Advances in technology have now made it possible to analyze cardiac output (Q) with only a single-breath, making measurements during exercise quicker and less invasive for the subject. Certain non-invasive techniques allow for measurement of the disappearance of a soluble inert gas as it diffuses across the blood-gas barrier in the lungs. The rate of disappearance of the gas is directly proportional to the flow of blood past the lungs and subsequently provides an estimate of pulmonary capillary blood flow (Qc), or Q. The SensorMedics® Corporation (Yorba Linda, CA) has developed a single-breath acetylene (C₂H₂) technique (SensorMedics Vmax 229TM), which includes a simple device to linearize expiratory flow rate by increasing the time by which the sensors can measure the disappearance of the marker gas and improve quantification. The purpose of this investigation was to determine the reproducibility of the C₂H₂ single-breath technique during ramping exercise testing with the addition of a starling resistor in 11 apparently healthy, sedentary volunteers (7 male and 4 female). Subjects performed three maximal ramping exercise test sessions over a 6-week period and Qc was measured at rest and at three time points during the exercise test. The C₂H₂ single-breath Qc measurement technique was shown to be repeatable when systematically related to VO₂ (Qc/VO₂ relation highly correlated r² = 0.72-.74), but slightly lower than previously reported. Means and 95% confidence intervals revealed the precision of the technique over repeated testing days. This method was able to capture Qc measurements at intensities greater than 75% VO₂pk in all subjects with the use of the Starling resistor. Bland-Altman plots reveal Qc measures to be about 50% more variable than highly reproducible measures such as VO₂ and HR. Intraclass reliability coefficients (r) found through repeated measures ANOVA were found to perform low (rx,x= -0.11-0.31) from rest throughout all intensities of exercise. This device is limited in the ability of the sensors to accurately analyze Qc with subjects who are unfamiliar and have difficulty with the single-breath maneuver. Such instances make it difficult for objective, accurate determinations to be made by the clinician. The C₂H₂ single-breath method was found to capture Qc at higher intensities and a high level of precision with the addition of the starling resistor. However, more evidence needs to be analyzed before use of this device can be put into clinical practice. / Master of Science

The recent trend in bioenergy feedstock development focuses on the use of large-statured perennial grasses that pose a relatively high risk of becoming invasive species due to the similarity in desirable agronomic traits with those of many of our worst invaders. Thus, it would be prudent to evaluate the potential ecological benefits and consequences of widespread cultivation of potentially invasive species. Miscanthus sinensis and its sterile daughter species, Miscanthus × giganteus, are two prominent bioenergy feedstock candidates due to their low input requirements and significant biomass production in a broad range of growing conditions. Despite being an extremely popular ornamental grass, and naturalizing in over half of US states, little is actually known about the biology, ecology and niche requirements of M. sinensis. Thus, the objective of our research is to characterize extant M. sinensis populations, and evaluate the niche requirements, especially in terms of the commonly limiting resources of light and soil moisture. In order to better assess the risk of M. sinensis (and subsequently M. × giganteus) cultivation, we surveyed 18 naturalized populations across the east coast to characterize habitat preferences, population structure, and plant performance across a latitudinal gradient. We found the vast majority of M. sinensis populations occurred in areas of high and low resource availability (e.g. soil nutrients and light) along roadsides and forest edges, with outlier individuals found in forest understories. We conducted a greenhouse study to compare shade and soil moisture tolerance among common ornamental cultivars and naturalized populations, where we found enhanced plant growth and vigor in naturalized biotypes compared to ornamentals across varying levels of shade. We also found that both naturalized and ornamental biotypes were not significantly affected by soil moisture stress, and thus express significant drought tolerance. Finally, we investigated the temperature and moisture requirements of M. sinensis seeds and determined a base temperature of approximately 8"C, as well as variable moisture and time to germination requirements between varieties and seed sources. These basic ecological studies will help refine and support future evaluations and weed risk assessments of both Miscanthus sinensis and M. × giganteus, which is critical in prevention of major ecological invasions. / Master of Science in Life Sciences

Yes / Purpose: Despite positive responses in phase II clinical trials, the bioreductive prodrug apaziquone failed to achieve statistically significant activity in non-muscle invasive bladder cancer in phase III trials. Apaziquone was administered shortly after transurethral resection and here we test the hypothesis that haematuria inactivates apaziquone. Methods: HPLC analysis was used to determine the ability of human whole blood to metabolise apaziquone ex vivo. An in vitro model of haematuria was developed and the response of RT112 and EJ138 cells following a 1-h exposure to apaziquone was determined in the presence of urine plus or minus whole blood or lysed whole blood. Results: HPLC analysis demonstrated that apaziquone is metabolised by human whole blood with a half-life of 78.6±23.0 min. As a model for haematuria, incubation of cells in media containing up to 75% buffered (pH 7.4) urine and 25% whole blood was not toxic to cells for a 1-h exposure period. Whole blood (5% v/v) significantly (p<0.01) reduced the potency of apaziquone in this experimental model. Lysed whole blood also significantly (p<0.05) reduced cell growth, although higher concentrations were required to achieve an effect (15% v/v). Conclusions: The results of this study demonstrate that haematuria can reduce the potency of apaziquone in this experimental model. These findings impact upon the design of further phase III clinical trials and strongly suggest that apaziquone should not be administered immediately after transurethral resection of non-muscle invasive bladder cancer when haematuria is common. / Financial support from Spectrum Pharmaceuticals Inc. for the conduct of the experiments.

Thesis (MSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Invasive alien plants (IAPs) are known for their detrimental impacts on biodiversity and ecosystem goods and services. A substantial body of research has contributed to our understanding of their impacts on ecology. In comparison the socio-economic aspects of IAPs, are not well understood. Additionally, valuation practises have usually excluded the positive and the non-monetary impacts (benefits and uses) that IAPs hold for local livelihoods. Holistic valuation has been regarded as imperative for decision-making and managerial frameworks. A study was conducted in Elim on the southern Cape coast of the Agulhas Plain, South Africa, which aimed to explore the various impacts of IAPs on the livelihoods of rural land-users. Individual qualitative interviews were conducted face to face with landholders (referred to as farmers) (N = 12) and individuals from the economically marginalized community (referred to as marginalized community) (N = 12). The grounded theory approach to data analysis was used and results of the coding method used were displayed by means of superscripts. Results indicate that farmers were aware of broader uses of IAPs although they themselves did not utilise them as extensively as members of the marginalized communities. Invasive alien and problem plants that held value for both land-users were not perceived as being „invasive‟. Invasive alien plants were believed to have detrimental impacts on biodiversity and ecosystems goods and services which support people‟s livelihoods. Alien clearing programmes such as Working for Water (WfW) and LandCare have done much to alleviate the socio-economic burden of unemployment in this marginalized community. Aside from the social development aims set out by WfW (i.e. employment of low-income communities, poverty alleviation and skills training), knock-on social development benefits (e.g. feelings of pride, responsibility and awareness as well as conflict management skills) were also realised by individuals from the marginalized community that were previously employed by the programme. Farmers regarded alien clearing and management as a process that demands excessive time, energy and financial resources. On single occasions it was found that farmers employed methods other than the conventional clearing and management strategies (e.g. livestock that feed on IAPs and giving refuse IAP biomass from clearing and felling to neighbouring poor communities). No clear consensus was reached about regarding alien clearing and management but more support is desired from government. Working for Water relies on private landholders for alien clearing as it is required by law. This study emphasizes that stronger relationships between government and private landholders as well as more substantial incentives to clear IAPs on private land are prerequisites if required outcomes are to be achieved. Educating society at large about the detrimental impacts of IAPs is fundamental. Additionally, informing landholders on effective alien clearing methods and policies and legislation pertaining to it are key activities for the South African government. Finally, clearing and management programmes need to consider the benefits that local land-users obtain from IAPs when prioritising areas for the management of alien vegetation. / AFRIKAANSE OPSOMMING: Uitheemse indringerplante (UIPe) is bekend vir die nadelige gevolge wat hulle vir biodiversiteit en ekosisteem goedere en dienste inhou. ʼn Aansienlike liggaam van navorsing het bygedra tot ons begrip van die impak daarvan op ekologie. In teendeel, die sosio-ekonomiese aspekte van UIPe word egter nie goed verstaan nie. Daarbenewens, evalueringspraktyke het gewoonlik die positiewe en nie-monetêre impakte (voordele en gebruike) wat UIPe vir plaaslike lewensbestaan hou, uitgesluit. Holistiese evaluering word as noodsaaklik beskou vir besluitneming en bestuursraamwerke. ʼn Studie was uitgevoer in Elim op die Suid-Kaapse kus van die Agulhas-vlakte, Suid-Afrika. Die doel was om die verskillende aspekte van UIP impakte op die lewensbestaan van landelike grondgebruikers aan te spreek. Individuele kwalitatiewe onderhoude is van aangesig tot aangesig gevoer met grondeienaars (na wie verwys word as boere) (N = 12) en individue van die ekonomies gemarginaliseerde gemeenskap (na wie verwys word as gemarginaliseerde gemeenskap) (N = 12). Die gegronde teorie metode tot data analise was gebruik en die resultate van die kodering metode is vertoon deur middel van boskrifte. Resultate dui daarop dat boere bewus was van ʼn wyer reeks van gebruike van UIPe alhoewel hulle dit nie so ekstensief benut het soos die lede van die gemarginaliseerde gemeenskappe nie. Uitheemse en probleem plante wat waarde gehou het vir beide landgebruikers,was nie soseer beskou as „indringers‟ nie. Daar was geglo dat UIPe nadelige impakte het op biodiversiteit en ekosisteme goedere en dienste wat mense se lewensbestaan ondersteun. Programme soos Werk vir Water (WvW) en LandCare wat fokus op die uitroeiing van UIPe, het baie gedoen om die sosio-ekonomiese laste as ʼn gevolg van werkloosheid in hierdie gemarginaliseerde gemeenskap te verlig. Benewens die sosiale ontwikkelings doelwitte uiteengesit deur WvW (o.a. indiensneming van lae-inkomste gemeenskappe, armoedeverligting en vaardigheidsopleiding), is daar ook domino-voordele (bv. gevoelens van trots, verantwoordelikheid en bewustheid sowel as konflik bestuursvaardighede) aangaande sosiale ontwikkeling ervaar deur individue van die gemarginaliseerde gemeenskap wat voorheen in diens van die program was. Boere beskou die uitroeiing en bestuur van UIPe as ʼn proses wat oormatige tyd, energie en finansiële hulpbronne vereis. Op enkele geleenthede was dit gevind dat boere gebruik maak van metodes anders as die konvensionele skoonmaak-en bestuurs strategieë (bv. vee wat voed op UIPe en biomassa wat na afloop van skoonmaak aan die naburige arm gemeenskappe gegee word). Geen duidelike konsensus is bereik met betrekking tot die uitroeiing en bestuur van UIP nie, maar meer ondersteuning van die regering word verlang. Werk vir Water maak staat op private grondeienaars vir die uitroeiing van UIPe. Hierdie studie beklemtoon dat sterker verhoudings tussen die regering en private grondeienaars sowel as meer aansienlike aansporings om UIPe op private grond skoon te maak ʼn voorvereiste is as verwagte uitkomste bereik wil word. Opvoeding van die breër gemeenskap oor die nadelige impakte van UIPe is fundamenteel. Om grondeienaars in te lig oor effektiewe UIP verwyderingsmetodes asook beleide en wetgewing met betrekking daartoe, is belangrikste aktiwiteite vir die Suid-Afrikaanse regering. Ten slotte, skoonmaak- en bestuursprogramme moet oorweging skenk aan die voordele wat plaaslike landgebruikers put uit UIPe wanneer daar geprioritiseer word vir gebiede vir die bestuur van indringerplante.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Invasive arthropod predators are one of the largest and most diverse groups of invasive insects in the world. Many are generalist predators, with cosmopolitan distributions due to their use as biological control agents in agriculture. Harmonia axyridis (Coleoptera: Coccinellidae), an invasive arthropod predator species native to Asia, which now has a world-wide distribution. It is considered one of the most successful biological control predator species and is generally considered to be economically beneficial. However, negative effects have recently emerged in agricultural and natural systems. Harmonia axyridis poses a threat to biodiversity as it outcompetes native species for food resources. It can also feed directly on native predatory arthropods that disrupt natural ecosystem processes. Their movement in-and-out of agricultural landscapes may depend on food availability with natural vegetation alongside agricultural areas often utilised for refuge and alternative food resources. This beetle has also been recorded in urban areas. The aim of this study was to determine how the invasive H. axyridis beetle uses the local landscape in the Western Cape province, South Africa, and to determine its threat to native species. I sampled urban landscapes, vineyards, natural vegetation/vineyard edge zones and pristine natural areas for arthropods every second month using a suction sampler. Data collected included the abundance and diversity of H. axyridis, herbivores, local predators and non-Harmonia ladybeetles. Most H. axyridis were collected in urban areas during all sampling periods. Highest abundance was recorded in May and July (winter). This indicates that urban areas were the preferred landscape feature and that these act as ovipositing areas, particularly as larval H. axyridis were also only collected in urban areas. Significantly, vineyards and natural vegetation had very low abundance of H. axyridis, questioning their value as a biological control agent in this region. Harmonia axyridis had a negative effect on the overall local arthropod community, as well as the predator and herbivore guilds, although it was positively correlated with the abundance of non-Harmonia ladybeetles. This suggests that H. axyridis and non-Harmonia ladybeetles are responding to the same resources in these landscapes. A negative correlation found between H. axyridis and the abundance of predators is most likely due to competition for the same resources (e.g. prey items). These negative impacts, along with their negligible value as biological control agents in agriculture, suggest that a programme should be implemented to control this invasive species. More specifically, control should be aimed in urban areas during winter when and where the species aggregates and when larvae are present. / AFRIKAANSE OPSOMMING: Geleedpotige roofdiere is een van die grootste en mees diverse groepe van uitheemse insekte in die wêreld. Die meeste is veelsydige roofdiere, met wêreldwye verspreiding te danke aan hul gebruik as biologiese beheer agente in landbou gebiede. Byvoorbeeld, Harmonia axyridis (Coleoptera: Coccinellidae), 'n indringer geleedpotige roofdier spesies inheems aan Asië, het nou 'n wêreldwye verspreiding. Dit word beskou as die mees suksesvolle roofdier spesies wat gebruik word vir biologiese beheer en word oor die algemeen beskou as ekonomies voordelig. Negatiewe effekte was onlangs aangeteken beide in landbou gebiede en natuurlike areas. Harmonia axyridis hou 'n bedreiging in vir inheemse biodiversiteit as dit inheemse spesies uitkompeteer vir voedsel bronne. Dit kan ook direk voed op plaaslike roofsugtige geleedpotiges wat trofiese vlakke ontwrig en uiteindelik, biodiversiteit. Hulle beweging in-en-uit landbou landskappe kan gekoppel word aan die beskikbaarheid van voedsel, en gebruik natuurlike plantegroei langs landbou gebiede dikwels as 'n toevlugs oord en area vir alternatiewe voedsel bronne. Harmonia axyridis word ook in stedelike gebiede aangeteken. Die doel van hierdie studie was om te bepaal hoe die indringer Harlekynkewer die plaaslike landskap gebruik met die fokus op wingerde in die Wes-Kaap provinsie van Suid-Afrika, en tweedens om die bedreiging wat hierdie kewer moontlik vir inheemse spesies te bepaal. Ek het arthropoda in stedelike landskappe, wingerde, natuurlike plantegroei / wingerd rand sones en ongerepte natuurlike areas elke twee maande met behulp van 'n D-vac versamel. Monsters was ontleed deur gebruik te maak van die getalle van H. axyridis, herbivore, plaaslike roofdiere en nie-Harmonia liewenheers kewers. Die meeste H. axyridis was in stedelike gebiede versamel gedurende al die seisoene, maar meeste individue was gedurende Mei en Julie (winter) versamel. Hierdie toon dat stedelike gebiede die voorkeur-landskappe is vir hierdie kewers en dat hierdie gebiede opgetree as eierleggende gebiede, veral omdat larwes van H. axyridis slegs in hierdie gebiede aangeteken was. Wingerde en die natuurlike plantegroei het baie lae getalle H. axyridis gehuisves wat hul waarde as biobeheermiddel bevraagteken. Harmonia axyridis het 'n negatiewe uitwerking op die algehele plaaslike geleedpotige gemeenskappe gehad, asook op die die roofdier en herbivoor gildes, maar hul getalle was positief gekorreleer met die getalle van nie-Harmonia liewenheerskewers. Dit dui daarop dat H. axyridis en nie-Harmonia liewenheerskewers beide reageer op dieselfde hulpbronne in hierdie landskappe. 'n Negatiewe korrelasie was gevind tussen die getalle van H. axyridis en die getalle van ander predatoriese geleedpotiges at waarskynlik te danke was aan mededinging tussen hierdie groepe vir dieselfde hulpbronne (bv prooi). Hierdie negatiewe invloede, asook hul verminderde waarde as biobeheeragente in die landbou, dui daarop dat 'n program in werking gestel moet word om hierdie indringerspesies te beheer. Meer spesifiek, beheer moet gedurende die winter en in stedelike gebiede geskied, waar en wanneer hierdie spesie op sy volopste is en waar larwes teenwoordig is.

Due au champignon Aspergillus fumigatus, l’aspergillose pulmonaire invasive représente une grave menace pour les individus souffrant d’immunodépression sévère. En parallèle d’un diagnostic manquant de spécificité, les traitements actuels présentent une forte toxicité. Ces travaux se sont dans un premier temps intéressés au développement d’anticorps thérapeutiques dirigés contre les protéines pariétales Chitin ring formation du champignon. Le ciblage de ces protéines impliquées dans la croissance fongique a permis la mise en évidence d’effets modérés in vitro, et ont induit, in vivo, un recrutement significatif de cellules immunitaires impliquées dans la défense anti-aspergillaire. Dans un second temps, ces travaux se sont intéressés au ciblage du microenvironnement et de la réponse de l’hôte au cours de l’aspergillose, afin de mieux comprendre les processus physiopathologiques induits au cours de la maladie, et de permettre l’identification de nouveaux biomarqueurs et cibles thérapeutiques. L’utilisation de la spectrométrie de masse iTRAQ®, chez des rats et des manchots, a permis la mise en évidence de plusieurs voies de signalisation surreprésentées. Ces travaux se sont également intéressés à la caractérisation immunologique d’un modèle rat d’API. En plus de la mise en évidence des effets du champignon sur le recrutement de certaines populations de cellules immunitaires, l’utilisation de l’iTRAQ® a permis la mise en évidence de la surexpression de l’interleukine-33 et de son récepteur ST2 au cours de la maladie. Ces travaux ouvrent d’intéressantes perspectives dans la mise en place de nouveaux traitements contre l’API. / Caused by the fungus Aspergillus fumigatus, invasive pulmonary aspergillosis is a serious threat for individuals suffering from severe immunosuppression. In parallel of a diagnosis lacking specificity, current treatments present a high toxicity. This work first focused on the development of therapeutic antibodies directed against cell wall proteins Chitin ring formation of the fungus. Targeting of these proteins involved in fungal growth highlighted moderate effects in vitro, and induced, in vivo, a significant recruitment of immune cells involved in anti-aspergillary defense. In a second time, this work focused on targeting the microenvironment and the host response during aspergillosis, in order to better understand pathophysiological processes induced during the disease, and allow the identification of new biomarkers and therapeutic targets. Use of iTRAQ® mass spectrometry in rat and penguins allowed the identification of several overrepresented signaling pathways. This work also focused on the immune characterization of a rat model of IPA. In addition of highlighting the effects of the fungus in the recruitment of some immune cell populations, use of iTRAQ® exhibited an overexpression of interleukin-33 and its receptor ST2 during the disease. Overall, this work is bringing interesting insights in the establishment of new treatments against IPA.

MSc., Faculty of Science, University of the Witwatersrand, 2011 / This research investigated the susceptibility of South African indigenous aquatic plants to competition from invasive species, using the competitive interactions of two sets of aquatic plants as a potential indicator. These interactions were studied in two separate experiments: the submersed weeds, Hydrilla verticillata (L.F.) Royle (Hydrocharitaceae) and an indigenous species, Lagarosiphon major (Ridley) Moss (Hydrocharitaceae) and; the floating weeds, Azolla filiculoides Lamarck (Azollaceae) and the indigenous Spirodela polyrhiza (L.) Schleid (Lemnaceae). Plants were grown under differing nutrient levels, and in an addition series of eight different densities, using the reciprocal yield model to estimate competitive ability. The invasive Hydrilla outcompeted Lagarosiphon in terms of mean length, dry mass, and survival. Major algal infestation in the high nutrient level of the Hydrilla/Lagarosiphon experiment altered light and nutrient conditions, which may have played a significant role in the lack of establishment of Lagarosiphon and the poor growth performance of Hydrilla. The invasive Azolla and indigenous Spirodela both performed well in terms of plant mass and increase in number. While Azolla was affected by intraspecific competition, it showed a steady increase in growth and multiplication with an increase in nutrients. The individual mass of Spirodela plants was highest in the low nutrient level, and multiplication rates were greatest in the high nutrient level. Results indicate that the susceptibility of indigenous plants may be increased in highnutrient systems, and that a continuous monitoring programme of aquatic alien species is vital in protecting our indigenous plants from extinction. This research recommends that the method of investigating competitive interactions between alien and indigenous plants be repeated with a variety of aquatic plants, as a means of anticipating susceptibility to invasions.

Endometriose (EM) ist eine häufige gynäkologische Erkrankung, die bei betroffenen Frauen unter anderem mit chronischen Unterleibsschmerzen und Unfruchtbarkeit einhergeht (VALLE 2002). Bisher war es bei den zur Forschung verwendeten Modelltieren für EM (z.B. Rhesusaffe, ZONDERVAN et al. 2004; Weißbüschelaffe, EINSPANIER et al. 2006) nicht möglich festzustellen, ob bei ihnen schmerzhafte Beeinträchtigungen durch die Erkrankung bestehen. Um die Auswirkungen neuer Therapeutika auf das Wohlbefinden der Patientinnen bewerten zu können, werden Methoden benötigt, mit denen EM bedingte Beeinträchtigungen der Modelltiere dargestellt werden können. Daher war es das Ziel dieser Studie, bei einem Primatenmodell für EM, dem Weißbüschelaffen, neue nicht invasive Testsysteme zu etablieren, die zur Darstellung von EM bedingten Schmerzen und Beeinträchtigungen geeignet sind. Unter der Annahme, dass schmerzhafte Erkrankungen das Verhalten (WALLACE et al. 1990), die Beweglichkeit (FLECKNELL 1986) sowie die kognitiven Fähigkeiten (SMITH et al. 2006) der betroffenen Tiere beeinträchtigen können, wurden drei nicht invasive Testsysteme auf ihre Eignung untersucht, Schmerzen bei an EM erkrankten Weißbüschelaffen im Vergleich zu Kontrolltieren darzustellen. Zur Untersuchung des Verhaltens wurde die Videoüberwachung, für die motorischen Fähigkeiten der Futterbaum (modifiziert nach ROBERTS et al. 1993) und für die kognitiven Fähigkeiten der Wisconsin General Test Apparatus (WGTA, HARLOW 1949) sowie der Futterbaum verwendet. Im ersten Abschnitt dieser Studie wurde das Normalverhalten von neun Weißbüschelaffenpaaren per Videokamera über den gesamten Tagesverlauf von zwölf Stunden aufgezeichnet und unter anderem in Bezug auf Aktivität, soziale und eigene Körperpflege sowie Futter- und Wasseraufnahme analysiert. Der Verlauf der Tagesaktivität zeigte drei Maxima zwischen 7:00 und 8:00 Uhr, 11:00 und 12:00 Uhr sowie 14:00 und 15:00 Uhr, dabei war die ansteigende Aktivität als Futtersuchverhalten vor den Mahlzeiten zu werten. Das im ersten Abschnitt der Studie dargestellte Aktivitätsmuster wurde im zweiten Abschnitt verwendet, um die Versuche mit WGTA und Futterbaum besser in den Tagesverlauf der Tiere einzuordnen und darüber ihre Kooperativität zu steigern. Die Tiere führten die Tests immer zur gleichen Tageszeit durch, deshalb wurde somit eine optimale Vergleichbarkeit und Homogenität der Ergebnisse gewährleistet. Bei der Auswertung der Videodokumentation im zweiten Abschnitt dieser Studie zeigte sich, dass erkrankte Weibchen ihren Partner im Gegensatz zu den Kontrolltieren gar nicht pflegen (p=0,029) und die Aktivität der erkrankten Weibchen zwar deutlich, aber nicht signifikant (p=0,057) verringert war. Diese verringerte Aktivität ist möglicherweise ein Hinweis auf Schmerzen der an EM erkrankten Weibchen, während die nicht vorhandene soziale Körperpflege den partnerschaftlichen Problemen betroffener Frauen entsprechen könnte. In den ersten beiden kognitiven Tests mit dem WGTA führten die erkrankten Weibchen signifikant weniger Versuche pro Tag durch als die Kontrolltiere (p=0,006/ p=0,008). Darüber hinaus benötigten die erkrankten Tiere signifikant mehr Versuche, um den ersten Test zu verstehen (p=0,008). Diese Unterschiede zu den Kontrolltieren ließen sich in den folgenden drei Versuchsabschnitten nicht mehr nachweisen. Daraus lässt sich ableiten, dass die Weibchen mit EM sich schlecht auf neue Anforderungen einstellen und sich weniger lange auf eine gestellte Aufgabe konzentrieren können. Nach der International Primatological Society (MC CANN et al. 2007) kann eine verminderte Fähigkeit, sich auf neue Situationen einzustellen, als Anzeichen für Beeinträchtigungen gewertet werden. Bei der Auswertung der Futterbaum Testreihen, in denen sowohl kognitive als auch motorische Fähigkeiten der Tiere mit einer Art „Kletterbaum“ überprüft wurden, ergaben sich demgegenüber keine signifikanten Unterschiede zwischen der EM-Gruppe und den Kontrolltieren. Zusammenfassend eignen sich die Videodokumentation und der WGTA zur Darstellung von Beeinträchtigungen bei an EM erkrankten Weißbüschelaffen. Die beiden Testsysteme können in folgenden pharmakologischen Studien verwendet werden, um erstmals die Auswirkungen neuer Therapeutika auf das Wohlbefinden der Modelltiere zu bewerten. Zusätzlich ermöglichen die Ergebnisse dieser Studie ein Refinement (RUSSELL und BURCH 1959), da die bisher verwendeten invasiven Methoden (Laparoskopie, Laparotomie) zur Bewertung des Verhaltens der EM Läsionen unter einer Therapie ergänzt und sogar ersetzt werden könnten. / Endometriosis (EM) is a common gynecological disease, which is known to cause chronic pelvic pain and infertility in women (VALLE 2002). Up to now, it was not possible to assess, whether the animal models for research (e.g. rhesus macaque, ZONDERVAN et al. 2004; common marmoset, EINSPANIER et al. 2006) suffer from pain or impairments due to the disease. Therefore, new test systems are needed to obtain pain and discomfort in animal models for EM to enable the validation of new therapeutic agents with a view to the patients well being. It was the aim of this study, to establish new non invasive test systems to investigate signs of discomfort in an animal model for EM, the marmoset monkey. Assuming that painful diseases can influence the behaviour (WALLACE et al. 1990), the mobility (FLECKNELL 1986) and the cognitive abilities (SMITH et al. 2006) of animals, three non invasive test systems were reviewed for their ability to detect EM associated pain in common marmosets. They were based on behaviour (videotaping), mobility and exploratory behaviour (food tree, modified after ROBERTS et al. 1993) and cognitive abilities (Wisconsin General Test Apparatus (HARLOW 1949) and food tree). In the first part of this study, the daily activity patterns, allo- and autogrooming as well as water and food intake of nine common marmoset couples were monitored over a 12-hour light phase by video recording. The animals showed a trimodal course of activity per day with maxima from 7:00-8:00h, 11:00-12:00h and 15:00-16:00h. These activity maxima represented foraging behaviour, as they were followed by frequent food intake phases. The knowledge of the daily activity patterns allowed to optimize the experimental conditions for the tasks with the food tree and the Wisconsin General Test Apparatus (WGTA; HARLOW 1949) in the second part of this study. As every animal solved the tasks at the same time of day, the comparability and homogeneity of the results were optimized. By analysing the video documentation in the second part of this study, the females with EM, in contrast to the control females, did not show any social grooming behaviour (p=0.029). Furthermore, their activity level was almost significantly decreased (p=0.057). This reduced activity could indicate towards pain in the diseased females, while the lack of social grooming is similar to partnership problems in diseased women. The WGTA tasks revealed, that the females with EM performed significantly less trials per day in the first two settings (p=0.006/ p=0.008) and needed more trials to solve the first setting than the control animals (p=0.008). Those differences between diseased females and control animals were not detectable in the following three settings of the WGTA tasks. These results demonstrate, that EM affected marmosets have difficulties to concentrate on cognitive tasks and to cope with new situations. According to the International Primatological Society (MC CANN et al. 2007), these difficulties to cope with new situations can be interpreted as signs of distress. The food tree, a kind of jungle gym, was used to assess the animals` cognitive abilities as well as their mobility, but there were no significant differences between the EM diseased females and the control animals. In conclusion, the videotaping and the WGTA are suitable methods to demonstrate signs for impairments due to EM in marmoset monkeys. In following pharmacological studies, both test systems will allow to evaluate the benefit of new therapeutic agents on the animal model`s well being. In addition, the results of this study can help to refine procedures by replacing invasive methods like laparotomy according to the Refinement of RUSSELL and BURCH (1959).

Weltweit ist eine rasante Zunahme des Artensterbens auch bei der Klasse Aves zu verzeichnen. Durch Umweltveränderungen und unzählige andere menschliche Einflüsse (z.B. illegaler Handel) ist fast ein Drittel der Papageienpopulation (Psittaciformes) vom Aussterben bedroht. Eine Möglichkeit, diesen Trend aufzuhalten, besteht in der gezielten und effektiven Nachzucht bedrohter Arten in der Obhut von Menschen mit dem Ziel der späteren Wiederauswilderung. Leider waren bisher solche Bemühungen oft erfolglos. Dies ist der Tatsache geschuldet, dass fundierte wissenschaftliche Untersuchungen zum Reproduktionsstatus nahezu fehlen und ein Transfer der hormonanalytischen Methoden vom Säugetier zum Vogel nicht so einfach möglich ist. Ziel der vorliegenden Arbeit war die Etablierung von Methoden zur Hormonbestimmung in verschiedenen Medien beim männlichen Papagei, mit deren Hilfe eine Einordnung des Reproduktionsstatus möglich ist. Im Vordergrund standen dabei vor allem nicht-invasive Techniken, die mit deutlich geringerem Stress für die Tiere verbunden sind. Als Vertreter für die Gruppe der Papageienartigen wurden Wellensittiche (Melopsittacus undulatus, n=11), Nymphensittiche (Nymphicus hollandicus, n=9) und Halsbandsittiche (Psittacula krameri, n=7) ausgewählt und endokrinologisch untersucht. Diese Vögel wurden vom Bundesverband für fachgerechten Natur- und Artenschutz e.V. (BNA) zur Verfügung gestellt. Die Hormonanalyse erfolgte in den regelmäßig gesammelten Blut-, Speichel- und Kotproben der männlichen Psittaziden. Neben dem Sexualhormon Testosteron wurden die Blutspiegel des Stresshormons Corticosteron bestimmt, da eine mögliche Beziehung zwischen Stress und Testosteronsekretion besteht. In den Vorversuchen wurden zunächst geeignete Methoden für die Hormonanalyse in den verschiedenen Medien beim Papagei entwickelt. Zur Extraktion von Testosteron aus den Blut- und Kotproben erwies sich Diethylether als gut geeignet, während Speichel direkt ohne Extraktion im Testosteron-Enzymimmunoassay eingesetzt wurde. Da Papageien hauptsächlich primär konjugierte Testosteronmetabolite (85%) ausscheiden, wurden die Kotproben nach dem Trocknen und Einwiegen mit Hilfe der β-Glucuronidase/Arylsulfatase hydrolysiert und dann mit Diethyether extrahiert. Die Corticosteronanalyse im Plasma der Papageien erfolgte durch Fällung der Proteine mittels absolutem Alkohol und Einsatz der Plasmaextrakte in den Radioimmunoassay. Bei den verschiedenen Papageienspezies traten während der Untersuchungsperiode vergleichbare Plasma-Testosteronkonzentrationen auf. Die höchsten Plasmaspiegel (0,36 ng/ml) wiesen die Wellensittiche im März 2007 auf, ähnliche Konzentrationen (0,34 ng/ml) erreichten die Nymphensittiche im Februar 2007. Demgegenüber zeigten die Halsbandsittiche geringere maximale Konzentrationen (0,26 ng/ml) im November 2007. Im Kot der Papageien wurden erwartungsgemäß deutlich höhere Testosteronwerte gemessen, weil die Steroidausscheidung im Kot kumulativ eine zurückliegende Zeitperiode und Blut den aktuellen Hormonstatus zum Zeitpunkt der Probennahme widerspiegelt. Bezüglich der Haltungs- und Umweltbedingungen zeigten die Papageien maximale Testosteronspiegel während der kalten Jahreszeit, bei kurzer (Halsbandsittich) bzw. zunehmender Tageslichtlänge (Wellen- und Nymphensittich) und Haltung in der Innenvoliere. Dabei spielte die Niederschlagsmenge in der gemäßigten Klimazone offenbar weniger eine Rolle in der aviären Reproduktion. Die Verlaufsuntersuchungen des Stresshormons Corticosteron im Blut der Papageien ergaben speziesspezifische Unterschiede hinsichtlich der Konzentrationen, zeitlichen Verläufe und in Bezug zum Testosteronspiegel. Auffällig hohe Corticosteronkonzentrationen zeigten die nicht domestizierten Halsbandsittiche (15,9 – 35,6 ng/ml) im Vergleich zu den Wellensittichen (1,76 – 17,1 ng/ml) und Nymphensittichen (4,06 – 12,1 ng/ml), bei denen sich vermutlich im Laufe der Domestikation eine verminderte Sensibilität der HPA-Achse ausgebildet hat. In Bezug zum Plasma-Testosteronspiegel war bei den Wellen- und Halsbandsittichen ein gegenläufiger Zusammenhang erkennbar, wobei beim Nymphensittich eine positive Korrelation zwischen der Testosteron- und Corticosteronkonzentrationim Plasma bestand. Zusammenfassend lässt sich sagen, dass durch die Testosteronanalyse in Kot und Plasma eine Einordnung des Reproduktionsstatus beim Wellen-, Nymphen- und Halsbandsittich möglich ist. Es ist jedoch sinnvoll, Proben zu verschiedenen Zeitpunkten vergleichend zu betrachten, um die tierindividuellen Unterschiede zu berücksichtigen. Offensichtlich stehen die Steroidhormone der Gonaden und der Nebenniere zueinander in Beziehung, sodass auch Corticosteron in der Reproduktionsdiagnostik von männlichen Psittaziden Anwendung finden sollte.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 160-166).