Em ultimas décadas, a conversão de alcanos leves em suas correspondentes olefinas tem sido objeto de intensas pesquisas, impulsionadas inclusive pelo aumento crescente da demanda do propileno como um importante produto petroquímico. A desidrogenação oxidativa (ODH) do propano representa uma via alternativa promissor para a produção de propeno, ao apresentar-se como uma reação exotérmica e não limitada termodinamicamente. Diferentes óxidos suportados ou mistos têm sido desenvolvidos com a finalidade de aumentar a atividade e seletividade em relação as olefinas. Metais alcalinos são importantes agentes promotores que proporcionam uma melhor seletividade as olefinas devido a redução da acidez e aumento da basicidade da superfície do catalisador. A proposta deste presente trabalho foi desenvolver metodologias de síntese de catalisadores de oxido de vanádio suportado em aluminas de diferentes fases cristalinas e dopados com sódio ou potássio a fim de avalia-los em testes catalíticos de desidrogenação oxidativa do propano. Para tanto, foram utilizadas as seguintes técnicas de caracterização: volumetria N2, difratometria de raios X (DRX) e redução a temperatura programada (RTP). As características acidas e/ou básicas dos suportes e catalisadores foram avaliadas pelas reações de decomposição de isopropanol. / In recent decades, the conversion of light alkanes to their corresponding olefins has been the subject of intense research, mainly driven by the increasing demand of propylene as an important petrochemical product. Oxidative dehydrogenation (ODH) propane is a promising alternative way to propylene production, which it is presented as an exothermic reaction and not limited thermodynamically. Different supported or mixed oxides have been developed in order to increase the activity and selectivity to olefins. Alkali metals are important promoters, which provide improved selectivity to olefins due to reduction of acidity and increasing basicity of the catalyst surface. The purpose of the present study was to develop synthesis methods of vanadium oxide catalysts supported on alumina of the different crystalline phases and doped with sodium or potassium in order to evaluate them in catalytic tests of propane oxidative dehydrogenation. For in such a way, the following characterization techniques were used: N2 volumetry, X-ray diffractometry (XRD) and temperature programmed reduction (TPR). The properties acid and/or basic of supports and catalysts were evaluated by the isopropanol decomposition reaction.

No description available.

No description available.

Les résultats présentés dans cette thèse précisent certains aspects de la fonction du cotransporteur Na+/glucose (SGLT1), une protéine transmembranaire qui utilise le gradient électrochimique favorable des ions Na+ afin d’accumuler le glucose à l’intérieur des cellules épithéliales de l’intestin grêle et du rein. Nous avons tout d’abord utilisé l’électrophysiologie à deux microélectrodes sur des ovocytes de xénope afin d’identifier les ions qui constituaient le courant de fuite de SGLT1, un courant mesuré en absence de glucose qui est découplé de la stoechiométrie stricte de 2 Na+/1 glucose caractérisant le cotransport. Nos résultats ont démontré que des cations comme le Li+, le K+ et le Cs+, qui n’interagissent que faiblement avec les sites de liaison de SGLT1 et ne permettent pas les conformations engendrées par la liaison du Na+, pouvaient néanmoins générer un courant de fuite d’amplitude comparable à celui mesuré en présence de Na+. Ceci suggère que le courant de fuite traverse SGLT1 en utilisant une voie de perméation différente de celle définie par les changements de conformation propres au cotransport Na+/glucose, possiblement similaire à celle empruntée par la perméabilité à l’eau passive. Dans un deuxième temps, nous avons cherché à estimer la vitesse des cycles de cotransport de SGLT1 à l’aide de la technique de la trappe ionique, selon laquelle le large bout d’une électrode sélective (~100 μm) est pressé contre la membrane plasmique d’un ovocyte et circonscrit ainsi un petit volume de solution extracellulaire que l’on nomme la trappe. Les variations de concentration ionique se produisant dans la trappe en conséquence de l’activité de SGLT1 nous ont permis de déduire que le cotransport Na+/glucose s’effectuait à un rythme d’environ 13 s-1 lorsque le potentiel membranaire était fixé à -155 mV. Suite à cela, nous nous sommes intéressés au développement d’un modèle cinétique de SGLT1. En se servant de l’algorithme du recuit simulé, nous avons construit un schéma cinétique à 7 états reproduisant de façon précise les courants du cotransporteur en fonction du Na+ et du glucose extracellulaire. Notre modèle prédit qu’en présence d’une concentration saturante de glucose, la réorientation dans la membrane de SGLT1 suivant le relâchement intracellulaire de ses substrats est l’étape qui limite la vitesse de cotransport. / The results presented in this thesis clarify certain functional aspects of the Na+/glucose cotransporter (SGLT1), a membrane protein which uses the downhill electrochemical gradient of Na+ ions to drive the accumulation of glucose in epithelial cells of the small intestine and the kidney. We first used two microelectrodes electrophysiology on Xenopus oocytes to indentify the ionic species mediating the leak current of SGLT1, a current measured in the absence of glucose that is uncoupled from the strict 2 Na+/1 glucose stoichiometry characterising cotransport. Our results showed that cations such as Li+, K+ and Cs+, which interact weakly with SGLT1 binding sites and are unable to generate the conformational changes that are triggered by Na+ binding, were however able to generate leak currents similar in amplitude to the one measured in the presence of Na+. This suggests that the leak current permeating through SGLT1 does so using a pathway that differs from the conformational changes associated with Na+/glucose cotransport. Moreover, it was found that the cationic leak and the passive water permeability could share a common pathway. We then sought to estimate the turnover rate of SGLT1 using the ion-trap technique, where a large tip ion-selective electrode (~100 μm) is pushed against the oocyte plasma membrane, thus enclosing a small volume of extracellular solution referred to as the trap. The variations in ionic concentration occurring in the trap as a consequence of SGLT1 activity made it possible to assess that the turnover rate of Na+/glucose cotransport was 13 s-1 when the membrane potential was clamped to -155 mV. As a last project, we focused our interest on the development of a kinetic model for SGLT1. Taking advantage of the simulated annealing algorithm, we constructed a 7-state kinetic scheme whose predictions accurately reproduced the currents of the cotransporter as a function of extracellular Na+ and glucose. According to our model, the rate limiting step of cotransport under a saturating glucose concentration is the reorientation of the empty carrier that follows the intracellular release of substrates.

Racional: A epilepsia do lobo temporal está comumente associada à farmacorresistência e tem a esclerose hipocampal como achado neuropatológico em mais da metade dos casos. Histologicamente, a esclerose hipocampal está associada à perda neuronal diferencial e gliose, além de alterações nos níveis de moléculas associadas à homeostase da água tecidual, como a aquaporina 4 e a molécula de matriz sulfato de condroitina. Em imagens de ressonância nuclear magnética, a esclerose é caracterizada por redução de volume em sequências ponderadas em T1, aumento de sinal e tempo de relaxamento em sequências ponderadas em T2 e redução na transferência de magnetização. Justificativa e Objetivos: Uma vez que tanto o sinal T2 quando a transferência de magnetização são dependentes da água tecidual, nosso objetivo é avaliar, na formação hipocampal de pacientes com epilepsia do lobo temporal, as correlações entre populações celulares e moléculas ligadas à homeostase da água e as imagens ponderadas em T2 e transferência de magnetização. Visamos ainda definir, na formação hipocampal de indivíduos sem alterações neuropatológicas, o volume de cada um dos subcampos hipocampais. Metodologia: Pacientes com epilepsia do lobo temporal farmacorresistente (ELT, n = 43), bem como voluntários sadios (controle radiológico, CH, n = 20), foram submetidos a exames de ressonância magnética em máquina de 3T para mensuração da volumetria hipocampal, tempo de relaxamento T2 e transferência de magnetização hipocampal (exames in vivo). Após o tratamento cirúrgico para o controle das crises, os hipocampos dos pacientes com ELT foram fixados por 8 dias e submetidos aos exames ex vivo em máquina de 3T para cálculo do tempo de relaxamento T2 de cada subcampo hipocampal. Hipocampos controle (Controle historadiológico, CHR, n = 14), foram obtidos de autópsias de pacientes sem histórico ante-mortem de doença neurológica ou presença de patologia no exame do encéfalo pos mortem. Ambos os grupos controle foram pareados para idade em relação ao grupo ELT. Alguns dos casos CHR (n = 6) foram também submetidos à imagem 3D T2 em máquina de 4,7T para cálculo de volumetria dos subcampos hipocampais. Após emblocamento em parafina, secções coronais hipocampais dos casos CHR e ELT foram submetidas às técnicas de histoquímica básica Hematoxilina e Eosina e Luxol Fast Blue, e às imuno-histoquímicas para avaliação das populações neuronais (NeuN), astrócitos reativos (GFAP), micróglias ativadas (HLA-DR) e para a expressão de aquaporina 4 (AQP4) e níveis de sulfato de condroitina (CS-56). Para a comparação entre os grupos, foram realizados testes t para dados paramétricos e Mann-Whitney para dados não-paramétricos. Testes de correlação foram empregados para análise da associação entre as avaliações histológicas e os exames de ressonância magnética. Resultados: Pacientes com ELT apresentaram menor volume hipocampal, maior tempo de relaxamento T2 e menor transferência de magnetização no exame in vivo, quando comparados com o CR. O exame ex vivo para a volumetria dos subcampos hipocampais em casos do grupo CHR indicou que a fascia dentata, a região CA1 e o subículo correspondem à 85 % do volume hipocampal total. Quanto ao tempo de relaxamento T2 ex vivo, foi observado aumento em todos os subcampos hipocampais do grupo ELT, à exceção da fascia dentata, quando comparados ao CHR. A avaliação da densidade neuronal indicou redução significativa em todos os subcampos dos casos ELT, à exceção do subículo, quando comparados ao CHR. Em relação aos valores do grupo CHR, foi observada astrogliose em quase todos subcampos da formação hipocampal (a exceção da zona subgranular e do hilo) e microgliose em todos os subcampos (exceto pelo subículo) dos casos com ELT. Pacientes com ELT apresentaram redução na expressão de aquaporina 4 perivascular em todos os subcampos do hipocampo, comparados ao CHR. Aumento nos níveis de sulfato de condroitina foi observado em todos os subcampos da formação hipocampal, à exceção da camada granular, nos pacientes com ELT. O volume hipocampal e a transferência de magnetização in vivo dos pacientes com ELT correlacionaram-se tanto com a população neuronal como com os níveis de sulfato de condroitina, enquanto que o tempo de relaxamento in vivo correlacionou-se com a população astroglial e os níveis de sulfato de condroitina. O exame ex vivo corroborou a correlação entre a população glial e o tempo de relaxamento observado nos pacientes com ELT. A diferença entre o tempo de relaxamento in vivo e ex vivo correlacionou-se tanto com a difusibilidade da água no tecido como com os níveis de sulfato de condroitina. Conclusões: Nossos dados indicam correlação entre a patologia hipocampal e as imagens de ressonância nuclear magnética, sendo que a maior qualidade das imagens ex vivo permitiu uma avaliação mais direta entre o sinal de ressonância e a patologia, indicando importância da população celular e matriz extracelular para o volume hipocampal e a transferência de magnetização, e da astrogliose para o tempo de relaxamento T2. Finalmente, nossos dados mostraram que CA1, subículo e fascia dentata tem grande participação no volume hipocampal, sendo que alterações nestas regiões tem um papel mais relevante nas alterações observadas na ressonância magnética, como indicado por nossas correlações. / Rationale: Drug resistant temporal lobe epilepsy is often associated with hippocampal sclerosis. Histological evaluation reveals differential neuronal loss, gliosis and changes in molecules associated with water homeostasis, such as aquaporin 4 and chondroitin sulfate. Magnetic resonance imaging in these cases often reveals hippocampal atrophy, increased T2 signal and T2 relaxation and reduced magnetization transfer ratio in the hippocampus. Aims: Once both T2 signal and magnetization transfer are affected by tissue water, our goal was to evaluate, in the hippocampus of drug-resistant temporal lobe epilepsy patients who underwent surgery for seizure control, the associations between cellular populations, aquaporin 4 and chondroitin sulfate with T2 relaxation time and magnetization transfer. Additionally, we intended to measure the individual volume of each hippocampal subfield in hippocampus from patients without neurological disease. Methods: Patients with drug-resistant temporal lobe epilepsy (TLE, n = 43) and age-matched health volunteers (radiological control, RC, n = 20) were submitted to magnetic resonance in a 3T machine for hippocampal volumetry measure, T2 relaxation and magnetization transfer (in vivo examination). After surgical treatment for seizure control, hippocampi from the TLE patients were fixed in formalin for 8 days and then submitted to ex vivo imaging in 3T for relaxation time of every hippocampal subfield. Control hippocampi were obtained from autopsies of age-matched patients without ante mortem history of neurological disease or post mortem neurological pathology, and underwent the same ex vivo imaging (histo-radiological control, HRC, n = 14). Six cases from the HRC underwent 3D T2 imaging in a 4.7T machine, in order to measure the volumes of the hippocampal subfields. Paraffin embedded hippocampal sections from TLE and HRC were submitted to Hematoxilin-Eosin and Luxol Fast Blue histochemistries, and to immunohistochemistries for the evaluation of neurons (NeuN), reactive astrocytes (GFAP), activated microglia (HLA-DR), for aquaporin 4 (AQP4) and for chondroitin sulfate (CS-56). Students t-test or Mann-Whitneys test were performed for comparison between groups, and correlation tests were performed for the comparison between histological and magnetic resonance measures. Results: Patients with TLE presented reduced hippocampal volume, increased T2 relaxation time and reduced magnetization transfer, when compared to RC. The ex vivo volumetry of the hippocampal subfields revealed that fascia dentata, CA1 and subiculum together correspond to 85 % of the total hippocampal volume. Ex vivo relaxation time, as the in vivo, were increased in the subfields of TLE patients, when compared to HRC. Compared to HRC, TLE patients presented neuron loss and microgliosis in all hippocampal subfields but the subiculum, and astrogliosis in all hippocampal subfields but the subgranule zone and the hilus. Reduced perivascular aquaporin 4 was observed in all hippocampal subfields of TLE patients, and increased chondroitin sulfate was observed in all hippocampal subfields, with the exception of granule cell layer, of TLE patients, when compared to HRC. In TLE, both in vivo hippocampal volume and magnetization transfer correlated with the levels of chondroitin sulfate and the neuronal population, whereas the in vivo relaxation time correlated with the astroglial population and the levels of chondroitin sulfate. Ex vivo relaxation time also correlated with the astroglial population in TLE patients. The difference between in vivo and ex vivo relaxation values correlated with water difusibility and the levels of chondroitin sulfate. Conclusion: Our data indicate the importance of neuron population and extracellular matrix to both hippocampal volume and magnetization transfer, and of the reactive astrocytes for T2 relaxation. Ex vivo relaxation time allowed a more detailed evaluation, and indicated more robust correlations between reactive astrocytes and T2 relaxation. Finally, Our data indicated that CA1, the subiculum and fascia dentata are the major contributors to hippocampal volume, so changes in these subfields most likely will affect magnetic resonance imaging.

Proton MR spectroscopy is a non-invasive tool for measuring in vivo concentrations of several metabolites. The aim of this thesis was to test its applicability and reliability in neurosurgical praxis. In the first part of the study multiple MR spectroscopy methods were applied in a group of patients after surgery and oncologic treatment for high-grade glioma to test which method performed best in discriminating recurrent tumor from radionecrosis in the presence of a new enhancing lesion. The best diagnostic yield was achieved by comparison of choline, creatine and lactate between lesion and contralateral side (sensitivity 93.3%, specificity 78.6%). Creatine was significantly decreased in patients compared to controls. The inhibiting effect of ongoing oncologic treatment on cerebral and tumoral metabolism makes differential diagnosis trickier. Therefore, a diagnosis of radionecrosis assessed during ongoing radio- and chemotherapy should be confirmed after its completion. In the second part of the study MR spectroscopy data was compared with MR hippocampal volumetry and transcranial doppler examination in a cohort of patients with unilateral occlusion of the internal carotid artery. The N-acetylaspartate/choline ratio and hippocampal volume were significantly lower in both hemispheres of patients...

Zusammenfassung Fanny Schnauß Volumetrie der Leber aus Spiral-CT-Datensätzen von 43 Hunden mit Portosystemischem Shunt Klinik für Kleintiere der Veterinärmedizinischen Fakultät der Universität Leipzig Eingereicht im April 2022 83 Seiten, 34 Abbildungen, 13 Tabellen, 197 Literaturangaben, 7 Seiten Anhang Schlüsselwörter: Portosystemischer Shunt, Hund, Leber, Computertomographie, Lebervolumina, Mikrohepatie, Volumetrie Einleitung: Portosystemische Shunts (PSS) sind Gefäßanomalien, welche Blut des portalen Gefäßsystems unter Umgehung der Leber in den systemischen Kreislauf leiten. Die resultierende Minderdurchblutung der Leber führt u. a. zu einem Mangel an Wachstumsfaktoren und folglich zu einer Mikrohepatie. In der vorliegenden Arbeit wurden computertomographische (CT) Daten zur Bestimmung präziser Lebervolumina genutzt. Dies ermöglicht einen direkten Vergleich der Lebergrößen von Hunden mit PSS und ohne (Referenzgruppen). Ziele der Untersuchung: Es wurden folgende Zielstellungen bearbeitet: • Bestimmung der Präzision und Genauigkeit der Messwerte aus den CT-Daten (ex vivo Untersuchung). • Vergleich der Lebervolumina der Shunt-Patienten und der verschiedenen Subtypen mit denen der Referenzgruppen (ohne PSS, s.u.) • Die Normierung der Lebervolumina erfolgte anhand des Körpergewichts (BW), des metabolischen Körpergewichts (mBW), der Querschnittsfläche der Aorta (AAo) sowie der Querschnittsfläche des Rückenmarkkanals (AMc). Diese Normierungsmethoden wurden zur statistischen Signifikanzanalyse herangezogen und auf ihre Aussagekraft bewertet. • Analyse des präoperativen Lebervolumens als möglicher prospektiver Indikator für den Operationsverlauf sowie für den Grad der chirurgischen Einengung des Shunts. • Eruierung der postoperativen Zunahme des Lebervolumens. Tiere, Material und Methoden: Die Studie umfasst 43 Patienten mit PSS der Klinik für Kleintiere der Universität Leipzig aus den Jahren 2006 bis 2015. Als Referenzgruppe dienten 22 Hunde ohne PSS. Diese Referenzgruppe konnte weiterführend in unbestätigte Verdachtsfälle von PSS (10 Hunde) und Fälle ohne Hepatopathie (12 Hunde) unterteilt werden. Anhand der CT-Datensätze wurden retrospektiv die Lebervolumina der Tiere mittels Segmentierung und Volume-Rendering gemessen. Bei sechs Hunden mit PSS existieren Daten einer Folgeuntersuchung nach chirurgischer Versorgung, wodurch deren prä- und postoperative Lebervolumina gegenübergestellt werden konnten. In einer ex vivo Studie wurden zur Kontrolle der Messgenauigkeit der angewandten Methode sechs Lebern von Schlachtschweinen in unterschiedlichen Umgebungen (Luft, Wasser, Milch) einer CT unterzogen, anschließend deren Volumina mittels Wasserverdrängung im Wasserbad bestimmt und die Werte verglichen. Statistische Signifikanzprüfungen zwischen den unabhängigen Datengruppen erfolgten mittels Wilcoxon-Mann-Whitney-U-Test (keine Normalverteilung). Für die Prüfung auf signifikante Veränderungen der Messwerte vor und nach erfolgter Operation (verbundene Stichproben) wurde der Wilcoxon-Test verwendet (keine Normalverteilung). Ergebnisse: Es zeigten sich in allen vier Normierungen signifikant (p < 0,001) kleinere Lebervolumina für die 43 Hunde mit PSS im Vergleich zu den 22 Referenztieren (Normierung zum BW: 19,3 cm³/kg vs. 24,9 cm³/kg; mBW: 26,2 cm³/kg0,75 vs. 51,3 cm³/kg0,75; AAo: 2,6 cm vs. 4,6 cm; AMc: 2,6 cm vs. 7,5 cm). Beide Untergruppen unterschieden sich ebenfalls signifikant (jeweils p < 0,001) von der Gruppe der PSS Patienten. Keine signifikanten Unterschiede zeigten sich allerdings beim Vergleich der Hunde mit kongenitalem vs. erworbenem PSS, intra- (inPSS) vs. extrahepatischem Shunt (exPSS), rechtsseitigem vs. zentralem intrahepatischen PSS, den Subtypen der extrahepatischen PSS (portocavaler vs. Portophrenico- vs. Portoazygos-Shunt) und den Subtypen der portocavalen Shunts (gastroduodenal vs. splenocaval). Entgegen der Erwartung zeigten sich keine signifikanten Unterschiede der präoperativen Lebervolumina zwischen den Patienten bei denen in der ersten Operation (a) eine vollständige Ligatur des Shunts möglich war zu denen, die nur eingeengt werden konnten (b). Im Fall von 6 Patienten konnten prä- und postoperative CT- Aufnahmen verglichen werden. Nach einer medianen Zeitdifferenz von 72 Tagen zwischen den CT-Untersuchungen betrug die Volumenzunahme der Lebern 46,9 % (bzgl. der nicht nach Merkmalen normierten Lebervolumina). Zur Überprüfung der Richtigkeit des gewählten Analyseansatzes wurde in der ex vivo-Studie die mittlere Abweichung der Messwerte mit 5,1 ± 2,2 % bestimmt (CT-Daten vs. Wasserverdrängung der Schweinelebern). Die dreifachen Messungen ergeben eine mittlere Abweichung von nur 1,0 % (Präzision). Schlussfolgerungen: Die Messergebnisse der vorliegenden Studie zeigen klar auf, dass die Lebervolumina der Shunt-Patienten signifikant kleiner als die der Referenzgruppen ohne PSS sind. Diese signifikanten Unterschiede sind in allen Normierungen ersichtlich (jeweils p < 0,001). Allerdings ergaben sich keine signifikanten Unterschiede zwischen den verschiedenen Untergruppen der PSS-Patienten. Zur Vergleichbarkeit der Zunahme der Lebervolumina post OP erwiesen sich die Normierungen über die Querschnittsfläche der Aorta sowie über die Querschnittsfläche des Rückenmarkkanals als besonders geeignet, da diese weniger abhängig von den postoperativen metabolischen Veränderungen sind. Die Daten zeigen, dass das präoperative Lebervolumen ein insuffizienter Prädiktor sowohl für den Operationsverlauf als auch den Grad der möglichen Einengung des Shunt-Gefäßes in der Erst-OP ist. Das Lebervolumen nach chirurgischer Einengung des Shunts nahm durchschnittlich um 46,9 % zu, erreichte jedoch in dem betrachteten Zeitraum in keiner der Normierung das mediane Volumen der Patienten ohne Shunt.:Inhaltsverzeichnis 1. Einleitung 2. Literaturübersicht 2.1 Funktion, Anatomie und Gefäßsystem der Leber 2.2 Pfortaderkreislauf 2.3 Ductus venosus (Ductus Arantii) 2.4 Portosystemischer Shunt 2.5 Kongenitaler portosystemischer Shunt 2.5.1 Pathogenese und Pathophysiologie 2.5.2 Ätiologie und Prädispositionen 2.5.3 Extrahepatischer Portosystemischer Shunt 2.5.4 Intrahepatischer portosystemischer Shunt 2.6 Erworbener portosystemischer Shunt 2.7 Diagnostik des portosystemischen Shunts 2.7.1 Anamnese und klinische Symptome 2.7.2 Hepatoenzephales Syndrom 2.8 Bildgebende Diagnostik des portosystemischen Shunts 2.8.1 Sonographie 2.8.2 Projektionsradiographie 2.8.3 Computertomographie 2.8.3.1 Nativ-CT und Kontrastmittelphasen der Leber 2.8.3.2 Dynamische Computertomographie 2.8.3.3 Segmentierung und Volume Rendering/Volumendarstellung 2.8.3.4 Leber-Volumetrie 2.8.3.5 Volume-Rendering 2.9 Therapie und Prognose des portosystemischen Shunts 3. Tiere, Material und Methoden 3.1 Patienten 3.2 Anästhesieprotokoll 3.3 Computertomographische Untersuchung 3.4 Auswertung der Datensätze und Volumetrie 3.5 Referenzmessung zur Bestimmung der Messgenauigkeit 3.6 Statistische Analyse 4. Ergebnisse 4.1 Getrennte Betrachtung der beiden Referenzgruppen 4.2 Vergleich aller Shunt-Patienten mit den Referenzgruppen 4.3 Klassifizierung der Untergruppen 4.3.1 Kongenitaler und erworbener portosystemischer Shunt 4.3.2 Extrahepatischer und intrahepatischer portosystemischer Shunt 4.3.3 Vergleich der Patienten nach dem Grad der Ligatur in der Erst-OP 4.4 Bestimmung des Lebervolumens nach erfolgter Erst-Operation 4.5 Referenzmessung zur Bestimmung der Messgenauigkeit 5. Diskussion 5.1 Messmethoden, Fehlerquellen 5.2 Normierungsmethoden 5.3 Vergleich der Lebervolumina der Hunde mit PSS und beider RG 5.4 Evaluation der verschiedenen Shunt-Typen 5.5 Zunahme des Lebervolumens nach erfolgter Erst-Operation 5.6 Vollständiger oder unvollständiger Verschluss in der ersten OP 5.7 Rasse, Geschlecht, Alter und Gewicht der zu vergleichenden Gruppen 5.8 Klinische Schlussfolgerungen 6. Zusammenfassung 7. Summary 8. Literaturverzeichnis 9. Anhang 9.1 Abbildungsverzeichnis 9.2 Tabellenverzeichnis 9.3 Anhang: weitere Abbildungen und Tabellen / Summary Fanny Schnauß Liver volumetry from spiral CT datasets of 43 dogs with portosystemic shunt Department for Small Animals, Faculty of Veterinary Medicine, University of Leipzig Submitted in April 2022 83 pages, 34 figures, 13 tables, 197 references, 7 pages appendices Key words: portosystemic shunt, dog, liver, computed tomography, liver volume, microhepatia, volumetry Introduction: Portosystemic shunts (PSS) are vascular anomalies that divert blood from the portal vasculature into the systemic circulation, bypassing the liver. This results in a reduced blood supply to the liver leading, for instance, to a lack of growth factors and consequently to microhepatia. In the present work, computed tomography (CT) data was used to precisely determine liver volumes enabling a comparison of liver sizes of dogs with PSS to control animals. Objectives of this study: • Determination of the precision and accuracy of the measured values from the CT data. • Comparison of the liver volumes of the shunt patients (and various subtypes) with corresponding reference groups. • The liver volumes were normalized via body weight (BW), metabolic body weight (mBW), cross-sectional area of the aorta (AAo) and cross-sectional area of the spinal canal (AMc). These normalization methods were used for statistical significance analysis and to differentiate the patient groups. • Analysis of the preoperative liver volume as a possible prospective indicator for the course of the operation as well as for the degree of surgical narrowing of the shunt. • Determination of the postoperative increase of the liver volume. Animals, material and methods: The study included 43 shunt patients from the Clinic for Small Animals at the University of Leipzig, during the years from 2006 to 2015. 22 dogs served as the reference group. The reference group could be further subdivided into unconfirmed suspected cases of PSS (10 dogs) and cases without hepatopathy (12 dogs). Using the CT data sets, the liver volumes of the animals were measured retrospectively by means of segmentation and volume rendering. For six dogs with PSS, follow-up CT examinations after surgical treatment were conducted enabling a comparison of their pre- and post-operative liver volumes. To check the measurement accuracy of the method used, six livers from slaughter pigs were subjected to a CT examination in different environments (air, water, milk). These recordings went through the same volumetric analysis process as the dogs’ livers. This procedure further enabled a direct determination of the liver volumes by means of water displacement in a water bath. Statistical significance tests between the independent data groups were carried out using the Wilcoxon-Mann-Whitney U test. The Wilcoxon test was used to test for significant changes in the measured values before and after the operation (paired samples). Results: Significantly (p<0.001) smaller liver volumes for the 43 dogs with PSS compared to the 22 reference animals were found for all four normalizations (normalization to BW: 19.3 cm³/kg vs. 24.9 cm³/kg; mBW: 26.2 cm³/kg0,75 vs. 51.3 cm³/kg0,75; AAo: 2.6 cm vs. 4.6 cm; AMc: 2.6 cm vs. 7.5 cm). Both subgroups also differed significantly (each with p<0.001) from the group of PSS patients. However, no significant differences were found when comparing dogs with congenital vs. acquired PSS, inPSS vs. exPSS, right-sided vs. central inPSS, the subtypes of exPSS (portocaval vs. portophrenico vs. portoazygos shunt) and the subtypes of portocaval shunts (gastroduodenal vs. splenocaval). Contrary to expectations, there were no significant differences in the preoperative liver volumes between the patients where (a) a complete ligation of the shunt or (b) only a partial ligation was possible during the first operation. In the case of 6 patients, pre- and postoperative CT images could be evaluated and compared. After a median time-difference of 72 days between the CT examinations, the increase in volume of the livers was 46.9 % (liver volumes without normalization). Examinations of livers from slaughter pigs enabled both CT recordings and actual volume determinations using water displacement. These ex vivo experiments yielded a mean deviation from the measured values of 5.1 ± 2.2 % (accuracy). In addition, all volume measurements of the dog livers were carried out in triplicates, which in average only deviated by 1.0 % (precision). Conclusion: The results of the present study clearly show that the liver volumes of the shunt patients are significantly smaller than those of the reference groups. These significant differences can be seen in all normalizations (p<0.001 each). However, there were no significant differences between the various subgroups of PSS patients. The normalizations over the cross-sectional area of the aorta and over the cross-sectional area of the spinal canal are particularly suitable for comparing the increase in liver volumes after surgery. The data showed that the preoperative liver volume is an insufficient predictor for the course of the operation as well as for the degree of possible narrowing of the shunt vessel in the first OP. The liver volume after surgical narrowing of the shunt increased by an average of 46.9 %, but did not reach the median volume of the patients without a shunt by the time of the follow-up CT (independent of the normalization).:Inhaltsverzeichnis 1. Einleitung 2. Literaturübersicht 2.1 Funktion, Anatomie und Gefäßsystem der Leber 2.2 Pfortaderkreislauf 2.3 Ductus venosus (Ductus Arantii) 2.4 Portosystemischer Shunt 2.5 Kongenitaler portosystemischer Shunt 2.5.1 Pathogenese und Pathophysiologie 2.5.2 Ätiologie und Prädispositionen 2.5.3 Extrahepatischer Portosystemischer Shunt 2.5.4 Intrahepatischer portosystemischer Shunt 2.6 Erworbener portosystemischer Shunt 2.7 Diagnostik des portosystemischen Shunts 2.7.1 Anamnese und klinische Symptome 2.7.2 Hepatoenzephales Syndrom 2.8 Bildgebende Diagnostik des portosystemischen Shunts 2.8.1 Sonographie 2.8.2 Projektionsradiographie 2.8.3 Computertomographie 2.8.3.1 Nativ-CT und Kontrastmittelphasen der Leber 2.8.3.2 Dynamische Computertomographie 2.8.3.3 Segmentierung und Volume Rendering/Volumendarstellung 2.8.3.4 Leber-Volumetrie 2.8.3.5 Volume-Rendering 2.9 Therapie und Prognose des portosystemischen Shunts 3. Tiere, Material und Methoden 3.1 Patienten 3.2 Anästhesieprotokoll 3.3 Computertomographische Untersuchung 3.4 Auswertung der Datensätze und Volumetrie 3.5 Referenzmessung zur Bestimmung der Messgenauigkeit 3.6 Statistische Analyse 4. Ergebnisse 4.1 Getrennte Betrachtung der beiden Referenzgruppen 4.2 Vergleich aller Shunt-Patienten mit den Referenzgruppen 4.3 Klassifizierung der Untergruppen 4.3.1 Kongenitaler und erworbener portosystemischer Shunt 4.3.2 Extrahepatischer und intrahepatischer portosystemischer Shunt 4.3.3 Vergleich der Patienten nach dem Grad der Ligatur in der Erst-OP 4.4 Bestimmung des Lebervolumens nach erfolgter Erst-Operation 4.5 Referenzmessung zur Bestimmung der Messgenauigkeit 5. Diskussion 5.1 Messmethoden, Fehlerquellen 5.2 Normierungsmethoden 5.3 Vergleich der Lebervolumina der Hunde mit PSS und beider RG 5.4 Evaluation der verschiedenen Shunt-Typen 5.5 Zunahme des Lebervolumens nach erfolgter Erst-Operation 5.6 Vollständiger oder unvollständiger Verschluss in der ersten OP 5.7 Rasse, Geschlecht, Alter und Gewicht der zu vergleichenden Gruppen 5.8 Klinische Schlussfolgerungen 6. Zusammenfassung 7. Summary 8. Literaturverzeichnis 9. Anhang 9.1 Abbildungsverzeichnis 9.2 Tabellenverzeichnis 9.3 Anhang: weitere Abbildungen und Tabellen

L’objectif de ce travail était d’étudier la mémoire autobiographique (MAb) aux stades débutants de la maladie d’Alzheimer et d’analyser le lien avec le Self défini selon le modèle de Prebble et collaborateurs. (2013) et en investiguant les substrats neuro-anatomiques. Notre étude a confirmé qu’il existait une altération de la MAb chez les patients atteints de maladie d’Alzheimer, dans sa composante épisodique et émotionnelle, quelle que soit l’ancienneté des souvenirs. Nous avons pu rattacher ce déficit épisodique à l’atrophie des régions temporales internes et en suggérer l’implication de l’hippocampe gauche dans le contexte temporel des souvenirs et de l’amygdale droite dans la composante émotionnelle. En revanche, il existait une relative préservation du niveau des détails des souvenirs émotionnels résiduels, et surtout, des souvenirs sémantisés, ces derniers étant supportés par le néocortex temporal. Concernant le Self de façon plus générale, les résultats mettent en évidence un lien entre Self-conceptuel et MAb, par le biais des processus de sémantisation et d’intégration des souvenirs qui permettent de former des représentations abstraites à partir des expériences vécues. Par ailleurs, nous avons également montré que le sens subjectif de soi est inhérent à toutes les autres composantes du Self. Par l’étude d’un cas unique et d’imagerie volumétrique de groupe, le cortex préfrontal médian a été mis en évidence comme substrat commun à toutes les composantes du Self, suggérant un rôle clé de cette structure pour supporter le sens subjectif de soi. Ces résultats ouvrent des pistes de remédiation par la réminiscence basée sur les mécanismes de sémantisation, d’intégration et sur les aspects émotionnels, au centre desquels se trouvent les souvenirs définissant-le-soi. Aussi notre étude engage-t-elle à analyser ces composantes du Self au sein de réseaux, en connectivité fonctionnelle et anatomique. / The present study aimed at studying autobiographical memory (AbM) in patients at early stages of Alzheimer’s disease, as well as at analyzing the link between AbM and the Self components (as defined by Prebble et al., 2013), and finally, at investigating its neuro-anatomical correlates. The results we obtained confirmed AbM is damaged in patients with regards to episodic and emotional components, whatever the age of the memory. The deficit in episodic memory was associated with medial temporal lobe atrophy, with the left hippocampus seemingly involved in the temporal context of the memories and the right amygdala in the emotional component. Conversely, specificity of remaining emotional memories was relatively preserved, as well as semanticized memories, which rely on the temporal neocortex. In the context of the Self more generally, our results highlight a relationship between the conceptual-Self and autobiographical memories, through semanticization and integration processes, which allow the formation of the most abstracted forms of self-representations. Moreover, the subjective sense of Self appears as a prerequisite to all other Self components. Based upon a case study and a volumetric group study, we were able to show that the implication of the medial prefrontal cortex is common to all Self components, suggesting its key role for the subjective sense of Self. Our results point to a potential rehabilitation therapy based on reinforcing self-defining memories to strengthen the Self. This work will be completed by the study of functional and anatomical networks sustaining the Self.

Le stress prénatal est un sujet d'intérêt éthologique croissant en raison de ses effets sur la santé humaine et le bien-être des animaux. Cette thése de doctorat s’intéresse à la seiche Sepia officinalis, un modèle pratique dans lequel la progéniture en développement peut être séparée de leurs mères pour examiner diverses sources potentielles de stress en isolement expérimental. Plusieurs catégories de facteurs de stress ont été appliquées aux embryons et aux juvéniles et la progéniture résultante a été testée dans une série d'épreuves physiologiques et comportementales. L'objectif était de déterminer si différents types de stress prénatal affectent la seiche et, dans l'affirmative, comment ces effets se transmettent. Les données présentées démontrent que les stresseurs appliqués aux femelles reproductrices (stress maternel), ainsi que les stresseurs appliqués directement aux embryons (stress embryonnaire), affectent le comportement postnatal (y compris la structuration corporelle, la latéralisation cérébrale, la prédation et les schémas d'activité) la mémoire et / ou la neurobiologie (y compris les concentrations et le renouvellement de la monoamine, la taille des différents lobes cérébraux et la division cellulaire). Les résultats mettent en évidence la présence de trois voies par lesquelles le stress peut exercer des effets: sur le nombre de descendants produits par la femelle, la transmission de la femelle à sa progéniture et directement sur la progéniture elle-même. Les expériences ont également démontré qu'un facteur de stress complètement artificiel (lumière forte) affectait un éventail plus large de comportements chez la progéniture qu’un stress naturel (odeur de prédateur). Enfin, les données ont montré que l'environnement d'incubation et d’élevage peuvent également affecter la progéniture et méritent donc une attention particulière dans la formulation et l'interprétation des expériences avec cette espèce. Ces découvertes informent à la fois les pratiques de bien-être des seiches et d'autres céphalopodes (par exemple, réduisent la manipulation pour maximiser la reproduction) et élucident et renforcent les principes éthologiques qui s'appliquent au stress animal en général (par exemple la transmission des effets de stress de la mère à la progéniture). Compte tenu des informations fournies ici et dans de nombreuses autres études, la seiche et d'autres céphalopodes devraient continuer à servir de modèles comportementaux en éthologie et en biologie en général. / Prenatal stress is a subject of growing ethological interest due to its effects on human health and animal welfare. This Ph.D. thesis utilizes the cuttlefish Sepia officinalis, a convenient model in which developing offspring can be separated from their mothers to examine various potential sources of stress in experimental isolation. Several categories of stressors were applied to cuttlefish and cuttlefish eggs and the resulting offspring were tested in a range of physiological and behavioral tests. The goal was to determine if various types of prenatal stress affect cuttlefish, and if so, how these effects are transmitted. The data presented demonstrate that both stressors applied to reproducing females (maternal stress), as well as stressors applied directly to embryos (embryonic stress), affected post-natal behavior (including body patterning, brain lateralization, predation and activity patterns), learning, memory and/or neurobiology (including monoamine concentrations and turnover, the size of various brain lobes and cell division). The results highlight the presence of three pathways by which stress can exert effects: on the number of offspring produced by the female, transmission from the female to her offspring and directly on the offspring themselves. The experiments also demonstrated that a completely artificial stressor (bright light) affected a wider range of behaviors in offspring than a natural-occurring one (predator odor). Finally, the data showed that incubation and spawning environment can also affect offspring, and thus deserve attention in the formulation and interpretation of experiments with this species. These findings inform both welfare practices for cuttlefish and other cephalopods (e.g. reduce handling to maximize reproduction) as well as elucidating and reinforcing ethological principles that apply to animal stress in general (e.g. the transmission of stress effects from mother to offspring). Given the insight provided here and in numerous other studies, cuttlefish and other cephalopods should continue to serve as behavioral models in ethology and biology in general.

A polineuropatia inflamatória desmielinizante crônica (PIDC) é uma síndrome caracterizada fundamentalmente pela disfunção do Sistema Nervoso Periférico e que afeta muito a qualidade de vida dos pacientes. O envolvimento da PIDC com o Sistema Nervoso Central tem sido descrito, maiormente como sendo subclínico, porém não há estudos sobre a caracterização deste envolvimento de uma forma ampla e quantitativa. Avaliamos 11 pacientes com PIDC, todos tratados e sem sinais clínicos de alterações centrais, e 11 controles, pareados em gênero e faixa etária de 19 a 69 anos. Foram adquiridas neuroimagens em uma máquina de Ressonância Magnética de alto campo (3T) usando diferentes técnicas de imagens; volumétricas ponderadas em T1, volumétricas de inversão e recuperação com atenuação de fluidos e ponderadas em T2, relaxométricas de cinco ecos para mapas de T2, de transferência de magnetização e por tensor de difusão. As imagens foram processadas em diferentes ferramentas computacionais e foram obtidos resultados para estudos da difusibilidade, volumetria, morfometria, tratometria e conectividade cerebral, além de achados radiológicos para os pacientes. As análises de grupos foram executadas por; 1) testes paramétricos monocaudais de duas amostras pareadas para os resultados da volumetria, da tratometria e conectividade cerebral; 2) mapeamento estatístico paramétrico para os resultados da morfometria baseada em voxel e; 3) estatística espacial baseada em tratos para os resultados da difusibilidade. Foram detectas alterações em todas as comparações. Os principais achados indicam um envolvimento possivelmente caracterizado por uma perda volumétrica encefálica generalizada, sobretudo nas regiões periventriculares associadas a ventrículos proeminentes acrescido de, um aumento da difusibilidade transversa e oblíqua nos maiores tratos de substância branca e, também há uma perda de densidade na substância branca periventricular e um aumento na substância cinzenta em uma região que sinaliza para o espessamento trigeminal bilateral e, uma redução geral da conectividade cerebral estrutural. / Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a severe disease fundamentally characterized by dysfunction of the Peripheral Nervous System and affects greatly the quality of life of patients. The Central Nervous System (CNS) involvement in CIDP has not been described using recent quantitative neuroimaging techniques. We evaluated 11 patients with CIDP, all treated and without clinical signs of central alterations and 11 controls matched for gender and age group of 19 to 69 years. Magnetic Resonance Imaging were performed on a 3T scanner using different imaging techniques; structural 3D T1-weighted, fluid-attenuated inversion recovery, relaxometry with 5 echoes pulse sequence for T2 maps, magnetization transfer weighted and diffusion tensor imaging. The images were processed on different tools and were obtained results for the studies of diffusivity, volumetry, morphometry, tractometry, brain connectivity, and radiological findings of patients. Different statistical group analyses were performed in the quantitative results: 1) Parametric test for volumetry, tractometry and brain connectivity; 2) Parametric mapping for voxel morphometry; 3) Tract-based spatial statistics (TBSS) for diffusion coefficients. Changes were detected in all comparisons. In the patients, our main findings are: generalized loss brain volume more pronounced in periventricular regions associated with prominent ventricles, increased simultaneously perpendiculars and parallel diffusivity in the major tracts of the TBSS analyze, white matter density loss in the periventricular area, some bilateral trigeminal thickening, and general reduction of the brain connectivity. The CIDP affects the global brain and represents a demyelination in the CNS.