Characterization of amiodarone metabolites and impurities using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry

Using the high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC/APCI-MS/MS) technique, together with established trends from the literature, the structures of metabolites and impurities of amiodarone, an anti-arrhythmic drug, have been assigned. By comparing analyses of products of incubation with rat liver microsomes with controls in which glucose 6-phosphate dehydrogenase was omitted, metabolites could be distinguished from impurities. Structures for the two proposed metabolites and four impurities are proposed.     

A fluorescent-labeled oligopeptide for monitoring PKA-mediated phosphorylation

A fluorescent-labeled oligopeptide (DACM-CLRRASLK-fluorescein), containing a consensus amino acid sequence (RRXSL) of cyclic AMP (cAMP) dependent protein kinase A (PKA) substrate-proteins, was designed. The fluorescent peptide was a good substrate of PKA, and the phosphorylation of its serin residue caused an intensive change in fluorescent intensity. We expect that the peptide will be useful as a fluorescent indicator for monitoring PKA activity in living cells.     

Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways

Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades.     

The Effects of Beating,Web Forming and Sizing on the Surface Energy of <Emphasis Type="Italic">Eucalyptus globulus</Emphasis> Kraft Fibres Evaluated by Inverse Gas Chromatography

In this work attention has been focused on the effects of papermaking beating, web forming and sizing operations on the physical/chemical surface properties of bleached Eucalyptus globulus kraft fibres. Inverse gas chromatography (IGC) was used to determine the dispersive component of surface tension (γ_s^d) as well as the acidic/basic character (according to the Lewis concept) of the solid surfaces (pulp fibres and pulp handsheets). The results have shown that the main effect of beating is to increase the fibre's Lewis acidic character. Web forming caused a strong decrease in γ_s^d and significant increments in the adhesion works of both acidic and basic probes, lowering the ratio between the two. Nevertheless, the surface of handsheets still exhibited a dominant acidic character. The sizing operation did not change the dispersive component of the surface tension significantly but decreased the difference between the adhesion works of the acidic and basic probes, rendering the handsheet surface less Lewis acidic and more Lewis basic. Thus, although internal sizing is expected to strongly influence liquid spreading at the paper surface and liquid penetration of the fibre's network, it is concluded that beating and web forming lead to important changes in the surface energetic properties of the Eucalyptus globulus kraft fibres.     

Sixth algebraic order trigonometrically fitted predictor–corrector methods for the numerical solution of the radial Schrödinger equation

Our new trigonometrically fitted predictor–corrector (P–C) schemes presented here are based on the well known Adams–Bashforth–Moulton methods: the predictor is based on the fifth order Adams–Bashforth scheme and the corrector on the sixth order Adams–Moulton scheme. We tested the efficiency of our newly developed schemes against well known methods, with excellent results. The numerical experiments showed that at least one of our schemes is noticeably more efficient compared to other methods, some of which are specially designed for this type of problem. It is also worth mentioning that this is the first time that sixth algebraic order trigonometrically fitted Adams–Bashforth–Moulton P–C schemes are used to efficiently solve the radial Schrödinger equation.Active Member of the European Academy of Sciences and Arts     

Synthesis and Stereochemistry of New Bis(1,3-Oxathian-2-yl) Derivatives: Epimerisation and Chair–Twist Equilibria

The synthesis and stereochemistry of some new bis(1,3-oxathian-2-yl) derivatives are reported. The conformational behavior of these compounds and the orientation of their substituents are deduced from the NMR spectra, from the X-ray crystal structures of two compounds and from the ab-initio level calculations. The epimerization of diastereoisomers and the chair ⇌ 22,5-twist equilibria were studied by variable temperature NMR.     

<Emphasis Type="Italic">Ab initio</Emphasis> study of small coinage metal telluride clusters Au<Subscript>n</Subscript>Te<Subscript>m</Subscript> (<Emphasis Type="Italic">n,m</Emphasis> = 1, 2)

The geometries of the most stable isomers of gold telluride systems AuTe, Au₂Te, and AuTe₂ are determined using the MP2 method. The aspect of gold—telluride interaction, the electron correlation, and relativistic effects on geometry and stability are investigated at the MP2 and CCSD(T) theoretical levels. The results show that the electron correlation and relativistic effects are responsible not only for gold—gold attraction but also for additional gold—telluride interaction. The gold—telluride interaction is strong enough to modify the known pattern of bare gold clusters. Both effects are essential for determining the geometry and relative stability of this type of systems.     

Influence of post-annealing temperature on properties of ZnO:Li thin films

Li-doped ZnO thin films were prepared on glass substrates by DC reactive magnetron sputtering. The influence of post-annealing temperature on the electrical, structural, and optical properties of the films was investigated. A conversion from p-type conduction to n-type in a range of temperature was confirmed by Hall measurement. The optimal p-type conduction is achieved at the annealing temperature of 500 °C with a resistivity of 57 Ω cm, carrier concentration of 1.07 × 10¹⁷ cm⁻³ and Hall mobility of 1.03 cm² V⁻¹ s⁻¹. From the temperature-dependent PL analysis, the energy level of Li_Zn acceptor was determined to be 140 meV above the valence band.     

Characterization of CNS disorders and evaluation of therapy using structural and functional MRI

Modern drug development requires technologies that allow rapid translation from the preclinical to the clinical stage. It is obvious that non-invasive imaging modalities such as magnetic resonance imaging (MRI) will play a central role in this regard. This article reviews the use of structural and functional MRI readouts for characterization of central nervous system (CNS) disorders and evaluation of the efficacy of potential CNS drugs. Examples comprise dementia of Alzheimer's type, cerebral ischemia, and neuroinflammation covering both clinical and preclinical aspects. In these examples MRI has been used to obtain relevant structural information on brain atrophy, on the location and extent of ischemic brain areas, and on the number and distribution of demyelinated plaques. These structural data are complemented by readouts assessing the functional consequences associated with the pathomorphological changes. In the last decade, MRI has evolved into a standard tool for the development of CNS drugs. With regard to target-specific/molecular imaging applications MRI is limited by its inherently low sensitivity; complementary imaging modalities utilizing optical and radionuclear reporter systems will thus be required.     

Electrochemical and spectral studies on the reductive nitrosylation of water-soluble iron porphyrin

The reaction of iron(III) (meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (Fe(III)TMPyP) with nitric oxide (NO) was studied by electronic absorption spectroscopy, ESR, and electrochemical and spectroelectrochemical techniques in aqueous solutions with pH from 2.2 to 12.0. Fe(III)TMPyP has been found to undergo a reductive nitrosylation in all pHs, and the product of nitric oxide binding to the porphyrin has been determined as iron(II) porphyrin nitrosyl complex ([Fe(II)(NO)TMPyP]). The rate of the reductive nitrosylation exhibits a tendency to get faster with increase in pH. An intermediate species was observed around neutral pH by spectroelectrochemical technique and was proposed to be the iron(II) nitrosyl complex of the mu-oxo dimeric form of FeTMPyP, which is known to be a predominant in neutral solutions.