Selective inhibition of cyclooxygenase (COX) derived oxylipins reduces disease progression in the Han:SPRD-Cy rat model of cystic kidney disease, but the roles of lipoxygenase (LOX) and cytochrome P450 (CYP) derived products in this disease are not known. Dietary soy protein (SP), fish oil (FO) and flax oil (FXO) are beneficial in retarding renal disease progression in this and other models of cystic kidney disease and can alter renal oxylipin production through different mechanisms. The general objectives of this thesis were to: 1) investigate the effects of disease on renal oxylipin levels (produced from the three enzymatic pathways); 2) investigate the synergistic and additive effects of combining dietary SP with FO or FXO on disease progression, renal fatty acid composition, and renal oxylipin levels; 3) compare the effects of COX and LOX inhibitors on oxylipin levels and disease progression, in the Han:SPRD-Cy rat model of cystic kidney disease. Our research demonstrates that COX oxylipins are elevated and n-6 derived LOX metabolites are reduced in diseased kidneys in this model of cystic kidney disease. N-3 polyunsaturated fatty acid (PUFA) derived LOX oxylipins, including those derived from alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) were also lower in diseased kidneys, as were CYP derived oxylipins. The beneficial effect of SP on disease was associated with amelioration of several oxylipin alterations in parallel with a reduction in kidney disease progression, improvement in kidney function and blood pressure. However, adding dietary FO or FXO to the SP diet improved some but worsened other oxylipin alterations and did not provide further disease protection. Since both COX1 and COX2 activities are elevated in diseased kidneys, the effect of aspirin was examined; this treatment slowed disease progression and the decline in kidney function. On the other hand, inhibiting the LOX pathway had no effects on disease. Thus interventions that specifically inhibit COX while maintaining LOX and CYP may be more effective than general oxylipin inhibitors in slowing disease in this renal disorder. / October 2015

Objetivo - Avaliar o estado nutricional (EN) e sua associação com força muscular de membros inferiores (FMI) e de preensão manual (FPM), flexibilidade (FLX) e equilíbrio (EQ) de idosos do município de São Paulo. Delineamento - Estudo epidemiológico transversal, de base populacional e domiciliar, parte de estudo multicêntrico (Pesquisa SABE), coordenado pela Organização Pan-Americana de Saúde. Casuística - A Pesquisa SABE abrangeu 2143 idosos (≥ 60 anos), de ambos os sexos, no período de janeiro/2000 a março/2001, selecionados por amostragem probabilística; sendo que 1894 (88,4%), participaram deste estudo. Métodos - Os idosos foram estratificados segundo sexo e grupo etário (60-69, 70-79 e ≥ 80 anos) e o EN foi avaliado de acordo com Índice de Massa Corporal (IMC): baixo peso (IMC ≤ 23kg/m2) e obesidade (IMC ≥ 28kg/m2). A FMI e a FLX foram avaliados por tempo, a FPM por dinamômetro e o EQ por 4 medidas estáticas. As associações foram verificadas por análise de sobrevida, segundo Cox (FMI e FLX) e por quiquadrado (FPM e EQ). Resultados - Verificou-se maior prevalência de obesidade em mulheres e de baixo peso em homens. Houve aumento na freqüência de baixo peso e redução da obesidade nos grupos etários mais avançados. Observaram-se associações estatisticamente significativas entre FLX e EQ e mulheres obesas; e entre FPM e baixo peso em homens e mulheres. Conclusão: A inadequação nutricional foi constatada em ambos os sexos e todos os grupos etários. As associações entre EN e capacidade funcional mostraram-se específicas para sexo, grupo etário e teste utilizado. / Objective - To evaluate the nutritional status (NS) and its association with handgrip strength (HS), lower limb muscle strength (LMS), flexibility (FLX) and balance (BL) of the elderly of the city of São Paulo. Design - Cross-sectional epidemiological study, in a population and household basis, is part of a multicenter study (the SABE Survey), which was coordinated by the Pan-American Health Organization. Setting - The SABE survey reached 2143 elderly (≥ 60 yrs old), from both genders, from january/2000 to march/2001, who were selected by probabilistic sampling; out of those, 1894 (88.4%) took part in this study. Methods - The elderly were separated by gender and age group (60-69, 70-79 e ≥ 80 yrs old) for the tests, and the NS was evaluated according to the Body Mass Index (BMI): underweight (BMI ≤ 23kg/m2) and obesity (BMI ≥ 28kg/m2). The LMS and the FLX were measured by timing, the HS by a dynamometer and the BL by four static measurements. The associations were verified through Cox Regression analysis (LMS e FLX) and by chi square (HS e BL). Results - A larger prevalence of obesity was verified in women and of underweight in men. There was an increase in the underweight frequency and a reduction of the obesity level in the oldest age group. There were associations (statistically significant) between FLX and BL and obese women; and HS and underweight (men and women). Conclusions: The nutritional inadequacy was verified in both genders and all age groups. The associations between nutritional status and functional capacity were proved to be specific to each gender, age group and test.

Objetivo - Avaliar o estado nutricional (EN) e sua associação com força muscular de membros inferiores (FMI) e de preensão manual (FPM), flexibilidade (FLX) e equilíbrio (EQ) de idosos do município de São Paulo. Delineamento - Estudo epidemiológico transversal, de base populacional e domiciliar, parte de estudo multicêntrico (Pesquisa SABE), coordenado pela Organização Pan-Americana de Saúde. Casuística - A Pesquisa SABE abrangeu 2143 idosos (≥ 60 anos), de ambos os sexos, no período de janeiro/2000 a março/2001, selecionados por amostragem probabilística; sendo que 1894 (88,4%), participaram deste estudo. Métodos - Os idosos foram estratificados segundo sexo e grupo etário (60-69, 70-79 e ≥ 80 anos) e o EN foi avaliado de acordo com Índice de Massa Corporal (IMC): baixo peso (IMC ≤ 23kg/m2) e obesidade (IMC ≥ 28kg/m2). A FMI e a FLX foram avaliados por tempo, a FPM por dinamômetro e o EQ por 4 medidas estáticas. As associações foram verificadas por análise de sobrevida, segundo Cox (FMI e FLX) e por quiquadrado (FPM e EQ). Resultados - Verificou-se maior prevalência de obesidade em mulheres e de baixo peso em homens. Houve aumento na freqüência de baixo peso e redução da obesidade nos grupos etários mais avançados. Observaram-se associações estatisticamente significativas entre FLX e EQ e mulheres obesas; e entre FPM e baixo peso em homens e mulheres. Conclusão: A inadequação nutricional foi constatada em ambos os sexos e todos os grupos etários. As associações entre EN e capacidade funcional mostraram-se específicas para sexo, grupo etário e teste utilizado. / Objective - To evaluate the nutritional status (NS) and its association with handgrip strength (HS), lower limb muscle strength (LMS), flexibility (FLX) and balance (BL) of the elderly of the city of São Paulo. Design - Cross-sectional epidemiological study, in a population and household basis, is part of a multicenter study (the SABE Survey), which was coordinated by the Pan-American Health Organization. Setting - The SABE survey reached 2143 elderly (≥ 60 yrs old), from both genders, from january/2000 to march/2001, who were selected by probabilistic sampling; out of those, 1894 (88.4%) took part in this study. Methods - The elderly were separated by gender and age group (60-69, 70-79 e ≥ 80 yrs old) for the tests, and the NS was evaluated according to the Body Mass Index (BMI): underweight (BMI ≤ 23kg/m2) and obesity (BMI ≥ 28kg/m2). The LMS and the FLX were measured by timing, the HS by a dynamometer and the BL by four static measurements. The associations were verified through Cox Regression analysis (LMS e FLX) and by chi square (HS e BL). Results - A larger prevalence of obesity was verified in women and of underweight in men. There was an increase in the underweight frequency and a reduction of the obesity level in the oldest age group. There were associations (statistically significant) between FLX and BL and obese women; and HS and underweight (men and women). Conclusions: The nutritional inadequacy was verified in both genders and all age groups. The associations between nutritional status and functional capacity were proved to be specific to each gender, age group and test.