Since lithium salts are used as pharmaceutically active compounds against manic-depressive psychosis, there is a demand to monitor the lithium concentration in blood in the narrow range of 0.6-1.2 mM effectively and safely. Here we report on an optical sensor approach for the determination of Li+, based on the design and synthesis of a novel lithium fluoroionophore KLI-1 and its polymer immobilizable derivative KLI-2, and the application to an optode. The novel lithium fluoroionophores rely on a tetramethyl "blocking subunit" bearing 14-crown-4 as a Li+-selective binding site and 4-methylcoumarin as a fluorophore, intramolecularly connected to show ICT-type wavelength shift for ratiometric fluorescence measurements. The fluoroionophores showed high selectivity for Li+ with binding-induced blue shift in the fluorescence spectra, no response to major biological interfering cations (K+, Ca2+, Mg2+), a selectivity of log kLi+,Na+ = -2.4 over Na+ in solution, and no response to pH in the range of pH 3-10. A hydrophilic optode membrane with KLI-2 immobilized also showed good selectivity for Li+, pH independence in the physiological range (pH 6-8), and fully reversible signal changes. KLI-1 and KLI-2 are excellent Li+ fluorescent chemosensors that can be applied to quantitative measurements of lithium in clinical samples, although possible interference from Na+ has to be considered at the lower therapeutic level of Li+.

Deregulated activation of protein tyrosine kinases, such as the epidermal growth factor receptor (EGFR) and Abl, is associated with human cancers including non-small cell lung cancer (NSCLC) and chronic myeloid leukemia (CML). Although inhibitors of such activated kinases have proved to be of therapeutic benefit in individuals with NSCLC or CML, some patients manifest intrinsic or acquired resistance to these drugs.We now show that, whereas blockade of either the extracellular signal-regulated kinase Co-administration of a cytostatic signaling pathway inhibitor may contribute to the development of safer anticancer strategies by lowering the required dose of cytotoxic HDAC inhibitors for a variety of cancers.

We have established a unique enzymatic approach for obtaining sulfated disaccharides using Bacillus circulans beta-D-galactosidase-catalyzed 6-sulfo galactosylation. When 4-methyl umbelliferyl 6-sulfo beta-D-galactopyranoside (S6Gal beta-4MU) was used as a donor, the enzyme induced transfer of 6-sulfo galactosyl residue to GlcNAc acceptor. As a result, the desired compound 6'-sulfo N-acetyllactosamine (S6Gal beta1-4GlcNAc) and its positional isomer 6'-sulfo N-acetylisolactosamine (S6Gal beta1-6GlcNAc) were observed by HPAEC-PAD, in 49% total yield based on the donor added, and in a molar ratio of 1:3.5. With a glucose acceptor, the regioselectivity was substantially changed and S6Gal beta1-2Glc was mainly produced along with beta-(1-1)alpha, beta-(1-3), beta-(1-6) isomers in 74% total yield. When methyl alpha-D-glucopyranoside (Glc alpha-OMe) was an acceptor, the enzyme also formed mainly S6Gal beta1-2Glc alpha-OMe with its beta-(1-6)-linked isomer in 41% total yield based on the donor added. In both cases, it led to the predominant formation of beta-(1-2)-linked disaccharides. In contrast, with the corresponding methyl beta-D-glucopyranoside (Glc beta-OMe) acceptor, S6Gal beta1-3Glc beta-OMe and S6Gal beta1-6Glc beta-OMe were formed in a low total yield of 12%. These results indicate that the regioselectivity and efficiency on the beta-D-galactosidase-mediated transfer reaction significantly depend on the anomeric configuration in the glucosyl acceptors.

A highly sensitive gas chromatographic-mass spectrometric (GC-MS) method was developed for dithiocarbamates (DTCs) and milneb in foods. DTCs and milneb were extracted from foods with cysteineῌEDTA solution as sodium salts, and methylated with methyl iodide. Methyl derivatives of DTCs and milneb were cleaned up on a neutral alumina mini column and determined by GC-MS. The mean recoveries of DTCs and milneb were in the range of 72ῌ120ῌ, except for methiram. The quantification limits were 0.01 mg/kg (as CS 2 ) in foods except tea (0.1 mg/kg as CS 2 ). The developed method was applied to 10 compounds (4 dimethyldithiocarbamates, 3 ethylenebisdithiocarbamates, polycarbamates, propineb and milneb).