Prediction of glycyrrhizin disposition in rat and man by a physiologically based pharmacokinetic model

Three physiologically based pharmacokinetic models A--C, incorporating enterohepatic recycling, were developed to predict glycyrrhizin (GLZ) disposition in rat plasma and tissues, and human serum. Model A, which included fourteen compartments (artery, vein, tissues except brain, and gut lumen) with the assumption of direct excretion of GLZ from the liver into the gut lumen gave fairly good agreement between the observed and predicted disposition profiles in rat, but was unsuitable in man, where elimination is very rapid. Models B and C for man were obtained by adding a gallbladder compartment (drug storage organ) for the excretion from the liver into the gut lumen and by assuming continuous transfer from the storage compartment or instantaneous emptying from it during meal ingestion as the excretion process from the gallbladder into the gut lumen, respectively. The agreement between the observed and predicted serum concentration time-course profiles was better with model C than model B, especially in the terminal elimination phase, where secondary peaks appeared. However, it was thought that the observed serum disposition can be sufficiently well predicted by model B. In conclusion, prediction in rat was successful in all compartments except the brain, which shows a negligible distribution. Scale-up of the disposition kinetics of GLZ from rat to man was also successful.     

The properties of BCN films formed by ion beam assisted deposition

A study has been made on the formation and the properties of boron carbonnitride (BCN) thin films. The BCN films were produced by ion beam assisted deposition, in which boron and carbon were deposited by electron beam heating and nitrogen was supplied by ion implantation simultaneously. The mechanical properties of BCN films were measured using a ultra micro hardness tester and a friction tester. The atomic ratio and the structure of BCN thin films were estimated by means of X-ray photoelectron spectroscopy, laser Raman spectroscopy and Fourier transform infrared spectroscopy. As preliminary results, it was found that the BCN films are higher in hardness and lower in friction coefficient than diamond-like carbon (DLC) films. The mechanical properties are discussed with the relation of surface composition and structure.     

Study of the dissociation of a charge-reduced phosphopeptide formed by electron transfer from an alkali metal target

Doubly protonated phosphopeptide (YGGMHRQET(p)VDC) ions obtained by electrospray ionization were collided with Xe and Cs targets to give singly and doubly charged positive ions via collision-induced dissociation (CID). The resulting ions were analyzed and detected by using an electrostatic analyzer (ESA). Whereas doubly charged fragment ions resulting from collisionally activated dissociation (CAD) were dominant in the CID spectrum with the Xe target, singly charged fragment ions resulting from electron transfer dissociation (ETD) were dominant in the CID spectrum with the Cs target. The most intense peak resulting from ETD was estimated to be associated with the charge-reduced ion with H2 lost from the precursor. Five c-type fragment ions with amino acid residues detached consecutively from the C-terminal were clearly observed without a loss of the phosphate group. These ions must be formed by N--Calpha bond cleavage, in a manner similar to the cases of electron capture dissociation (ECD) and ETD from negative ions. Although the accuracy in m/z of the CID spectra was about +/-1 Th because of the mass analysis using the ESA, it is supposed from the m/z values of the c-type ions that these ions were accompanied by the loss of a hydrogen atom. Four z-type (or y--NH3, or y--H2O) ions analogously detached consecutively from the N-terminal were also observed. The fragmentation processes took place within the time scale of 4.5 micros in the high-energy collision. The present results demonstrated that high-energy ETD with the alkali metal target allowed determination of the position of phosphorylation and the amino acid sequence of post-translational peptides.     

Surface functionalization chemistries on highly sensitive silica-based sensor chips

The surfaces of silica-based sensor chips, designed for evanescent-field-coupled waveguide-mode sensors, were functionalized using various surface chemistries. The immobilization of molecular entities on the functionalized silica surfaces was monitored using various microscopic techniques (scanning electron, fluorescence, and atomic force microscopies). Further, gold nanoparticle-based signal enhancement analyses were performed with protein conjugation on different functionalized surfaces using a waveguide-mode sensor. Based on these analyses, the sensor surfaces modified with glutaraldehyde (Glu) and carbonyldiimidazole were found to be good for molecules of different sizes. In addition, it can be inferred that the Glu-modified surface may be suitable for small molecules with diameters around 5 nm owing to its surface roughness. The modified surface with carbonyldiimidazole is suitable for the direct immobilization of larger molecules especially for biomolecular assemblies without intermediate chemical modifications.     

Evaluation of nucleic acid duplex formation on gold over layers in biosensor fabricated using Czochralski-grown single-crystal silicon substrate

With a view to developing an economical and elegant biosensor chip, we compared the efficiencies of biosensors that use gold-coated single-crystal silicon and amorphous glass substrates. The reflectivity of light over a wide range of wavelengths was higher from gold layer coated single-crystal silicon substrates than from glass substrates. Furthermore, the efficiency of reflection from gold layers of two different thicknesses was examined. The thicker gold layer (100 nm) on the single-crystal silicon showed a higher reflectivity than the thinner gold film (10 nm). The formation of a nucleic acid duplex and aptamer–ligand interactions were evaluated on these gold layers, and a crystalline silicon substrate coated with the 100-nm-thick gold layer is proposed as an alternative substrate for studies of interactions of biomolecules.     

Determination of optical properties in double integrating sphere measurement by artificial neural network based method

Optical Review - An accurate inversion technique in double integrating sphere (DIS) measurement is essential for determining the optical properties of biological tissue. Although there are several...     

Atmospheric pressure laser desorption/ionization using a 6–7 µm‐band mid‐infrared tunable laser and liquid water matrix

Due to the characteristic absorption peaks in the IR region, various molecules can be used as a matrix for infrared matrix‐assisted laser desorption/ionization (IR‐MALDI). Especially in the 6–7 µm‐band IR region, solvents used as the mobile phase for liquid chromatography have absorption peaks that correspond to their functional groups, such as O–H, CO, and CH₃. Additionally, atmospheric pressure (AP) IR‐MALDI, which is applicable to liquid‐state samples, is a promising technique to directly analyze untreated samples. Herein we perform AP‐IR‐MALDI mass spectrometry of a peptide, angiotensin II, using a mid‐IR tunable laser with a tunable wavelength range of 5.50–10.00 µm and several different matrices. The wavelength dependences of the ion signal intensity of [M + H]⁺ of the peptide are measured using a conventional solid matrix, α‐cyano‐4‐hydroxycinnamic acid (CHCA) and a liquid matrix composed of CHCA and 3‐aminoquinoline. Other than the O–H stretching and bending vibration modes, the characteristic absorption peaks are useful for AP‐IR‐MALDI. Peptide ions are also observed from an aqueous solution of the peptide without an additional matrix, and the highest peak intensity of [M + H]⁺ is at 6.00 µm, which is somewhat shorter than the absorption peak wavelength of liquid water corresponding to the O–H bending vibration mode. Moreover, long‐lasting and stable ion signals are obtained from the aqueous solution. AP‐IR‐MALDI using a 6–7 µm‐band IR tunable laser and solvents as the matrix may provide a novel on‐line interface between liquid chromatography and mass spectrometry. Copyright © 2015 John Wiley & Sons, Ltd.