Myrtucommulone from Myrtus communis: metabolism, permeability, and systemic exposure in rats

Nonsteroidal anti-inflammatory drug intake is associated with a high prevalence of gastrointestinal side effects, and severe cardiovascular adverse reactions challenged the initial enthusiasm in cyclooxygenase-2 inhibitors. Recently, it was shown that myrtucommulone, the active ingredient of the Mediterranean shrub Myrtus communis, dually and potently inhibits microsomal prostaglandin E₂ synthase-1 and 5-lipoxygenase, suggesting a substantial anti-inflammatory potential. However, one of the most important prerequisites for the anti-inflammatory effects in vivo is sufficient bioavailability of myrtucommulone. Therefore, the present study was aimed to determine the permeability and metabolic stability in vitro as well as the systemic exposure of myrtucommulone in rats. Permeation studies in the Caco-2 model revealed apparent permeability coefficient values of 35.9 · 10⁻⁶ cm/s at 37 °C in the apical to basolateral direction, indicating a high absorption of myrtucommulone. In a pilot rat study, average plasma levels of 258.67 ng/mL were reached 1 h after oral administration of 4 mg/kg myrtucommulone. We found that myrtucommulone undergoes extensive phase I metabolism in human and rat liver microsomes, yielding hydroxylated and bihydroxylated as well as demethylated metabolites. Physiologically-based pharmacokinetic modeling of myrtucommulone in the rat revealed rapid and extensive distribution of myrtucommulone in target tissues including plasma, skin, muscle, and brain. As the development of selective microsomal prostaglandin E₂ synthase-1 inhibitors represents an interesting alternative strategy to traditional nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for the treatment of chronic inflammation, the present study encourages further detailed pharmacokinetic investigations on myrtucommulone

Detection of a flow induced magnetic field eigenmode in the Riga dynamo facility

In an experiment at the Riga sodium dynamo facility, a slowly growing magnetic field eigenmode has been detected over a period of about 15 seconds. For a slightly decreased propeller rotation rate, additional measurements showed a slow decay of this mode. The measured results correspond satisfactory with numerical predictions for the growth rates and frequencies

Solvability and PT-symmetry in a double-well model with point interactions

We show that and how point interactions offer one of the most suitable guides towards a quantitative analysis of properties of certain specific non-Hermitian (usually called PT-symmetric) quantum-mechanical systems. A double-well model is chosen, an easy solvability of which clarifies the mechanisms of the unavoided level crossing and of the spontaneous PT-symmetry breaking. The latter phenomenon takes place at a certain natural boundary of the domain of the "acceptable" parameters of the model. Within this domain the model mediates a nice and compact explicit illustration of the not entirely standard probabilistic interpretation of the physical bound states in the very recently developed (so called PT symmetric or, in an alternative terminology, pseudo-Hermitian) new, fairly exciting and very quickly developing branch of Quantum Mechanics.Comment: 24 p., written for the special journal issue "Singular Interactions in Quantum Mechanics: Solvable Models". Will be also presented to the int. conference "Pseudo-Hermitian Hamiltonians in Quantum Physics III" (Instanbul, Koc University, June 20 - 22, 2005) http://home.ku.edu.tr/~amostafazadeh/workshop/workshop.ht

Projective Hilbert space structures at exceptional points

A non-Hermitian complex symmetric 2x2 matrix toy model is used to study projective Hilbert space structures in the vicinity of exceptional points (EPs). The bi-orthogonal eigenvectors of a diagonalizable matrix are Puiseux-expanded in terms of the root vectors at the EP. It is shown that the apparent contradiction between the two incompatible normalization conditions with finite and singular behavior in the EP-limit can be resolved by projectively extending the original Hilbert space. The complementary normalization conditions correspond then to two different affine charts of this enlarged projective Hilbert space. Geometric phase and phase jump behavior are analyzed and the usefulness of the phase rigidity as measure for the distance to EP configurations is demonstrated. Finally, EP-related aspects of PT-symmetrically extended Quantum Mechanics are discussed and a conjecture concerning the quantum brachistochrone problem is formulated.Comment: 20 pages; discussion extended, refs added; bug correcte

Effect of melt convection on the secondary dendritic arm spacing in peritectic Nd-Fe-B alloy

Dendrites are one of the major microstructural constituents of peritectic alloys. In the present work, the effect of melt convection on the secondary dendritic arm spacing (SDAS) and volume fraction of properitectic alpha-Fe was investigated during solidification of stoichiometric Nd-Fe-B alloys using the forced crucible rotation technique. The resulting microstructure of the alloy in consideration of melt convection has been investigated using scanning electron microscopy and optical microscopy. The average SDAS was determined for each sample from the whole cross-section of the cylindrical test samples using image analyzing software LEICA QWIN. A detailed statistical analysis of the spacing distribution was performed on the basis of the variation of SDAS values, averaged from about 80 to 120 dendrites in different zones. The alpha-Fe volume fraction, measured by vibrating sample magnetometer (VSM), reduces with increasing crucible rotation frequency. Similarly, the SDAS values decrease with increasing rotation frequency. These results are explained from the viewpoint of a reduced melt convection state under steady forced crucible rotation leading to a reduced effective mass transfer coefficient. (C) 2009 Published by Elsevier B.V

Electromagnetic Induction Tomography for Monitoring Liquid Metal Flow During Continuous Casting

Monitoring of the steel flow through the submerged entry nozzle (SEN) during continuous casting presents a challenge for the instrumentation system because of the high temperature environment and the limited access to the nozzle in between the tundish and the mould. In this paper, we describe the development of electromagnetic instrumentation as a new tool to visualize the steel flow profile within the SEN. The presentation will cover the development of the technique from first principles, initial hot tests to subsequent plant tests. Recent work has focussed on experiments on a scaled (approx. 10:1) laboratory model of the continuous casting process. The experiments were performed with argon gas and GaInSn as an analogue for liquid steel, which has similar conductive properties as molten steel and allows the measurements at room temperature. In this work two inductive imaging techniques have been combined for the first time to simultaneously image the two phase distribution in the SEN and the velocity profile in the mould