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A. Haase, J. Tentschert, H. Jungnickel, P. Graf, A. Mantion, F. Draude, J. Plendl, M. Goetz et al.

Silver nanoparticles (SNP) are among the most commercialized nanoparticles worldwide. They can be found in many diverse products, mostly because of their antibacterial properties. Despite its widespread use only little data on possible adverse health effects exist. It is difficult to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles. Here, we applied a novel synthesis approach to obtain SNP, which are covalently stabilized by a small peptide. This enables a tight control of both size and shape. We applied these SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages. Similar gold nanoparticles with the same coating (Au20Pep) were used for comparison and found to be non-toxic. We assessed the cytotoxicity of particles and confirmed their cellular uptake via transmission electron microscopy and confocal Raman microscopy. Importantly a majority of the SNP could be detected as individual particles spread throughout the cells. Furthermore we studied several types of oxidative stress related responses such as induction of heme oxygenase I or formation of protein carbonyls. In summary, our data demonstrate that even low doses of SNP exerted adverse effects in human macrophages.

D. Završnik, S. Muratović, D. Makuc, J. Plavec, M. Cetina, A. Nagl, E. De Clercq, J. Balzarini et al.

We report on the synthesis of 4-hydroxycoumarin dimers 1–15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16–20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The chemical identities and structure of compounds 1–20 were deduced from their homo- and heteronuclear NMR measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1D difference NOE enhancements. Unequivocal proof of the stereostructure of compounds 7, 9, 16 and 18 was obtained by single crystal X-ray diffraction method. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyl- and 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. Consequently, the compounds 7 and 9 adopt conformations in which two 4-hydroxy-coumarin moieties are anti-disposed. Antiviral activity evaluation results indicated that the 4-bromobenzylidene derivative of bis-(4-hydroxycoumarin) (compound 3) possesses inhibitory activity against HSV-1 (KOS), HSV-2 (G), vaccinia virus and HSV-1 TK- KOS (ACVr) at a concentration of 9–12 μM and at a minimum cytotoxic concentration (MCC) greater than 20 μM. Compounds 4–6, 8, and 20 were active against feline herpes virus (50% effective concentration, EC50 = 5–8.1 μM), that is at a 4-7-fold lower concentration than the MCC.

A. Bajraktarević, S. Putica, S. Trninic, A. Skopljak, N. D. Kreso, B. Djukic, A. Hadzimuratović, E. Selimovic et al.

T. Klokocovnik, Miha Antonic, Juš Kšela, Alisa Krdžalić, Mirsada Selimoć

P. Bizarro, K. Chandy, N. Stojanović

S. Samurović, A. Lalović

Aims. We investigate the predictions of Newtonian dynamics and the MOND theory related to the Milky Way galaxy using the Jeans equation. Methods. We used the measurements of the radial velocities of the blue horizontal branch (BHB) halo stars to test the predictions of Newtonian gravity and to also extend our study to different MOND models, taking orbital anisotropies that we calculate into account. Results. The halo stars of the Galaxy were used as a tracer of the Galaxy’s gravitational potential. The Jeans equation was calculated for both the Newtonian and the MOND approaches. We assumed spherical symmetry and calculated the Jeans equation by taking orbital anisotropies into account. Circular velocities for both approaches were also analyzed. Conclusions. We solved the Jeans equation in spherical approximation and confirm that the Newtonian model without dark matter cannot fit the observed velocity dispersion profile and that the truncated flat model with dark matter can provide a good fit to the observed velocity dispersion. For the MOND models, from the Jeans modeling and the models of the circular velocity curves, we found that two models can provide a fit to the data without significant anisotropies whereas two other tested models need various anisotropies to obtain the same result.

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