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Permeability Increase (permeability + increase)

Distribution by Scientific Domains

Medical Sciences	33%

Selected Abstracts

Blood,brain barrier damage and brain penetration of antiepileptic drugs: Role of serum proteins and brain edema

EPILEPSIA, Issue 4 2009
Nicola Marchi
Summary Purpose:, Increased blood,brain barrier (BBB) permeability is radiologically detectable in regions affected by drug-resistant epileptogenic lesions. Brain penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We studied the effects of BBB damage on brain distribution of hydrophilic [deoxy-glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We tested the hypothesis that lipophilic and hydrophilic drug distribution is differentially affected by BBB damage. Methods:, In vivo BBB disruption (BBBD) was performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3-sucrose, 3H-deoxy-glucose, 14C-phenytoin, and C14-diazepam) or unlabeled phenytoin was measured and correlated to brain water content and protein extravasation. In vitro hippocampal slices were exposed to different osmolarities; drug penetration and water content were assessed by analytic and densitometric methods, respectively. Results:, BBBD resulted in extravasation of serum protein and radiolabeled drugs, but was associated with no significant change in brain water. Large shifts in water content in brain slices in vitro caused a small effect on drug penetration. In both cases, total drug permeability increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the amount of free phenytoin in the brain. Discussion:, After BBBD, drug binding to protein is the main controller of total brain drug accumulation. Osmotic BBBD increased serum protein extravasation and reduced free phenytoin brain levels. These results underlie the importance of brain environment and BBB integrity in determining drug distribution to the brain. If confirmed in drug-resistant models, these mechanisms could contribute to drug brain distribution in refractory epilepsies. [source]

Self-Supporting, Double Stimuli-Responsive Porous Membranes From Polystyrene- block -poly(N,N -dimethylaminoethyl methacrylate) Diblock Copolymers

ADVANCED FUNCTIONAL MATERIALS, Issue 7 2009
Felix Schacher
Abstract Asymmetric membranes are prepared via the non-solvent-induced phase separation (NIPS) process from a polystyrene- block -poly(N,N -dimethylaminoethyl methacrylate) (PS- b -PDMAEMA) block copolymer. The polymer is prepared via sequential living anionic polymerization. Membrane surface and volume structures are characterized by scanning electron microscopy. Due to their asymmetric character, resulting in a thin separation layer with pores below 100,nm on top and a macroporous volume structure, the membranes are self-supporting. Furthermore, they exhibit a defect-free surface over several 100,µm2. Polystyrene serves as the membrane matrix, whereas the pH- and temperature-sensitive minority block, PDMAEMA, renders the material double stimuli-responsive. Therefore, in terms of water flux, the membranes are able to react on two independently applicable stimuli, pH and temperature. Compared to the conditions where the lowest water flux is obtained, low temperature and pH, activation of both triggers results in a seven-fold permeability increase. The pore size distribution and the separation properties of the obtained membranes were tested through the pH-dependent filtration of silica particles with sizes of 12,100,nm. [source]

Permeability change of electroplated Ni,Fe permalloy thin films by a leveller added to the electrolyte

PHYSICA STATUS SOLIDI (A) APPLICATIONS AND MATERIALS SCIENCE, Issue 12 2007
Wonbae Bang
Abstract We investigated the correlation between the surface roughness and the magnetic properties in electroplated Ni,Fe Permalloy thin films. The Ni,Fe Permalloy thin films electroplated with electrolytes containing a leveling additive showed reduction of coercivity and increase of permeability compared with those prepared with pure inorganic electrolytes. The decrease of the surface roughness resulted in the reduction of coercivity and showed a strong correlation. The improvements in the surface roughness and coercivity caused the initial and incremental permeability increase by 450% and 130%, respectively. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
C. A. Glass
Vascular permeability is assumed to be regulated by the cytosolic Ca2+ concentration ([Ca2+]c) of the endothelial cells. When permeability is increased, however, the maximum [Ca2+]c appears to occur after the maximum permeability increase, suggesting that Ca2+ -dependent mechanisms other than the absolute Ca2+ concentration may regulate permeability. Here we investigate whether the rate of increase of the [Ca2+]c (d[Ca2+]c/dt) may more closely approximate the time course of the permeability increase. Hydraulic conductivity (Lp) and endothelial [Ca2+]c were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased Lp, [Ca2+]c and d[Ca2+]c/dt were examined. Lp peaked significantly earlier than [Ca2+]c in all drug treatments examined (Ca2+ store release, store-mediated Ca2+ influx, and store-independent Ca2+ influx). When Lp was increased in a store-dependent manner the time taken for Lp to peak (3.6 ± 0.9 min during store release, 1.2 ± 0.3 min during store-mediated Ca2+ influx) was significantly less than the time taken for [Ca2+]c to peak (9.2 ± 2.8 min during store release, 2.1 ± 0.7 min during store-mediated influx), but very similar to that for the peak d[Ca2+]c/dt to occur (4.3 ± 2.0 min during store release, 1.1 ± 0.5 min during Ca2+ influx). Additionally, when the increase was independent of intracellular Ca2+ stores, Lp (0.38 ± 0.03 min) and d[Ca2+]c/dt (0.30 ± 0.1 min) both peaked significantly before the [Ca2+]c (1.05 ± 0.31 min). These data suggest that the regulation of vascular permeability by endothelial cell Ca2+ may be regulated by the rate of change of the [Ca2+]c rather than the global [Ca2+]. [source]

Validation of a differential in situ perfusion method with mesenteric blood sampling in rats for intestinal drug interaction profiling

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5-6 2010
Joachim Brouwers
Abstract The present study explored the feasibility of a differential setup for the in situ perfusion technique with mesenteric cannulation in rats to assess drug interactions at the level of intestinal absorption. In contrast to the classic, parallel in situ perfusion setup, the differential approach aims to identify intestinal drug interactions in individual animals by exposing the perfused segment to a sequence of multiple conditions. First, the setup was validated by assessing the interaction between the P-glycoprotein (P-gp) inhibitor verapamil and the transport probes atenolol (paracellular transport), propranolol (transcellular) and talinolol (P-gp mediated efflux). While transport of atenolol and propranolol remained constant for the total perfusion time (2,h), a verapamil-induced increase in talinolol transport was observed within individual rats (between 3.2- and 5.2-fold). In comparison with the parallel setup, the differential in situ perfusion approach enhances the power to detect drug interactions with compounds that exhibit strong subject-dependent permeability. This was demonstrated by identifying an interaction between amprenavir and ketoconazole (P-gp and CYP3A inhibitor) in five out of seven rats (permeability increase between 1.9- and 4.2-fold), despite high inter-individual differences in intrinsic permeability for amprenavir. In combination with an increased throughput (up to 300%) and a reduced animal use (up to 50%), the enhanced power of the differential approach improves the utility of the biorelevant in situ perfusion technique with mesenteric blood sampling to elucidate the intestinal interaction profile of drugs and drug candidates. Copyright © 2010 John Wiley & Sons, Ltd. [source]