MSc. (Zoology) / The Albasini Dam was used as a reference site outside the DDT (1, 1, 1-trichloro-2, 2-bis (p-chlorophenyl) ethane) - sprayed area in a previous survey conducted from 2006 to 2008. DDT, endocrine disrupting chemicals and inorganic chemicals were detected in the dam. A histological analysis of fish from the dam showed histological alterations in heart, liver, gills, and gonads. Therefore, it was necessary to follow up the health status of the dam by monitoring the levels of organic and inorganic chemicals and their effects on fish. The aim of the present study was to determine the health status of three freshwater fish species, Clarias gariepinus, Oreochromis mossambicus, and Coptodon (Tilapia) rendalli from the Albasini Dam, using fish histology as a biomonitoring tool. In total, 18 fish were sampled using gill nets; these included Clarias gariepinus (n=5); Coptodon (Tilapia) rendalli (n=4) and Oreochromis mossambicus (n=9). The histology-based fish health assessment included a standard fish necropsy; a calculation of blood parameters (haematocrit, leukocrit and total plasma protein); somatic indices and the condition factor and a qualitative and semi-quantitative histological assessment of five target organs: liver, heart, gills, kidney and gonads. Water, sediment and fish muscles samples were collected and analysed for inorganic chemicals and organic chemicals. Inorganic chemicals were analysed by means of Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and Inductively Coupled Plasma-Optic Emission Spectrometry (ICP-OES). Organic chemicals in water and fish muscles were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). Nutrients and physical parameters of water were also measured...

M.Sc. (Aquatic Health) / The North West Province is mineral rich and known for its extensive mining and agricultural activities. These activities drain organic and inorganic pollutants in our waterways, possibly resulting in reduced water quality in dams. Organic and inorganic pollutants such as nutrients, organochlorine pesticides and metals may be present in unacceptable levels possibly affecting fish as well as human health. The North West dams are known for their high nutrient loads and are mostly classified as hypertrophic. In order to better understand the possible effects of the combined pollutant loads on fish health and edibility of fish, (1) a fish health assessment and (2) a human health risk assessment should be conducted. The fish health assessment and the human health risk assessment form an important role in the establishment of water quality standards or/and guidelines for acceptable levels of safe consumption of fish respectively. The aim of this study was to determine (1) if Oreochromis mossambicus from the Klipvoor -, Roodekopjes - and Vaalkop Dams show adverse effects and (2) if consumed, pose a human health risk. The results were compared to the reference site, the Marico-Bosveld Dam.

Studies on the health status of lions (Panthera leo) in the Kruger National Park (KNP) have revealed certain lions suffering from chronic debility (“poor doers”). Clinical signs include chronic emaciation, renal failure and chronic bacterial infections. The diagnosis of Mycobacterium bovis in KNP lions in 1995 raised the question of whether these “poor doer” lions were suffering from tuberculosis. Tests confirmed tuberculosis in some cases, but no aetiology for the poor condition was found in a large percentage of the animals tested. Extensive literature review failed to reveal reports of similar findings of chronic debility in free living lion populations, although various disease outbreaks and infectious diseases of lions are described. These are briefly reviewed. Surveys have confirmed that the majority of the KNP lions are serologically positive for feline immunodeficiency virus (FIV), the clinical importance of which is questioned as a possible cause of immunosuppression in lions. Tissue samples from eleven lions suffering from chronic debility and six clinically healthy lions were studied by light microscopy. Changes in the various organ systems were reported and tabulated with reference to degree and relevance. Frozen lymph node samples from some animals in both groups were collected for immunohistochemical staining for T and B lymphocytes and CD4 and CD8 subsets. In some cases serology was done for FIV using a Puma Lentivirus ELISA and a Puma Lentivirus Western Blot technique. Mycobacterial culture results were available for some animals. The histopathological features varied, but notable changes were seen in the lymph nodes. These included generalized lymphoid hyperplasia (predominantly affecting clinically healthy lions), progressing through combined hyperplasia and atrophy in different nodes to lymphoid atrophy affecting most of the lions suffering from chronic debility. These are non-specific findings seen in various systemic diseases, including canine distemper virus infection and toxoplasmosis, but they have also been described in domestic cats suffering from FIV infection and humans with HIV. Further findings in lymph node sections included mineral deposition and multifocal cystic spaces. Other important histopathological changes included chronic interstitial pneumonia, renal amyloidosis, chronic interstitial nephritis, Wallerian degeneration of the spinal cord, encephalomalacia and anterior uveitis. Two animals suffered from multifocal, multisystemic granulomatous inflammation. Mycobacterium bovis was cultured from one of these cases, but no apparent aetiology could be found in the other. Eosinophilia was a consistent finding in many tissues and most likely related to the high parasite load in many of the animals. Parasites found included Hepatozoon spp., microfilaria, cestodes, nematodes and trematodes and Sarcocystis spp. and Trichinella spp. Immunohistochemical staining for B and T lymphocytes and CD4 and CD8 subsets showed a normal distribution of the staining pattern within the lymph node sections, although the samples were all from FIV positive lions. The histopathology in both study groups was of a non-specific nature and not indicative of any particular disease syndrome, although many of the changes are similar to those described in domestic cats infected with FIV. There are indications of possible immunocompromise in the “poor doer” lions, which warrants further investigation. / Dissertation (MMedVet (Pathology))--University of Pretoria, 2006. / Oral Pathology and Oral Biology / unrestricted

A influenza suína (IS) é uma doença altamente contagiosa, de curso rápido e pronta recuperação, causada pelo vírus Influenza tipo A (VIS). Os principais sinais clínicos são tosse, febre, anorexia e baixo desenvolvimento. A doença está presente em outros países e, geralmente, está associada com outros agentes infecciosos. Porém, no Brasil, a sua primeira descrição ocorreu em 2011 e foi associada ao vírus H1N1 pandêmico (pH1N1). O principal objetivo deste estudo foi caracterizar as alterações histológicas mais importantes em casos de doença respiratória suína sugestiva de IS e estudar a associação dessas alterações com os resultados de imuno-histoquímica (IHQ) anti-vírus da influenza A (VIA), anti-circovírus suíno tipo 2 (PVC2) e anti-vírus da síndrome reprodutiva e respiratória suína (PRRSV). Para tanto, foram estudadas 60 amostras de pulmões suínos selecionadas dos materiais do arquivo do Setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul (SPV-UFRGS), de casos de doença respiratória remetidos no período de 2009 a 2010 e que apresentavam alterações histopatológicas compatíveis com pneumonia viral causada pelo VIS. Trinta e uma amostras (52%) foram provenientes do estado do Rio Grande do Sul, 14 (23%) do Paraná, 11 (18%) de Santa Catarina e quatro (7%) do Mato Grosso do Sul. A IHQ para IA confirmou a presença do agente viral em 45% das amostras analisadas. Os achados histológicos mais significativos associados à IHQ positiva para IA foram bronquiolite necrótica, atelectasia, broncopneumonia purulenta e hiperemia. Por outro lado, as alterações histológicas dos pulmões estudados mais significativamente associadas à IHQ negativa para IA foram hiperplasia dos pneumócitos tipo II, estruturas alveolares e bronquiolares similares a pólipos, hiperplasia de tecido linfoide associado a brônquios (BALT) e pleurite, que são alterações associadas a processos crônicos. Somente dois casos apresentaram marcação positiva na IHQ para PCV2 e nenhum pulmão foi positivo para PRRSV. Esses resultados sugerem que as lesões histológicas encontradas no presente estudo foram compatíveis com as causadas pelo VIS. Os casos negativos de IHQ para IA (55%) podem ser explicados pela baixa frequência do antígeno viral nos tecidos estudados. Como o curso da doença é muito rápido, o teste de IHQ é mais indicado para diagnóstico no início da infecção. Este estudo evidenciou novas alterações em amostras de pulmões de suínos com problemas respiratórios enviadas para o SPV UFRGS a partir de 2009, com ênfase para bronquiolite necrótica, e reforça a importância do estudo histopatológico dos casos de campo para auxiliar na monitoria da sanidade dos rebanhos. / Swine influenza is caused by swine influenza type A virus (SIV). It is a highly contagious disease with a rapid course and recovery. The main clinical signs are cough, fever, anorexia and poor performance. Usually, it is associated with other infectious agents in many countries; however, it has not been described yet in Brazil. The first report of pandemic H1N1 influenza A virus in Brazilian swine herd occurred in 2011. The main aim of this study was to characterize histological features in association with immunohistochemical (IHC) results for influenza A (IA), porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) from lung samples from 60 pigs with lesions suggestive of viral pneumonia and collected during the period 2009-2010 and diagnosed at the Setor de Patologia Veterinária of Universidade Federal do Rio Grande do Sul (SPV-UFRGS), Brazil. All the pigs in this study had clinical respiratory disease. Sample distribution was 31 (52%) from Rio Grande do Sul, 14 (23%) Paraná, 11 (18%) from Santa Catarina State and four (7%) from Mato Grosso do Sul State. Positive anti-IA IHC was observed in 45% of the cases and was associated with necrotizing bronchiolitis, atelectasia, purulent bronchopneumonia and hyperemia. Moreover, type II pneumocyte hyperplasia, alveolar and bronchiole polyp-like structures, BALT (bronchus-associated lymphoid tissue) hyperplasia and pleuritis were the significant features of negative samples by anti-IA IHC, which were associated with chronic lesions. Only two cases were positive to PCV2 and none to PRRSV, supports the hypothesis that SIV was the viral agent infecting swine’s lungs. Negative IHC to IA (55%) cases could be explained due to the absence of viral antigens associated with the rapid progress of SI; hence, IHC should be requested in the beginning of the infection. This work has shown how important a careful histological evaluation should be done in order to give the diagnosis. Since 2009, a new histological feature of swine pneumonia from animals with respiratory clinical sign has been observed at samples submitted to SPV-UFRGS. In addition, these results described here proved the importance of histological evaluation in swine herd health management.

Organophosphates are neurotoxic compounds that inhibit acetylcholinesterase producing excess cholinergic stimulation. This produces various toxic signs including excitotoxic neuronal damage. Oximes can be used as a treatment for organophosphate poisoning by reactivating inhibited acetylcholinesterase. Traditional oximes do not penetrate the blood-brain barrier, limiting protection of the central nervous system. Novel, brain-penetrating oximes have the potential to protect the brain from organophosphate induced damage. Adult male rats were used to examine the ability of model organophosphates to produce neuropathology and the ability of novel oximes to prevent this damage. Additionally, adult male rats were used to examine changes in gene expression of the MAP kinase system resultant of treatment with model organophosphates and novel oximes. Results of these experiments support that the model organophosphates can be used to study neurodegeneration, the novel oximes may prevent neurodegeneration, and both organophosphates and novel oximes affect expression of MAP kinase genes.

Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset wasting syndrome, frequently occur in captive colonies of common marmosets (Callithrix jacchus). Early identification and diagnosis of affected animals are desirable. Endoscopic examination of the colon in marmosets is described, but the small intestine can harbor significant mucosal lesions not representing those in the colon. Evaluating the small intestine currently requires invasive surgical biopsies due to the small patient size, carrying a risk of severe complications. Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum are demonstrated in 10 marmosets under general anesthesia. Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets with chronic gastrointestinal signs. Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations into the pathogenesis of chronic gastroenteropathies will benefit from these data, leading to improved animal welfare and better individual and colony health management.

No description available.

Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset wasting syndrome, frequently occur in captive colonies of common marmosets (Callithrix jacchus). Early identification and diagnosis of affected animals are desirable. Endoscopic examination of the colon in marmosets is described, but the small intestine can harbor significant mucosal lesions not representing those in the colon. Evaluating the small intestine currently requires invasive surgical biopsies due to the small patient size, carrying a risk of severe complications. Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum are demonstrated in 10 marmosets under general anesthesia. Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets with chronic gastrointestinal signs. Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations into the pathogenesis of chronic gastroenteropathies will benefit from these data, leading to improved animal welfare and better individual and colony health management

Tumour cell dissemination is a major issue with the treatment of cancer, thus new therapeutic strategies which can control this process are needed. Antagonism of integrins highly expressed in tumours is one potential strategy. The integrins are transmembrane glycoprotein adhesive receptors. Two of the integrins, αVβ3 and αIIbβ3, are highly expressed in a number of tumours and induce bi-directional signalling through their interaction with extracellular matrix proteins, and growth factor receptors. Through this signalling they play an important role in a number of cellular processes that are involved in tumour dissemination such as tumour growth, migration, invasion, metastasis and angiogenesis. Dual αIIbβ3 and αVβ3 integrin antagonism will have a direct effect on β3-expressing tumour cells that leads to the inhibition of cell migration and dissemination. Furthermore, through targeting tumour cell interaction with endothelial cells and platelets, this will also lead to inhibition of angiogenesis and metastasis. The aim of this project was to characterise the expression of αVβ3 and αIIbβ3 integrin in a panel of tumour cell lines and in human tumour xenograft samples, and to develop and utilise cell-based models to investigate potential novel β3 antagonists. The expression of αV and β3 subunits was detected in xenograft tissue using immunoblotting techniques. A panel of cell lines of different tumour types including melanoma, prostate, breast, colon and non small cell lung carcinoma was then characterised for αVβ3 and αIIbβ3 integrin expression using immunoblotting and immunocytochemistry. Melanoma cell lines demonstrated the strongest αVβ3 expression. No αIIbβ3 integrin expression was seen in any of the cell lines evaluated. A selection of cell lines with varying αVβ3 expression were then used to develop a functional test for cell migration, the scratch wound healing assay. Migration of tumour cells that expressed αVβ3 integrin was inhibited by the known β3 antagonists, cRGDfV peptide and LM609 antibody. A panel of 12 potential novel β3 integrin antagonists was screened for cytotoxicity and activity in the validated scratch assay. ICT9055 was the most effective antagonist in inhibition of M14 cell migration as determined by the scratch assay, with an IC50 of < 0.1 µM. Therefore the work presented in this thesis has established models and tools for evaluating potential novel β3 integrin antagonists, and identified a promising molecule to progress for further preclinical evaluation. / Public Authority for Applied Education and Training (PAAET)

Introduction: The placenta is essential for fetal development and pregnancy prolongation. Its dysfunction can lead to short and long-term health consequences for mother and child. A subset of diseases resulting from placental dysfunction have been collectively termed placental-mediated diseases (PMD) - which includes the common and serious hypertensive disorder of pregnancy preeclampsia (PE), among others. PMDs are independent risk factors for maternal cardiovascular disease (CVD) in later life. This thesis presents a multi-pronged body of work, which includes: 1) A systematic review, aimed at summarizing the current state of knowledge on the risk for future maternal CVD after PMDs; 2) A cohort study, aimed at assessing the utility of placenta pathology examination at delivery to identify women at high lifetime risk for CVD following PE; and 3) An assessment of an immunohistochemistry screening panel for 3 placenta protein markers of interest, aimed at determining if these markers can accurately identify women deemed to be at high-risk for future CVD following a PE pregnancy. Methods: 1) We searched 4 databases for observational studies evaluating clinical and biochemical markers of CVD risk and/or a subsequent calculated risk score based on these parameters in women with a history of PMD. We excluded interventional studies and studies measuring these outcomes during or prior to pregnancy. 2) A cohort study was established across two clinical sites (Kingston, Ottawa), in which patients with PE (N=85) underwent cardiovascular risk assessments at 6-months postpartum. The placentas from these pregnancies also underwent detailed placenta histopathology examination to determine the presence, absence, and severity of 35 distinct placental lesions. The associations between distinct placental lesions and estimated lifetime cardiovascular risk were evaluated by odds ratios (OR) and receiver operator curve analysis (ROC). 3) Immunohistochemistry (IHC) analysis was performed on placental samples from a subset of the previously described cohort (N=41; Ottawa site only). Protein expression for FLT-1, ENG, and CD68 was quantified. Using a multivariate logistic regression model, the association between placenta protein expression, with and without clinical and placenta pathology findings, and cardiovascular risk was assessed. Results: 1) The search yielded 11,039 articles of which 104 met our inclusion criteria. All PMD types demonstrated evidence of increased CVD risk markers at varying timepoints postpartum. At least one study per PMD type had non-optimal measures of systolic blood pressure, BMI, and total cholesterol. 2) In the analysis of placenta pathology lesions within the cohort of individuals with PE, lesions of maternal vascular malperfusion (MVM) were found to be associated with elevated life-time risk for maternal CVD at 6 months postpartum (OR: 3.10[1.20-7.92]). We also found that adding these lesions to a logistic regression model improved the predictive accuracy for elevated maternal lifetime CVD risk (AUC: 73.0, sensitivity: 78.4%, specificity: 51.6%). 3) Individually, no significant differences were found in FLT-1, ENG, and CD68 expression between the individuals deemed to be at high and low-risk for lifetime CVD. Although, when added to a model that included placenta pathology lesions and clinical data the predictive accuracy for elevated maternal lifetime CVD risk increased (AUC: 1.0, sensitivity: 100%, specificity: 100%). Conclusions: In conclusion, this thesis provides further evidence of the utility of assessing placenta features in the prediction of future maternal CVD. This is evidenced by the association between PMDs, placental pathology, and placental protein biomarkers with elevated risk profiles for lifetime CVD. Thus, specific placental phenotypes of PMDs may be at increased risk for CVD. The use of placental data should be further explored as a triage strategy to identify these high-priority of women following delivery.