Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Pain control of synovitis is important in the reduction of stress responses, suffering and occurrence of laminitis on the contralateral limb. The use of epidural opioids stands out for its analgesic quality, reduction of doses of the drugs used, reduction of their side effects and prolonged period of action. The study aimed to evaluate the physiological and the analgesic effects of epidural administration of 0.1 mg/kg of morphine or 5 μg/kg of buprenorphine in ponies submitted to synovitis induced with E. coli lipopolysacharide (LPS) in the radiocarpal articulation. Six healthy ponies weighing 131.3 kg and age between 3.5 to 9 years were used and divided randomly in 3 groups and arranged in a Latin Square. The control group (GC) received 0.15 mL/kg of 0.9% NaCl solution, morphine group (GM) received 0.1 mg/kg of morphine and buprenorphine group (GB) 5 μg/kg of buprenorphine via epidural and dilluted in 0.9% NaCl solution, using a stardard total volume of 0.15 mL/kg and time of administration of 10 seconds/mL. After general and specific clinical examination, they were sedated and the carpal synovitis was induced with 0.5 ng of LPS administered to the radiocarpal articulation. Subsequently, an epidural catheter was introduced in the epidural space, so that the treatments would be placed in the thoracolumbar region. 6 hours after LPS, the animals were submitted to a new general and specific clinical exam (time 0) and assigned to one of the treatments. The general physical examination (HR, RR, SAP, CRT, color of mucous membranes, TºC and intestinal motility) and specific (pain on palpation, maximum angle of carpal flexion, pain on maximum flexion, grade of articulation movement, stride lenght and lameness degree) were carried out 30 minutes and 1, 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours after epidural administration of the assigned treatment by a blind examinator. Parametric variables were analyzed with ANOVA, followed by Dunnett test for intra group and Tukey test between groups. For the non-parametric variable Wilcoxon test was used. Differences was considered significant when P<0.05. The synovitis induction model produced changes in the lameness degree, pain on palpation and angle of flexion, maintaining present pain on maximum flexion and reduced grade of articulation movement, but it did not cause changes in the physiological parameters. The control group showed changes in lameness in relation to physiological parameters up to 12 hours. Lameness degree was reduced in GM and GB for 30 minutes up to 12 hours and 6 up to 12 hours, respectively. Regarding physiological parameters, alterations were observed in the intestinal motility, where hypomotility occurred at 1 hour in GM and for 30 minutes up to 1 hour in GB; and body temperature, which was maintained higher in GM and GB up to 10 hours. The intra-articular synovitis induction model with the use of LPS was efficient for 12 hours. Morphine provided analgesia starting at 30 minutes and lasting for 12 hours after its administration, whereas buprenorphine was effective only after 6 hours, lasting for another 6 hours. / O controle da dor da sinovite é importante na diminuição das respostas ao estresse, do sofrimento e da ocorrência de laminite no membro contralateral. O uso de opióides pela via epidural destaca-se pela qualidade analgésica, redução da dose dos fármacos empregados e redução de efeitos colaterais e prolongado período de ação. O estudo objetivou avaliar os efeitos fisiológicos e analgésicos da administração epidural de 0,1 mg/kg de morfina ou 5 μg/kg de buprenorfina em pôneis submetidos à sinovite induzida com lipopolissacarídeo (LPS) de E. coli na articulação radiocarpiana. Foram utilizados 6 pôneis hígidos, divididos em 3 grupos autocontrole e dispostos em um Quadrado Latino. O controle (GC) recebeu 0,15 mL/kg de solução de NaCl 0,9%, o grupo morfina (GM) recebeu 0,1 mg/kg de morfina e o grupo buprenorfina (GB) 5 μg/kg de buprenorfina, ambos pela via epidural e diluídos em solução de NaCl 0,9%, padronizando-se um volume final de 0,15 mL/kg e tempo de administração de 10 segundos/mL. Após avaliação dos parâmetros fisiológicos basais, os animais foram sedados e submetidos ao modelo de indução da sinovite, administrando-se 0,5 ng de LPS na articulação radiocarpiana. Ato contínuo foi introduzido um cateter epidural no referido espaço, até a região tóraco-lombar. 6 horas após a administração do LPS, os animais foram submetidos a um novo exame clínico geral e específico (tempo 0) e administrados um dos tratamentos. Os exames clínicos geral (FC, f, PAS, TPC, coloração das mucosas, TºC e motilidade intestinal) e específico (dor à palpação, ângulo de flexão máxima do carpo, dor à flexão máxima, grau de movimentação da articulação, comprimento do passo e grau de claudicação) foram realizados aos 30 minutos e 1, 2, 4, 6, 8, 10, 12, 16, 20 e 24 horas após a administração epidural, por um observador cego aos tratamentos. Para as variáveis paramétricas utilizou-se análise de variância para amostras pareadas, com posterior teste de Dunnett. Para comparações entre os grupos, realizou-se análise de variância, seguido de teste de Tukey. Para as variáveis não-paramétricas utilizou-se o teste de Wilcoxon para amostras pareadas. As diferenças foram consideradas significantes quando P<0,05. O modelo de indução da sinovite produziu alterações no grau de claudicação, dor à palpação e ângulo de flexão, mantendo presentes dor à flexão máxima e reduzido grau de movimentação da articulação, mas não causou alterações nos parâmetros fisiológicos. O GC apresentou diferença na análise da claudicação em relação aos parâmetros basais até 12 horas. GM e GB apresentaram redução de claudicação entre 30 minutos e 12 horas, e 6 e 12 horas, respectivamente. Dentre os parâmetros fisiológicos, observaram-se alterações na motilidade intestinal, ocorrendo hipomotilidade aos 30 minutos no GM e entre 30 minutos e 1 hora no GB; e na temperatura corporal, que se manteve elevada até 10 horas em GM e GB. O modelo de indução da sinovite foi eficiente por 12 horas. A morfina proporcionou analgesia entre 30 minutos e 12 horas após a sua administração, enquanto que a buprenorfina apresentou esse efeito somente após 6 horas, permanecendo por mais 6 horas.

Das Equine metabolische Syndrom, das Equine Cushing Syndrom und die häufig daraus resultierende Hufrehe stellen den behandelnden Tierarzt noch immer vor Probleme bezüglich Diagnostik und Therapie. Grund hierfür sind fehlende einheitliche endokrinologische Parameter, die eine Einschätzung des Krankheitszustandes des jeweiligen Tieres ermöglichen. Für Ponys fehlt es gänzlich an statistisch validen Referenzbereichen für die, an den Krankheiten beteiligten Hormonen. In der vorliegenden Arbeit wurde die Aktivität von Insulin, sowie die Konzentration von Insulinwachstumsfaktor-1 (IGF-1) und adrenocorticotropem Hormon (ACTH) im Blut von 130 klinisch gesunden, erwachsenen Ponys bestimmt. Damit liegen erstmals Ergebnisse vor, welche auf einer für die Erstellung von Referenzwerten ausreichend großen Fallzahl basieren. Die Analyse fand mittels eines immunometrischen Chemielumineszenz-Assays an drei aufeinander folgenden Tagen statt. Anhand einer Dreifachuntersuchung am ersten Untersuchungstag wurde für jedes Hormon der 95 %-Referenzbereich bestimmt. Für Insulin konnte ein Referenzbereich von 2,0 - 34,3 µU/ml ermittelt werden. Damit liegen die Werte unterhalb den für Großpferde veröffentlichen Werten, wobei ein direkter Vergleich nur bedingt möglich ist. Für Insulinwachstumsfaktor-1 wurden für Pferde noch keine Werte erhoben. Somit ist ein Vergleich zwischen Großpferden und Ponys diesbezüglich noch nicht möglich. Für Ponys liegt der hier ermittelte Referenzbereich zwischen 48,3 und 382,6 ng/ml. Für die Konzentration von adrenocorticotropem Hormon gibt es in der Literatur unterschiedliche Angaben sowohl für Ponys als auch für Großpferde. Mit dieser Studie wurde der 95 %-Referenzbereich für Ponys bei 6,5 bis 23,3 pg/ml ermittelt. Es konnte ein Zusammenhang zwischen dem Alter der Tiere und der ACTH-Konzentration nachgewiesen werden. Der Referenzbereich der Gruppe B (13 bis 32 Jahre) reicht von 7,1 pg/ml bis 27,7 pg/ml und unterscheidet sich damit signifikant von dem Referenzbereich der Gruppe A (drei bis 12 Jahre), welcher zwischen 5,9 pg/ml und 22,2 pg/ml ermittelt wurde. Durch die Bestimmung der Hormonkonzentration an drei aufeinander folgenden Tagen konnte die Empfindlichkeit der Hormone gegenüber enzymatischem Abbau überprüft werden. Die Proben wurden an Tag 1 aufgetaut und anschließend bei 4°C gelagert. Lediglich für adrenocorticotropes Hormon konnte eine signifikante Reduzierung (p< 0,001) der Werte um 5,4 % an Tag 3 im Vergleich zu Tag 1 festgestellt werden. Das Chemielumineszens-Assay-Testverfahren mit den Geräten der IMMULITE 2000-Reihe wurde hinsichtlich seiner Präzisionen überprüft, indem der Variationskoeffizient für die Intra-Assay-Untersuchung und die Inter-Assay-Untersuchung berechnet wurde. Für das Verfahren konnte eine ausreichende (Variationskoeffizienten ACTH: 5,2 % bzw. 5,4%), für die Untersuchung von Insulin und IGF-1 sogar eine hervorragende (Variationskoeffizienten Insulin: 3,9 % bzw. 4,7 %; Variationskoeffizienten IGF-1: 2,6 % bzw.2,9 %) Testgenauigkeit nachgewiesen werden.

Studying genetic diversity in natural and domestic populations is of major importance in evolutionary biology. The recent advent of next generation sequencing (NGS) technologies has dramatically changed the scope of these studies, enabling researchers to study genetic diversity in a whole-genome context. This thesis details examples of studies using NGS data to: (i) characterize evolutionary forces shaping the genome of the Atlantic herring, (ii) detect the genetic basis of speciation and domestication in the rabbit, and, (iii) identify mutations associated with skeletal atavism in Shetland ponies. The Atlantic herring (Clupea harengus) is the most abundant teleost species inhabiting the North Atlantic. Herring has seasonal reproduction and is adapted to a wide range of salinity (3-35‰) throughout the Baltic Sea and Atlantic Ocean. By using NGS data and whole-genome screening of 20 populations, we revealed the underlying genetic architecture for both adaptive features. Our results demonstrated that differentiated genomic regions have evolved by natural selection and genetic drift has played a subordinate role. The European rabbit (Oryctolagus cuniculus) is native to the Iberian Peninsula, where two rabbit subspecies with partial reproductive isolation have evolved. We performed whole genome sequencing to characterize regions of reduced introgression. Our results suggest key role of gene regulation in triggering genetic incompatibilities in the early stages of reproductive isolation. Moreover, we studied gene expression in testis and found misregulation of many genes in backcross progenies that often show impaired male fertility. We also scanned whole genome of wild and domestic populations and identified differentiated regions that were enriched for non-coding conserved elements. Our results indicated that selection has acted on standing genetic variation, particularly targeting genes expressed in the central nervous system. This finding is consistent with the tame behavior present in domestic rabbits, which allows them to survive and reproduce under the stressful non-natural rearing conditions provided by humans. In Shetland ponies, abnormally developed ulnae and fibulae characterize a skeletal deformity known as skeletal atavism. To explore the genetic basis of this disease, we scanned the genome using whole genome resequencing data. We identified two partially overlapping large deletions in the pseudoautosomal region (PAR) of the sex chromosomes that remove the entire coding sequence of the SHOX gene and part of CRLF2 gene. Based on this finding, we developed a diagnostic test that can be used as a tool to eradicate this inherited disease in horses.

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