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Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

Submitted by Milena Rubi (milenarubi@ufscar.br) on 2017-08-16T16:46:54Z No. of bitstreams: 1 ANUNCIACAO_Eduardo_2017.pdf: 22889091 bytes, checksum: eaec97b1dbf9de44c126b87bb16c49c5 (MD5) / Approved for entry into archive by Milena Rubi (milenarubi@ufscar.br) on 2017-08-16T16:47:02Z (GMT) No. of bitstreams: 1 ANUNCIACAO_Eduardo_2017.pdf: 22889091 bytes, checksum: eaec97b1dbf9de44c126b87bb16c49c5 (MD5) / Approved for entry into archive by Milena Rubi (milenarubi@ufscar.br) on 2017-08-16T16:47:10Z (GMT) No. of bitstreams: 1 ANUNCIACAO_Eduardo_2017.pdf: 22889091 bytes, checksum: eaec97b1dbf9de44c126b87bb16c49c5 (MD5) / Made available in DSpace on 2017-08-16T16:47:17Z (GMT). No. of bitstreams: 1 ANUNCIACAO_Eduardo_2017.pdf: 22889091 bytes, checksum: eaec97b1dbf9de44c126b87bb16c49c5 (MD5) Previous issue date: 2017-03-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Uric acid is an endogenous substance produced from the metabolism of purines. The concentration of serum uric acid in the human body considered normal is between 0.24 - 0.52 mmol.L-1 . High levels of uric acid in the body lead to a condition known as hyperuricemia. Therefore, the monitoring of uric acid in the body is of great importance. In this work we present amperometric biosensors based on the association of the enzyme UOx with platinum nanoparticles to detect uric acid. The technique used to assemble the films that compose the biosensor was the Layer-by-Layer (LbL). Two techniques were used for the synthesis of nanoparticles for the construction of two different film architectures. In the first architecture, the nanoparticles were deposited in situ on a polyethyleneimine (PEI) and sodium polyvinyl sulfate (PVS) film - by reducing hexachloroplatinic acid hexahydrate with sodium borohydride. The bilayers composed of (PEI/UOx)n were deposited on a film containing platinum nanoparticles deposited in situ. In the second architecture, the nanoparticles were synthesized by mixing PEI solution with hexachloroplatinic acid solution and sodium borohydride solution. This solution was deposited alternating with enzymatic solution. The amperometric analyses were performed at +0.347 V potential, with successive additions of 2 mmol.L-1 of uric acid in an electrochemical cell containing phosphate buffered saline (PBS) pH 7.4. For the first architecture, the limit of detection found by the amperometric method was 5.17 µmol.L-1 with the linear detection range comprised in the range between 3.92 - 11.3 µmol.L-1 . For the second architecture, the limit of detection found by the amperometric method was 4.68 µmol.L-1 with a linear detection range between 14.18 - 55.56 µmol.L-1 . For the same architecture an using the differential pulse voltammetry method the values of limit of detection and linear detection range were 0.11 µmol.L-1 and particles / mL, respectively. The biosensors presented limits of detection close to the values found in the literature for other biosensor proving to be efficient for the detection of uric acid. / O ácido úrico é uma substância endógena produzida a partir do metabolismo das purinas. A concentração de ácido úrico sérico no organismo humano considerado normal é entre 0,24 - 0,52 mmol.L-1 . Altos níveis de ácido úrico no organismo levam a um quadro conhecido como hiperuricemia. Portanto, o monitoramento de ácido úrico no organismo é de grande importância. Neste trabalho apresentamos biossensores amperométricos baseados na associação da enzima UOx com nanopartículas de platina para detecção de ácido úrico. A técnica utilizada para a fabricação dos filmes que compõem o biossensor foi a Layer-by-Layer (LbL). Duas técnicas foram utilizadas para a síntese de nanopartículas para a construção de duas arquiteturas diferentes na construção dos filmes. Na primeira arquitetura, as nanopartículas foram depositadas in situ sobre um colchão de polieletrólitos – polietilenoimina (PEI) e polivinil sulfato de sódio (PVS) – pela redução do ácido hexacloroplatínico hexaidratado com boroidreto de sódio. As bicamadas compostas por (PEI/UOx)n foram depositadas sobre colchão contendo nanopartículas de platina depositadas in situ. Na segunda arquitetura, as nanopartículas foram sintetizadas misturando-se solução de PEI com solução de ácido hexacloroplatínico e solução de borohidreto de sódio. Esta solução foi depositada alternando-se com solução enzimática. As análises amperométricas foram realizadas em potencial +0,347 V, com adições sucessivas de ácido úrico de concentração 2 mmol.L-1 em uma célula eletroquímica contendo tampão fosfato salino (PBS) pH 7,4. Para a primeira arquitetura, o limite de detecção encontrado pelo método amperométrico foi de 5,17 µmol.L-1 com a faixa linear de detecção compreendido no intervalo entre 3,92 - 11,3 µmol.L-1 . Para a segunda arquitetura, o limite de detecção encontrado pelo método amperométrico foi de 4,68 µmol.L-1 com a faixa linear de detecção compreendido no intervalo entre 14,18 – 55,56 µmol.L-1 , e para o método DPV os valores de LD e faixa linear de detecção encontrados foram 0,11 µmol.L-1 e 1,8×10& ± 0,2×10& partículas/mL, respectivamente. Os biossensores apresentaram limites de detecção próximos aos valores encontrados na literatura, mostrando-se eficientes para detecção de ácido úrico.

Neste trabalho foram estudadas as potencialidades eletroanalíticas de um material híbrido condutor baseado em acetato de celulose e grafite com eletrodeposição de filme condutor de Azul da Prússia (CA/G/PB) como sensor para espécies com importância biológica. O material híbrido foi preparado pelo processo de inversão de fase e caracterizado pelas técnicas de microscopia eletrônica de varredura acoplada com espectroscopia de energia dispersiva (SEM-EDS) e voltametria cíclica. O composto Azul da Prússia (PB) foi imobilizado na superfície do material por eletropolimerização, aplicando-se um potencial fixo de 20 mV em uma janela de -0,3 V a 1,2 V. Os estudos eletroquímicos do eletrodo modificado CA/G/PB foram realizados em solução de KCl 0,1 mol.L-1, sendo obtidos dois pares redox para a espécie eletroativa imobilizada com potenciais médios (E0) em 0,204 V e 0,842 V, indicando um comportamento quase-reversível. O eletrodo demonstrou alta estabilidade após 500 ciclos redox, não sendo observada lixiviação da espécie eletroativa da superfície da matriz modificada. Os dois pares redox do material híbrido CA/G/PB permaneceram praticamente constantes entre os pH 5,0 e 8,0, indicando que as intensidades de pico não são significativamente afetadas nessa faixa de pH. A correlação linear entre as intensidades de pico e a raiz quadrada da velocidade de varredura, indicou que o sistema possui um comportamento similar aqueles em que o processo é controlado por difusão das espécies eletroativas à superfície do eletrodo. O azul da Prússia imobilizado foi aplicado na determinação de dopamina (DP), ácido úrico (AU), ácido ascórbico (AA) e Paracetamol (PCT) através da técnica de voltametria cíclica, voltametria de pulso diferencial e cronoamperometria. / In this work, we studied the electroanalytical potential of a conductive hybrid material based on cellulose acetate and graphite with electrodeposition Blue conductor film of Prussia (CA / G / PB) as a sensor for species with biological importance. The hybrid material was prepared by phase inversion process and characterized by the techniques of scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS) and cyclic voltammetry. The dye of Prussian blue (PB) was immobilized on the surface of the material by electropolymerization applying a fixed potential of 20 mV in a interval from -0.3 V to 1.2 V. The electrochemical behavior of the modified electrode CA / G / PB were performed in solution of 0.1 mol L-1 KCl being obtained two redox couples for the electroactive species immobilized with midpoint potentials (E0) in 0.204 V and 0.842 V, indicating a quasi-reversible behavior. The electrode showed high stability after 500 redox cycles with no observed leaching of electroactive species to the surface of the modified electrode. The two redox pair of the CA / G / PB electrode was kept practically constant within pH 5.0 and 8.0, indicating that the peak intensities are not significantly affected in this pH range. The linear correlation between peak intensities and the square root of scan rate, indicated that the system has a similar behavior those in which the process is controlled by diffusion of electroactive species to the electrode surface. The immobilized Prussian blue was applied to determine dopamine (DP), uric acid (UA), ascorbic acid (AA) and paracetamol (PCT) by analytical techniques of cyclic voltammetry, differential pulse voltammetry and chronoamperometry.

Submitted by ANDRESSA TRECENTI DAMACENA null (dretrecenti@hotmail.com) on 2016-05-04T11:16:43Z No. of bitstreams: 1 Dissertacao Andressa - Repositório.pdf: 2946507 bytes, checksum: 9abbfaa6ae7910659e2f50cdfcba9757 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-05-04T20:44:45Z (GMT) No. of bitstreams: 1 damacena_at_me_bot.pdf: 2946507 bytes, checksum: 9abbfaa6ae7910659e2f50cdfcba9757 (MD5) / Made available in DSpace on 2016-05-04T20:44:45Z (GMT). No. of bitstreams: 1 damacena_at_me_bot.pdf: 2946507 bytes, checksum: 9abbfaa6ae7910659e2f50cdfcba9757 (MD5) Previous issue date: 2016-02-23 / Introdução: Pré-eclâmpsia é uma síndrome sistêmica específica da gestação com etiopatogenia ainda não esclarecida, porém acredita -se ser decorrente de alterações no processo de invasão trofoblástica, com consequente inadequado suprimento sanguíneo uterino e estresse oxidativo do tecido placentário. O aumento da concentração de ácido úrico sérico materno (AU) em mulheres com pré-eclâmpsia tem sido associado com a gravidade da hipertensão, proteinúria e prognóstico materno e perinatal na gestação. Objetivos: Identificar a associação entre a concentração sérica de ácido úrico e resultados maternos e perinatais adversos e correlacionar a concentração sérica do ácido úrico materno com recémnascidos pequenos para idade gestacional e proteinúria materna. Sujeitos e Métodos: Foi realizado estudo retrospectivo, em gestantes com pré-eclâmpsia, as quais foram estratificadas de acordo com a dosagem de ácido úrico sérico em dois grupos: I (inferior a 6 mg/dL) e II (igual ou superior a 6 mg/dL) e avaliados resultados adversos maternos e perinatais. Resultados: No grupo II houve maior frequência de crise hipertensiva(25%), eclampsia(6,9%), síndrome HELPP parcial (7,8%) e síndrome HELLP(6,9%), maior número de recém-nascidos pequenos para idade gestacional(47%), menor peso do recém-nascido, maior porcentagem de óbito fetal(1,8%), de prematuridade(68%) e de índice de Apgar no 1º minuto(38%). Conclusões: Os resultados demonstram que as paciente com ácido úrico elevado apresentam piores resultados adversos tanto maternos quanto perinatais, sendo assim a dosagem de ácido úrico sérico materna associadas a outros exames clínicos e laboratoriais, pode auxiliar nos processos de decisão na prática obstétrica. / Introduction: Preeclampsia is a specific systemic disease of pregnancy with unknown etiology, but it is believed to be due to changes in the process of trophoblastic invasion, leading to an inadequate uterine blood supply and oxidative stress of the placental tissue. Increasing of maternal uric acid serum concentration (UA) in women with pre-eclampsia has been associated with the severity of hypertension, proteinuria and maternal and perinatal outcome on pregnancy. Objectives: Identify the association between serum uric acid and adverse maternal and perinatal outcomes. More specifically, the correlation of maternal UA serum concentration with newborn size for gestational age and maternal proteinuria. Subjects and Methods: Cross observational study in pregnant women with preeclampsia, which were stratified according to dose of serum uric acid into two groups, as follow: I (below 6 mg/dL) and II (greater or equal to 6 mg/dL). Maternal and perinatal adverse outcomes were examined. Results were analyzed by T - Student and chi-square tests and correlations were evaluated by Pearson test. The level of significance used was 5%. Results: In group II there were a greater frequency of hypertensive crisis, eclampsia, partial HELPP syndrome and HELLP syndrome. Also it were observed an increased number of small newborns for gestational age, lower weight of the newborn, the higher percentage of fetal death, prematurity and index Apgar at 1 minute. Conclusions: The results suggest that patients with higher uric acid have worse adverse outcomes both for maternal and perinatal. In conclusion, the dosage of maternal serum uric acid associated with other clinical and laboratory tests can help in the decision on obstetrical practice.

Submitted by Tony Rogerio de Lima Dadamos null (tonyrlrl@yahoo.com.br) on 2018-02-20T16:25:35Z No. of bitstreams: 1 Tese_AU_TRLD_2018.pdf: 2071412 bytes, checksum: ba59227c90cba94171f8548d07346f1a (MD5) / Approved for entry into archive by Elza Mitiko Sato null (elzasato@ibilce.unesp.br) on 2018-02-21T19:00:37Z (GMT) No. of bitstreams: 1 dadamos_trl_dr_sjrp.pdf: 2071412 bytes, checksum: ba59227c90cba94171f8548d07346f1a (MD5) / Made available in DSpace on 2018-02-21T19:00:37Z (GMT). No. of bitstreams: 1 dadamos_trl_dr_sjrp.pdf: 2071412 bytes, checksum: ba59227c90cba94171f8548d07346f1a (MD5) Previous issue date: 2018-01-24 / Este trabalho apresenta metodologias de desenvolvimento, otimização, e validação de procedimentos de medição eletroquímica de parâmetros bioquímicos em fluidos biológicos. As ferramentas desenvolvidas foram aplicadas à medição voltamétrica, simples e de baixo custo de ácido úrico (AU) em soro humano que se apresenta como uma alternativa confiável às medições realizadas pelo método de referência espectrofométrico. Foi estudada a medição de AU no soro visto a ser utilizada no diagnóstico de várias doenças, tais como gota, doenças cardiovasculares e neoplasias. O eletrodo de trabalho modificado desenvolvido e otimizado é composto por 25 % de lignina, 60 % de nanografite, 15 % de óleo mineral e cobre metálico eletrodepositado. As medições foram realizadas por um método de adição cumulativa de padrão (MAP-C), recorrendo a um novo tratamento estatístico dos dados de calibração, que permite a calibração da instrumentação num pequeno volume de soro. A incerteza da medição foi estimada recorrendo a diversas abordagens bottom-up desenvolvidas e usando abordagens pragmáticas top-down apresentadas na bibliografia. As componentes de incerteza foram combinadas usando a Lei de Propagação de Incertezas ou os métodos numéricos de Kragten e Monte Carlo. Procedeu-se igualmente a uma avaliação bayesiana da incerteza da medição que envolve a atualização de dados da prevalência de ácido úrico na população com o resultado da medição do soro específico analisado. Os modelos metrológicos desenvolvidos foram implementados em folhas de cálculo MSExcel de fácil utilização pelo analista. As avaliações bottom-up da incerteza da medição recorreram a estimativas da incerteza de extrapolação produzidas pelo modelo de regressão ou usando simulações de Monte Carlo aplicáveis quando os pressupostos do modelo de regressão não são cumpridos. O método de adição cumulativa de padrão foi aplicado com sucesso à análise de soro humano pela adição de 1,0, 3,0, 5,0, 7,0 e 9,0 mg dL-1 de AU a 5 mL de soro. A adequação da qualidade das medições eletroquímicas foi avaliada comparando sua incerteza com um valor alvo de 0,56 mg dL-1 (uma oitava parte das faixas de AU de indivíduos saudáveis) e avaliado a compatibilidades das medições com determinações realizadas pelo procedimento de referência. As medições realizadas revelaram-se válidas e com menor custo do que as produzidas pelo método de referência. As ferramentas desenvolvidas para a construção e otimização de eletrodos de trabalho são aplicáveis à medição de outras espécies de análise e em outras matrizes. O método de adição cumulativa de padrão desenvolvido, bem como os modelos de medição respectivos desenvolvidos, são aplicáveis a qualquer tipo de medição instrumental não destrutiva de soluções. / This work presents methodologies for the development, optimization and validation of procedures for the electrochemical measurement of biochemical parameters in biological fluids. The developed tools were applied to voltammetric, simple and low-cost measurements of uric acid (AU) in human serum, which proved to be a reliable alternative to the spectrophotometric reference method. It was studied the measurement of AU in serum since it is used in the diagnosis of various diseases, such as gout, cardiovascular diseases and neoplasms. The developed and optimized modified working electrode is composed of 25 % lignin, 60 % nanocarbon, 15 % mineral oil and electrodeposited copper. The measurements were performed using a cumulative standard addition method (MAP-C), using a new statistical treatment of the calibration data, which allows the calibration of the instrumentation in a small volume of serum. The measurement uncertainty was estimated using developed bottom-up approaches and using pragmatic top-down approaches presented in the literature. The uncertainty components were combined using the Uncertainty Propagation Law or the numerical Kragten and Monte Carlo methods. A bayesian evaluation of the measurement uncertainty was performed, involving the updating of uric acid prevalence in the population with the result of the measurement of AU in the specific serum sample. The developed metrological models were implemented in user-friendly MS-Excel spreadsheets. The bottom-up assessments of measurements uncertainty involve the estimation of the extrapolation uncertainty from the regression model or using Monte Carlo simulations applicable to when the assumptions of the regression model are not valid. The cumulative standard addition method was successfully applied to the analysis of human serum by adding 1.0, 3.0, 5.0, 7.0 and 9.0 mg dL-1 of AU to 5 mL of serum. The adequacy of the electrochemical measurements was assessed by comparing their uncertainty with a target value of 0.56 mg dL-1 (one-eighth of the range of AU in healthy individuals) and by evaluating the compatibility of measurements with determinations performed by the reference procedure. The performed measurements are valid and significantly cheaper than those produced by the reference method. The tools developed for the construction and optimization of working electrodes are applicable to the measurement of other analytes and matrices. The developed cumulative standard addition method and respective measurement models, are applicable to any kind of non-destructive chemical measurement of a solution.

Orientador: Iguatemy Lourenço Brunetti / Banca: Mariza Pires de Melo / Banca: Eduardo Maffud Cilli / Resumo: Em pacientes com doença renal crônica é observado à presença de estresse oxidativo e a exacerbação desse estresse com o tratamento hemodialítico, bem como tem se postulado a ação antioxidante de alguns solutos urêmicos. Esse contexto instigou-nos explorar, a ação antioxidante dos solutos urêmicos: L-arginina, Ácido Úrico, Ácido Hipúrico, Creatinina, Fenol, Metilguanidina, p-Cresol, L-tirosina e Uréia, utilizando sistemas-modelo in vitro. Quatro desses solutos mostraram eficiência (expressa via o IC50 em µmol/L) para os sistemas-modelo: Capacidade de captura sobre o ABTS + , p-Cresol (3,99 ± 0,01), L-tirosina (5,23 ± 0,02), Fenol (12,98 ± 0,09) e o Ácido Úrico (16,75 ± 0,14); Capacidade de captura sobre o HOCl / OCl -, L-tirosina (2,83 ± 0,04), Ácido Úrico (5,75 ± 0,13), Fenol (8,95 ± 0,10) e p- Cresol (15,75 ± 0,12), e o bleaching da crocina (lipoperoxidação), Ácido Úrico (6,90), Fenol (1125,81) e p-Cresol (1162,31). Em relação à capacidade de captura sobre o Ânion Radical Superóxido e o Peróxido de Hidrogênio nenhum dos solutos apresentou atividade significativa. Em todos os ensaios onde não foi observada atividade antioxidante, investigou-se desde concentrações fisiológicas, urêmicas e até 10 vezes maior que as concentrações urêmicas médias. Como os solutos urêmicos, Ácido Úrico, p-Cresol, Fenol e L-tirosina capturaram significativamente as espécies reativas, ABTS + , HOCl / OCl - e ROO  , estudou-se o comportamento da mistura desses solutos, tendo como referência o IC50 de cada soluto. Obteve-se nos ensaios de captura do ABTS + e do HOCl / OCl - os IC50, como uma fração de concentração de 26 e 27%, respectivamente, para cada soluto na mistura, o que demonstrou um efeito aditivo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Patients with chronic kidney disease suffer from oxidative stress and this stress is exacerbated by hemodialysis. It has been postulated that some uremic solutes have antioxidant effects. This context prompted us to explore the antioxidant action of the uremic solutes: L-arginine, uric acid, hippuric acid, creatinine, phenol, methylguanidine, p-cresol, L-tyrosine and urea, by means of 5 in vitro model systems. Only four of these solutes were effective antioxidants (assessed by their IC50 in µmol/L) in 3 model systems: ABTS + scavenging: p-cresol (3.99±0.01), L-tyrosine (5.23±0.02), phenol (12.98±0.09) and uric acid (16.75±0.14); hypochlorous acid scavenging: L-tyrosine (2.83±0.04), uric acid (5.75±0.13), phenol (8.95±0.10) and p-cresol (15.75±0.12); and crocin bleaching (lipoperoxidation): uric acid (6.90), phenol (1,125.81) and p-cresol (1,162.31). In tests with the superoxide radical anion and hydrogen peroxide, none of the solutes showed antioxidant activity. In each of the assays in which no activity was detected, tests were carried out over a range of solute concentrations, from normal physiological levels, through typical uremic up to ten times higher than mean uremic concentrations. As the 4 uremic solutes, uric acid, p-cresol, phenol and L-tyrosine showed significant scavenging activity for 3 reactive species, ABTS + , HOCl / OCl - and ROO  , the behavior of mixture of these solutes was investigated, with reference to the IC50 of each solute. In the ABTS + and HOCl / OCl - scavenging assays, the IC50 involved a concentration of 26% and 27%, respectively, of each solute in the mixture, demonstrating... (Complete abstract click electronic access below) / Mestre

Orientador: Vera Terezinha Medeiros Borges / Resumo: Introdução: Pré-eclâmpsia é uma síndrome sistêmica específica da gestação com etiopatogenia ainda não esclarecida, porém acredita -se ser decorrente de alterações no processo de invasão trofoblástica, com consequente inadequado suprimento sanguíneo uterino e estresse oxidativo do tecido placentário. O aumento da concentração de ácido úrico sérico materno (AU) em mulheres com pré-eclâmpsia tem sido associado com a gravidade da hipertensão, proteinúria e prognóstico materno e perinatal na gestação. Objetivos: Identificar a associação entre a concentração sérica de ácido úrico e resultados maternos e perinatais adversos e correlacionar a concentração sérica do ácido úrico materno com recémnascidos pequenos para idade gestacional e proteinúria materna. Sujeitos e Métodos: Foi realizado estudo retrospectivo, em gestantes com pré-eclâmpsia, as quais foram estratificadas de acordo com a dosagem de ácido úrico sérico em dois grupos: I (inferior a 6 mg/dL) e II (igual ou superior a 6 mg/dL) e avaliados resultados adversos maternos e perinatais. Resultados: No grupo II houve maior frequência de crise hipertensiva(25%), eclampsia(6,9%), síndrome HELPP parcial (7,8%) e síndrome HELLP(6,9%), maior número de recém-nascidos pequenos para idade gestacional(47%), menor peso do recém-nascido, maior porcentagem de óbito fetal(1,8%), de prematuridade(68%) e de índice de Apgar no 1º minuto(38%). Conclusões: Os resultados demonstram que as paciente com ácido úrico elevado apresentam piores resulta... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Preeclampsia is a specific systemic disease of pregnancy with unknown etiology, but it is believed to be due to changes in the process of trophoblastic invasion, leading to an inadequate uterine blood supply and oxidative stress of the placental tissue. Increasing of maternal uric acid serum concentration (UA) in women with pre-eclampsia has been associated with the severity of hypertension, proteinuria and maternal and perinatal outcome on pregnancy. Objectives: Identify the association between serum uric acid and adverse maternal and perinatal outcomes. More specifically, the correlation of maternal UA serum concentration with newborn size for gestational age and maternal proteinuria. Subjects and Methods: Cross observational study in pregnant women with preeclampsia, which were stratified according to dose of serum uric acid into two groups, as follow: I (below 6 mg/dL) and II (greater or equal to 6 mg/dL). Maternal and perinatal adverse outcomes were examined. Results were analyzed by T - Student and chi-square tests and correlations were evaluated by Pearson test. The level of significance used was 5%. Results: In group II there were a greater frequency of hypertensive crisis, eclampsia, partial HELPP syndrome and HELLP syndrome. Also it were observed an increased number of small newborns for gestational age, lower weight of the newborn, the higher percentage of fetal death, prematurity and index Apgar at 1 minute. Conclusions: The results suggest that pati... (Complete abstract click electronic access below) / Mestre

This thesis provides an appraisal of the structure of clustering of metabolic phenotypes and evaluates the pathophysiological mechanisms underlying the relationship between urinary uric acid and albumin excretion. Two population-based studies were involved. In the first part, we used data obtained in a large representative cross-sectional survey in the Czech Republic (Czech post-MONICA study). We showed that the urinary albumin/creatinine ratio (uACR) was an independent factor for an increase in serum uric acid (SUA) levels in adults without manifest metabolic syndrome (MetS), but with 1-2 MetS component(s). Furthermore, SUA levels increased by the synergistic interaction of uACR with visceral adiposity and blood pressure, which may suggest obesity-related hypertension with altered renal hemodynamics as the primary mechanism. In the second part, we analyzed data captured in a representative population sample of French Canadians (CARTaGENE study) with more detailed urine biochemical analyses available. This study yielded two novel observations. First, we showed that the rs13129697 major T allele, which has been associated with increased SUA levels in our analysis as well as in prior publications, was associated with a paradoxical decrease in uACR. The reason for this discrepant finding is the...