Transient hydrophilic

The rate of transmembrane diffusion of ions and molecules across a membrane is usually described in terms of a permeability constant (P), defined so that the unitary flux of molecules per unit time [J) across the membrane is 7 = P(co - f,), where co and Ci are the concentrations of the permeant species on opposite sides of membrane correspondingly, P has units of cm s. Two theoretical models have been proposed to account for solute permeation of bilayer membranes. The most generally accepted description for polar nonelectrolytes is the solubility-diffusion model [24]. This model treats the membrane as a thin slab of hydrophobic matter embedded in an aqueous environment. To cross the membrane, the permeating particle dissolves in the hydrophobic region of the membrane, diffuses to the opposite interface, and leaves the membrane by redissolving in the second aqueous phase. If the membrane thickness and the diffusion and partition coefficients of the permeating species are known, the permeability coefficient can be calculated. In some cases, the permeabilities of small molecules (water, urea) and ions (proton, potassium ion) calculated from the solubility-diffusion model are much smaller than experimentally observed values. This has led to an alternative model wherein permeation occurs through transient hydrophilic defects, or pores , formed by thermal fluctuations of surfactant monomers in the membrane [25]. 

Overall membrane compression Lipid-domain interface fluctuations Free volume fluctuations Local depressions and distortions Transient hydrophobic pores Transient hydrophilic pores Foot-in-the-door hydrophilic pores Composite hydrophilic pores Membrane enzyme changes Membrane macromolecule protrusion changes Rupture and REB not actually described (5) Suggested alternative to transient pores (6) Transport of nonpolar species (7) Possible precursors to hydrophilic pores (8, 9) Possible precursor to hydrophilic pores (10) Key to quantitative descriptions (10-16) Candidate metastable pores" Candidate metastable pores Coupling to membrane macromolecules (17) Candidate signaling change mechanism... 

Transient hydrophilic pores can be regarded as excitations of the membrane because their frequency-of-occurrence is dependent on thermal fluctuations, the local transmembrane voltage, and the local composition of the membrane, and any participating membrane macromolecules. As pathways for ionic conduction, hydrophilic pores act much like ion channels, but with the... 

Only recently, we have shown experimentally for a selection of neutral ionophores and carefully purified, typical PVC plasticizers that in absence of ionic sites Nernstian EMF responses could not be obtained [55]. For plasticizers of low polarity no EMF responses were observed at all. Transient responses due to salt extraction even with the highly hydrophilic counterion chloride were observed in the case of the more polar nitrobenzene. Lasting primary ion-dependent charge separation at the liquid liquid interfaces of ISEs, resulting in a stable EMF response, seemed therefore only possible in the presence of ionic sites confined to the membrane phase. Because membranes free of impurity sites... 

Using liposomes made from phospholipids as models of membrane barriers, Chakrabarti and Deamer [417] characterized the permeabilities of several amino acids and simple ions. Phosphate, sodium and potassium ions displayed effective permeabilities 0.1-1.0 x 10 12 cm/s. Hydrophilic amino acids permeated membranes with coefficients 5.1-5.7 x 10 12 cm/s. More lipophilic amino acids indicated values of 250 -10 x 10-12 cm/s. The investigators proposed that the extremely low permeability rates observed for the polar molecules must be controlled by bilayer fluctuations and transient defects, rather than normal partitioning behavior and Born energy barriers. More recently, similar magnitude values of permeabilities were measured for a series of enkephalin peptides [418]. 

In case (a), an equilibrium is reached. It can be considered here that there are only reversible physical interactions between the polymer and water. Drying leads to a curve that is practically a mirror image of the absorption curve. The behavior of the material can be characterized by two quantities the equilibrium water concentration W, which characterizes the polymer affinity for water (hydrophilicity), and the duration Id of the transient, which is sharply linked to the sample thickness L and to a parameter characteristic of the rate of transport of water molecules in the polymer - the diffusion coefficient D. 

In recent years, spin traps have been used extensively to detect transient oxygen-derived radicals formed during myocardial ischemia and reperfusion [85-110]. However, except for few studies [110-115], the cardiovascular effects of spin traps have not been considered in detail. Since spin traps are reactive organic molecules, it is very plausible that they exert both pharmacologic and toxic effects on the myocardium. The objective of this study was to determine the effect of several structurally similar spin traps (either hydrophilic, lefthand side of Fig. 4) or hydrophobic, righthand side of Fig. 4) upon normal aerobic cardiac function and coronary flow rate in the isolated perfused rat heart. 

Studies on the ciearance (pi/h) of modei hydrophilic solutes such as calcein (MW 623) and dextrans FD-4 (MW 4400) and FD-40 (MW 38000) in tritiated water across the skin under the influence of US have revealed a good flux correlation with H20. Unexpectedly, the slopes obtained by linear regression of the plots were consistent for all solutes examined [116]. In other words, the permeability coefficients of the solutes were comparable with those of tritiated water and independent of molecular size up to 40 kDa under the effect of US. This can be ascribed to the above-described asymmetric collapse of transient cavitation bubbles at the liquid-solid interface, which can produce transport routes for hydrophilic solutes in the stratium corneum. 

Although the objective of most absorption enhancers is to avoid direct interaction with the mucosal membrane, cell permeation enhancers use this as a means to increase drug absorption. One form of enhancer currently of interest consists of glycosylated molecules, or facial amphiphiles. It is claimed that these compounds temporarily increase membrane permeability. Molecules are designed to self-assemble in membranes to form transient pores that permit hydrophilic com-poimds to cross the membrane. This technology has considerable potential for absorption enhancement. No adverse effects have been reported to date. ... 

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