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.

Phosphate absorption across multiple epithelia in the Pacific hagfish (Eptatretus stoutii)

Inorganic phosphate (Pi) is an essential nutrient for all organisms, but in seawater, Pi is a limiting nutrient. This study investigated the primary mechanisms of Pi uptake in Pacific hagfish (Eptatretus stoutii) using ex vivo physiological and molecular techniques. Hagfish were observed to have the capacity to absorb Pi from the environment into at least three epithelial surfaces: the intestine, skin, and gill. Pi uptake in all tissues was concentration dependent, and saturable Pi transport was observed in the skin and gill at <2.0 mmol/l Pi. Gill and intestinal Pi uptake was sodium dependent, but Pi uptake into the skin increased under low sodium conditions. Gill Pi transport exhibited an apparent affinity constant ∼0.23–0.6 mmol/l Pi. A complete sequence of a type II sodium phosphate cotransporter (Slc34a) was obtained from the hagfish gill. Phylogenetic analysis of the hagfish Slc34a transporter indicates that it is earlier diverging than, and/or ancestral to, the other identified vertebrate Slc34a transporters (Slc34a1, Slc34a2, and Slc34a3). With the use of RT-PCR, the hagfish Slc34a transcript was detected in the intestine, skin, gill, and kidney, suggesting that this may be the transporter involved in Pi uptake into multiple epithelia in the hagfish. This is the first measurement of Pi uptake across the gill or skin of any vertebrate animal and first sodium phosphate cotransporter identified in hagfish.

Polypyrrole nanoparticles and dye absorption properties

Polypyrrole (PPy) nanoparticles were prepared by using microemulsion polymerization processes at 3 °C. Particle characterization was performed by using FTIR, elementary analysis, UV–vis spectra and scanning electron microscope (SEM). The size of the nanoparticles varied from about 50 to 100 to 100 to 200 nm with the change in concentration of surfactant from 0.8 to 0.44 M. Polypyrrole nanoparticles were dedoped by a 10% NaOH solution, followed by a redoping process using a nuclear fast red kernechtrot dye, which has a sulfonate group. Dedoping changed the optical absorption properties of the nanoparticles.

The relative absorption of fatty acids in brown trout (Salmo trutta) fed a commercial extruded pellet coated with different lipid sources

The objective of the present study was to investigate the fatty acid absorption capabilities of brown trout (Salmo trutta) fed commercial extruded diets. Five commercial extruded pellets, different only in the lipid sources used for fat coating, were tested on juvenile brown trout for 45 days. The trout were reared in fresh water at 14.6 ± 0.4° C and 7.7 ±
0.3 mg/l, temperature and dissolved oxygen, respectively. The tested lipid sources were fish oil, canola oil, oleine oil, swine fat and poultry fat. After the adaptation period faeces were collected by gently stripping from naesthetized fish. Fatty acid analysis was performed on experimental diets and on collected faeces to evaluate the relative absorption capabilities of the trout digestive system with respect to each detected fatty acid. The use of the relative absorption efficiency (rAE) was opted to evaluate the intrinsic capability of each fatty acid to be absorbed. Brown trout showed a
specific preferential order of absorption of the fatty acids, preferring shorter over longer chain fatty acids and preferring the more unsaturated to the more saturated fatty acids. The fatty acid that showed the best relative absorbability was the C18:4n-3 (rAE = 5.14 ± 0.72), which has a fairly short carbon chain, but at the same time a high unsaturation level, followed by the C18:3n-3 (rAE = 3.38 ± 0.30). The fatty acid that showed the worst relative absorbability (rAE = 0.21 ± 0.02) was C24:1n-9.

Copper exposure induces trafficking of the Menkes protein in intestinal epithelium of ATP7A transgenic mice

The final steps in the absorption and excretion of copper at the molecular level are accomplished by 2 closely related proteins that catalyze the ATP-dependent transport of copper across the plasma membrane. These proteins, ATP7A and ATP7B, are encoded by the genes affected in human genetic copper-transport disorders, namely, Menkes and Wilson diseases. We studied the effect of copper perfusion of an isolated segment of the jejunum of ATP7A transgenic mice on the intracellular distribution of ATP7A by immunofluorescence of frozen sections. Our results indicate that ATP7A is retained in the trans-Golgi network under copper-limiting conditions, but relocalized to a vesicular compartment adjacent to the basolateral membrane in intestines perfused with copper. The findings support the hypothesis that the basolateral transport of copper from the enterocyte into the portal blood may involve ATP7A pumping copper into a vesicular compartment followed by exocytosis to release the copper, rather than direct pumping of copper across the basolateral membrane.

The effects of dye dopants on the conductivity and optical absorption properties of polypyrrole

Ten anionic compounds, including four acidic dyes, were used to dope polypyrrole powder. The effects of the dopants on density, optical absorption and conductivity of the polypyrroles were studied. The presence of the dopant in the conducting polymer matrix was verified by ATR-FTIR spectroscopy. Density function theory (DFT) simulation was used to understand the effect of the dopants on the solid structure, optical absorption and energy band structures. Anthraquinone-2-sulfonic acid-doped polypyrrole yielded the highest conductivity. The dye-doped polypyrrole showed an enhancement in its UV–vis optical absorption.

Runoff absorption potential of roofing materials

The main objectives of this work are to establish a relationship between solar radiation and equivalent temperatures for the radiation heat source (oven) to be used in the laboratory and to determine the impact of solar radiation on the absorption and evaporation potential of roofing tiles (glazed and unglazed). Based on the results obtained, it is justifiable to conclude that solar radiation do affect the evaporation and absorption potential of the glazed and unglazed tiles. There is a trend of decrease in both the absorption and evaporation potential of both tiles when exposed to decreasing solar radiation. The evaporation potential of the roof tiles is much higher than its absorption potential. This is clearly displayed in both types of tiles.

Electromagnetic interference shielding and radiation absorption in thin polypyrrole films

Results of permittivity measurements, electromagnetic interference shielding effectiveness, and heat generation due to microwave absorption in conducting polymer coated textiles are reported and discussed. The intrinsically conducting polymer, polypyrrole, doped with anthraquinone-2-sulfonic acid (AQSA) or para-toluene-2-sulfonic acid (pTSA) was applied on textile substrates and the resulting materials were investigated in the frequency range 1–18 GHz. The 0.54 mm thick conducting textile/polypyrrole composites absorbed up to 49.5% of the incident 30–35 W microwave radiation. A thermography station was used to monitor the temperature of these composites during the irradiation process, where absorption was confirmed via visible heat losses. Samples with lower conductivity showed larger temperature increases caused by microwave absorption compared to samples with higher conductivity. A sample with an average sheet resistivity of 150 Ω/sq. showed a maximum temperature increase of 5.27 °C, whilst a sample with a lower resistivity (105 Ω/sq.) rose by 3.85 °C.

Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge

The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and traditionally used in the treatment of angina pectoris, acute myocardial infarct, hyperlipidemia and stroke in China and other Asian countries. In this study, we have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption of tanshinone IIA (TSA), a major active constituent of Danshen, using several in vitro and in vivo models. The oral bioavailability of TSA was about 2.9

Role of the ATP-binding cassette drug transporters in the intestinal absorption of tanshinone IIB, one of the major active diterpenoids from the root of Salvia miltiorrhiza

There is an increasing use of herbal medicines worldwide, and the extracts from the root of Salvia miltiorrhiza are widely used in the treatment of angina and stroke. In this study, we investigated the mechanism for the intestinal absorption of tanshinone IIB (TSB), a major constituent of S. miltiorrhiza. The oral bioavailability of TSB was about 3% in rats with less proportional increase in its maximum plasma concentration (C_max) and area under the plasma concentration-time curve (AUC) with increasing dosage. The time to C_max (T_max) was prolonged at higher oral dosage. In a single pass rat intestinal perfusion model, the permeability coefficients (P_app) based on TSB disappearance from the lumen (P_lumen) were 6.2- to 7.2-fold higher (p < 0.01) than those based on drug appearance in mesenteric venous blood (P_blood). The uptake and efflux of TSB in Caco-2 cells were also significantly altered in the presence of an inhibitor for P-glycoprotein (PgP) or for multi-drug resistance associated protein (MRP1/2). TSB transport from the apical (AP) to basolateral (BL) side in Caco-2 monolayers was 3.3- to 5.7-fold lower than that from BL to AP side, but this polarized transport was attenuated by co-incubation of PgP or MRP1/2 inhibitors. The P_app values of TSB in the BL-AP direction were significantly higher in MDCKII cells over-expressing MDR1 or MRP1, but not in cells over-expressing MRP2-5, as compared with the wild-type cells. The plasma AUC_0-24hr in mdr1a and mrp1 gene-deficient mice was 10.2- to 1.7-fold higher than that in the wild-type mice. Furthermore, TSB significantly inhibited the uptake of digoxin and vinblastine in membrane vesicles containing PgP or MRP1. TSB also moderately stimulated PgP ATPase activity. Taken collectively, our findings indicate that TSB is a substrate for PgP and MRP1 and that drug resistance to TSB therapy and drug interactions may occur through PgP and MRP1 modulation.

Mechanical properties and energy absorption of ceramic particulate and resin-impregnation reinforced aluminium foams

The mechanical properties of aluminium foams can be improved by matrix reinforcement and resin-impregnation methods. In the present study, aluminium foams were reinforced by both ceramic particulate reinforcing of the aluminium matrix and resin-impregnating pores. The mechanical properties and the energy absorption of the reinforced aluminium foams were investigated by dynamic and quasi-static compression. Results indicated that the ceramic particle additions of CBN, SiC and B4C in aluminium foams increase the peak stress, elastic modulus and energy absorption of the aluminium foams, under both conditions of dynamic and quasi-static compression. Moreover, the aluminium foams with and without ceramic particle additions exhibited obvious strain rate sensitivity during dynamic compression. Furthermore, the resin-impregnation improves the mechanic properties and energy absorption of aluminium foams significantly. However, aluminium foams with resin-impregnation showed negligible strain rate sensitivity under dynamic compression. It is reported that both the ceramic particle addition and resin-impregnation can be effective techniques to improve the mechanical and the energy absorption properties of aluminium foams.

Strain rate effects on the energy absorption of rapidly manufactured composite tubes

As a result of recent increases in fuel prices and the growing number of accident fatalities, the two major concerns of the automotive industry and their customers are now occupant safety and fuel economy {1, 2]. Increasing the amount of energy and optimizing the manner in which energy is absorbed within vehicle crush zones can improve occupant survivability in the event of a crash, while fuel economy is improved through a reduction in weight.  Axial crush tests were conducted on tubular specimens of Carbon/Epoxy (Toray T700/G83C) and Glass/Polypropylene (Twintex). This paper presents results from the tests conducted at quasi-static rates at Deakin Unniversity, Victoria Australia, and intermediate rate tests performed at the Oak Ridge National Laboratory, Tennessee  USA.   The quasi-static tests were conducted at 10mm/min (1.67x10-4m/s) using 5 different forms of initiation. Tests at intermediate rates were performed at speeds of 0.25m/s, 0.5m/s, 0.75m/s 1m/s, 2m/s and 4m/s. Quasi-static tests of tubular specimens showed high specific energy absorption (SEA) values with 86 kJ/kg for Carbon/Epoxy specimens. The SEA of the Glass/Polypropylene specimens was measured to be 29 kJ/kg. Results from the intermediate test rates showed that SEA values did not fall below 55kJ/kg for carbon specimens or 35kJ/kg for the Glass/Polypropylene specimens. When compared with typical steel and aluminium, SEA values of 15 kJ/kg and 30kJ/kg respectively, the benefits of using composite materials in crash structures is apparent.                                                                     

Energy absorption and crushing behaviour of foam-filled aluminium tubes

The crushing behaviour and energy absorption of foam filled aluminium tubular structures were investigated using the quasi-static compressive tests. The crushing behaviour of the tubular structures changed due to foam filling. The energy absorption of the foam filled tubular structures was improved significantly. Foam filling caused an interaction effect between the tube and the foam during progressive crushing, leading to an increase in the mean crushing load compared to that of the foam or tube itself. This interaction effect might be affected by several parameters such as the density of the foam, the properties of both the foam material and tube material, and the thickness and outer diameter of the tube. In particular, the interaction effect essentially depended on the ratio of the mean crushing force of the foam to that of the tube.

Compressive properties and energy absorption of hollow sphere aluminium

Manufactured cellular aluminums have been developed for a wide range of automotive applications where weight savings, improved safety, crashworthiness and comfort are required. The plateau deformation behavior of cellular aluminums under compressive loading makes this new class of lightweight materials suitable for energy absorption and comes close to ideal impact absorbers. In the present study, aluminum hollow hemispheres were firstly processed by pressing. Hollow sphere aluminum samples with a body-centered cubic (BCC) packing were then fabricated by bonding together single hollow spheres, which were prepared by adhering together hollow hemispheres. Hollow sphere aluminum samples with various kinds of sphere wall thicknesses of 0.1 mm, 0.3 mm and 0.5 mm but the same outside diameter of 4 mm were investigated by compressive tests. The effects of the sphere wall thickness on the mechanical properties and energy absorption characteristics were investigated.