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PubMedDate not supplied

Ionic strength affects diffusive permeability to an inorganic phosphate ion of negatively charged dialysis membranes.

Electrolytes undergo electrostatic resistances in reaching membrane surfaces and passing through membrane pores when weakly charged dialysis membranes are used in hemodialysis treatments. Diffusive permeability to an electrolyte of weakly charged dialysis membranes depends upon the effective charge density of the membranes, which varies with ionic strength. The authors carried out dialysis experiments at a temperature of 310 K, with 32P-Na2HPO4 in aqueous NaCl and bovine serum, to obtain diffusive permeability to an inorganic phosphate ion of regenerated cellulose, and polymethylmethacrylate membranes of various fixed charge densities at varying ionic strengths ranging from 1.66 to 100 mol/m3. Diffusive permeability to an inorganic phosphate ion increased with ionic strength. Bovine serum, having an ionic strength of approximately 150 mol/m3, gave higher diffusive permeability to an inorganic phosphate ion. The internal structure of dialysis membranes, such as pore size, surface porosity, and tortuosity, also affects diffusive permeability. The electrolyte diffusion theory gives an effective charge density of -5.3 mol/m3 for the cellulosic membrane. In conclusion, ionic strength enhances diffusive permeability to an inorganic phosphate ion in both aqueous NaCl and bovine serum. Inorganic phosphate ion transport through negatively charged dialysis membranes depends upon the degree of dissociation of inorganic phosphate, the molecular size and valence of hydrated inorganic phosphate ion, the effective charge density and internal structure of the membrane, and ionic strength.

Animals↗
PubMed2001

Progress and limitations in the use of in vitro cell cultures to serve as a permeability screen for the blood-brain barrier.

A relatively simple, widely applicable, and robust in vitro method of predicting blood-brain barrier (BBB) permeability to central nervous system-acting drugs is an increasing need. A cell-based model offers the potential to account for transcellular and paracellular drug diffusional processes, metabolism, and active transport processes, as well as nondefined interactions between a drug and cellular material that may impact upon a membrane's overall permeability profile. Any in vitro BBB cell model to be utilized for the transendothelial BBB permeability screening of potential central nervous system drugs must display reproducible solute permeability, and a number of other general criteria including: a restrictive paracellular barrier; a physiologically realistic cell architecture; the functional expression of key transporter mechanisms; and allow ease of culture to meet the technical and time constraints of a screening program. This article reviews the range of in vitro cell-based BBB models available, including the primary/low passage bovine and porcine brain endothelial cultures as well as the spectrum of immortalized brain endothelial cell lines that have been established. The article further discusses the benefits and limitations of exploiting such systems as in vitro BBB permeability screens.

Animals↗
PubMed1994

Frog striated muscle is permeable to hydroxide and buffer anions.

Hydroxide, bicarbonate and buffer anion permeabilities in semitendinosus muscle fibers of Rana pipiens were measured. In all experiments, the fibers were initially equilibrated in isotonic, high K2SO4 solutions at pHo = 7.2 buffered with phosphate. Two different methods were used to estimate permeabilities: (i) membrane potential changes were recorded in response to changes in external ion concentrations, and (ii) intracellular pH changes were recorded in response to changes in external concentrations of ions that alter intracellular pH. Constant field equations were used to calculate relative or absolute permeabilities. In the first method, to increase the size of the membrane potential change produced by a sudden change in anion entry, external K+ was replaced by Cs+ prior to changes of the anion under study. At constant external Cs+ activity, a hyperpolarization results from increasing external pH from 7.2 to 10.0 or higher, using either CAPS (3-[cyclohexylamino]-1-propanesulfonic acid) or CHES (2-[N-cyclohexylamino]-ethanesulfonic acid) as buffer. For each buffer, the protonated form is a zwitterion of zero net charge and the nonprotonated form is an anion. Using reported values of H+ permeability, calculations show that the reduction in [H+]o cannot account for the hyperpolarizations produced by alkaline solutions. Membrane hyperpolarization increases with increasing total external buffer concentration at constant external pH, and with increasing external pH at constant external buffer anion concentration. Taken together, these observations indicate that both OH- and buffer anions permeate the surface membrane. The following relative permeabilities were obtained at pHo = 10.0 +/- 0.3: (POH/PK) = 890 +/- 150, (PCAPS/PK) = 12 +/- 2, (PCHES/PK) = 5.3 +/- 0.9, and (PNO3/PK) = 4.7 +/- 0.5. PNO3/PK was independent of pHo up to 10.75. At pHo = 9.6, (PHCO3/PK) = 0.49 +/- 0.03; at pHo = 8.9, (PCl/PK) = 18 +/- 2 and at pHo = 7.1, (PHEPES/PK) = 20 +/- 2. In the second method, on increasing external pH from 7.2 to 10.0, using 2.5 mM CAPS (total buffer concentration), the internal pH increases linearly with time over the next 10 min. This alkalinization is due to the entry of OH- and the absorption of internal H+ by entering CAPS- anion. The rate of CAPS- entry was determined in experiments in which the external CAPS concentration was increased at constant external pH. Such increases invariably produced an increase in the rate of internal alkalinization, which was reversed when the CAPS concentration was reduced to its initial value.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Sequential onset of permeability changes in mouse ascites cells induced by Sendai virus.

The addition of haemolytic Sendai virus to cells induces membrane changes in the following sequence: (i) Increased permeability to ions, (ii) increased permeability to low molecular weight metabolites, (iii) increased permeability to proteins. The consequences of an increased permeability to ions are: (a) alteration of membrane potential, (b) net changes in intracellular cations and (c) cell swelling, in that order. Depending on virus: cell ratio, Ca2+ concentration and temperature, it is possible to observe ion leakage without metabolite or protein leakage, and ion and metabolite leakage without protein leakage. A model for the induction of permeability changes is presented.

Animals↗
PubMedDate not supplied

Modulation of human endothelial cell permeability by combinations of the cytokines interleukin-1 alpha/beta, tumor necrosis factor-alpha and interferon-gamma.

The permeability of human umbilical vein endothelial cell (HUVEC) monolayers to [125I]-labelled bovine serum albumin (BSA) was examined following pretreatment of the cells with various cytokines. The electrical resistance measured across untreated, confluent, intact HUVEC monolayers was 18.2 +/- 3.8 omega.cm2 (mean +/- S.D. of 4 observations). Human recombinant (hr) interleukin-1 alpha/beta (IL-1 alpha/beta), hr tumor necrosis factor-alpha (TNF-alpha), and hr interferon-gamma (IFN-gamma) each increased HUVEC monolayer permeability in a time- and dose-dependent manner. These effects were inhibitable by neutralizing antibodies (nAb) to the corresponding cytokines, and were not due to contamination by endotoxin (abolition of cytokine effect by heat treatment, and no effect on cytokine action of the endotoxin inhibitor polymyxin B). The effects of these cytokines were not due to endothelial cell (EC) interleukin-6 (IL-6) induction (IL-6 shown not to increase permeability) and the effect of hrTNF-alpha could not be accounted for by induction of IL-1 (effect not inhibited by hrIL-1 alpha/beta nAb). The effects of three different combinations of the cytokines (each combination at two different concentrations) on HUVEC monolayer permeability were also examined. hrIFN-gamma with hrTNF-alpha or hrIL-1 alpha/beta gave an increase in permeability (at both concentration combinations) greater than that seen with either cytokine alone. hrTNF-alpha and hrIL-1 alpha/beta in combination however produced an enhanced effect only at low concentrations, high concentrations in combination producing an effect no greater than either agent alone. These results highlight the importance of investigating actions of cytokine combinations on in vitro models of endothelial cell activation.

Capillary Permeability↗
PubMed2005

Osmotic tolerance and membrane permeability characteristics of rhesus monkey (Macaca mulatta) spermatozoa.

Biophysical characteristics of the plasma membrane, such as osmotic sensitivity and water and cryoprotectant permeability are important determinants of the function of spermatozoa after cryopreservation. A series of experiments was conducted with rhesus macaque spermatozoa at 23 degrees C to determine their: (1) cell volume and osmotically inactive fraction of the cell volume; (2) permeability coefficients for water and the cryoprotectants dimethyl sulfoxide, glycerol, propylene glycol, and ethylene glycol; (3) tolerance to anisosmotic conditions; and (4) motility after a one step addition and removal of the four cryoprotectants. An electronic particle counter and computer aided semen analysis were used to determine the cell volume and permeability coefficients, and motility, respectively. Rhesus spermatozoa isosmotic cell volume was 27.7+/-3.0 microm3 (mean+/-SEM) with an osmotically inactive cell fraction of 51%. Hydraulic conductivity in the presence of dimethyl sulfoxide, glycerol, propylene glycol, and ethylene glycol was 1.09+/-0.30, 0.912+/-0.27, 1.53+/-0.53, and 1.94+/-0.47 microm/min/atm, respectively. Cryoprotectant permeability was 1.39+/-0.31, 2.21+/-0.32, 3.38+/-0.63, and 6.07+/-1.1 (x10(-3)cm/min), respectively. Rhesus sperm tolerated all hyposmotic exposures. However, greater than 70% motility loss was observed after exposure to solutions of 600 mOsm and higher. A one step addition and removal of all four cryoprotectants did not cause significant motility loss. These data suggest that rhesus sperm are tolerant to hyposmotic conditions, and ethylene glycol may be the most appropriate cryoprotectant for rhesus sperm cryopreservation, as it has the highest permeability coefficient of the tested cryoprotectants.

Animals↗
PubMed2006

Polymerization kinetics of dental adhesives cured with LED: correlation between extent of conversion and permeability.

OBJECTIVES: The aim of this study was to analyze the polymerization kinetics of different adhesive films in relation to their permeability after exposure to different LED curing units. METHODS: One adhesive from each class was analyzed: a three-step etch-and-rinse (OptiBond FL; Sybron-Kerr), a two-step etch-and-rinse (One-Step, Bisco), a two-step self-etch (Clearfil Protect Bond, Kuraray) and a one-step self-etch adhesive (Xeno III; Dentsply DeTrey). Adhesive films were prepared and cured with SmartLite IQ (Dentsply) or L.E. Demetron I (Demetron Kerr) up to complete curing. Polymerization kinetic curves of the tested adhesives were obtained with differential scanning calorimetry (DSC). In particular, total reaction time and extent of polymerization (Ep) at 20, 40 or 60s were compared. Permeability of the adhesive films was evaluated on flat dentin surfaces of human extracted teeth connected to a permeability device and statistically analyzed. RESULTS: Total reaction time differed among the adhesives tested: OptiBond FL<Clearfil Protect Bond<One-Step<Xeno III with both curing units (p<0.05). At 20s OptiBond FL showed the highest Ep, while the lowest values were obtained with One-Step and Xeno III (p<0.05). E(p) increased when curing time was prolonged (40 and 60s) for all adhesives tested (p<0.05), however, on simplified adhesives, incomplete polymerization took place even after prolonged exposure intervals. An inverse correlation was found between Ep of the adhesives and their permeability using LED curing units. SIGNIFICANCE: This study supports the hypothesis that, longer curing times than those recommended by the respective manufacturer decrease permeability of the bonded interfaces.

Adhesives↗
PubMed2004

Dynamic intravital fluorescence microscopy--a novel method for the assessment of microvascular permeability in acute pancreatitis.

Edema formation is the first manifestation of acute pancreatitis. Microcirculatory derangements like leukocyte-endothelial cell interaction and perfusion failure result in enhancement of microvascular permeability to large molecules playing a pivotal role in the progression of the acutely altered pancreatic tissue. Due to the lack of suitable methods the crucial mechanisms of enhanced permeability in vivo are not very well investigated. Sprague-Dawley rats were randomly assigned to three groups: (a) sham operated animals with normal pancreas, (b) the pancreatitis group induced by 60 min temporary occlusion of the arterial supply followed by reperfusion and (c) the histamine group in which the pancreas was superfused with 10(-5)M histamine. The pharmacokinetics of tetramethylrhodamine-labelled BSA in the intravital microscopic images of a capillary network of the pancreas were densitometrically quantified over 20 min. From these data the effective microvascular permeability was calculated taking also into account morphology of microvessels, elimination rate of the tracer from the intravascular space and capillary microhematocrit. In addition macromolecular leakage of gold-labelled BSA was investigated by electron microscopy. Microvascular permeability was 0.10 +/- 0.02 x 10(-7) cm/s, 0.49 +/- 0.04 x 10(-7) cm/s and 1.21 +/- 0.29 x 10(-7) cm/s for control, ischemia and histamine group, respectively (P < 0.05 ischemia, histamine vs. control and ischemia vs. histamine). Electron microscopy revealed albumin extravasation in the last two groups. We established a technique allowing to quantify microvascular permeability in pancreatic tissue by dynamic intravital microscopy being independent of the investigator. This technique enabling accurate pathophysiologic characterisation in terms of edema formation can form the basis for evaluating in the future novel treatment strategies directed against acute pancreatitis.

Animals↗
PubMed2003

Epidermal cell culture model derived from rat keratinocytes with permeability characteristics comparable to human cadaver skin.

The permeability characteristics of an organotypic epidermal culture model derived from rat epidermal keratinocytes, ROC, and isolated human cadaver epidermis, HEM, were compared. Rat epidermal keratinocyte (REK) cell line was grown for 3 weeks on collagen gel in the absence of feeder cells in culture inserts at an air-liquid interface. Transdermal permeabilities of 18 compounds ranging from 92 to 504 in molecular weight and from -4.3 to 3.9 in log of octanol-water partition coefficient, charged or uncharged, were measured in the culture model and isolated human epidermis. The REK organotypic culture model (ROC) provided a close estimate of human epidermal permeabilities over the whole range of the solutes used with on the average of 2-fold higher permeability coefficients (range 0.3-5.2) than those obtained from isolated human cadaver epidermis. The easily maintained and reproducible ROC model may be useful in screening transepidermal drug permeabilities together with possessing potential for research on dermal formulations, irritation, toxicity and gene therapy.

Animals↗
PubMed2003

Annexin A4 reduces water and proton permeability of model membranes but does not alter aquaporin 2-mediated water transport in isolated endosomes.

Annexin A4 (Anx4) belongs to a ubiquitous family of Ca2+-dependent membrane-binding proteins thought to be involved in membrane trafficking and membrane organization within cells. Anx4 localizes to the apical region in epithelia; however, its physiological role is unclear. We show that Anx4 exhibited binding to liposomes (phosphatidylcholine:phosphatidylserine, 1:1) in the presence of Ca2+ and binding was reversible with EDTA. Anx4 binding resulted in liposome aggregation and a reduction in membrane water permeability of 29% (P < 0.001) at 25 degrees C. These effects were not seen in the presence of Ca2+ or Anx4 alone and were reversible with EDTA. Measurements of membrane fluidity made by monitoring fluorescence anisotropy of 2-(12-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl-1-hexadecanoyl-sn-glycero-3-phosphocholine (NBD-HPC) demonstrated that Anx4 binding rigidified the outer leaflet of the bilayer (P < 0.001), thus providing a molecular explanation for the inhibition of water flux. To determine whether Anx4 would produce similar effects on physiological membranes we constructed liposomes which recapitulated the lipid composition of the inner leaflet of the MDCK apical membrane. These membranes exhibited reductions to water permeability upon Anx4 binding (19.5% at 25 degrees C, 31% at 37 degrees C; P < 0.01 and P < 0.001, respectively) and to proton permeability (15% at 25 degrees C, 19.5% at 37 degrees C; P < 0.05). Since our in vitro experiments indicated an effect on membrane permeability, we examined localization of Anx4 in the kidney collecting duct, a region of the nephron responsible for concentrating urine through water reabsorbtion. Anx4 was shown to colocalize apically with aquaporin 2 (AQP2) in collecting duct epithelia. To test for the existence of a functional interaction between Anx4 and AQP2 we isolated AQP2-containing endosomes and exposed them to Anx4/Ca2+. Water flux rates were unchanged, indicating Anx4 does not directly regulate AQP2. We conclude that Anx4 can alter the physical properties of membranes by associating with them and regulate passive membrane permeability to water and protons. These properties represent important new functions for Anx4.

Animals↗
PubMed1956

The role of water in protoplasmic permeability and in antagonism.

The behavior of the cell depends to a large extent on the permeability of the outer non-aqueous surface layer of the protoplasm. This layer is immiscible with water but may be quite permeable to it. It seems possible that a reversible increase or decrease in permeability may be due to a corresponding increase or decrease in the water content of the non-aqueous surface layer. Irreversible increase in permeability need not be due primarily to increase in the water content of the surface layer but may be caused chiefly by changes in the protoplasm on which the surface layer rests. It may include desiccation, precipitation, and other alterations. An artificial cell is described in which the outer protoplasmic surface layer is represented by a layer of guaiacol on one side of which is a solution of KOH + KCl representing the external medium and on the other side is a solution of CO(2) representing the protoplasm. The K(+) unites with guaiacol and diffuses across to the artificial protoplasm where its concentration becomes higher than in the external solution. The guaiacol molecule thus acts as a carrier molecule which transports K(+) from the external medium across the protoplasmic surface. The outer part of the protoplasm may contain relatively few potassium ions so that the outwardly directed potential at the outer protoplasmic surface may be small but the inner part of the protoplasm may contain more potassium ions. This may happen when potassium enters in combination with carrier molecules which do not completely dissociate until they reach the vacuole. Injury and recovery from injury may be studied by measuring the movements of water into and out of the cell. Metabolism by producing CO(2) and other acids may lower the pH and cause local shrinkage of the protoplasm which may lead to protoplasmic motion. Antagonism between Na(+) and Ca(++) appears to be due to the fact that in solutions of NaCl the surface layer takes up an excessive amount of water and this may be prevented by the addition of suitable amounts of CaCl(2). In Nitella the outer non-aqueous surface layer may be rendered irreversibly permeable by sharply bending the cell without permanent damage to the inner non-aqueous surface layer surrounding the vacuole. The formation of contractile vacuoles may be imitated in non-living systems. An extract of the sperm of the marine worm Nereis which contains a highly surface-active substance can cause the egg to divide. It seems possible that this substance may affect the surface layer of the egg and cause it to take up water. A surface-active substance has been found in all the seminal fluids examined including those of trout, rooster, bull, and man. Duponol which is highly surface-active causes the protoplasm of Spirogyra to take up water and finally dissolve but it can be restored to the gel state by treatment with Lugol solution (KI + I). The transition from gel to sol and back again can be repeated many times in succession. The behavior of water in the surface layer of the protoplasm presents important problems which deserve careful examination.

Animals↗
PubMed2002

Water permeability of capillaries in the subfornical organ of rats determined by Gd-DTPA(2-) enhanced 1H magnetic resonance imaging.

The water permeability of capillaries in the subfornical organ (SFO) of rat was measured by a (1)H nuclear magnetic resonance method in combination with a venous injection of a relaxation reagent, gadolinium-diethylene triamine-N,N,N',N",N"-pentaacetic acid (Gd-DTPA(2-)), which could not pass through the blood-brain barrier (BBB). Judging from results of Gd-DTPA(2-) dose dependency in the intact brain and the BBB-permeabilized brain, Gd-DTPA(2-) could not have leaked out from the capillaries in the cortex, thalamus or SFO, but it could have been extravasated in the posterior lobe of the pituitary gland. The longitudinal (T(1)) relaxation time of water in the SFO region was measured by inversion-recovery magnetic resonance imaging at 4.7 T. The T(1) relaxation rates (1/T(1)) before and after Gd-DTPA(2-) infusion were 0.70 +/- 0.02 s(-1) (mean +/- S.E.M., n = 9) and 1.53 +/- 0.11 s(-1) (n = 9), respectively. The rate constant for water influx to the capillaries was estimated to be 0.84 +/- 0.11 s(-1) (n = 9) which corresponds with a diffusive membrane permeability (P(d)) of 3.7 x 10(-3) cm s(-1). Compared with values found in the literature available on this subject, this P(d) value for the capillaries in the SFO was the same order of magnitude as that for transmembrane permeability of water for the vasa recta, and it may be 10-100 times larger than that of the blood-brain barrier in the cortex. Areas of the cortex and thalamus showed minimal changes in the T(1) relaxation rate (ca 0.09 s(-1)), but these values were not statistically significant and they corresponded to P(d) values much smaller than those found in the SFO. From these results, we conclude that the capillaries in the SFO have one of the highest water permeability values among all of the capillaries in the brain. It is also suggested that this magnetic resonance imaging, based on T(1) relaxation rate, is a useful method to detect local water permeability in situ.

Animals↗
PubMed1963

Quantitative molecular approach to the permeability changes of excitation.

Functional relationships, available from only a few monolayer studies, can be applied to a relatively simple model of the excitable membrane to give permeability-potential curves quite similar to the conductance-potential curves obtained experimentally in voltage-clamped giant axons. Contrary to the usual view in terms of "carrier systems," the present model considers the permeability to sodium and potassium to be reduced by the increase in the surface pressure induced by large lipophilic cations and anions in the outer layer of the lipoidal bimolecular leaflet constituting the living membrane; hence, the increase in permeability during depolarization, for example, is due to a decrease in the amount of the organic anions in this layer, whereas the decrease in sodium permeability during inactivation is caused by a rise in content of organic cations. The present proposal has the advantage that it is in keeping with known phenomena observed in simple physico-chemical systems as well as in excitable systems; moreover, the current actually transferred by the postulated lipophilic ions can be negligible compared to that transferred by the inorganic cations they control. The latter situation, as well as the steepness of the permeability-potential relationships obtained, have been pointed out to be critical requirements of a satisfactory molecular hypothesis.

Axons↗
PubMed2004

Permeabilities of teleost and elasmobranch gill apical membranes: evidence that lipid bilayers alone do not account for barrier function.

Teleosts and elasmobranchs faced with considerable osmotic challenges living in sea water, use compensatory mechanisms to survive the loss of water (teleosts) and urea (elasmobranchs) across epithelial surfaces. We hypothesized that the gill, with a high surface area for gas exchange must have an apical membrane of exceptionally low permeability to prevent equilibration between seawater and plasma. We isolated apical membrane vesicles from the gills of Pleuronectes americanus (winter flounder) and Squalus acanthias (dogfish shark) and demonstrated approximately sixfold enrichment of the apical marker, ADPase compared to homogenate. We also isolated basolateral membranes from shark gill (enriched 2.3-fold for Na-K-ATPase) and using stopped-flow fluorometry measured membrane permeabilities to water, urea, and NH(3). Apical membrane water permeabilities were similar between species and quite low (7.4 +/- 0.7 x 10(-4) and 6.6 +/- 0.8 x 10(-4) cm/s for shark and flounder, respectively), whereas shark basolateral membranes showed twofold higher water permeability (14 +/- 2 x 10(-4) cm/s). Permeabilities to urea and NH(3) were also low in apical membranes. Because of the much lower apical to basolateral surface area we conclude that the apical membrane represents an effective barrier. However, the values we obtained were not low enough to account for low water loss (teleosts) and urea loss (elasmobranchs) measured in vivo by others. We conclude that there are other mechanisms which permit gill epithelia to serve as effective barriers. This conclusion has implications for the function of other barrier epithelia, such as the gastric mucosa, mammalian bladder, and renal thick ascending limb.

Ammonia↗
PubMed1984

Lung epithelial permeability: relation to nonspecific airway responsiveness.

Lung epithelial permeability was measured in five normal, five asthmatic, and five smoking subjects by quantifying removal from the lung and accumulation in the blood of an inhaled radiolabeled low-molecular-weight substance, technetium-99m-labeled diethyleneaminepentaacetate (99mTc-DTPA). Measurements on 2 control days were highly reproducible. Nonspecific bronchial responsiveness to histamine was determined in all subjects on a 3rd day, and the results were expressed as the provocation concentration producing a fall in forced expiratory volume in 1 s of 20% (PC20 histamine). Lung epithelial permeability was similar for the normal and asthmatic subjects. However, smokers had greatly increased permeability when compared with the other two groups. The responsiveness to histamine was increased in the asthmatics but within the normal range for normal subjects and smokers. No relationship was established between increased epithelial permeability and increased responsiveness to histamine. Results indicate that increased permeability of the epithelial lining of the bronchi is not a dominant factor in the increased nonspecific responsiveness to histamine observed in asthma.

Adult↗
PubMed1977

The capillary and sarcolemmal barriers in the heart. An exploration of labeled water permeability.

Although the exchange of labeled water between blood and tissue in the heart has usually been assumed to be flow-limited, the outflow patterns of labeled water, relative to intravascular references, in a multiple indicator dilution experiment, have appeared to be anomalous in terms of the models used to explain the transport of less permeable substances. Data showing a change in the shape of the labeled water outflow curve after vasodilation and after the infusion of toxic doses of 2,4-dinitrophenol led us to propose a new model for labeled water permeation which includes barriers at both the capillary wall and the sarcolemmal membrane. This model explains adequately the form of the outflow curve, provides parameters related to the permeability at the two barriers, and gives an estimate of the ratio of the intracellular to interstitial space. Dinitrophenol infused intra-arterially in a dose sufficient to cause S-T elevation in the electrocardiogram is found to reduce the sarcolemmal water permeability by an order of magnitude, but to have no effect on capillary water permeability. We conclude that water transport in the heart is barrier-limited at both the capillary and sarcolemmal membranes and that sarcolemmal water permeability is probably mediated at least in part by a structure sensitive to the effects of dinitrophenol, presumably a protein channel. Since the outflow patterns of inert gases resemble that of labeled water, it is possible that oxygen distribution is also barrier-limited.

Animals↗
PubMed1986

Quantitative assessment of microvascular permeability in endotoxin-induced lung injury in anaesthetized dogs.

We quantitatively assessed the change of pulmonary microvascular permeability following E. coli endotoxin infusion (1 mg/kg) in anaesthetized dogs. We used mathematical analysis to estimate membrane parameters from lung lymph data. Lung lymph was collected from the afferent lymphatic connecting to the left tracheobronchial lymph node whose lymph could be considered to represent an average sample of lung tissue fluid. To separate the effects of changes in the driving pressures and surface area on lymph fluid and protein flux from those in membrane permeability, lymph flow (Jv) was increased greater than 6 times baseline by left atrial pressure (Pla) elevation until lymph protein concentration (CL) approached to a constant value independent of Jv. Membrane parameters for plasma total protein, i.e., osmotic reflection coefficient (sigma d), solvent-drag reflection coefficient (sigma f), permeability surface area product (PS), filtration coefficient (Kfc), were calculated from lung lymphatic data in control (Pla elevation alone (n = 10), and endotoxin group (n = 7). Among these parameters, osmotic reflection coefficient (sigma d) decreased significantly to 0.61 in endotoxin group from the value of 0.71 in control group. This result indicates a moderate increase in pulmonary microvascular permeability following E. coli endotoxin infusion. However, there was no significant difference in the other membrane parameters (sigma f, PS, Kfc) between control and endotoxin group. Based on these results, we conclude that sigma d could quantitatively represent the moderate change of the microvascular permeability in endotoxin-induced lung injury in anaesthetized dogs.

Animals↗
PubMed2006

Predicting Caco-2 permeability using support vector machine and chemistry development kit.

PURPOSE: To predict Caco-2 permeability is a valuable target for pharmaceutical research. Most of the Caco-2 prediction models are based on commercial or special software which limited their practical value. This study represents the relationship between Caco-2 permeability and molecular descriptors totally based on open source software. METHODS: The Caco-2 prediction model was constructed based on descriptors generated by open source software Chemistry Development Kit (CDK) and a support vector machine (SVM) method. Number of H-bond donors and three molecular surface area descriptors constructed the prediction model. RESULTS: The correlation coefficients (r) of the experimental and predicted Caco-2 apparent permeability for the training set and the test set were 0.88 and 0.85, respectively. CONCLUSION: The results suggest that the SVM method is effective for predicting Caco-2 permeability. Membrane permeability of compounds is determined by number of H-bond donors and molecular surface area properties.

Caco-2 Cells↗