A multiple-site competitive model has been developed to evaluate quantitatively the equilibrium competition of drugs that bind to multiple classes of binding sites on human serum albumin (HSA). The equations, which are based on the multiple-class binding site model, assume that competition exists at individual sites, that the binding parameters for drug or drug competitor pertain to individual sites, and also that the binding parameters for drug or competitor at any given site are independent of drug or competitor bound at other sites. For the drug-competitor pairs, ethacrynic acid (EA) -caproic acid (C6), -lauric acid (C12), and -palmitic acid (C16), the reaction heat of EA binding to HSA was measured in the absence and the presence of fatty acids at the molar ratio of 3:1 with HSA at pH 7.4 and 37°C by isothermal titration microcalorimetry. The calorimetric titration data induced by the presence of fatty acids were directly compaired to the computer simulation curves by the corresponding multiple-site competititve models, which were precedently calculated from binding parameters of EA and fatty acids. In the case of EA-C12 or -C16 competitive binding, EA binding at the first and the second classes of binding sites on HSA were instantaneously inhibited by C12 or C16, resulting that the binding constant of the first class of binding sites of EA were decreased and that the second class of binding sites on HSA entirely disappeared. In the competition between EA and C6, the first class of binding sites of EA was diminished by C6, resulting in the decrease of the binding constants and the number of binding sites in the first class of EA, whereas, the second class of binding sites was unaffected. The multiple-site competitive model assuming site-site competition could be directly comparable to the calorimetric data and be suitable to account for the competitive processes for drugs bound to the multiple-class of binding sites on HSA.
Authors:A. Kimura, Y. Toh, M. Oshima, Y. Hatsukawa, and J. Goto
Recycled steel products demands a new technique for determining tramp elements in steel. In this paper, As and Sb in iron
certified reference materials were determined by neutron activation analysis with the multiple gamma-ray detection method.
The determined values are in good agreement with certified and reference values. The lower determination limits (LDL) for
As and Sb in high purity iron are 0.012 and 0.0025 ppm, respectively. As the demanded LDL for As and Sb is 0.1 ppm, the method
described in this work is suitable for determining As and Sb in recycled steel.
Authors:H. Aki, T. Niiya, Y. Iwase, M. Goto, and T. Kimura
The formation of inclusion complexes between amoxicillin (AMPC) and 2-hydroxypropyl-β-cyclodextrin (HPCD) was investigated
by isothermal microcalorimetry and molecular dynamics simulation to evaluate the inhibitory effects on the degradation of
AMPC in aqueous solutions at various pH. The process depended significantly on the ionic species of AMPC in the solution.
In a strong acid solution, cationic AMPC and HPCD formed two different types of inclusion complexes with a 1:1 stoichiometry:
the first-type had a high association constant K1 of 4.0-8.0103 M-1 and included the penam ring of AMPC in the HPCD cavity (Mode I), while the second-type with a K2 of 1.0103 M-1 contained the phenyl group of AMPC (Mode II). Furthermore, a complex with a 1:2 (AMPC:HPCD) stoichiometry was realized in
a two-step reaction and was characterized by a smaller K1:2of 4.0102 M-1 and larger negative enthalpy and entropy changes than the complexes with a 1:1 stoichiometry. Since the β-lactam ring of
AMPC could be protected by inclusion with HPCD in the 1:2 complex and Mode I of 1:1 complexes, the degradation of AMPC in
the presence of HPCD was approximately four times slower than in its absence at pH 1.2 and 37C. In weak acid and neutral
solutions, zwitterionic AMPC and HPCD formed only one type of inclusion complex with a 1:1 stoichiometry, where the phenyl
group was included (Mode II). AMPC was very stable in these solutions (t1/2=226 h at pH=6.0) and there is little significant difference in the degradation rate between complexed AMPC and uncomplexed
AMPC. Thus, the results indicated that the inclusion complex of AMPC with HPCD, effectively increasing the stability of AMPC
in a strong acidic solution like that the stomach, would be useful for eradicating Helicobacter pylori infection and as a drug delivery system.
Authors:Y. Toh, M. Oshima, K. Furutaka, A. Kimura, M. Koizumi, Y. Hatsukawa, and J. Goto
A neutron beam line for multiple prompt gamma-ray analysis was constructed at the Japan Atomic Energy Agency. A detector system
for the MPGA was constructed at the C2-3-2 beam line in January 2005. It comprised eight (upgraded in March 2007) clover Ge
detectors with a BGO Compton suppressor. High efficiency detector system provides an advantage in terms of the detection limit
of MPGA when compared to the result of PGA. The supermirror neutron bender was improved and a supermirror neutron guide was
installed upstream of the sample position.
Authors:Y. Toh, M. Oshima, A. Kimura, M. Koizumi, K. Furutaka, Y. Hatsukawa, and J. Goto
Low-energy photons produced by the Compton scattering from hydrogen increase the background in the lower-energy region of
the gamma-ray spectrum. This results in an increase in the detection limit for trace elements. In multiple photon detection
prompt gamma-ray analysis (MPGA), only those elements that simultaneously emit two or more prompt gamma-rays, which have cascade
relation and are emitted within a short interval, can be measured. Therefore, the influence of hydrogen can be reduced. In
this study, standard polymer and food samples are measured. The hydrogen background is reduced in MPGA.
Authors:Y. Toh, M. Koizumi, M. Oshima, A. Kimura, Y. Hatsukawa, A. Osa, and J. Goto
In order to improve the sensitivity for the quantification of trace elements, we propose the combination of prompt gamma-ray
analysis (PGA) and a multiple gamma-ray detection method. A new Ge detector system for multiple prompt gamma-ray analysis
(MPGA) was constructed at the neutron guide-hall of the JRR-3M reactor of the Japan Atomic Energy Agency (JAEA). The first
demonstration of this system was given with a plastic sample containing traces of cadmium. The quantification limit of cadmium
in a plastic sample was found to be about 0.1 ppm.
Authors:S. Goto, D. Kaji, H. Kudo, M. Fujita, T. Shinozuka, and M. Fujioka
Isomeric yield ratios of 11 fission products were measured in the system of 13 MeV proton-induced fission of232Th by an on-line ion-guide isotope separator. It was found that the closed shell structures of primary fragments and their
complementary fragments affect the isomeric yield ratios. Isomeric yield ratios of121Cd (11/2−, 3/2+) and135Xe (11/2−, 3/2+) were measured precisely in the proton energy range of 13 to 26 MeV to investigate their energy dependence. It was found
that the isomeric yield ratios increased slightly with proton energy. The results were discussed in connection with the deformation
of fission fragments and fission modes.
Authors:Y. Hatsukawa, Y. Miyamoto, Y. Toh, M. Oshima, M. Hosein Mahmudy Gharaie, K. Goto, and K. Toyoda
In this study, using neutron activation analysis with multi-parameter coincidence method which was developed at Japan Atomic
Energy Agency (JAEA), a non-destructive, ultra-high sensitive multi-elemental determination has been realized. The multi-parameter
coincidence method is carried out with an array of 19 germanium detectors, GEMINI-II. Using this system, very weak γ-rays
emitted from trace amounts of elements can be detected. The iridium concentration has been determined by means of neutron
activation analysis with multi-parameter coincidence method for Cuban sediment samples across the K/T boundary strata.
Authors:T. Kaneko, S. Ono, S. Goto, H. Haba, M. Asai, K. Tsukada, Y. Nagame, and H. Kudo
An isothermal chromatographic apparatus was developed for the on-line experiments of super heavy elements in gas phase. As a model of Rf, we investigated the gas phase chemistry of Zr and Hf chlorides. The dependence of the reaction efficiency on temperature was examined. It was found that about 80% of Zr and Hf reacted with chlorinating gas at 900 °C. Adsorption enthalpies of Zr and Hf chlorides were deduced from the isothermal chromatograph by the Monte Carlo simulation based on the microscopic model proposed by Zvára.
Authors:Y. Zhao, I. Nishinaka, Y. Nagame, K. Tsukada, K. Sueki, S. Goto, M. Tanikawa, and H. Nakahara
The primary fragment mass-yield distribution for the asymmetric fission path in heavy nuclei, 233Pa, 239Np, 245Am and 249Bk at the excitation energy of ~20 MeV are experimentally constructed based on the intensities of total kinetic energies for individual mass splits. The results revealed an interesting phenomenon: in all the studied fissioning systems, the inner wings of the mass-yield distributions in the asymmetric fission path appear along the same mass-wall of A = 130 fragment mass. The asymmetric mass-yield distribution indicates the strong effect of structural shells in fragments on the final mass division process of the asymmetric fission path.