Relation between drug-induced taste disorder and chelating behavior with zinc ion; statistical approach to the drug-induced taste disorder, part II

There are many reports that the drug-induced taste disorder is ascribable to the chelate reaction of a drug with zinc ion and the following zinc deficiency. As a quantitative measure of the chelating ability of drugs with zinc ions, the chelating ability was estimated from the electrode potential change of the Zn2+/Zn(Hg) system during the addition of a drug. The electrode potential was measured in a water-N,N-dimethylformamide mixed solution and in an aqueous solution depending on the solubility of the drugs. The observed electrode potential change showed a positive correlation to the frequency of the drug-induced taste disorder that was supplied from the manufacturer of the original drug. The regression analysis was carried out assuming that the frequency of the taste disorder and the electrode potential change was linear. The F-values, p-values, and R2-values were 4.29, 0.13, 0.589, and 4.15, 0.13, 0.580, respectively. The positive correlation between the drug-induced taste disorder and the electrode potential change appeared evident if the uncertainty in the frequency of the taste disorder was taken into consideration. Thus the assumption of the zinc ion chelating mechanism on the drug-induced disorder was also evident except for cisplatin. The frequency of the drug-induced taste disorder of bezafibrate was estimated to be 0.4--0.5 from the regression analysis.     

Reaction of 2-propargylphenylcarbamates with diphenyliodonium salts via Meyer-Schuster rearrangement

The syntheses of 2,3-dihydro-4-quinolones from 2-propargylphenylcarbamates by one-pot tandem process that involves Meyer-Schuster rearrangement or arylative Meyer-Schuster rearrangement/Michael addition of carbamate nitrogen to the resulting vinyl ketones have been developed. Phenylcarbamates tethering tertiary propargyl alcohols underwent arylative Meyer-Schuster rearrangement/Friedel-Crafts alkylation to produce 2,3-dihydroindenones.     

Synthesis and characterization of A4[Re6Q8L6]@SiO2 red-emitting silica nanoparticles based on Re6 metal atom clusters (A = Cs or K, Q = S or Se, and L = OH or CN)

Metal atom clusters constitute very promising candidates as luminophores for applications in biotechnology because they are nanosized entities offering robust luminescence in the near-infrared field (NIR). However, they cannot be used as prepared for biological applications because of potential toxic effects and quenching of the clusters' luminescence in aqueous media, and they therefore need to be dispersed in a biocompatible matrix. We describe herein the encapsulation of octahedral rhenium clusters, denoted as A(4)[Re(6)Q(8)L(6)] (A = Cs or K, Q = S or Se, and L = OH or CN), in silica nanoparticles by a water-in-oil microemulsion process, paying particular attention to the clusters' stability. The obtained A(4)[Re(6)Q(8)L(6)]@SiO(2) nanoparticles are 30 nm in size with good monodispersity and a perfectly spherical shape, as shown by scanning electron microscopy (SEM). The presence of cluster units inside the silica matrix was evidenced by scanning transmission electron microscopy in annular dark-field mode (ADF-STEM). From the point of view of their optical properties, the A(4)[Re(6)Q(8)L(6)]@SiO(2) nanoparticles show red and NIR emission under UV excitation, even when dispersed in water. The evolution of the structural and luminescence properties of clusters before and after encapsulation was followed by Raman and photoluminescence spectroscopy.     

Medicinal Flowers. XXXI. Acylated oleanane-type triterpene saponins, Sasanquasaponins I-V, with antiallergic activity from the flower buds of Camellia sasanqua

The methanolic extract and its 1-butanol-soluble fraction from the flower buds of Camellia sasanqua THUNB. were found to show inhibitory activities on the release of β-hexosaminidase from rat basophile leukemia (RBL-2H3) cells. From the 1-butanol-soluble fraction, five new acylated oleanane-type triterpene saponins, sasanquasaponins I-V, were isolated together with a known saponin and their chemical structures were elucidated on the basis of chemical and physicochemical evidence. The principal saponin constituents, sasanquasaponins I-III, with an acyl group at the 22-position of the aglycon part showed the inhibitory effects on the release of β-hexosaminidase and some structure-activity relationships were reported.     

Oxygen‐sensing properties of 5,10,15,20‐tetraphenylporphinato platinum(II) and palladium(II) covalently bound on poly(isobutyl‐co‐2,2,2‐trifluoroethyl methacrylate)

A novel methacrylate monomer bearing 5,10,15,20‐tetraphenylporphyrinato palladium(II) (PdTPP) (monomer 1a ) was synthesized and copolymerized with isobutyl methacrylate (IBM) and 2,2,2‐trifluoroethyl methacrylate (TFEM) to give poly (IBM‐co‐TFEM) bearing PdTPP (copolymer 2a ) as a dye‐conjugated oxygen‐permeable polymer for pressure‐sensitive paint applications. The introduction of PdTPP into copolymer 2a was confirmed by UV–vis spectroscopy and extended X‐ray absorption fine structure analysis. The Stern–Volmer plots of the copolymer 2a and a mixture of PdTPP and poly(IBM‐co‐TFEM) both showed downward curvature, unlike that of the platinum complex analogue (copolymer 2b ) previously reported. The plots were successfully fitted with a two‐site model to give two distinct Stern–Volmer constants (K_SV1 and K_SV2) and the partition ratio f₁. Interestingly, the f₁ values for the copolymer 2a were almost constant at about 0.98, whereas those of the mixture of PdTPP and poly(IBM‐co‐TFEM) increased from 0.889 to 0.967 as the temperature was increased. This finding suggests that there are two distinct microheterogeneities, one temperature‐dependent and the other temperature‐independent, in the mixture of PdTPP and poly(IBM‐co‐TFEM). The dye‐conjugation approach effectively eliminates the temperature‐dependent, but not the temperature‐independent microheterogeneity. The luminescence decays of copolymers 2a and 2b and the corresponding mixtures in the absence of oxygen indicated that the temperature‐dependent microheterogeneity involves an oxygen diffusion process, whereas the temperature‐independent one appears to be inherent nature in PdTPP. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 663–670, 2010     

Formation of a liquid organic ion associate in aqueous solution and its application to the GF-AAS determination of trace cadmium in environmental water as a complex with 2-(5-bromo-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol

The formation of a liquid organic ion associate in an aqueous sample was applied to the concentration and determination of cadmium in environmental water samples. Cadmium was converted into a complex with 2-(5-bromo-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol (5-Br-PAPS) in a 40-mL sample solution, and was extracted into a liquid ion associate of phenolsulfonate and benzethonium during phase formation. More than 400-fold enrichment was easily attained by this technique, because the volume of the liquid organic phase formed was very small, ca. 2 microL. After dilution of the organic phase with a small volume of 2-methoxyethanol, the cadmium in the solution was determined by GF-AAS. The detection limit was 0.09 ng/L (3sigma(b)). This method was applied to the determination of cadmium in river water and seawater.     

Evaluation of the abilities of ��-cyclodextrin to form complexes by surface plasmon resonance with a Biacore? system

Although phase-solubility studies have often been used to evaluate the interaction of cyclodextrins (CDs) with various drugs, hundreds of milligrams of both CD and drug are required to prepare a phase diagram. A method that would require considerably less material for evaluating complex formation between a CD and guest compound is therefore needed. We previously reported the detection of the interactions between ??-CD and various drugs using a Biacore^® system. In this study, we succeeded in immobilizing 6-monodeoxy-6-monoamino-??-CD on the gold surface of a sensor chip and in detecting the interactions between the immobilized ??-CD and various drugs. The interaction processes were kinetically analyzed using Biacore^®. The surface plasmon resonance sensorgrams indicated that the association and dissociation rates of the interactions between ??-CD and drugs were faster than those between ??-CD and drugs. Although the association constants calculated from the sensorgrams were smaller than those calculated from phase-solubility studies, good correlation was shown between these data.     

Importance of sialic acid residues illuminated by live animal imaging using phosphorylcholine self-assembled monolayer-coated quantum dots

Glycans are expected to be one of the potential signal molecules for controlling drug targeting/delivery or long-term circulation of biopharmaceuticals. However, the effect of the carbohydrates of artificially glycosylated derivatives on in vivo dynamic distribution profiles after intravenous injection of model animals remains unclear due to the lack of standardized methodology and a suitable platform. We report herein an efficient and versatile method for the preparation of multifunctional quantum dots (QDs) displaying common synthetic glycosides with excellent solubility and long-term stability in aqueous solution without loss of quantum yields. Combined use of an aminooxy-terminated thiol derivative, 11,11'-dithio bis[undec-11-yl 12-(aminooxyacetyl)amino hexa(ethyleneglycol)], and a phosphorylcholine derivative, 11-mercaptoundecylphosphorylcholine, provided QDs with novel functions for the chemical ligation of ketone-functionalized compounds and the prevention of nonspecific protein adsorption concurrently. In vivo near-infrared (NIR) fluorescence imaging of phosphorylcholine self-assembled monolayer (SAM)-coated QDs displaying various simple sugars (glyco-PC-QDs) after administration into the tail vein of the mouse revealed that distinct long-term delocalization over 2 h can be achieved in cases of QDs modified with α-sialic acid residue (Neu5Ac-PC-QDs) and control PC-QDs, while QDs bearing other common sugars, such as α-glucose (Glc-PC-QDs), α-mannose (Man-PC-QDs), α-fucose (Fuc-PC-QDs), lactose (Lac-PC-QDs), β-glucuronic acid (GlcA-PC-QDs), N-acetyl-β-D-glucosamine (GlcNAc-PC-QDs), and N-acetyl-β-D-galactosamine (GalNAc-PC-QDs) residues, accumulated rapidly (5-10 min) in the liver. Sequential enzymatic modifications of GlcNAc-PC-QDs gave Galβ1,4GlcNAc-PC-QDs (LacNAc-PC-QDs), Galβ1,4(Fucα1,3)GlcNAc-PC-QDs (Le(x)-PC-QDs), Neu5Acα2,3Galβ1,4GlcNAc-PC-QDs (sialyl LacNAc-PC-QDs), and Neu5Acα2,3Galβ1,4(Fucα1,3)GlcNAc-PC-QDs (sialyl Le(x)-PC-QDs) in quantitative yield as monitored by direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry analyses. Live animal imaging uncovered for the first time that Le(x)-PC-QDs also distributed rapidly in the liver after intravenous injection and almost quenched over 1 h in similar profiles to those of LacNAc-PC-QDs and Lac-PC-QDs. On the other hand, sialyl LacNAc-PC-QDs and sialyl Le(x)-PC-QDs were still retained stably in the whole body after 2 h, while they showed significantly different in vivo dynamics in the tissue distribution, suggesting that structure/sequence of the neighboring sugar residues in the individual sialyl oligosaccharides might influence the final organ-specific distribution. The present results clearly visualize the evidence of an essential role of the terminal sialic acid residue(s) for achieving prolonged in vivo lifetime and biodistribution of various glyco-PC-QDs as a novel class of functional platforms for nanomaterial-based drug targeting/delivery. A standardized protocol using multifunctional PC-QDs should facilitate live animal imaging of ligand-displayed QDs using versatile NIR fluorescence photometry without influence of size-dependent accumulation/excretion pathway for nanoparticles (e.g., viruses) >10 nm in hydrodynamic diameter by the liver.     

Nonexistence of type II blowup solution for a semilinear heat equation

A solution u of a Cauchy problem for a semilinear heat equation

     

A sufficient condition for type I blowup in a parabolic-elliptic system

This paper is concerned with blowup of positive solutions to a Cauchy problem for a parabolic-elliptic system