@article{AppelScholzKocabeyetal.2016, author = {Appel, Mirjam and Scholz, Claus-J{\"u}rgen and Kocabey, Samet and Savage, Sinead and K{\"o}nig, Christian and Yarali, Ayse}, title = {Independent natural genetic variation of punishment- versus relief-memory}, series = {Biology Letters}, volume = {12}, journal = {Biology Letters}, number = {12}, doi = {10.1098/rsbl.2016.0657}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186554}, pages = {20160657}, year = {2016}, abstract = {A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment-versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly, Drosophila melanogaster as a study case, we found that both punishment-and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications.}, language = {en} } @article{BahnikStuchlik2015, author = {Bahn{\´i}k, Štěp{\´a}n and Stuchl{\´i}k, Aleš}, title = {Temporal and spatial strategies in an active place avoidance task on Carousel: a study of effects of stability of arena rotation speed in rats}, series = {PeerJ}, volume = {3}, journal = {PeerJ}, number = {e1257}, doi = {10.7717/peerj.1257}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141931}, year = {2015}, abstract = {The active place avoidance task is a dry-arena task used to assess spatial navigation and memory in rodents. In this task, a subject is put on a rotating circular arena and avoids an invisible sector that is stable in relation to the room. Rotation of the arena means that the subject's avoidancemust be active, otherwise the subject will be moved in the to-be-avoided sector by the rotation of the arena and a slight electric shock will be administered. The present experiment explored the effect of variable arena rotation speed on the ability to avoid the to-be-avoided sector. Subjects in a group with variable arena rotation speed learned to avoid the sector with the same speed and attained the same avoidance ability as rats in a group with a stable arena rotation speed. Only a slight difference in preferred position within the room was found between the two groups. No difference was found between the two groups in the dark phase, where subjects could not use orientation cues in the room. Only one rat was able to learn the avoidance of the to-be-avoided sector in this phase. The results of the experiment suggest that idiothetic orientation and interval timing are not crucial for learning avoidance of the to-be-avoided sector. However, idiothetic orientation might be sufficient for avoiding the sector in the dark.}, language = {en} } @phdthesis{Bathe2006, author = {Bathe, Katharina}, title = {Einfluss des Hepatozytenwachstumsfaktors(HGF) auf das linksventrikul{\"a}re Remodeling: Charakterisierung von Geometrie, Mechanik und Narbenentwicklung mittels NMR-Technik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28177}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2006}, abstract = {Diese Dissertation beschreibt den Einfluss von HGF auf das ventrikul{\"a}re Remodeling des Rattenherzens in der 1. und 16. Woche nach Isch{\"a}mie und Reperfusion. Die funktionalen Parameter wurden mit Hilfe des NMR gemessen. In der 16. Woche nach Isch{\"a}mie und Reperfusion wurde die histologisch ermittelte Narbengr{\"o}ße mit dem Wert, der mittels NMR ermittelt wurde, verglichen.}, subject = {Hepatozyten-Wachstumsfaktor}, language = {de} } @phdthesis{Bertelsmann2022, author = {Bertelsmann, Dietmar}, title = {Analysis of the Frequency of Kidney Toxicity in Preclinical Safety Studies using the eTOX Database}, doi = {10.25972/OPUS-25710}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257104}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {This research aimed to obtain reliable data on the frequency of different types of renal toxicity findings in 28-day oral gavage studies in Wistar rats, their consistency across species and study duration, as well as the correlation between histopathological endpoints and routinely used clinical chemistry parameters indicative of kidney injury. Analysis of renal histopathological findings was carried out through extraction of information from the IMI eTOX database. Spontaneous renal histopathological findings in 28-day oral gavage studies in control Wistar rats and beagle dogs confirmed tubular basophilia and renal dilation as the most frequent incidental findings in controls, whereas necrosis and glomerulosclerosis were not identified at all or only rarely as a background lesion. Histopathological evidence of necrosis and glomerulosclerosis was associated with changes in clinical chemistry parameters in 28-day oral gavage Wistar rat studies. Necrosis was frequently accompanied by a statistically significant rise in serum creatinine and serum urea, whereas serum albumin was frequently found to decrease statistically significantly in treatment groups in which necrosis was recorded. In contrast to necrosis, glomerulosclerosis was not associated with statistically significant changes in serum creatinine and urea in any of the 28-day oral gavage Wistar rat treatment groups, but appears to be best reflected by a pattern of statistically significantly lowered serum albumin and serum protein together with a statistically significant increase in serum cholesterol. As might have been expected based on the high background incidences of tubular basophilia and dilation, no consistent changes in any of the clinical chemistry parameters were evident in animals in which renal lesions were con� fined to renal tubular basophilia or dilation. In summary, the routinely provided clinical chemistry parameters are rather insensitive - novel kidney biomarkers such as Cystatin C, β-trace protein and Kidney injury molecule 1 should further be evaluated and integrated into routine preclinical and clinical practice. However, evaluation of clinical chemistry data was limited by the lack of individual animal data. Even though an extensive amount of preclinical studies is accessible through the eTOX database, comparison of consistency across time was limited by the limited number of shorter- and longer term studies conducted with the compounds identified as causing renal histopathological changes within a 28- day study in rats. A high consistency across time for both treatment-related tubular basophilia and treatment-related dilation cannot be confirmed for either of the two effects as these two findings were both induced only rarely in studies over a different treatment-duration other than 28 days after administration of the compounds which provoked the respective effect in a 28-day study. For the finding of necrosis consistency across time was low with the exception of "AZ_GGA_200002321", in which renal papillary necrosis was identified consist� ently throughout different treatment durations (2, 4, 26, 104 weeks). No shorter and longer-term studies were available for the compounds identified as causing glomerulosclerosis within a 28-day study in rats. No consistent findings of the selected histopathological endpoints were identified in any of the corresponding 28-day oral gavage beagle dog studies after treatment with the identical compounds, which caused the respective ef� fect after 28-day treatment in rats. However, in the overwhelming majority of cases, beagle dogs were administered lower doses in these studies in compar� ison to the corresponding 28-day Wistar rat studies. Searching the eTOX database yielded no 28-day oral gavage studies in Wistar and Wistar Han rats in which accumulation of hyaline droplets, tubular atrophy or hyperplasia was recorded. Only one 28-day oral gavage Wistar rat study was identified with the histopathological result of neutrophilic inflammation. Consequently, evaluation of these four renal findings in relation to clinical chemistry parameters and consistency across time and species cannot be made. In summary, this work contributes knowledge through mining and evaluating the eTOX database on a variety of specific renal endpoints that frequently occur after administration of trial substances in 28-day oral gavage studies in Wistar rats in the field of preclinical toxicity with specific focus on their frequency relation to background findings, as well as consistency across time and species. Targeted statistical evaluation of in vivo data within joint research ventures such as the eTOX project, presents an enormous opportunity for an innovative future way of aiding preclinical research towards a more efficient research in the preclinical stage of drug development. This could be achieved through the aug� mentation of methodological strategies and possibly novel software tools in order to predict in vivo toxicology of new molecular entities by means of information that is already available before early stages of the drug development pipeline begin.}, language = {en} } @phdthesis{Boenhof2011, author = {B{\"o}nhof, Leoni Jacobea}, title = {Herzinfarkt-scheinoperierte Ratten vs. gesunde Ratten: Ein Vergleich in der Cine-Herzmagnetresonanztomografie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71520}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {In der vorliegenden Arbeit wurde {\"u}berpr{\"u}ft, ob sich sham-operierte Versuchsratten und gesunde Vergleichsratten in via Cine-Herz-MRT zu erfassenden Parametern signifkant unterscheiden. Hierzu wurden an einem Bruker 7 Tesla-Magnetresonanztomografen drei verschiedene Tiergruppen {\`a} 6 Tiere untersucht. Der erste Vergleich fand statt zwischen der gesunden Vergleichsgruppe und einer {\"a}hnlich schweren Shamtiergruppe, die sich in der 8. postoperativen Woche befand. Nachdem hier keinerlei signifikante Unterschiede zwischen den beiden Gruppen festzustellen waren, wurde der Vergleich ausgeweitet: Die Shamgruppe wurde zu einem fr{\"u}hen postoperativen Zeitpunkt (7-14 Tage postoperativ) ein zweites Mal mit der gesunden Gruppe verglichen.}, subject = {Herz}, language = {de} } @article{FrerichsSirenFeuersteinetal.1992, author = {Frerichs, K. and Sir{\`e}n, Anna-Leena and Feuerstein, G. and Hallenbeck, JM}, title = {The onset of postischemic hypoperfusion in rats is precipitous and may be controlled by local neurons}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47980}, year = {1992}, abstract = {Background and Purpose: Reperfusion following transient global cerebral ischemia is characterized by an initial hyperemic phase, which precedes hypo perfusion. The pathogenesis of these flow derangements remains obscure. Our study investigates the dynamics of postischemic cerebral blood flow changes, with particular attention to the role of local neurons. Metho(Js: We assessed local cortical blood flow continuously by laser Doppler flowmetry to permit observation of any rapid flow changes after forebrain ischemia induced by four-vessel occlusion for 20 minutes in rats. To investigate the role of local cortical neurons in the regulation of any blood flow fluctuations, five rats received intracortical microinjections of a neurotoxin (10 p,g ibotenic acid in 1 p,1; 1.5-mm-depth parietal cortex) 24 hours before ischemia to induce selective and localized neuronal depletion in an area corresponding to the sampie volume of the laser Doppler probe (1 mm3 ). Local cerebral blood flow was measured within the injection site and at an adjacent control site. Results: Ischemia was followed by marked hyperemia (235 ±23\% of control, n =7), followed by secondary hypoperfusion (45±3\% of control, n=7). The transition from hyperemia to hypoperfusioo occurred not gradually but precipitously (maximal slope of flow decay: 66±6\%/min; n=7). In ibotenic acid-injected rats, hyperemia was preserved at the injection site, but the sudden decline of blood flow was abolished (maximal slope of flow decay: 5±3\%/min compared with 53±8\%/min at the control site; n=5, p