Bone is a dynamic, living tissue that constantly undergoes remodeling through the coordinated actions of osteoblasts (cells that build bone) and osteoclasts (cells that break down bone). Parathyroid hormone (PTH) is used clinically to treat osteoporosis due to its anabolic actions on bone. PTH binds to its receptor (PPR), which is highly expressed in cells of the osteoblastic lineage, including osteocytes. Radiotherapy, a common cancer treatment, adversely impacts bone health by impairing osteoblast and osteoclast functions, leading to conditions such as osteopenia and osteoporosis. Pre-clinical and cell culture studies have indicated that radiotherapy damages bone. This study investigates whether pretreatment with parathyroid hormone (PTH1-34) can protect osteocytes from radiation-induced DNA damage and cell death. We utilized a conditionally immortalized murine osteocytic cell line, Ocy454-12H, treated it with PTH, and exposed it to varying radiation doses. Results showed that PTH significantly reduced γH2AX foci, indicating decreased DNA damage. qPCR analysis revealed modulated expression of DNA damage-related genes (FOXO1, P53, MKi67), suggesting enhanced DNA repair and reduced apoptosis. Additionally, PTH mitigated radiation-induced bystander effects, reducing osteoclast activity. These findings highlight PTH's potential as a therapeutic agent to protect bone health in radiotherapy patients.

African Swine Fever Virus (ASFV) is an Asfivirus and is the only member of the family Asfarviridae. It manifests as a disease that varies from acute to sub-acute or chronic forms. A true carrier state in domestic pigs is unknown but chronically affected individuals may carry and spread the virus for extended periods. African Swine Fever (ASF) is a socio-economically important disease characterized by high morbidity and mortality affecting the livelihood of many small to big scale farmers and seriously compromising international trade. Strategic measures to control this disease are by physical containment and culling in outbreak situations. There is no vaccine available. Nevertheless, every pork producer should ideally be actively involved in having biosecurity measures in place to avoid contamination and contacting their veterinary services in case of suspicion of ASF to have appropriate samples analysed. Official veterinary services must be equipped with proper diagnostic tools in order to provide a quick response. The sensitivity of currently available diagnostic tests at the Transboundary Animal Diseases Programme, Onderstepoort Veterinary Institute was analysed in order to report the best technique available. Sensitivity to ASF virus infection and therefore diagnostic potential of cell primary cultures as bone marrow macrophages, blood macrophages and alveolar macrophages was done via comparison of titre results from inoculations of ASFV SPEC 257 as control, and ASFV MOZ 1/98. In addition, molecular detection of specific DNA fragments within the viral genome were compared using five different PCRs. Bone marrow macrophage cultures and blood macrophage cultures were the most reliable cells whereas alveolar macrophages more often showed contamination. Results show that PPA PCR and real time PCR detected the highest diluted samples, thus the lowest concentration of virus, in both trials done with ASFV MOZ 1/98 and ASFV SPEC 257. In addition, animal trials were performed by inoculating domestic pigs with four different ASFV isolates of varying pathogenicity. These viruses were all from distinct geographic origins. Non-virulent ASFV OURT 3/88 and high virulent ASFV BENIN 1/97 were previously described and used as reference viruses. ASFV MOZ 1/98, suspected of having high virulence and ASFV MKUZE, which was thought to be of low virulence were included in this study to provide further information on the pathological and clinical outcome of the disease as well as measuring viral replication in various organs and blood. The study showed that ASFV MKUZE was of intermediate virulence, whilst ASFV MOZ 1/98 was highly virulent with a high mortality rate. Results confirmed the inadequacy of ASFV MKUZE to act as vaccine opposed to ASFV OURT 3/88. Following this, a potential vaccine by use of attenuated Portuguese ASFV OURT 3/88 tested against virulent heterologous challenge with a strain now known with certainty to cause acute ASF, the isolate ASFV MOZ 1/98 collected from a diseased pig in Mozambique. Domestic commercial pigs where submitted to either one or two vaccinations before challenge. Viral load in blood and tissue samples was higher in unvaccinated animals and higher in single vaccinated than in pigs vaccinated twice. However, acute ASF afflicted all groups with severe clinical signs and post-mortem lesions. Although it did not confer total immunity it was determined that pigs vaccinated with European attenuated ASFV OURT 3/88 acquired partial protection against challenge with virulent southern Africa ASFV MOZ 1/98. / Dissertation (MSc)--University of Pretoria, 2012. / gm2014 / ab2015 / Veterinary Tropical Diseases / unrestricted

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal