Thesis (M App Sc) -- University of South Australia, 1992

Thesis (M App Sc) -- University of South Australia, 1992

Equine protozoal myeloencephalitis (EPM), predominantly caused by the protozoa Saracocystis neurona, is a common neurologic disease in horses from North America. Equine exposure to the parasite occurs frequently as the protozoa is excreted in opossum (Didelphis virginiana) feces and contaminates the horse's environment. However, clinical neurologic disease only emerges in a small fraction of exposed horses. The seemingly protective immune response that develops in some exposed horses but not all is not fully defined. Previous reports utilizing horse EPM models and immune compromised mouse models, which develop disease simulating EPM after infection with S. neurona, have reported a role of T-lymphocytes and the cytokine interferon gamma, in disease protection. As part of this dissertation, the role of T-lymphocytes and IFNγ was further elucidated. It was determined that IFNγ production is essential for T-lymphocytes to offer protection against S. neurona induced encephalitis, in immune compromised mice. Another factor hindering prognosis of EPM affected horses is treatment failure. The efficacy of the antiprotozoal decoquinate, was tested and found to be ineffective at preventing S. neurona encephalitis, in immune compromised mice. However, the antiprotozoal, diclazuril, was found to be effective at preventing S. neurona encephalitis in immunocompromised mice but once treatment was terminated, infection persisted, and neurologic disease developed. In-situ methods were employed to extensively evaluate the immunopathology of spinal cord tissue samples collected from EPM affected horses. A novel in-situ hybridization technique was successfully utilized to identify S. neurona in tissue samples collected from horses with EPM. This technique will create new opportunities for investigating the immunopathology of EPM. Overall results from the studies conducted in this dissertation suggest that IFNγ production from T lymphocytes is essential for them to offer protection against S. neurona encephalitis. Additionally, further insight on FDA approved and non-FDA approved treatment options for S. neurona infection was gained through the use of the B6Ifnγ -/- mouse model. Collectively, these studies expanded on the knowledge of an understudied equine neurologic disease. / Doctor of Philosophy / Horses are susceptible to the neurologic disease Equine Protozoal Myeloencephalitis, more commonly referred to as EPM by equine enthusiasts. The disease results from ingestion of the parasite, Saracocystis neurona, which contaminates the horse's natural environment; therefore, horses are likely to come in contact with the parasite while eating or drinking. Not all horses that encounter S. neurona develop neurologic disease, some will be protected by their immune system with the only evidence of exposure being serological antibodies. In efforts to not experimentally induce EPM in horses, an immunocompromised mouse model is often used instead. Through the use of the immunocompromised mouse model, researchers have discovered that the immune cell, T lymphocytes, and signaling molecule, interferon gamma, are important for protection against S. neurona infection. In one study conducted for this dissertation it was found that T lymphocytes need to be able to produce interferon gamma in order to provide protection. Another issue that the immunocompromised mouse model has helped address, is EPM treatment efficacy. The inability of antiprotozoal drugs that are utilized for EPM treatment to fully eliminate the parasite from the horse's body is thought to cause reoccurring disease in some horses. One non-FDA approved treatment was evaluated here and determined not to be effective in the immunocompromised mouse model. One FDA approved treatment option, which is commonly used to treat EPM, was evaluated as well. This drug was proven to be effective at preventing disease while mice were being treated but termination of treatment led to development of neurologic disease, exemplifying treatment failure. One final study was conducted to examine the different types of immune cells and signaling molecules in spinal cord tissue samples collected, from horses which had to be euthanized due to poor prognosis related to EPM. In this study a novel experimental technique was successfully used which will help progress EPM research. Overall results of these studies offered more explanation on the immune response that protects against neurologic disease from S. neurona infection and demonstrated that not all treatments are effective and reoccurring disease may be a result of treatment failure.

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Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Thesis (M.S.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 56 pages. Includes Vita. Includes bibliographical references.

Orientadores: Anamarli Nuccic Alberto Cliquet Jr / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T03:23:57Z (GMT). No. of bitstreams: 1 Casanova_ManuelaAmaralMucci_M.pdf: 2345728 bytes, checksum: f66ccc6bdf60b6250a95b5911fe73602 (MD5) Previous issue date: 2008 / Resumo: A Distrofia Miotônica tipo 1 é doença multisistêmica que afeta com freqüência o músculo estriado, repercutindo na marcha, a qual pode apresentar-se em um espectro, desde muito anormal a sutis alterações de difícil caracterização através da visão humana. O objetivo deste trabalho foi analisar as variáveis espaciais, temporais e cinemáticas da marcha de afetados pela doença. Desenhou-se estudo prospectivo do tipo caso (n = 10) e controles (n = 20); os sujeitos foram investigados quanto à clínica da marcha e submetidos ao teste de força muscular. Marcadores reflexivos foram fixados em membros superiores, inferiores, tronco e pelve. A marcha, com pés descalços, ocorreu em passarela de 6 metros, capturada por 6 câmeras. Foram coletadas e analisadas 3 amostras de cada participante através do Sistema Qualisys®. Utilizou-se o Teste Exato de Fisher e o Teste de Mann-Whitney para a comparação das variáveis demográficas entre os grupos e a estatística descritiva dos casos. Encontrou-se alterações laboratoriais nos 10 pacientes, embora 04 não tivessem clínica de marcha anormal. O comprimento da passada foi diminuído em 80% dos casos, cadência menor em 30% e velocidade lenta em 40%. Anormalidade no movimento do quadril foi observada em 100% dos pacientes, da pelve em 90% e do tornozelo em 70%. O exame laboratorial da marcha permitiu diagnosticar alterações precoces, antes do aparecimento de déficit muscular à oposição de força, como ocorreu em 2 casos. A disfunção da marcha em laboratório esteve associada à fraqueza muscular distal isoladamente em 40%; e em associação com déficit proximal e distal em outros 40% / Abstract: Myotonic Dystrophy type 1 is a multisystemic disease that frequently affects the striated muscle with repercussion on gait. Gait function may be very abnormal or exhibit subtle alterations of difficult characterization by the human eyes. With objective to analyse the spatiotemporal and kinematics variables parameters of gait in patients affected by the disease, a prospective study of type case (n = 10) and controls (n = 20) was designed. The subjects were investigated in relation to clinical aspects of gait and submitted to the muscular force test. Reflexive markers were affixed in the upper and lower extremities, trunk and pelvis. A barefooted gait was performed in a 6-meter runway and captured by 6 ProReflex cameras. Three samples of each patient were collected and analyzed by the Qualisys® System. The Exact Test of Fisher and the Mann-Whitney Test were used for comparison of demographic variables between the groups and a descriptive statistic for cases. Abnormalities were found in all 10 patients, although 4 had no clinical evidence of gait problems. Stride was diminished in 80% of the cases, cadence in 30% and slow speed in 40%. Gait dysfunction was observed in 100% of the patients¿ hips, 90% of pelvis and 70% of ankles. The laboratory examination of gait allows early detection of alterations, even before the appearance of muscular deficit by manual force opposition test as occurred in two cases. Gait dysfunction observed in the laboratory was associated with distal muscular weakness in 40% of the patients and in association with proximal and distal deficits in others 40% / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

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Thesis (M.A.)--Missouri State University, 2008. / "May 2008." Includes bibliographical references (leaves 87-96). Also available online.