Basal nonselective cation permeability in rat cardiac microvascular endothelial cells

The presence of a basal nonselective cation permeability was mainly investigated in primary cultures of rat cardiac microvascular endothelial cells (CMEC) by applying both the patch-clamp technique and Fura-2 microfluorimetry. With low EGTA in the pipette solution, the resting membrane potential of CMEC was -21.2 +/- 1.1 mV, and a Ca2+-activated Cl- conductance was present. When the intracellular Ca2+ was buffered with high EGTA, the membrane potential decreased to 5.5 +/- 1.2 mV. In this condition, full or partial substitution of external Na+ by NMDG(+) proportionally reduced the inward component of the basal I-V relationship. This current was dependent on extracellular monovalent cations with a permeability sequence of K+ > Cs+ > Na+ > Li+ and was inhibited by Ca2+, La3+, Gd3+, and amiloride. The K+/Na+ permeability ratio, determined using the Goldman-Hodgkin-Katz equation, was 2.01. The outward component of the basal I-V relationship was reduced when intracellular K+ was replaced by NMDG(+), but was not sensitive to substitution by Cs+. Finally, microfluorimetric experiments indicated the existence of a basal Ca2+ entry pathway, inhibited by La3+ and Gd3+. The basal nonselective cation permeability in CMEC could be involved both in the control of myocardial ionic homeostasis, according to the model of the blood-heart barrier, and in the modulation of Ca2+ -dependent processes. (C) 2002 Elsevier Science (USA).

Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers

In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP , and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.

A unique behavior of sub-critical hydrocarbon permeability in activated carbon at low pressures

In our study on sub-critical hydrocarbon permeation in activated carbon, a minimum in the total permeability (B-T) at low pressure has been observed for only long-chain hydrocarbons such as n-hexane and n-heptane. Such an observation suggests that the minimum appearance depends on the properties of permeating vapors as well as the porous medium. In this paper a permeation model is presented to explain the minimum behavior with the allowance of the collision-reflection factor in the Knudsen diffusivity to be a function of surface loading. Surface diffusion was found to be very significant compared to other transport mechanisms such as Knudsen diffusion and gaseous viscous flow at low pressures. Since the gaseous viscous flow contributes negligibly to the B, at low pressures, the minimum appearance in the B, is mainly attributed to the interplay between Knudsen diffusion and surface diffusion. Also, the molecular structure of adsorbates plays an important role in the minimum appearance.

Permeability studies of alkylamides and caffeic acid conjugates from echinacea using a Caco-2 cell monolayer model

Background: Echinacea is composed of three major groups of compounds that are thought to be responsible for stimulation of the immune system-the caffeic acid conjugates, alkylamides and polysaccharides. This study has focussed on the former two classes, as these are the constituents found in ethanolic liquid extracts. Objective: To investigate the absorption of these two groups of compounds using Caco-2 monolayers, which are a model of the intestinal epithelial barrier. Results: The caffeic acid conjugates (caftaric acid, echinacoside and cichoric acid) permeated poorly through the Caco-2 monolayers although one potential metabolite, cinnamic acid, diffused readily with an apparent permeability (P-app) of 1x10(-4) cm/s. Alkylamides were found to diffuse through Caco-2 monolayers with P-app ranging from 3x10(-6) to 3x10(-4) cm/s. This diversity in P-app for the different alkylamides correlates to structural variations, with saturation and N-terminal methylation contributing to decreases in P-app. The transport of the alkylamides is not affected by the presence of other constituents and the results for synthetic alkylamides were in line with those for the alkylamides in the echinacea preparation. Conclusion: Alkylamides but not caffeic acid conjugates are likely to cross the intestinal barrier.

Permeability of subcritical hydrocarbons in activated carbon

A new diffusion and flow model is presented to describe the behavior of hydrocarbon vapors in activated carbon. The micro/mesopore size distribution (PSD) is obtained according to Do's method which consists of two sequential processes of pore layering and pore filling. This model uses the micro/meso PSD obtained from each adsorbate equilibrium isotherm, which reflects the dynamics behavior of adsorbing molecules through the solid. The initial rise in total permeability is mainly attributed to adsorbed-phase diffusion (that is, surface diffusion), whereas the decrease over reduced pressure of about 0.9 is attributed to the reduction of pore space available for gas phase diffusion and flow. A functional form of surface diffusivity is proposed and validated with experimental data. This model predicts well the permeability of condensable hydrocarbon vapors in activated carbon. (C) 2005 American Institute of Chemical Engineers.

Predictors of cultural adjustment: Intergroup status relations and boundary permeability

We examined intergroup predictors of cultural adjustment among Asian international students in Australia. Sociostructural beliefs (status, legitimacy, and permeability) and initial adjustment were assessed (N = 113) at Time 1, and measures of adjustment were obtained (N = 80) at Time 2 eight weeks later. International students who perceived their cultural group to be relatively low in status experienced lower levels of psychological adjustment. Also, as expected, the effects of status were moderated by perceptions of both the permeability of intergroup boundaries and the legitimacy of the status differential. At high levels of legitimacy, perceptions of permeable group boundaries were associated with better psychological, sociocultural, and academic adjustment among international students perceiving their group to be low in status, but lower levels of adjustment among students who perceived their group to be high in status. At low levels of legitimacy, irrespective of group status position, perceived permeability was not related to adjustment.

Percutaneous absorption of steroids: Determination of in vitro permeability and tissue reservoir characteristics in human skin layers

The skin localization of steroids following topical application is largely unknown. We determined the distribution of five steroids in human skin using excised epidermal, dermal, and full-thickness membranes in vitro. There was no significant difference in steroid maximum flux through epidermal and full-thickness membranes, other than significantly lower fluxes for the most polar steroid, aldosterone. Hydrocortisone had the highest dermal diffusivity and dermal penetration, and the accumulation of hydrocortisone and corticosterone was higher than that of the other steroids. Slower penetration and higher accumulation in the viable epidermis of progesterone in full-thickness skin were consistent with dermal penetration limitation effects associated with high lipophilicity. Copyright (c) 2006 S. Karger AG, Basel