High-throughput synchrotron X-ray diffraction for combinatorial phase mapping.

Discovery of new materials drives the deployment of new technologies. Complex technological requirements demand precisely tailored material functionalities, and materials scientists are driven to search for these new materials in compositionally complex and often non-equilibrium spaces containing three, four or more elements. The phase behavior of these high-order composition spaces is mostly unknown and unexplored. High-throughput methods can offer strategies for efficiently searching complex and multi-dimensional material genomes for these much needed new materials and can also suggest a processing pathway for synthesizing them. However, high-throughput structural characterization is still relatively under-developed for rapid material discovery. Here, a synchrotron X-ray diffraction and fluorescence experiment for rapid measurement of both X-ray powder patterns and compositions for an array of samples in a material library is presented. The experiment is capable of measuring more than 5000 samples per day, as demonstrated by the acquisition of high-quality powder patterns in a bismuth-vanadium-iron oxide composition library. A detailed discussion of the scattering geometry and its ability to be tailored for different material systems is provided, with specific attention given to the characterization of fiber textured thin films. The described prototype facility is capable of meeting the structural characterization needs for the first generation of high-throughput material genomic searches.

Cardiac mechanoenergetics replicated by cross-bridge model.

The aim of this work is to reproduce the experimentally measured linear dependence of cardiac muscle oxygen consumption on stress-strain area using a model, composed of a three-state Huxley-type model for cross-bridge interaction and a phenomenological model of Ca2+-induced activation. By selecting particular cross-bridge cycling rate constants and modifying the cross-bridge activation model, we replicated the linear dependence between oxygen consumption and stress-strain area together with other important mechanical properties of cardiac muscle such as developed stress dependence on the sarcomere length and force-velocity relationship. The model predicts that (1) the amount of the "passenger" cross bridges, i.e., cross bridges that detach without hydrolyzing ATP molecule, is relatively small and (2) ATP consumption rate profile within a beat and the amount of the passenger cross bridges depend on the contraction protocol.

Optimization of cardiac fiber orientation for homogeneous fiber strain during ejection.

The strain of muscle fibers in the heart is likely to be distributed uniformly over the cardiac walls during the ejection period of the cardiac cycle. Mathematical models of left ventricular (LV) wall mechanics have shown that the distribution of fiber strain during ejection is sensitive to the orientation of muscle fibers in the wall. In the present study, we tested the hypothesis that fiber orientation in the LV wall is such that fiber strain during ejection is as homogeneous as possible. A finite-element model of LV wall mechanics was set up to compute the distribution of fiber strain at the beginning (BE) and end (EE) of the ejection period of the cardiac cycle, with respect to a middiastolic reference state. The distribution of fiber orientation over the LV wall, quantified by three parameters, was systematically varied to minimize regional differences in fiber shortening during ejection and in the average of fiber strain at BE and EE. A well-defined optimum in the distribution of fiber orientation was found which was not significantly different from anatomical measurements. After optimization, the average of fiber strain at BE and EE was 0.025 +/-0.011 (mean+/-standard deviation) and the difference in fiber strain during ejection was 0.214+/-0.018. The results indicate that the LV structure is designed for maximum homogeneity of fiber strain during ejection.

Decreased citrate improves iron availability from infant formula: application of an in vitro digestion/Caco-2 cell culture model.

We have applied an in vitro digestion/Caco-2 cell culture model to the assessment of iron availability from human milk and a generic cow's milk-based infant formula. Experiments were designed to determine the availability of iron from human milk relative to infant formula and whether known promoters of iron absorption would increase Caco-2 cell iron uptake and availability from the infant formula. In addition, we sought to determine if decreasing the citrate concentration in the infant formula would increase the iron uptake. Although approximately twice as much iron was in solution from digests of the infant formula relative to that of human milk, smaller or equal amounts of iron were taken up from the infant formula relative to the human milk digest. These results are qualitatively similar to in vivo studies. Addition of known iron uptake promoters to infant formula did not enhance Caco-2 cell iron uptake from the infant formula digest, indicating that the iron in the infant formula existed predominantly in a tightly bound unavailable form(s). Enzymatic pretreatment of the infant formula with citrate lyase and oxalacetate decarboxylase decreased the citrate concentration by 67% and resulted in a 64% increase of iron in solution, which corresponded to a 46% increase in the cell iron uptake. Iron uptake from the "low citrate" formula plus cysteine was 102% greater relative to the nontreated formula. The results indicate that too much citrate can reduce iron uptake, particularly if it is present at concentrations greater than promoters such as ascorbic acid and cysteine.

Optimization of cardiac fiber orientation for homogeneous fiber strain at beginning of ejection.

Mathematical models of left ventricular (LV) wall mechanics show that fiber stress depends heavily on the choice of muscle fiber orientation in the wall. This finding brought us to the hypothesis that fiber orientation may be such that mechanical load in the wall is homogeneous. Aim of this study was to use the hypothesis to compute a distribution of fiber orientation within the wall. In a finite element model of LV wall mechanics, fiber stresses and strains were calculated at beginning of ejection (BE). Local fiber orientation was quantified by helix (HA) and transverse (TA) fiber angles using a coordinate system with local r-, c-, and l-directions perpendicular to the wall, along the circumference and along the meridian, respectively. The angle between the c-direction and the projection of the fiber direction on the cl-plane (HA) varied linearly with transmural position in the wall. The angle between the c-direction and the projection of the fiber direction on the cr-plane (TA) was zero at the epicardial and endocardial surfaces. Midwall TA increased with distance from the equator. Fiber orientation was optimized so that fiber strains at BE were as homogeneous as possible. By optimization with TA = 0 degree, HA was found to vary from 81.0 degrees at the endocardium to -35.8 degrees at the epicardium. Inclusion of TA in the optimization changed these angles to respectively 90.1 degrees and -48.2 degrees while maximum TA was 15.3 degrees. Then the standard deviation of fiber strain (epsilon f) at BE decreased from +/- 12.5% of mean epsilon f to +/- 9.5%. The root mean square (RMS) difference between computed HA and experimental data reported in literature was 15.0 degrees compared to an RMS difference of 11.6 degrees for a linear regression line through the latter data.

Iron uptake is enhanced in Caco-2 cell monolayers by cysteine and reduced cysteinyl glycine.

Human and animal studies have shown that amino acids and peptides influence iron absorption from the intestinal lumen. This study was conducted using Caco-2 cell monolayers as the experimental model to determine whether similar effects on iron absorption occur. Conditions were chosen to mimic the pH of the intestinal lumen and the most likely order whereby ferric and ferrous forms of iron would combine with various amino acids and dipeptides resulting from protein digestion. We demonstrated the enhancing effect of cysteine and reduced cysteinyl glycine on iron uptake by Caco-2 cells. The addition of glutathione to the transport media had no effect on uptake from ferrous or ferric iron complexes, nor did it affect iron solubility. Cysteine and reduced cysteinyl glycine increased iron solubility when added to a solution containing insoluble iron. This effect is different from that of ascorbate, which must be combined with soluble ferric iron at pH 2 to reduce and solubilize iron. Taken together, these observations are evidence that cysteine and reduced N-terminal cysteine peptides are capable of enhancing iron uptake from soluble and insoluble ferric iron. These results qualitatively reflect those observed in human studies. Our results indicate that glutathione requires digestion to Cys or Cys-Gly in order to promote iron uptake. The similarity between this study and human studies further reinforces that the Caco-2 cell model is a useful tool in studies of iron absorption and bioavailability.

Ferrous iron uptake but not transfer is down-regulated in Caco-2 cells grown in high iron serum-free medium.

Caco-2 cells in culture provide an attractive model for the study of human iron absorption. Because iron status has a marked effect on human iron absorption, we devised serum-free growth conditions that allow manipulation of Caco-2 cell iron stores while maintaining growth. Caco-2 cells were cultured in serum-free media containing 0-20 micromol/L added iron. Intracellular ferritin, measured by radioimmunoassay, increased 100-fold with the addition of 20 micromol/L iron to the serum-free growth medium. Iron uptake and transfer across Caco-2 cell monolayers were measured from balanced salt solutions of ferrous and ferric forms of iron. Uptake from ferrous, but not ferric, iron was inversely related to cell ferritin concentration and culture medium iron concentration. Kinetic analysis of uptake data from solutions of ferrous and ferric iron revealed saturable and nonsaturable components for ferrous iron, but only a nonsaturable component for ferric iron. Uptake by the nonsaturable pathway was not affected by cell ferritin concentration for either form of iron. Maximal uptake from a ferrous iron solution via the saturable pathway was nearly 100% greater in cells cultured under low compared with high iron conditions. Iron transfer across Caco-2 monolayers was not proportional to iron uptake, but was related to monolayer permeability. Iron uptake by Caco-2 cells was a reliable indicator of relative iron availability. We observed no difference in iron transfer that was related to the iron status of the cell monolayer. The lack of this effect suggests that this model may be inadequate for studies of iron transfer.

Caco-2 cell iron uptake from meat and casein digests parallels in vivo studies: use of a novel in vitro method for rapid estimation of iron bioavailability.

We developed a model for assessing iron bioavailability from foods which combines simulated peptic and intestinal digestion with measurement of iron uptake by Caco-2 cell monolayers. Our objective was to further validate this model by determining if meat enhances Caco-2 cell iron uptake relative to casein. Caco-2 cell monolayers were covered with Hank's balanced salt solution (HBSS) buffered with HEPES, pH 7.4. An upper chamber was created over the cells by fitting the bottom of a Costar Transwell insert with a 12,000-14,000 molecular weight cut-off dialysis membrane. This membrane allowed low molecular weight iron complexes to diffuse into the media bathing the cells and prevented damage to the cells from the digestive enzymes. Prior to digestion, each sample (homogenate of beef, chicken, fish or casein) was mixed with 59FeCl3 to achieve an iron concentration of 10 mumol/L. Following pepsin digestion (pH2), pH was adjusted to 7.4, pancreatic enzymes and bile extract were added to each digest, and an aliquot was then introduced into the upper chamber of the culture dish. During this intestinal digestion period, 59Fe uptake occurred from iron that dialyzed into the lower chamber. The 59Fe uptake from beef, chicken and fish digests was 300-400% of the 59Fe uptake from a casein digest. Our results parallel human absorption studies indicating that meat enhances iron absorption. The results suggest that digestion products of the meat proteins were at least partially responsible for the enhancement of iron uptake. Overall, this study supports the usefulness of our model as a means of assessing iron bioavailability.

Regional wall mechanics in the ischemic left ventricle: numerical modeling and dog experiments.

The mechanics of the ischemic left ventricle during a complete cardiac cycle were simulated using a finite-element model accounting for the thick-walled ventricular geometry, the fibrous nature of the myocardial tissue, and the dependency of active muscle fiber stress on time, strain, and strain rate. Ischemia was modeled by disabling the generation of active stress in a region comprising approximately 12% of total wall volume. In the model simulations, the approximately 12% reduction in the amount of normally contracting tissue resulted in an approximately 25% reduction in stroke work compared with the normal situation. The more-than-proportional loss of stroke work may partly be attributed to storage of elastic energy in the bulging ischemic region. Furthermore the mechanical performance in the nonischemic border zone deteriorated because of reduced systolic fiber stress (if fibers were in series with those in the ischemic region) or reduced fiber shortening (if fibers were parallel). The deformation pattern of the ventricle was asymmetric with respect to the ischemic region because of the anisotropy of the myocardial tissue. Epicardial fiber shortening in and around the ischemic region, as predicted from the model simulations, was in qualitative agreement with shortening, as measured in four dogs in which ischemia was induced by occlusion of the distal part of the left anterior interventricular coronary artery.

Optimization of left ventricular fibre orientation of the normal heart for homogeneous sarcomere length during ejection.

UNLABELLED: During the ejection phase of the cardiac cycle, left ventricular muscle fibres shorten while generating force. It was hypothesized that fibres are oriented in the wall such that the amount of shortening is the same for all fibres. We evaluated this hypothesis for the equatorial region of the left ventricle. In a finite element model of left ventricular wall mechanics fibre orientation was quantified by a helix angle which varied linearly from the inner to the outer wall. Fibre length was characterized by sarcomere length, set at 1.95 microns everywhere in the passive state of 0 transmural pressure. For a cavity pressure of 15 kPa, considered representative for ejection, inhomogeneity in mechanical loading was expressed by the variance of the sarcomere length. The variance was minimized by adapting the transmural course of fibre angle. First, only the slope was optimized and in a second optimization this was done for both slope and intercept. Optimal helix fibre angles were 69.6 degrees endocardially, 0 degree at the middle of the wall and -69.6 degrees epicardially for the first optimization and 78.2 degrees, 20.7 degrees and, -36.7 degrees respectively for the second. Sarcomere length changed from 1.95 to 1.975 +/- 0.012 and 1.981 +/- 0.004 microns (mean +/- SD) respectively. CONCLUSION: After optimization calculated helix fibre angles were in the physiological range. Describing the transmural course of fibre angle with slope and intercept significantly improved homogeneity in mechanical load.

Bathophenanthrolene disulfonic acid and sodium dithionite effectively remove surface-bound iron from Caco-2 cell monolayers.

Iron uptake by Caco-2 cell monolayers is commonly assessed by incubating the cells under radiolabeled iron solutions, removing the radiolabeled solution, rinsing to stop uptake and measuring the radioactivity retained by the cells. It is therefore essential to differentiate between iron that is nonspecifically bound to the cell surface from that which has been taken up by the cell. We report here on a method for removal of surface-bound iron from Caco-2 cell monolayers. We used a 140 mmol/L NaCl, 10 mmol/L PIPES, pH 6.7 solution containing 5.0 mmol/L sodium dithionite (Na2S2O4) and 5.0 mmol/L bathophenanthroline disulfonic acid to reduce, remove and chelate iron bound to the cell surface. We validated our method by demonstrating the removal of 97% of an insoluble iron complex from the apical surface of Caco-2 cell monolayers. Our data indicate that the removal solution does not damage the apical membrane and thereby does not have access to intracellular iron; thus only surface bound iron is removed. The remaining cell-associated iron represents that which has been transported into the cell. We present data on the uptake and nonspecific binding of iron from iron complexes of both ferrous and ferric forms, and show that iron removal treatment resulted in uptake measurements that agree more closely with accepted principles of iron uptake by intestinal epithelium. The iron removal method used in this study should provide investigators with a valuable tool for accurately determining iron uptake by epithelial cells in culture.

Enhanced Fe(3+)-reducing capacity does not seem to play a major role in increasing iron absorption in iron-deficient rats.

Some eucaryotic organisms, including many plants, yeast and mice, have a higher iron uptake during iron deficiency because the capacity to reduce Fe3+ from the environment to Fe2+ is greatly enhanced. To determine whether this occurs in rats, a common experimental model for iron absorption in humans, we compared the in vivo capacity to reduce intraluminal Fe3+ in iron-deficient and normal rats. We also measured potential Fe(3+)-reducing components within the intestinal lumen and on the mucosal surface. Iron-reducing capacity was higher in iron-deficient rats, by a significant (P = 0.026) but modest 20%, in parallel with higher mucosal weight (R2 = 0.501, P = 0.003). In vitro iron reduction by lumen contents was correlated with mucosal weight, even though mucosal tissue was not present in the assays. This capacity was not related to ascorbic acid, glutathione or other nonprotein sulfhydryls. Mucosal ferric reductase activity was higher in iron-deficient rats in parallel with higher tissue weight, but the specific activity did not differ and the higher total activity was not associated with the brush border fraction. The role of endogenous Fe3+ reduction in regulating iron absorption should be investigated in humans and in other experimental models.

Aflatoxin B1 reduces Na(+)-P(i) co-transport in proximal renal epithelium: studies in opossum kidney (OK) cells.

In vivo studies indicate that aflatoxin B1 (AFB1) may affect the renal regulation of inorganic phosphate (P(i)), possibly by altering the renal response to parathyroid hormone (PTH). Therefore, the present study utilized opossum kidney (OK) cells, a mammalian renal epithelial cell line, to determine whether AFB1 exposure alters sodium-phosphate (Na(+)-P(i)) co-transport and the hormonal modulation thereof. OK cells are an established renal cell line with many properties analogous to the proximal renal epithelium, including receptors for PTH, insulin, and high levels of Na(+)-P(i) co-transport. PTH and insulin have been shown to decrease and increase Na(+)-P(i) co-transport, respectively, in OK cells. In the present study, AFB1-treated cells responded to PTH; however, AFB1 exposure decreased Na(+)-P(i) uptake such that additional decreases in Na(+)-P(i) uptake in response to PTH were minimal. In the presence of insulin, AFB1-treated cells were only able to increase Na(+)-P(i) uptake to levels 30% below that of control cells. The net result was that the range of the proximal renal epithelium to adjust Na(+)-P(i) co-transport in response to hormonal modulation was reduced by AFB1 exposure. Sodium-dependent L-alanine uptake was measured and was found not to be affected by the highest concentration of AFB1; thus, indicating that AFB1 exposure may have specific effects on Na(+)-P(i) uptake and does not generally inhibit Na(+)-dependent transport. These observations are evidence that AFB1 exposure may alter key elements of renal function. Such effects raise concern that AFB1 exposure may have broad physiological impact in addition to its known carcinogenic properties.

Influence of endocardial-epicardial crossover of muscle fibers on left ventricular wall mechanics.

The influence of variations of fiber direction on the distribution of stress and strain in the left ventricular wall was investigated using a finite element model to simulate the mechanics of the left ventricle. The commonly modelled helix fiber angle was defined as the angle between the local circumferential direction and the projection of the fiber path on the plane perpendicular to the local radial direction. In the present study, an additional angle, the transverse fiber angle, was used to model the continuous course of the muscle fibers between the inner and the outer layers of the ventricular wall. This angle was defined as the angle between the circumferential direction and the projection of the fiber path on the plane perpendicular to the local longitudinal direction. First, a reference simulation of left ventricular mechanics during a cardiac cycle was performed, in which the transverse angle was set to zero. Next, we performed two simulations in which the spatial distribution of either the transverse or the helix angle was varied with respect to the reference situation, the spatially averaged variations being about 3 and 14 degrees, respectively. The changes in fiber orientation hardly affected the pressure-volume relation of the ventricle, but significantly affected the spatial distribution of active muscle fiber stress (up to 50% change) and sarcomere length (up to 0.1 micron change). In the basal and apical region of the wall, shear deformation in the circumferential-radial plane was significantly reduced by introduction of a nonzero transverse angle. Thus, the loading of the passive tissue may be reduced by the endocardial-epicardial crossover of the muscle fibers.

Dependence of local left ventricular wall mechanics on myocardial fiber orientation: a model study.

The dependence of local left ventricular (LV) mechanics on myocardial muscle fiber orientation was investigated using a finite element model. In the model we have considered anisotropy of the active and passive components of myocardial tissue, dependence of active stress on time, strain and strain rate, activation sequence of the LV wall and aortic afterload. Muscle fiber orientation in the LV wall is quantified by the helix fiber angle, defined as the angle between the muscle fiber direction and the local circumferential direction. In a first simulation, a transmural variation of the helix fiber angle from +60 degrees at the endocardium through 0 degrees in the midwall layers to -60 degrees at the epicardium was assumed. In this simulation, at the equatorial level maximum active muscle fiber stress was found to vary from about 110 kPa in the subendocardial layers through about 30 kPa in the midwall layers to about 40 kPa in the subepicardial layers. Next, in a series of simulations, muscle fiber orientation was iteratively adapted until the spatial distribution of active muscle fiber stress was fairly homogeneous. Using a transmural course of the helix fiber angle of +60 degrees at the endocardium, +15 degrees in the midwall layers and -60 degrees at the epicardium, at the equatorial level maximum active muscle fiber stress varied from 52 kPa to 55 kPa, indicating a remarkable reduction of the stress range. Moreover, the change of muscle fiber strain with time was more similar in different parts of the LV wall than in the first simulation. It is concluded that (1) the distribution of active muscle fiber stress and muscle fiber strain across the LV wall is very sensitive to the transmural distribution of the helix fiber angle and (2) a physiological transmural distribution of the helix fiber angle can be found, at which active muscle fiber stress and muscle fiber strain are distributed approximately homogeneously across the LV wall.

Porous medium finite element model of the beating left ventricle.

The axisymmetric model described represents myocardial tissue as a spongy anisotropic viscoelastic material. It includes torsion around the axis of symmetry of the ventricle, transmural variation of fiber angle, and redistribution of intracoronary blood in the myocardial wall. In simulations, end-systolic principal strains were equal to 0.45, -0.01, and -0.24 at two-thirds of the wall thickness from the epicardium and 0.26, 0.00, and -0.19 at one-third of the wall thickness from the epicardium. The direction of maximal shortening varied by less than 30 degrees from epicardium to endocardium, whereas fiber direction varied by greater than 100 degrees from epicardium to endocardium. During a normal cardiac cycle peak, equatorial intramyocardial pressure differed by less than 5% from peak intraventricular pressure. When redistribution of intracoronary blood in the ventricular wall was suppressed, peak equatorial intramyocardial pressure was found to exceed peak intraventricular pressure by greater than 30%. Simulated contraction of an unloaded left ventricle (left ventricular pressure = 0 kPa) produced similar magnitude for systolic intramyocardial pressures as the normal cardiac cycle. Transmural systolic fiber stress distribution was very sensitive to the chosen transmural fiber angle distribution.

Experimental and numerical analyses of the steady flow field around an aortic Björk-Shiley standard valve prosthesis.

To develop a numerical method for the description of the flow field around a Björk-Shiley (BS) standard valve prosthesis in aortic position, detailed experimental measurements and numerical calculations are performed under steady flow conditions. The experiment was conducted at Reynolds numbers up to 800. In order to perform LDA measurement of velocity in the vicinity of the valve with a curved sinus boundary, a mixture of oil and kerosine was used as the fluid which exactly matches the refractive index of the perspex aortic model. The velocity profiles at six positions in the vicinity and downstream of the valve were measured, including both axial and radial velocity components. The results show very clearly the existence of two nearly symmetric spiral vortex streams downstream of the valve. There is no recirculation area in the aorta downstream and also no obvious stagnation area in the minor orifice region near the valve when Re less than or equal to 800. Theoretically, the flow field of a BS valve is simulated by the flow pattern around a circular plate with an angle of incidence to the approaching stream. The numerical calculations were carried out by means of a 2-D model using the FEM together with the penalty function method. The maximum Reynolds number is 700. The results agree with the experimental results in the plane of symmetry when the Reynolds number is small. However, as the Reynolds number increases, the difference becomes evident. Our conclusion is that the steady flow field of a BS valve is completely 3-dimensional, featured by two spiral vortices. It cannot be simulated exactly by 2-D numerical calculations. To get more detailed and complete information about the flow field of this valve, 3-D numerical calculations are needed.

Partitioning of cadmium, copper, lead and zinc amongst above-ground parts of seed and grain crops grown in selected locations in the USA.

The distribution of Cd, Cu, Pb and Zn in above-ground parts of corn, small grains and pulse crops was investigated. Sampled parts included grain or seed, leaves, stems, silk and husks of corn-ears, rachilla and chaff of small grains and pods of bean plants. The distribution of these elements was variable and reflected, primarily, their relative mobility between plant parts including transfer into the grain. Generally, Zn and Cu were preferentially transferred into the seed or grain, while Cd and Pb were selectively excluded from these organs. For example, the distribution pattern in ears of corn was: for Cd, husks > silk > grain; for Zn, silk > grain > husks. The selective transfer of Zn and Cu into seed or grain, in contrast to the restricted movement of Cd and Pb into these organs, may be the result of selective absorption of Zn and Cu over Cd and Pb by vascular transfer cells within the plant's reproductive tissues. The effect of soil type on Cd, Cu, Pb and Zn levels in cereal grain or pulse seed was small compared to the differences found in the concentrations of these elements between different plant organs. Thus, grain and seed crops serve as natural barriers to the movement of the potentially toxic heavy metals, Cd and Pb, into the animal/human food chain, minimising their transfer from soils while conserving Zn and Cu levels in edible portions of these crops.

Ferric iron absorption in rats: relationship to iron status, endogenous sulfhydryl and other redox components in the intestinal lumen.

Based on the hypothesis that Fe+3 must be reduced before Fe absorption, we investigated luminal factors that might participate in the physiological Fe+3 reduction. Rats were fed diets containing 7 mg Fe/kg diet [adequate iron (+Fe]) for 3 wk prior to a 10-min test of 59Fe absorption from an in vivo ligated duodenal segment. During absorption of 59Fe, the oxidation-reduction potential became more reducing and the pH rose in segment contents. There were small but significant differences between the -Fe and +Fe rats. In one experiment, the lumen environment was modified by bile duct ligation and/or intestinal perfusion prior to the absorption test. Ascorbic acid, nonprotein sulfhydryl compounds, Fe+2 and total ionizable Fe were measured in luminal contents. Nonprotein sulfhydryl concentration was positively correlated with, and the best predictor of, Fe absorption in -Fe rats.

Mucus and iron absorption regulation in rats fed various levels of dietary iron.

We tested two hypotheses: (1) that iron binding by secreted mucus enhances iron absorption (Quarterman, Digestion 37: 1, 1987) and (2) that iron binding by secreted mucus prevents excess iron absorption. Rats were fed diets containing 6, 200 or 500 mg Fe/kg diet (Fe-0, Fe-200 and Fe-500 rats, respectively) for 3 wk. Iron absorption was measured in fasted rats using 59FeCl3 in a 10-min in situ duodenal ligated-segment procedure. After draining the segment contents, the mucus layer was separated from the under-lying mucosal surface using Quarterman's agar cast technique. In comparison with that in Fe-200 rats, iron absorption in Fe-0 rats was markedly increased, but the 59Fe and the total mucus in the mucus layer were decreased. The 59Fe absorption and total mucus and total iron in the mucus layer were similar in Fe-500 rats and Fe-200 rats, but the 59Fe in the mucus layer was marginally lower in Fe-500 rats. There was no evidence that mucus enhanced iron absorption; it appeared to trap or bind iron proportionally to the amount of secreted mucus, suggesting protection against excess absorption. Mucus secretion and possibly synthesis were decreased in the Fe-0 rats.