Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references. Also available in print.

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "December 2008." Includes bibliographical references (leaves 287-298). Online version available on the World Wide Web.

Thesis (Ph. D.)--University of Nevada, Reno, 2007. / "December, 2007." Includes bibliographical references (leaves 125-129). Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2008]. 1 microfilm reel ; 35 mm. Online version available on the World Wide Web.

The purpose of this study is to examine the association between serum bilirubin and the development of age-related macular degeneration (AMD). The study design includes the utilization of a USA-nationally representative population based cross-sectional study in the National Health and Nutrition Examination Survey: specifically, the NHANES III and continuous NHANES from years 2005-2008. 15,501 survey participants from the NHANES studies chosen for this analysis were interviewed for demographic, behavioral, and medical information, put through a comprehensive medical examination segment, and a laboratory analysis portion. The 15,501 participants were chosen based on their age (40 and above) and the presence of fundus photographs. Fundus photographs were graded using standardized protocol to diagnose early and later AMD, which were combined to form the outcome "AMD" in a binary variable. Serum bilirubin levels were measured using spectrophotometry. Of the 15,501 participants in the study, 1305 (8.9%) were diagnosed with AMD. In a multivariate logistic regression adjusted for age, sex, smoking status, race, and serum C-reactive protein (CRP) levels, bilirubin was significantly associated with AMD (odds ratio, 0.728; confidence interval, 0.547-0.969; P value, 0.0296). The findings of this study indicate that the antioxidative effects of bilirubin may play protective role in the pathology of AMD.

Identification and functional characterization of numerous transport systems at the sinusoidal and canalicular membrane of hepatocytes have significantly expanded our understanding of bilirubin metabolism and contributed to elucidation of molecular basis of hereditary jaundice. Moreover, dysregulation of hepatobiliary transport systems could explain jaundice in many acquired liver disorders. This thesis is focused on the new aspects of bilirubin handling in hepatocytes based on elucidation of the molecular basis of Rotor syndrome. The first study is focused on the antioxidative properties of bilirubin in liver tissue in a model of obstructive cholestasis. In the second part of the thesis we present several novel mutations in ABCC2, the gene associated with Dubin-Johnson syndrome, identified in patients selected for the Rotor locus mapping study. In the key third study concerned with Rotor syndrome we demonstrated that biallelic inactivating mutations causing complete absence of transport proteins OATP1B1 and OATP1B3 result in disruption of hepatic reuptake of bilirubin, which is the molecular basis of Rotor-type jaundice. These results indicate that apart from secretion of conjugated bilirubin into bile, a significant fraction of bilirubin glucuronide is secreted via MRP3 into sinusoidal blood and...

Identification and functional characterization of numerous transport systems at the sinusoidal and canalicular membrane of hepatocytes have significantly expanded our understanding of bilirubin metabolism and contributed to elucidation of molecular basis of hereditary jaundice. Moreover, dysregulation of hepatobiliary transport systems could explain jaundice in many acquired liver disorders. This thesis is focused on the new aspects of bilirubin handling in hepatocytes based on elucidation of the molecular basis of Rotor syndrome. The first study is focused on the antioxidative properties of bilirubin in liver tissue in a model of obstructive cholestasis. In the second part of the thesis we present several novel mutations in ABCC2, the gene associated with Dubin-Johnson syndrome, identified in patients selected for the Rotor locus mapping study. In the key third study concerned with Rotor syndrome we demonstrated that biallelic inactivating mutations causing complete absence of transport proteins OATP1B1 and OATP1B3 result in disruption of hepatic reuptake of bilirubin, which is the molecular basis of Rotor-type jaundice. These results indicate that apart from secretion of conjugated bilirubin into bile, a significant fraction of bilirubin glucuronide is secreted via MRP3 into sinusoidal blood and...

No description available.

A icterícia é uma manifestação caracterizada pelo amarelamento da pele e mucosas devido ao excesso de bilirrubina no sangue do paciente. Cerca de 60% dos recém nascidos (RN) manifestam a icterícia nas primeiras semanas de vida, sendo este índice muito maior em neonatos prematuros. Se não corretamente diagnosticada, a alta concentração de bilirrubina pode intoxicar a massa encefálica, provocando uma encefalopatia conhecida como kernicterus. Existem vários métodos para medir a concentração de bilirrubina, e entre eles pode-se citar: métodos bioquímicos laboratoriais que utilizam amostras de sangue coletadas e reagentes específicos, medidores de bilirrubina transcutâneos e espectrofotometria em amostras de soro. O princípio básico desses métodos é a análise colorimétrica, que se baseia na alta absorbância da molécula de bilirrubina no comprimento de onda de 455 nm. O presente trabalho descreve um bilirrubinômetro, que foi desenvolvido para medir a concentração da bilirrubina utilizando a espectrofotometria direta no soro de amostras sanguíneas de neonatos. No projeto do bilirrubinômetro levou-se em consideração o baixo custo de produção, uma boa precisão comparada com outros equipamentos, e a utilização de componentes de alta tecnologia tais como LED com alta intensidade luminosa e fotorreceptores especiais para medir concentrações nas faixas de luz específica. Para a validação do equipamento foram obtidas amostras de sangue de recém nascidos, junto ao Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, e os resultados das medidas realizadas com o bilirrubinômetro construído foram comparados com os obtidos com um bilirrubinômetro comercial e com métodos bioquímicos clássicos. Os resultados da comparação mostraram que o bilirrubinômetro construído apresenta um erro relativo de ± 1,05 mg/dl, que se encontra dentro da média dos bilirrubinômetros diretos e custo de produção relativamente baixo. / Jaundice is a manifestation described as the yellowish staining of the skin and mucous membranes caused by the excessive levels of bilirubin in the patient blood. About 60% of the newborns present this feature in the first weeks of life, and this percentage is much higher in premature neonates. If not correctly detected and treated, the bilirubin can intoxicate the encephalic mass, causing an encephalopathy knowed as kernicterus. There are many methods to measure the bilirubin concentration such as: blood laboratory methods using specific reagents, transcutaneous bilirubin and serum spectrophotometric equipments. The basic principle of these devices is the colorimetric analysis based on the high absorption of the bilirubin molecule in the 455 nm wavelength. This work describes a bilirubin meter that was developed for measure the bilirubin concentration using direct spectrophotometry in the serum of neonates\' blood samples. In the bilirubin meter project it was considered the low production cost, a good precision compared with others similar equipments, and the use of high technology components as high intensity LED and special photoreceptors to measure specific wavelengths. For validation of the equipment it was used newborns blood samples from the Clinics Hospital at the Faculty of Medicine of Ribeirão Preto, and the results obtained with the equipment were compared with the values of a commercial bilirubin meter and with biochemical tests. The results showed that the developed bilirubin meter has a relative error around 1,05 mg/dl, similar to commercial bilirubin meters and a low relative cost.

Inherited hyperbilirubinemias are a group of metabolic disorders, characterized by increased levels of total serum bilirubin or its conjugated fraction. Most of these hyperbilirubinemias are inherited autosomal recessively and are manifested in young age. Increased bilirubin reflects the genetic disturbances in one of the enzymes of heme degradation pathway, the defect of bilirubin conjugation (UGT1A1 gene) or its transport (ABCC2, OATP1B1, OATP1B3). All of these proteins are involved not only in elimination of bilirubin, but various substrates; therefore the performed studies have a great pharmacogenomics impact. We have studied the molecular pathology of hereditary hyperbilirubinemias in Caucasian and Roma population and to compare the clinical and biochemical results with the molecular genetic data. We described the impact of compound defect of c.-3279T>G and g.175492_175493insTA on total serum bilirubin and calculated the linkage disequlibrium of these two variants in promoter region of UGT1A1 gene. We also verified, that the population distribution of both variants is in concordance with the literature. In our second study, we have described the rare conjugated hyperbilirubinemia Dubin-Johnson type among 7 Roma families. We have found a novel variant NG_011798.1:c.[1013_1014delTG] together with...

A icterícia é uma manifestação caracterizada pelo amarelamento da pele e mucosas devido ao excesso de bilirrubina no sangue do paciente. Cerca de 60% dos recém nascidos (RN) manifestam a icterícia nas primeiras semanas de vida, sendo este índice muito maior em neonatos prematuros. Se não corretamente diagnosticada, a alta concentração de bilirrubina pode intoxicar a massa encefálica, provocando uma encefalopatia conhecida como kernicterus. Existem vários métodos para medir a concentração de bilirrubina, e entre eles pode-se citar: métodos bioquímicos laboratoriais que utilizam amostras de sangue coletadas e reagentes específicos, medidores de bilirrubina transcutâneos e espectrofotometria em amostras de soro. O princípio básico desses métodos é a análise colorimétrica, que se baseia na alta absorbância da molécula de bilirrubina no comprimento de onda de 455 nm. O presente trabalho descreve um bilirrubinômetro, que foi desenvolvido para medir a concentração da bilirrubina utilizando a espectrofotometria direta no soro de amostras sanguíneas de neonatos. No projeto do bilirrubinômetro levou-se em consideração o baixo custo de produção, uma boa precisão comparada com outros equipamentos, e a utilização de componentes de alta tecnologia tais como LED com alta intensidade luminosa e fotorreceptores especiais para medir concentrações nas faixas de luz específica. Para a validação do equipamento foram obtidas amostras de sangue de recém nascidos, junto ao Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, e os resultados das medidas realizadas com o bilirrubinômetro construído foram comparados com os obtidos com um bilirrubinômetro comercial e com métodos bioquímicos clássicos. Os resultados da comparação mostraram que o bilirrubinômetro construído apresenta um erro relativo de ± 1,05 mg/dl, que se encontra dentro da média dos bilirrubinômetros diretos e custo de produção relativamente baixo. / Jaundice is a manifestation described as the yellowish staining of the skin and mucous membranes caused by the excessive levels of bilirubin in the patient blood. About 60% of the newborns present this feature in the first weeks of life, and this percentage is much higher in premature neonates. If not correctly detected and treated, the bilirubin can intoxicate the encephalic mass, causing an encephalopathy knowed as kernicterus. There are many methods to measure the bilirubin concentration such as: blood laboratory methods using specific reagents, transcutaneous bilirubin and serum spectrophotometric equipments. The basic principle of these devices is the colorimetric analysis based on the high absorption of the bilirubin molecule in the 455 nm wavelength. This work describes a bilirubin meter that was developed for measure the bilirubin concentration using direct spectrophotometry in the serum of neonates\' blood samples. In the bilirubin meter project it was considered the low production cost, a good precision compared with others similar equipments, and the use of high technology components as high intensity LED and special photoreceptors to measure specific wavelengths. For validation of the equipment it was used newborns blood samples from the Clinics Hospital at the Faculty of Medicine of Ribeirão Preto, and the results obtained with the equipment were compared with the values of a commercial bilirubin meter and with biochemical tests. The results showed that the developed bilirubin meter has a relative error around 1,05 mg/dl, similar to commercial bilirubin meters and a low relative cost.