@article{ShityakovPuskasPapaietal.2015, author = {Shityakov, Sergey and Pusk{\´a}s, Istv{\´a}n and P{\´a}pai, Katalin and Salvador, Ellaine and Roewer, Norbert and F{\"o}rster, Carola and Broscheit, Jens-Albert}, title = {Sevoflurane-sulfobutylether-\(\beta\)-cyclodextrin complex: preparation, characterization, cellular toxicity, molecular modeling and blood-brain barrier transport studies}, series = {Molecules}, volume = {20}, journal = {Molecules}, doi = {10.3390/molecules200610264}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148543}, pages = {10264-10279}, year = {2015}, abstract = {The objective of the present investigation was to study the ability of sulfobutylether-\(\beta\)-cyclodextrin (SBECD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBE\(\beta\)CD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (P\(_{app}\)). In addition, SEV binding affinity to SBE\(\beta\)CD was confirmed by a minimal Gibbs free energy of binding (ΔG\(_{bind}\)) value of -1.727 ± 0.042 kcal・mol\(^{-1}\) and an average binding constant (K\(_{b}\)) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.}, language = {en} } @article{MostovayaGrootemanBasileetal.2015, author = {Mostovaya, Ira M. and Grooteman, Muriel P.C. and Basile, Carlo and Davenport, Andrew and de Roij van Zuijdewijn, Camiel L.M. and Wanner, Christoph and Nub{\´e}, Menso J. and Blankestijn, Peter J.}, title = {High convection volume in online post-dilution haemodiafiltration: relevance, safety and costs}, series = {Clinical Kidney Journal}, volume = {8}, journal = {Clinical Kidney Journal}, number = {4}, doi = {10.1093/ckj/sfv040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149814}, pages = {368-373}, year = {2015}, abstract = {Increasing evidence suggests that treatment with online post-dilution haemodiafiltration (HDF) improves clinical outcome in patients with end-stage kidney disease, if compared with haemodialysis (HD). Although the primary analyses of three large randomized controlled trials (RCTs) showed inconclusive results, post hoc analyses of these and previous observational studies comparing online post-dilution HDF with HD showed that the risk of overall and cardiovascular mortality is lowest in patients who are treated with high-volume HDF. As such, the magnitude of the convection volume seems crucial and can be considered as the 'dose' of HDF. In this narrative review, the relevance of high convection volume in online post-dilution HDF is discussed. In addition, we briefly touch upon some safety and cost issues.}, language = {en} } @article{HarterBernatzScholzetal.2015, author = {Harter, Patrick N. and Bernatz, Simon and Scholz, Alexander and Zeiner, Pia S. and Zinke, Jenny and Kiyose, Makoto and Blasel, Stella and Beschorner, Rudi and Senft, Christian and Bender, Benjamin and Ronellenfitsch, Michael W. and Wikman, Harriet and Glatzel, Markus and Meinhardt, Matthias and Juratli, Tareq A. and Steinbach, Joachim P. and Plate, Karl H. and Wischhusen, J{\"o}rg and Weide, Benjamin and Mittelbronn, Michel}, title = {Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {38}, doi = {10.18632/oncotarget.5696}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137107}, pages = {40836 -- 40849}, year = {2015}, abstract = {The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.}, language = {en} }