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The mouse ortholog of the human bile salt export pump (BSEP) transporter was expressed in a baculovirus-infected insect cell (Sf9) system to study the effect of membrane cholesterol content on the transporter function. The transport activity of cholesterol-loaded mouse Bsep-HAM-Sf9 vesicles was determined in a vesicular transport assay with taurochenodeoxycholate (TCDC), a known BSEP substrate. Mouse Bsep transports TCDC at a high rate that can be sensitively detected in the ATPase assay. Cholesterol upload of the Sf9 membrane potentiates both TCDC transport and TCDC-stimulated ATPase activities. Inhibitory effect of BSEP interactors on probe substrate transport was tested in both vesicular transport and ATPase assays using cholesterol-loaded membrane vesicles. A good rank order correlation was found between IC50 values measured in TCDC-stimulated mBsep ATPase assay and in the human BSEP vesicular transport assay utilizing taurocholate (TC) as probe substrate. This upgraded form of the mouse Bsep-HAM ATPase assay is a user friendly, sensitive, nonradioactive method for early high-throughput screening of drugs with BSEP-related cholestatic potential. It may complement the human BSEP-mediated taurocholate vesicular transport inhibition assay. [ABSTRACT FROM AUTHOR]

Iron and molybdenum containing sol–gel catalysts were prepared using various methods, i.e. different solvents, metal salts and different drying processes – including the application of chelating agent or freeze-drying – and investigated in the synthesis of single wall carbon nanotubes. The quality and quantity of the product proved to be very sensitive to the synthesis parameters and also to the composition and preparation way of the catalyst. It was demonstrated that there is no significant correlation between the catalytic activity and the specific surface area, while the texture of the catalyst influenced by the preparation way is a much more important factor. [Copyright &y& Elsevier]

Multiwall carbon nanotubes (MWNTs) were synthesized by a novel method of mesoporous MCM-41 and MCM-48 silicates in the absence of any metal traces. A transmission electron microscopy (TEM) study shows that the diameter distribution of the obtained carbon nanotubes is very narrow – 5–6 nm in diameter and 200 nm in length – compared to nanotube samples produced by other catalytic chemical vapor deposition (CCVD) techniques. [Copyright &y& Elsevier]

Catalytically prepared multiwall carbon nanotubes (MWNTs) were cut and functionalised by mechanical and/or chemical methods. Products were characterised by transmission electron microscopy, infrared spectroscopy and BET method. It can be concluded that physical and chemical breaking procedures complete each other very well. With certain MWNT samples containing surface oxides preliminary investigations were done for testing them as catalyst support. [Copyright &y& Elsevier]

Seliciclib, a cyclin-dependent kinase inhibitor, is a promising candidate to treat a variety of cancers. Pharmacokinetic studies have shown high oral bioavailability but limited brain exposure to the drug. This study shows that seliciclib is a high-affinity substrate of ATP-binding cassette B1 (ABCB1) because it activates the ATPase activity of the transporter with an EC(50) of 4.2 μM and shows vectorial transport in MDCKII-MDR1 cells, yielding an efflux ratio of 8. This interaction may be behind the drug's limited penetration of the blood-brain barrier. ABCB1 overexpression, on the other hand, does not confer resistance to the drug in the models tested. These findings should be considered when treatment strategies using seliciclib are designed.

Background: The last 15 years have marked an expansion in our understanding of how ABC transporters modulate the pharmacokinetic properties of drugs. Assays based on different membrane preparations were one of the first methods developed to study ABC transporters. Later, they turned out to be valuable tools to gain insight into the nature of drug-ABC transporter interactions., Objectives: Membranes prepared from different sources have been used and characterized; based on the biochemical characteristics of the transport process, a number of different assay types have been developed., Methods: This review focuses on the current experiences on how different membrane-based assays can be utilized in pharmaceutical R&D. Sources of membrane preparations, available assay types and correlation studies between different in-vitro and in-vivo methods are discussed., Results/conclusion: Membrane-based assays are valuable tools in drug discovery to characterize drug-ABC transporter interactions.

Carbon nanotubes were produced from either a template or the polymer-filled pore systems of mesoporous silicates of various structures and dimensions by heat treatment in the absence of air. Successful synthesis was done when the template molecules contained little or no oxygen. For SBA-15 material, where the structure-directing molecule used for synthesis of mesoporous silicate was polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer, no carbon nanostructures were formed. A peculiar carbon nanostructure was generated from the template for pore expanded MCM-41. To demonstrate carbon nanotube formation from polymer in the mesoporous silicates, the mesopores of MCM-41, MCM-48, and SBA-15 silicates were filled with divinyl-benzene polymer and then graphitized at 1300 K. The polymer was successfully transformed into carbon nanotubes for the MCM class silicate but not the SBA-15 silicate.