to assess the quantitative contribution of each absorption process to overall absorption. For carbohydrate molecules, residence time in the depot (td) accounted for most of the absorption time after injection, whereas for 3H-water, residence times in muscle (tm) and in the depot (td) were similar.

Absorption

The measurement of food iron absorption in man. A methodological study on the measurement of dietary non-haem-Fe absorption when the subjects have a free choice of food items.

1. The present study was considered as a first step to develop a method to measure food iron absorption from realistic common meals prepared and consumed by the subjects themselves in their own homes. The absorption of Fe from the meals was measured by means of the extrinsic-tag method modified to allow for a free choice of food items. 2. The mean Fe intake was 2.79 mg and the mean Fe absorption approximately 0.30 mg. The Fe status of the subjects corresponded to 31.5% absorption from a reference dose solution containing 3 mg elemental Fe as ferrous ascorbate. The variation in food Fe absorption obtained in this field study was found to be of the same magnitude as that obtained in studies performed under more controlled conditions as in the laboratory. 3. The conclusion was drawn that the proposed method could be used in realistic field studies aimed at, for example, explaining or preventing a high prevalence of deficiency. A suffciently long run-in period and a careful instruction of the subjects was considered essential for the design of future field studies.

Adult

Volume absorption in the pars recta. III. Luminal hypotonicity as a driving force for isotonic volume absorption.

This paper examines the possibility that osmotic disequilibrium between luminal and bathing solutions may account for isotonic fluid absorption coupled to active Na+ absorption observed when superficial proximal straight tubules isolated from rabbit kidney are perfused and bathed with NaCl solutions in the absence of CO2, HCO3-, and luminal organic solutes. If luminal hypotonicity provides a driving force for isotonic fluid absorption under these conditions, the luminal fluid must be nearly isotonic; and steady-state luminal hypotonicity should develop sufficiently rapidly that the absolute rate of volume absorption ('JV, nl min-1) coupled to active Na+ transport is relatively independent of perfusion rate, so that the normalized rate of fluid absorption (JV, nl min-1 mm-1) is approximately constant. Our theoretical calculations indicate that these expectations are fulfilled. A 0.42-0.56 mM reduction in luminal NaCl concentration adequately accounts for the JV observed under such conditions, because of the high hydraulic conductivity of these tubules; and within the range of tubule lengths normally employed with isolated proximal straight tubules, JV is relatively indepedent of perfusion rate within the generally observed range of experimental error.

Absorption

Absorption of vitamin A in patients with cystic fibrosis. Absorption is best with emulsified vitamin A alcohol.

Vitamin A absorption tests using vitamin A palmitate and alcohol separately in oil and oil-water emulsions were done on 43 patients with cystic fibrosis. Patients were given 7,000 units of vitamin A per kilogram of body weight with a fatty breakfast. Pancreatic enzymes were not given with the test meal and were withheld for five hours from start of test. Blood was drawn before administration of the vitamin and at three and five hours after administration. Serum vitamin A levels were estimated using the Carr-Price technique. The percentages of patients with normal vitamin A absorption were 85 with vitamin A alcohol in oil-water emulsion, 61 with vitamin A alcohol dissolved in oil, 64 with vitamin A palmitate in oil-water emulsion, and 19 with vitamin A palmitate in oil. The number of stools per day is an inverse indicator of retention time in the intestine. Absorption of fat soluble vitamins is always abnormal when a patient has four or more stools a day. The observations that cystic fibrosis patients with abnormal liver biopsies have poor absorption of vitamin A were not statistically significant. The question of the effect of cirrhosis in cystic fibrosis on vitamin A absorption remains unresolved.

Adolescent

Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits.

The absorption of insulin (from porcine pancreas) from the rectum of rabbits after the administration of hollow-type suppositories containing insulin and five kinds of cyclodextrins (CyDs) was investigated. Three types of suppositories were employed: suppository I containing insulin (approximately 26 IU/mg) and various amounts of each CyD in citric buffer solution at pH 3.0 or powder in its cavity, suppository II containing CyD without insulin, and suppository III containing insulin without CyD. Without CyD, the insulin and glucose levels in plasma were unchanged, whereas a significant increase in the plasma insulin concentration and a marked decrease in the glucose levels were found following simultaneous administration of insulin and CyDs by suppository I. The enhancing effect of CyD on rectal insulin absorption (absorption-enhancing effect) by chemically modified CyDs (heptakis(2,6-di-O-methyl)-beta-CyD (DM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD)) was higher than those by natural CyDs (alpha-, beta-, and gamma-CyD). The area under the plasma concentration-time curve (AUC) and Cmax of insulin significantly decreased with the preadministration (administration of CyD 6, 24 and 48 h before rectal insulin administration) of DM-beta-CyD. The absorption-enhancing effect disappeared 24 h after preadministration. These results suggest that CyDs enhance insulin absorption from the rectum, and that attenuation of the membrane transport barrier function in the rectum recovers at a maximum of 24 h after administration of CyDs.

Absorption

Absorption of supplemental iron during pregnancy - a longitudinal study with repeated bone-marrow studies and absorption measurements.

Iron absorption, bone-marrow smears and haematological parameters were repeatedly studied during pregnancy in 50 women. The same studies were repeated two months after delivery. The material was randomly divided into two groups. Twenty-four women were treated with 200 mg of ferrous iron daily while 26 were given placebo. The iron absorption was measured from radioiron-labelled test doses of 100 mg ferrous iron in a whole-body counter with high sensitivity. In the placebo group the iron absorption increased throughout pregnancy from an average of 6.5 % at the 12th week to 14.3 % at the 35th week of gestation. Two months after delivery the absorption was higher than initially. In the iron-treated group the absorption increased between the 24th and 35th week of gestation from 6.0 to 8.6 %. After delivery 5.5 % of the test dose was absorbed. The haemosiderin iron in the bone-marrow was mobilized during pregnancy. In the placebo group no woman had more than trace of haemosiderin in the bone-marrow smears at the 35th week of gestation. In the iron-treated group 65 % had the same bone-marrow findings. The amount of bone-marrow haemosiderin at term seems not to have the same significance for the diagnosis of iron deficiency in pregnancy as in non-pregnant subjects. Two months after delivery about 50 % of the women in the placebo group had restored their iron deposits. In the iron-group the haemosiderin content in the bone-marrow smears was enhanced in most women compared to early pregnancy. In the placebo group haematological data indicated a high frequency of iron deficiency in late pregnancy while in the iron-treated group iron deficiency was prevented.

Adult