Innovative Agents for Actinic Keratosis and Nanocarriers Enhancing Skin Penetration

Actinic keratosis and cutaneous squamous cell carcinoma are of increasing importance with aging and increased ultraviolet light exposure in Western societies. Efficient and well-tolerated therapy is still a matter of concern. As with tumours of other organs, new target sites and innovative drugs selectively addressing them are widely looked for. Due to the relevance for DNA synthesis and thus cell proliferation, human DNA polymerase alpha should be such a target, the more so as the three-dimensional structure of the active site has been proposed based on the application of molecular modelling methods and molecular dynamics simulations. The modelled structure of the active site was used for docking nucleotide analogues in order to design selective inhibitors. Consequently, well-fitting thymidine and guanosine analogues were synthesized and tested in vitro for their influence on normal and transformed human keratinocytes. In fact, the combination of modelling studies and in vitro tests allowed us to design antiproliferative and cytotoxic agents which are new drug candidates for the therapy of skin tumours, given the agents are no relevant substrates of nucleotide transporters (MRP-4, MRP-5) expressed by skin cancer cells. Essential kinases for nucleoside activation were detected, too, corresponding with the observed effects of nucleoside analogues. Due to the rather high molecular weight and poor solubility, however, skin penetration should be poor and thus topical therapy may require carriers to improve the uptake. This becomes feasible by lipidic and non-lipidic nanoparticles which can enhance the uptake of lipophilic agents up to 13-fold. Copyright (C) 2010 S. Karger AG, Base

Glucocorticoids for human skin: New aspects of the mechanism of action

Topical glucocorticoids have always been considered first-line drugs for inflammatory diseases of the skin and bronchial system. Applied systemically, glucocorticoids are used for severe inflammatory and immunological diseases and the inhibition of transplant rejection. Owing to the progress in molecular pharmacology, the knowledge of the mechanism of action has increased during the last years. Besides distinct genomic targets, which are due to the activation of specific cytoplasmatic receptors resulting in the (trans-) activation or (trans-) repression of target genes, there are non-genomic effects on the basis of the interference with membrane-associated receptors as well as with membrane lipids. In fact, various glucocorticoids appear to differ with respect to the relative influence on these targets. Thus, the extended knowledge of glucocorticoid-induced cellular signalling should allow the design and development of even more specifically acting drugs-as it has been obtained with other steroids, e.g. estrogens for osteoporosis prevention. Copyright (C) 2005 S. Karger AG, Basel

Dynamics of photoinduced Charge Density Wave-metal phase transition in K0.3MoO3

We present first systematic studies of the photoinduced phase transition from the ground charge density wave (CDW) state to the normal metallic (M) state in the prototype quasi-1D CDW system K0.3MoO3. Ultrafast non-thermal CDW melting is achieved at the absorbed energy density that corresponds to the electronic energy difference between the metallic and CDW states. The results imply that on the sub-picosecond timescale when melting and subsequent initial recovery of the electronic order takes place the lattice remains unperturbed.Comment: Phys. Rev. Lett., accepted for publicatio

Excitation Induced Dephasing in Semiconductor Quantum Dots

A quantum kinetic theory is used to compute excitation induced dephasing in semiconductor quantum dots due to the Coulomb interaction with a continuum of states, such as a quantum well or a wetting layer. It is shown that a frequency dependent broadening together with nonlinear resonance shifts are needed for a microscopic explanation of the excitation induced dephasing in such a system, and that excitation induced dephasing for a quantum-dot excitonic resonance is different from quantum-well and bulk excitons.Comment: 6 pages, 4 figures. Extensively revised text, two figures change

Debye screening and Meissner effect in a three-flavor color superconductor

I compute the gluon self-energy in a color superconductor with three flavors of massless quarks, where condensation of Cooper pairs breaks the color and flavor SU(3)_c x U(3)_V x U(3)_A symmetry of QCD to the diagonal subgroup SU(3)_{c+V}. At zero temperature, all eight electric gluons obtain a Debye screening mass, and all eight magnetic gluons a Meissner mass. The Debye as well as the Meissner masses are found to be equal for the different gluon colors. These masses determine the coefficients of the kinetic terms in the effective theory for the low-energy degrees of freedom. Their values agree with those obtained by Son and Stephanov.Comment: 10 pages, 1 figure (eps

Superfluidity in a Model of Massless Fermions Coupled to Scalar Bosons

We study superfluidity in a model of massless fermions coupled to a massive scalar field through a Yukawa interaction. Gap equations for a condensate with total spin J=0 are solved in the mean-field approximation. For the Yukawa interaction, the gaps for right- and left-handed fermions are equal in magnitude and opposite in sign, so that condensation occurs in the J^P = 0^+ channel. At finite scalar mass, there are two different gaps for fermions of a given chirality, corresponding to condensation of particle pairs or of antiparticle pairs. These gaps become degenerate in the limit of infinite scalar mass.Comment: 26 pages, 9 figures, RevTeX, epsf and psfig style files required. Revised version, discussion of the excitation spectrum extended, Fig. 2 adde

QCD and the eta prime Mass: Instantons or Confinement?

We argue that lattice calculations of the $\eta'$ mass in QCD with $N_c=2$ colors performed at non-zero baryon chemical potential can be used to study the mechanism responsible for the mass of the $\eta'$. QCD with two colors is an ideal laboratory because it exhibits confinement, chiral symmetry breaking and a would-be $U(1)_A$ Goldstone boson at all densities. Since the instanton density and the confinement scale vary with density in a very different way, instantons are clearly distinguishable from other possible mechanisms. There is an instanton prediction for the $\eta'$ mass at large density that can be compared to lattice results. The density dependence of the instanton contribution is a simple consequence of the integer topological charge carried by the instanton. We also argue that $N_c=3$ color QCD at finite isospin density can be used in order to study the origin of OZI-violation in the scalar sector.Comment: 6 pages, 2 figure

Adsorption transition of a self-avoiding polymer chain onto a rigid rod

The subject of this work is the adsorption transition of a long flexible self-avoiding polymer chain onto a rigid thin rod. The rod is represented by a cylinder of radius R with a short-ranged attractive surface potential for the chain monomers. General scaling results are obtained by using renormalization group arguments in conjunction with available results for quantum field theories with curved boundaries [McAvity and Osborn 1993 Nucl. Phys. B 394, 728]. Relevant critical exponents are identified and estimated using geometric arguments.Comment: 19 pages, 4 figures. To appear in: J. Phys.: Condens. Matter, special issue dedicated to Lothar Schaefer on the occasion of his 60th birthda