Cytochrome bc1 regulates the mitochondrial permeability transition by two distinct pathways

The mitochondrial permeability transition (MPT) pore is a calcium-sensitive channel in the mitochondrial inner membrane that plays a crucial role in cell death. Here we show that cytochrome bc₁ regulates the MPT in isolated rat liver mitochondria and in CEM and HL60 cells by two independent pathways. Glutathione depletion activated the MPT via increased production of reactive oxygen species (ROS) generated by cytochrome bc₁. The ROS producing mechanism in cytochrome bc₁ involves movement of the "Rieske" iron-sulfur protein subunit of the enzyme complex, because inhibition of cytochrome bc₁ by pharmacologically blocking iron-sulfur protein movement completely abolished ROS production, MPT activation, and cell death. The classical inhibitor of the MPT, cyclosporine A, had no protective effect against MPT activation. In contrast, the calcium-activated, cyclosporine A-regulated MPT in rat liver mitochondria was also blocked with inhibitors of cytochrome bc₁. These results indicate that electron flux through cytochrome bc1 regulates two distinct pathways to the MPT, one unregulated and involving mitochondrial ROS and the other regulated and activated by calcium.

Effect of dietary fatty acids on the intestinal permeability of marker drug compounds in excised rat jejunum

The aim of this study was to explore the effects of diets containing saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and ω-3 and ω-6 polyunsaturated fatty acids (ω-3 and ω-6 PUFA, respectively) on the passive and active transport properties of rat jejunum using marker compounds. Rats were fed diets supplemented with 18.4% (w/w) lipid (4 groups) or standard rat chow (1 group) for a period of 30 days. At the end of the dietary period, mucosal scrapings were taken for the determination of membrane phospholipids, and the apparent jejunal permeability of radiolabelled marker compounds was determined using modified Ussing chambers. Changes in the phospholipid content of the brush border membrane reflected the different lipid content of the diets. The passive paracellular permeability of mannitol was not significantly affected by the fatty acid composition of the diet, although there was a trend toward decreased mannitol permeability in the rats fed both the ω-3 and ω-6 PUFA diets. In comparison, the transcellular diffusion of diazepam was reduced by 20% (P < 0.05) in rats fed diets supplemented with ω-3 and ω-6 PUFA. In the lipid-fed rats, the serosal to mucosal flux of digoxin, an intestinal P-glycoprotein substrate, was reduced by 20% (P < 0.05) relative to the chow-fed group, however there were no significant differences between the different lipid groups. The active absorption of D-glucose via the Na+-dependent transport pathway was highest in the SFA, MUFA and PUFA ω-3 dietary groups, intermediate in the low-fat chow group and lowest in the PUFA ω-6 group, and was positively correlated with short-circuit current. These studies indicate that dietary fatty acid changes can result in moderate changes to the active and passive transport properties of excised rat jejunum.

Examination of the role of intestinal Fatty acid-binding protein in drug absorption using a parallel artificial membrane permeability assay

Transcellular diffusion across the absorptive epithelial cells (enterocytes) of the small intestine is the main route of absorption for most orally administered drugs. The process by which lipophilic compounds transverse the aqueous environment of the cytoplasm, however, remains poorly defined. In the present study, we have identified a structurally diverse group of lipophilic drugs that display low micromolar binding affinities for a cytosolic lipid-binding protein—intestinal fatty acid-binding protein (I-FABP). Binding to I-FABP significantly enhanced the transport of lipophilic drug molecules across a model membrane, and the degree of transport enhancement was related to both drug lipophilicity and I-FABP binding affinity. These data suggest that intracellular lipid-binding proteins such as I-FABP may enhance the membrane transport of lipophilic xenobiotics and facilitate drug access to the enterocyte cytoplasm and cytoplasmic organelles.

Determination of resin acids in pulp mill effluent and receiving waters by high performance liquid chromatography

Resin acids are reported to be of major toxicological importance in pulp mill effluents for Rainbow Trout. Their determination, using a high performance liquid chromatographic method, is described.

Permeability mapping in porous media by magnetization prepared centric-scan SPRITE

The ability of porous media to transmit fluids is commonly referred to as permeability. The concept of permeability is central for hydrocarbon recovery from petroleum reservoirs and for studies of groundwater flow in aquifers. Spatially resolved measurements of permeability are of great significance for fluid dynamics studies. A convenient concept of local Darcy’s law is suggested for parallel flow systems. The product of porosity and mean velocity images in the plane across the average flow direction is directly proportional to permeability. Single Point Ramped Imaging with T 1 Enhancement (SPRITE) permits reliable quantification of local fluid content and flow in porous media. It is particularly advantageous for reservoir rocks characterized by fast magnetic relaxation of a saturating fluid. Velocity encoding using the Cotts pulsed field gradient scheme improves the accuracy of measured flow parameters. The method is illustrated through measurements of 2D permeability maps in a capillary bundle, glass bead packs and composite sandstone samples.

Functionalization of bamboo pulp fabrics with noble metal nanoparticles

Noble metal (gold and silver) nanoparticles (NPs) were synthesized in-situ on bamboo pulp fabrics. The gold NPs were reduced by bamboo pulp fabrics and bonded to fibers under heating, and an alkaline condition was needed to synthesize silver NPs in the presence of bamboo pulp fabrics. The synthesized gold and silver NPs endowed bamboo pulp fabrics with different colors because of their localized surface plasmon resonance (LSPR) property. The colors of the fabrics treated with metal NPs were extended through complex synthesis of gold and silver NPs in different proportions. The bamboo pulp fabrics treated with noble metal NPs showed good fastness to light and rubbing. In addition, the gold and silver NPs imparted bamboo pulp fabrics excellent UV protection property and remarkable antibacterial activity.

Peanut allergens alter intestinal barrier permeability and tight junction localisation in Caco-2 cell cultures

Allergen absorption by epithelia may play an important role in downstream immune responses. Transport mechanisms that can bypass Peyer's patches include transcellular and paracellular transport. The capacity of an allergen to cross via these means can modulate downstream processing of the allergen by the immune system. The aim of this study was to investigate allergen-epithelial interactions of peanut allergens with the human intestinal epithelium.

Preparation of cellulose nanofiber from softwood pulp by ball milling

This paper reports the possibility of producing cellulose nanofiber from softwood pulp using a simple ball milling technique under ambient pressure and at room temperature. The effects of milling conditions including the ball-to-cellulose mass ratio, milling time, ball size and alkaline pretreatment were investigated. It was found that milling-ball size should be carefully selected for producing fibrous morphologies instead of particulates. Milling time and ball-to-cellulose mass ratio were also found important to control the fiber morphology. Alkali pre-treatment helped in weakening hydrogen bonds between cellulose fibrils and removing small particles, but with the risks of damaging the fibrous morphology. In a typical run, cellulose nanofiber with an average diameter of 100 nm was obtained using soft mechanical milling conditions using cerium-doped zirconia balls of 0.4–0.6 mm in diameter within 1.5 h without alkaline pretreatment.

Understanding water and ion transport behaviour and permeability through poly(amide) thin film composite membrane

Molecular dynamics (MD) together with the adaptive biasing force (ABF) and metadynamics free energy calculation methods was used to investigate the permeation properties of salt water through poly(amide) thin film composite reverse osmosis membranes. The thin films were generated by annealing an amorphous cell of poly(amide) chains through an MD method. The MD results showed they have typical structural properties of the active layer of thin film composite membranes and comparable water diffusivity (2.13×10^-5cm²/s for the film with a density of 1.06g/cm³) and permeability (9.27×10^-15cm³cm/cm²sPa) to experimental data. The simulations of water permeation through the films under different transmembrane pressures revealed the behaviours of water molecules in the thin films and the dynamic regimes of water permeation, including Brownian diffusion, flush and jump diffusion regimes. The intermolecular interactions of water and ions with poly(amide) chains showed a strong dependence on the local structure of films. The attraction between water and ploy(amide) molecules can be up to 8.5kcal/mol in dense polymer regions and 5kcal/mol in the pores of about 3nm. The ABF and metadynamics simulations produced the profiles of free energy potential of water and ions along the depth of the thin films, which provided important information for quantitatively determining the barrier energy required for water permeation and rejection of ions. The thin film with a density of 1.06g/cm³ and a thickness of 6nm offers a rejection to Na⁺ but a slight absorption of Cl^- (0.25kcal/mol) at 0.3-0.4nm distance to its surface. Water molecules must overcome 63kcal/mol energy to move to the centre of the film. The dependences of the barrier energy and the water-polymer interaction energy on the local free volume size in the thin film were analysed. The simulations of water permeation under high transmembrane pressures showed a nonlinear response of the concentration and distribution of water molecules in the film to the imposed pressure. Compaction of the film segments close to the porous substrate and water congestion in dense regions significantly influenced the water permeation when the membrane was operated under pressures of more than 3.0MPa.