Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance the Angiogenic Effect of Biological Burn-wound Bandages.

Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality in burn patients. Such wound infections serve as bacterial reservoir for nosocomial infections and are associated with significant morbidity and costs. Anti-microbial polycationic dendrimers G3KL and G3RL, able to kill multi-drug resistant P. aeruginosa, have been previously developed. The combination of these dendrimers with a class of biological bandages made of progenitor skin cells, which secrete growth factors, could positively impact wound-healing processes. However, polycations are known to be used as anti-angiogenic agents for tumor suppression. Since, neovascularization is pivotal in the healing of deep burn-wounds, the use of anti-microbial dendrimers may thus hinder the healing processes. Surprisingly, we have seen in this study that G3KL and G3RL dendrimers can have angiogenic effects. Moreover, we have shown that a dendrimer concentration ranging between 50 and 100 μg/mL in combination with the biological bandages can suppress bacterial growth without altering cell viability up to 5 days. These results show that antimicrobial dendrimers can be used in combination with biological bandages and could potentially improve the healing process with an enhanced angiogenesis

Gravitational waves from supernova matter

We have performed a set of 11 three-dimensional magnetohydrodynamical core collapse supernova simulations in order to investigate the dependencies of the gravitational wave signal on the progenitor's initial conditions. We study the effects of the initial central angular velocity and different variants of neutrino transport. Our models are started up from a 15 solar mass progenitor and incorporate an effective general relativistic gravitational potential and a finite temperature nuclear equation of state. Furthermore, the electron flavour neutrino transport is tracked by efficient algorithms for the radiative transfer of massless fermions. We find that non- and slowly rotating models show gravitational wave emission due to prompt- and lepton driven convection that reveals details about the hydrodynamical state of the fluid inside the protoneutron stars. Furthermore we show that protoneutron stars can become dynamically unstable to rotational instabilities at T/|W| values as low as ~2 % at core bounce. We point out that the inclusion of deleptonization during the postbounce phase is very important for the quantitative GW prediction, as it enhances the absolute values of the gravitational wave trains up to a factor of ten with respect to a lepton-conserving treatment.Comment: 10 pages, 6 figures, accepted, to be published in a Classical and Quantum Gravity special issue for MICRA200

Comparison of desferrioxamine and NODAGA for the gallium-68 labeling of exendin-4

Introduction Radiolabeled exendin-4 (Ex4) derivatives are used to target the glucagon-like peptide-1 receptor (GLP-1R) for the clinical diagnosis of insulinomas, a rare type of neuroendocrine tumor. Gallium-68 is an ideal diagnostic nuclide for this application and a study evaluating an exendin-4-NODAGA conjugate is currently underway. However, in complexion with the chelator DFO, its in vivo stability has been a matter of dispute. The aim of this work was to directly compare [68Ga]Ga-Ex4NOD with [68Ga]Ga-Ex4DFO in vitro and in vivo. Methods In our approach, we directly compared N′-[5-(acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl)propanoylamino]pentyl]-N-hydroxy-butane diamide (desferriox-amine B, DFO) and 2-(4,7-bis (carboxymethyl)-1,4,7-triazonan-1-yl) pentanedioic acid (NODAGA) conjugated to exendin-4 in vitro and in vivo. We radiolabeled the peptides with gallium-68, followed by HPLC quality control. In vitro characterization was performed in CHL cells overexpressing the GLP-1R and in vivo studies were conducted with CD1 nu/nu mice carrying tumors derived from these cells. Results We found that both peptides could be radiolabeled with a molar activity of about 9.33 MBq/nmol without further purification. They internalized equally well into GLP-1R-expressing cells and their IC50 was similar with 15.6 ± 7.8 nM and 18.4 ± 3.0 nM for [natGa]Ga-Ex4NOD and [natGa]Ga-Ex4DFO, respectively. In vivo, [68Ga]Ga-Ex4NOD accumulated more in all tissue, while [68Ga]Ga-Ex4DFO exhibited a more favorable target-to-kidney ratio. Conclusion and relevance DFO is a suitable chelator for the radiolabeling of exendin-4 derivatives with gallium-68 for in vitro and preclinical in vivo studies. DFO performed better in vivo due to its significantly lower kidney accumulation (p < 0.0001). It was also found to be stable in vivo in mice, contrary to earlier reports. Based on our results, the DFO chelating system in combination with exendin-4 would be an interesting option for clinical imaging of insulinomas

What are the astrophysical sites for the r-process and the production of heavy elements?

This article addresses three of the four nucleosynthesis processes involved in producing heavy nuclei beyond Fe (with a main focus on the r-process). Opposite to the fourth process (the s-process), which operates in stellar evolution during He- and C-burning, they are all related to explosive burning phases, (presumably) linked to core collapse supernova events of massive stars. The (classical) p-process is identified with explosive Ne/O-burning in outer zones of the progenitor star. It is initiated by the passage of the supernova shock wave and acts via photodisintegration reactions like a spallation process which produces neighboring (proton-rich) isotopes from pre-existing heavy nuclei. The reproduction of some of the so-called lighter p-isotopes with A <100 faces problems in this environment. The only recently discovered vp-process is related to the innermost ejecta, the neutrino wind expelled from the hot proto-neutron star after core collapse and the supernova explosion. This neutrino wind is proton-rich in its early phase, producing nuclei up to Ge-64. Reactions with neutrinos permit to overcome decay/reaction bottlenecks for the flow beyond Ge-64, thus producing light p-isotopes, which face problems in the classical p-process scenario. The understanding of the r-process, being identified for a long time with rapid neutron captures and passing through nuclei far from stability, is still experiencing major problems. These are on the one hand related to nuclear uncertainties far from stability (masses, half-lives, fission barriers), affecting the process speed and abundance peaks. On the other hand the site is still not definitely located, yet. (i) Later, possibly neutron-rich, high entropy phases of the neutrino wind (if they materialize!) could permit its operation. (ii) Other options include the ejection of very neutron-rich neutron star-like matter, occurring possibly in neutron star mergers or core collapse supernova events with jets, related to prior stellar evolution with high rotation rates and magnetic fields. Two different environments are required for a weak and a main/strong r-process, witnessed by observations of low metallicity stars and meteoritic inclusions, which could possibly be identified with the two options listed above, i.e. the weak r-process could be related to the neutrino wind when changing from p-rich to n-rich conditions. (C) 2011 Elsevier B.V. All rights reserved.Peer reviewe