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At least 19 recordsLinked to original sources
PubMed1955

A quantitative electrochemical theory of the electrolyte permeability of mosaic membranes composed of selectively anion-permeable and selectively cation-permeable parts, and its experimental verification. II. A quantitative test of the theory in model systems which do not involve the use of auxiliary electrodes.

The theory of the electrolyte permeability of mosaic membranes composed of ideally anion-selective and ideally cation-selective parts in juxtaposition is tested in a model which consists of an all-electrolytic cyclic arrangement of four component parts: dilute solution/anion-selective membrane/concentrated solution/cation-selective membrane/dilute solution. In this system cations move from the concentrated to the dilute solution across the cation-selective membrane and an equivalent number of anions move through the anion-selective membrane. This movement of ions corresponds to a flow of current in the system. According to the theory, the number of equivalents of electrolyte which penetrate in any given time across the membranes must be identical with the number of faradays of electricity which flow during the same period. The system is essentially a combination of two menbrane-concentration cells arranged in series in a short-circuited state without the presence of electrodes. Experimentally the magnitude of the current was determined by measuring with probe electrodes the potential across an element of the circuit whose resistance was known and constant. The number of faradays of electricity (determined from time-current data) flowing in the system during a measured time was compared with the analytically determined number of equivalents of electrolyte which moved across the membranes during the same period. In a variety of experimental systems the two values show a 1:1 ratio with a mean deviation of +/- 1.8 per cent.

Anions↗
PubMed1999

Role of P-glycoprotein-mediated secretion in absorptive drug permeability: An approach using passive membrane permeability and affinity to P-glycoprotein.

It has been shown in vivo and in vitro that P-glycoprotein (P-gp) may be able to influence the permeability of its substrates across biological membranes. However, the quantitative contribution of the secretion process mediated by P-gp on the overall permeability of membranes has not been determined yet. In particular, observations need to be clarified in which substrates showing high affinity to P-glycoprotein, e.g., verapamil, apparently do not seem to be greatly influenced by P-gp in their permeability and consequently also with respect to their extent of GI-absorption after oral administration, whereas weaker substrates of P-gp, e.g., talinolol, have clearly shown P-gp-related absorption phenomena such as nonlinear intestinal permeability and bioavailability. Experiments with Caco-2 cell monolayers and mathematical simulations based on a mechanistic permeation model should aid in clarifying the underlying mechanism for these observations and quantifying the influence of passive membrane permeability and affinity to P-gp to the overall transmembrane drug flux. In addition, the concentration range of drug at which P-glycoprotein-mediated transport across the biological membrane is relevant should be examined. The permeability of various drugs in Caco-2 monolayers was determined experimentally and modeled using a combination of passive absorptive membrane permeability and a Michaelis-Menten-type transport process in the secretory direction. The passive permeabilities were experimentally obtained for the apical and basolateral membrane by efflux experiments using Caco-2 monolayers in the presence of a P-gp inhibitor. The Michaelis-Menten parameters were determined by a newly developed radioligand-binding assay for the quantification of drug affinity to P-gp. The model was able to accurately simulate the permeability of P-glycoprotein substrates, with differing passive membrane permeabilities and P-glycoprotein affinities. Using the outlined approach, permeability vs donor-concentration profiles were calculated, and the relative contribution of passive and active transport processes to the overall membrane permeability was evaluated. A model is presented to quantitatively describe and predict direction-dependent drug fluxes in Caco-2 monolayers by knowing the affinity of a compound to the exsorptive transporter P-gp and its passive membrane permeability. It was shown that a combination of high P-gp affinity with good passive membrane permeability, e.g., in the case of verapamil, will readily compensate for the P-gp-mediated reduction of intestinal permeability, resulting in a narrow range in which the permeability depends on the apical drug concentration. On the other hand, the permeability of compounds with low passive membrane permeability (e. g., talinolol) might be affected over a wide concentration range despite low affinity to P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Relationship between permeability status of the blood-brain barrier and in vitro permeability coefficient of a drug.

OBJECTIVE: The aim was to test the hypothesis that the assessment of basal and drug-induced changes in permeability of the blood-brain barrier (BBB) during in vitro drug transport assays is essential for an accurate estimation of the permeability coefficient of a drug. METHODS: An in vitro BBB model was used, comprising of brain capillary endothelial cells (BCEC) and astrocytes co-cultured on semi-permeable filter inserts. Experiments were performed under control and challenged experimental circumstances, induced to simulate drug effects. The apparent BBB permeability coefficient for two markers for paracellular drug transport, sodium fluorescein (P(app,FLU), M(w) 376 Da) and FITC-labeled dextran (P(app,FD4), M(w) 4 kDa), was determined. Transendothelial electrical resistance (TEER) was used to quantify basal and (simulated) drug-induced changes in permeability of the in vitro BBB. The relationship between P(app) and TEER was determined. Drug effects were simulated by exposure to physiologically active endogenous and exogenous substances (i.e., histamine, deferroxamine mesylate, adrenaline, noradrenaline, bradykinin, vinblastine, sodium nitroprusside and lipopolysaccharide). RESULTS: P(app,FLU) and P(app,FD4) in control experiments varied from 1.6 up to 17.6 (10(-6)cm/s) and 0.3 up to 7. 3 (10(-6)cm/s), respectively; while for individual filters P(app, FLU) was 4 times higher than P(app,FD4) (R(2)=0.97). As long as TEER remained above 131.Omega cm(2) for FLU or 122.Omega cm(2) for FD4 during the transport assay, P(app) remained independent from the basal permeability of the in vitro BBB. Below these TEER values, P(app) increased exponentially. This nonlinear relationship between basal BBB permeability and P(app) was described by a one-phase exponential decay model. From this model the BBB permeability status independent permeability coefficients for FLU and FD4 (P(FLU) and P(FD4)) were estimated to be 2.2+/-0.1 and 0.48+/-0.03 (10(-6)cm/s), respectively. In the experimentally challenged experiments, a reliable indication for P(FLU) and P(FD4) could be estimated only after the (simulated) drug-induced change in BBB permeability was taken into account. CONCLUSIONS: The assessment of basal BBB permeability status during drug transport assays was essential for an accurate estimation of the in vitro permeability coefficient of a drug. To accurately extrapolate the in vitro permeability coefficient of a drug to the in vivo situation, it is essential that drug-induced changes in the in vitro BBB permeability during the drug transport assay are determined.

Animals↗
PubMed1994

Intestinal permeability of ophthalmic beta-blockers for predicting ocular permeability.

The purpose of this study was to investigate the intestinal permeability of ophthalmic beta-blockers and evaluate the utility of intestinal membrane for predicting the ocular permeability. The penetrations of beta-blockers were measured across the isolated jejunum and colon of the albino rabbit using a two-chamber glass diffusion cell. beta-Blockers tested include atenolol, carteolol, tilisolol, timolol, and befunolol. Colonic membrane showed lower permeability of hydrophilic drugs than jejunal membrane. Scraping the entire cell monolayer of jejunum increased the drug permeability. There was a significant correlation between colonic permeability coefficients and lipophilicities of beta-blockers. The permeability coefficients through jejunum and scraped jejunum were not susceptible to drug lipophilicities. Jejunum, scraped jejunum, and colon showed permeability coefficients almost equal to those of sclera, conjunctiva, and cornea, respectively. There was a significant correlation between permeability coefficients through colon and cornea. These results indicate that the steady-state permeability of ophthalmic beta-blockers through ocular membranes may be predicted by measuring the permeability through certain intestinal membranes. However, the analyses of intestinal permeability using Fick's equation showed the functional difference of intestinal permeability from ocular permeability of ophthalmic beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1998

Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins.

Vascular permeability factor/vascular endothelial growth factor stimulates endothelial proliferation, angiogenesis, and increased vascular permeability in vivo. We investigated mechanisms of vascular permeability factor-mediated endothelial monolayer permeability changes in vitro. [14C]Albumin flux across endothelial monolayers was measured following a 90-min exposure to vascular permeability factor (660 pM). Vascular permeability factor increased albumin flux to 3.4 times that of control albumin flux. Endothelial monolayers were also incubated for 90 min with vascular permeability factor plus Gö6976 (10 nM), staurosporine (1 microM), wortmannin (10 nM), AG126 (1 and 2.67 microM), and PD98059 (20 microM). Vascular permeability factor-mediated permeability was not blocked by Gö6976, an antagonist of "classical" protein kinase C, staurosporine, a pan-protein kinase C antagonist, nor wortmannin, a PI3-kinase blocker, but was blocked by incubation with AG126 or PD98059, inhibitors of mitogen-activated protein kinase activation. Immunofluorescent staining of the junctional proteins VE-cadherin and occludin showed a loss of these proteins from the endothelial junction that was prevented by co-incubation with AG126 or PD98059. These data demonstrate that vascular permeability factor increases albumin permeability across endothelial monolayers in vitro and suggests that permeability increases through rearrangement of endothelial junctional proteins involving the mitogen-activated protein kinase signal transduction pathway.

Androstadienes↗
PubMedDate not supplied

Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacyclin.

BACKGROUND: Vascular endothelial growth factor (VEGF), an endothelial cell mitogen that promotes angiogenesis, was initially identified as a vascular permeability factor (VPF). Abundant evidence suggests that angiogenesis is preceded and/or accompanied by enhanced microvascular permeability. The mechanism by which VEGF/VPF increases vascular permeability (VP), however, has remained enigmatic. Accordingly, we used an in vivo assay of VP (Miles assay) to study the putative mediators of VEGF/VPF-induced permeability. METHODS AND RESULTS: VEGF/VPF and positive controls (platelet-activating factor [PAF], histamine, and bradykinin) all increased vascular permeability. Prior administration of the tyrosine kinase inhibitors genistein or herbimycin A prevented VEGF/VPF-induced permeability. Placenta growth factor, which binds to Flt-1/VEGF-R1 but not Flk-1/KDR/VEGF-R2 receptor tyrosine kinase, failed to increase permeability. Other growth factors such as basic fibroblast growth factor (FGF), acidic FGF, platelet-derived growth factor-BB, transforming growth factor-beta, scatter factor, and granulocyte macrophage-colony stimulating factor (8 to 128 ng) failed to increase permeability. VEGF/VPF-induced permeability was significantly attenuated by the nitric oxide (NO) synthase inhibitors N(omega)-nitro-L-arginine (10 mg/kg) or N(omega)-nitro-L-arginine methyl ester (20 mg/kg) and the cyclooxygenase inhibitor indomethacin (5 mg/kg). The inactive enantiomer N(omega)-nitro-D-arginine methyl ester (20 mg/kg) did not inhibit VEGF/VPF-induced permeability. In vitro studies confirmed that VEGF/VPF stimulates synthesis of NO and prostaglandin metabolites in microvascular endothelial cells. Finally, NO donors and the prostacyclin analogue taprostene administered together but not alone reproduced the increase in permeability observed with VEGF/VPF. CONCLUSIONS: These results implicate NO and prostacyclin produced by the interaction of VEGF/VPF with its Flk-1/KDR/VEGF-R2 receptor as mediators of VEGF/VPF-induced vascular permeability. Moreover, this property appears unique to VEGF/VPF among angiogenic cytokines.

Animals↗
PubMed1982

Permeability of thermally damaged skin v: permeability over the course of maturation of a deep partial-thickness wound.

The permeability of eschar is an important factor governing rational approaches to topical control of burn wound sepsis. Previous work has shown the burn wound to have a highly variable permeability immediately after burning depending on the manner of burning. But the burn is also a dynamic wound and its physical state changes during the process of maturation. The present studies are an early attempt to characterize wound permeability as a function of maturation. Hairless mice were burned dorsally for 15 seconds on a metal surface maintained at 80 degree C. The time and temperature conditions were chosen to effect a deep partial-thickness to full-thickness injury on the animal. Mice were sacrificed daily post burn over a 2-week period and the permeabilities of 3H-methanol and 14C-butanol through the excised eschar were measured. Te eschar permeability coefficients were directly compared to permeability coefficients for the same compounds found with abdominal skin sections taken concurrently from each animal. It was observed that the branding initially caused a 50 per cent increase in the permeability of methanol and a 300-400 per cent increase in the permeability of maturation. Thereafter permeabilities tended to increase, gradually at first, but accelerating to a maximum which was observed at approximately 10 days. At the maximum, methanol's permeability was 20 times and butanol's 12 times their normal values. For both compounds permeability of eschar decreased past the maximum until termination of the studies at 14 days.

Administration, Topical↗
PubMed2001

Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: implications for the permeability of compromised skin.

The permeability of compromised skin barrier was investigated in vitro using acetone-disrupted hairless mouse skin as a model membrane. The effect of compound lipophilicity was studied using sucrose, caffeine, hydrocortisone, estradiol, and progesterone as model compounds. The results demonstrated that permeability barrier disruption by acetone treatment significantly enhanced the permeability of the skin to both hydrophilic and amphipathic compounds, including sucrose, caffeine and hydrocortisone. This effect was more prominent with caffeine and hydrocortisone at different transepidermal water loss (TEWL) levels. Acetone treatment, however, didn't appear to alter the percutaneous penetration of highly lipophilic compounds, such as estradiol and progesterone. The characteristics of skin permeability were described by parabolic relationships between log P(WS) (permeability coefficient of whole skin) and log K(O/W) (octanol/water partition coefficient) at different degrees of permeability barrier disruption. The optimal log K(O/W) of compounds for skin penetration appeared to decrease with an increase in TEWL levels. The maximal permeability achieved was similar through skin displaying different TEWL levels. In an attempt to explore the underlying mechanisms for the changes in skin permeability, the stratum corneum/normal saline partition coefficients of water, caffeine, and hydrocortisone either decreased or remained unaffected with an increase in TEWL. Electron microscopic examinations have revealed reductions in stratum corneum lipid content and alterations in intercellular membrane structures as a result of acetone treatment, whereas negligible changes in the number of horny layers were observed by safranin staining of the stratum corneum. We have concluded that the enhancement in skin permeability to both hydrophilic and amphipathic compounds by acetone treatment arose mainly because of the increase in stratum corneum diffusivity at higher TEWL levels. The results imply the possibility of using both TEWL and drug lipophilicity to predict alterations in skin permeability and hence the dose adjustment of topically applied medication for patients with impaired skin barrier function.

Acetone↗
PubMed1996

Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor.

Brain tumor-associated cerebral edema arises because tumor capillaries lack normal blood-brain barrier function; vascular permeability factor (VPF, also known as vascular endothelial growth factor, VEGF) is a likely mediator of this phenomenon. Clinically, dexamethasone reduces brain tumor-associated vascular permeability through poorly understood mechanisms. Our goals were to determine if suppression of permeability by dexamethasone might involve inhibition of VPF action or expression, and if dexamethasone effects in this setting are mediated by the glucocorticoid receptor (GR). In two rat models of permeability (peripheral vascular permeability induced by intradermal injection of 9L glioma cell-conditioned medium or purified VPF, and intracerebral vascular permeability induced by implanted 9L glioma), dexamethasone suppressed permeability in a dose-dependent manner. Since 80% of the permeability-inducing activity in 9L-conditioned medium was removed by anti-VPF antibodies, we examined dexamethasone effects of VPF expression in 9L cells. Dexamethasone inhibited FCS- and PDGF-dependent induction of VPF expression. At all levels (intradermal, intracranial, and cell culture), dexamethasone effects were reversed by the GR antagonist mifepristone (RU486). Dexamethasone may decrease brain tumor-associated vascular permeability by two GR-dependent mechanisms: reduction of the response of the vasculature to tumor-derived permeability factors (including VPF), and reduction of VPF expression by tumor cells.

Animals↗
PubMed1998

Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition.

Some compounds are known to induce solute-nonselective permeability of the inner mitochondrial membrane (IMM) in Ca2+-loaded mitochondria. Existing data suggest that this process, following the opening of a mitochondrial permeability transition pore, is preceded by different solute-selective permeable states of IMM. At pH 7, for instance, the K0.5 for Ca2+-induced pore opening is 16 microM, a value 80-fold above a therapeutically relevant shift of intracellular Ca2+ during ischemia in vivo. The present work shows that in the absence of Ca2+, phenylarsine oxide and tetraalkyl thiuram disulfides (TDs) are able to induce a complex sequence of IMM permeability changes. At first, these agents activated an electrogenic K+ influx into the mitochondria. This K+-specific pathway had K0.5 = 35 mM for K+ and was inhibited by bromsulfalein with Ki = 2.5 microM. The inhibitors of mitochondrial KATP channel, ATP and glibenclamide, did not inhibit K+ transport via this pathway. Moreover, 50 microM glibenclamide induced by itself K+ influx into the mitochondria. After the increase in K+ permeability of IMM, mitochondria become increasingly permeable to protons. Mechanisms of H+ leak and nonselective permeability increase could also be different depending on the type of mitochondrial permeability transition (MPT) inducer. Thus, permeabilization of mitochondria induced by phenylarsine oxide was fully prevented by ADP and/or cyclosporin A, whereas TD-induced membrane alterations were insensitive toward these inhibitors. It is suggested that MPT in vivo leading to irreversible apoptosis is irrelevant in reversible ischemia/reperfusion injury.

Acids↗
PubMed1991

Glycosylation is essential for efficient secretion but not for permeability-enhancing activity of vascular permeability factor (vascular endothelial growth factor).

The hyperpermeability of the microvasculature supplying solid tumors is largely attributable to a heterodimeric Mr 34,000-43,000 tumor-secreted protein, vascular permeability factor. Upon reduction, the vascular permeability factor secreted by line 10 tumor cells is resolved by SDS-PAGE into 3 discrete bands of Mr 24,000, 19,500, and 15,000. We demonstrate here that line 10 vascular permeability factor is an N-linked glycoprotein. Nonglycosylated vascular permeability factor migrates on reduced SDS-PAGE as two bands of Mr 20,000 and 15,000. Pulse-chase studies demonstrated that all three chains of native vascular permeability factor were secreted rapidly following synthesis and at equal rates, with a cellular half-retention time of approximately 37 min. When glycosylation was prevented by tunicamycin, individual bands of nonglycosylated vascular permeability factor were also secreted at equivalent rates, but much more slowly (approximately 60 min) than native glycoprotein. Both glycosylated and nonglycosylated forms of vascular permeability factor were equally potent at increasing dermal vessel permeability.

Animals↗
PubMed2002

Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability.

Although water, small nonelectrolytes, and gases are freely permeable through most biological membranes, apical membranes of certain barrier epithelia exhibit extremely low permeabilities to these substances. The role of integral membrane proteins in this barrier function has been unclear. To study this problem, we have ablated the mouse gene encoding uroplakin III (UPIII), one of the major protein subunits in urothelial apical membranes, and measured the permeabilities of these membranes. Ablation of the UPIII gene greatly diminishes the amounts of uroplakins on the apical urothelial membrane (Hu P, Deng FM, Liang FX, Hu CM, Auerbach AB, Shapiro E, Wu XR, Kachar B, and Sun TT. J Cell Biol 151: 961-972, 2000). Our results indicate that normal mouse urothelium exhibits high transepithelial resistance and low urea and water permeabilities. The UPIII-deficient urothelium exhibits a normal transepithelial resistance (normal 2,024 +/- 122, knockout 2,322 +/- 114 Omega. cm(2); P > 0.5). However, the UPIII-deficient apical membrane has a significantly elevated water permeability (normal 0.91 +/- 0.06, knockout 1.83 +/- 0.14 cm/s x 10(-5); P < 0.05). The urea permeability of the UPIII-deficient membrane also increased, although to a lesser extent (normal 2.22 +/- 0.24, knockout 2.93 +/- 0.31 cm/s x 10(-6); P = 0.12). These results indicate that reduced targeting of uroplakins to the apical membrane does not significantly alter the tight junctional barrier but does double the water permeability. We provide the first demonstration that integral membrane proteins contribute to the apical membrane permeability barrier function of urothelium.

Animals↗
PubMed1996

Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody.

The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber. The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 micrograms/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection. Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment. However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody. In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors. These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/ VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression-i.e., blocking the interactions between VEFG/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which may block the passage of blood elements and thus lead to vascular regression.

Animals↗
PubMed1985

The permeability of skin and oral mucosa to water and horseradish peroxidase as related to the thickness of the permeability barrier.

The permeability of porcine skin and keratinized and nonkeratinized oral mucosa to tritium-labeled water and horseradish peroxidase (HRPO) was determined using perfusion chambers. Small blocks from each tissue were also incubated with HRPO and the extent of penetration visualized microscopically; this enabled measurements to be made of the thickness of the permeability barrier to this water-soluble tracer. Results obtained after inverting the oral mucosa in the chambers or adding metabolic inhibitors indicated that both compounds diffuse across the tissue. The permeability constants derived directly in the study showed that skin was less permeable than oral mucosa and that the floor of the mouth was significantly more permeable than all other regions. When these constants were normalized in terms of a standard permeability barrier thickness and the different tissues compared, the values obtained for skin were again less than those of the oral regions but, of these, the buccal mucosa was significantly higher. The difference in permeability between epidermis and keratinized oral epithelium may be due to differences in the volume density of membrane-coating granules known to exist between the tissues; differences between the oral mucosal regions may reflect differences in the nature of the intercellular barrier material.

Animals↗
PubMed2002

Induction of permeability across endothelial cell monolayers by tumor necrosis factor (TNF) occurs via a tissue factor-dependent mechanism: relationship between the procoagulant and permeability effects of TNF.

Tumor necrosis factor (TNF) has marked effects on permeability and procoagulant activity on tumor-associated neovasculature when used in isolation perfusion, the latter effect primarily mediated via induction of cell surface expression of tissue factor (TF) on endothelial tissue. However, the cellular events that result in rapid alterations in endothelial cell (EC) permeability after intravascular TNF administration in isolation perfusion are not well characterized. We demonstrate that short exposure intervals to TNF induces TF expression on ECs but has no effect on permeability as assessed by flux of Evans blue-bound albumin across confluent EC monolayers using a 2-compartment model under basal culture conditions. However, a rapid and significant increase in EC permeability occurred with TNF in the presence of factor VIII-deficient plasma. Permeability was induced only with luminal versus abluminal TNF exposure and was blocked by antithrombin III, TF pathway inhibitor, or anti-TF antibody cotreatment. These data indicate that EC surface expression of TF and extrinsic clotting factors are critical in augmenting capillary leak following intravascular TNF administration. Alterations in permeability were associated with intercellular gap formation at sites of down-regulation of vascular endothelial (VE)-cadherin expression, the primary endothelial intercellular adhesion molecule, and intracellular contraction and alignment of F-actin cytoskeletal elements. Rapid induction of TF by TNF may be the primary EC response that results in alterations in permeability and procoagulant activity observed following intravascular TNF administration in isolation perfusion.

Antibodies, Monoclonal↗
PubMed1984

Membrane permeability of secondary hydatid cysts of Echinococcus granulosus. Determination of the water diffusional and osmotic permeability coefficients through a syncytial membrane.

Diffusional (Pw) and osmotic (Pf) water permeability coefficients were determined for the syncytial epithelium of larval Echinococcus granulosus. Pw was calculated from simultaneous influx measurements of tritiated water and n-[14C]butanol through the hydatid cyst wall. The total diffusional water permeability coefficient, P'w, was found to be 2.2 X 10(-4) cm s-1; which is similar to that previously reported by Rotunno et al. (1974, J. Parasitol. 60, 13-620). Nevertheless, when P'f is corrected for the unstirred water layer effects, a Pw value of 6.2 X 10(-4) cm s-1 is obtained. Thus, the unstirred water layer effects have a very important contribution to P'w. Total steady state osmotic permeability coefficient, P'f, was bound to be about 15 X 10(-4) cm s-1 and it is scarcely affected by those mechanisms that tend to distort the evaluation of Pf. The experimentally determined osmotic coefficient differs from the corrected Pf by only 6%. The Pf/Pw ratio was found to be 2.4. The present study clearly confirms that syncytial membranes can be highly permeable to water, in spite of the fact that they lack tight junctions. Thus, water permeability through epithelial syncytium must be exclusively controlled by the permeability of the apical and/or basocellular membranes.

Animals↗
PubMed2004

Relationships between structure and high-throughput screening permeability of peptide derivatives and related compounds with artificial membranes: application to prediction of Caco-2 cell permeability.

To evaluate absorption of compounds across the membrane via a transcellular route, the permeability of peptide derivatives and related compounds was measured by the parallel artificial membrane permeation assay (PAMPA). The permeability coefficients by PAMPA were analyzed quantitatively using classical QSAR and Volsurf approaches with the physicochemical parameters. The results from both approaches showed that hydrogen bonding ability of molecules in addition to hydrophobicity at a particular pH were significant in determining variations in PAMPA permeability coefficients. The relationship between Caco-2 cell permeability and artificial lipid membrane permeability was then determined. The compounds were sorted according to their absorption pathway in the plot of the Caco-2 cell and PAMPA permeability coefficients.

Caco-2 Cells↗