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Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

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

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-06, page: 3221. Adviser: Eric Boerwinkle. Includes bibliographical references.

Thesis (Ph. D.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains xi, 172 p. : ill. Includes abstract. Includes bibliographical references.

No description available.

O hiperadrenocorticismo é uma das endocrinopatias mais frequentes em cães. As manifestações clínicas e as lesões associadas com o hiperadrenocorticismo resultam primariamente da hipercortisolemia crônica. Várias são as alterações clínicas observadas em diversos sistemas orgânicos, como também as laboratoriais que ocorrem como consequência dos efeitos gliconeogênico, lipolítico, catabólico, protéico e anti-inflamatório dos glicocorticóides. No que concerne aos rins, a hipercortisolemia crônica pode causar lesão do glomérulo, como também esta estrutura pode sér comprometida secundariamente pela hipertensão arterial sistêmica e, assim, evoluir para doença renal crônica. Neste estudo foram avaliados 10 cães normotensos com hiperadrenocorticismo hipófise dependente, antes e após a terapia com trilostano, com o intuito de verificar a existência ou não de proteinúria patológica pelos métodos quantitativos (razão proteína-creatinina urinária) e qualitativos (eletroforese de proteínas urinárias), como também de acompanhar a intensidade da mesma ao longo da evolução da doença e do curso da terapia. A principal lesão renal detectada nos cães com HAC foi no segmento tubular, constatada pelo predomínio de bandas de proteínas urinárias de baixo peso molecular, indicando o comprometimento na absorção dessas proteínas no segmento proximal do néfron, sendo que a presença dessas bandas perduraram ao longo da terapia, mesmo quando as concentrações séricas de cortisol diminuíram gradativamente após a terapia com trilostano. Ainda, o bom controle do hiperadrenocorticismo pela terapia e a pressão arterial sistêmcia dentro dos valores de normalidade podem ter contribuído para a prevenção do desenvolvimento de lesão glomerular. / Hyperadrenocorticism is one of the most common endocrine disorders in dogs. Clinical sings and organs lesions associated with hyperadrenocorticism result primarily from chronic hypercortisolemia. There are several clinical changes observed in different organ systems, as well as laboratory alterations that occur as a result of the effects of gluconeogenic, lipolytic, catabolic, protein and anti-inflammatory glucocorticoids. Regarding to the kidneys, chronic hypercortisolemia can cause damage to the glomerulus, but also that structure may be compromised by secondary hypertension and, thus, evolve into chronic kidney disease. This study evaluated 10 normotensive dogs with pituitary dependent hyperadrenocorticism, before and after therapy with trilostane, in order to verify the existence of pathological proteinuria by quantitative (urinary protein-to-creatipine) and qualitative (urinary protein electrophoresis) methods, and also to monitor its intensity over the course of the disease and therapy. The main renal lesion detected in dogs with hyperadrenocorticism was in the tubular segment, evidenced by the prevalence of urinary protein bands of lower molecular weight, indicating the lack absorption of these proteins in the proximal segment of the nephron. Low molecular weight proteins persisted throughout therapy, even when serum cortisol concentrations gradually decreased after treatment with trilostane. Moreover, good control of hyperadrenocorticism and blood pressure within the normal range may have contributed to the prevention ofthe development of glomerular injury.

This dissertation describes the background, setting, set-up and analysis of several 11-year prospective longitudinal studies with exposures of Proteinuria or Dyspnea and the primary outcome of all-cause mortality. Cause-specific mortality was also obtained for each exposed/unexposed group to determine whether exposures are at all related to mortality outcome. These studies came out of the Health Effects of Arsenic Longitudinal Study (HEALS). The objectives of this dissertation are to: 1) assess the reproducibility of dyspnea as determined by questionnaire in evaluating for the presence or absence of dyspnea; 2) examine the association between arsenic exposure and dyspnea cross-sectionally since one of the longitudinal studies proposed, evaluating the symptom of dyspnea as a predictor of mortality, is embedded in an ongoing study evaluating the effects of chronic exposure to arsenic in well water; 3) review the worlds relevant literature on the potential for dyspnea, a symptom, to be a predictor of all-cause mortality; 4) try to determine whether dyspnea, a symptom, is a predictor of all-cause and cause-specific mortality in the developing country of Bangladesh; 5) try to determine whether simple dipstick proteinuria, is a predictor of all-cause and cause-specific mortality in rural Bangladesh. A methodologic study was done on a small subgroup of subjects to determine whether dyspnea determined by simple questionnaire was reproducible. If the presence or absence of dyspnea on questionnaire occurred by chance, then using dyspnea as the exposure variable would not be valid. The results of this study revealed that: 1) dyspnea as determined by questionnaire was reproducible ie the same response occurs when the same question on dyspnea was asked at a later time and disguised by being buried in a list of questions; 2) the reproducibility of the response was greater than 90%, independent of whether dyspnea was present or absent on the initial response. A second preliminary cross-sectional evaluation was done to determine whether the exposure variables of proteinuria or dyspnea were associated with arsenic exposure at baseline since the primary overall focus of HEALS is related to arsenic exposure. No definitive association for proteinuria and arsenic was found. However, an analysis and study found a strong dose-response relationship between arsenic well water concentration (exposure) and the presence of dyspnea, independent of smoking. A weak dose-response relationship was also found between smoking and dyspnea. Clearly, both arsenic exposure and smoking are two of a number of important variables that need to be controlled for in these prospective studies. In addition, dyspnea was found in a longitudinal study to be associated with all-cause and cause-specific mortality, diseases most related to the heart and lungs. Finally, dipstick proteinuria at the 1+ level (not trace) was found to be a predictor of all-cause and cardiovascular disease mortality in rural Bangladesh. Further discussion is on the implications of the study findings including the concepts of dipstick proteinuria in screening and dyspnea in screening and directions of future research.

O hiperadrenocorticismo é uma das endocrinopatias mais comuns em cães, sendo caracterizado pela exposição excessiva de glicocorticóides secretados pelas adrenais. A hipercortisolemia crônica pode promover várias complicações, incluindo hipertensão sistêmica e glomerulonefrite. A glomerulonefrite pode desencadear variáveis graus de proteinúria e uma tendência de evolução para doença renal crônica. A perda de proteínas na urina, principalmente da albumina, é uma característica das doenças glomerulares e a determinação de variáveis laboratoriais, como a razão proteína:creatinina urinária (RPC), albuminúria (teste de ELISA) e eletroforese das proteínas urinárias, são recomendadas para a elucidação do diagnóstico. Assim, o objetivo do estudo é avaliar a relação entre proteinúria e hipertensão arterial sistêmica em cães com hiperadrenocorticismo e verificar, pela avaliação da albuminúria e do peso molecular das proteínas urinárias, o segmento do néfron que foi comprometido ou lesado. Foram avaliados 30 cães com diagnóstico de hiperadrenocorticismo, subdivididos em 13 cães com hipertensão arterial sistêmica (grupo I) e 17 cães normotensos (grupo II). Foram determinados a razão proteína:creatinina urinária (RPC); a albuminúria pela avaliação da albumina normalizada e razão albumina: creatinina urinária (RAC) e a eletroforese de proteínas pela técnica em gel de poliacrilamida, contendo dodecil sulfato de sódio (SDS - PAGE). Os resultados foram comparados com os dados obtidos de 30 cães clinicamente saudáveis e foi constatado que não houve influência da hipertensão arterial sistêmica nos cães com hiperadrenocorticismo em relação à quantificação da albuminúria, determinada pelo método ELISA, e nem na qualidade e quantidade das bandas de proteínas de baixo (< 60 kDa) e de alto peso molecular (> 60 kDa) determinada pela eletroforese. No entanto foi determinado que cães com hiperadrenocorticismo podem desenvolver lesões glomerulares e tubulares, caracterizadas pela presença de albuminúria e de proteínas de alto e de baixo pesos moleculares, independentemente da presença de hipertensão arterial sistêmica. Concluindo que os métodos laboratoriais, a eletroforese de proteína urinária em gel de poliacrilaminda associada à avaliação quantitativa da proteína total, como a determinação quantitativa da albuminúria, são passíveis de serem empregadas para a avaliação dos segmentos dos néfrons comprometidos que causaram as perdas de proteínas na urina. / Hyperadrenocorticism is a common endocrinopathie in dogs characterized by excessive glucocorticoid expousure secondary to adrenal secretion. Chronic hypercortisolemia may promote several complications, including sistemic hypertension and glomerulonephritis. Glomerulonephritis may lead to different proteinuria degrees and chronic renal disease. Urine protein loss, specially albumin, is characteristic in glomerular diseases. Laboratorial determination by the urinary protein/creatinin ratio (PCR), albuminuria (ELISA test) and urinary protein electrophoresis are recommended for diagnosis. The aim of this study is to evaluate the relationship between proteinuria and sistemic arterial hypertension in dogs with hyperadrenocorticism and to identify the nephron injured segment by evaluating albuminuria and urinary protein molecular weight. Thrithy dogs with hyperadrenocorticism were subdivided in 2 groups as following: 13 dogs with sistemic arterial hypertension (group I) and 17 normal dogs (group II). Urinary protein/creatinin ratio (PCR); albuminuria using the evaluation of normalized albumin and urinary albumin/creatinin ratio (ACR); and protein electrophoresis using polyacrylamide gel with sodium dodecil sulfate (SDS - PAGE) were performed. Results were compared with data of 30 clinically healthy dogs. No influence of sistemic arterial hypertension in dogs with hyperadrenocorticism was noticed in albuminuria magnitude using the ELISA method, nor in the quality and quantity of low (<60 kDa) and high (> 60 kDa) molecular weight bands observed in electrophoresis. However, dogs with hyperadrenocorticism can develop glomerular and tubular lesions, characterized by albuminuria and by the presence of high and low molecular weight proteins in urine independently of sistemic arterial hypertension. Furthermore, urinary protein electrophoresis in polyacrylaminde gel associated to quantitative evaluation of total protein such as the quantitative determination of the albuminuria, may be used in evaluating committed nephrons segments that caused urine protein loss.

<p><em>Background </em>The proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (ERL) are the potent immunosuppressive drugs using in organ transplantation and has been used successfully in renal transplant recipients (RTX) as well. PSIs are the key factors to overcome the allograft rejections after successful organ transplantation since the immune system starts to react against the graft. SRL and ERL prevents the action of immune system b inhibits the proliferation of T- and B-cells by inhibiting the intracellular signaling of interleukin-2. The presence of excess amount of serum proteins including albumin in the urine is considered as proteinuria, which reflects the loss of kidney function. The occurrence of proteinuria can be the result of abnormal glomerular filtration and/or impaired tubular endocytic function of renal proximal tubular epithelial cells (PTECs). Megalin and cubulin are two scavenger receptors present on epical surface of PTECs and involved in reabsorption of proteins after glomerular ultrafiltration process in the kidney. Proteinuria appears too high in renal transplanted patients during ongoing   treatment with PSIs.</p><p><em>Aim</em> Our study aimed to investigate and correlate the expression level of megalin and cubilin and albumin uptake in PTEC of renal transplanted patients before and after conversion to PSI.</p><p><em>Methods</em> To retrieve the maximal expression of our interest molecules in renal PTECs, we optimized antigen retrieval (AR) method and primary antibody dilution for each molecule separately. An optimization experiment was performed on 3 different normal patients renal biopsies were used. Later, human renal biopsy specimens originated from 4 different renal transplanted patients were used in this study. From all the 4 patients biopsy specimens were taken before and ongoing administration of PSIs (SRL, ERL). The expression of megalin, cubilin and albumin uptake in PTEC of renal transplant patients was determined by immunohistochemical staining.</p><p><em>Results</em> Based on the optimization experiments, we selected the AR method and primary antibody dilution for the expression of megalin, cubilin and albumin uptake. In 4 renal transplanted patients following administration of PSIs results in patients 1, 2, 3 expression of megalin, cubilin and albumin uptake during ongoing PSI treatment was not comparable or even more intense than before PSIs introduction. The expression of megalin, cubilin and albumin uptake was reduced in patient 4 during ongoing PSI treatment.</p><p><em>Conclusion</em> Our findings suggest that the renal transplant patient 4 developed proteinuria during PSI medication. The expression of megalin, cubilin and albumin uptake was markedly decreased during ongoing PSI treatment in patient 4. We concluded that there is a direct link between PSI medication and tubular dysfunction, which might cause proteinuria</p>