Diabetic nephropathy (DN) remains the most common cause of end stage renal failure. Nearly 10% of patients with diabetes develop nephropathy. Hyperglycaemia in the kidneys leads to the activation of alternative metabolic pathways of glucose (glycation, activation of protein kinase C, and polyol pathway). These biochemical alterations lead to hypoxia and oxidative stress due to the increased formation of reactive oxygen species (ROS). Cellular response to hypoxia is controlled by hypoxia-induced factor 1 (HIF1), which is involved in the regulation of more than 800 genes. Target molecules of the HIF1 pathway participate in a wide range of physiological and pathological processes, e.g. angiogenesis, energy metabolism, apoptosis, migration, and proliferation. DN is associated with the pathological tissue remodelling process, epithelial-mesenchymal transition (EMT), and inflammation. HIF1 regulates key molecules of these pathological processes. EMT is regulated by TGFß1, CTGF, and SOX9. The progression of inflammation is regulated by VEGFA and AngII. The exact role of HIF1 signalling in the development of DN is not yet fully understood. This thesis evaluates the functional role of the HIF1 signalling pathway in the development of DN using a global heterozygous mutant with the deletion of the Hif1α gene....

Made available in DSpace on 2016-12-08T16:24:06Z (GMT). No. of bitstreams: 1 PGCV07MA048.pdf: 2534646 bytes, checksum: 9ccc6e39362dcc90e7ad0070a0d03f75 (MD5) Previous issue date: 2007-10-05 / This report describes the occurrence of four natural outbreaks of Infectious Bronchitis (IB) accompanied by nephritis and pectoral myopathy. The objectives are to describe the macro and microscopical injuries of the kidneys and muscle. Three outbreaks affected different flocks of broilers. One case occurred in broiler breeders affecting two houses of a farm. In the broilers, high mortality and high index of discarding was observed and also high condemnation in the abattoir. Respiratory snicks, apathy and ununiformity were observed. In the flock of broiler breeders, decline of production and high mortality were noticed. All the animals where positive for IB serology, and positive results were also obtained on the flock where PCR was carried through. In the necropsy, swollen and renal pallor were observed, pallor and white streaks mainly of the deep pectoral muscles, and in some cases mild edema. In the histopathology examination, the kidney injuries consisted of moderate to intense glomerular hyperplasia, in some cases interstitial multifocal inflammatory infiltrate and tubular degeneration. In the muscle, interstitial edema was found, hyaline degeneration, vacuolation, hypercontraction and myophagia of the muscle fibres. In one case, moderate fibrosis was observed. In other cases, mild to moderate lymphocytic infiltration was observed in the trachea. In the broiler breeders, other than the described lesions, a peribrochial lymphoid hyperplasia and hyaline degeneration was noted in the pulmonary vessels. In all the cases a close relation was observed between renal and muscular injury / Relata-se a ocorrência de quatro surtos espontâneos de Bronquite Infecciosa (BI) cursando com nefrite e miopatia peitoral objetivando descrever as lesões macro e microscópicas do rim e músculo. Três surtos ocorreram em frangos de corte afetando diversos lotes. Um surto ocorreu em matrizes afetando dois núcleos de criação. Nos frangos de corte, foi observado em alguns lotes alta mortalidade, alto índice de descarte e em outros alta condenação no abatedouro. Também observou-se, ronquidão, apatia e desuniformidade. No lote de matriz, foi observada queda de produção e mortalidade elevada. Todos os animais em que foi realizada sorologia foram positivos para BI, o mesmo para o lote em que foi realizada PCR. Na necropsia, observou-se tumefação e palidez renal, palidez e estrias esbranquiçadas principalmente do músculo peitoral profundo, e em alguns casos leve edema. No exame histopatológico, as lesões renais consistiam de hiperplasia glomerular de moderada a intensa, em alguns casos degeneração tubular e infiltrado inflamatório multifocal intersticial. No músculo, foi observado edema intersticial, degeneração hialina, vacuolização, hipercontração e miofagia de fibras musculares. Em um caso observou-se fibrose moderada. Em outros foram observadas infiltração linfocitária de leve a moderada na traquéia. Nas matrizes, além das lesões descritas, observou-se hiperplasia linfóide peribronquial e degeneração hialina nos vasos pulmonares. Em todos os casos foi observada uma estreita relação entre lesão renal e muscular