TY - JOUR A1 - Dietl, Alexander A1 - Prieschenk, Christine A1 - Eckert, Franziska A1 - Birner, Christoph A1 - Luchner, Andreas A1 - Maier, Lars S. A1 - Buchner, Stefan T1 - 3D vena contracta area after MitraClip© procedure: precise quantification of residual mitral regurgitation and identification of prognostic information JF - Cardiovascular Ultrasound N2 - Background Percutaneous mitral valve repair (PMVR) is increasingly performed in patients with severe mitral regurgitation (MR). Post-procedural MR grading is challenging and an unsettled issue. We hypothesised that the direct planimetry of vena contracta area (VCA) by 3D–transoesophageal echocardiography allows quantifying post-procedural MR and implies further prognostic relevance missed by the usual ordinal scale (grade I-IV). Methods Based on a single-centre PMVR registry containing 102 patients, the association of VCA reduction and patients’ functional capacity measured as six-minute walk distance (6 MW) was evaluated. 3D–colour-Doppler datasets were available before, during and 4 weeks after PMVR. Results Twenty nine patients (age 77.0 ± 5.8 years) with advanced heart failure (75.9% NYHA III/IV) and severe degenerative (34%) or functional (66%) MR were eligible. VCA was reduced in all patients by PMVR (0.99 ± 0.46 cm\(^2\) vs. 0.22 ± 0.15 cm\(^2\), p < 0.0001). It remained stable after median time of 33 days (p = 0.999). 6 MW improved after the procedure (257.5 ± 82.5 m vs. 295.7 ± 96.3 m, p < 0.01). Patients with a decrease in VCA less than the median VCA reduction showed a more distinct improvement in 6 MW than patients with better technical result (p < 0.05). This paradoxical finding was driven by inferior results in very large functional MR. Conclusions VCA improves the evaluation of small residual MR. Its post-procedural values remain stable during a short-term follow-up and imply prognostic information for the patients’ physical improvement. VCA might contribute to a more substantiated estimation of treatment success in the heterogeneous functional MR group. KW - percutaneous mitral valve repair KW - MitraClip KW - 3D echocardiography KW - vena contracta area KW - six-minute walk test KW - NT-proBNP KW - prognosis KW - functional mitral regurgitation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225318 VL - 16 ER - TY - THES A1 - Wäldchen, Felix T1 - 3D Single Molecule Imaging In Whole Cells Enabled By Lattice Light-Sheet Illumination T1 - 3D Einzelmolekülbildgebung in ganzen Zellen ermöglicht durch Gitterlichtblattbeleuchtung N2 - Single molecule localization microscopy has seen a remarkable growth since its first experimental implementations about a decade ago. Despite its technical challenges, it is already widely used in medicine and biology and is valued as a unique tool to gain molecular information with high specificity. However, common illumination techniques do not allow the use of single molecule sensitive super-resolution microscopy techniques such as direct stochastic optical reconstruction microscopy (dSTORM) for whole cell imaging. In addition, they can potentially alter the quantitative information. In this thesis, I combine dSTORM imaging in three dimensions with lattice lightsheet illumination to gain quantitative molecular information from cells unperturbed by the illumination and cover slip effects. Lattice light-sheet illumination uses optical lattices for beam shaping to restrict the illumination to the detectable volume. I describe the theoretical background needed for both techniques and detail the experimental realization of the system as well as the software that I developed to efficiently evaluate the data. Eventually, I will present key datasets that demonstrate the capabilities of the developed microscope system with and without dSTORM. My main goal here was to use these techniques for imaging the neural cell adhesion molecule (NCAM, also known as CD56) in whole cells. NCAM is a plasma membrane receptor known to play a key role in biological processes such as memory and learning. Combining dSTORM and lattice light-sheet illumination enables the collection of quantitative data of the distribution of molecules across the whole plasma membrane, and shows an accumulation of NCAM at cell-cell interfaces. The low phototoxicity of lattice light-sheet illumination further allows for tracking individual NCAM dimers in living cells, showing a significant dependence of its mobility on the actin skeleton of the cell. N2 - Die Einzelmoleküllokalisationsmikroskopie hat seit der ersten experimentellen Umsetzung vor etwa 10 Jahren einen bemerkenswerten Aufschwung erfahren. Trotz des hohen technischen Anspruchs findet sie bereits weite Verbreitung in der Biologie und Medizin und wird als einzigartiges Werkzeug geschätzt, um molekulare Information mit hoher Spezifität zu erlangen. Dennoch erschweren die gebräuchlichen Beleuchtungsmethoden die Anwendung von Methoden der Einzelmoleküllokalisationsmikroskopie wie dSTORM (engl. direct stochastic optical reconstruction microscopy) auf das Volumen ganzer Zellen, denn hier kann die Beleuchtung selbst die quantitativen Daten beeinflussen. In dieser Arbeit kombiniere ich dreidimensionale dSTORM-Bildgebung mit Gitterlichtblattbeleuchtung (engl. lattice light-sheet illumination) um quantitative, molekulare Information ohne durch die Beleuchtung verursachte Störungen zu gewinnen. Die Gitterlichtblattbeleuchtung nutzt optische Gitter zur Strahlformung, um das beleuchtete Volumen auf das detektierbare Volumen zu beschränken. Ich stelle den nötigen, theoretischen Hintergrund für beide Methoden dar und beschreibe die experimentelle Umsetzung sowie die von mir zur effizienten Datenauswertung entwickelte Software. Schließlich präsentiere ich verschiedene Datensätze, die die Fähigkeiten des Systems mit und ohne dSTORM demonstrieren. Mein Hauptziel war hierbei, beide Methoden zu nutzen, um das neuronale Zelladhäsionsmolekül (NCAM, engl. neural cell adhesion molecule) in ganzen Zellen abzubilden. NCAM (auch bekannt als CD56) ist ein Rezeptor auf der Plasmembran, der für seine Schlüsselrolle im Zusammenhang mit biologischen Prozessen wie Lernen und Gedächtnis bekannt ist. Die Kombination von dSTORM und Gitterlichtblattbeleuchtung ermöglicht das sammeln quantitativer Daten der Verteilung über die komplette Plasmamembran, wobei sich eine Akkumulation an Zell-Zell Kontaktflächen zeigt. Die niedrige Photoschädigung der Gitterlichtblattbeleuchtung ermöglicht weiterhin das Verfolgen von einzelnen NCAM-Dimeren in lebenden Zellen. Dort zeigt sich eine signifikante Abhängigkeit ihrer Mobilität vom Aktinskelett der Zelle. KW - Einzelmolekülmikroskopie KW - Optik KW - Light-Sheet KW - Lattice Light-Sheet KW - dSTORM KW - Single Molecule Imaging KW - Localization Microscopy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207111 ER - TY - JOUR A1 - Westermaier, Thomas A1 - Linsenmann, Thomas A1 - Homola, György A. A1 - Loehr, Mario A1 - Stetter, Christian A1 - Willner, Nadine A1 - Ernestus, Ralf-Ingo A1 - Soymosi, Laszlo A1 - Vince, Giles H. T1 - 3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms – assessment of feasibility and image quality JF - BMC Medical Imaging N2 - Background Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms. Materials and methods Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency. Results Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants. Conclusion This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality. KW - aneurysm surgery KW - clip control KW - angiography KW - 3D fluoroscopy KW - image quality KW - intraoperative KW - vessel patency KW - contrast KW - post-processing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146381 VL - 16 IS - 30 ER - TY - JOUR A1 - Gensler, Marius A1 - Leikeim, Anna A1 - Möllmann, Marc A1 - Komma, Miriam A1 - Heid, Susanne A1 - Müller, Claudia A1 - Boccaccini, Aldo R. A1 - Salehi, Sahar A1 - Groeber-Becker, Florian A1 - Hansmann, Jan T1 - 3D printing of bioreactors in tissue engineering: A generalised approach JF - PLoS One N2 - 3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process. KW - stem cells KW - technology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231368 VL - 15 IS - 11 ER - TY - INPR A1 - Schaefer, Natascha A1 - Janzen, Dieter A1 - Bakirci, Ezgi A1 - Hrynevich, Andrei A1 - Dalton, Paul D. A1 - Villmann, Carmen T1 - 3D Electrophysiological Measurements on Cells Embedded within Fiber-Reinforced Matrigel T2 - Advanced Healthcare Materials N2 - 2D electrophysiology is often used to determine the electrical properties of neurons, while in the brain, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, we established 3D electrophysiology within a fiber-reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, we performed 3D electrophysiology on a glycine receptor-transfected Ltk-11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behaviour. The average thickness of the MEW scaffold was 141.4 ± 5.7µm, using 9.7 ± 0.2µm diameter fibers, and square pore spacings of 100 µm, 200 µm and 400 µm. We demonstrate, for the first time, the electrophysiological characterization of glycine receptor-transfected cells with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiology measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions. KW - 3D cultures Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244194 ER - TY - JOUR A1 - Grunz, Jan-Peter A1 - Wenig, Andreas Max A1 - Kunz, Andreas Steven A1 - Veyhl-Wichmann, Maike A1 - Schmitt, Rainer A1 - Gietzen, Carsten Herbert A1 - Pennig, Lenhard A1 - Herz, Stefan A1 - Ergün, Süleyman A1 - Bley, Thorsten Alexander A1 - Gassenmaier, Tobias T1 - 3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT JF - European Radiology Experimental N2 - Background Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows. Methods A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDI\(_{vol(16 cm)}\)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDI\(_{vol(16 cm)}\) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used. Results The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100% of the cases by both readers for RD CBCT, 100% (R1) and 93.8% (R2) for LD CBCT, 62.6% and 43.8% for RD MDCT, and 0.0% and 0.0% for LD MDCT. Single-measure ICC was 0.95 (95% confidence interval 0.91–0.97; p < 0.001). Software-based assessment supported subjective findings with less “undecided” pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT. Conclusions In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction. KW - Cancellous bone KW - Cone-beam computed tomography KW - Elbow KW - Elbow joint KW - Multidetector computed tomography Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229877 VL - 4 ER - TY - JOUR A1 - Lanzendörfer, Franz A1 - Christl, Manfred T1 - 3,4-Bismethylentricyclo[3.1.0.02,6]hexan - Synthese und Diels-Alder-Addition an Tetracyanethylen N2 - No abstract available Y1 - 1983 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30263 ER - TY - JOUR A1 - Thurner, Annette A1 - Augustin, Anne Marie A1 - Bley, Thorsten Alexander A1 - Kickuth, Ralph T1 - 2D-perfusion angiography for intra-procedural endovascular treatment response assessment in chronic mesenteric ischemia: a feasibility study JF - BMC Medical Imaging N2 - Background Endovascular revascularization has become the first-line treatment of chronic mesenteric ischemia (CMI). The qualitative visual analysis of digital subtraction angiography (DSA) is dependent on observer experience and prone to interpretation errors. We evaluate the feasibility of 2D-Perfusion Angiography (2D-PA) for objective, quantitative treatment response assessment in CMI. Methods 49 revascularizations in 39 patients with imaging based evidence of mesenteric vascular occlusive disease and clinical signs of CMI were included in this retrospective study. To assess perfusion changes by 2D-PA, DSA-series were post-processed using a dedicated, commercially available software. Regions of interest (ROI) were placed in the pre- and post-stenotic artery segment. In aorto-ostial disease, the inflow ROI was positioned at the mesenteric artery orifice. The ratios outflow to inflow ROI for peak density (PD), time to peak and area-under-the-curve (AUC) were computed and compared pre- and post-interventionally. We graded motion artifacts by means of a four-point scale. Feasibility of 2D-PA and changes of flow parameters were evaluated. Results Motion artifacts due to a mobile vessel location beneath the diaphragm or within the mesenteric root, branch vessel superimposition and inadequate contrast enhancement at the inflow ROI during manually conducted DSA-series via selective catheters owing to steep vessel angulation, necessitated exclusion of 26 measurements from quantitative flow evaluation. The feasibility rate was 47%. In 23 technically feasible assessments, PD\(_{outflow}\)/PD\(_{inflow}\) increased by 65% (p < 0.001) and AUC\(_{outflow}\)/AUC\(_{inflow}\) increased by 85% (p < 0.001). The time to peak density values in the outflow ROI accelerated only minimally without reaching statistical significance. Age, BMI, target vessel (celiac trunk, SMA or IMA), stenosis location (ostial or truncal), calcification severity, plaque composition or the presence of a complex stenosis did not reach statistical significance in their distribution among the feasible and non-feasible group (p > 0.05). Conclusions Compared to other vascular territories and indications, the feasibility of 2D-PA in mesenteric revascularization for CMI was limited. Unfavorable anatomic conditions contributed to a high rate of inconclusive 2D-PA results. KW - 2D-perfusion angiography KW - chronic mesenteric ischemia KW - endovascular treatment KW - mesenteric stenting Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301131 VL - 22 ER - TY - JOUR A1 - Andelovic, Kristina A1 - Winter, Patrick A1 - Kampf, Thomas A1 - Xu, Anton A1 - Jakob, Peter Michael A1 - Herold, Volker A1 - Bauer, Wolfgang Rudolf A1 - Zernecke, Alma T1 - 2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis JF - Biomedicines N2 - Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe\(^{−/−}\), n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe\(^{−/−}\) mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability. KW - atherosclerosis KW - mouse KW - 4D flow MRI KW - aortic arch KW - flow dynamics KW - WSS KW - mapping KW - PWV KW - plaque characteristics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252164 SN - 2227-9059 VL - 9 IS - 12 ER - TY - JOUR A1 - Meyer, Malin Tordis A1 - Watermann, Christoph A1 - Dreyer, Thomas A1 - Ergün, Süleyman A1 - Karnati, Srikanth T1 - 2021 update on diagnostic markers and translocation in salivary gland tumors JF - International Journal of Molecular Sciences N2 - Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their low incidence rates and complex histological patterns, they are difficult to diagnose accurately. Malignant tumors of the salivary glands are challenging in terms of differentiation because of their variability in histochemistry and translocations. Therefore, the primary goal of the study was to review the current literature to identify the recent developments in histochemical diagnostics and translocations for differentiating salivary gland tumors. KW - salivary gland tumors KW - epithelial salivary gland KW - adenoid cystic carcinoma (ACC) KW - pleomorphic adenoma KW - mucoepidermoid carcinoma KW - diagnostic markers Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261057 SN - 1422-0067 VL - 22 IS - 13 ER - TY - JOUR A1 - Lohse, M. J. A1 - Klotz, Karl-Norbert A1 - Schwabe, U. A1 - Cristalli, G. A1 - Vittori, S. A1 - Grifantini, M. T1 - 2-Chloro-N\(^6\)-cyclopentyladenosine: a highly selective agonist at A\(_1\) adenosine receptors N2 - 2-Chloro-N\(^6\)-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for At adenosine receptors. Binding of [\(^3\)H]PIA to A1 receptors of rat brain membranes was inhibited by CCP A with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N\(^6\)-cyclopentyladenosine (CPA). Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A\(_1\)-selectivity of CCPA. CCP A inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A\(_1\) receptor, with an IC\(_{50}\)-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC\(_{50}\)-value of 3500 nM. The more than 100-fold A\(_1\)-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A\(_1\) adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard At receptor agonist R-N\(^6\) -phenylisopropyladenosine (R-PIA). CCP A represents the agonist with the highest selectivity for A\(_1\) receptors reported so far. KW - Toxikologie KW - Adenosine receptors KW - Adenylate cyclase Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60279 ER - TY - JOUR A1 - Klotz, Karl-Norbert A1 - Lohse, M. J. A1 - Schwabe, U. A1 - Cristalli, G. A1 - Vittori, S. A1 - Grifantini, M. T1 - 2-Chloro-N\(^6\)-[\(^3\)H]cyclopentyladenosine ([\(^3\)H]CCPA) - a high affinity agonist radioligand for A\(_1\) adenosine receptors N2 - The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCP A was prepared with a specifi.c radioactivity of 1.58 TBqjmmol ( 43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinity K0 -value of 0.2 nmol/1. In the presence of GTP a K0 -value of 13 nmol/1 was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgC12, as has been shown for the agonist [ 3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K0 -value of 0.4 nmol/1 and a Bmax-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmoljl, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [ 3H]CCPA proved to be a useful agonist radioligand for characterization of A 1 adenosine receptors also in tissues with very low receptor density. KW - Toxikologie KW - Adenosine receptors KW - Radioligauds KW - agonists Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60328 ER - TY - JOUR A1 - Cristalli, G. A1 - Eleuteri, A. A1 - Vittori, S. A1 - Volpini, R. A1 - Lohse, M. J. A1 - Klotz, Karl-Norbert T1 - 2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamides as selective agonists at A\(_2\) adenosine receptors N2 - In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A\(_2\) receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cycla.se, and platelet aggregation studies. Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited by compounds 2a-d with K\(_i\) values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affmity binding at solubilized A\(_2\) receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [\(^3\)H]DPCPX and for the agonist [\(^3\)H]CCPA gave K\(_i\) values in the nanomolar range, and the compounds showed moderate A\(_2\) selectivity. In order to improve this selectivity, the correaponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. A\(_1\) expected, the 5'-N-ethyluronamide derivatives retained the A\(_2\) affinity whereas the A\(_1\) affinity was attenuated, resulting in an up to 10-fold increase in A\(_2\) selectivity. A similar patternwas observed in adenylate cyclase assays andin platelet aggregation studies. A 30- to 45-fold selectivity for platelet A\(_2\) receptors compared to A\(_1\) receptors was found for compounds 8a-c in adenylate cyclase studies. KW - Toxikologie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60412 ER - TY - JOUR A1 - Kole, Goutam Kumar A1 - Merz, Julia A1 - Amar, Anissa A1 - Fontaine, Bruno A1 - Boucekkine, Abdou A1 - Nitsch, Jörn A1 - Lorenzen, Sabine A1 - Friedrich, Alexandra A1 - Krummenacher, Ivo A1 - Košćak, Marta A1 - Braunschweig, Holger A1 - Piantanida, Ivo A1 - Halet, Jean-François A1 - Müller-Buschbaum, Klaus A1 - Marder, Todd B. T1 - 2- and 2,7-substituted para-N-methylpyridinium pyrenes: syntheses, molecular and electronic structures, photophysical, electrochemical, and spectroelectrochemical properties and binding to double-stranded (ds) DNA JF - Chemistry - A European Journal N2 - Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm\(^{-1}\). The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc\(^+\) in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents. KW - inorganic chemistry KW - viologens KW - chromophores KW - luminescent KW - pyrenes KW - pyridinium Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256642 VL - 27 IS - 8 ER - TY - JOUR A1 - Gleiter, Rolf A1 - Bischof, Peter A1 - Gubernator, Klaus A1 - Christl, Manfred A1 - Schwager, Luis A1 - Vogel, Pierre T1 - 2,3-Bis(methylene)bicyclo[2.1.1]hexane and 3,4-Bis(methylene)tricyclo[3.1.0.0\(^{2,6}\)]hexane : Interaction between a π System and a Cyclobutane or Bicyclobutane Moiety N2 - The He (I) photoelectron spectra of 2-bicyclo[2.1.l]hexene (1), 2,3-bis(methylene)bicyclo[2.1.l]hexane (3), and 3,4-bis(methylene)tricyclo[3.l.O.0\(^{2.6}\)]hexane (4) have been investigated. The assignment given is based on a ZDO model and semiempirical calculations. Tagether with the PE data of benzvalene (2), the reported data allow a comparison between 1-2 and 3-4. This yields a measure of the interactions between 8 cyclobutane or 8 bicyclobutane moiety and a double bond system within a ZDO model. The resonance integral found in the case of 1 and 3 amounts to -1.9 eV, that for 2 and 4, to -2.3 eV. The investigations furthermore reveal that the electronic factors which contribute to the higher reactivity of the bicyclobutane compounds amount to 5 kcal/mol. KW - Chemie Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31845 ER - TY - JOUR A1 - Finze, Maik A1 - Reiss, Guido J. A1 - Frohn, Hermann-Josef T1 - 2,3,5,6-Tetrafluoro-1,4-bis(trimethylsilyl)benzene N2 - no abstract available KW - Chemie KW - single-crystal X-ray study KW - T = 199 K KW - R factor = 0.027 KW - wR factor = 0.068 KW - data-to-parameter ratio = 14.0. Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75401 ER - TY - JOUR A1 - Liu, Siyuan A1 - Légaré, Marc-André A1 - Seufert, Jens A1 - Prieschl, Dominic A1 - Rempel, Anna A1 - Englert, Lukas A1 - Dellermann, Theresa A1 - Paprocki, Valerie A1 - Stoy, Andreas A1 - Braunschweig, Holger T1 - 2,2′-Bipyridyl as a Redox-Active Borylene Abstraction Agent JF - Inorganic Chemistry N2 - 2,2′-Bipyridyl is shown to spontaneously abstract a borylene fragment (R–B:) from various hypovalent boron compounds. This process is a redox reaction in which the bipyridine is reduced and becomes a dianionic substituent bound to boron through its two nitrogen atoms. Various transition metal–borylene complexes and diboranes, as a well as a diborene, take part in this reaction. In the latter case, our results show an intriguing example of the homolytic cleavage of a B═B double bond. KW - Borylene KW - Heterocycles KW - Boron KW - Main-group chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215595 N1 - This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Inorganic Chemistry, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.inorgchem.0c01383. VL - 59 IS - 15 ER - TY - JOUR A1 - Lohse, M. J. A1 - Klotz, Karl-Norbert A1 - Diekmann, E. A1 - Friedrich, K. A1 - Schwabe, U. T1 - 2',3'-Dideoxy-N\(^6\)-cyclohexyladenosine: an adenosine derivative with antagonist properties at adenosine receptors N2 - Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. However, it antagonized the inhibition by R-PIA of adenylate cyclase activity of fat cell membranes via A\(_1\) receptors with a K\(_i\) value of 13 \(\mu\)M. ddCHA competed for the binding of the selective A1 receptor antagonist, [\(^3\) HJ8-cyclopentyl-1,3-dipropylxantbine ([\(^3\)H]DPCPX), to rat brain membranes with a K\(_i\) value of 4.8 \(\mu\)M; GTP did not affect the competition curve. In contrast to the marked stereoselectivity of the A\(_1\) receptor for the cx- and the natural ß-anomer of adenosine, the cx-anomer of ddCHA showed a comparable affinity for the A\(_1\) receptor (K\(_i\) value 13.9 \8\mu\)M). These data indicate that the 2'- and 3'-hydroxy groups of adenosine and its derivatives are required foragonist activity at and high affinity binding to A\(_1\) adenosine receptors and for the distinction between the cx- and ß-forms. KW - Toxikologie KW - Adenosine receptors KW - Adenylate cyclase KW - Adenosine receptor antagonists Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60282 ER - TY - THES A1 - Skiera, Christina T1 - 1H NMR spectroscopic determination of deterioration marker compounds in fats and oils T1 - 1H-NMR spektroskopische Bestimmung von Fettverderbsmarkern in Fetten und Ölen N2 - In food and pharmaceutical analysis, the classical indices peroxide value (PV), acid value (AV) and p-anisidine value (ANV) still play an important role as quality and authenticity control parameters of fats and oils. These indices are sum parameters for certain deterioration products (PV for hydroperoxides, AV for free fatty acids, ANV for aldehydes) and are obtained using volumetric or UV/VIS spectroscopic analytical approaches. 1H NMR spectroscopy provides a fast and simple alternative to these classical approaches. In the present work, novel 1H NMR methods to determine hydroperoxides, free fatty acids and aldehydes in fats and oils were developed. Hydroperoxides: The influence of solvent, water, free fatty acids and sample weight on the hydroperoxide group proton (OOH) signal was investigated. On the basis of the obtained results, the sample preparation procedure of the new 1H NMR method was established. A rough assignment of the hydroperoxide group signals in edible fats and oils to methyl oleate, methyl linoleate and methyl linolenate was conducted. Furthermore, to gain information on how many different hydroperoxide species originate from trioleate autoxidation, a kinetic study on trioleate monohydroperoxides was performed. The evaluation of the data strongly indicates that all of the conceivable 18 trioleate monohydroperoxides were formed during trioleate autoxidation. The analytical performance of the NMR method was compared to that of the classical PV approach by means of the so-called “relative sensitivity” according to Mandel. It was shown that both methods exhibit a similar analytical performance. A total of 444 edible oil samples were analysed using both methods. For some oil varieties considerable discrepancies were found between the results. In the case of black seed oil and olive oil two substances were identified that influence the classical PV determination and thus cause positive (black seed oil) and negative (olive oil) deviations from the theoretical PV expected from the NMR values. Free fatty acids: In order to find the optimal solvent mixture to measure the carboxyl group protons (COOH) of free fatty acids in fats and oils, the effect of solvent on the COOH signal was investigated for different mixtures of CDCl3 and DMSO-d6. The comparison of the NMR method with the classical AV method by means of the relative sensitivity revealed that both methods exhibit a similar analytical performance. 420 edible oil samples were analysed by both approaches. Except for pumpkin seed oil, where slight deviations were observed, there was a good compliance between the results obtained from the two methods. Furthermore, the applicability of the 1H NMR assay to further lipids with relevance in pharmacy was tested. For hard fat, castor oil, waxes and oleyl oleate modifications of the original sample preparation procedure of the NMR method were necessary to achieve comparable results for both methods. Aldehydes: The new 1H NMR method enables the determination of the molar amounts of n-alkanals, (E)-2-alkenals and (E,E)-2,4-alkadienals. It was illustrated that the ANV can be modelled as a linear combination of the NMR integrals of these aldehyde species. A functional relationship was derived on the basis In conclusion, the new 1H NMR methods provide an excellent alternative to of calibration experiments. The suitability of the model was shown by comparing the NMR-determined ANVs with the measured classical ANVs of 79 commercially available edible oils of different oil types. In conclusion, the new 1H NMR methods provide an excellent alternative to the determination of the classical indices PV, AV and ANV. They have several advantages over the classical methods including the consumption of small solvent amounts, the ability to automatize measurement and to acquire several different parameters out of the same NMR spectrum. Especially concerning their selectivity, the 1H NMR methods are highly superior to the classical methods. N2 - Im Bereich der Lebensmittel- und pharmazeutischen Analytik besitzen die klassischen Fettkennzahlen Peroxidzahl (POZ), Säurezahl (SZ) und p-Anisidinzahl (AnZ) bis heute eine große Bedeutung in der Qualitäts- und Authentizitätskontrolle von Fetten und Ölen. Diese Kennzahlen sind Summenparameter für bestimmte Verderbsprodukte (POZ für Hydroperoxide, SZ für freie Fettsäuren, AnZ für Aldehyde) und werden mittels volumetrischer oder UV/VIS-spektroskopischer Verfahren ermittelt. 1H-NMR Spektroskopie bietet eine einfache und schnelle Alternative zu den klassischen Fettkennzahlen. In der vorliegenden Arbeit wurden neue 1H-NMR Methoden zur Bestimmung von Hydroperoxiden, freien Fettsäuren und Aldehyden in Fetten und Ölen entwickelt. Hydroperoxide: Der Einfluss des Lösungsmittels, von Wasser, freien Fettsäuren und der Probeneinwaage auf das Hydroperoxidgruppensignal wurde untersucht. Anhand der Ergebnisse wurde die Probenaufarbeitungsprozedur für die neue 1H-NMR Methode erarbeitet. Es wurde eine grobe Zuordnung der Hydroperoxidgruppensignale in Fetten und Ölen zu Methyloleat, Methyllinoleat und Methylinolenat vorgenommen. Weiterhin wurde eine kinetische Studie für Trioleat-Monohydroperoxide durchgeführt, um Informationen darüber zu erhalten, wieviel verschiedene Hydroperoxidspezies bei der Autoxidation von Trioleat gebildet werden. Das Ergebnis weist stark darauf hin, dass alle 18 möglichen Monohydroperoxide entstehen. Die analytische Leistungsfähigkeit der NMR-Methode und der klassischen POZ-Methode wurde mit Hilfe der sog. „relative sensitivity“ nach Mandel verglichen. Es wurde gezeigt, dass beide Methoden eine vergleichbare analytische Leistungsfähigkeit besitzen. Insgesamt wurden 444 Speiseölproben mit beiden Methoden untersucht. Für einige Ölarten wurden beträchtliche Diskrepanzen zwischen der POZ und den NMR-Ergebnissen beobachtet. Im Fall von Schwarzkümmelöl und Olivenöl wurden zwei Substanzen identifiziert, die bei der klassischen POZ-Bestimmung miterfasst werden und dadurch für die positiven (Schwarzkümmelöl) und negativen (Olivenöl) Abweichungen von den aufgrund der NMR-Ergebnisse theoretisch zu erwartenden POZ-Werten verantwortlich sind. Freie Fettsäuren: Zur Optimierung der Messbedingungen wurde der Einfluss des Lösungsmittels auf das Carboxylgruppensignal von freien Fettsäuren für verschiedene Mischungen von CDCl3 und DMSO-d6 untersucht. Die NMR-Methode wurde mit der klassischen SZ-Methode mit Hilfe der „relative sensitivity“ verglichen. Dabei wurde eine vergleichbare analytische Leistungsfähigkeit für beide Methoden festgestellt. 420 Speiseöle wurden mit beiden Methoden analysiert. Mit Ausnahme der Analysenergebnisse von Kürbiskernölen, die geringe Abweichungen zeigten, wurde eine gute Übereinstimmung der Ergebnisse beider Methoden beobachtet. Weiterhin wurde die Anwendbarkeit der 1H-NMR-Methode für weitere Lipide mit Bedeutung in der Pharmazie getestet. Durch Modifikation der ursprünglichen Analysenvorschrift der NMR-Methode wurden für Hartfett, Rizinusöl, Wachse und Oleyloleat mit beiden Methoden vergleichbare Ergebnisse erhalten. Aldehyde: Mit der neuen 1H-NMR Methode können die molaren Gehalte von n-Alkanalen, (E)-2-Alkenalen und (E,E)-2,4-Alkadienalen bestimmt werden. Die vorliegende Arbeit zeigt, dass die AnZ als eine Linearkombination der normalisierten NMR-Integrale der Aldehyde modelliert werden kann. Ein funktionaler Zusammenhang wurde auf Grundlage von Kalibrationsexperimenten abgeleitet. Die Eignung des Modells wurde durch den Vergleich der mittels NMR bestimmten AnZ mit der klassischen AnZ von 79 kommerziell erhältlichen Speiseölen verschiedener Ölarten gezeigt. Abschließend lässt sich sagen, dass die neuen 1H-NMR-Methoden eine sehr gute Alternative zu der Bestimmung der klassischen Fettkennzahlen POZ, SZ and AnZ darstellen. Sie besitzen mehrer Vorteile gegenüber den klassischen Methoden wie beispielsweise der geringe Lösungsmittelverbrauch, die Automatisierbarkeit der Messung und die Möglichkeit mehrere unterschiedliche Parameter aus demselben NMR-Spektrum bestimmen zu können. Es hat sich gezeigt, dass die 1H-NMR-Methoden den klassischen Methoden insbesondere hinsichtlich ihrer Selektivität weit überlegen sind und damit fehlerhafte Befunde, wie sie z. B. bei der POZ-Bestimmung auftreten können, vermieden werden. KW - Fett KW - Öl KW - Verderb KW - NMR-Spektroskopie KW - Fettkennzahlen KW - lipid deterioration markers KW - hydroperoxides KW - free fatty acids KW - aldehydes KW - lipid deterioration KW - Protonen-NMR-Spektroskopie KW - Lipide KW - Hydroperoxide KW - Aldehyde Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95756 ER - TY - JOUR A1 - Wondergem, Marielle J. A1 - Herrmann, Ken A1 - Syrbu, Sergei A1 - Zijlstra, Josée M. A1 - Hoetjes, Nikie A1 - Hoekstra, Otto S. A1 - Cillessen, Saskia A. G. M. A1 - Moesbergen, Laura M. A1 - Buck, Andreas K. A1 - Vose, Julie M. A1 - Juweid, Malik E. T1 - 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair JF - EJNMMI Research N2 - BACKGROUND: We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL). METHODS: We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed. RESULTS: 18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively. CONCLUSIONS: This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma. KW - 18-F-fluorothymidine uptake KW - positron emission tomography KW - follicular lymphoma KW - non-Hodgkin's lymphoma KW - DNA repair Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121233 VL - 4 ER -