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Tumor-secreted vascular permeability factor/vascular endothelial growth factor influences photosensitizer uptake.

The role of vascular permeability in the preferential accumulation of photosensitizers in tumor tissue was investigated. Two murine tumors [experimental mammary tumor carcinoma (EMT-6) and methylcholanthrene-induced rhabdomyosarcoma (M1S)] and a human bladder carcinoma (EJ) were grown s.c. on the flank in athymic nude mice and analyzed for in vivo vessel permeability, vascular permeability factor (VPF) secretion, and accumulation of the photosensitizer, chloroaluminum sulfonated phthalocyanine. In vivo tumor vessel permeability and vascular volume were quantitated by measuring Evans blue extravasation and accumulation of a high molecular weight fluoresceinated dextran, respectively. VPF was isolated from serum-free tumor cell conditioned medium using heparin-Sepharose affinity chromatography. Dot and Western blots stained with anti-VPF antiserum positively identified VPF in samples from each tumor. Chloroaluminum sulfonated phthalocyanine pharmacokinetics in tumor-bearing mice were measured using a fiber-based spectrofluorometer. In vivo vessel permeability was found to be greatest in M1S tumors, next in EMT-6 tumors and finally in EJ tumors. Consistent with in vivo data, M1S and EMT-6 tumor cells in culture secrete significantly more VPF than EJ tumor cells. Chloroaluminum sulfonated phthalocyanine accumulation was approximately 2 times greater in M1S and EMT-6 tumors compared to EJ tumors. Our data present evidence that photosensitizer accumulation can be correlated to in vivo tumor vessel permeability and VPF secretion of that tumor. Taken together, the data support the hypothesis that vascular permeability differences among tumors play a significant role in the uptake and retention of photodynamic agents.

Animals↗

Phorbol ester modulation of rabbit corneal endothelial permeability.

PURPOSE: Phorbol esters have been shown to have a profound influence on cellular activity in many cell types. The purpose of this study was to examine the influence of phorbol esters on the function and structure of corneal endothelial cells. METHODS: Corneas were placed under a specular microscope, and the endothelium was superfused with glutathione bicarbonate Ringer's solution (GBR); with GBR and 10 nM, 100 nM, or 1 microM 4 beta-phorbol 12-myristate 13-acetate (PMA); or with 100 nM 4-alpha-PMA. Corneal swelling curves were generated, and endothelial permeability was determined. Corneal endothelial structure was examined with a scanning electron microscope. RESULTS: Significant increases in swelling and endothelial permeability were found in corneas perfused with 100 nM PMA versus that observed in controls (swelling rate = 26 microns/hr versus 6.9 microns/hr; permeability = 6 x 10(-4) cm/min versus 3.4 x 10(-4) cm/min) and in corneas receiving 1 microM PMA versus that in controls (swelling rate = 26.3 microns/hr versus 0.12 micron/hr; permeability = 6.9 x 10(-4) cm/min versus 4.9 x 10(-4) cm/min). Application of 10 nM PMA did not significantly alter either parameter. Study with transmission electron microscope demonstrated significant morphologic changes in cells perfused with all concentrations of PMA. Corneas perfused with 100 nM 4-alpha-PMA versus 100 nM PMA had significantly lower slope and permeability values (swelling rate = 5.9 microns/hr versus 25.1 microns/hr; permeability = 3 x 10(-4) cm/min versus 6.7 x 10(-4) cm/min). CONCLUSIONS: Phorbol esters are detrimental for corneal endothelial function, creating significant corneal swelling, increases in endothelial permeability, and changes in endothelial cell structure. This effect appears to be mediated through a protein kinase C pathway.

Animals↗

Modulation of the permeability of H2 receptor antagonists cimetidine and ranitidine by P-glycoprotein in rat intestine and the human colonic cell line Caco-2.

The influence of secretory transporters on intestinal permeability characteristics of the H2 receptor antagonists ranitidine and cimetidine was studied in Caco-2 monolayers and rat intestinal mucosa mounted in Ussing chambers. Both drugs exhibited vectorial transport across rat ileum with significantly greater (2-4-fold) permeability in the serosal-to-mucosal than the mucosal-to-serosal direction, indicative of net mucosal secretion. Mucosal ranitidine secretion was also observed in rat distal colon, although to a lesser degree. Ileal ranitidine secretion was concentration dependent and significantly reduced by the P-glycoprotein (P-gp) substrates verapamil and cyclosporin. In contrast, probenicid, an inhibitor of the multidrug-related protein, had no effect on ranitidine permeability. The paracellular marker mannitol showed no evidence of asymmetric permeability or sensitivity to P-gp inhibitors. Significant expression of P-gp protein in rat intestinal epithelial cells was confirmed by immunoblotting. Caco-2 monolayers, which overexpress P-gp, also showed asymmetric permeability of ranitidine and cimetidine. In this model, ranitidine permeability in the mucosal-to-serosal direction decreased by approximately 95% as monolayer resistance increased from 150 to 500 Omega/cm2, indicating a primarily paracellular route of transport. However, serosal-to-mucosal permeability was insensitive to resistance changes, consistent with a primarily transcellular route in this direction. These data indicate that ranitidine and cimetidine can act as substrates for intestinal P-gp and suggest that the balance between absorptive and secretory mechanisms as a factor in determining intestinal absorption needs to be a routine consideration even for compounds expected to have a predominantly paracellular route of absorption.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

VEGF-induced permeability increase is mediated by caveolae.

PURPOSE: To determine the cellular route by which vascular endothelial cell growth factor (VEGF) increases the permeability of cultured retinal endothelial cells and to test whether nitric oxide (NO) production by NO synthase (NOS) is involved in signaling VEGF's permeability enhancing effects. METHODS: Cultured bovine retinal microvascular endothelial (BRE) cells were used for bioassay of permeability function and its ultrastructural correlates. The role of NOS activity in VEGF's permeability enhancing effects was tested with the use of an NOS inhibitor. Because activity of endothelial NOS (eNOS) is thought to be regulated by its interaction with the caveolar protein caveolin-1, structural relationships between eNOS, caveolin-1, and the VEGF receptor FIk-1/KDR were analyzed with double-label immunofluorescence and cell fractionation procedures. RESULTS: Bioassays of permeability function and structure demonstrated that VEGF increases permeability of cultured BRE cells by an NOS-dependent process of transcytotic transport in caveolae. Double-label analysis showed that Flk-1/KDR and eNOS colocalize with caveolin-1 in plasma membrane caveolae. Cell fractionation and immunoblot analysis confirmed this effect. Densitometry showed that Flk-1/KDR, eNOS, and caveolin-1 levels were highest in caveolar fractions. Similar results were obtained in studies with bovine aortic endothelial cells. CONCLUSIONS: These results demonstrate that VEGF increases endothelial cell permeability by an eNOS-dependent mechanism of transcytosis in caveolae. Localization of Flk-1/KDR and eNOS with caveolin-1 suggests that VEGF signaling occurs within the caveolar compartment.

Actins↗

The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeability.

The role of changes in blood-brain barrier permeability in the pathogenesis of hepatic encephalopathy remains uncertain. To test the hypothesis that brain microvessel permeability is nonselectively increased in hepatic encephalopathy we measured the blood-brain barrier permeability-surface area product in rats with acute liver failure induced by intraperitoneal injection of galactosamine. The permeability-surface area products to the diffusion-limited tracers, sucrose and methylaminoisobutyric acid, were determined as a measure of blood-brain barrier permeability. Animals were examined 24, 36 and 42 hr after injection, at times when they were stuporous, but not comatose. No significant elevations of the permeability-surface area products for either compound were detected in clinically affected experimental animals when compared to controls. Our results indicate there is no generalized increase in brain vascular permeability during hepatic insufficiency in precomatose animals.

Animals↗

The effect of age on pulmonary epithelial permeability in unanesthetized lambs.

Pulmonary epithelial permeability was measured 1) in unanesthetized sheep, and 2) longitudinally in growing lambs. Awake sheep were intubated and a solution of 51Cr-ethylenediaminetetraacetic acid and 125I-antipyrine was instilled in the intrathoracic trachea via the nasotracheal tube. Arterial blood was drawn 1-25 minutes after the instillation. The ratios of the counts of 51Cr to 125I at 7, 10, and 13 min were calculated and averaged for each animal. Data from six adult sheep showed that the mean +/- SE of the permeability ratio was 0.012 +/- 0.003 and was reproducible over three months. When measured twice within two hours, the second ratio was significantly higher than the first (0.021 +/- 0.004 vs. 0.011 +/- 0.003, n = 6, P less than 0.05). One hour of general anesthesia with methoxyflurane did not alter the permeability ratio significantly. Ten lambs were studied longitudinally 10 hours and 5, 10, 20, and 30 days after delivery. Within the first 24 hours of life the permeability ratio was 0.035 +/- 0.007, significantly greater (P less than 0.05) than the adult value. At five days there was no significant difference between lambs and adult sheep. Throughout the first month of life, the permeability ratio in lambs remained at at the adult level. In summary, 1) pulmonary epithelial permeability can be assessed in awake lambs and adult sheep, 2) the permeability ratio is reproducible for three months but should not be measured within two hours, 3) newborn lambs have a significantly higher ratio than older lambs or adult sheep, and 4) the ratio reaches the adult level within five days after birth.

Aging↗

Hageman factor dependent pathway in local vascular permeability enhancement.

The possibility of an involvement of the kallikrein-kinin system in increasing vascular permeability induced by intradermal injection of the guinea pig activated Hageman factor (beta HFa) was examined. In vitro system, the kinin generation was observed in guinea pig plasma when the plasma was incubated with beta HFa. This kinin generation was dependent upon the dose of beta HFa added and upon the presence of plasma prekallikrein, since 97 percent of the kinin release was diminished by removing the prekallikrein in plasma by treatment with anti-prekallikrein antibody. These results suggested that the Hageman factor-kallikrein-kinin cascade in guinea pig was similar to those in human and bovine plasma. In the permeability experiment in vivo, a simultaneous injection of soybean trypsin inhibitor (10(-6) M), which is the inhibitor of guinea pig plasma kallikrein, inhibited the permeability response to beta HFa by more than 90 percent. The permeability response to beta HFa was attenuated 5 fold in animals depleted of the circulating plasma prekallikrein by intraarterial antibody administration. These results indicated the participation of plasma prekallikrein in the permeability reaction to beta HFa. A simultaneous injection of a kinin destructive enzyme, carboxypeptidase B, diminished the permeability reaction to beta HFa, without any inhibition of the amidolytic activity of beta HFa or plasma kallikrein. A simultaneous injection of an inhibitor of a kinin destructive enzyme (kininase II), SQ 20,881(Glu-Tyr-Pro-Arg-Pro-Gln-Ile-Pro-Pro-OH), augmented the permeability reaction to beta HFa 10 fold, without any effect on the amidolytic activity of beta HFa or plasma kallikrein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intercellular communication and the control of growth: X. Alteration of junctional permeability by the src gene. A study with temperature-sensitive mutant Rous sarcoma virus.

To study changes of junctional membrane permeability associated with transformation, the junctions and the nonjunctional membranes of quail embryo-, chick embryo- and mouse-3T3 cell cultures, infected with temperature-sensitive mutant Rous sarcoma virus, were probed with fluorescent-labelled glutamate. Junctional permeability fell in the transformed state. In the quail cells, the fall was detectable within 25 min of shifting the temperature down to the level (permissive) at which tyrosine-phosphorylation by the viral src gene product is expressed. This reduction of junctional permeability is one of the earliest manifestations of viral transformation. Normal permeability was restored within 30 min of raising the temperature to the nonpermissive level, a reversibility that could be displayed several times during the span of a cell generation. The reversal seems to reflect a reopening of cell-to-cell channels rather than a synthesis of new ones; it is not blocked by protein-synthesis inhibition. Treatments with cyclic AMP and phosphodiesterase inhibitor or with forskolin, which stimulate serine and threonine phosphorylation--the type of phosphorylation on which normal junctional permeability depends (Wiener & Loewenstein, 1983, Nature 305:433)--did not abolish, in general, the junctional effect of the virus; src tyrosine-phosphorylation apparently overrides the junctional upregulation mediated by cyclic AMP. Nonjunctional membrane permeability was not sensibly affected by the virus. It was affected, however, by temperature: lowering the temperature from the nonpermissive to the permissive level caused the nonjunctional permeability to fall, and vice versa. This change was unrelated to transformation. Its secondary effect on junctional transfer is in the opposite direction to that produced by the temperature-activated viral transformation.

Animals↗

Erythrocyte aggregation and erythrocyte deformability modify the permeability of erythrocyte enriched fibrin network.

Intravascular thrombus formed under low shear conditions consists of red cells enmeshed within a fibrin network. Since red cells reduce the permeability of fibrin network by surface drag and by volume occupancy the significance of red cell aggregability and deformability in network permeability needs examination. In this study networks were developed by the addition of thrombin to washed red cells suspended in platelet free plasma. The effects of the polymers polyvinylpyrrolidone (PVP) and poloxamer 188 on network permeability were compared to gauge the influence of red cell aggregation. Both polymers increase network permeability by an action on fibrin polymerisation but PVP alone enhances red cell aggregation. PVP was found to increase network permeability significantly both by increasing the permeability of the fibrin component of the network and by increasing red cell aggregation and thus reducing red cell surface drag. In separate experiments red cells were pre-treated with heat, glutaraldehyde, or diamide to reduce cell deformability. Decreased cell deformability caused significant reductions in network permeability. This was ascribed to the reduced aggregability of hardened red cells. Red cell aggregation during coagulation enhances molecular transport through modifying the network. This may have implications for the penetration of fibrinolytic agents.

Blood Coagulation↗

Changes in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs.

Brain microvessel endothelial cell monolayers have been shown to be a suitable blood-brain barrier in vitro system to study adrenergic regulation of permeability. We tested adrenergic drugs on bovine brain microvessel endothelial cell monolayer permeability to a biomembrane impermeant molecule, sodium fluorescein. Endogenous catecholamines noradrenaline and adrenaline were tested as well as the alpha-adrenoceptor agonist phenylephrine, the beta-adrenoceptor agonist clenbuterol and the alpha-adrenoceptor antagonist prazosin. Results showed an alpha-adrenoceptor mediated increase and a beta-adrenoceptor mediated decrease in monolayer permeability. Both alpha- and beta-adrenoceptor mediated changes in permeability were abolished by inhibiting fluid-phase pinocytosis, either by vincristine or by avoiding bovine brain microvessel endothelial cell's energy utilization. The reverse transport (i.e., from brain to blood side) was also influenced by adrenergic drugs; alpha- or beta-adrenoceptor stimulation induced a permeability-reducing effect. We conclude that alpha-adrenoceptor stimulation increases bovine brain microvessel endothelial cell monolayer permeability and that beta-adrenoceptor stimulation has the opposite effect. Reverse transport results obtained with beta-adrenoceptor stimulation seem controversial and deserve further study. These results also support in vivo findings that demonstrated adrenergic influences on blood brain barrier permeability.

Adrenergic Agents↗

Effect of vehicles and sodium lauryl sulphate on xenobiotic permeability and stratum corneum partitioning in porcine skin.

Dermal contact with potentially toxic agricultural and industrial chemicals is a common hazard encountered in occupational, accidental spill and environmental contamination scenarios. Different solvents and chemical mixtures may influence dermal absorption. The effects of sodium lauryl sulphate (SLS) on the stratum corneum partitioning and permeability in porcine skin of 10 agricultural and industrial chemicals in water, ethanol and propylene glycol were investigated. The chemicals were phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. SLS decreased partitioning into stratum corneum from water for lipophilic compounds, decreased partitioning from propylene glycol and did not alter partitioning from ethanol. SLS effects on permeability were less consistent, but generally decreased permeability from water, increased permeability from ethanol and had an inconsistent effect on permeability from propylene glycol. It was concluded that, for the compounds tested, partitioning into the stratum corneum was determined by the relative solubility of the solute in the donor solvent and the stratum corneum lipids. Permeability, however, reflected the result of successive, complex processes and was not predictable from stratum corneum partitioning alone. Addition of SLS to solvents altered partitioning and absorption characteristics across a range of compounds, which indicates that partition coefficients or skin permeability from neat chemical exposure should be used with caution in risk assessment procedures for chemical mixtures.

Agrochemicals↗

The use of computerized videokeratography as an aid in fitting rigid gas permeable contact lenses.

PURPOSE: To assess the efficacy of computerized corneal topography in (1) fitting cosmetic rigid gas permeable contact lenses on normal corneas and (2) patients who have keratoconus. METHODS: In study 1, 26 patients were fitted with cosmetic contact lenses. In 13 patients, the first rigid gas permeable lens was chosen on the basis of corneal topography using the EyeSys videokeratoscope and contact lens software version 2.11w. Thirteen control patients were fitted with rigid gas permeable contact lenses by means of diagnostic contact lenses. The number of parameter changes required in each group to reach the best fit were compared. In study 2, the records of 28 patients (41 eyes) with keratoconus who had been successfully fit with rigid gas permeable lenses were reviewed. Topographic analysis using the EyeSys videokeratoscope was conducted. The following 8 data points were analyzed: maximum dioptric curvature with respect to the central visual axis, the power at the visual axis (VK), the average keratometry readings within the 3-mm zone, the average flat K at 3-mm central and 5-mm paracentral regions, and the K reading at 1.5, 2.0, and 2.5 mm superior to the visual axis. RESULTS: Study 1: In 10 eyes (38%) fitted with cosmetic contact lenses utilizing corneal topography and the EyeSys contact lens program, the first lens chosen by the computer program was correct with no additional changes in lens parameters required. In the other 16 eyes, 21 parameter changes were required. In the control group, 14 eyes (53%) required no additional change in parameters from the original contact lens that was fitted using diagnostic lenses. In the other 12 eyes, 12 parameter changes were required. Study 2: In the keratoconus group, of the 9 measurements analyzed, the final base curve of patients' rigid gas permeable lenses was correlated most closely with the average flat corneal curvature at the 3-mm central zone. CONCLUSION: Study 1: In fitting cosmetic rigid gas permeable contact lenses, the videokeratoscope with the EyeSys software 2.11w contact lens program proved to be inferior to diagnostic lenses in selecting the final correct contact lens parameters. However, it may be useful in selecting an initial diagnostic lens with which to begin rigid gas permeable fitting. Study 2: In patients with irregular corneas such as keratoconus, corneal topography is helpful in determining the initial base curve of the contact lens. In patients with keratoconus, it appears to be the average flat corneal curvature at the 3.0-mm zone.

Contact Lenses↗

A baculovirus enhancin alters the permeability of a mucosal midgut peritrophic matrix from lepidopteran larvae.

The peritrophic matrix (PM) in lepidopterous larvae may function as a defensive barrier against ingested viral pathogens. PMs isolated from Trichoplusia ni and Pseudaletia unipuncta larvae, were treated with a baculovirus-encoded metalloprotease (enhancin) from Trichoplusia ni granulosis virus (TnGV) and their in vitro permeability to blue dextran and fluorescent-labelled Autographa californica nuclear polyhedrosis virus (AcMNPV) was determined using a dual chamber permeability apparatus. Incubation of T. ni PMs with 0.0, 0.5, 1.0, and 2.0mg/ml enhancin resulted in a blue dextran 2000 flux of 4.4, 6.3, 9.9, and 15.6&mgr;g/mm(2)/h, respectively. In addition, T. ni PMs treated with enhancin were found to be significantly more permeable to fluorescent-labelled AcMNPV than non-treated control PMs. The permeability of T. ni PMs treated with 3.0mg/ml enhancin was 0.017 cumulative percent crossing/mm(2)/h, whereas the permeability of the control PM was below the detectable limit. Similarly, enhancin treatment greatly increased the permeability of P. unipuncta PMs to AcMNPV. These results provide evidence that the PM from two lepidopteran species can block the passage of baculovirions across this matrix thus reducing the probability of larval infection. Furthermore, these results support the hypothesis that enhancin facilitates NPV infection of larvae by altering the permeability of the PM.

Journal Article↗

TR146 cells grown on filters as a model of human buccal epithelium: permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate.

The aim of the present study was to characterize the TR146 cell culture model as an in vitro model of human buccal epithelium with respect to the permeability of test substances with different molecular weights (M(w)). For this purpose, the apparent permeability (P(app)) values for mannitol and for fluorescein isothiocyanate (FITC)-labelled dextrans (FD) with various M(w) (4000-40000) were compared to the P(app) values obtained using porcine buccal mucosa as an in vitro model of the human buccal epithelium. The effect of 10 mM sodium glycocholate (GC) on the P(app) values was examined. To identify the pathways by which FD of M(w) 4000-40000 were transported, the confocal laser scanning microscope (CLSM) was used. The P(app) values obtained with the TR146 cell culture model in the absence of a permeability enhancer linearly decreased with increasing M(w) of the test substance from 0. 65+/-0.055x10(-8) to 44+/-7.5x10(-8) cm/s, as the P(app) values obtained with porcine buccal mucosa. In the presence of the permeability enhancer, GC, the permeability of the FD across the cultured TR146 cell culture model increased in a parabolic manner, reaching maximum at M(w) 10000. In the absence of the enhancer, only paracellular localization of FD was observed while, in the presence of GC, FD also could be detected in the cytosol of some of the superficial cells. The GC-induced enhancement of FD permeation may be partially attributed to changed permeation pathways. The present results indicate that the TR146 cell culture model is a suitable in vitro model for mechanistic permeability studies of human buccal drug permeability.

Animals↗

MRI measurement of blood-brain barrier permeability following spontaneous reperfusion in the starch microsphere model of ischemia.

Quantification of the acute increases in blood-brain barrier (BBB) permeability that occur subsequent to experimental ischemic injury has been limited to single time-point, invasive methodologies. Although permeability can be qualitatively assessed to visualise regional changes during sequential studies on the same animal using contrast-enhanced magnetic resonance imaging (MRI), quantitative information on the magnitude of change is required to compare barrier function during sequential studies on the same animal or between different animals. Recently, improvements in MRI tracer kinetic models and in MR hardware design mean that an estimate of permeability in vivo can now be obtained with acceptable accuracy and precision. We report here the use of such methods to study acute changes following spontaneous reperfusion in an animal model of ischemia. We have obtained estimates of BBB permeability following spontaneous reperfusion, subsequent to forebrain ischemia by unilateral carotid injection of starch microspheres in the rat. T2*-weighted and diffusion-trace imaging were used to monitor the initial reduction in CBF and the time-course of ischemia, respectively. Following reperfusion, an intraveneous bolus of dimeglumine gadopentetate (Gd-DTPA) and horseradish peroxidase (HRP) was given during a continuous acquisition of T1 maps with a 48 s temporal resolution. Permeability maps were constructed using a 4-compartment model; K(trans), the permeability-surface area product of the capillary walls was estimated to be 9.2 +/- 0.6 x 10(-4) min(-1) in the cortex. Visualisation of the regional extent of HRP extravasation on histological sections following termination of the experiment demonstrated very little correspondence to the region of Gd-DTPA leakage. Quantitative MRI assessment of BBB permeability following ischemia-reperfusion is consistent with published values obtained by invasive methods. Differences between Gd-DTPA-enhancement and HRP may reflect differences in the molecular size of the tracers.

Animals↗

Permeability of acetic acid through organic films at the air-aqueous interface.

Recent field studies of collected aerosol particles, both marine and continental, show that the outermost layers contain long-chain (C >or= 18) organics. The presence of these long-chain organics could impede the transport of gases and other volatile species across the interface. This could effect the particle's composition, lifetime, and heterogeneous chemistry. In this study, the uptake rate of acetic acid vapor across a clean interface and through films of long-chain organics into an aqueous subphase solution containing an acid-base indicator (bromocresol green) was measured under ambient conditions using visible absorption spectroscopy. Acetic acid is a volatile organic compound (VOC) and is an atmospherically relevant organic acid. The uptake of acetic acid through single-component organic films of 1-octadecanol (C(18)H(38)O), 1-triacontanol (C(30)H(62)O), cis-9-octadecen-1-ol (C(18)H(36)O), and nonacosane (C(29)H(60)) in addition to two mixed films containing equimolar 1-triacontanol/nonacosane and equimolar 1-triacontanol/cis-9-octadecen-1-ol was determined. These species represent long-chain organic compounds that reside at the air-aqueous interface of atmospheric aerosols. The cis-9-octadecen-1-ol film had little effect on the net uptake rate of acetic acid vapor into solution; however, the uptake rate was reduced by almost one-half by an interfacial film of 1-triacontanol. The measured uptake rates were used to calculate the permeability of acetic acid through the various films which ranged from 1.5 x 10(-3) cm s(-1) for 1-triacontanol, the least permeable film, to 2.5 x 10(-2) cm s(-1) for cis-9-octadecen-1-ol, the most permeable film. Both mixed films had permeabilities that were between that of the single-component films comprising the mixture. This shows that the permeability of a mixed film may not be solely determined by the most permeable species in the mixture. The permeabilities of all the films studied here are discussed in relation to their molecular properties, pressure-area isotherms, and atmospheric implications.

Journal Article↗

Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility.

The absorption of the polar drug phenol red was assessed in a rat intestinal perfusion model, in the presence of a variety of potential intestinal permeability enhancers. Both the absorption rate constant KA and the plasma phenol red concentration were measured. Perfusates were also assayed for the presence of lactate dehydrogenase (LDH) and lipid phosphate, as biochemical markers of intestinal wall damage. Histological evaluation of surfactant-perfused intestines was also carried out. The potential permeability enhancers studied were the surfactants sodium dodecyl sulfate (SDS), sodium taurocholate (TC), sodium taurodeoxycholate (TDC), polysorbate-80 (PS-80), and nonylphenoxypolyoxyethylene (NP-POE) with an average polar group size of 10.5 POE units. Among these, SDS and NP-POE-10.5 were the most potent permeability enhancers. The bile salt TDC was a more effective enhancer than the more polar TC. The polar non-ionic surfactant PS-80 was an ineffective enhancer. Phenol red KA and plasma level were generally correlated with biochemical and histological measures of intestinal damage. These observations indicate that permeability enhancement and local damage are closely related sequelae of the interaction of surfactants with the intestinal wall, and suggest that local wall damage may be involved in the mechanism of permeability enhancement. The reversibility of permeability enhancement and acute local damage was assessed for the surfactants TDC and NP-POE-10.5. Enhancement of phenol red permeability was reversed within 1-2 hr of the cessation of enhancer treatment. Biochemical markers of local damage also fell to control values within 1-2 hr of removal of enhancer from the perfusate. Histological evaluation of perfused intestines revealed that morphological damage was reversed within 3 hr. These results demonstrate that surfactant-induced acute intestinal wall damage is rapidly repaired.

Animals↗

Seismic waves increase permeability.

Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Piñon Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults.

Letter↗