Note on an urban diffusion simulation model for carbon monoxide and the need for accurate span gas analysis.
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Aqueous solutions of several ionizable substances were stored in plastic infusion bags and the sorption of the substances monitored with time. The substances used were p-nitrophenol, p-toluidine, warfarin sodium [3-(alpha-acetonylbenzyl)-4-hydroxycoumarin sodium salt] and trifluoperazine hydrochloride (10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)phenothiazine dihydrochloride). The rate and extent of sorption for each substance varied with pH and was consistent with a preferential uptake of the un-ionized species. The uptake of p-nitrophenol and p-toluidine was adequately described by a diffusion model derived assuming that sorption is rate-controlled by the diffusivity of the solute in the plastic matrix, and that only the un-ionized species was sorbed by the plastic matrix. However, the uptake of warfarin sodium and trifluoperazine hydrochloride was described more accurately by a diffusion model in which the diffusional resistance of the plastic matrix and of an interfacial resistance barrier both contributed to the diffusional resistance encountered in the sorption process. It appeared that the rate of uptake of the un-ionized form of these solutes was diminished due to the influence of interfacial or aqueous diffusional barriers. Solute lipophilicity and degree of ionization appeared to be important factors determining the relative contribution of the respective barriers to the overall diffusional resistance.
The time course of sorption of diazepam and nitroglycerin from aqueous solutions into plastic materials has been represented by the diffusion and compartmental models for a variety of storage conditions. The diffusion model seemed to be the more satisfactory model in respect to both description and prediction of the drug uptake for all conditions. The compartment model appeared to be useful for describing the drug uptake at earlier times, giving a satisfactory fit to the data and reliable final parameter estimates. However, that model was not able to describe the loss as equilibrium was approached or accurately predict the disappearance profiles for these solutes with alterations in solution volume or infusion bag size. Approximations of the diffusion model gave parameter estimates consistent with those obtained by nonlinear regression using the full equations.
The reverse hemolytic plaque assay enables the detection of secretion products from individual cells in cultures by visualizing the plaques formed after complement-mediated hemolysis around the secreting cells. However, the precise quantitation of the amount of secretion remains problematic. In this study we propose a computation model for estimating the spreading of the secreted molecules, based on the underlying processes of diffusion and antigen adsorption by immobilized antibodies. The translational diffusion coefficient of rat prolactin at 37 degrees C, determined by laser light scattering, was 9.89 x 10(-7) cm2/s. The time-dependent concentration distribution around a constantly secreting cell in a flat quasi infinite layer, was derived from the diffusion equation, using an analytical approach based on Laplace transformation. The relations between plaque size, incubation time and secretion level were expressed as a function of the threshold concentration of secretion product that can be detected and the effective diffusion coefficient, taking antigen adsorption into account. We obtained very good agreement between observed and predicted results for plaque formation by dispersed prolactin secreting cells of 14-day-old female rat pituitaries. This study confirms the validity of the assumptions underlying the reverse hemolytic plaque assay, provided that the cell density is low, the incubation time is moderately long and the concentration of specific antiserum is sufficiently high.
Five patients with various types of brain tumours were infused with x-ray contrast material in a schedule designed to maintain a constant plasma concentration of tracer over a period of 3 hours. CT scans from an equatorial section of the tumour were taken at frequent intervals the first hour; then at 2 and 3 hours, and when possible up to 14 hours. Two different mathematical models-1. simple diffusion, and 2. transport by bulk flow plus diffusion were used to analyze the changes in tracer amount along profiles placed radially from the tumour center into the oedematous white matter. We found that the simple diffusion model could not account for the spread of contrast material in 3 cases. Adding bulk flow transport gave a very good fit to the measurements, also for the late scans. This model gave bulk flow rates of 0.0005 to 0.005 ml cm-2 min-1 for the extratumoural tissue close to the tumour, and values from 0.25 to 0.55 for the extracellular space in this region. We conclude that the peritumoural tissue is "perfused" by oedema fluid at relatively high flow rates and that this flow transports tracer and other components of plasma into the extracellular space.
The fluorescence recovery kinetics of succinyl-fluorescein Concanavalin A (S-F-ConA) in glycerol-physiological saline solutions of high viscosity and when bound to the surface of mouse fibroblasts were measured following brief photobleaching using a laser excited fluorescence microscope. In the high viscosity solutions, the recovery kinetics, interpreted on the basis of a simple diffusion model, yielded a diffusion coefficient in close agreement with the values predicted by the Stokes-Einstein equation. Recovery kinetics for S-F-ConA bound to the surface of mouse 3T3 and SV3T3 cells cultured in vitro yielded diffusion coefficients in the range of 5-10-10(-11) cm2/s, values considerably lower than those reported previously for membrane proteins. These measurements indicated that a considerable fraction of the S-F-ConA molecules bound to the cell surface are immobilized. These results are discussed in relation to current concepts of lateral motion of protein components within natural membranes.
Frequency-resolved fluorescence measurements have been performed to quantitate the lateral stress of the lipid layer containing nonbilayer phase preferring dioleoylphosphatidylethanolamine (DOPE). On the basis of a new rotational diffusion model, the wobbling diffusion constant (Dw), the curvature-related hopping diffusion constant (DH), and the two local orientational order parameters ([P2] and [P4]) of 1-palmitoyl-2-[[2-[4-(6-phenyl-trans-1,3,5-hexatrienyl)phenyl]ethyl] carbonyl]-3-sn-phosphatidylcholine (DPH-PC) in fully hydrated DOPE and DOPE/dioleoylphosphatidylcholine (DOPC) mixtures were calculated from the frequency-domain anisotropy data. The values of [P2], [P4], and DH for DOPE were found to increase significantly at approximately 12 degrees C, the known lamellar liquid crystalline (L alpha) to inverted hexagonal (HII) phase transition temperature of DOPE. Similar features as well as a decline of Dw were detected in the DOPE/DOPC mixtures as the DOPE content was increased from 85% to 90% at 23 degrees C, corresponding to the known lyotropic phase transition of the DOPE/DOPC. In contrast, for DOPC (0-40 degrees C) and DOPE/DOPC (0-100% DOPE at 3 degrees C), which remained in the L alpha phase, these changes were not detected. The most probable local orientation of DPH-PC in the DOPE/DOPC mixtures shifted progressively toward the normal of the lipid/water interface as the content of DOPE increased. We concluded that the curvature-related lateral stress in the lipid layer increases with the content of the nonbilayer phase preferring lipids.
The mechanism of potential loss of nitroglycerin stored in plastic and glass containers was studied from an equilibrium and kinetic approach. Plastic strips equilibrated with dilute aqueous solutions of neat nitroglycerin showed that the drug was lost by absorption. Drug loss was followed by an electron-capture GLC assay. The same assay of control solutions in glass showed no drug loss in 48 hr at pH 5.7. The kinetics of nitroglycerin absorption and desorption were determined using synthesized 14C-labeled drug. Absorption can be quantified using a diffusion model, where the concentration in the aqueous phase falls with time. Curve fitting yielded an average diffusion coefficient in plastic of 2.05 x 10(-9) cm2/sec and a partition coefficient of 104 (plastic-water) at 30 degrees. Temperature-dependence studies of absorption showed that the diffusion coefficient followed an Arrhenius relationship with an energy requirement of 19.6 kcal/mole, whereas effects on the partition coefficient were negligible. Nitroglycerin desorption from plastic disks under sink conditions into water can be quantified by assuming a diffusion model where the concentration at the surface of a plane sheet remains constant. Nonlinear least-squares curve fitting generated a diffusion coefficient of 1.14 x 10(-9) cm2/sec for the desorption process at 30 degrees.
The usefulness of a diffusion chamber method for determination of concentrations of cytostatic drugs in the interstitial fluid of tissues was tested. Chambers with a permeable membrane (pore size: 0.45 micrometer) were implanted in the liver, kidney, bladder wall, and prostate of dogs. After administration of high doses of methotrexate (100 mg/kg body wt) the concentrations in the chamber fluid and in serum were measured simultaneously and repeatedly for 72 h. The method proved to be effective for collecting data on the distribution of drugs in different organs. The results show that knowledge of the serum concentration does not permit predictions of the drug concentration in the interstitial fluid of various tissues to be made.
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The dissolution rates for hydrocortisone alcohol and acetate were determined using a stationary disk/rotating fluid system. The hydrocortisone was compressed in a tablet die, and the die placed in a vessel above a rotating magnetic bar. Dissolution rates were evaluated in aqueous media under conditions involving the following independent variables: solubility (Cs), diffusion coefficient (D), viscosity (v), rotational speed (omega), and tablet radius (r). A design equation which relates dissolution rate (R) to these variables was formulated for the system R alpha Cs D2/3 (v) -1/6(omega)1/2(r)3/2 This design equation adequately represents the system, which is related to fluid mechanics and convective diffusion models. The fluid mechanics model assumes that the fluid ideally rotates as solid-body rotation and the momentum layer is initiated at the outside radius of the tablet die. The convective diffusion model is based on the formation of a diffusion layer at the outside radius of the dissolving surface and a predictable relationship between the momentum and the mass transport quantities of bulk viscosity and diffusion coefficient. This configuration, like the rotating disk in a stationary fluid, offers the attractive attribute of being useful to study drug release mechanisms for systems of pharmaceutical interest.
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