This Ph.D. research project targets Cooper Basin oil reservoirs of very low permeability (approximately 1mD) where injectivities required for water flooding are not achievable. However, the use of injection gases such as CO₂ would not have injectivity problems. CO₂ is abundant in the region and available for EOR use. CO₂ was compared to other CO₂-rich injection gases with a hydrocarbon content including pentane plus components. While the effect of hydrocarbon components up to butane have been investigated in the past, the effect of n-pentane has on impure CO₂ gas streams has not. One particular field of the Cooper Basin was investigated in detail (Field A). However, since similar reservoir and fluid characteristics of Field A are common to the region it is expected that the data measured and developed has applications to many other oil reservoirs of the region and similar reservoirs elsewhere. The aim of this Ph.D. project is to determine the applicability of CO₂ as an injection gas for Enhanced Oil Recovery (EOR) in the Cooper Basin oil reservoirs and to compare CO₂ with other possible CO₂-rich injection gases. The summarised goals of this research are to: • Determine the compatibility of Field A reservoir fluid with CO₂ as an injection gas. • Compare CO₂ to other injection gas options for Field A. • Development of a correlation to predict the effect of nC₅ on MMP for a CO₂- rich injection gas stream. These goals were achieved through the following work: • Extensive experimental studies of the reservoir properties and the effects of interaction between CO₂-rich injection gas streams and Field A reservoir fluid measuring properties related to: • Miscibility of the injection gas with Field A reservoir fluid • Solubility and swelling properties of the injection gas with Field A reservoir fluid • Change in viscosity-pressure relationship of Field A reservoir fluid due to addition of injection gas • A reservoir condition core flood experiment • Compositional simulation of the reservoir condition core flood to compare expected recoveries from different injection gases • Development of a set of Minimum Miscibility Pressure (MMP) measurements targeted at correlating the effect of nC₅ on CO₂ MMP. The key findings of this research are as follows: • Miscibility is achievable at practical pressures for Field A and similar reservoir fluids with pure CO₂ or CO₂-rich injection gases. • For Field A reservoir fluid, viscosity of the remaining flashed liquid will increase at pressures below ~2500psi due to mixing the reservoir fluid with a CO₂-rich injection gas stream. • Comparison of injection gases showed that methane rich gases are miscible with Field A so long as a significant quantity of C₃+ components is also present in the gas stream. • There is a defined trend for effect of nC₅ on MMP of impure CO₂. This trend was correlated with an error of less than 4%. • Even though oil composition is taken into account with the base gas MMP, it still affects the trend for effect of nC₅ on MMP of a CO₂-rich gas stream. • An oil characterisation factor was developed to account for this effect, significantly improving the results, reducing the error of the correlation to only 1.6%. The significance of these findings is as follows: • An injection pressure above ~3000psi should be targeted. At these pressures miscibility is achieved and the viscosity of the reservoir fluid injection gas mix is reduced. • CO₂ should be compared to gases such as Tim Gas should after considering the cost of compression, pipeline costs and distance from source to destination will need to be considered. • The addition of nC₅ will reduce the MMP and increase the recovery factor, however the cost of the nC₅ used would be more than the value of increased oil recovered. • The developed correlation for the effect of nC₅ on impure CO₂ MMP can be used broadly within the limits of the correlation. • Further research using more oils is necessary to validate the developed oil characterisation factor and if successful, using the same or similar method used to improve other correlations. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1369016 / Thesis (Ph.D.) -- University of Adelaide, Australian School of Petroleum, 2009.

Zusammenfassung Ulrike Jörn Untersuchung des Glukose-, Harnstoff- und Kreatiningehalts in der Tränenflüssigkeit bei Katzen mit normalen und erhöhten Blutplasmawerten Klinik für Kleintiere der Veterinärmedizinischen Fakultät, Universität Leipzig Eingereicht im Februar 2018, verteidigt im Oktober 2018 73 Seiten, 13 Abbildungen, 20 Tabellen, 208 Literaturangaben Die Entnahme von Tränenflüssigkeit und Untersuchung von klinisch relevanten Metaboliten ist derzeit ein hochinteressantes Forschungsthema in der Diabetesforschung beim Menschen. Auch für die Tiermedizin ist dieses schnelle und einfache Verfahren relevant und könnte Blutuntersuchungen ergänzen, reduzieren oder sogar ersetzen. Aufgrund der Minimalinvasivität eignet sich die Tränenanalyse insbesondere bei der stressempfindlichen Katze und trägt so zum Tierwohl bei. Zum gegenwärtigen Zeitpunkt gibt es keine Untersuchungen der Glukosekonzentration bei der Katze. Die derzeit vorliegenden Untersuchungen beinhalten die semiquantitative Untersuchung der Harnstoffkonzentration bei Hunden und Katzen und die quantitative Untersuchung der Harnstoff- und Kreatininkonzentration beim Pferd. Ziele dieser Arbeit waren (1) die Bestimmung eines geeignetes Material für eine praktikable Tränenentnahme und (2) die quantitative Analyse der Metaboliten Glukose, Harnstoff und Kreatinin in der Tränenflüssigkeit von Katzen mit normalen und erhöhten Blutplasmakonzentrationen. Dazu wurden zunächst an einer kleineren Anzahl an Tieren (n=13) die Materialien Kapillare, Filterpapierstreifen und Polyurethanschwamm auf die Kriterien Handhabung, Verletzungsgefahr, Flüssigkeitsaufnahme und -abgabe und Entnahmezeit getestet. Im Anschluss wurde aufgrund der Praktikabilität der Polyurethanschwämme die quantitative Analyse bei 60, 72 und 48 Katzen durchgeführt. In der statistischen Untersuchung wurde kein signifikanter Unterschied für Glukose und Harnstoff zwischen beiden Augen bestimmt. Die lakrimale Glukosekonzentration konnte bei 60 Katzen erfasst werden und lag mit 16 % deutlich unter der Glukosekonzentration des Blutplasmas. Es wurde eine moderate Korrelation zwischen Tränenflüssigkeit und Blutplasma gefunden (r=0,743; p<0,001). Bei einem Cut-Off-Wert von 1,6 mmol/l waren Sensitivität und Spezifität 90 % und 81%. Harnstoff konnte bei 72 Katzen in der Tränenflüssigkeit bestimmt werden und lag mit 7 % etwas über der Glukosekonzentration des Blutplasmas. Es wurde eine starke Korrelation zwischen Tränenflüssigkeit und Blutplasma nachgewiesen (r=0,971; p<0,0001). Bei einem Cut-Off-Wert von 14,35 mmol/l lagen Sensitivität und Spezifität bei 100 %. Die Ergebnisse der lakrimalen Kreatininbestimmung (n=48) konnten nur deskriptiv beschrieben werden, da viele Tiere Konzentrationen unter der gerätespezifischen Nachweisgrenze von 18 µmol hatten. Die Konzentrationen in der Tränenflüssigkeit bei Katzen mit normalen und erhöhten Blutplasmawerten lagen dabei deutlich unter der Konzentration des Blutplasmas. Diese Arbeit zeigt, dass die Entnahme, Verarbeitung und Analyse von den Metaboliten Glukose, Harnstoff und Kreatinin in der Tränenflüssigkeit möglich ist. Die vorliegenden Ergebnisse der quantitativen Studie sind trotz Limitationen ein wichtiger Beitrag für die Etablierung neuer minimalinvasiver Verfahren durch Nutzung der Tränenflüssigkeit zur Diagnostik bei der Katze.:Inhaltsverzeichnis 1 Einleitung 1 2 Literaturübersicht 4 2.1 Aufbau und Funktion des Tränenfilmes 4 2.2 Übertritt von Metaboliten in die Tränenflüssigkeit 5 2.2.1 Permeabilität von Kornea und Konjunktiva 5 2.2.1.1 Aufbau und Funktion der Kornea 6 2.2.1.2 Aufbau und Funktion der Konjunktiva 6 2.2.1.3 Zusätzliche Permeabilitätsfaktoren 7 2.2.2 Übertritt von Glukose in die Tränenflüssigkeit 8 2.2.2.1 Untersuchung der lakrimalen Glukosekonzentration 8 2.2.2.2 Transportsysteme für Glukose 10 2.2.2.3 Veränderungen von Kornea und Konjunktiva bei Diabetes mellitus 11 2.2.2.4 Anwendung der lakrimalen Glukosemessung in Human- und Tiermedizin 13 2.2.3 Übertritt von Harnstoff in die Tränenflüssigkeit 14 2.2.3.1 Untersuchung der lakrimalen Harnstoffkonzentration 14 2.2.3.2 Transportsysteme für Harnstoff 15 2.2.4 Übertritt von Kreatinin in die Tränenflüssigkeit 17 2.2.4.1 Untersuchung der lakrimalen Kreatininkonzentration 17 2.2.4.2 Metabolismus des Kreatinins 18 2.2.4.3 Sekretion von Kreatinin durch Transportsysteme (OCTS, MATE, MDR1) 19 2.2.5 Veränderungen der Kornea und Konjunktiva bei Niereninsuffizienz 20 2.2.6 Vergleich der Metabolitkonzentrationen in beiden Augen 21 2.3 Methodische Verfahren zur Entnahme von Tränenflüssigkeit 21 2.3.1 Tränenentnahme mit Kapillaren 21 2.3.2 Tränenentnahme mit Filterpapierstreifen 22 2.3.3 Tränenentnahme mit Polyurethantupfer, Zelluloseacetat und Polyesterkegel 23 2.3.4 Experimentelle Materialuntersuchungen zum Aufnahme- und Abgabeverhalten 24 3 Material und Methoden 26 3.1 Testmaterialien zur Tränenentnahme 26 3.2 In-vitro-Vorversuche 26 3.2.1 Untersuchung der Flüssigkeitsaufnahme der Materialien 26 3.2.2 Untersuchung der Flüssigkeitsabgabe der Materialien 27 3.3 In-vivo-Studien 29 3.3.1 Untersuchte Katzen 29 3.3.2 Durchführung der In-vivo-Versuche 30 3.4 Statistische Analysen 35 4 Ergebnisse 37 4.1 In-vitro-Versuche 37 4.1.1 Untersuchung der Flüssigkeitsaufnahme der Materialien 37 4.1.2 Untersuchung der Flüssigkeitsabgabe der Materialien 37 4.2 In-vivo-Studien 39 4.2.1 Vergleich der verschiedenen Materialien an der Katze 39 4.2.2 Quantitative Bestimmung der Glukosekonzentration 40 4.2.2.1 Vergleich der Tränenkonzentrationen untereinander 41 4.2.2.2 Vergleich der Tränenkonzentration mit dem Blutplasma 44 4.2.3 Quantitative Bestimmung der Harnstoffkonzentration 47 4.2.3.1 Vergleich der Tränenkonzentrationen untereinander 48 4.2.3.2 Vergleich der Tränenkonzentrationen mit dem Blutplasma 50 4.2.4 Quantitative Bestimmung der Kreatininkonzentration 53 5 Diskussion 56 5.1 In-vitro-Versuche 56 5.2 In-vivo-Versuche 56 5.2.1 Anwendung der verschiedenen Testmaterialien an der Katze 56 5.2.1.1 Handhabung der Probenentnahme 57 5.2.1.2 Entnahmezeit und Volumen 58 5.2.2 Quantitative Bestimmung der Glukosekonzentration 59 5.2.3 Quantitative Bestimmung der Harnstoffkonzentration 63 5.2.4 Quantitative Bestimmung der Kreatininkonzentration 65 5.3 Klinische Relevanz dieser Untersuchungen 67 6 Zusammenfassung 70 7 Summary 72 8 Literaturverzeichnis 74

A detecção de antígenos em amostras de líquido cefalorraquiano (LCR) de pacientes com neurocisticercose (NC) foi realizada empregando-se o teste ELISA com soros policlonais de coelhos imunizados com os antígenos total de Taenia solium (T-Tso), líquido vesicular de Taenia crassiceps (LV-Tcra) e peptídeos &#60;30kDa de LV-Tcra. Os soros policlonais foram fracionados para a obtenção da fração IgG - IgG anti-Tso, IgG antiTcra e IgG anti-Tcra&#60;30kDa. Também foi empregado o anticorpo monoclonal específico para o antígeno de excreção e secreção de Taenia crassiceps (ES-Tcra). A seleção dos clones foi realizada por ELISA empregando-se os antígenos T-Tso e LV-Tcra. Foram analisados diferentes grupos de amostras divididos em: grupo de pacientes com NC (grupo NC), incluindo pacientes em diferentes fases evolutivas da doença, grupo de pacientes \"suspeito\" de NC (grupo \"suspeito\" NC), grupo controle (grupo C) e grupo de outros patologias (grupo OP). No teste ELISA empregando-se as frações IgG anti-Tso, IgG anti-Tcra e IgG anti-Tcra&#60;30kDa, a sensibilidade obtida foi de 70%, 82,5% e 95,8% e a especificidade de 82,5%, 98% e 100%, respectivamente nas amostras do grupo NC e grupo C. Nas amostras do grupo diferentes fases evolutivas da doença, não houve diferença significativa de reatividade entre as amostras com as frações empregadas. Para as 21 amostras do grupo NC - fase ativa da doença, com a fração IgG anti-Tcra e o anticorpo monoclonal anti-ES-Tcra, respectivamente, 13 e 16 amostras foram positivas para a pesquisa de antígenos. As amostras de LCR do grupo C não apresentaram reatividade com os anticorpos empregados nos ensaios. Também foram ensaiadas 68 amostras de LCR de pacientes com \"suspeita\" de NC. De acordo com as características citoprotéicas além da reatividade para a pesquisa de anticorpos anti-T solium, as amostras de LCR apresentaram, neste grupo, padrão de reatividade para a pesquisa de antígenos que variou também de acordo com a presença de anticorpos, além das alterações de proteína e/ou células, que as amostras apresentavam ou não. Frações de 14 e 18kDa foram identificadas pelo teste imunoblot somente nas amostras de LCR de pacientes com NC utilizando as frações IgG anti-Tso, IgG anti-Tcra e anticorpo monoclonal anti-ES-Tcra. O anticorpo monoclonal anti-ES-Tcra mostrou-se eficiente para a pesquisa de antígenos no teste de competição por ELISA nas amostras de LCR de pacientes com NC e o antígeno ES-Tcra. / Antigen detection in cerebrospinal fluid (CSF) samples of patients with neurocysticercosis (NC) was performed through ELISA test using rabbits polyclonal sera immune with total antigens of Taenia solium (T-Tso) cysticercus, vesicular liquid of Taenia crassiceps (VL-Tcra) and vesicular liquid peptides (VLP-Tcra&#60;30kDa) cysticercus. The polyclonal sera were separated obtaining IgG-lgG anti-Tso, IgG anti-Tcra and IgG anti-Tcra&#60;30kDa fractions. A specific monoclonal antibody was also applied for reaching the excretion and secretion antigen of the T. crassiceps (ES-Tcra) larvae culture. Clones selection was performed through Elisa test applying the T-Tso and VL-Tcra antigens. When IgG anti-Tso, IgG anti-Tcra and IgG anti-Tcra&#60;30kDa fractions were applied in the ELISA test, the accuracy obtained was 70%, 82,5% and 95,8% and the specificity of 82,5%, 98% and 100%, respectively, in samples of both NC and C groups. In the samples of the group in different stages of the disease there was no significant difference on reactivity between the samples when the fractions were applied. For the 21 samples of the NC group - active stage of the disease with IgG anti-Tcra fraction and the anti-ES-Tcra monoclonal antibody respectively, 13 and 16 samples were positive for antigen analyses. The CSF samples of the C group did not present reactivity with the antibodies applied in the tests. Tests for 68 CSF samples of \"suspected\" NC group, were also conducted. According to the cytoproteic characteristics besides the reactivity for the anti-T. solium antibody study, the CSF samples of this group showed standard reactivity for antigen detection ranging also in accordance with the presence of antibodies and of the protein and/or cell alterations that the samples would or not present. Fractions of 14 and 18kDa were identified by immunoblot test only in the CSF samples of patients with NC using the IgG anti-Tso IgG anti-Tcra fractions and the anti-ES-Tcra monoclonal antibody. The anti-ES-Tcra monoclonal antibody has shown to be efficient for analyzing antigens by a comparing method of the ELISA test in CSF samples of patients with NC and the ES-Tcra antigen.

A detecção de antígenos em amostras de líquido cefalorraquiano (LCR) de pacientes com neurocisticercose (NC) foi realizada empregando-se o teste ELISA com soros policlonais de coelhos imunizados com os antígenos total de Taenia solium (T-Tso), líquido vesicular de Taenia crassiceps (LV-Tcra) e peptídeos &#60;30kDa de LV-Tcra. Os soros policlonais foram fracionados para a obtenção da fração IgG - IgG anti-Tso, IgG antiTcra e IgG anti-Tcra&#60;30kDa. Também foi empregado o anticorpo monoclonal específico para o antígeno de excreção e secreção de Taenia crassiceps (ES-Tcra). A seleção dos clones foi realizada por ELISA empregando-se os antígenos T-Tso e LV-Tcra. Foram analisados diferentes grupos de amostras divididos em: grupo de pacientes com NC (grupo NC), incluindo pacientes em diferentes fases evolutivas da doença, grupo de pacientes \"suspeito\" de NC (grupo \"suspeito\" NC), grupo controle (grupo C) e grupo de outros patologias (grupo OP). No teste ELISA empregando-se as frações IgG anti-Tso, IgG anti-Tcra e IgG anti-Tcra&#60;30kDa, a sensibilidade obtida foi de 70%, 82,5% e 95,8% e a especificidade de 82,5%, 98% e 100%, respectivamente nas amostras do grupo NC e grupo C. Nas amostras do grupo diferentes fases evolutivas da doença, não houve diferença significativa de reatividade entre as amostras com as frações empregadas. Para as 21 amostras do grupo NC - fase ativa da doença, com a fração IgG anti-Tcra e o anticorpo monoclonal anti-ES-Tcra, respectivamente, 13 e 16 amostras foram positivas para a pesquisa de antígenos. As amostras de LCR do grupo C não apresentaram reatividade com os anticorpos empregados nos ensaios. Também foram ensaiadas 68 amostras de LCR de pacientes com \"suspeita\" de NC. De acordo com as características citoprotéicas além da reatividade para a pesquisa de anticorpos anti-T solium, as amostras de LCR apresentaram, neste grupo, padrão de reatividade para a pesquisa de antígenos que variou também de acordo com a presença de anticorpos, além das alterações de proteína e/ou células, que as amostras apresentavam ou não. Frações de 14 e 18kDa foram identificadas pelo teste imunoblot somente nas amostras de LCR de pacientes com NC utilizando as frações IgG anti-Tso, IgG anti-Tcra e anticorpo monoclonal anti-ES-Tcra. O anticorpo monoclonal anti-ES-Tcra mostrou-se eficiente para a pesquisa de antígenos no teste de competição por ELISA nas amostras de LCR de pacientes com NC e o antígeno ES-Tcra. / Antigen detection in cerebrospinal fluid (CSF) samples of patients with neurocysticercosis (NC) was performed through ELISA test using rabbits polyclonal sera immune with total antigens of Taenia solium (T-Tso) cysticercus, vesicular liquid of Taenia crassiceps (VL-Tcra) and vesicular liquid peptides (VLP-Tcra&#60;30kDa) cysticercus. The polyclonal sera were separated obtaining IgG-lgG anti-Tso, IgG anti-Tcra and IgG anti-Tcra&#60;30kDa fractions. A specific monoclonal antibody was also applied for reaching the excretion and secretion antigen of the T. crassiceps (ES-Tcra) larvae culture. Clones selection was performed through Elisa test applying the T-Tso and VL-Tcra antigens. When IgG anti-Tso, IgG anti-Tcra and IgG anti-Tcra&#60;30kDa fractions were applied in the ELISA test, the accuracy obtained was 70%, 82,5% and 95,8% and the specificity of 82,5%, 98% and 100%, respectively, in samples of both NC and C groups. In the samples of the group in different stages of the disease there was no significant difference on reactivity between the samples when the fractions were applied. For the 21 samples of the NC group - active stage of the disease with IgG anti-Tcra fraction and the anti-ES-Tcra monoclonal antibody respectively, 13 and 16 samples were positive for antigen analyses. The CSF samples of the C group did not present reactivity with the antibodies applied in the tests. Tests for 68 CSF samples of \"suspected\" NC group, were also conducted. According to the cytoproteic characteristics besides the reactivity for the anti-T. solium antibody study, the CSF samples of this group showed standard reactivity for antigen detection ranging also in accordance with the presence of antibodies and of the protein and/or cell alterations that the samples would or not present. Fractions of 14 and 18kDa were identified by immunoblot test only in the CSF samples of patients with NC using the IgG anti-Tso IgG anti-Tcra fractions and the anti-ES-Tcra monoclonal antibody. The anti-ES-Tcra monoclonal antibody has shown to be efficient for analyzing antigens by a comparing method of the ELISA test in CSF samples of patients with NC and the ES-Tcra antigen.

Die Liquordiagnostik im Rahmen von Demenzerkrankungen ist trotz neuer diagnostischer Möglichkeiten im Bereich der PET(Positronen-Emissions-Tomographie)-Bildgebung weiterhin von hoher klinischer Relevanz. Insbesondere für die Alzheimer-Erkrankung existieren validierte Biomarker, die die Diagnose untermauern und bei der diagnostischen Abgrenzung anderer Demenzätiologien hilfreich sein können.Während unauffällige Liquorbefunde mit negativen Demenz- und Destruktionsmarkern die überwiegende Mehrzahl neurodegenerativer Demenzursachen mit hoher diagnostischer Sicherheit ausschließen, stellen in der klinischen Praxis vor allem überlappende Biomarkerprofile bei primär neurodegenerativen Demenzursachen ein substanzielles Problem bei der Befundinterpretation dar. Deshalb bedarf die Liquorbefundinterpretation stets einer kontextualisierten Betrachtung unter Würdigung der klinischen Symptomatik und Verlaufscharakteristika des entsprechenden demenziellen Syndroms. Außerdem stellen auchMischbefunde eine häufige diagnostische Herausforderung dar, ür deren Interpretation es profunder Kenntnisse im Bereich von Präanalytik, möglicher Liquorbefundkonstellationen und natürlich der verschiedenen in Betracht kommenden Demenzätiologien bedarf. Auch Liquorbiomarker für Synukleinopathien, Tauopathien sowie TDP43(Transactive response DNA binding protein 43 kDa)-Proteinopathien sind Gegenstand aktueller Untersuchungen, wenngleich diese noch nicht den Weg in die klinische Routinediagnostik gefunden haben.