Across Barriers

1 Primary Cultures of Brain Capillary Endothelial Cells 522 

l Primary Cultures of Porcine Brain Microvascular Endothelial Cells.. 522 

2 Cocultures of Bovine Brain Microvascular Endothelial Cells and Rat Astrocytes 525 

1 Drug Transport Mediated by SLC Transporters Using Eukaryotic Cells 532 

1 Drag Transport Mediated by SLC and ABC Transporters Using Double Transfected Cells 539 

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Barrier layer formation Diffusion across barrier control (reaction deceleratory)... 

Unstirred Water Layer Effect (Transport across Barriers in Series and in Parallel)... 

Equation (52) shows an important property of diffusion across barriers in series The diffiisional resistance is additive. Therefore, in the case of diffusion involving n barriers in series, the total resistance can be calculated as... 

Pharmaceutical scientists assess and express drug permeation across membrane barriers in terms of flux. Flux measures the molar unit of a drug that permeates a resistant barrier (e.g., skin or gastrointestinal epithelial cells) per unit time and surface area (Box 13.1). Permeation enhancers, such as alcohols and surfactants, increase flux by modulating resistance factors that counteract drug diffusion across barriers at the site of administration. 

There is not space here to explain the process of nerve impulse transmission. It is an electrical process and involves pumping of Na+ and K+ ions across barriers. It should be noted that there are cells other than neurons in the nervous system, of which the most abundant are glial cells. 

The resistance to diffusion of a molecular species across a barrier equals the reciprocal of its permeability coefficient (Chapter 1, Section 1.4B). In this regard, we will let f COi be the permeability coefficient for CO2 diffusion across barrier j. To express the resistance of a particular mesophyll or chlo-roplast component on a leaf area basis, we must also incorporate Am sIA to allow for the actual area available for diffusion—the large internal leaf area acts like more pathways in parallel and thus reduces the effective resistance (Fig. 8-4). Because the area of the plasma membrane is about the same as that of the cell wall, and the chloroplasts generally occupy a single layer around the periphery of the cytosol (Figs. 1-1 and 8-11), the factor AmesIA applies to all of the diffusion steps of CO2 in mesophyll cells (all five individual resistances in Eq. 8.21). In other words, we are imagining for simplicity that the cell wall, the plasma membrane, the cytosol, and the chloroplasts are all in layers having essentially equal areas (Fig. 8-11). Thus, the resistance of any of the mesophyll or chloroplast components for CO2 diffusion,, is reduced from 1 /P co, by the reciprocal of the same factor, Ames/A ... 

Fig. 4. Transitions between states of radical occupant required for derivetion of inJit by the O Toole approach, (a) shows transitions across barrier between states < and i + I (b) shows tiansilions between states / — I and i.

The control of reaction rates by a bulk difiusion process is not usually demonstrable by microscopic observations, but support may be obtained from measurements of diffusion coefficients of appropriate species within the structure concerned. This approach has been invaluable in formulating the mechanisms of oxidation of metals, where rates of reaction have been correlated with rates of transportation of ions across barrier layers of product. Sometimes the paths by which such movements occur correspond to regions of high difi isivity, involving imperfect zones within the barrier layer, compared with normal rates of intracrystalline diffusion across more perfect regions of material [63]. Difiusion measurements have been made for ions in nickel sulfide and it was concluded that the decomposition of NiS is diffiision controlled [50]. 

This suggests that the rate determining steps are associated with tunnel 1 ling across barriers (chain ends or to another chain) rather than phonon assisted hopping processes. 

Dmgs pass across barriers by a number of mechanisms. Passive mechanisms utilize the forces of concentration differences or pressure differences to move substances from one site to another. Active transport of a drug is typically via a specific transporter, requires energy, and moves solute against its electrochemical gradient. Figure 4 illustrates these definitions. 

Squeezing of unmelted polymer across barrier-flight... 

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