@article{MaerzKurlbaumRocheLancasteretal.2021, author = {M{\"a}rz, Juliane and Kurlbaum, Max and Roche-Lancaster, Oisin and Deutschbein, Timo and Peitzsch, Mirko and Prehn, Cornelia and Weismann, Dirk and Robledo, Mercedes and Adamski, Jerzy and Fassnacht, Martin and Kunz, Meik and Kroiss, Matthias}, title = {Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors}, series = {Frontiers in Endocrinology}, volume = {12}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2021.722656}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245710}, year = {2021}, abstract = {Context Pheochromocytomas and paragangliomas (PPGL) cause catecholamine excess leading to a characteristic clinical phenotype. Intra-individual changes at metabolome level have been described after surgical PPGL removal. The value of metabolomics for the diagnosis of PPGL has not been studied yet. Objective Evaluation of quantitative metabolomics as a diagnostic tool for PPGL. Design Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens and statistical modeling using ML-based feature selection approaches in a clinically well characterized cohort study. Patients Prospectively enrolled patients (n=36, 17 female) from the Prospective Monoamine-producing Tumor Study (PMT) with hormonally active PPGL and 36 matched controls in whom PPGL was rigorously excluded. Results Among 188 measured metabolites, only without considering false discovery rate, 4 exhibited statistically significant differences between patients with PPGL and controls (histidine p=0.004, threonine p=0.008, lyso PC a C28:0 p=0.044, sum of hexoses p=0.018). Weak, but significant correlations for histidine, threonine and lyso PC a C28:0 with total urine catecholamine levels were identified. Only the sum of hexoses (reflecting glucose) showed significant correlations with plasma metanephrines. By using ML-based feature selection approaches, we identified diagnostic signatures which all exhibited low accuracy and sensitivity. The best predictive value (sensitivity 87.5\%, accuracy 67.3\%) was obtained by using Gradient Boosting Machine Modelling. Conclusions The diabetogenic effect of catecholamine excess dominates the plasma metabolome in PPGL patients. While curative surgery for PPGL led to normalization of catecholamine-induced alterations of metabolomics in individual patients, plasma metabolomics are not useful for diagnostic purposes, most likely due to inter-individual variability.}, language = {en} } @article{BeyhoffLohrThieleetal.2020, author = {Beyhoff, Niklas and Lohr, David and Thiele, Arne and Foryst-Ludwig, Anna and Klopfleisch, Robert and Schreiber, Laura M. and Kintscher, Ulrich}, title = {Myocardial Infarction After High-Dose Catecholamine Application—A Case Report From an Experimental Imaging Study}, series = {Frontiers in Cardiovascular Medicine}, volume = {7}, journal = {Frontiers in Cardiovascular Medicine}, doi = {10.3389/fcvm.2020.580296}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217959}, year = {2020}, abstract = {Although heart failure following myocardial infarction (MI) represents a major health burden, underlying microstructural and functional changes remain incompletely understood. Here, we report on a case of unexpected MI after treatment with the catecholamine isoproterenol in an experimental imaging study in mice using different state-of-the-art imaging modalities. The decline in cardiac function was documented by ultrahigh-frequency echocardiography and speckle-tracking analyses. Myocardial microstructure was studied ex vivo at a spatial resolution of 100 × 100 × 100 μm\(^{3}\) using diffusion tensor magnetic resonance imaging (DT-MRI) and histopathologic analyses. Two weeks after ISO treatment, the animal showed an apical aneurysm accompanied by reduced radial strain in corresponding segments and impaired global systolic function. DT-MRI revealed a loss of contractile fiber tracts together with a disarray of remaining fibers as corresponding microstructural correlates. This preclinical case report provides valuable insights into pathophysiology and morphologic-functional relations of heart failure following MI using emerging imaging technologies.}, language = {en} } @article{FauserWeselekHauptmannetal.2020, author = {Fauser, Mareike and Weselek, Grit and Hauptmann, Christine and Markert, Franz and Gerlach, Manfred and Hermann, Andreas and Storch, Alexander}, title = {Catecholaminergic Innervation of Periventricular Neurogenic Regions of the Developing Mouse Brain}, series = {Frontiers in Neuroanatomy}, volume = {14}, journal = {Frontiers in Neuroanatomy}, doi = {10.3389/fnana.2020.558435}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212485}, year = {2020}, abstract = {The major catecholamines—dopamine (DA) and norepinephrine (NE)—are not only involved in synaptic communication but also act as important trophic factors and might ultimately be involved in mammalian brain development. The catecholaminergic innervation of neurogenic regions of the developing brain and its putative relationship to neurogenesis is thus of pivotal interest. We here determined DA and NE innervation around the ventricular/subventricular zone (VZ/SVZ) bordering the whole ventricular system of the developing mouse brain from embryonic day 14.5 (E14.5), E16.5, and E19.5 until postnatal day zero (P0) by histological evaluation and HPLC with electrochemical detection. We correlated these data with the proliferation capacity of the respective regions by quantification of MCM\(^{2+}\) cells. During development, VZ/SVZ catecholamine levels dramatically increased between E16.5 and P0 with DA levels increasing in forebrain VZ/SVZ bordering the lateral ventricles and NE levels raising in midbrain/hindbrain VZ/SVZ bordering the third ventricle, the aqueduct, and the fourth ventricle. Conversely, proliferating MCM\(^{2+}\) cell counts dropped between E16.5 and E19.5 with a special focus on all VZ/SVZs outside the lateral ventricles. We detected an inverse strong negative correlation of the proliferation capacity in the periventricular neurogenic regions (log-transformed MCM\(^{2+}\) cell counts) with their NE levels (r = -0.932; p < 0.001), but not their DA levels (r = 0.440; p = 0.051) suggesting putative inhibitory effects of NE on cell proliferation within the periventricular regions during mouse brain development. Our data provide the first framework for further demandable studies on the functional importance of catecholamines, particularly NE, in regulating neural stem/progenitor cell proliferation and differentiation during mammalian brain development.}, language = {en} } @phdthesis{Schwaerzel2003, author = {Schw{\"a}rzel, Martin}, title = {Localizing engrams of olfactory memories in Drosophila}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5065}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {Zars and co-workers were able to localize an engram of aversive olfactory memory to the mushroom bodies of Drosophila (Zars et al., 2000). In this thesis, I followed up on this finding in two ways. Inspired by Zars et al. (2000), I first focused on the whether it would also be possible to localize memory extinction.While memory extinction is well established behaviorally, little is known about the underlying circuitry and molecular mechanisms. In extension to the findings by Zars et al (2000), I show that aversive olfactory memories remain localized to a subset of mushroom body Kenyon cells for up to 3 hours. Extinction localizes to the same set of Kenyon cells. This common localization suggests a model in which unreinforced presentations of a previously learned odorant intracellularly antagonizes the signaling cascades underlying memory formation. The second part also targets memory localization, but addresses appetitive memory. I show that memories for the same olfactory cue can be established through either sugar or electric shock reinforcement. Importantly, these memories localize to the same set of neurons within the mushroom body. Thus, the question becomes apparent how the same signal can be associated with different events. It is shown that two different monoamines are specificaly necessary for formation of either of these memories, dopamine in case of electric shock and octopamine in case of sugar memory, respectively. Taking the representation of the olfactory cue within the mushroom bodies into account, the data suggest that the two memory traces are located in the same Kenyon cells, but in separate subcellular domains, one modulated by dopamine, the other by octopamine. Taken together, this study takes two further steps in the search for the engram. (1) The result that in Drosophila olfactory learning several memories are organized within the same set of Kenyon cells is in contrast to the pessimism expressed by Lashley that is might not be possible to localize an engram. (2) Beyond localization, a possibible mechanism how several engrams about the same stimulus can be localized within the same neurons might be suggested by the models of subcellular organisation, as postulated in case of appetitive and aversive memory on the one hand and acquisition and extinction of aversive memory on the other hand.}, subject = {Taufliege}, language = {en} } @phdthesis{Buchberger2001, author = {Buchberger, Christoph}, title = {Einfluss von Stress am Computerarbeitsplatz auf den Gasaustausch sowie Kreislaufparameter}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1180056}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2001}, abstract = {Studienobjekte: Um angemessene Reaktionen auf die gebotene Stresssituation zu bekommen wurden 29 Probanden, davon 14 M{\"a}nner und 15 Frauen verglichen. Dabei wurde auf einen breiten Querschnitt der beruflichen T{\"a}tigkeit geachtet. Versuchsaufbau: Die Probanden wurden anhand von Rechenaufgaben an einem Computer in Stress gesetzt, die dadurch auftretenden Reaktionen der Atmung wurden mittels Spirometrie aufgezeichnet. Gleichzeitig wurden durchgehend der Blutdruck und die Herzfrequenz bestimmt, zudem in regelm{\"a}ßigen Abst{\"a}nden die Blutgase sowie Urin-Katecholamine abgenommen. Versuchsort: Universit{\"a}t W{\"u}rzburg, Abteilung f{\"u}r Betriebsmedizin Versuchspersonen: 15 Frauen im Alter von 17-31 sowie 15 M{\"a}nner von 19-33 Jahren nahmen an den Versuchen teil. Ergebnisse: Bezugnehmend auf die Urin-Katecholamine zeigte sich ein Anstieg w{\"a}hrend der Stressphase, sowohl bei Frauen, als auch bei M{\"a}nnern. RQ, VO2, VCO2, Vt sowie VE ergaben allesamt einen Anstieg w{\"a}hrend der Stressphase bei beiden Geschlechtern. Die Atemfrequenz fiel stressinduziert ab. Der Blutdruck stieg erwartungsgem{\"a}ß, sowohl systolisch als auch diastolisch an. Der periphere Widerstand verzeichnete seinen h{\"o}chsten Wert direkt im Anschluss an das Testende. Zusammenfassung: W{\"a}hrend Stressbelastung kam es wohl als Ausdruck einer vermehrten Glucoseutilisation zu einem RQ Anstieg, gleichzeitig im Rahmen der Kompensationsmechanismen zu einem Abfall der Atemfrequenz bei gleichzeitigem Anstieg des Atemzugvolumens. Trotz Anstiegs der Blutdruckwerte bei gleichzeitig erh{\"o}hten Katecholaminen kam es zu einem Abfall des peripheren Widerstandes, was als Zentralisationsmechanismus zu deuten ist. Im Anschluss an die Stressbelastung erreichte dieser seinen h{\"o}chsten Wert, somit ist von einer vermehrten Gef{\"a}hrdung eines gef{\"a}ßstenosierenden Prozesses akut nach Beendigung einer psychischen Belastungssituation auszugehen.}, language = {de} } @phdthesis{Brede2001, author = {Brede, Marc}, title = {Kardiovaskul{\"a}re Ph{\"a}notypisierung von Angiotensin II AT2-Rezeptor- und adrenergen Rezeptor-"Knockout"-M{\"a}usen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1179726}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2001}, abstract = {Die Deletion des AT2-Rezeptors (AT2-KO) f{\"u}hrt zu erh{\"o}hter Blutdruckempfindlichkeit und vaskul{\"a}rer Hypertrophie durch Aktivit{\"a}tszunahhme der P70S6-Kinase. Die Vasodilatation von Blutgef{\"a}ßen wird maßgeblich durch beta1-adrenerge Rezeptoren vermittelt. Die Deletion von alpha2-adrenergen Rezeptoren (alpha2-KO) f{\"u}hrt zur Entwicklung einer Herzinsuffizienz nach Aortenstenose. Der Mortalit{\"a}tanstieg ist mit erh{\"o}hten Plasmanoradrenalin-Spiegeln (a2A-KO), bzw. Plasmaadrenalin-Spiegeln (a2C-KO) assoziiert.}, language = {de} }