Transports mechanisms

The transport mechanisms that operate in distribution and elimination processes of drugs, drug-carrier conjugates and pro-drugs include convective transport (for example, by blood flow), passive diffusion, facilitated diffusion and active transport by carrier proteins, and, in the case of macromolecules, endocytosis. The kinetics of the particular transport processes depend on the mechanism involved. For example, convective transport is governed by fluid flow and passive diffusion is governed by the concentration gradient, whereas facilitated diffusion, active transport and endocytosis obey saturable MichaeUs-Menten kinetics. 

The mechanisms by which various components in a liquid or gaseous feed stream to the membrane system are transported through the membrane structure determine the sq aiation properties of the membrane. These transport mechanisms are quite different in liquid and in gas or vapor phases. So are their effects on permeate flux (or permeability) and retention (or rejection) coefficient or separation factor in the case of gas separation. 

In contrast, less effort has apparently been directed to the transport of xenobiotics, and there is an intrinsic difficulty that in contrast to organisms that utilize carbohydrates or amino acids, suitable mutants defective in the metabolism of the substrate may not be available. This limitation makes it impossible to determine directly whether active transport is involved. Although the genes encoding permeases have been described quite frequently, details of their mechanisms have been less well documented  

A detailed investigation by Groenewegen et al. (1990) has examined the uptake of 4-chlorobenzoate by a coryneform bacterium that degraded this compound. The uptake was inducible and occurred in cells grown with 4-chlorobenzoate but not with glucose. A proton motive force (Ap)-driven mechanism was almost certainly involved, and uptake could not take place under anaerobic conditions unless an electron acceptor such as nitrate was present. 

Uptake was inducible by the substrate, did not occur with fructose-grown cells, and was inhibited by cyanide that prevents development of a protomotive force, and by the protophore carbonylcyanide-3-chlorophenylhydrazone (Leveau et al. 1998). The protein involved was encoded by an open reading frame on the plasmid designated tfdK. 

In Oxalobacter formigenes, oxalate and its decarboxylation product formate form a one-to-one antiport system, which involves the consumption of an internal proton during decarboxylation, and serves as a proton pump to generate ATP by decarboxylative phosphorylation (Anantharam et al. 1989). 

The enthusiasm for using Caco-2 cells and other epithelial cell cultures in studies of drug transport processes has been explained by the ease with which new information can be derived from these fairly simple in vitro models [7]. For instance, drug transport studies in Caco-2 cells grown on permeable supports are easy to perform under controlled conditions. This makes it possible to extract information about specific transport processes that would be difficult to obtain in more complex models such as those based on whole tissues from experimental animals. Much of our knowledge about active and passive transport mechanisms in epithelia has therefore been obtained from Caco-2 cells and other epithelial cell cultures [10-15]. This has been possible since Caco-2 cells are unusually well differentiated. In many respects they are therefore functionally similar to the human small intestinal enterocyte, despite the fact that they originate from a human colorectal carcinoma [16, 17]. 

A variety of transport systems are extensively expressed in Caco-2 cells and this 

The abundant expression of a variety of transporters in Caco-2 cells also makes it attractive to apply functional genomics tools, such as cDNA arrays in order to map the expression [31] and relative abundance of these transporters [32], Also, genomic mapping of surface receptors on Caco-2 cells can be performed to study receptor-mediated endocytosis and other endocytotic pathways for larger molecules in enterocytes [33-36]. 

When the pore radius is much greater than the mean free path of permeating gas molecules (i.e., rlX 3), viscous flow occurs if a pressure gradient is applied to such a pore regime. The mean free path is defined as 

When r/X 0.05, the molecules collide on average more frequently with the pore wall than with one another and Knudsen diffusion occurs under a pressure gradient. This mechanism is often predominant in macroporous and mesoporous membranes. The flowing flux in a capillary pore can be described by the Knudsen equation  

In the intermediate range between viscous flow and Knudsen flow, that is, 0.05 r/X 3, a gas molecule may travel a certain distance and collide with another one after the last collision with the pore wall. As a result, the velocity of gas molecules at the wall surface is not zero. This mechanism - combining both viscous flow and Knudsen diffusion - is thus called slip flow. The slip effect is negligibly small when r X but becomes significant when r is close to X. A correction has to be applied to the viscous flow with a wall velocity to describe the permeation flux as 

Surface flow occurs when the gas molecules are strongly adsorbed on the pore walls and migrate along the pore surface. Usually this is the case with gases which condense rather easily at moderate temperature-pressure conditions. The flux is generally described by a Pick s law type of expression  

The relationship between adsorption capacity q and pressure can be expressed by an adsorption isotherm such as a Langmuir equation. 

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Liquid-phase sintering is significantly more complex tlian solid-state sintering in tliat tliere are more phases, interfaces, and material transport mechanisms to consider. In general, densification will occur as long as it is... 

The thermal conductivity of polymeric fluids is very low and hence the main heat transport mechanism in polymer processing flows is convection (i.e. corresponds to very high Peclet numbers the Peclet number is defined as pcUUk which represents the ratio of convective to conductive energy transport). As emphasized before, numerical simulation of convection-dominated transport phenomena by the standard Galerkin method in a fixed (i.e. Eulerian) framework gives unstable and oscillatory results and cannot be used. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

AH of these technologies require careful attention to the film transport mechanism to avoid imaging defects. The sizes of the features produced on the film, typicaHy resolution of 1000 spots/cm or greater, and the accuracy of spot placement both require high precision equipment. Even minute misplacements of spots can produce objectionable visible artifacts. 

The concentration boundary layer forms because of the convective transport of solutes toward the membrane due to the viscous drag exerted by the flux. A diffusive back-transport is produced by the concentration gradient between the membranes surface and the bulk. At equiUbrium the two transport mechanisms are equal to each other. Solving the equations leads to an expression of the flux ... 

In addition, uranium and lead transport mechanisms ia radioactive minerals have been studied ia order to evaluate the suitabiUty of mineral phases as hosts for radioactive wastes. Zircon is one of the most commonly used geochronometers, as well as a proposed nuclear waste matrix material, and there are many mechanisms by which uranium and lead can migrate through its stmcture (19). 

A simplified diagram representing the various reservoirs and transport mechanisms and pathways involved in the cycles of nutrient elements at and above the surface of the Earth is given in Eigure 1. The processes are those considered to be the most important in the context of this article, but others of lesser significance can be postulated. Eor some of the elements, notably carbon, sulfur, chlorine, and nitrogen, considerable research has been done to evaluate (quantitatively) the amount of the various elements in the reservoirs and the rates of transfer. 

Eig. 1. Generalized cycle of the various reservoirs and transport mechanisms and pathways involved in the circulation of nutrient elements. The numbered arrows represent processes by which elements transfer among the reservoirs. Processes shown are those considered to have the most important influence... 

Transport. Wood is composed of a complex capillary network through which transport occurs by capillarity, pressure permeability, and diffusion. A detailed study of the effect of capillary stmcture on the three transport mechanisms is given in Stamm (13). 

Because bretylium is poody absorbed from the GI tract (- 10%), it is adrninistered iv or im. Very litde dmg is protein bound in plasma. Bretylium is taken up by an active transport mechanism into and concentrated in postganglionic nerve terminals of adrenergicahy innervated organs. Peak plasma concentrations after im injections occur in about 30 min. Therapeutic plasma concentrations are 0.5—1.0 p.g/mL. Bretylium is not metabolized and >90% of the dose is excreted by the kidneys as unchanged dmg. The plasma half-life is 4—17 h (1,2). 

Semiconducting Ceramics. Most oxide semiconductors are either doped to create extrinsic defects or annealed under conditions in which they become non stoichiometric. Although the resulting defects have been carefully studied in many oxides, the precise nature of the conduction is not well understood. Mobihty values associated with the various charge transport mechanisms are often low and difficult to measure. In consequence, reported conductivities are often at variance because the effects of variable impurities and past thermal history may overwhelm the dopant effects. 

Eddy diffusion as a transport mechanism dominates turbulent flow at a planar electrode ia a duct. Close to the electrode, however, transport is by diffusion across a laminar sublayer. Because this sublayer is much thinner than the layer under laminar flow, higher mass-transfer rates under turbulent conditions result. Assuming an essentially constant reactant concentration, the limiting current under turbulent flow is expected to be iadependent of distance ia the direction of electrolyte flow. 

FIGt 22-48 Transport mechanisms for separation membranes a) Viscous flow, used in UF and MF. No separation achieved in RO, NF, ED, GAS, or PY (h) Knudsen flow used in some gas membranes. Pore diameter < mean free path, (c) Ultramicroporoiis membrane—precise pore diameter used in gas separation, (d) Solution-diffusion used in gas, RO, PY Molecule dissolves in the membrane and diffuses through. Not shown Electro-dialysis membranes and metallic membranes for hydrogen. 

Similarly, contaminant concentrations in rivers or streams can be roughly assessed based on rate of contaminant introduction and dilution volumes. Estuary or impoundment concentration regimes are highly dependent on the transport mechanisms enumerated. Contaminants may be localized and remain concentrated or may disperse rapidly and become diluted to insignificant levels. The conservative approach is to conduct a more in-depth assessment and use model results or survey data as a basis for determining contaminant concentration levels. 

Ratner, M.A. (2000), Polymer Electrolytes Ionic Transport Mechanisms and Relaxation Coupling, MRS Bull. 25(3), 31. 

We begin by reviewing the regulatory driving force in the United States for air pollution abatement. To appreciate the objectives of our Federal air pollution control regulations, an understanding of the fate and transport mechanisms in the environment is important. Hence, some general discussions on the behavior of pollutants in the atmosphere are included in this chapter. 

First order parameters affecting dispersion stem from meteorological conditions. These, as much as any other consideration, determine how a stack is to be designed for air pollution control purposes. Since the operant transport mechanisms are determined by the micro-meteorological conditions, any attempt to predict ground-level pollutant concentrations is dependent on a reasonable estimate of the convective and dispersive potential of the local air. The following are meteorological conditions which need to be determined ... 

At any instant, pressure is uniform throughout a bubble, while in the surrounding emulsion pressure increases with depth below the surfaee. Thus, there is a pressure gradient external to the bubble which causes gas to flow from the emulsion into the bottom of the bubble, and from the top of the bubble back into the emulsion. This flow is about three times the minimum fluidization velocity across the maximum horizontal cross section of the bubble. It provides a major mass transport mechanism between bubble and emulsion and henee contributes greatly to any reactions which take place in a fluid bed. The flow out through the top of the bubble is also sufficient to maintain a stable arch and prevent solids from dumping into the bubble from above. It is thus responsible for the fact that bubbles can exist in fluid beds, even though there is no surface tension as there is in gas-liquid systems. 

Bitter, J. G. A. (1991) Transport Mechanisms in Membrane Separation Processes, Plenum Press, New York. 

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