Effects of physicochemical properties of TiO2 nanomaterials for pulmonary inflammation, acute phase response and alveolar proteinosis in intratracheally exposed mice

Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed C57BL/6 J mice to a single dose of four anatase TiO2 NMs with various sizes and shapes by intratracheal instillation and assessed the pulmonary toxicity 1, 3, 28, 90 or 180 days post-exposure. The quartz DQ12 was included as benchmark particle. Pulmonary responses were evaluated by histopathology, electron microscopy, bronchoalveolar lavage (BAL) fluid cell composition and acute phase response. Genotoxicity was evaluated by DNA strand break levels in BAL cells, lung and liver in the comet assay. Multiple regression analyses were applied to identify specific TiO2 NMs properties important for the pulmonary inflammation and acute phase response. The TiO2 NMs induced similar inflammatory responses when surface area was used as dose metrics, although inflammatory and acute phase response was greatest and more persistent for the TiO2 tube. Similar histopathological changes were observed for the TiO2 tube and DQ12 including pulmonary alveolar proteinosis indicating profound effects related to the tube shape. Comparison with previously published data on rutile TiO2 NMs indicated that rutile TiO2 NMs were more inflammogenic in terms of neutrophil influx than anatase TiO2 NMs when normalized to total deposited surface area. Overall, the results suggest that specific surface area, crystal phase and shape of TiO2 NMs are important predictors for the observed pulmonary effects of TiO2 NMs.Peer reviewe

Influence of cancerostatic perifosine on membrane fluidity of liposomes and different cell lines as measured by electron paramagnetic resonance

AIM: To test whether membrane fluidity and its changes are important for the sensitivity of cells to the action of perifosine (OPP), a new anticancer drug targeting cell membrane and not DNA. METHOD: Influence of OPP on the membrane structure of OPP-resistant MCF7, and OPP-sensitive MT3 breast cancer cell lines, as well as of mouse fibroblasts (L929) cell lines, and model cells (liposomes) was investigated by electron paramagnetic resonance, using spin labeled derivative of OPP (P5) and 5-doxylpalmitoyl methylester (MeFASL(10,3)) as spin probes. RESULTS: OPP increased membrane fluidity of all cell lines at concentrations higher than 50 µM (on the level of P ≤ 0.05, t test). In cells, the differences were observed only by P5 and not by MeFASL(10,3). Average order parameter S(eff) decreased for about 12% in MCF7 and L929 and only for 8% in OPP-sensitive MT3 cells, showing that there was no correlation between membrane fluidity changes and sensitivity of cells to OPP. The only correlation we found was between OPP sensitivity and the cell growth rate. In liposomes, both spin probes were sensitive to the action of OPP. S(eff) decreased with increasing concentration of OPP. For MeFASL(10,3) a significant decrease was observed at 4 mol% OPP, while for P5 it was observed at 8 mol%. CONCLUSION: Influence of OPP on plasma membrane fluidity of breast cancer cells is not the determining factor in the sensitivity of cells to OPP

iPriročnik iPhone

iPriročnik iPhone je predvsem namenjen osnovnim uporabnikom, ki bi radi kaj več kot zgolj telefonarili naokrog in izgledali šik. Seveda pa bodo tudi naprednejši uporabniki izvedeli kakšen nov trik. Zgoščeno so razložene osnove rokovanja z iPhonom (navigacija, telefoniranje, povezovanje z internetom in osebnimi računalniki, iskanje, prenašanje, nameščanje in odnameščanje aplikacij, nastavitve ipd.). Razložena je tudi osnovna uporaba prednaloženih in drugih zanimivejših aplikacij

Method for controlled tissue theranostics using a single tunable laser source

Tissue diseases and related disorders need to be first recognized using diagnostic methods and then later treated by therapeutic methods–a joint procedure called theranostics. One of the main challenges in the field of retinal therapies remains in the success of the treatment, typically improving the local metabolism, by sparing the surrounding tissue and with the immediate information of the laser effect. In our study, we present a concept for real-time controlled tissue theranostics on a proof-of-concept study capable of using a single tunable ps laser source (in terms of irradiance, fluence, and repetition rate), done on ex-vivo human retinal pigment epithelium. We have found autofluorescence intensity and lifetime imaging diagnostics very promising for the recognition and quantification of laser effects ranging from selective non-destructive molecular tissue modification to complete tissue ablation. The main novelty of our work presents the developed algorithm for optimized theranostics based on the model function used to quantify laser-induced tissue changes through the diagnostics descriptors, fluorescence lifetime and fluorescence intensity parameters. This approach, together with the operation of the single adaptable laser source, can serve as a new theranostics method in personalized medicine in the future not only limited to treat retinal diseases