Orientadores: Alan Roger dos Santos Silva, Mario Fernando de Goes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-23T09:16:37Z (GMT). No. of bitstreams: 1 Neves-Silva_Rodrigo_M.pdf: 5413631 bytes, checksum: ab90c8e96a1f20d4fc91dd76675b90ad (MD5) Previous issue date: 2013 / Resumo: A pigmentação dental intrínseca verde pode ser causada por diversas doenças, sobretudo, doenças hepáticas da infância que geram hiperbilirrubinemia. Esta dissertação testou a hipótese de que a hiperbilirrubinemia é capaz de gerar alterações na microestrutura do esmalte e da dentina. Para isto, investigou-se o perfil clínico de 8 pacientes com histórico de hiperbilirrubinemia que desenvolveram pigmentação dental verde. Foi realizada uma análise macroscópica e radiográfica em 22 dentes provenientes desta amostra de pacientes. Posteriormente, a micromorfologia do esmalte, da dentina e da junção amelodentinária (JAD) foi avaliada em 16 dos 22 dentes por meio da microscopia de luz óptica (MLO) e em 14 dos 22 dentes por meio da microscopia de luz polarizada (MLP) e da microscopia eletrônica de varredura (MEV). Realizou-se a análise da densidade e do diâmetro médio dos túbulos dentinários e da espessura da dentina peritubular por meio da MEV. A média de idade dos pacientes foi de 10 anos, sem predileção por gênero. Dentre as doenças que afetaram os pacientes da amostra, 4 (50%) foram atresia das vias biliares, 1 (12,5%) cirrose biliar primária, 1 (12,5%) hipoplasia das vias biliares intra-hepáticas, 1 (12,5%) colestase familiar e 1 (12,5%) cirrose hepática. A pigmentação verde afetou os 22 (100%) espécimes, enquanto a análise radiográfica identificou alargamento da câmara pulpar e do canal radicular em 14 (63,63%) espécimes. Não foram identificadas alterações dos componentes micromorfológicos do esmalte ou da JAD, entretanto, diversas alterações foram observadas em dentina, incluindo a identificação de linhas escuras paralelas às linhas incrementais de dentina, a diminuição da densidade média dos túbulos dentinários (p<0,01) e a diminuição da espessura da dentina peritubular dos espécimes verdes (p<0,01). Em conclusão, a hiperbilirrubina foi capaz de gerar pigmentação dental verde em dentina, alargamento da câmara pulpar/canais radiculares, alterações na micromorfologia da dentina humana, na densidade de túbulos dentinários e na espessura da dentina peritubular / Abstract: Dental intrinsic green pigmentation can be caused by several diseases especially liver diseases of childhood, which generate hyperbilirubinemia. This dissertation tested the hypothesis that hyperbilirubinemia is able to generate changes in the microstructure of enamel and dentin. With this purpose, it investigated the clinical and pathological profile of 8 patients with previous history of hyperbilirubinemia who developed green dental pigmentation. A macroscopic and radiographic analysis of 22 teeth obtained from this patient's sample was performed. Posteriorly, the micromorphology of enamel, dentin and dentinoenamel junction (DEJ) was evaluated in 16 of 22 teeth by optical light microscopy (OLM) and 14 of 22 teeth by polarized light microscopy (PLM) and scanning electron microscopy (SEM). The analysis of the mean density and diameter of the dentinal tubules as well as the thickness of peritubular dentin were analyzed by SEM. The mean age of patients was 10 years, without gender predilection. Among the diseases that affected the patients enrolled in this sample, 4 (50%) were biliary atresia, 1 (12.5%) primary biliary cirrhosis, 1 (12.5%) hypoplasia of intrahepatic biliary tract, 1 (12.5%) familial cholestasis and 1 (12.5%) liver cirrhosis. The green pigmentation affected 22 (100%) specimens whereas radiographic analysis identified 14 (63.63%) specimens with enlarged pulp chamber and root canal. No changes were identified in enamel micromorphologic components or in DEJ, however, several changes were observed in dentin, including the identification of parallel dark lines to the incremental lines of the dentin, the decrease in average density of the dentinal tubules (p<0,01) and the decrease in thickness of the green peritubular dentin specimens (p<0,01). In conclusion, hyperbilirubinemia was able to produce green tooth pigmentation in dentin, enlargement of pulp chamber/root canals, changes in the micromorphology of the human dentin, in the dentin tubules density and in the thickness of peritubular dentin / Mestrado / Patologia / Mestre em Estomatopatologia

This thesis focuses on finding a possible link between genotype typical for Gilberts syndrome and specific diseases. It nvestigates a possible protective effect of the 7TA allele. It explains the origin, symptoms, pathology of this syndrome and its consequences for clinical medicine. Possible protective effect of this polymorphic mutation including reduced incidence of vascular diseases (myocardial infarction, stroke, atherosclerosis, etc.). is discussed. Reduced oxidative stress in hyperbilirubinaemia can be the mechanism behind. The work was carried out in the co-operation with the GENVIA laborator.

Adverse reactions to the antiarrhythmic medication amiodarone are severe, potentially life-threatening, and not rare. One in three patients on long-term therapy experience elevated liver enzymes, and clinically apparent liver toxicity occurs in 1% of patients treated. We report the case of a 76-year-old patient with amiodarone-induced intrahepatic cholestasis and prolonged hyperbilirubinemia despite the discontinuation of the offending agent. Current research hypothesizes that amiodarone leads to hepatic injury both by direct hepatotoxicity and by increasing the likelihood of hepatocytes to create abnormal, toxic metabolites. Increased awareness of such an adverse effect can guide clinicians toward the possible underlying etiologies of prolonged jaundice.

No description available.

Eine Erhöhung des Bilirubins über 2 mg/dl betrifft 90 % aller Neugeborenen. Sie ist meist physiologisch und tritt optisch sichtbar bei 60-70 % dieses Kollektivs auf. In der pathologischen, exzessiv erhöhten Form ist sie der häufigste Grund für eine stationäre Wiederaufnahme während der ersten sieben Lebenstage. Ihre schwerste Komplikation, der Kernikterus, scheint - trotz allgemein verfügbarer, preiswerter und sicherer Therapiemöglichkeiten - wieder vermehrt aufzutreten. Die Gründe liegen im Überwachungsdefizit bei früher Entlassung von schlecht aufgeklärten Eltern, Nichtbeachtung der Besonderheiten der Neugeborenen ≤ 38 Schwangerschaftswochen und der zunehmenden Tendenz zum Stillen bei häufig unzureichender Anleitung. Ferner werden ikterische Kinder nur zu oft lediglich visuell bezüglich des Grades der Bilirubinämie eingeschätzt und die Therapie somit erheblich verzögert. Gegenstand dieser Arbeit ist die Frage, ob aus der Dynamik des Serumbilirubinspiegels von der Geburt bis zum 3. Lebenstag die Wahrscheinlichkeit des Auftretens einer phototherapiepflichtigen Hyperbilirubinämie abgeschätzt werden kann. Dazu wurde der Serumbilirubinspiegel direkt postnatal aus dem Nabelschnurblut, bzw. am 3. Lebenstag gleichzeitig mit dem Stoffwechselscreening ermittelt und der Phototherapiebedarf im Verlauf festgehalten. Um die Aussage zu präzisieren, wurde die Studienpopulation aus 2573 Kindern weiter unterteilt in 2180 reife tAGA- (hier Eu- und Hypertrophe), 267 reife tSGA-Kinder (Hypotrophe) und 126 FG (Frühgeborene). In allen 3 Gruppen korrelierten das Nabelschnurbilirubin und der Serumbilirubinwert vom 3. Lebenstag positiv mit der Entwicklung einer Hyperbilirubinämie. Anhand dieser Ausgangswerte konnten Grenzen für Hoch-, Mittelhoch-, Mittelniedrig- und Niedrigrisikogruppen definiert werden, welche die Entwicklung einer Hyperbilirubinämie mit einer Wahrscheinlichkeit von ≥ 20 %, 5-20 %, 0 < x <5 % und 0 % voraussagen. Damit kann man bereits früh eine Vorabselektion entsprechend dem Gefährdungspotential treffen und die Verlaufskontrollen entsprechend terminieren. Als Risikofaktoren einer therapiepflichtigen Hyperbilirubinämie wurden außerdem Frühgeburtlichkeit, seltener tSGA, geringes Geburtsgewicht und niedriges Gestationsalter (in der vorliegenden FG-Gruppe nicht signifikant) gefunden. Im Falle einer Sectiogeburt und bei Zuhilfenahme von Hilfsmitteln im Rahmen einer vaginalen Entbindung nahm der Bedarf an Phototherapie in der tAGA- und tSGA-Gruppe zu.

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...

This research focused on the identification and description of predictors of pediatric and adult cochlear implantation outcomes in a South African cohort and the depiction of profound childhood hearing loss in terms of risk and intervention profiles. Study I described profound childhood hearing loss in a South African cohort of pediatric cochlear implant (CI) recipients in terms of risk profile and age of diagnosis and intervention. A retrospective review of patient files for 264 pediatric CI recipients from five CI programs was conducted. For all subjects, permanent congenital and early onset hearing loss (PCEHL) was confirmed under the age of five years old. The most prevalent risks for profound PCEHL were neonatal intesive care unit (NICU) admittance (28.1%), family history of childhood hearing loss (19.6%) and prematurity (15.1%). An associated syndrome was diagnosed in 10% of children and 23.5% had at least one additional developmental condition. Hearing loss for most (77.6%) children was confirmed as congenital or early onset, while 20.3% presented with postnatal onset of hearing loss. Auditory Neuropathy Spectrum Disorder (ANSD) was diagnosed in 5% of children, with admittance to NICU (80%) and hyperbilirubinemia (50%) being the most prevalent risk factors for these cases. Hearing loss was typically diagnosed late (15.3 months), resulting in delayed initial hearing aid fitting (18.8 months), enrollment in early intervention services (19.5 months), and eventual cochlear implantation (43.6 months). Delayed diagnosis and intervention predispose this population to poorer outcomes. / Thesis (DPhil)--University of Pretoria, 2016. / Speech-Language Pathology and Audiology / DPhil / Unrestricted

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...

Background: Improvement in neonatal care has changed the features of severe hyperbilirubinemia and reduced the number of babies who need exchange transfusion (ET) to avoid bilirubin-induced neurological dysfunction. We conducted this study to determine the demographic and clinical characteristics of the exchanged babies, in order to identify their risk factors, and to determine the adverse effects and outcomes associated with ET. Methodology: This was a retrospective descriptive study, reviewing folders of infants who required ET at CMJAH from June 2006 to December 2011. Results: There were 63 patients who underwent 66 exchange transfusions. Patients exchanged in the neonatal unit accounted for 60.3%, with the rest of the patients (39.7%) being exchanged in the general ward. Preterm babies accounted for 45.7%, and the majority were inborn (44%). The majority were male (58.7%), term (54.3%), and the mean birth weight was 2.29 Kg (±0.89). The median age at exchange was 5 days (mean 4.5 days ±2.1 SD). The cause of jaundice was undetermined in most patients (84.1%), while ABO incompatibility and Rhesus disease accounted for 7.9% and 6.3%, respectively. Seven babies (11.1%) had an abnormal neurological examination before exchange and five (7.9%) were labelled as kernicterus. The mean bilirubin before exchange was 325 mmol/l ±118. The complications of ET were seen in 22.2% of patients. These were Necrotising Enterocolitis (NEC) (1.58%); seizure (1.58%); apnoea (4.76%); bleeding (3.1%); renal failure (3.1%); hypoglycaemia (4.76%); thrombocytopenia (67.6%); and hypercalcemia (85%). We had three deaths, of which two were due to neonatal sepsis acquired prior to exchange, with one case of perforated NEC in an infant with other comorbidities. Hence, the mortality associated with ET in our study was 1.5 percent. At discharge, three infants remained with signs of kernicterus (4.7%). Conclusion: Kernicterus remains a cause of concern in our settings, and mechanisms ought to be put in place to detect severe jaundice in discharged term babies who may benefit from early phototherapy (PTT) and ET; as this is shown to be a relatively safe procedure in our settings, especially in infants without other severe comorbidities. ACKNOWLEDGEMENTS I would like to take this opportunity to thank Prof Daynia Ballot, my research supervisor, who has been an inspiration for research and accepted the task of guiding me through the challenging journey of conducting and writing this review.

For a long time, bilirubin (BR) has been considered a waste molecule with potential toxic effects especially on the central nervous system. Later, it was found that BR exhibited cytoprotective effects and mildly elevated BR levels showed antioxidant, anti-inflammatory and immunomodulatory properties, however, exact mechanisms of the anti-inflammatory actions of BR have not been fully understood yet. The main aim of this study was to assess the protective effects of BR using experimental in vivo and in vitro models in relation to inflammation and oxidative stress. Partial goal was to establish validated analytical method for determination of BR and lumirubin. Gunn and heterozygous rats were treated with lipopolysaccharide (LPS, 6 mg/kg, IP) or vehicle (saline). After 12 hours, blood and organs were collected for analyses of inflammatory and hepatic injury markers. Primary rat hepatocytes were treated with BR and TNF-α, HepG2 and SH-SY5Y cell lines were treated with BR and chenodeoxycholic acid. LPS-treated Gunn rats had a significantly decreased inflammatory response and hepatic injury compared to LPS- treated normobilirubinemic controls. We found different profile of leukocytes subsets and decreased systemic mRNA expressions and concentrations of IL-6, TNF-α, IL-1β and IL-10 in Gunn rats. Hepatic mRNA...