Permeability Research Papers - Academia.edu (original) (raw)

The applicability of a two-parameter Fickian diffusion model for predicting the skin steady-state permeability based on measurements of the transient transport of permeants across the skin was tested. Using five model permeants possessing different physicochemical properties and pig skin as the model membrane, the skin permeabilities predicted by the two-parameter Fickian diffusion model were compared with the measured skin permeabilities. Results show that the transient skin permeation profiles of the hydrophobic permeants, estradiol, testosterone, and dolichol, across splitthickness pig skin can be modeled adequately by the two-parameter Fickian diffusion model (with constant parameter values), and therefore, that this model can be utilized to shorten the experimental time required to determine the skin permeabilities of these compounds. However, the skin permeabilities of the highly hydrophilic permeants, mannitol and sucrose, predicted by the two-parameter Fickian diffusion model (with constant parameter values) were significantly lower than the experimentally determined values, indicating that the dominant skin pathway of polar permeants within the excised pig skin undergoes significant structural changes during the in vitro diffusion cell studies. Although the skin permeability values determined experimentally using the traditional steady-state method normally correspond to a highly hydrated skin sample, the two-parameter Fickian diffusion model enables an estimation of the skin permeability of the skin membrane at its less-hydrated state (a condition more representative of in vivo and clinical situations). Using the two-parameter Fickian diffusion model and a recently developed skin porous-pathway theory, the effects of skin hydration on the skin porous pathway within the excised pig skin were characterized. Specifically, we found that hydration leads to induction of new pores/reduction of the tortuosity of existing pores within the excised pig skin during the 48 h diffusion cell studies conducted, while the skin average pore radii remain relatively constant ($26 Å ) for up to 48 h. ß

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- Algorithms, Physical Chemistry, Kinetics, Porosity

In the past decades, it has become increasingly apparent that in addition to therapeutic effect, drugs need to exhibit favourable absorption, distribution, metabolism and excretion (ADME) characteristics to produce a desirable response in vivo. As the recent progress in drug discovery technology enables rapid synthesis of vast numbers of potential drug candidates, robust methods are required for the effective screening of compounds synthesized within such programs, so that compounds with poor pharmacokinetic properties can be rejected at an early stage of drug development. Furthermore, a viable in silico method would save resources by enabling virtual screening of drug candidates already prior to synthesis. This review gives a general overview of the approaches aimed at predicting biological permeation, one of the cornerstones behind the ADME behaviour of drugs. The most important experimental and computational models are reviewed. Physicochemical factors underlying the permeation process are discussed.

- by Lasse Murtomaki
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- Algorithms, Physical Chemistry, Membranes, Prediction

The goal of the present paper was to develop a quantitative structure-activity relationship (QSAR) method using a simple statistical approach, such as multiple linear regression (MLR) for predicting the blood-brain barrier (BBB) permeability of chemical compounds. The "best" MLR models, comprised log P and either molecular mass (M) or isolated atomic energy (E isol ), tested on a structurally diverse set of 66 compounds, is characterized the by correlation coefficients (R) around 0.8. The obtained models were validated using leave-one-out (LOO) cross-validation technique and the correlation coefficient of leave-one-out-R 2 LOO (Q 2 ) was at least 0.6. Analysis of a case from legal medicine demonstrated informative value of our QSAR model. To best authors' knowledge the present study is a first application of the developed QSAR models of BBB permeability to case from the legal medicine. Our data indicate that molecular energy-related descriptors, in combination with the well-known descriptors of lipophilicity may have a supportive value in predicting blood-brain distribution, which is of utmost importance in drug development and toxicological studies.

- by Roman Kaliszan and +1
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- Analytical Chemistry, Toxicology, Linear models, Permeability

Microperforated films (perforation diameter <200 lm) are an option for achieving the appropriate gaseous composition in modified atmosphere packaging, especially for fresh-cut products. In this project, static techniques were used to experimentally measure the oxygen and carbon dioxide transmission rates of microperforated films. Twenty nine microperforations of different dimensions (from 40 Â 30 lm to 350 Â 110 lm) and thickness (from 29 to 57 lm) were tested in the project. A potential equation was found to provide a good prediction of the dependence of the O 2 and CO 2 transmission rates on the perforation area. The data predicted by the equation was compared with those from five other bibliographic models. The empirical equation agrees, within the experimental range, with the modified Fick's law (considering the total diffusive pass length of a perforation as the sum of the perforation length and end correction term). The predictions of the proposed equation for thicker films and holes of larger dimensions (equivalent radius >3000 lm) correspond to those of the empirical models.

- by Jaime Eduardo Gonzalez-Díaz
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- Food Engineering, Carbon Dioxide, Packaging, Film

One of the approaches suggested for sequestering C02 is by injecting it in coalbed methane (CBM) reservoirs. Despite its potential importance for C02 sequestration, to our knowledge, C02 injection in CBM reservoirs for the purpose of sequestration has not been widely studied. Furthermore, a key element missing in most of the existing studies is the comprehensive characterization of the CBM reservoir structure. CBM reservoirs are complex porous media, since in addition to their primary pore structure, generated during coal formation, they also contain a variety of fractures, which may potentially play a key role in C02 sequestration, as they generally provide high permeability flow paths for both CO2 and C&. In this report we present an overview of our ongoing experimental and modeling efforts, which aim to investigate the injection, adsorption and sequestration of CO2 in CBM reservoirs, the enhanced C& production that results, as well as the main factors that affect the overall operation. We describe the various experimental techniques that we utilize, and discuss their range of application and the value of the data generated. We conclude with a brief overview of our modeling efforts aiming to close the knowledge gap and fill the need in this area. ..

- by Muhammad Sahimi
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- Production, Adsorption, Simulation, Natural Gas

Reservoir simulations of CO* injection into a water flooded oil reservoir show that significant amounts of oil may be recovered, and a high storage capacity of CO, is obtained also through displacement of water. Simulated storage capacities for CO, injection into an aquifer vary in the range 13-68% pore volume, depending on the prevailing displacement mechanisms.

- by Erik Lindeberg
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- Conservation, Migration, Enhanced Oil Recovery, Reservoir Simulation

Shale gas has become an increasingly important source of natural gas (CH 4) in the United States over the last decade. Due to its unconventional characteristics, injecting carbondioxide (CO 2) to enhance shale gas recovery (ESGR) is a potentially feasible method to increase gas-yield while both affording a sink for CO 2 and in reducing the potential for induced seismicity. However, understanding of this issue is limited with few pilot field studies proposed. This study examines CO 2-ESGR to better understand its feasibility and effectiveness. We explore the roles of important coupled phenomena activated during gas substitution especially vigorous feedbacks between sorptive behavior and permeability evolution. Permeability and porosity evolution models developed for sorptive fractured coal are adapted to the component characteristics of gas shales. These adapted models are used to probe the optimization of CO 2-ESGR for injection of CO 2 at overpressures of 0 MPa, 4 MPa and 8 MPa to investigate magnitudes of elevated CH 4 production, CO 2 storage rate and capacity, and of CO 2 early-breakthrough and permeability evolution in the reservoir. For the injection pressures selected, CH 4 production was enhanced by 2.3%, 14.3%, 28.5%, respectively, over the case where CO 2 is not injected. Distinctly different evolutions are noted for permeability in both fractures and matrix due to different dominating mechanisms. Fracture permeability increased by~1/3 for the injection scenarios due to the dominant influence of CH 4 de-sorption over CO 2 sorption. CO 2 sequestration capacity was only of the order of 10 4 m 3 when supercritical for a net recovery of CH 4 of 10 8 m 3. We investigated the potential of optimal CO 2-pulsed injection to enhance CH 4 production (absolute mass recovered)-without the undesirable effects of CO 2 early-breakthrough and also minimum cost on CO 2 injection. This utilizes the competitive sorptive behavior between CH 4 and CO 2 , can also reduce the potential for induced seismicity hence the entire system can be near net neutrality in terms of its carbon and seismic footprint.

- by Derek Elsworth
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- Engineering, Environmental Science, Geomechanics, Permeability

The main reason for the flux decline during the initial period of all filtration processes is the usual phenomena of concentration polarization and fouling. After this stage follows the cake filtration process that allows to obtain the steady state flux. The solute accumulated on the membrane surface forms a high concentration gel layer, which increases the effective membrane thickness and so reduces its hydraulic permeability. Different techniques are used to reduce this formation and use of helical baffles inside the membrane element is one of such techniques. The selection of appropriate helical baffle is vital to get improved permeation flux with minimum pressure drop for cross-flow feed. The number of helices per unit length has a considerable influence on the selected helical baffle. All experiments have been conducted with an inorganic tubular ultrafiltration membrane for filtering a supernatant from activated sludge plant consisting of suspended and biological solids. The influence of the operational parameters is studied in this paper. Nevertheless, the feed temperature and the concentration were kept constant at the industrial values. We found 1 bar as an optimal pressure, above this pressure the permeation flux decreases, contrarily to several works, which observe a plateau after certain value of pressure. Progressive fouling can be limited by use of helical baffles in the filtration element operated at low pressures and the flocculation of particles is reduced. On the other hand, we have found that the influence of Reynolds number inside the membrane tube and the feed flow-rate are similar to other studies that used different helical baffles.

- by Rahim Jassim
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- Engineering, Turbulence, Filtration, Activated Sludge

The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2c 2/2 ) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated with increased spontaneous and carcinogen-induced systemic tumorigenesis in Gucy2c 2/2 mice. GUCY2C regulated barrier integrity by repressing AKT1, associated with increased junction proteins occludin and claudin 4 in mice and Caco2 cells in vitro. Thus, GUCY2C defends the intestinal barrier, opposing colitis and systemic genotoxicity and tumorigenesis. The therapeutic potential of this observation is underscored by the emerging clinical development of oral GUCY2C ligands, which can be used for chemoprophylaxis in inflammatory bowel disease and cancer.

- by Michael Valentino
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- Membrane Proteins, DNA damage, Multidisciplinary, Intestinal Mucosa

Background and aims: Probiotics exert a beneficial effect on the host through modulation of gastrointestinal microflora. The aim of this study was to investigate the effect of the probiotic Lactobacillus plantarum 299v on gut barrier... more

- by John Macfie
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- Nutrition and Dietetics, Probiotics, Inflammation, Treatment Outcome

The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K p) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most lipophilic) have low penetration rates through intact skin. The present experiment not only confirms the proportionality between lipophilicity and potential for percutaneous penetration, but also illustrates that at a certain degree of lipophilicity of a model compound, the different skin compartments become more attractive for temporary deposition of model compounds. Moreover, a clear change from epidermal deposition towards a dominating dermis deposition of chemicals temporarily deposited within the skin is seen following damage to the skin barrier. Thus, the distribution of chemicals within the skin compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating the possibility of removing chemicals from the skin through different cleansing procedures following unintended dermal exposures.

- by Flemming Nielsen
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- Kinetics, Dermatology, In Vitro, Caffeine

PCER10 (4.84 ± 0.79), but none of them had an influence on ibuprofen. Conclusion: The investigated PCERs exhibited a penetration-enhancing effect on caffeine and testosterone but not on ibuprofen.

- by S. Calenbergh
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- Chemistry, Medicine, Caffeine, Testosterone

Magnetorheological fluids (MRFs) are typically thought of as Bingham-plastic (BP) fluids characterized by a yield stress. Partial substitution of micrometer-scale Fe particles with nanometer-scale Fe particles leads to bidisperse MRFs. This partial substitution mitigates particle sedimentation, but can reduce yield stress for high nanoparticle concentrations. We examine tradeoffs between increasing suspension stability versus decreasing in yield stress as nanoparticles are substituted for microparticles. Four groups of fluids with total Fe concentration of 50, 60, 70, and 80 wt% were considered. A sedimentation measuring device quantified sedimentation velocity of MRFs in a gravitational field. This sensor relates the rate of change of inductance relative to settling rate as Fe wt% decreases because of sedimentation. MRF flow curves were measured using a parallel disk rheometer and yield stress was identified using the BP flow model.

- by Norman Wereley
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- Engineering, Materials Science, Magnetic Materials, Stress

In the past several years, there has been a trend in the sunscreen/ cosmetics industry to replace micron-sized titanium dioxide (TiO 2) particles with nanoscale materials. The increased use of nanoscale TiO 2 has resulted in questions about these and other nanoproducts. This study examines the effects of using nanoscale TiO 2 on ultraviolet (UV) attenuation in simple to complex sunscreen formulations. UV light attenuation, product stability, and potential damage to the skin barrier were examined with both nanoscale and microscale TiO 2 particles. Results indicate that none of the formulations decreased the barrier function of the skin and the best UV attenuation occurs when the TiO 2 particles are stabilized with a coating and evenly distributed such as with non-agglomerated coated nanoscale materials. This indicates that nanoscale TiO 2 may have better efficacy while lacking toxicity. Ré sumé Au cours des dernières années, nous avons constaté une tendance dans l'industrie solaire/cosmétique pour le remplacement des particules micron-taille de dioxyde de titane (TiO 2) avec des matériaux de nano-échelle. L'utilisation accrue des particules de TiO 2 l'échelle du nanométre a engendré des questions sur tous les produits contenant des matériaux nano-échelle. Cette étude examine les effets de l'utilisation de particule de TiO 2 a l'échelle du nanomètre sur l'atténuation des rayons UV dans les formulations de crème solaire simple et complexe. Nous avons étudié l'atténuation de la luminosité ultraviolet (UV), la stabilité du produit et les effets sur la fonction barrière de la peau, avec les particules de TiO 2 nano-échelle et micro-échelle. Les résultats indiquent que les particules a l'échelle du nanométre, enduits et non-aggloméré, fournissent une excellente atténuation UV, sans diminuer la fonction barrière de la peau. Ceci suggére que les particules de TiO 2 a l'échelle du nanométre ont une meilleure efficacité, sans poser des inquiétudes en ce qui concerne leur securité.

- by Bill Doub
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- Nanoparticle, Scanning Electron Microscopy, Morphology, Titanium

elsewhere (Jones and Chapman, 1995a, b), but more to discuss the rationale of such approaches, including consid-Artificial membrane systems are being used increaserations and controls. It is hoped that the references ingly to study the function and role of plant membrane provided will supply the reader with any more detailed proteins, particularly solute transporters which catainformation that is required. lyse counter-exchange of metabolites. Performing

- by M. Emes
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- Plant Biology, Permeability, Experimental Botany, Surfactant

In medical diagnosis and therapy, finding an appropriate method to evaluate the effect of various drugs is crucial. There are several ways to qualify a drug for a specific disease and one way is through medical image analysis. This process varies with the tissues we want to analyze and the imaging technique that is employed. For hydrous tissues such as nasal and trachea, Magnetic Resonance Imaging can be helpful for further evaluations. Trachea can be challenged by an antigen which will increase both nasal vascular permeability and intranasal pressure. Another effect of antigen challenge into nasal cavity which may cause nasal blockage, is swelling of nasal mucosa and a decrease in nasopharyngeal airway. In this paper, we study the effect of an antihistamine drug on swelling of mucosa. This antihistamine is called Azelastine and is injected to guinea pig to evaluate the swelling changes of nasal and trachea mucosa. After 20 minutes of injection, a MR image of the motionless animal is taken and this imaging will continue for 30, 40, 50 and 60 minutes from injection. Due to the ambiguous nature of respiratory tract, finding a precise method for processing has useful results. Watershed algorithm has widespread function in medical images but its defects in segmentation can be modified by different methods. An enhanced level set method is used here; a nonparametric active contour for nasal and trachea detection. This automatic image segmentation and tissue detection can help physicians evaluate the effect of a specific drug from medical images.

- by Miad Faezipour
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- Magnetic Resonance Imaging, Image segmentation, Permeability, Level Set

A diffusion model is presented to account for the disposition of chemicals applied to skin as transient exposures. Two conditions are considered that apply to the skin surface following the exposure period, which are applicable to chemicals exhibiting two extremes of chemical volatility. For one case, representing highly volatile compounds, the solution is generalized to apply to multiple transient exposures. For both cases, algebraic expressions are derived to calculate the total amount of chemical that penetrates the skin. The theory is applied to experimental measurements of the in vitro penetration of diethyl phthalate applied to hairless guinea pig (HGP) skin and silicone rubber membranes (SRMs) as transient exposures. The transient exposure theory ably models the experimental data, with coefficients of determination greater than 0.97 (HGP) and greater than 0.99 (SRM). The ability of parameters derived from concurrent infinite dose experiments to predict the time course of absorption from transient exposures is explored. Discrepancies were found between measured cumulative penetration of chemical from transient exposure experiments and penetration predicted from parameters derived from infinite dose experiments, particularly for HGP. Possible reasons are explored. The current model may provide a realistic framework for estimating absorption from occupational, environmental and pharmaceutical dermal exposures. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1578–1592, 2008

- by Ana Barbero
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- Diffusion, Permeability, Pharmaceutical Sciences, Membrane transport
- by Babette Weksler
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- Permeability, Cell Fractionation, Skin, Time Factors

The overall goal of this study was to develop cremophor-free oral microemulsions of paclitaxel (PAC) to enhance its permeability and oral absorption. The mechanism of this enhancement, as well as characteristics of the microemulsions relevant to the increase in permeability and absorption of the low solubility, low permeability PAC was investigated. Phase diagrams were used to determine the macroscopic phase behavior of the microemulsions and to compare the efficiency of different surfactant-oil mixtures to incorporate water. The microemulsion region on the phase diagrams utilizing surfactant-myvacet oil combinations was in decreasing order: lecithin: butanol: myvacet oil (LBM, 48.5%) > centromix CPS: 1butanol: myvacet oil (CPS, 45.15%) > capmul MCM: polysorbate 80: myvacet oil (CPM, 27.6%) > capryol 90: polysorbate 80: myvacet oil (CP-P80, 23.9%) > capmul: myvacet oil (CM, 20%). Oil-in-water (o/w) microemulsions had larger droplet sizes (687-1010 nm) than the water-in-oil (w/o) microemulsions (272-363 nm) when measured using a Zetasizer nano series particle size analyzer. Utilizing nuclear magnetic resonance spectroscopy (NMR), the self-diffusion coefficient (D) of PAC in CM, LBM and CPM containing 10% of deuterium oxide (D 2 O) was 2.24 Â 10 À11 , 1.97 Â 10 À11 and 0.51 Â 10 À11 m 2 /s, respectively. These values indicate the faster molecular mobility of PAC in the two w/o microemulsions (CM and LBM) than the o/w microemulsion -CPM. The in situ permeability of PAC through male CD-IGS rat intestine was 3-and 11-fold higher from LBM and CM, respectively, than that from the control clinical formulation, Taxol Ò (CE, cremophor: ethanol) in a single pass perfusion study. PAC permeability was significantly increased in the presence of the pgp/CYP3A4 inhibitor cyclosporine A (CsA). This enhancement may be attributed to the pgp inhibitory effect of the surfactants, oil and/or the membrane perturbation effect of the surfactants. The oral disposition of PAC in CM, LBM and CPM compared to CE was studied in male CD-IGS rats after a single oral dose (20 mg/kg). The area-under-the-curve of PAC in CM was significantly larger than LBM, CPM and CE. Oral microemulsions of PAC were developed that increased both the permeability and AUC of PAC as compared to CE.

- by Kurunthachalam Kannan
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- Pharmacokinetics, Oils, Microemulsion, Permeability

Soft and semi-soft farm cheeses made from pasteurized milk and having high moisture content are common craft products in Ireland. Theses cheeses have limited shelf-life and needs to consider the release of CO 2 and consumption of O 2 for packaging design. The objective of this work was to analyze the effect of the storage temperature (4, 12 and 20°C) and different gas compositions (O 2 and CO 2) on the gas exchange rate of whole soft cheese (camembert-type). The O 2 consumption rate was found to be 26.21 ml kg À1 h À1 at 4°C when stored in 19% O 2 and 10% CO 2 gas composition. It increased to 91.03 ml kg À1 h À1 when temperature increased to 20°C at the same gas composition. A Pareto analysis showed that the temperature and O 2 concentration have a significant effect on the gas exchange rate, whereas the effect of CO 2 concentration was negligible. The effect of O 2 concentration on the gas exchange rate was found to be well described by a Michaelis-Menten equation whereas an Arrhenius equation was used to fit the effect of temperature. Combining the effect of O 2 and temperature, a global model was developed and validated which provided a good fit to the experimental data, explaining 94% of the variance of the data.

- by Jorge Oliveira
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- Food Engineering, Packaging, Food, Mathematical Modelling

The aim of the present study was to investigate the effect of poly(acrylic acid)-cysteine (PAA-cysteine) exhibiting a molecular mass of 100 and 250 kDa and reduced glutathione (GSH) on the absorption of the P-glycoprotein (P-gp) and cytochrome P450 (CYP450) substrate paclitaxel in vitro and in vivo. In vitro transport studies were performed with Caco-2 monolayers. Furthermore, the delivery system based on PAA-cysteine, GSH and paclitaxel was evaluated in vivo in rats. In vitro, the formulation comprising 0.5% (m/v) PAA-cysteine (100 kDa)/0.5% (m/v) GSH improved the transport of paclitaxel 6.7-fold (P app ¼ 8.7 AE 1.3 Â 10 À6 cm/s) in comparison to paclitaxel itself serving as buffer only control (P app ¼ 1.3 AE 0.4 Â 10 À6 cm/s). Moreover, in the presence of the formulation containing 0.5% (m/v) PAAcysteine (250 kDa)/0.5% (m/v) GSH paclitaxel absorption was even 7.4-fold (P app ¼ 9.7 AE 0.3 Â 10 À6 cm/s) improved in comparison to the buffer only control. In vivo, the oral administration of formulations containing 1 mg of paclitaxel, 1 mg of GSH and 8 mg of PAA-cysteine (100 kDa or 250 kDa) resulted in an improved paclitaxel plasma concentration and bioavailability. The area under the plasma concentrationtime curve (AUC 0e8) of paclitaxel was 4.7-fold and 5.7-fold improved in comparison to the oral formulation containing paclitaxel alone, respectively. Moreover, c max was improved by 6.3-fold and even 7.3fold in comparison to the oral formulation containing paclitaxel alone, respectively. Thus, according to the achieved results it is suggested that PAA-cysteine in combination with GSH would be a potentially valuable tool for improving the oral bioavailability of P-gp and CYP450 substrates such as paclitaxel.

- by Javed Iqbal
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- Biomaterials, Drug delivery, Drug Delivery System, Multidisciplinary

The Enhanced Geothermal System (EGS) of Soultz-sous-Forêts (France) is made of three boreholes (GPK2, GPK3 and GPK4). The hydraulic connection between the wells, which is crucial to get an efficient geothermal exchanger, may be unfortunately hindered by the more or less complete sealing of fractures by hydrothermal neoformed minerals. This paper takes over the recent work of the authors that quantified the amounts of calcite on a random sampling within the three boreholes in order to assess the role of this mineral on the exchanger zone and in particular its influence on the permeability of the flow pathways. In the present study we focused the sampling on the fracture zones that have been identified as flow pathways. Now, all the three wells show high (above 10 wt.%) and moderate to low (between 2.0 and 7.0 wt.%) calcite anomalies. In GPK2, fracture zones with a high conductivity are characterized by high calcite content, and those with a low conductivity by low calcite content. The fracture zones of GPK3 show the opposite relationship: the most efficient flow pathways have a low calcite content, whilst the less conductive show a high calcite content. Fluid flow in GPK4 is mainly accommodated by the fracture zone at 4775 m MD that is not calcite rich. The other fracture zones of GPK4, which are interpreted with a similar and low conductivity, show low, moderate and high calcite contents. These data show clearly that GPK2 is different from GPK3 and GPK4, these two later being more comparable. It suggests that the fracture zones themselves may be of different type, and that the connectivity to the fracture network may be different too. This difference of behaviour is consistent with microseismicity data showing that GPK2 is characterized by a rather compact and well structured network of medium-scale fracture whereas GPK3 and GPK4 are altogether characterized by more localized and discrete fracture zones. Some issues remain such as the occurrence of calcite anomalies with no evident relationship with fracture zones, as well as the occurrence of identified flow pathways with no abnormal calcite content.

- by Albert GENTER
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- Geology, Geochemistry, Geophysics, Hydraulics
- by LIz Vanderlinde
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- Morphology, Desiccation Tolerance, Biological Sciences, Cell morphology

Background: Zinc carnosine (ZnC) is a health food product claimed to possess health-promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited. Aim: To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial. Methods: In vitro studies used pro-migratory (wounded monolayer) and proliferation ([ 3 H]-thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small-intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration. Results: ZnC stimulated migration and proliferation of cells in a dose-dependent manner (maximum effects in both assays at 100 mmol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p,0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small-intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p,0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p,0.01), whereas no significant increase in permeability was seen when ZnC was coadministered. Conclusion: ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted.

- by asif mahmood
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- Clinical Trial, Treatment, Wound Healing, Cell Division

The thick film NixZn(1−x)Fe2O4 on alumina substrate was prepared by screen printing of the ferrite powder synthesized by chemical co-precipitation method using nitrate precursors. These NixZn(1−x)Fe2O4 thick films of varying x were characterized by X-ray diffraction, FTIR spectroscopy and SEM (scanning electron microscopy). The permittivity and permeability were measured by overlay technique. Voltage standing wave ratio method was also used to measure the dielectric constant. The permittivity was found to increase with Ni content varying between 13 and 18. The permeability was ∼3.01. The overlay technique provides an easy method for measurement of permittivity and permeability of ferrite thick film.

3,5-Seco-4-nor-cholestan-5-one oxime-3-ol (TRO40303) is a new cardioprotective compound coming from a chemical series identified initially for neuroprotective properties. TRO40303 binds specifically to the mitochondrial translocator protein 18 kDa (TSPO) at the cholesterol site. After intravenous administration, TRO40303 tissue distribution was comparable to that of TSPO, and, in particular, the drug accumulated rapidly in the heart. In a model of 35 min of myocardial ischemia/24 h of reperfusion in rats, TRO40303 (2.5 mg/kg) reduced infarct size by 38% (p Ͻ 0.01 versus control), when administered 10 min before reperfusion, which was correlated with reduced release of apoptosis-inducing factor from mitochondria to the cytoplasm in the ischemic area at risk. Although TRO40303 had no effect on the calcium retention capacity of isolated mitochondria, unlike cyclosporine A, the drug delayed mitochondrial permeability transition pore (mPTP) opening and cell death in isolated adult rat cardiomyocytes subjected to 2 h of hypoxia followed by 2 h of reoxygenation and inhibited mPTP opening in neonatal rat cardiomyocytes treated with hydrogen peroxide. The effects of TRO40303 on mPTP in cell models of oxidative stress are correlated with a significant reduction in reactive oxygen species production and subsequent calcium overload. TRO40303 is a new mitochondrial-targeted drug and inhibits mPTP triggered by oxidative stress. Its mode of action differs from that of other mPTP inhibitors such as cyclosporine A, thus providing a new pharmacological approach to study mPTP regulation. Its efficacy in an animal model of myocardial infarctions makes TRO40303 a promising new drug for the reduction of cardiac ischemia-reperfusion injury.

- by THIERRY BORDET and +2
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- Pharmacology, Calcium, Oxidative Stress, Western blotting

Cryopreservation currently is the only method for long-term preservation of cellular viability and function for uses in cellular therapies. Characterizing the cryobiological response of a cell type is essential in the approach to designing and optimizing cryopreservation protocols. For cells used in therapies, there is significant interest in designing cryopreservation protocols that do not rely on dimethyl sulfoxide (Me 2 SO) as a cryoprotectant, since this cryoprotectant has been shown to have adverse effects on hematopoietic stem cell (HSC) transplant patients. This study characterized the cryobiological responses of the human erythroleukemic stem cell line TF-1, as a model for HSC. We measured the osmotic parameters of TF-1 cells, including the osmotically-inactive fraction, temperature-dependent membrane hydraulic conductivity and the membrane permeability to 1 M Me 2 SO. A two-step freezing procedure (interrupted rapid cooling with hold time) and a graded freezing procedure (interrupted slow cooling without hold time) were used to characterize TF-1 cell recovery during various phases of the cooling process. One outcome of these experiments was high recovery of TF-1 cells cryopreserved in the absence of traditional cryoprotectants. The results of this study of the cryobiology of TF-1 cells will be critical for future understanding of the cryobiology of HSC, and to the design of cryopreservation protocols with specific design criteria for applications in cellular therapies.

- by Lisa Ross-Rodriguez
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- Cryobiology, Methodology, Treatment, Cryopreservation

The Vapor Extraction (VAPEX) process, a newly developed Enhanced Oil Recovery (EOR) process to recover heavy oil and bitumen, has been studied theoretically and experimentally and is found a promising EOR method for certain heavy oil... more

- by behzad rostami
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- Petroleum, Enhanced Oil Recovery, Gravity, Permeability

The Hermod sand of the Stine Segments, Siri Field, Danish North Sea, displays large permeability variations (1-600 mD). These permeability variations represent horizontal layering in the reservoir, largely formed by diagenetic processes. They have a significant impact on reservoir performance, because horizontal producers in fairly thin reservoirs ($30 m) are protected against bottom-water influx and can produce water-free for long periods of time. This paper presents the results of a detailed multidisciplinary study where the observed variation in permeability can be explained by two main diagenetic phases: silica, as opal cement and microquartz, and berthierine, a serpentine mineral that is closely related to chlorite. Opal/microquartz and berthierine cements dominate in separate parts of the reservoir bodies. Opal/ microquartz cemented sands have high permeability (typically 500-600 mD). Berthierine cement has a different growth pattern in the oil and water zones, resulting in intermediate permeability in the oil zone (typically 50-100 mD) and very low permeability in the water zone (typically 1-10 mD).

- by Henrik Friis
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- Geology, Geophysics, Diagenesis, Growth

The two-part article aimed to investigate poloxamer 407-based microspheres as a novel platform for enhancing and controlling the delivery of atenolol across the oromucosal tissue. In the Part I of the work, atenolol-loaded poloxamers 407 microparticles were prepared by the solvent free spray congealing technology. This approach was feasible upon the high viscosity of the systems allowing for high loaded (20% w/w) non-aggregated microspheres. Several formulations were studied and the results demonstrated that the drug release patterns, solubility data, mucoadhesion to buccal tissue and gelling properties in saliva could be modified by adding different amount of an amphiphilic polymer-lipid excipient (Gelucire(®) 50/13) to poloxamer 407. Particularly, microspheres based only on poloxamer 407 exhibited very high solubility, mucoadhesive strength and gelling behaviour. To assess their potential as matrix for buccal application, the gelling property and the drug release from tablets obta...

- by Lars Holden
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- Uncertainty, Porosity, Permeability, Markov chain

Numerical programs for simulating flow and reactive transport in porous media is essential for predicting reservoir properties related to CO 2 sequestration performance, subsurface storage and risk assessment. In this paper we solve the Navier Stokes' equation using finite difference method, on a simulated porous rock structure, to study the velocity distribution of fluid flowing through it under a constant pressure gradient. A reactive solute carried through the fluid is allowed to interact with the minerals in the rock. This chemical reaction dissolves the mineral which changes the rock structure thus affecting its flow properties. These changes of flow properties are studied with variation in reactive solute concentration and pressure field. The different mechanisms of dissolution responsible for the variation of flow properties for the different parameters is predicted. Before the onset of homogeneous dissolution, variation in porosity follows a power-law behaviour with change in permeability when the latter is scaled by the concentration of the reactive species. The simulation results are compared with available experimental data and found to give a reasonable match.

- by DR SUPTI SADHUKHAN
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- Hydrology, Multidisciplinary, Porosity, Permeability

Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8 cells, a cell line from a human ileocoecal carcinoma, we studied the effects of spices on transepithelial electrical resistance (TER), permeability for fluorescein isothiocyanate (FITC)-labeled dextrans with graded molecular weight, and morphological alterations of tight junctions by immunofluorescence using an anti-ZO-1 antibody, a marker for tight junction integrity. Two different reactivity patterns were observed: paprika and cayenne pepper significantly decreased the TER and increased permeability for 10-, 20-and 40-kDa dextrans but not for -70 kDa dextrans. Simultaneously, tight junctions exhibited a discontinuous pattern. Applying extracts from black or green pepper, bay leaf or nutmeg increased the TER and macromolecular permeability remained low. Immunofluorescence ZO-1 staining was preserved. In accordance with the above findings, capsaicin transiently reduced resistance and piperine increased resistance, making them candidates for causing the effects seen with crude spice extracts. The observation that Solanaceae spices (paprika, cayenne pepper) increase permeability for ions and macromolecules might be of pathophysiological importance, particularly with respect to food allergy and intolerance. J. Nutr. 128: 577-581, 1998. KEY WORDS: • spices • intestinal epithelia • transepithelial electrical resistance • permeability • tight junctions • HCT-8 cells MATERIALS AND METHODS 1 The costs of publication of this article were defrayed in part by the payment Spice extracts. Spices (black and green pepper grains, bay leaves, of page charges. This article must therefore be hereby marked ''advertisement'' nutmeg, chili pepper, cayenne pepper and paprika powder) were purin accordance with 18 USC section 1734 solely to indicate this fact.

- by Erika Jensen-Jarolim
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- Nutrition and Dietetics, Nutrition, Pepper, Animal Production

Effective cancer therapy remains one of the most challenging tasks to the scientific community, with little advancement on overall cancer survival landscape during the last two decades. A major limitation inherent to most conventional anticancer chemotherapeutic agents is their lack of tumor selectivity. One way to achieve selective drug targeting to solid tumors is to exploit abnormalities of tumor vasculature, namely hypervascularization, aberrant vascular architecture, extensive production of vascular permeability factors stimulating extravasation within tumor tissues, and lack of lymphatic drainage. Due to their large size, nano-sized macromolecular anticancer drugs administered intravenously (i.v.) escape renal clearance. Being unable to penetrate through tight endothelial junctions of normal blood vessels, their concentration builds up in the plasma rendering them long plasma half-life. More importantly, they can selectively extravasate in tumor tissues due to its abnormal vascular nature. Overtime the tumor concentration will build up reaching several folds higher than that of the plasma due to lack of efficient lymphatic drainage in solid tumor, an ideal application for EPR-based selective anticancer nanotherapy. Indeed, this selective high local concentration of nano-sized anticancer drugs in tumor tissues has proven superior in therapeutic effect with minimal side effects in both preclinical and clinical settings.

- by Arun Iyer and +1
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- Nanomedicine, Polymers, Micelles, Liver

A theoretical approach was used to determine the distribution of a poly(methylmethacrylate) cement after its injection into a porous structure. The predictions of the model were then compared to experimental results obtained by injecting a polymethylmethacrylate cement into an open-porous ceramic filter. The goal was to define a model that could predict what factors affect the risk of cement extravasation and hence how the risk of cement extravasation can be minimized. The calculations were based on two important rheological laws: the law of Hagen-Poiseuille and the law of Darcy. The law of Hagen-Poiseuille describes the flow of a fluid in a cylindrical tube. The law of Darcy describes the flow of a fluid through a porous media. The model predicted that the extravasation risk was decreased when the cement viscosity, the bone pore size, the bone permeability and the bone porosity were increased, and when the diameter of the extravasation path and the viscosity of the marrow were decreased. Experimentally, the effect of the marrow viscosity and extravasation path could be evidenced. Therefore, the model was believed to be an adequate approximation of the experimental behavior. In conclusion, the experimental results demonstrated that the model was adequate and that the best practical way to decrease the risk of extravasation is to increase the cement viscosity. r

- by Marc Bohner
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- Biomaterials, Rheology, Multidisciplinary, Soil Cementation

The treatment of brain malignancies with boron neutron capture therapy depends on their ability to cross the blood-brain barrier (BBB). An especially promising class of boron-containing compounds is the rhenacarboranes that, if able to cross the BBB, could act as delivery vehicles as well as a source of boron. Here, we examined the ability of the 3-NO-3,3-2 -(2,2Ј-N 2 C 10 H 6 (Me){(CH 2 ) 7 131 I}-4,4Ј)-closo-3,1,2-ReC 2 B 9 H 11 (rhenacarborane) labeled with iodine-131 to be taken up into the bloodstream after subcutaneous administration and to cross the BBB. The 131 I-rhenacarborane was quickly absorbed from the injection site and reached a steady state in arterial serum of 2.59%/ml of the administered dose. Between 73 and 95% of the radioactivity in serum 6 h after administration represented intact 131 I-rhenacarborane. Its octanol/buffer partition coefficient was 1.74, showing it to be lipophilic. Tissue/serum ratios for brain, lung, and liver showed classic patterns for a lipidsoluble substance with high levels immediately achieved and rapid redistribution. For brain, a steady state of approximately 0.107% of the administered dose/gram-brain was rapidly reached, and 71% of the radioactivity in brain 6 h after subcutaneous administration represented intact 131 I-rhenacarborane. Steady-state values were 1.53 and 0.89% of the injected dose per gram for lung and liver, respectively. 131 I-Rhenacarborane was quickly effluxed from brain by a nonsaturable system after its injection into the lateral ventricle of the brain. In conclusion, these results show that a rhenacarborane was enzymatically resistant and able to cross the BBB by transmembrane diffusion and accumulate in brain in substantial amounts. This supports their use as therapeutic agents for targeting the central nervous system. ABBREVIATIONS: BNCT, boron neutron capture therapy; CNS, central nervous system; BBB, blood-brain barrier; THF, tetrahydrofuran; PPh 4 Br, tetraphenylphosphonium bromide; IR, infrared; TLC, thin layer chromatography; DMSO, dimethyl sulfoxide; %Inj/g, percentage of an intravenous dose taken up per gram of brain; %Inj/brain, residual in brain expressed as a percentage of the dose injected into the lateral ventricle of the brain; vis., visible; PC, partition coefficient; complex 1, 3,3-(CO) 2 -3-NO-closo-3,1,2-ReC 2 B 9 H 11 ; complex 2, PPh 4 ][3-Br

- by Paul Jelliss
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- Pharmacology, Permeability, Mice, Blood brain barrier

We investigated the effects of corticosteroid and doxycycline on expression of matrix metalloproteinase (MMP)-9 and inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) signaling pathways, c-jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK) and p38, in experimental murine dry eye. Experimental dry eye (EDE) was created in C57BL6 mice, with or without or topical treatment consisting of 1% methylprednisolone, 0.025% doxycycline or balanced salt solution four times per day. MMP-9 expression in the cornea epithelia was evaluated by laser scanning confocal microscopy. Gelatinase activity in the cornea was evaluated by in situ zymography and MMP-9 activity in tear washings was evaluated by gelatin zymography. Total and phosphorylated MAPKs (JNK1/2, ERK1/2, p38) were detected by Luminex immunobead assay. Levels of MMP-9, interleukin (IL)-1alpha, IL-1beta and tumor necrosis factor (TNF)-alpha RNA transcripts were evaluated by real-time PCR. MMP-9 immunoreactivity was localized to the apical corneal epithelial cell membranes in normal control eyes. Desiccating stress significantly increased production of MMP-9 by the corneal epithelium and increased its activity in the corneal epithelium and tear fluid. Dryness also increased expression of IL-1alpha, IL-1beta and TNF-alpha mRNA and stimulated phosphorylation of JNK1/2, ERK1/2 and p38 MAPKs in the corneal epithelium. Both methylprednisolone and doxycycline reduced expression and activity of MMP-9, decreased levels of inflammatory cytokines transcripts and reduced activation of MAPKs in the corneal epithelium in response to EDE. Desiccating stress stimulates expression of MMP-9, IL-1alpha, IL-1beta and TNF-alpha mRNA , as well as activates MAPK signaling pathways in the corneal epithelium. Both corticosteroid and doxycycline suppressed this molecular stress response.

- by Cintia De Paiva
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- Immunohistochemistry, Confocal Microscopy, real time PCR, Permeability

The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effects of this drug. Here, we demonstrate that dimebon enhances the resistance of the isolated rat brain and liver mitochondria to the induction of mitochondrial permeability transition (MPT) by calcium ions even in the presence of atractyloside, a MPT pore (MPTP) opener, but is ineffective against atractyloside-induced mitochondria swelling. Unlike cyclosporine A (CsA), a MPTP inhibitor, Dimebon does not influence the adenine nucleotide translocase (ANT) conformational changes and is not able to prevent the MPT of de-energized mitochondria. Using three different assays, and using amyloid-β peptide for inducing mitochondrial toxicity, we show that the influence of dimebon ...

- by Gjumrakch Aliev
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- Calcium, Enzyme Inhibitors, Mitochondria, Brain

The objective of the present study was to investigate the iontophoretic transport behavior across multiple membranes of different barrier properties. Spectra/ Por 1 (SP) and Ionac membranes were the synthetic membranes and sclera was the biomembrane in this model study. The barrier properties of SP membranes were determined individually in passive and iontophoresis transport experiments with tetraethylammonium ion (TEA), chloride ion (Cl), and mannitol as the model permeants. Passive and iontophoretic transport experiments were then conducted with an assembly of SP membranes. The contribution of electroosmosis to iontophoresis was assessed using the mannitol data. Model analysis was performed to study the contribution of diffusion and electromigration to electrotransport across the multiple membrane system. The effects of membrane barrier thickness upon ion-exchange membrane-enhanced iontophoresis were examined with Ionac, SP, and sclera. The present study shows that iontophoretic transport of TEA across the membrane system was related to the thicknesses and permeability coefficients of the membranes and the electromobilities of the permeant across the individual membranes in the assembly. Model analysis suggests significant contribution of diffusion within the membranes across the membrane system, and this mechanism is relatively independent of the current density applied across the system in iontophoresis dominant transport. ß Ã Mean AE SD, n ! 3. a Number of membranes in parentheses. b Calculated using Eq. (3).

- by Sarah Molokhia
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- Computer Simulation, Diffusion, Permeability, Pharmaceutical Sciences

The permeability and strength of pervious concrete depend on the particle sizes and proportions of the constituent materials of which the concrete is made of. In this paper, structural property and permeability of pervious concrete made with different coarse aggregate sizes is presented. For the different aggregate/cement ratio used in this study, coarse aggregate size 9.375 mm has higher compressive strength values compared to those made from 18.75 mm aggregate size while 18.75 mm aggregate size had higher permeability value compared to that of 9.38 mm. The average specific gravity of the two aggregates sizes used was 2.7. Aggregate/cement ratio of 6:1, 8:1 and 10:1 respectively were used to produce three different batches of fresh concrete using 18.75mm aggregate size and same ratios were used for 9.375mm coarse aggregate size to produce another three different batches. In each case, aggregate/cement ratio of 6:1 gave the highest compressive strength compared to other aggregate/ce...

- by Johnson Oluremi
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- Materials Science, Porosity, Permeability, Compressive Strength

Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the fi...

- by Lajos Szente
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- Chemistry, Flow Cytometry, Fluorescence, Confocal Microscopy

Pseudomonas aeruginosa, when cultured under the appropriate conditions, secretes rhamnolipids to the external medium. These glycolipids constitute one of the most interesting classes of biosurfactants so far. A dirhamnolipid fraction was isolated and purified from the crude biosurfactant, and its action on model and biological membranes was studied. Dirhamnolipid induced leakage of internal contents, as measured by the release of carboxyfluorescein, in phosphatidylcholine unilamellar vesicles, at concentrations below its CMC. Membrane solubilization was not observed within this concentration range. The presence of inverted cone-shaped lipids in the membrane, namely lysophosphatidylcholine, accelerated leakage, whereas cone-shaped lipids, like phosphatidylethanolamine, decreased leakage rate. Increasing concentrations of cholesterol protected the membrane against dirhamnolipid-induced leakage, which was totally abolished by the presence of 50 mol% of the sterol. Dirhamnolipid caused hemolysis of human erythrocytes through a lytic mechanism, as shown by the similar rates of K + and hemoglobin leakage, and by the absence of effect of osmotic protectants. Scanning electron microscopy showed that the addition of the biosurfactant changed the usual disc shape of erythrocytes into that of spheroechinocytes. The results are discussed within the frame of the biological actions of dirhamnolipid, and the possible future applications of this biosurfactant.

- by Jose A. Teruel
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- Engineering, Chemistry, Kinetics, Medicine

Data from the Canada-U.S.A. (CANUSA) Study have recently confirmed a long-suspected linkage between total clearance and patient survival in peritoneal dialysis (PD). Recognizing that what we have historically accepted as adequate PD simply is not, the Ad Hoc Committee on Peritoneal Dialysis Adequacy met in January, 1996. This committee of invited experts was convened by Baxter Healthcare Corporation to prepare a consensus statement that provides clinical recommendations for achieving clearance guidelines for peritoneal dialysis. Through an analysis of 806 PD patients, the group concluded that adequate clearance delivered with PD can be achieved in almost all patients if the prescription is individualized according to the patient's body surface area, amount of residual renal function, and peritoneal membrane transport characteristics. Use of 2.5 L to 3.0 L fill volumes, the addition of an extra exchange, and giving automated peritoneal dialysis patients a "wet" day are ...

- by Alan Hull and +2
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- Quality of life, Life Style, Treatment Outcome, Clinical Practice
- by John Macfie
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- Nutrition and Dietetics, Probiotics, Clinical Nutrition, Intestinal Mucosa

The degradation of polyamide (PA) nanofiltration and reverse osmosis membranes by chlorine needs to be understood in order to develop chlorine-resistant membranes. Coated and uncoated fully aromatic (FA) and piperazine (PIP) semi-aromatic PA membranes were treated with hypochlorite solution and analyzed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR). XPS results showed that in chlorine treated FA PA membranes the ratio of bound chlorine to surface nitrogen was 1:1 whereas it was only 1:6 in the case of PIP PA membranes. Surface oxygen of uncoated FA and PIP membranes increased with increasing hypochlorite concentration whereas it decreased for coated FA membranes. High resolution XPS data support that chlorination increased the number of carboxylic groups on the PA surface, which appear to form by hydrolysis of the amide bonds (C(O)−N). FTIR data indicated the disappearance of the amide II band (1541 cm −1 ) and aromatic amide peak (1609 cm −1 ) in both coated and uncoated chlorinated FA membranes, consistent with the N-chlorination suggested by the XPS results. Furthermore, the surface charge of chlorinated membranes at low pH (<6) became negative, consistent with amide-nitrogen chlorination. Chlorination appeared to both increase and decrease membrane hydrophobicity depending on chlorination exposure conditions, which implied that Nchlorination and hydrolysis may be competing processes. The effects of property changes on the membrane performance were also observed for NF90, BW30, and NF270 membranes.

- by James O. Leckie
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- Water, Calcium, Filtration, Nanotechnology

Alpha-tocopherol (AT) is the vitamin E homologue with the highest in vivo biological activity. AT protects against the carcinogenic and mutagenic activity of ionizing radiation and chemical agents, and possibly against UV-induced cutaneous damage. For stability consideration, alpha-tocopherol is usually used as its prodrug ester, alpha-tocopherol acetate (ATA), which once absorbed into the skin is hydrolyzed to alpha-tocopherol, the active form. The objective of this research was to characterize in vitro the permeation properties of ATA from various solutions and gel formulations. Permeation studies were conducted using modified Franz diffusion cells and human cadaver skin as the membrane. Specifically, 5% (w/w) alpha-tocopherol acetate was formulated in the following vehicles: ethanol, isopropyl myristate, light mineral oil, 1% Klucel gel in ethanol, and 3% Klucel gel in ethanol (w/w). The receiver temperature was 37 degrees C. Samples from the receiver were collected at 2, 4, 6, 8...

- by Grazia Stagni
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- In Vitro, Diffusion, Permeability, Skin

NMR is a popular logging technique used to estimate pore size information, formation permeability, wettability and irreducible water saturation. Quantitative interpretation of NMR data is based on a set of fundamental assumptions (e.g., pore isolation and fast diffusion). These assumptions establish the quantitative link between NMR response and petrophysical predictions. While there is a need to test these assumptions directly, to date no quantitative study on reservoir core material has been undertaken. The ability to digitally image reservoir rock in 3D, calculate petrophysical properties directly from the images coupled with a comprehensive simulation tool to numerically generate a range of NMR response data may help to address this need.

- by Christoph Arns
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- Geology, Petrophysics, Nuclear Magnetic Resonance, Permeability

The surface of all tissues, including the stratum corneum, carries a negative charge. Following that fact it is assumed that a positively charged topical formulation could lead to an enhanced penetration because of an increased interaction with the negative charge of the membrane. The intention of this study is to prove an enhanced penetration of a positively charged nanoemulsion compared to a negatively charged nanoemulsion, both containing prednicarbate. The release and penetration of these nanoemulsions, produced with the high pressure homogenization method, were investigated. Regarding these results reveals that the release of the negatively charged formulation is higher compared to the positively charged nanoemulsion, while the penetration of the positively charged nanoemulsion is enhanced compared to the negatively charged formulation. The results of the investigated positively charged nanoemulsion containing prednicarbate show that its topical use could be advantageous for the therapy of atopic dermatitis, especially regarding phytosphingosine, which was responsible for the positive charge.

- by Yücel Baspinar
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- Kinetics, Nanoparticles, Nanotechnology, Pharmaceutics

Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring in vivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use of in vitro and in silico tools as well as reduce the number of in vivo studies required, a team-based discussion tool is proposed that provides a 'road map' to guide the selection of profiling assays that should be considered when optimising oral bioavailability. This road map divides the factors that contribute to poor oral bioavailability into two interrelated categories: absorption and metabolism. This road map provides an interface for cross discipline discussions and a systematic approach to the experimentation that drives the drug discovery process towards a common goal -acceptable oral bioavailability using minimal resources in an acceptable time frame.

- by Ayman El-kattan
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- Pharmacology, Biochemistry, Chemistry, Pharmacy