Determination of aluminum in large volume parenteral drug products used in total parenteral nutrition therapy by ICP-MS with a dynamic reaction cell

The proposed method was developed for the determination of aluminum (Al) in large volume parenteral (LVP) drug products used in total parenteral nutrition (TPN) therapy. The determination of Al in LVP drug products was performed by an inductively coupled plasma mass spectrometer equipped with a dynamic reaction cell (DRC-ICP-MS). DRC-ICP-MS conditions for the analysis of Al were studied to obtain the best signal to background (S/N) ratios. The interfering polyatomic ions at mass 27 (Al) were reduced by using NH(3) as a reaction gas. The detection limit of Al in a 1% (v/v) HNO(3) aqueous solution was 2 ng/l. The Al contents in LVP drug products obtained by this method were in the range of 1.16-4.33 microg/l and were less than 25 microg/l, that is, the regulation value of Food and Drug Administration (FDA). In order to trace the origin of Al in LVP drug products, each part of the LVP drug product, which is composed of three chambers, was investigated. However, a clear difference of the Al contents in each chamber was not observed. Furthermore, the Al contents in injection bags were quantified. Although the Al contents in injection bags were relatively high (in the range of 27.5-33.6 microg/g), dissolution of Al from the injection bags was not observed in the stability testing. From all of these results, it was concluded that the Al contents in the LVP drug products investigated originated in the amount of the Al in each raw material.     

Potent Th2 Cytokine Bias of Natural Killer T Cell by CD1d Glycolipid Ligands: Anchoring Effect of Polar Groups in the Lipid Component

Th2‐biasing CD1d ligands are attractive potential candidates for adjuvants and therapeutic drugs. However, the number of potent ligands is limited, and their biasing mechanism remain unclear. Herein, a series of novel Th2‐biasing CD1d glycolipid ligands, based on modification of their lipid part, have been identified. These have shown high binding affinities and efficient Th2 cytokine production. Importantly, the truncated acyl chain containing variants still retain their binding affinities and agonistic activities, which can be associated with an “anchoring effect,” that is, formation of a buried hydrogen bond between a polar group on the acyl chain and the CD1d lipid‐binding pocket. The analysis indicated that the appearance rates of ligand–CD1d complexes on the cell surface were involved in Th2‐biasing responses. The designed ligands, having the anchor in the shorter lipid part, are one of the most potent Th2‐biasing ligands among the known ligands.     

Syntheses, crystal structures, and water adsorption behaviors of jungle-gym-type porous coordination polymers containing nitro moieties

NO₂ containing dicarboxylate bridging ligands, nitroterephthalate (bdc-NO₂) and 2,5-dinitroterephthalate (bdc-(NO₂)₂), afford porous coordination polymers, {[Zn₂(bdc-NO₂)₂(dabco)]·solvents}_n (2⊃solvents) and {[Zn₂(bdc-(NO₂)₂)₂(dabco)]·solvents}_n (3⊃solvents). Both compounds form jungle-gym-type regularities, where a 2D square grid composed of dinuclear Zn₂ units and dicarboxylate ligands is bridged by dabco molecules to extend the 2D layers into a 3D structure. In 2⊃solvents and 3⊃solvents, a rectangle pore surrounded by eight Zn₂ corners contains two and four NO₂ moieties, respectively. Thermal gravimetry (TG) and X-ray powder diffraction (XRPD) measurements reveal that both compounds maintain the frameworks regularities without guest molecules and with solvents such as MeOH, EtOH, i-PrOH, and Me₂CO. Adsorption measurements reveal that dried 2 and 3 adsorb H₂O molecules to be {[Zn₂(bdc-NO₂)₂(dabco)]·4H₂O}_n (2⊃4H₂O) and {[Zn₂(bdc-(NO₂)₂)₂(dabco)]·6H₂O}_n (3⊃6H₂O), showing the pore hydrophilicity enhancement caused by NO₂ group introduction.     

Extraction and transport of lithium ion by a crown ether-alkylphosphoric acid system [1]

Mixed carrier systems composed of crown ethers and alkylphosphoric acids have been studied as lithium ionophores using a solvent extraction technique and in transport across liquid membranes. The combination of dibenzo-14-crown-4 and bis(2-ethylhexyl) phosphoric acid showed a synergistic enhancement on both lithium ion selectivity and transport rate. The synergistic effects depended strongly upon crown ether structure and the enhancement was observed only when the metal cation corresponded to the crown ether's cavity diameter. Complex formation in the organic phase was assessed by use of FAB-mass spectrometry.     

Comparison of the migration behavior of nanoparticles based on polyethylene glycol and silica using micellar electrokinetic chromatography

Nanoparticles, spherical particles with diameters less than 100 nm, are promising theranostic devices for noninvasive diagnosis and therapy. In this study, nanoparticles composed of polyethylene glycol and silica were prepared, and their migration behavior was examined using capillary electrophoresis. The effects of the sodium dodecyl sulfate concentration in the electrolyte, the nanoparticle size, and the encapsulated molecule on the migration were examined. The addition of sodium dodecyl sulfate into the electrolyte had a significant effect on the electrophoretic mobility of polyethylene glycol nanoparticles, but a small effect on that of silica nanoparticles. As for the size effect, the mobility became a little faster for smaller nanoparticle sizes for both polyethylene glycol and silica nanoparticles. The encapsulated molecule affected the mobility of the nanoparticles through interactions between the encapsulated molecules and sodium dodecyl sulfate. We propose that the large effect of sodium dodecyl sulfate on the migration of the polyethylene glycol nanoparticles was due to the large spaces within the nanoparticles. These results indicate that nanoparticle migration is mainly determined by the nanoparticle components.     

Synthesis of peptidoglycan fragments and evaluation of their biological activity

The peptidoglycan (PG) bacterial cell wall glycoconjugate has been well known as a strong immunopotentiator. Partial structures of PG were chemically synthesized for elucidation of precise biological activities. Effective construction of distinct repeating glycans of PG was accomplished by the coupling of a key disaccharide glucosaminyl-beta(1-4)-muramic acid unit. Stereoselective glycosylation of disaccharide units was achieved by neighboring group participation of the N-Troc (Troc = 2,2,2-trichloroethoxycarbonyl) group and appropriate reactivity of N-Troc-glucosaminyl trichloroacetimidate. By using an efficient synthetic strategy, mono-, di-, tetra- and octasaccharide fragments of PG were synthesized in high yields. The biological activity of synthetic fragments of PG was evaluated by induction of tumor necrosis factor-alpha (TNF-alpha) from human monocytes, and toll-like receptor 2 (TLR2) and Nod2 dependencies by using transfected HEK293 cells, respectively. Here we reveal that TLR2 was not stimulated by the series of synthetic PG partial structures, whereas Nod2 recognizes the partial structures containing the MDP moiety.     

Surface modification of GC and HOPG with diazonium, amine, azide, and olefin derivatives

Surface modification of glassy carbon (GC) and highly oriented pyrolytic graphite (HOPG) was carried out with diazonium, amine, azide, and olefin derivatives bearing ferrocene as an electroactive moiety. Features of the modified surfaces were evaluated by surface concentrations of immobilized molecule, blocking effect of the modified surface against redox reaction, and surface observation using cyclic voltammetry and electrochemical scanning tunneling microscope (EC-STM). The measurement of surface concentrations of immobilized molecule revealed the following three aspects: (i) Diazonium and olefin derivatives could modify substrates with the dense-monolayer concentration. (ii) The surface concentration of immobilized amine derivative did not reach to the dense-monolayer concentration reflecting their low reactivity. (iii) The surface modification with the dense-monolayer concentration was also possible with azide derivative, but the modified surface contained some oligomers produced by the photoreaction of azides. Besides, the blocking effect against redox reaction was observed for GC modified with diazonium derivative and for HOPG modified with diazonium and azide derivatives, suggesting fabrication of a densely modified surface. Finally, the surface observation for HOPG modified with diazonium derivative by EC-STM showed a typical monolayer structure, in which the ferrocene moieties were packed densely at random. On the basis of those results, it was demonstrated that surface modification of carbon substrates with diazonium could afford a dense monolayer similar to the self-assembled monolayer (SAM) formation.     

Charge-transport in tin-iodide perovskite CH3NH3SnI3: origin of high conductivity

The structural and electrical properties of a metal-halide cubic perovskite, CH(3)NH(3)SnI(3), have been examined. The band structure, obtained using first-principles calculation, reveals a well-defined band gap at the Fermi level. However, the temperature dependence of the single-crystal electrical conductivity shows metallic behavior down to low temperatures. The temperature dependence of the thermoelectric power is also metallic over the whole temperature range, and the large positive value indicates that charge transport occurs with a low concentration of hole carriers. The metallic properties of this as-grown crystal are thus suggested to result from spontaneous hole-doping in the crystallization process, rather than the semi-metal electronic structure. The present study shows that artificial hole doping indeed enhances the conductivity.     

Perception and production boundaries between single and geminate stops in Japanese

The theory of relational acoustic invariance [Pickett, E. R., et al. (1999). Phonetica 56, 135-157] was tested with the Japanese stop quantity distinction in disyllables spoken at various rates. The questions were whether the perceptual boundary between the two phonemic categories of single and geminate stops is invariant across rates, and whether there is a close correspondence between the perception and production boundaries. The durational ratio of stop closure to word (where the "word" was defined as disyllables) was previously found to be an invariant parameter that classified the two categories in production, but the present study found that this ratio varied with different speaking rates in perception. However, regression and discriminant analyses of perception and production data showed that treating stop closure as a function of word duration with an intercept term represented the perception and production boundaries very well. This result indicated that the durational ratio of adjusted stop closure (i.e., closure with an added constant) to the word was invariant and distinguished the two phonemic categories clearly. Taken together, the results support the relational acoustic invariance theory, and help refine the theory with regard to exactly what form 'invariance' can take.