Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Permeability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources
PubMed1980

Osmotic properties of differentiating bone marrow precursor cells: membrane permeability to non-electrolytes.

Membrane permeability to the non-electrolyte probes urea and thiourea was measured in a population of differentiating bone marrow precursor cells (Cicoria and Hempling, '80). The phenomenologic equations of Kedem and Katchalsky ('58) were applied. The population of cells, which can be separated by velocity sedimentation, was examined over the maturation range of 400 to 1,000 cubic micra. Several membrane properties were observed: 1) Solute permeability (omega RT) increased linearly as the cell volume increased, while the reflection coefficients (sigma) remained constant. 2) Membrane permeability to urea was significantly greater than to thiourea; however, their respective sigmas did not differ significantly. Solute permeability was independent of sigma at 22 degrees C. 3) In the two maturation phases observed, omega RT varied directly with the volume of osmotically active water. 4) The permeability to urea and to thiourea has provided information on the characteristics of the pathways used for water and non-electrolytes, as well as a description of the phenomenologic membrane events accompanying cellular maturation.

Animals↗
PubMed1984

Cellular responses to external ATP which precede an increase in nucleotide permeability in transformed cells.

Transformed mouse fibroblasts, such as 3T6, exhibit an increase in plasma membrane permeability to nucleotides and other normally impermeant molecules when incubated with external ATP in an alkaline medium low in divalent cations. Increased nucleotide permeability, induced by external ATP, occurs after a 3- to 5-min lag period. Prior to this event, there is a dramatic Na+ influx and K+ efflux, a significant reduction in the levels of intracellular ATP and organic phosphates, and a reduction in the plasma membrane potential. Accordingly, we postulate that these cellular responses to external ATP play a role in the efflux of nucleotides. Ouabain, a specific inhibitor of the plasma membrane (Na+,K+)-ATPase, acts together with low concentrations of external ATP to increase nucleotide permeability in 3T6 cells. This effect occurs at concentrations of ouabain and ATP which alone do not increase nucleotide permeability. In addition, ouabain and low concentrations of ATP alone have little effect on the level of intracellular ATP. This is in contrast to energy inhibitors and uncouplers which appear to enhance nucleotide permeability by lowering the intracellular ATP concentration. Ouabain alone causes a threefold increase in intracellular Na+ levels and a similar reduction in intracellular K+ levels under our experimental conditions, supporting the idea that ion fluxes are involved in the mechanism of permeabilization.

Adenosine Triphosphate↗
PubMed1987

Effects of alterations in endothelial cell volume on transendothelial albumin permeability.

We examined the effects of alterations in endothelial cell volume on transendothelial albumin permeability. Studies were done using a confluent monolayer of bovine pulmonary artery endothelial cells grown on gelatinized microporous filters. When endothelial cells were exposed to media made hypertonic with 200 mM mannitol, the intracellular volume (measured with 14C-urea) decreased twofold and remained decreased over a 30-minute time-span, thus showing no significant regulatory volume increase (RVI) within this time period. When endothelial cells were exposed to hypotonic media, intracellular volume rapidly doubled within 2 minutes, and then decreased to baseline values within 10 minutes in spite of the sustained hypotonic environment, a process known as regulatory volume decrease (RVD). We also measured the transendothelial flux of 125I-albumin with the cells exposed to the same osmotic changes. We observed that only under hypertonic conditions was there a significant change in the 125I-albumin permeability. These results indicate that the pulmonary artery endothelial cells in culture alter their cell volume when exposed to variations in the osmotic environment, and also show RVD in response to hypotonic conditions but no RVI within 40 minutes after exposure to hypertonic conditions. The transendothelial albumin permeability did not change under hypotonic conditions but increased under hypertonic conditions. Thus, endothelial cells shrinkage may be an important mechanism of increased endothelial macromolecule permeability. These volume changes may occur in endothelial cells in situ and have a role in inducing alterations in the transendothelial permeability to proteins.

Albumins↗
PubMed1990

Lanthanum probing of cell membrane permeability in the rat heart: pathological versus artefactual alterations.

The influence of fixation on membrane permeability has been examined in the isolated rat heart using lanthanum as a permeability probe. Normal and ischaemic hearts were probed at various stages during a conventional fixation programme with either ionic or colloidal lanthanum and compared with lanthanum saline administered prior to fixation. Fixation of the myocardium coincident with or followed by lanthanum probing resulted in an influx of the probe into most myocytes in normal tissue. Alterations in permeability after ischaemic episodes could not be distinguished from the artefact. However, lanthanum saline prior to fixation showed exclusion of the probe from normal tissue, while the increased permeability demonstrated after ischaemia was associated with declining myocardial performance during subsequent reperfusion. These results illustrate the need for caution in the application and evaluation of methods determining permeability in fixed tissue. Probes of differing size and charge permeated fixed tissue to varying degrees thereby implicating the formation of specific lesions during chemical fixation.

Animals↗
PubMed1976

The development of the oxygen permeability of the avian egg shell and its membranes during incubation.

The 02-permeability of the avian egg shell and shell membranes is initially low (approximately equal to 0.1-10(-6) ml O2 STP-sec-1cm-2-mmHg-1) during incubation but increases about 10-fold after the first week. This increase correlates with a decline in water content of the membranes. A major increase in colloid osmotic pressure (up to 50 cm Hg) occurs and is the suggested cause for the onset of rapid removal of water from the membranes. A high membrane water content correlates with low O2-permeability and vice versa. The final degree of membrane hydration reached during incubation is independent of ambient humidity; that is, the O2-permeability of the shell and its membranes is controlled by conditions inside the egg. An hypothesis is presented to explain the profound increase in O2-permeability while the rate of water loss from the egg remains stable during incubation. The removal of water from the shell membranes by the increased colloid osmotic pressure will increase the number of gas filled channels in the membranes which in turn will increase the O2-permeability. In spite of the change in water content, the water vapor pressure in the shell membranes will always be very close to that of a free water surface and water loss will hence be determined by the ambient humidity and the porosity of the mineral shell.

Animals↗
PubMed1995

Oocyte and zygote zona pellucida permeability to macromolecules.

Zona pellucida intact mouse pre- and post-ovulatory oocytes and zygotes were investigated for permeability to macromolecules using graded neutral fluorescein isothiocyanate (FITC) dextrans (molecular weight range 3.84-170 kDa) and a range of galactose-binding lectins (molecular weight range 40-247 kDa). The use of both FITC neutral dextrans and FITC galactose-binding lectins gave good agreement in the zona pellucida permeability studies. Zona pellucida intact pre- and post-ovulatory oocytes were permeable to both markers up to a molecular weight range of 170 kDa although movement across the zona pellucida was diminished between 100 to 150 kDa with no detectable permeability at molecular weight range of 170 kDa. Zygotes demonstrated a decreased zona pellucida permeability at around 110 kDa. Two galactose-containing oligosaccharide-rich zones in the zona pellucida were identified, and changes in zygote vitelline membrane galactose-binding lectin affinity were detected.

Animals↗
PubMed2002

Parametric imaging of tumor perfusion using flow- and permeability-limited tracers.

PURPOSE: To quantitatively evaluate the spatial distribution of flow- and permeability-limited perfusion in MCF7 human breast cancer tumors orthotopically implanted in CD1-NU mice. MATERIALS AND METHODS: Flow-limited perfusion was derived from (2)H-MRI recorded before and after infusion of deuterated water. Permeability-limited perfusion was evaluated from GdDTPA-enhanced (1)H-MRI. RESULTS: The dominant processes in tumor perfusion, namely blood flow and capillary permeability, were mapped in orthotopically implanted MCF7 human breast cancer tumors. The dynamic data were processed according to physiological models, yielding parametric maps of intravascular volume fraction, water perfusion rate, GdDTPA permeability rate constant, and extracellular volume fraction accessible to GdDTPA. The maps exhibited the heterogeneous distribution of each perfusion parameter. Most of the tumor tissue (> or =95%) was perfused with HDO, while GdDTPA was perfused in only about 50% of it. In most loci the perfusion rate was limited by capillary permeability to GdDTPA. CONCLUSION: The results demonstrated the instructive value of tracers with different properties used in conjunction to achieve a deeper understanding of tumor perfusion capacity. This study offers tools for the accurate, noninvasive evaluation of drug delivery efficacy.

Animals↗
PubMedDate not supplied

Comparison of albumin-(Gd-DTPA)30 and Gd-DTPA-24-cascade-polymer for measurements of normal and abnormal microvascular permeability.

The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). TI-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)30 or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)30 demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.

Analysis of Variance↗
PubMed2003

Supernatants from dengue virus type-2 infected macrophages induce permeability changes in endothelial cell monolayers.

The ability of dengue virus-infected human monocyte-derived macrophages to induce permeability changes in primary human umbilical vein endothelial cells was investigated. Supernatants from dengue virus type 2-infected monocyte-derived macrophages increased permeability in human umbilical vein endothelial cell monolayers without inducing endothelial cell infection. Production of permeabilising activity from monocyte-derived macrophages occurred after the peak of progeny virus release. TNF-alpha, a known inducer of endothelial cell permeability, was released from dengue virus infected monocyte-derived macrophages but its release did not coincide with release of endothelial cell permeabilising activity. Permeability induction was enhanced by pre-incubation with supernatants from infected monocyte-derived macrophages harvested at the time of peak release of TNF-alpha and infectious virus. Thus, supernatants from dengue virus-infected monocyte-derived macrophages contain factors that increase human umbilical vein endothelial cell permeability, but this is not accompanied by endothelial cell infection or directly correlated with release of dengue virus or TNF-alpha from monocyte-derived macrophages. This model system can be used for further in vitro analysis of mechanisms that may relate to capillary leakage and the development of dengue haemorrhagic fever/dengue shock syndrome.

Cell Membrane Permeability↗
PubMed2004

Effect of heat preconditioning on the uptake and permeability of R123 in brain microvessel endothelial cells during mild heat treatment.

The purpose of this study was to assess the effect of mild heat and heat preconditioning on the uptake and permeability of a P-glycoprotein (P-gp) substrate, rhodamine 123 (R123), in a cell culture model of the blood-brain barrier (BBB). An immediate goal was to determine whether prior mild heat treatment could render brain microvessel endothelial cells more resistant to future heat stress and affect BBB drug permeation by future ultrasound-induced mild heat (USMH) treatment. To address this issue, the expression level of two proteins, P-gp and heat shock protein 70 (Hsp70), and their effects on uptake of R123 and permeability of R123 and [14C]-sucrose in combination with mild heat and P-gp modulator PSC833 during and after mild heat treatment in heat-preconditioned and heat-unconditioned bovine brain microvessel endothelial cell (BBMEC) monolayers were studied. Mild heat caused a significant increase in BBB permeability of R123 and [14C]-sucrose when compared with control and PSC833. Exposure of BBMECs to heat preconditioning caused a slight but insignificant decrease in cellular uptake of R123 both during and immediately after mild heat treatment. Heat preconditioning also caused a slight but insignificant decrease in permeability of R123 and [14C]-sucrose in BBMEC monolayers during mild heat treatment. Because exposure of BBMEC monolayers to mild heat did not affect P-gp expression but slightly affected Hsp70 expression, a heat preconditioning that results in a reinforcement of the BBB other than increased expression of P-gp is suggested. However, heat preconditioning is not sufficient to override the permeation-enhancing effects of mild heat because mild heat caused a significant increase in R123 uptake and permeability of R123 and [14C]-sucrose in both heat-preconditioned and heat-unconditioned cells. Because Hsp70 is known to play a major role in cellular repair and protective mechanisms, our results would imply a relative benign nature of mild heat treatment. Because heating produced by ultrasonic waves can be controlled and localized to a small volume within the tissue, the present results also suggest that USMH could play a pivotal role in the treatment of brain tumors and other brain-related diseases.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Permeability of tritiated water through human cervical and vaginal tissue.

The increased incidence of human immunodeficiency virus infection in women has identified an urgent need to develop a female-controlled method to prevent acquisition of human immunodeficiency virus and other sexually transmitted diseases. Women would apply the product intravaginally before intercourse. Development of such a product requires a better understanding of the permeability characteristics of the tissues with which such products would come into contact. However, limited studies have been performed in this area. In the present study, water permeability of fresh human cervical and vaginal tissue was evaluated. The average apparent permeability coefficient was found to be 8 x 10(-5) cm/s for fresh human cervical tissue and 7 x 10(-5) cm/s for fresh human vaginal tissue. Considering the lack of regularity in obtaining cervical and vaginal tissue from surgical specimens, additional tests were performed to evaluate the effect of freezing on tritiated water permeability. No statistically significant differences were observed in the permeability values obtained when comparing fresh versus frozen tissues.

Administration, Topical↗
PubMed1980

Analysis of models for determining intestinal wall permeabilities.

In determining intestinal wall permeabilities, several mass transport models may be applied to analyze the results from external perfusion experiments. The appropriateness of any given model depends on the applicability of the model assumptions to the experimental system. This report compares several mass transport models with respect to their assumptions and applicability to a particular experimental design. The models are shown to differ in their assumptions regarding convection and diffusion in the perfusing fluid. However, since the wall permeability is an unknown parameter in each model and is estimated from the data, all of the models fit the mass transfer results reasonably well, despite fundamentally different assumptions. However, the determined permeabilities differ. Residence time distribution analysis of the experimental system is more sensitive to the model assumptions. It is shown that, in a particular experimental system, laminar flow in a cylindrical tube is the most appropriate model. The model also has the advantage of implicitly accounting for the convection-diffusion problem in the perfusing fluid. Hence, the diffusion layer thickness is not estimated from the data. With the hydrodynamics defined, the relative permeabilities resulting from the application of the several models to the data can be interpreted. The wall permeability determined in the suggested manner provides an estimate of the limiting assistance under perfect mixing conditions.

Animals↗
PubMed1982

Hydration and percutaneous absorption III: Influences of stripping and scalding on hydration alteration of the permeability of hairless mouse skin to water and n-alkanols.

The influence of hydration on the permeability of stripped and scalded skins of hairless mice was investigated in vitro using water and n-alkanols as test permeants. Irrespective of pretreatment, the permeation rates of water, methanol, and ethanol were unaffected by aqueous immersion of skin sections in a diffusion cell, consistent with earlier data on unprocessed skins. The permeation rates of butanol and hexanol also were insensitive to hydration, differing from earlier studies on normal, intact skin in which both solutes' rates doubled after 10 hr of soaking. Following both pretreatments, the permeability of octanol declined over the first 5-10 hr of maceration, but remained invariant thereafter. The decline was most pronounced for the scalded skins. With untreated skin, octanol permeability initially increased and then declined before assuming a constant value. This study indicates that the barrier properties of the epidermis and dermis are not particularly sensitive to extended hydration except in the case of octanol. Scalding at 60 degrees for 60 sec rapidly hydrates the skin, altering tissue permeability to about the same extent as a 10-hr (or longer) immersion in water at 37 degrees. Octanol's unique hydration profile is explained by locating the origin of permeability decline in tissue beneath the horny exterior of the skin.

Abdomen↗
PubMed1983

Topical vaginal drug delivery I: effect of the estrous cycle on vaginal membrane permeability and diffusivity of vidarabine in mice.

Preliminary studies showed that the vaginal membrane permeability coefficients for vidarabine (9-beta-D-arabinofuranosyladenine) varied widely within a group of mice of the same species and age. This finding prompted an investigation of the influence of the female mouse sexual cycle on the vidarabine permeability. By means of a vaginal smear technique, the sexual cycle, which was approximately 5 days in duration, was divided into five phases. The vaginal membrane permeability of vidarabine was determined during each phase. The results revealed that the permeability coefficients for vidarabine during the diestrus phase (3 X 10(-6)-4 X 10(-5) cm/sec) were 10-100 times higher than those obtained at the early estrus or estrus phases (1-3 X 10(-7) cm/sec). Further permeation studies on membranes at early estrus and estrus were performed by separating the cornified layer from the noncornified portion of the membrane. The low permeability coefficient of vidarabine across the cornified layer (4 X 10(-7) cm/sec) suggests that this layer may be the major diffusion barrier for vidarabine when the drug is topically applied. Collectively, the data also suggest that during estrus a three-layer diffusion model is appropriate, that during early diestrus a single-layer diffusion model may apply, and that during proestrus and postestrus the situations are intermediate and more complicated.

Animals↗
PubMed1993

Permeabilities of alkyl p-aminobenzoates through living skin equivalent and cadaver skin.

The in vitro permeabilities of alkyl p-aminobenzoates through living skin equivalent (LSE) and cadaver skin were compared. Methyl, ethyl, and butyl p-aminobenzoates were used as model compounds. The permeabilities of these compounds through LSE and cadaver skin from an aqueous drug suspension were determined with a flow-through diffusion cell. The permeability coefficients of these esters in LSE were an order of magnitude higher than in cadaver skin. This was primarily because of low resistances offered by the outermost layer (i.e., stratum corneum) of LSE. In the case of cadaver skin, the permeability coefficient increased as the carbon chain length increased, whereas no appreciable change in the permeability coefficients of these esters in LSE was observed. These results clearly suggest that the LSE membrane offered very little resistance as opposed to cadaver skin. Therefore, the LSE membrane may not quantitatively represent a good human skin model for evaluating skin permeation of a drug from topical or transdermal formulations.

Alkylation↗
PubMed1995

Different properties of the paracellular pathway account for the regional small intestinal permeability to the peptide desmopressin.

The regional small intestinal permeability to the vasopressin analogue desmopressin (dDAVP) was further characterized in proximal jejunal and distal (ileocecal) segments of the rat. Administration of the peptide to closed small intestinal loops confirmed the existence of regional absorption differences also in vivo in rats. Thus, the extent of absorption was about 4 times as high from the ileocecal part of the small intestine. The mucosal to serosal passage of dDAVP was studied in small intestinal segments from rats, mounted in Grass diffusion chambers. Increasing the mucosal concentration of dDAVP 100-fold had no effect on permeability coefficients (Papp) and the regional permeability distal:proximal ratio was maintained. Excessive amounts of unlabeled dDAVP to reduce the passage of [3H]dDAVP had no effect either. These findings make the existence of an active, receptor-mediated transport mechanism unlikely, and dDAVP probably does not affect its own transport rate. The higher ileocecal permeability could either be due to the presence of more permeable or dynamic pores in this region, where the epithelial surface area is smaller, or to an increased capacity for paracellular water flux. These results may have relevance for drug transport in the small intestine, where site-specific delivery of drug or enhancing agents may be optimized.

Animals↗
PubMed1995

Development of a combined NMR paramagnetic ion-induced line-broadening/dynamic light scattering method for permeability measurements across lipid bilayer membranes.

A combined method using NMR line-broadening for permeant lifetime determination and dynamic light scattering for vesicle size determination has been developed for the measurement of permeability coefficients of ionizable permeants across phospholipid:cholesterol large unilamellar vesicles. The method has been validated by examining its reproducibility and the influence of various factors that might affect the permeability measurements. The vesicle hydrodynamic diameter was varied between 0.1 and 0.2 micron by extruding multilamellar vesicles through polycarbonate membranes with different pore sizes (0.03-0.2 microns). For these large unilamellar vesicles, the normalized size distributions analyzed by the CONTIN method had standard deviations < 0.36, which led to errors in permeability coefficients < 10% as predicted from a theoretical model developed here. The permeability coefficient for acetic acid is independent of its concentration, vesicle hydrodynamic diameter, the concentration of Pr3+, and ionic strength over the ranges 0.01-0.2 M, 0.1-0.2 microns, 0.004-0.04 M, and 0.03-0.3, respectively. Membrane/water and decane/water partition coefficient measurements of acetic acid indicate that the effects of permeant binding onto the bilayer membrane and self-association are negligible within the permeant concentration range 0.01-0.2 M. The addition of Pr3+ ions induces vesicle fusion with rates increasing with temperature and decreasing with cholesterol concentration in the membranes. While the intravesicular resonance intensity for acetic acid decreases continuously with time due to vesicle fusion under certain conditions, the corresponding line width and chemical shift remain constant over the same period, highlighting an important advantage of this NMR method over those based on detecting net flux in response to a concentration gradient as there is no means in the latter experiments of discerning vesicle leakiness from passive diffusion rates. The effective chemical nature of a dimristoylphosphatidylcholine:cholesterol bilayer barrier microenvironment was explored by comparing the transport of two permeants, D-(-)-mandelic acid and phenylacetic acid, to their relative bulk solvent/water partition coefficients using three reference solvents (n-decane, 1,9-decadiene, and isoamyl alcohol). Using the NMR line-broadening method, the permeability coefficients for these two permeants were determined to be (2.9 +/- 0.4) x 10(-4) cm/s and (3.9 +/- 0.7) x 10(-2) cm/s, respectively, at 294 K and Xchol = 0.3. The incremental free energy of transport for the additional OH group in D-(-)-mandelic acid, delta delta G0 = +2.9 kcal/mol, resembles most closely that for the transfer of this group from water to 1,9-decadiene, suggesting that the barrier domain resides in the acyl chain region and is slightly more polar/polarizable than a saturated hydrocarbon, possibly due to the presence of a double bond in cholesterol and/or the proximity of the barrier domain to the hydrophilic interface.

Acetates↗
PubMed1985

The effects of hyperthermia on vascular permeability in experimental liver metastasis.

The effects of hyperthermia on vascular permeability in Walker carcinosarcomas and host liver tissue were studied in Sprague-Dawley rats. A quantitative Evans blue technique was used to measure permeability. With tumors heated to 40 degrees C, a nontherapeutic level, no changes in tumor vascular permeability as compared to control levels were noted. However, with tumors heated to 43 degrees C, within the therapeutic range of hyperthermia, significant rises in tumor vascular permeability occurred. Permeability was increased at both time periods studied, 30 minutes and 6 hours after hyperthermia and injection of Evans blue. These changes are similar to those seen after physical damage from freeze-thaw. It is likely that alterations in tumor microcirculation play a role in the therapeutic effect of intense hyperthermia.

Animals↗