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Albertus G De Boer - One of the best experts on this subject based on the ideXlab platform.
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relationship between Permeability status of the blood brain barrier and in vitro Permeability Coefficient of a drug
European Journal of Pharmaceutical Sciences, 2000Co-Authors: Pieter J Gaillard, Albertus G De BoerAbstract:Abstract 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 (Papp,FLU, Mw 376 Da) and FITC-labeled dextran (Papp,FD4, Mw 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 Papp 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: Papp,FLU and Papp,FD4 in control experiments varied from 1.6 up to 17.6 (10−6cm/s) and 0.3 up to 7.3 (10−6cm/s), respectively; while for individual filters Papp,FLU was 4 times higher than Papp,FD4 (R2=0.97). As long as TEER remained above 131·Ω cm2 for FLU or 122·Ω cm2 for FD4 during the transport assay, Papp remained independent from the basal Permeability of the in vitro BBB. Below these TEER values, Papp increased exponentially. This nonlinear relationship between basal BBB Permeability and Papp was described by a one-phase exponential decay model. From this model the BBB Permeability status independent Permeability Coefficients for FLU and FD4 (PFLU and PFD4) were estimated to be 2.2±0.1 and 0.48±0.03 (10−6cm/s), respectively. In the experimentally challenged experiments, a reliable indication for PFLU and PFD4 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.
John K Critser - One of the best experts on this subject based on the ideXlab platform.
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determination of water Permeability Coefficient for human spermatozoa and its activation energy
Biology of Reproduction, 1993Co-Authors: E E Noiles, Peter Mazur, P F Watson, F W Kleinhans, John K CritserAbstract:: Four experiments were conducted to determine the Permeability Coefficient of human sperm to water (Lp) and its activation energy (Ea). Critical tonicity (tonicity at which 50% of the cells swell and lyse) was determined by equilibrating sperm to 22 degrees C (experiments 1a and 1b), 30, 22, 8, or 0 degrees C (experiment 2a), and 0, -1, -3, -5, or -7 degrees C (experiment 2b) and then exposing them to various hypotonic media (215-3 mOsm). For Lp determination, sperm were equilibrated to 30, 22, 8, or 0 degrees C (experiment 3a), 8, 0, or -3 degrees C (experiment 3b), and -1, -3, -5, or -7 degrees C (experiment 3c), and then were exposed for increasing times to hypotonic (40 mOsm) media. Activation energies were calculated from the results of the latter experiments (experiment 4). Results indicate a temperature-dependent (p < 0.05) critical tonicity, with sperm exhibiting an increased membrane fragility at 8, 0, and -7 degrees C, relative to 30, 22, -1, -3, or -5 degrees C (67.5 +/- 2.4, [mean +/- SEM], 62.7 +/- 2.3, and 61.9 +/- 3.7 mOsm vs. 57.4 +/- 3.4, 57 +/- 1.2, 54.8 +/- 3.4, 60.1 +/- 5.3, and 59.8 +/- 5.2 mOsm, respectively). Human sperm have an Lp of 2.40 +/- 0.20 microns/min/atm at 22 degrees C and an Ea of 3.92 +/- 0.59 kcal/mol between 30 and -7 degrees C. The Ea for cells incubated at temperatures above 0 degrees C (3.92 kcal/mol) show an apparent discontinuity (p < 0.004) in water Permeability in supercooled conditions (7.48 kcal/mol). These data suggest that 1) human sperm have a high Lp and low Ea, relative to other cell types, above 0 degrees C; and 2) this high Lp and its low Ea change significantly below 0 degrees C.
Zhechao Wang - One of the best experts on this subject based on the ideXlab platform.
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estimation of the rev size and equivalent Permeability Coefficient of fractured rock masses with an emphasis on comparing the radial and unidirectional flow configurations
Rock Mechanics and Rock Engineering, 2018Co-Authors: Zhechao Wang, Wei Li, Liping Bi, Liping QiaoAbstract:A method to estimate the representative elementary volume (REV) size for the Permeability and equivalent Permeability Coefficient of rock mass with a radial flow configuration was developed. The estimations of the REV size and equivalent Permeability for the rock mass around an underground oil storage facility using a radial flow configuration were compared with those using a unidirectional flow configuration. The REV sizes estimated using the unidirectional flow configuration are much higher than those estimated using the radial flow configuration. The equivalent Permeability Coefficient estimated using the radial flow configuration is unique, while those estimated using the unidirectional flow configuration depend on the boundary conditions and flow directions. The influences of the fracture trace length, spacing and gap on the REV size and equivalent Permeability Coefficient were investigated. The REV size for the Permeability of fractured rock mass increases with increasing the mean trace length and fracture spacing. The influence of the fracture gap length on the REV size is insignificant. The equivalent Permeability Coefficient decreases with the fracture spacing, while the influences of the fracture trace length and gap length are not determinate. The applicability of the proposed method to the prediction of groundwater inflow into rock caverns was verified using the measured groundwater inflow into the facility. The Permeability Coefficient estimated using the radial flow configuration is more similar to the representative equivalent Permeability Coefficient than those estimated with different boundary conditions using the unidirectional flow configuration.
Pieter J Gaillard - One of the best experts on this subject based on the ideXlab platform.
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relationship between Permeability status of the blood brain barrier and in vitro Permeability Coefficient of a drug
European Journal of Pharmaceutical Sciences, 2000Co-Authors: Pieter J Gaillard, Albertus G De BoerAbstract:Abstract 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 (Papp,FLU, Mw 376 Da) and FITC-labeled dextran (Papp,FD4, Mw 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 Papp 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: Papp,FLU and Papp,FD4 in control experiments varied from 1.6 up to 17.6 (10−6cm/s) and 0.3 up to 7.3 (10−6cm/s), respectively; while for individual filters Papp,FLU was 4 times higher than Papp,FD4 (R2=0.97). As long as TEER remained above 131·Ω cm2 for FLU or 122·Ω cm2 for FD4 during the transport assay, Papp remained independent from the basal Permeability of the in vitro BBB. Below these TEER values, Papp increased exponentially. This nonlinear relationship between basal BBB Permeability and Papp was described by a one-phase exponential decay model. From this model the BBB Permeability status independent Permeability Coefficients for FLU and FD4 (PFLU and PFD4) were estimated to be 2.2±0.1 and 0.48±0.03 (10−6cm/s), respectively. In the experimentally challenged experiments, a reliable indication for PFLU and PFD4 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.
E E Noiles - One of the best experts on this subject based on the ideXlab platform.
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determination of water Permeability Coefficient for human spermatozoa and its activation energy
Biology of Reproduction, 1993Co-Authors: E E Noiles, Peter Mazur, P F Watson, F W Kleinhans, John K CritserAbstract:: Four experiments were conducted to determine the Permeability Coefficient of human sperm to water (Lp) and its activation energy (Ea). Critical tonicity (tonicity at which 50% of the cells swell and lyse) was determined by equilibrating sperm to 22 degrees C (experiments 1a and 1b), 30, 22, 8, or 0 degrees C (experiment 2a), and 0, -1, -3, -5, or -7 degrees C (experiment 2b) and then exposing them to various hypotonic media (215-3 mOsm). For Lp determination, sperm were equilibrated to 30, 22, 8, or 0 degrees C (experiment 3a), 8, 0, or -3 degrees C (experiment 3b), and -1, -3, -5, or -7 degrees C (experiment 3c), and then were exposed for increasing times to hypotonic (40 mOsm) media. Activation energies were calculated from the results of the latter experiments (experiment 4). Results indicate a temperature-dependent (p < 0.05) critical tonicity, with sperm exhibiting an increased membrane fragility at 8, 0, and -7 degrees C, relative to 30, 22, -1, -3, or -5 degrees C (67.5 +/- 2.4, [mean +/- SEM], 62.7 +/- 2.3, and 61.9 +/- 3.7 mOsm vs. 57.4 +/- 3.4, 57 +/- 1.2, 54.8 +/- 3.4, 60.1 +/- 5.3, and 59.8 +/- 5.2 mOsm, respectively). Human sperm have an Lp of 2.40 +/- 0.20 microns/min/atm at 22 degrees C and an Ea of 3.92 +/- 0.59 kcal/mol between 30 and -7 degrees C. The Ea for cells incubated at temperatures above 0 degrees C (3.92 kcal/mol) show an apparent discontinuity (p < 0.004) in water Permeability in supercooled conditions (7.48 kcal/mol). These data suggest that 1) human sperm have a high Lp and low Ea, relative to other cell types, above 0 degrees C; and 2) this high Lp and its low Ea change significantly below 0 degrees C.