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Showing 11 to 18 of 18 (0.076 seconds)Spelling suggestions: "subject:"animal desting"" "subject:"animal ingesting""
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The evaluation of bone strengthJain, Atul January 2008 (has links)
Bone drilling is a major part of orthopaedic surgery performed during the internal fixation of fractured bones. At present, information related to drilling force, drilling torque, rate of drill bit penetration and drill bit rotational speed is not available to orthopaedic surgeons, clinicians and researchers as bone drilling is performed manually. This research demonstrates that bone drilling force data if recorded in-vivo, during the repair of bone fractures, can provide information about the strength/quality of the bone. Drilling force does not give a direct measure of bone strength; therefore it has been correlated with the shear strength and screw pullout strength to determine the efficacy in estimating the bone strength. Various synthetic bone material densities and animal bones have been tested to demonstrate the use of drilling force data. A novel automated experimental test rig, which enables drilling tests, screw insertion and screw pullout tests to be carried out in a controlled environment, has been developed. Both drilling and screw pullout tests have been carried out in a single setting of the specimen to reduce the experimental errors and increase repeatability of the results. A significantly high value of correlation (r² > 0.99) between drilling force & shear strength and also between drilling force & normalised screw pullout strength in synthetic bone material was found. Furthermore, a high value of correlation (r² = 0.958 for pig bones and r² = 0.901 for lamb bones) between maximum drilling force & normalised screw pullout strength was also found. The result shows that drilling data can be used to predict material strength. Bone screws are extensively used during the internal fixation of fractured bones. The amount of screw been tightened is one of the main factor which affects the bone-screw fixation quality. Over tightening of screw can result into the loss of bone-screw fixation strength, whereas under tightening can result in the screw loosening. Therefore, optimum tightening of the screw is important to achieve the maximum bone-screw fixation strength. At present, optimum tightening of the screw is entirely dependent upon the skill and judgment of the surgeon, which is predominantly based on the feel of the screw tightening torque. Various studies have been reported in the literature to develop an algorithm to set an optimum tightening torque value to be used in surgery. A method which is based on the use of rotation angle of the screw while tightening, rather than using screw insertion/tightening torque, to optimise the bone-screw fixation strength is proposed in this research. The effectiveness of the proposed method has been successfully demonstrated on the synthetic bone material using the designed test rig. The optimum angle for the tested screw was found to be 120° which is equivalent to 33% of the screw pitch.
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Caractérisation, étude du pouvoir antioxydant et du potentiel thérapeutique d'extraits de bactéroïdes thetaiotaomicron / Characterization, study of the antioxidant power and therapeutic potential of extracts of bacteroids thetaiotaomicronHochart-Behra, Anne-Cécile 08 July 2011 (has links)
Notre équipe vient de découvrir une méthode originale d’obtention d’extraits de Bacteroides thetaiotaomicron (E) qui préserve sa viabilité. Après culture anaérobie de ce commensal intestinal en milieu gélosé pauvre en facteurs de croissance, puis exposition à l’air, la bactérie semble posséder et générer dans E tout l’équipement de détoxication des espèces réactives de l’oxygène in vitro. Il laisse alors augurer d’un pouvoir thérapeutique à visée anti-inflammatoire.Objectifs et méthodes : Le but est d’abord de caractériser E, aux plans glucidique, lipidique et protéique. Dans ce dernier cas, il s’agit de séparer les protéines produites par la bactérie vivante et contenues dans E par électrophorèse bidimensionnelle et de les identifier par la technique des cartes peptidiques massiques. Les gels (n≥6) sont traités statistiquement (PDQuest®, Bio-Rad). Pour mieux localiser ces protéines dans la bactérie, elles sont comparées avec celles obtenues par destruction de B. thetaiotaomicron et identifiées dans la fraction cellulaire relative à la membrane bactérienne externe. Un travail de microscopie électronique est aussi entrepris pour visualiser les éventuels évènements intervenant pendant l’extraction.Le but est alors de vérifier, in vitro, l’effet antioxydant de l’extrait bactérien standardisé et d’en contrôler l’innocuité en modèles cellulaires utilisant le granulocyte neutrophile. L’effet thérapeutique anti-inflammatoire est ensuite recherché chez l’animal. L’action de E est d’abord évaluée en modèle murin d’inflammation cutanée auriculaire induite par dépôt de chlorure de benzalkonium, sous anesthésie générale. Des témoins positifs et négatifs de traitement et d’autres ne subissant pas d’irritation sont testés en parallèle. L’épaisseur des oreilles est mesurée toutes les heures pendant 5 h et des coupes histologiques d’oreilles, effectuées au bout de 2 h chez certains animaux. Deux colorations différentes permettent alors d’évaluer la quantité de mastocytes dégranulant localement.L’action de E, administré par voie intra-rectale (IR), est ensuite testée chez des souris subissant les premières phases d’un processus inflammatoire, en modèle de colite aiguë. Celle-ci est induite per os par du dextran sulfate sodium (DSS) ; elle évolue sur 8 jours. Sont considérés en parallèle des témoins positifs et négatifs de traitement et d’autres ne subissant pas de colite. Des scores cliniques et des scores histologiques de sévérité sont établis tous les jours de l’expérience. Des marqueurs de l’inflammation sont suivis dans les tissus murins après autopsie des animaux. [...] / Our team had discovered a new method to obtain extracts of Bacteroides thetaiotaomicron (E) which preserved its viability. This intestinal symbiont was anaerobically grown on an agar medium poorly supplemented in growth factors. After exposure to air, the bacterium seemed to possess and generate in E all the equipment able in vitro to detoxify reactive oxygen species. It let us expect a therapeutic power referred to anti-inflammatory properties.Objectives and methods: The aim was first to characterize E, in terms of carbohydrates, lipids and proteins. To achieve this last-mentioned goal, proteins contained in E coming from living bacteria were separated by two-dimensional electrophoresis and identified by the peptide mass fingerprinting technique. The gels (n ≥ 6) were statistically analyzed (PDQuest®, Bio-Rad). To find the origin of these proteins in bacteria, they were compared with those obtained by destruction of B. thetaiotaomicron (BT) and identified in the cell fraction containing the bacterial outer membrane proteins. Electron microscopy work was also undertaken to visualize any event occurring during extraction.The antioxidative effect of standardized E extracts was checked in vitro. E safety was also controlled in cell models using polymorphonuclear neutrophils. An E anti-inflammatory effect was then searched in animal models. E was first evaluated using a skin irritation mouse model. Inflammation was induced by benzalkonium chloride on ears of anesthetized mice. Positive and negative controls were treated in parallel. The ear thickness was measured every hour for 5 h and histological ear sections were performed after 2h for some animals. Two different staining methods enabled the enumeration of degranulating mast cells in ear sections.The effect of the bacterial extract was next tested locally by intrarectal (IR) instillations in mice undergoing the early stages of inflammation in a dextran sodium sulfate (DSS)-induced colitis. This acute model evolved over 8 days. In parallel, positive and negative animal controls underwent or not the colitis and were treated or not. Clinical and colonic histological severity scores were daily determined. Inflammation markers were measured in mouse colonic tissues after animal autopsy. [...]
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Development of a computational consensus model for the in silico prediction of the skin sensitising potential of organic chemicals in the context of REACHHillebrand, Marcus 27 September 2018 (has links)
Die Hautsensibilisierung (Typ 4 Hautallergie) nimmt in der Toxizitätsbewertung einen wichtigen Stellenwert ein, was u.a. daran zu sehen ist, dass sie unter dem europäischen Chemikaliengesetz REACH schon sehr früh, d.h. ab einer Jahrestonne, abgeprüft werden soll. Die Dissertation untersucht, ob die derzeit im Tierversuch stattfindende Toxizitätsprüfung durch computerchemische Methoden ersetzt werden kann. Dazu wurde eine Datenbank aus über 2000 Stoffen erstellt, aus der wichtige Unterschiede zwischen den eingesetzten Tiermodellen herausgelesen werden konnten. In den Untersuchungen trat auch zu Tage, dass – entgegen vorheriger Annahmen – die Bioverfügbarkeit, d.h. die Aufnahme von Substanzen über die Haut, im Tierversuch nur eine untergeordnete Rolle spielt. Zudem ist eine Abschätzung des hautsensibilisierenden Effekts von Stoffen anhand eines Read-across (Interpolation aus strukturähnlichen Verbindungen) und von Strukturalarmen (Substrukturelemente als Indikatoren für einen bestimmten Effekt) möglich. Wenn beide Ansätze im Rahmen einer Konsensmodellierung miteinander verschränkt werden, ergibt sich sogar eine gute Vorhersagestatistik. / Skin sensitisation (type 4 skin allergy) is an important parameter in the toxicity assessment of chemicals, which is underlined by the fact that it is evaluated even at the lowest tonnage (1 t/a), which can be registered under the european chemicals regulation (REACH). In this thesis it was investigated if the currently used animal models can be replace or refined with computational (in silico toxicological) methods. In this regard a data base consisting of about 2000 substances was build. With its data important differences between the currently applied animal tests could be derived. Furthermore, the investigation found that – in contrast to previous assumptions – the bioavailability of a chemical compound, i.e. the uptake via the skin, has only a minor impact on the test result of the evaluated animal models. Moreover, it was demonstated that the skin sensitising potential of chemicals can be predicted by read-across (interpolation with structurally similar substances) and with structural alerts (substructural elements which indicate a particular effect). Combining both prediction methods with consensus modelling lead to a good prediction regarding the question whether a particular chemical compound is a sensitiser or not.
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Untersuchungen zum Metabolom der Leber von Milchkühen während der Transitphase unter besonderer Berücksichtigung des Effekts einer metaphylaktischen Verabreichung von Butafosfan und Cyanocobalamin sowie Evaluation der Auswirkungen des intensiven Studienprotokolls auf Leistungs- und Gesundheitsmerkmale der StudientiereSnedec, Teja 30 October 2024 (has links)
Einleitung: Die Transitphase ist bei Milchkühen mit gravierenden Veränderungen im Metabolismus verbunden. Darüber hinaus ist sie mit Umstellungen im Haltungsumfeld verbunden, welche die Adaptationsmechanismen der Kühe beanspruchen. Aufgrund dieser Herausforderungen erhöht sich das Risiko für produktionsbedingte Erkran¬kungen. Die Leber übernimmt aufgrund ihrer vielfältigen Funktionen, u.a. als Hauptorgan des Stoffwechsels, eine besondere Rolle. Nach wie vor sind die zu Grunde liegenden pathophysiologischen Abläufe nicht vollständig ergründet. Neue Analysemethoden, wie die Metabolomics Technologie, ermöglichen tiefere Einsichten in Stoffwechselvorgänge und Ursachen für individuelle Unterschiede der Erkran¬kungswahrscheinlichkeit sowie die Wirkweise von metaphylaktischen bzw. therapeu¬tischen Maßnahmen. Die positiven Wirkungen von Butafosfan und Cyanocobalamin (BCC) hinsichtlich Ketoseprävention und Leistung wurden bereits aufgezeigt. Die zugrundeliegenden Wirkmechanismen sind jedoch unzureichend erforscht. Zur Erlan¬gung evidenzbasierter Erkenntnisse sind auch in der Buiatrik aktuell noch prospektive, randomisierte, verblindete Tierversuche nötig. Sie sind mit Risiken für die Gesundheit und Produktivitätsverlusten bei den Versuchstieren verbunden. Genaue Angaben zu Qualität und Quantität derartiger Ausfälle für Feldversuche gibt es allerdings kaum.
Ziele der Untersuchung: Die Dissertationsschrift hatte das Ziel, das Metabolom im Lebergewebe in Bezug zu klinischen und laborchemischen Merkmalen sowie zu Gesundheits- und Produktionsdaten von Milchkühen während der Transitphase zu charakterisieren. Weiterhin sollte der Effekt der metaphylaktischen Behandlung mit BCC auf das Leber-Metabolom evaluiert sowie die Auswirkungen eines intensiven Versuchsprotokolls auf die Gesundheit und Leistungskennzahlen erfasst werden.
Tiere, Material und Methoden: Aus einer Herde mit 660 Deutsch-Holstein-Kühen wurden im ersten Teil der Studie 87 gesunde Kühe einbezogen (Publikation 1). Diese wurden ab Tag 14 ante partum (Tag –14) bis Tag 49 post partum (Tag 49) täglich klinisch überwacht. An den Tagen –7 bis –5 und 1 bis 3 wurden die Kühe intravenös mit BCC in zwei Dosierungen (5 / 10 ml Catosal® pro 100 kg Körpermasse; 0,05 mg / ml Cyanocobalamin, 100 mg / ml Butafosfan; Bayer Animal Health GmbH, Leverkusen, Deutschland) bzw. Natriumchlorid-haltigem Placebo behandelt. Die statistische Analyse wurde mit multivariaten [partielle Diskriminanzanalyse der kleinsten Quadrate (PLS-DA)] und univariaten Methoden (lineares gemischtes Modell) durchgeführt. Den Kühen wurden mehrfach Blut- (n = 8), Lebergewebe- (n = 4) und Harnproben (n = 13) entnommen. Zu sieben Zeitpunkten wurde die Leber sonographisch untersucht bzw. die Rückenfettdicke vermessen. Sämtliche Gesundheits-, Leistungs- und Reproduk¬tionsmerkmale wurden digital im Programm Herde® (dsp-Agrosoft GmbH, Ketzin / Havel, Deutschland) dokumentiert. Im zweiten Teil der Studie wurden gesundheitliche Schäden, die potenziell mit den Versuchsmaßnahmen im Zusammenhang standen, erfasst und ausgewertet. Dazu wurden 206 Kühe als nicht manipulierte Vergleichstiere für die Gesundheits- und Produktionsmerkmale hinzugezogen (Publikation 2). Die Milchleistung
Ergebnisse: Insgesamt bestätigen die Ergebnisse stoffwechselassoziierte Veränder¬ungen im Metabolom während der Transitphase. Die Kühe wurden anhand derartiger Unterschiede des Leber-Metaboloms in drei Metabotypen (A – C) eingeteilt. Die Be¬handlung mit BCC wirkte sich unterschiedlich auf diese Stoffwechselprofile aus. Die Veränderungen im Leber-Metabolom deuten auf die Steigerung der Beta-Oxidation und den effizienteren Triacylglycerol-Export in der Leber hin. Dieser Effekt war auf phänotypische Merkmale beim Einsatz der höheren Dosis im Vergleich zur niedrigeren Dosis signifikant. Der deutlichste Behandlungseffekt wurde beim Metabotyp B am Tag 7 beobachtet. Für den zweiten Teil der Dissertation wurden die Folgen des durch¬geführten Tierversuches näher untersucht. Die meisten Schäden waren mit der Entnahme der Leberbiopsien assoziiert (Biopsiestelle: diffuse Entzündung der Bauch¬wand, erhöhte Echogenität im Lebergewebe). Die Milchleistung der Versuchskühe lag unter und die somatische Zellzahl über der der nicht-manipulierten Vergleichskühe (statistisch signifikant, P=0.001). Bei den Versuchskühen wurde eine geringere Totgeburtenrate erreicht. Der Versuch hatte keinen Einfluss auf die Überlebensdauer der Versuchstiere.
Schlussfolgerungen: Es konnten Kühe identifiziert werden, die aufgrund ihres Metabotyps während der Transitphase einem besonderen Risiko ausgesetzt waren (Metabotyp B). Für diese Risikotiere konnte eine dosisabhängige, positive Wirkung der Behandlung mit BCC auf den Gesundheitsstatus erzielt werden. Weiterhin zeigte sich, dass ein intensives Studienprotokoll bei Milchkühen im Herkunftsbetrieb unterschiedliche Auswirkungen auf Gesundheits- und Produktionskennzahlen haben kann. Diese Analyse trägt zur Abschätzung der Risiken derartiger Verfahren bei und kann somit hilfreich bei der Planung und Durchführung weiterer Studien sein.:1. EINLEITUNG 1
2. LITERATURÜBERSICHT 4
2.1 Die Transitphase bei Milchkühen 4
2.1.1 Physiologie der Adaptation 4
2.1.2 Das Lipomobilisationssyndrom 7
2.2 Untersuchungen des Metaboloms zur Ergründung pathophysiologischer Reaktionsnetzwerke in der Transitphase 10
2.2.1 „Omics“-Methoden 10
2.2.2 Metabolomics 11
2.2.3 Technische Durchführung 11
2.2.4 Anwendung in der Veterinärmedizin 12
2.3 Prinzipien pro- und metaphylaktischer Maßnahmen in der Transitphase 14
2.3.1 Zufuhr von Energieträgern 19
2.3.2 Beeinflussung des Pansenmikrobioms 19
2.3.3 Beeinflussung des Leberstoffwechsels 220
2.4 Auswirkungen von Studienprotokollen auf den Organismus von Versuchstieren 23
2.4.1 Evidenzbasierte Medizin 23
2.4.2 Evidenzbasierte Veterinärmedizin: Versuche am Tier 24
2.4.3 Belastungen durch Studienprotokolle 25
2.4.4 Beurteilung studienassoziierter Belastungen 26
2.5 Schlussfolgerungen aus der Literaturrecherche und Arbeitshypothesen 27
3. MATERIAL UND METHODEN 29
3.1 Studiendesign 29
3.1.1 Tierversuchsantrag und Präambel 29
3.1.2 Patientenmaterial 29
3.2 Spezielle Untersuchungsgänge der Kühe der Versuchsgruppe 30
3.2.1 Untersuchungen 30
3.2.2 Probenentnahme 30
3.2.3 Probenhandling und Analyse von Blut-, Leber- und Harnproben 32
3.2.4 Sonographische Untersuchung 321
4. PUBLIKATION 1 332
5. PUBLIKATION 2 565
6. DISKUSSION 743
6.1 Präambel 743
6.2 Diskussion der Eignung des Versuchsprotokolls zur Beantwortung der Zielstellung 74
6.3 Angewandtes Therapieschema und Effekte der Butafosfan- und Cyanocobalamintherapie 75
6.3.1 Dosierung, Applikationsart und Behandlungshäufigkeit 754
6.3.2 Diskussion des Therapieschemas im Kontext der neuen EU-Tierarznei¬mittel-Verordnung 78
6.3.3 Mögliche Effekte bei erkrankten Tieren, Ausblick 79
6.4 Diskussion der Auswirkungen des intensiven Versuchsprotokolls auf die Gesundheit und Leistungskennzahlen der Milchkühe während des Versuchs 80
6.4.1. Direkte Schäden an den Tieren durch studienbedingte Manipulationen 80
6.4.2. Auswirkung auf die Gesamtgesundheit der Tiere 821
6.4.3. Einfluss auf das Abgangsgeschehen bei den Tieren 843
6.5 Bedeutung der Befunddokumentation in Protokollen und Verwendung von Scoring-Sheets zur Datenerhebung sowie der Wert einer Überwachung der Versuchstiere durch erfahrene Tierärzte 84
7 ZUSAMMENFASSUNG 87
8 SUMMARY 89
9 LITERATURVERZEICHNIS 91
10 ANHANG 118
11 DANKSAGUNG 151 / Introduction: The transition period in dairy cows is characterised by significant metabolic changes. Management changes commonly occur at the same time, causing stress and impairing the adaptation mechanisms of the cows, which increases the risk of production diseases. The liver is the main metabolic organ and therefore plays a crucial role in the adaptive changes that occur in the transition period. However, several basic pathophysiological mechanisms that occur in the transition period are not completely understood. Novel methods of analysis such as metabolomics technology improve the interpretation of metabolic processes and the individual differences in the probability of illness among cows. Furthermore, these techniques allow a better understanding of the modes of action of metaphylactic and therapeutic measures. The beneficial effects of Butafosfan and cyanocobalamin (BCC) with respect to ketosis prevention and milk yield have been established but the underlying mechanisms of action are not completely understood. Prospective, randomised and blinded animal testing remains a cornerstone of the search for evidence-based knowledge in many medical fields including buiatrics. However, animal testing is associated with an increased risk of health problems and loss of production, and the magnitude and types of risks are not clearly defined.
Objectives: The primary goal of this dissertation was to characterise the metabolome of liver tissue in relation to clinical and laboratory variables as well as health and production parameters in transitional dairy cows. A secondary goal was to investigate the effect of metaphylactic treatment with BCC on the metabolome of the liver and the effect of an intensive experimental protocol on the health and production parameters in dairy cows.
Animals, Materials and Methods: In the first part of the study (publication 1), 87 healthy cows from a herd of 660 German Holstein cows were used. The cows were monitored clinically every day from day 14 antepartum (day –14) until day 49 postpartum (day 49). On days –7 to –5 and 1 to 3, the cows received either 5 or 10 ml BCC (Catosal® per 100 kg body weight; 0.05 mg/ml cyanocobalamin, 100 mg/ml Buta¬fosfan; Bayer Animal Health GmbH, Leverkusen, Germany) or a placebo of coloured isotonic saline solution administered intravenously. Statistical analysis was performed using multivariate [partial least squares discriminant analysis (PLS-DA)] and univariate methods (linear mixed model). The cows underwent serial blood (n = 8), liver biopsy sample (n = 4) and urine (n = 13) collection and sonographic examination of the liver (n = 7) and measurement of the back fat (n = 7). The herd management software Herde® (dsp-Agrosoft GmbH, Ketzin/ Havel, Germany) was used to document health, fertility and production parameters. The second part of the study (publication 2) dealt with adverse health effects that were potentially associated with the experimental protocol. For this purpose, 206 control cows were used for the comparison of health and production data.
Results: Overall, the findings of this study confirm the occurrence of metabolomic changes related to metabolic processes during the transition period. The cows were divided into 3 metabolomic profiles (A to C) based on the changes in the liver metabolome. The effect of BCC on these profiles differed. The changes in the liver metabolome suggested an increase in β-oxidation and more efficient triacylglycerol export in the liver of cows treated with the higher dose of BCC. A comparison of the 2 doses of BCC showed that the higher dose had a significant effect on phenotypic traits. The largest treatment effect was seen in metabolomic profile B on day 7. Most study protocol-associated lesions were related to the liver biopsy procedure and included diffuse inflammation of the abdominal wall at the biopsy site and increased echogenicity of the hepatic tissue. In the experimental cows, the milk yield was lower, the somatic cell count was higher and the stillbirth rate was lower compared with the control cows (statistically significant, P=0.001). The survival rate did not differ between the experimental and control cows.
Conclusions: This study allowed the identification of cows with an increased risk of metabolic disease based on their metabolic profile (profile B) during the transition period. A positive and dose-dependent effect of BCC on the health status was seen in those cows. An intensive experimental protocol can have different effects on health and production parameters in dairy cows. This study improves risk assessment for intensive experimental protocols and facilitates the planning and execution of future studies that involve animal testing.:1. EINLEITUNG 1
2. LITERATURÜBERSICHT 4
2.1 Die Transitphase bei Milchkühen 4
2.1.1 Physiologie der Adaptation 4
2.1.2 Das Lipomobilisationssyndrom 7
2.2 Untersuchungen des Metaboloms zur Ergründung pathophysiologischer Reaktionsnetzwerke in der Transitphase 10
2.2.1 „Omics“-Methoden 10
2.2.2 Metabolomics 11
2.2.3 Technische Durchführung 11
2.2.4 Anwendung in der Veterinärmedizin 12
2.3 Prinzipien pro- und metaphylaktischer Maßnahmen in der Transitphase 14
2.3.1 Zufuhr von Energieträgern 19
2.3.2 Beeinflussung des Pansenmikrobioms 19
2.3.3 Beeinflussung des Leberstoffwechsels 220
2.4 Auswirkungen von Studienprotokollen auf den Organismus von Versuchstieren 23
2.4.1 Evidenzbasierte Medizin 23
2.4.2 Evidenzbasierte Veterinärmedizin: Versuche am Tier 24
2.4.3 Belastungen durch Studienprotokolle 25
2.4.4 Beurteilung studienassoziierter Belastungen 26
2.5 Schlussfolgerungen aus der Literaturrecherche und Arbeitshypothesen 27
3. MATERIAL UND METHODEN 29
3.1 Studiendesign 29
3.1.1 Tierversuchsantrag und Präambel 29
3.1.2 Patientenmaterial 29
3.2 Spezielle Untersuchungsgänge der Kühe der Versuchsgruppe 30
3.2.1 Untersuchungen 30
3.2.2 Probenentnahme 30
3.2.3 Probenhandling und Analyse von Blut-, Leber- und Harnproben 32
3.2.4 Sonographische Untersuchung 321
4. PUBLIKATION 1 332
5. PUBLIKATION 2 565
6. DISKUSSION 743
6.1 Präambel 743
6.2 Diskussion der Eignung des Versuchsprotokolls zur Beantwortung der Zielstellung 74
6.3 Angewandtes Therapieschema und Effekte der Butafosfan- und Cyanocobalamintherapie 75
6.3.1 Dosierung, Applikationsart und Behandlungshäufigkeit 754
6.3.2 Diskussion des Therapieschemas im Kontext der neuen EU-Tierarznei¬mittel-Verordnung 78
6.3.3 Mögliche Effekte bei erkrankten Tieren, Ausblick 79
6.4 Diskussion der Auswirkungen des intensiven Versuchsprotokolls auf die Gesundheit und Leistungskennzahlen der Milchkühe während des Versuchs 80
6.4.1. Direkte Schäden an den Tieren durch studienbedingte Manipulationen 80
6.4.2. Auswirkung auf die Gesamtgesundheit der Tiere 821
6.4.3. Einfluss auf das Abgangsgeschehen bei den Tieren 843
6.5 Bedeutung der Befunddokumentation in Protokollen und Verwendung von Scoring-Sheets zur Datenerhebung sowie der Wert einer Überwachung der Versuchstiere durch erfahrene Tierärzte 84
7 ZUSAMMENFASSUNG 87
8 SUMMARY 89
9 LITERATURVERZEICHNIS 91
10 ANHANG 118
11 DANKSAGUNG 151
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Semi-automated Ontology Generation for Biocuration and Semantic SearchWächter, Thomas 01 February 2011 (has links) (PDF)
Background:
In the life sciences, the amount of literature and experimental data grows at a tremendous rate. In order to effectively access and integrate these data, biomedical ontologies – controlled, hierarchical vocabularies – are being developed.
Creating and maintaining such ontologies is a difficult, labour-intensive, manual process. Many computational methods which can support ontology construction have been proposed in the past. However, good, validated systems are largely missing.
Motivation:
The biocuration community plays a central role in the development of ontologies. Any method that can support their efforts has the potential to have a huge impact in the life sciences.
Recently, a number of semantic search engines were created that make use of biomedical ontologies for document retrieval. To transfer the technology to other knowledge domains, suitable ontologies need to be created. One area where ontologies may prove particularly useful is the search for alternative methods to animal testing, an area where comprehensive search is of special interest to determine the availability or unavailability of alternative methods.
Results:
The Dresden Ontology Generator for Directed Acyclic Graphs (DOG4DAG) developed in this thesis is a system which supports the creation and extension of ontologies by semi-automatically generating terms, definitions, and parent-child relations from text in PubMed, the web, and PDF repositories. The system is seamlessly integrated into OBO-Edit and Protégé, two widely used ontology editors in the life sciences. DOG4DAG generates terms by identifying statistically significant noun-phrases in text. For definitions and parent-child relations it employs pattern-based web searches. Each generation step has been systematically evaluated using manually validated benchmarks. The term generation leads to high quality terms also found in manually created ontologies. Definitions can be retrieved for up to 78% of terms, child ancestor relations for up to 54%. No other validated system exists that achieves comparable results.
To improve the search for information on alternative methods to animal testing an ontology has been developed that contains 17,151 terms of which 10% were newly created and 90% were re-used from existing resources. This ontology is the core of Go3R, the first semantic search engine in this field. When a user performs a search query with Go3R, the search engine expands this request using the structure and terminology of the ontology. The machine classification employed in Go3R is capable of distinguishing documents related to alternative methods from those which are not with an F-measure of 90% on a manual benchmark. Approximately 200,000 of the 19 million documents listed in PubMed were identified as relevant, either because a specific term was contained or due to the automatic classification. The Go3R search engine is available on-line under www.Go3R.org.
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Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic ProductsMcCanna, David January 2009 (has links)
The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes.
The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations.
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Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic ProductsMcCanna, David January 2009 (has links)
The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes.
The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations.
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Semi-automated Ontology Generation for Biocuration and Semantic SearchWächter, Thomas 27 October 2010 (has links)
Background:
In the life sciences, the amount of literature and experimental data grows at a tremendous rate. In order to effectively access and integrate these data, biomedical ontologies – controlled, hierarchical vocabularies – are being developed.
Creating and maintaining such ontologies is a difficult, labour-intensive, manual process. Many computational methods which can support ontology construction have been proposed in the past. However, good, validated systems are largely missing.
Motivation:
The biocuration community plays a central role in the development of ontologies. Any method that can support their efforts has the potential to have a huge impact in the life sciences.
Recently, a number of semantic search engines were created that make use of biomedical ontologies for document retrieval. To transfer the technology to other knowledge domains, suitable ontologies need to be created. One area where ontologies may prove particularly useful is the search for alternative methods to animal testing, an area where comprehensive search is of special interest to determine the availability or unavailability of alternative methods.
Results:
The Dresden Ontology Generator for Directed Acyclic Graphs (DOG4DAG) developed in this thesis is a system which supports the creation and extension of ontologies by semi-automatically generating terms, definitions, and parent-child relations from text in PubMed, the web, and PDF repositories. The system is seamlessly integrated into OBO-Edit and Protégé, two widely used ontology editors in the life sciences. DOG4DAG generates terms by identifying statistically significant noun-phrases in text. For definitions and parent-child relations it employs pattern-based web searches. Each generation step has been systematically evaluated using manually validated benchmarks. The term generation leads to high quality terms also found in manually created ontologies. Definitions can be retrieved for up to 78% of terms, child ancestor relations for up to 54%. No other validated system exists that achieves comparable results.
To improve the search for information on alternative methods to animal testing an ontology has been developed that contains 17,151 terms of which 10% were newly created and 90% were re-used from existing resources. This ontology is the core of Go3R, the first semantic search engine in this field. When a user performs a search query with Go3R, the search engine expands this request using the structure and terminology of the ontology. The machine classification employed in Go3R is capable of distinguishing documents related to alternative methods from those which are not with an F-measure of 90% on a manual benchmark. Approximately 200,000 of the 19 million documents listed in PubMed were identified as relevant, either because a specific term was contained or due to the automatic classification. The Go3R search engine is available on-line under www.Go3R.org.
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