Optimization of protein therapies by polymer-conjugation as an effective DDS

Due to recent advances in disease proteomics, many disease-related proteins have been found. It is expected that there will be therapeutically useful proteins among them. However, it is clinically difficult to use most proteins as effective and safe drugs because of their very low stability and pleiotropic actions in vivo. To promote disease proteomic based drug development for protein therapies, we have attempted to develop an optimal polymer-conjugation system for improving the therapeutic potency of proteins. In this review, we introduce this innovative protein-drug system.     

Multitracer screening for in vivo element-element interrelations

Radioactive multitracer technique was applied to study the screening of in vivo interrelations between radioactive tracers (⁴⁶Sc, ⁵⁴Mn, ⁵⁸Co, ⁶⁵Zn, ⁷⁵Se, ⁸³Rb, ⁸⁵Sr and ⁸⁸Zr) and stable Zn species. Comparative uptake rates were examined in the blood, nine organs (thymus, lung, cardiac muscle, spleen, pancreas, kidney, liver, testes and bone) and eight brain regions (cerebral cortex, striatum, hippocampus, thalamus and hypothalamus, midbrain, cerebellum, pons and medulla, olfactory bulb) using 3-week-old mice fed by four kinds of Zn-deficient, -adequate and -excessive diets with Zn content from 0.7 to 3520 ppm. As a result, no significant difference between the dietary Zn-deficient state (Zn content: 3.6 ppm) and Zn-adequate state (Zn content: 36 ppm) was observed in the uptake rates of ⁶⁵Zn and other ⁴⁶Sc, ⁵⁴Mn, ⁵⁸Co and ⁷⁵Se, except for ⁸³Rb. In addition, significant differences among the organ and brain regional uptakes of ⁴⁶Sc, ⁵⁴Mn, ⁵⁸Co, ⁷⁵Se and ⁸³Rb were found in the dietary Zn-excessive state (Zn content: 3520 ppm). These results indicate that the organ and brain regional uptakes of tracers in Zn-deficient and excessive mice are strongly correlated with the blood uptakes and retentions of the tracers. Furthermore, the multitracer screening gives us new findings concerning the diet-related element-element interrelations in living bodies.     

The USCI approach and elementary superposition for combinatorial enumeration

Summary The elementary superposition theorems are presented for enumerating chemical compounds that contain achiral and chiral ligands. Subduced cycle indices (SCI-CF), partial cycle indices (PCI-CF), and cycle indices (CI-CF) with chirality fittingness are defined by starting from unit subduced cycle indices with chirality fittingness (USCI-CF). All of these indices afford generating functions that are proved to be applicable to combinatorial enumeration. In addition, the concept of elementary superposition with and without chirality fittingness is proposed to provide the elementary superposition theorems. These theorems provide us with a new methodology of enumerating compounds, in which the numbers of isomers are obtained without relying on generating functions and are itemized with respect to molecular formulas (weights) and symmetries. The operation is defined on the basis of the elementary superposition. Thereby, we derive superposition theorems concerning the PCI-CFs and the CI-CFs. These are applicable to combinatorial enumeration.     

Miscibility of dodecyltrimethylammonium bromide and dodecyltrimethylammonium chloride in surface-adsorbed film and micelle

Surface tension of aqueous solutions of mixtures of dodecyltrimethylammonium bromide (DTAB) and dodecyltrimethylammonium chloride (DTAC) has been measured and analyzed by using thermodynamic relations. The adsorbed film has been found to contain more DTAB molecules than the solution. The shape formed by the curves of the total molality at constant surface tension against the solution and surface compositions indicates the ideal mixing of the DTAB and DTAC molecules in the adsorbed film. Micellar composition has been estimated at the critical micelle concentration (CMC). The micelles have been found to be richer in DTAB than the solution, but poorer in DTAB than the adsorbed film at the CMC. The DTAB and DTAC molecules have been shown to mix ideally in the micelles. From the comparison with the results on the system of decylammonium bromide and decylammonium chloride, it has been concluded that, on the mixing of surfactants differing only in counter ions, the adsorbed film is influenced more significantly by the ionic head group of the surfactant than the micelle.     

Preparation of99Mo,132Te isotopes and99mTc,132I generators

Adsorption and desorption of⁹⁵Zr−⁹⁵Nb,⁹⁹Mo,¹⁰³Ru,¹³²Te and²³⁹Np in a HCl-alumina system were studied in order to purify⁹⁹Mo and¹³²Te obtained by the cation-exchange separation of fission products and to prepare highly pure^99mTc and¹³²I generators.⁹⁹Mo and¹³²Te, of which radionuclidic purity was over 99.99% and 99.999%, respectively, could be obtained by passing the cation-exchange separated Mo and Te fractions through alumina columns, by washing with HCl and finally by eluting⁹⁹Mo with 1M NH₄OH and¹³²Te with 3M NaOH. In order to raise the recovery of⁹⁹Mo and¹³²Te from the alumina columns, they should be eluted as quickly as possible after the adsorption. The direct use of the alumina column containing⁹⁹Mo or¹³²Te as the generator allowed milking of^99mTc or¹³²I, of which radionuclidic purity was over 99.999%. Milking yields of^99mTc with 0.1M HCl and¹³²I with 0.01M NH₄OH were 77% and 90%, respectively. The latter value was much higher than that in usual performance of the generator.     

Selective photocatalytic oxidation of light alkanes over alkali-ion-modified V2O5/SiO2; kinetic study and reaction mechanism

Alkali-ion-modified silica-supported vanadium oxides are photocatalysts available in the field of photooxidation of light alkanes using molecular oxygen. The photooxygenated reaction was promoted over the catalyst under irradiation at steady state. Acetone formation on the photooxidation of propane was investigated over a rubidium-ion-modified silica-supported vanadium oxide that is the most effective catalyst. The kinetic analysis demonstrated that the rate-determining step is the reaction of propane on the lattice oxygen of the photoexcited VO4Rb species to yield the vanadium isopropoxide species. It was suggested that the photocatalytic active sites are occupied by photogenerated acetone during photoreaction at 333 K. Heating the photocatalyst bed drastically enhanced not only product yield but also the selectivity to propionaldehyde that is a minor product in the photooxidation at 333 K. The product distribution of photoassisted oxidation of propane was described by Boltzmann's distribution of stabilization energy of the intermediates: an isopropoxide-like one for the precursor of acetone and an n-propoxide-like one for the precursor of propionaldehyde.     

Effects of the host matrix on the 57Fe-species produced through EC-decay in 57Co-labelled tris(phenanthroline) cobalt (II) perchlorate.

Emission M?ssbauer spectroscopic studies of 57Co-labelled [Co(phen)3]clO4)2 in host matrices [M(II)(phen)3](ClO4)2(M=Co, Fe, and Ni) indicate that the relative intensities of the anomalous species produced through the EC-decay depend on the kind of the host matrix. The largest intensity was observed with the cobalt (II) matrix, and the smallest with the iron (II) matrix. Emission spectra of 57Co-labelled [Co(2-CH3-phen)3](ClO4)2 2H2O in the matrix of [Fe(2-CH3-phen)3](ClO4)2 were also studied. The high-spin state (5T2) was predominantly observed at 4.2 K in the emission spectrum, while the low-spin state (1A1) was mainly observed in the absorption spectrum at 78 K. The results are discussed in terms of the stability of the lattice.     

Can a radioactive implant induced X-ray emission (RIXE) technique be used to in vivo measurement of heavy elements?

A radioactive implant induced X-ray emission (RIXE) technique was examined for the in vivo determination of heavy elements. By the use of⁶⁷Ga,^99mTc,¹²³I,¹²³Xe and²⁰¹Tl implant excitation sources, the excitation efficiency and X-ray attenuation were measured to reveal the potential pairs of source-heavy element of interest for in vivo elemental analysis by the RIXE technique. Detection limits for the RIXE in vivo analysis were evaluated according to Currie's criterion. Four pairs,^99mTc–Pb,²⁰¹Tl–I,¹³³Xe–Cd and¹²³I–Cd are potential.     

Preparation of lanthanide sulfide films by chemical vapor deposition using β-diketone chelates

Preparation of thin films of lanthanide (Ln) sulfides has been studied by the chemical vapor deposition (CVD) method, using metal -diketonato chelates with 2,2,6,6-tetramethyl-3,5-heptanedione and reactant H₂S gas as starting materials. Two kinds of sulfides, Ln₂O₂S oxysulfides and EuS monosulfide, were obtained as thin films at temperatures as low as 390–570 °C. The CVD method was confirmed to be suited for the above purpose.     

Enumerations of chemical structures by subduction of coset representations. Correlation of unit subduced cycle indices to Pólya's cycle indices

Subduction of the coset representations and the related concepts such as unit subduced cycle indices and subduced cycle indices yields the foundation for a new type of generating function for enumerating chemical structures. This method is related to Pó1ya's theorem.