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D G Levitt

Publications and source records attributed to D G Levitt.

At least 73 records · Page 4Linked to original sources
PubMed1980

Use of a model of small bowel mucosa to predict passive absorption.

The purpose of this study was to determine if the observed rate of passive absorption of inert gases from the canine small bowel could be predicted by the use of an anatomical model of the mucosa and measurements of villus blood flow and the diffusive barrier to absorption. Villus blood flow was measured with microspheres and the diffusive barrier separating bulk luminal contents and blood was estimated from CO absorption. The model predicts initial uptake of the inert gases (H2, He, CH4, and 133Xe) in blood at the villus tip, subsequent countercurrent exchange in the villus, and longitudinal diffusion of the gases down the villus to a subvillus blood flow. Observed absorption rates for each of these four gases were reasonably accurately predicted by the model at both basal villus blood flow and at low villus blood flow induced by hypotension. We suggest that this model can be used to predict passive absorption kinetics over a range of villus blood flows and to predict the influence of a variety of parameters on the rate of passive absorption of diffusible substances.

Animals↗
PubMed1979

Model for mucosal circulation of rabbit small intestine.

A theoretical model of the vascular network of normal rabbit small intestine mucosa was constructed from tissues injected with silicone latex. The segmental resistances of the network were calculated from Poiseuille's law by use of lengths and radii measured microscopically and a value of 0.03 P for the viscosity of blood. Where required for the theoretical calculations, published values were used for pressures in arteries down to 20 micrometer in diameter. Values for total-organ blood flow, its distribution between mucosa and nonmucosa, and the partition of mucosal flow between crypts and villi were similar to values measured in the same animals with microspheres. Blood pressures in arteries smaller than 20 micrometer in diameter were also similar to published values. Mean mucosal capillary pressures were close to published experimental estimations. The model seems to provide a useful starting point for describing the magnitudes and patterns of pressures and flow in the small intestine and for consideration of specific location of the sites of their control.

Animals↗
PubMed1978

Number of water molecules coupled to the transport of sodium, potassium and hydrogen ions via gramicidin, nonactin or valinomycin.

The number of water molecules (n) coupled to the transport of cations across lipid membranes was determined in two different wats: directly from the electro-osmotic volume flux per ion, and by the use of Onsager's relation, from the open circuit streaming potential produced by an osmotic pressure difference. The results of the two approaches were in general agreement. Monoolein membranes were formed on the ends of polyethylene or Teflon tubing connected to a microliter syringe and the volume change necessary to keep the membrane at a fixed position was measured. It was necessary to make corrections for unstirred layer effects. The results for gramicidin were: n approximately 12 for 0.15 M KCl and NaCl, n approximately 6 for 3.0 M KCl and NaCl, and n approximately 0 for 0.01 M HCl. For nonactin, n approximately 4 for both 0.15 and 3.0 M KCl and NaCl. Valinomycin (for 0.15 M KCl) behaved like nonactin. It is shown that for a channel mechanism, in general, n is less than or equal to the number of water molecules in a channel that does not contain any cations. Thus, the n of 12 for the 0.15 M salts implies that the gramicidin channel can hold at least 12 water molecules. This places an important constraint on models of the channel structure. The n of 0 for HCl is consistent with a process in which protons jump along a continuous row of water molecules. The decrease of n with the 3.0 M salts may indicate that the channel becomes multiply occupied at high salt concentrations. The n of 4 for nonactin and valinomycin means that at least four water molecules are associated with the carrier . cation complex, probably in the interstices between the complex and the disordered lipid.

Anti-Bacterial Agents↗
PubMed1978

Electrostatic calculations for an ion channel. I. Energy and potential profiles and interactions between ions.

The electrostatic energy profile of one, two, or three ions in an aqueous channel through a lipid membrane is calculated. It is shown that the previous solution to this problem (based on the assumption that the channel is infinitely long) significantly overestimates the electrostatic energy barrier. For example, for a 3-A radius pore, the energy is 16 kT for the infinite channel and 6.7 kT for an ion in the center of a channel 25 A long. The energy as a function of the position of the ion is also determined. With this energy profile, the rate of crossing the membrane (using the Nernst-Planck equation) was estimated and found to be compatible with the maximum conductance observed for the gramicidin A channel. The total electrostatic energy (as a function of position) required to place two or three ions in the channel is also calculated. The electrostatic interaction is small for two ions at opposite ends of the channel and large for any positioning of the three ions. Finally, the gradient through the channel of an applied potential is calculated. The solution to these problems is based on solving an equivalent problem in which an appropriate surface charge is placed on the boundary between the lipid and aqueous regions. The magnitude of the surface charge is obtained from the numerical solution for a system of coupled integral equations.

Biological Transport↗
PubMed1978

Electrostatic calculations for an ion channel. II. Kinetic behavior of the gramicidin A channel.

A theoretical model of the gramicidin A channel is presented and the kinetic behavior of the model is derived and compared with previous experimental results. The major assumption of the model is that the only interaction between ions in a multiply-occupied channel is electrostatic. The electrostatic calculations indicate in a multiply-occupied channel is electrostatic. The electrostatic calculations indicate that there will be potential wells at each end of the channel and, at high concentrations, that both wells can be occupied. The kinetics are based on two reaction steps: movement of the ion from the bulk solution to the well and movement between the two wells. The kinetics for this reaction rate approach are identical to those based on the Nernst-Planck equation in the limit where the movement between the two wells is rate limiting. The experimental results for sodium and potassium are consistent with a maximum of two ions per channel. To explain the thallium results it is necessary to allow three ions per channel. It is shown that this case is compatible with the electrostatic calculations if the presence of an anion is included. The theoretical kinetics are in reasonable quantitative agreement with the following experimental measurements: single channel conductance of sodium, potassium, and thallium; bi-ionic potential and permeability ratio between sodium-potassium and potassium-thallium; the limiting conductance of potassium and thallium at high applied voltages; current-voltage curves for sodium and potassium at low (but not high) concentrations; and the inhibition of sodium conductance by thallium. The results suggest that the potential well is located close to the channel mouth and that the conductance is partially limited by the rate going from the bulk solution to the well. For thallium, this entrance rate is probably diffusion limited.

Biological Transport↗
PubMed1977

Theoretical calculation of the dielectric constant of a bilayer membrane.

The dielectric constant (epsilon) and refractive index (n) of a bilayer lipid membrane is determined from the known values of the polarizabilities of the carbon-carbon and carbon-hydrogen bonds. It is assumed that the hydrocarbon chains are hexagonally arranged in an all-trans conformation perpendicular to the plane of the membrane. The only variable in the calculation is the average separation between the chains and the theory relates epsilon to this separation. The calculation and results differ significantly from those presented in a 1968 publication by Ohki. It is shown that a thin membrane is not homogeneously polarized by the applied field. This effect is analysed and the dependence of epsilon on the membrane thickness is determined. The theoretical results are in good quantitative agreement with experimental measurements on bulk paraffins and on oriented multilayers of saturated fatty acids. The most important conclusion is that the dielectric constant for an applied field perpendicular to the membrane (which is the appropriate value for capacitance measurements) differs by only a few percent from the value for the macroscopic (bulk) liquid hydrocarbon. Thus the dielectric constant of a bilayer membrane can be approximated by the value for the appropriate bulk hydrocarbon.

Electric Conductivity↗
PubMed1977

Quantitation of countercurrent exchange during passive absorption from the dog small intestine: evidence for marked species differences in the efficiency of exchange.

The present investigation was designed to quantitatively assess the possible influence of countercurrent exchange on passive absorption from the small intestine of the dog. Villus blood flow was measured with a modification of the microsphere method. Simultaneously, the absorption from the gut lumen of five diffusible gases (H2, He, CH4, 133Xe, and CO) was determined. Villus blood flow averaged 0.247 +/- 0.03 (SEM) ml/min per g. The observed absorption of H2, He, CH4, and 133Xe was only 16.2 +/- 1.8, 12.8 +/- 2.3, 12.0 +/- 1.8, and 15.8 +/- 1.4 %, respectively, of what this villus blood flow could carry away if it reached perfect equilibrium with the luminal gases. This low absorption rate could result from diffusion limitation to absorption or countercurrent exchange. The diffusive permeability of the barrier seperating the luminal gases and villus blood flow was assessed by measuring the absorption rate of CO. Because absorbed CO binds tightly to hemoglobin, it cannot exchange, and when present in low concentrations its uptake is entirely diffusion limited. Knowledge of the diffusion rate through tissue of the unbound gases relative to that of CO made it possible to calculate the degree to which each of the unbound gases should equilibrate with villus tip blood. The percentage equilibration between lumen and blood at the villus tip for H2, He, CH4, and 133Xe was 99.7, 99.9, 75.6, and 36.0% , respectively. Each of these values greatly exceeded the percentage equilibration of blood leaving the villus (calculated from the observed absorption rate and villus blood flow) and indicated an exchange of 83.8, 87.2, 84.1, and 56.1% of initially absorbed H2, He, CH4, and 133Xe. This result is in accord with theoretical calculations which suggest that countercurrent exchange should be exceedingly efficient in the dog. The striking effect of countercurrent exchange on passive absorption in the dog differs from our previous studies in the rabbit where no exchange was demonstrated. This marked species difference may result from anatomical differences in villus architecture. The dog has long, densely packed villi while the rabbit has broad, widely spaced villi. In the dog, only the villus tips may equilibrate with the lumen, hence a countercurrent gradient may be established in the villus. The entire villus of the rabbit may equilibrate with the lumen and no gradient for countercurrent exchange can therefore be established.

Animals↗
PubMed1975

General continuum analysis of transport through pores. I. Proof of Onsager's reciprocity postulate for uniform pore.

The nonelectrolyte (Js) and volume (Jv) flux across a membrane is usually described in terms of two equations derived from the theory of irreversible thermodynamics: (see article) where delta c and delta P are the concentration and pressure difference; omega and Lp are the diffuse and hydraulic permeability; and sigma s and sigma v are the reflection coefficients. If Onsager's reciprocity postulate is assumed, it can be shown that signa s and sigma v are equal. This is an important assumption because it allows one to apply the continuum theory relationship between sigma s and the pore radius to experimental measurements of sigma v. In this paper, general continuum expressions for both the Jv (a new result) and Js equation will be derived and the equality of sigma s and sigma v proved. The proof uses only general hydrodynamic results and does not require explicit solutions for the drag coefficients or, for example, the assumption that the solute is in the center of the pore. The proof applys to arbitrarily shaped solutes and any pore whose shape is independent of axial position (uniform). In addition, new expressions for the functional dependence of omega and sigma on the pore radius are derived (including the effect of the particle lying off the pore axis). These expressions differ slightly from earlier results and are probably more accurate.

Mathematics↗
PubMed1975

General continuum analysis of transport through pores. II. Nonuniform pores.

A general continuum derivation of the nonelectrolyte (Js) and volume (Jv) flux through a pore whose cross section is a function of axial position (nonuniform) is given. In general, the flux equations cannot be reduced to the same form as for a uniform pore and it is not possible to characterize the pore kinetics by three constants as in the uniform pore case. However, it is shown that under certain conditions, the nonuniform pore equations can be approximated by the uniform pore form and can be characterized by three constants (omega, sigma, Lp). The only condition needed to reduce the Jv equation to the uniform form is that the solution be dilute. The deviation of the Js equation from the uniform form is characterized by an asymmetrical function of Jv whose maximum value is estimated. It is shown that the maximum posible fractional deviation of the Js equation from the uniform form is given by the parameter: 0:5sigmaJv/omegaRT. Since this parameter is less then 0.15 for most membrane studies, the nonuniform Js equation can usually be approximated by the uniform pore form. The general results are illustrated by explicit calculations on several models of nonuniform pores. It is shown, for example, that the "equivalent pore radius" defined in the usual way is a function of the experimental parameter that is measured and is not unique.

Kinetics↗
PubMed1975

D2 18O (deuterium oxide) method for CO2 output in small mammals and economic feasibility in man.

A test of the validity of the isotopic steady state relationships of the doubly labeled water (H2O) method has been carried out with D2 18O in small mammals (three chipmunks and one mouse). CO2 outputs calculated just from 1) the rate of water intake and 2) the ratios of the isotopic concentrations in the body water to the intake water agreed satisfactorily with observed values. Moreover, reconstructed energy and material balances agreed reasonably with similar balances reconstructed for an immediately succeeding period on the same animals studied by the previously validated decay procedure. We conclude from an error analysis that by expressing the isotopic specific activities as abundances in excess of the body water of a subject on a given regimen, the decay procedure is economically feasible in the human with available accuracy of isotopic analyses and the present cost of H2 18O. The method therefore appears to be a useful tool ready for application to the field of human energy metabolism.

Animals↗
PubMed1974

Use of inert gases and carbon monoxide to study the possible influence of countercurrent exchange on passive absorption from the small bowel.

The purpose of the present study was to quantitate the influence of countercurrent exchange on passive absorption of highly diffusible substances from the small intestine of the rabbit. The absorption of carbon monoxide, which is tightly bound to hemoglobin and therefore cannot exchange, was compared to the absorption of four unbound gases (H(2), He, CH(4), and (133)Xe), which should exchange freely. The degree to which the observed absorption of the unbound gases falls below that predicted from CO absorption should provide a quantitative measure of countercurrent exchange.CO uptake at high luminal Pco is flow-limited and, assuming that villus and central hemoglobin concentrations are equal, the flow that equilibrates with CO (F(co)) was calculated to equal 7.24 ml/min/100 g. The observed absorption rate of the unbound gases was from two to four times greater than would have been predicted had their entire uptake been accounted for by equilibration with F(co). This is the opposite of what would occur if countercurrent exchange retarded absorption of the unbound gases. The unbound gases have both flow- and diffusion-limited components, and F(co) should account for only the fraction of absorption that is flow limited. A simple model of perfusion and diffusion made it possible to calculate the fraction of the total uptake of unbound gases that was flow limited. This fraction of the total observed absorption rate was still about 1.8 times greater than predicted by CO absorption. A possible explanation for this discrepancy is that plasma skimming reduces the hemoglobin of villus blood to about 60% of that of central blood. Thus, F(co) is actually about 1.7 times greater than initially calculated, and with this correction, there is close agreement between the predicted and observed rates of absorption of each of the unbound gases. We conclude that countercurrent exchange does not influence passive absorption under the conditions of this study.

Animals↗