Thesis (M. CM)--Hong Kong Baptist University, 2006. / Dissertation submitted to the School of Chinese Medicine. Includes bibliographical references (leaves 26-28).

Thesis (M.S.)--Georgia State University, 2006. / Title from title screen. Yu-Sheng Hsu, committee chair; Gengsheng (Jeff) Qin, Xu Zhang, committee members. Electronic text (116 p.) : digital, PDF file. Description based on contents viewed May 17, 2007. Includes bibliographical references (p. 61-67).

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 86-94).

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Orientador: José Carlos Peraçoli / Resumo: A proteinúria tem sido considerada um sinal importante para identificar o tipo de hipertensão que ocorre na gestação e está relacionada com o resultado materno e perinatal. Objetivo: o objetivo deste estudo foi avaliar, em gestantes hipertensas, por meio da eletroforese, o padrão das proteínas urinárias e seus pesos moleculares. Sujeitos e métodos: eletroforese em gel de poliacrilamida foi realizada em urina de 143 gestantes hipertensas, divididas em quatro grupos: hipertensão arterial crônica (HAC), pré-eclâmpsia/eclâmpsia (PE), hipertensão arterial crônica superposta por pré-eclâmpsia (HAC+PE) e hipertensão gestacional (HG). A presença e o número de bandas das proteínas tubular e glomerular e, seus pesos moleculares foram correlacionados com o tipo de hipertensão arterial, a presença (≥ 300 mg/24horas) ou não de proteinúria, o grau de proteinúria (leve: < 2g/24horas e grave: ≥ 2 g/24horas) e o valor do ácido úrico (< 6 mg% e ≥ 6 mg%). Para comparação das variáveis qualitativas foi usado o teste do qui-quadrado e para comparação das variáveis quantitativas foi usado o teste t de Student. Foi considerado significância quando valor de p < 0,05. Resultados: em todas as gestantes avaliadas foram encontradas proteínas tubular e glomerular e o número de bandas de proteínas não diferenciou os tipos de hipertensão arterial. A presença de pelo menos quatro bandas glomerulares foi significativamente maior nas gestantes com PE e HAC+PE, com proteinúria significativa, com proteinúria grave e com valor de ácido úrico ≥ 6 mg%. Quando comparada com proteínas de peso molecular ≤ 90 kDa a porcentagem de proteínas com peso molecular ≥ 160 kDa foi significativamente maior nas gestantes com PE, HAC+PE e HG, nas gestantes com proteinúria significativa e com ácido úrico ≥ 6 mg%... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Proteinuria has been considered an important sign to identify the hypertensive disorders encountered during pregnancy and it is related to the maternal and perinatal outcomes. Objective: the aim of this study was to evaluate the urinary protein patterns and their molecular weight in hypertensive pregnant women, through urinary electrophoresis. Subjects and methods: Sodium dodecyl sulphatepolyacrylamide gel electrophoresis (SDS-PAGE) was performed on the urine of143 hypertensive pregnant women that were divided into the following groups: chronic hypertension (CH), pre-eclampsia/eclampsia (PE), pre-eclampsia superimposed upon chronic hypertension (CH+PE), and gestational hypertension (GH). Presence and the number of tubular and glomerular protein bands, and their molecular weight were correlated with the type of hypertension, the proteinuria level (present: ≥ 300 mg/24h or absent: < 300 mg/24h; mild: < 2 mg/24h or severe: ≥ 2 mg/24h) and the uric acid level (< 6.0 mg/dL or ≥ 6.0 mg/dL). The chi-square test was used for comparing the qualitative date and the Student t test was used to compare the quantitative date. A p value of 0.05 was regarded as statistically significant. Results: glomerular and tubular proteins were found on all the hypertensive pregnant women and there were no significant differences in the number of protein bands. The glomerular protein band number was significantly higher in PE and CH+PE groups, in pregnant women with proteinuria, in pregnant women with severe proteinuria, and in pregnant women with uric acid level ≥ 6 mg/dL. When compared with the protein of molecular mass ≤90 kDa... (Complete abstract click electronic access below) / Doutor

Orientador: Cristina Antoniali Silva / Banca: Francisco Leydson Formiga Feitosa / Banca: Silmeia Garcia Zanati Bazan / Resumo: O Nebivolol (Neb) é um antagonista dos receptores β1-Adrenérgicos (β1-RA) de terceira geração que causa vasodilatação efeito mediado pelo óxido nítrico e redução do estresse oxidativo (EO) em modelos pré-clínicos e estudos clínicos de Hipertensão Arterial Sistêmica (HAS). Este estudo avaliou os níveis de biomarcadores de estresse oxidativo e atividade de sistemas antioxidantes enzimáticos e não-enzimáticos na saliva de pacientes hipertensos antes e após o tratamento com doses terapêuticas anti-hipertensivas de Neb. Vinte e quatro pacientes hipertensos foram tratados com 5 mg/dia de Neb por oito semanas consecutivas. Amostras de saliva não estimulada foram coletadas de pacientes com idade entre 25 a 70 anos para análise da capacidade antioxidante total (CAT), a qual foi medida pelo Método FRAP (Ferric Reducing Antioxidant Power), a atividade enzimática da superóxido dismutase (SOD) e quantificação do ácido úrico (AU) antes (NT, grupo não tratado) e após tratamento (T, grupo tratado) com Neb. Adicionalmente, parâmetros clínicos, bioquímicos e eletrocardiográficos foram avaliados em ambos os grupos. Os grupos foram comparados pelo teste t de Student, pareado (p<0,05). Neb não alterou os valores de CAT (NT:1,697 ± 0,433 versus T: 1,674 ± 0,092 mmol/L, p=0,8454), ou a atividade da SOD (EA- NT: 66,56 ± 4,977 versus T: 60,66 ± 6,376 UE/mL, p=0,4886) na saliva. No entanto, o tratamento com Neb aumentou a concentração do AU em pacientes tratados (NT: 24,64 ± 1,686 v... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Nebivolol (Neb) is third-generation selective β1-adrenergic receptor antagonist which causes vasodilation (by nitric oxide release) and has been shown to reduce oxidative stress (OS) in pre-clinical models and clinical studies. This study aimed to evaluate the OS levels and the enzymatic and non-enzymatic antioxidant systems in saliva of patients with ESH before and after anti-hypertensive therapeutic doses of Neb. Twenty-four essential hypertensive patients were treated with 5 mg Neb once daily for a total of 8 weeks. Unstimulated saliva samples were collected from 25 to 70 years-old patients for evaluation of total antioxidant capacity (TAC), which were measured by the ferric reducing antioxidant power (FRAP) assay, as well as to assess the activity of enzymatic (superoxide dismutase, SOD) and non-enzymatic (uric acid, UA) antioxidant systems, respectively before (C, control group) and after treatment (T, treated group) with Neb. Additionally, clinical, biochemical and electrocardiographic parameters were evaluated in both groups. Data were analyzed by paired Student's t-test (p < 0.05). Neb did not alter TAC values (UT: 1,697 ± 0,433 versus T: 1,674 ± 0,092 mmol/L, p=0,8454), or SOD activity (EA-UT: 66,56 ± 4,977 versus T: 60,66 ± 6,376 UE/mL, p=0,4886) in saliva. However, Neb treatment increased salivary UA activity in treated patients (UT: 24,64 ± 1,686 versus T: 35,56 ± 2,014 mg/mL, p=0,0002). Clinical, electrocardiographic and biochemical parameters were positively cha... (Complete abstract click electronic access below) / Mestre

Cardiac hypertrophy is a fundamental response to an increased workload on the heart characterized by cardiac myocyte (CM) growth and left ventricular (LV) wall thickening. In a model of hypertension, e.g. chronic pressure overload, this process may become maladaptive, initially leading to impaired myocardial relaxation and LV filling, and subsequently to LV dilation, wall thinning, and contractile failure. Hemodynamic overload activates Gαq-mediated signaling responsible for transcriptional reactivation of fetal growth programs, activation of the mitogen-activated protein kinase (MAPK) cascade, and oxidative stress. The precise mechanism by which MAPK is activated in pressure overload, and the role oxidative stress plays in mediating this hypertrophic signaling are still under investigation. In CMs, the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) maintains calcium stores, and thus may regulate calcium-dependent MAPK signaling. Our laboratory showed that SERCA is activated in CMs by reversible oxidative post-translational modification (OPTM) of its most reactive cysteine site (C674). We hypothesized that OPTMs mediate the effects of hypertrophic stimuli in CMs via reversible oxidation of SERCA at C674. To test this hypothesis, we employed a reductionist model: isolated adult rat ventricular myocytes (ARVM) overexpressing wild-type (WT) or mutant SERCA, in which C674 is substituted with a redox-insensitive serine (C674S). Using alpha-adrenergic receptor (αAR) stimulation as a model of Gq-mediated hypertrophy, we found that C674S expression decreased both CM growth and MAPK activation. Furthermore, biotin switch revealed that αAR stimulation induced a reversible OPTM of SERCA at C674. We generated a transgenic mouse expressing a single-allele C674S SERCA2 knock-in mutation (SKI) to explore this mechanism further in the setting of pressure overload, a disease model of Gq-activation in vivo. SKI mice subjected to ascending aortic constriction (AAC) had decreased hypertrophy compared to WT. Ventricular myocytes isolated from adult SKI mice also had diminished MAPK activation in response to hypertrophic stimulation in vitro and decreased SERCA function at baseline. These findings led us to the conclusion that redox-activation of SERCA via reversible modification of C674 is critical for the complete transduction of hypertrophic stimuli to MAPK signaling and CM hypertrophy.

Thesis (M.D.)--Boston University