@article{SpangardtKesslerDobrzewskietal.2022, author = {Spangardt, Christoph and Keßler, Christoph and Dobrzewski, Ramona and Tepler, Antonia and Hanio, Simon and Klaubert, Bernd and Meinel, Lorenz}, title = {Leveraging dissolution by autoinjector designs}, series = {Pharmaceutics}, volume = {14}, journal = {Pharmaceutics}, number = {11}, issn = {1999-4923}, doi = {10.3390/pharmaceutics14112544}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297271}, year = {2022}, abstract = {Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule's light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients' catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations.}, language = {en} } @article{KesslerHertelJungkunstetal.2012, author = {Kessler, Michael and Hertel, Dietrich and Jungkunst, Hermann F. and Kluge, J{\"u}rgen and Abrahamczyk, Stefan and Bos, Merijn and Buchori, Damayanti and Gerold, Gerhard and Gradstein, S. Robbert and K{\"o}hler, Stefan and Leuschner, Christoph and Moser, Gerald and Pitopang, Ramadhanil and Saleh, Shahabuddin and Schulze, Christian H. and Sporn, Simone G. and Steffan-Dewenter, Ingolf and Tjitrosoedirdjo, Sri S. and Tscharntke, Teja}, title = {Can Joint Carbon and Biodiversity Management in Tropical Agroforestry Landscapes Be Optimized?}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0047192}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132016}, pages = {e47192}, year = {2012}, abstract = {Managing ecosystems for carbon storage may also benefit biodiversity conservation, but such a potential 'win-win' scenario has not yet been assessed for tropical agroforestry landscapes. We measured above-and below-ground carbon stocks as well as the species richness of four groups of plants and eight of animals on 14 representative plots in Sulawesi, Indonesia, ranging from natural rainforest to cacao agroforests that have replaced former natural forest. The conversion of natural forests with carbon stocks of 227-362 Mg C ha\(^{-1}\) to agroforests with 82-211 Mg C ha\(^{-1}\) showed no relationships to overall biodiversity but led to a significant loss of forest-related species richness. We conclude that the conservation of the forest-related biodiversity, and to a lesser degree of carbon stocks, mainly depends on the preservation of natural forest habitats. In the three most carbon-rich agroforestry systems, carbon stocks were about 60\% of those of natural forest, suggesting that 1.6 ha of optimally managed agroforest can contribute to the conservation of carbon stocks as much as 1 ha of natural forest. However, agroforestry systems had comparatively low biodiversity, and we found no evidence for a tight link between carbon storage and biodiversity. Yet, potential win-win agroforestry management solutions include combining high shade-tree quality which favours biodiversity with cacao-yield adapted shade levels.}, language = {en} } @article{FeldheimKesslerFeldheimetal.2022, author = {Feldheim, Jonas and Kessler, Almuth F. and Feldheim, Julia J. and Schulz, Ellina and Wend, David and Lazaridis, Lazaros and Kleinschnitz, Christoph and Glas, Martin and Ernestus, Ralf-Ingo and Brandner, Sebastian and Monoranu, Camelia M. and L{\"o}hr, Mario and Hagemann, Carsten}, title = {Effects of long-term temozolomide treatment on glioblastoma and astrocytoma WHO grade 4 stem-like cells}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms23095238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284417}, year = {2022}, abstract = {Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O\(^6\)-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.}, language = {en} } @article{NeefMeisenzahlKessleretal.2020, author = {Neef, Vanessa and Meisenzahl, David and Kessler, Paul and Raimann, Florian J. and Piekarski, Florian and Choorapoikayil, Suma and Fleege, Christoph and Zacharowski, Kai D. and Meybohm, Patrick and Meurer, Andrea}, title = {Implementation of an anaemia walk-in clinic: Feasibility and preliminary data from the Orthopedic University Hospital}, series = {Transfusion Medicine}, volume = {30}, journal = {Transfusion Medicine}, number = {6}, doi = {10.1111/tme.12740}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224594}, pages = {467 -- 474}, year = {2020}, abstract = {Background Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. Objective Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. Material and Methods In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. Results A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6\%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6-40.2 pg]) compared to patients with ID (35.3 pg [28.9-38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2-39.4 pg]; p = 0.001). Conclusion Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.}, language = {en} } @article{FeldheimKesslerFeldheimetal.2023, author = {Feldheim, Jonas and Kessler, Almuth F. and Feldheim, Julia J. and Schmitt, Dominik and Oster, Christoph and Lazaridis, Lazaros and Glas, Martin and Ernestus, Ralf-Ingo and Monoranu, Camelia M. and L{\"o}hr, Mario and Hagemann, Carsten}, title = {BRMS1 in gliomas — an expression analysis}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {11}, issn = {2072-6694}, doi = {10.3390/cancers15112907}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319225}, year = {2023}, abstract = {The metastatic suppressor BRMS1 interacts with critical steps of the metastatic cascade in many cancer entities. As gliomas rarely metastasize, BRMS1 has mainly been neglected in glioma research. However, its interaction partners, such as NFκB, VEGF, or MMPs, are old acquaintances in neurooncology. The steps regulated by BRMS1, such as invasion, migration, and apoptosis, are commonly dysregulated in gliomas. Therefore, BRMS1 shows potential as a regulator of glioma behavior. By bioinformatic analysis, in addition to our cohort of 118 specimens, we determined BRMS1 mRNA and protein expression as well as its correlation with the clinical course in astrocytomas IDH mutant, CNS WHO grade 2/3, and glioblastoma IDH wild-type, CNS WHO grade 4. Interestingly, we found BRMS1 protein expression to be significantly decreased in the aforementioned gliomas, while BRMS1 mRNA appeared to be overexpressed throughout. This dysregulation was independent of patients' characteristics or survival. The protein and mRNA expression differences cannot be finally explained at this stage. However, they suggest a post-transcriptional dysregulation that has been previously described in other cancer entities. Our analyses present the first data on BRMS1 expression in gliomas that can provide a starting point for further investigations.}, language = {en} }