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Unconjugated bilirubin

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https://www.readbyqxmd.com/read/28206723/clinical-study-on-amplitude-integrated-electroencephalogram-in-cerebral-injury-caused-by-severe-neonatal-hyperbilirubinemia
#1
Hongwei Wu, Zhenguang Li, Jinfeng Liu, Gang Liu, Xia Yang
BACKGROUND: This study was designed in order to assess the validity of the use of amplitude-integrated electroencephalogram (aEEG) in cerebral injury caused by severe neonatal hyperbilirubinemia. METHODS: A total of 56 full-term neonates diagnosed with severe neonatal hyperbilirubinemia and admitted to the NICU of our hospital from July 2013 to December 2014 were continuously selected for the study. The total serum bilirubin (TSB) was higher than 342 μmo/l, and was dominated by a higher amount of unconjugated bilirubin...
February 15, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28183002/unconjugated-free-bilirubin-in-preterm-infants
#2
Lori W E van der Schoor, Peter H Dijk, Henkjan J Verkade, Anna C J Kamsma, Andrea B Schreuder, Henk Groen, Christian V Hulzebos
BACKGROUND: Hyperbilirubinemia guidelines are based on total serum bilirubin (TSB), in combination with either gestational age (GA) or birth weight (BW), postnatal age and specific risk factors. However, TSB is a poor predictor of bilirubin-induced neurotoxicity (BIND). Free unconjugated bilirubin (UCBfree) and the UCBfree/TSB ratio are more directly related to BIND, but data on their postnatal courses are unknown. AIMS: To characterize the postnatal courses of UCBfree and UCBfree/TSB ratio, and assess their relationships with clinical characteristics...
February 6, 2017: Early Human Development
https://www.readbyqxmd.com/read/28145671/evaluation-of-jaundice-in-adults
#3
Matthew V Fargo, Scott P Grogan, Aaron Saguil
Jaundice in adults can be an indicator of significant underlying disease. It is caused by elevated serum bilirubin levels in the unconjugated or conjugated form. The evaluation of jaundice relies on the history and physical examination. The initial laboratory evaluation should include fractionated bilirubin, a complete blood count, alanine transaminase, aspartate transaminase, alkaline phosphatase, ?-glutamyltransferase, prothrombin time and/or international normalized ratio, albumin, and protein. Imaging with ultrasonography or computed tomography can differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders...
February 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28127473/hemadsorption-with-adult-cytosorb%C3%A2-in-a-low-weight-pediatric-case
#4
Catalin Gabriel Cirstoveanu, Ileana Barascu, Samantha Mc Kenzie Stancu
Cytokine adsorber (CytoSorb) has been used successfully as adjunctive treatment for adult patients with elevated cytokine levels in the setting with severe sepsis and septic shock and to reduce blood myoglobin, unconjugated bilirubin, and conjugated bilirubin. In this article we present the case of a nine-month-old male infant who was admitted to the NICU due to sepsis after cardiac surgery, Fallot tetralogy, and multisystem organ failure (MSOF) including liver failure and renal failure which was successfully treated by a combination of continuous hemodiafiltration (HDF) and hemadsorption with CytoSorb...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/28108666/antibiotic-induced-elevations-of-plasma-bile-acids-in-rats-independent-of-bsep-inhibition
#5
Yutai Li, Michael J Hafey, Hong Duong, Raymond Evers, Kyeongmi Cheon, Daniel J Holder, Alema Galijatovic-Idrizbegovic, Frank D Sistare, Warren E Glaab
Drug-induced liver injury (DILI) is a common toxicity observed in drug development and can lead to withdrawal of approved drugs from the market. To better understand the numerous mechanisms of DILI, recent efforts have focused on transporter inhibition, specifically liver canalicular bile salt export pump (Bsep) as one mechanism of DILI, and on the potential use of plasma bile acids as monitorable mechanism-based biomarkers of Bsep inhibition. To explore alternative mechanisms of bile acid increases in plasma, six antibiotic and two non-antibiotic drugs unlikely to be Bsep inhibitors were evaluated in rat studies...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28100328/-repeated-yellowing-of-the-skin-and-sclera-for-2-years
#6
Xiao-Ye Yuan, Xiang-Ling He, Hui Zou, Run-Ying Zou
A two-year-old girl was admitted due to repeated yellowing of the skin and sclera for 2 years and had no other specific symptoms or signs. The use of phenobarbital could relieve the symptoms of jaundice. Multiple examinations showed increased indirect bilirubin levels, and the results of aminotransferases and liver imaging were normal. There was no evidence of hemolysis. The analysis of UGT1A1 gene in her family found that this child had double homozygous mutation of c.211G>A(G71R) and c.1456T>G(Y486D), which had been reported as the pathogenic mutation for Gilbert syndrome...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28096081/mice-with-hyperbilirubinemia-due-to-gilbert-s-syndrome-polymorphism-are-resistant-to-hepatic-steatosis-by-decreased-serine-73-phosphorylation-of-ppar%C3%AE
#7
Terry D Hinds, Peter A Hosick, Michael W Hankins, Andrea Nestor-Kalinoski, David E Stec
Gilbert's syndrome is derived from a polymorphism (TA repeat) in the hepatic UGT1A1 gene which results in decreased conjugation and increased levels of unconjugated bilirubin. Recently, we have shown that bilirubin binds directly to the fat burning nuclear peroxisome proliferator-activated receptor α (PPARα). Additionally, we have shown that serine 73 phosphorylation (Ser(P)(73)) of PPARα decreases activity by reducing its protein levels and transcriptional activity. The aim of this study was to determine if humanized mice with the Gilbert's polymorphism (HuUGT*28) have increased PPARα activation and reduced hepatic fat accumulation...
January 17, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28094087/-management-of-jaundice-in-the-newborn%C3%A2-35%C3%A2-gw-from-screening-to-follow-up-after-discharge-guidelines-for-clinical-practice
#8
A Cortey, L Renesme, J Raignoux, A Bedu, C Casper, P Tourneux, P Truffert
Jaundice due to unconjugated bilirubin is an everyday condition in the neonatal period because it results from the adaptation of bilirubin metabolism at this time of life. Hyperbilirubinemia has a potential neurotoxicity and although it most often resolves spontaneously, it can lead to acute and sometimes chronic encephalopathy. The latter condition is called kernicterus and induces severe and irreversible neurological sequelae. This rare complication is still reported in all countries throughout the world even if severe hyperbilirubinemia can be prevented and critical points points of failure in jaundice management are identified...
February 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28093842/gilbert-syndrome-in-patients-with-type-1-diabetes-prevalence-glycemic-control-and-microalbuminuria
#9
Sigal Singer, Nurit Pilpel, Orit Pinhas-Hamiel
BACKGROUND: Gilbert syndrome (GS) is a common hereditary condition, characterized by intermittent unconjugated hyperbilirubinemia. In adults with type 2 diabetes and GS, a markedly lower prevalence of nephropathy was documented, suggesting a beneficial effect of hyperbilirubinemia. We investigated the prevalence of GS among individuals with type 1 diabetes mellitus (T1DM), and the prevalence of microalbuminuria. METHODS: The prevalence of GS was assessed in 401 (204 female) patients with T1DM, median age 21...
January 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28063966/linking-organic-anion-transporting-polypeptide-1b1-and-1b3-oatp1b1-and-oatp1b3-interaction-profiles-to-hepatotoxicity-the-hyperbilirubinemia-use-case
#10
Eleni Kotsampasakou, Sylvia E Escher, Gerhard F Ecker
Hyperbilirubinemia is a pathological condition of excessive accumulation of conjugated or unconjugated bilirubin in blood. It has been associated with neurotoxicity and non-neural organ dysfunctions, while it can also be a warning of liver side effects. Hyperbilirubinemia can either be a result of overproduction of bilirubin due to hemolysis or dyserythropoiesis, or the outcome of impaired bilirubin elimination due to liver transporter malfunction or inhibition. There are several reports in literature that inhibition of organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) might lead to hyperbilirubinemia...
January 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28056490/knockout-of-the-primary-sclerosing-cholangitis-risk-gene-fut2-causes-liver-disease-in-mice
#11
Luca Maroni, Simon D Hohenester, Stan F J van de Graaf, Dagmar Tolenaars, Krijn van Lienden, Joanne Verheij, Marco Marzioni, Tom H Karlsen, Ronald P J Oude Elferink, Ulrich Beuers
: The etiopathogenesis of primary sclerosing cholangitis (PSC) is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome-wide association studies as risk factor for PSC. We investigated the role of Fut2 in murine liver pathophysiology by studying Fut2(-/-) mice. Fut2(-/-) mice were viable and fertile, had lower body weight than wild type (wt) littermates and grey fur, as described earlier. Half of the Fut2(-/-) mice showed serum bile salt levels 40 times higher than wt (Fut2(-/-)(high) ), whereas the remainder were normocholanemic (Fut2(-/-)(low) )...
January 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28036021/monitoring-the-response-of-hyperbilirubinemia-in-the-mouse-brain-by-in-vivo-bioluminescence-imaging
#12
Isabella Manni, Giuliana Di Rocco, Salvatore Fusco, Lucia Leone, Saviana Antonella Barbati, Carmine Maria Carapella, Claudio Grassi, Giulia Piaggio, Gabriele Toietta
Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28025333/modulation-of-bilirubin-neurotoxicity-by-the-abcb1-transporter-in-the-ugt1-lethal-mouse-model-of-neonatal-hyperbilirubinemia
#13
Luka Bočkor, Giulia Bortolussi, Simone Vodret, Alessandra Iaconcig, Jana Jašprová, Jaroslav Zelenka, Libor Vitek, Claudio Tiribelli, Andrés F Muro
Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma...
December 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28004508/the-molecular-basis-of-jaundice-an-old-symptom-revisited
#14
REVIEW
Silvia Gazzin, Flora Masutti, Libor Vitek, Claudio Tiribelli
Increased serum bilirubin level is a widely used diagnostic marker for hepatic illnesses. Nevertheless, mild elevation of unconjugated serum bilirubin (such as in Gilbert syndrome) has been recently demonstrated to correlate with low risk of chronic inflammatory and/or oxidative stress-mediated diseases. In accord, a low serum bilirubin level has emerged as an important predisposing factor or a biomarker of these pathologic conditions including cardiovascular, tumour, and possibly neurodegenerative diseases...
December 22, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27995906/acg-clinical-guideline-evaluation-of-abnormal-liver-chemistries
#15
Paul Y Kwo, Stanley M Cohen, Joseph K Lim
Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels...
January 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/27995496/neuroprotective-effect-of-erythropoietin-on-phenylhydrazine-induced-hemolytic-hyperbilirubinemia-in-neonatal-rats
#16
Asli Memisoglu, Meltem Kolgazi, Akan Yaman, Elif Bahadir, Serap Sirvanci, Berrak Ç Yeğen, Eren Ozek
Neonatal unconjugated hyperbilirubinemia might cause severe bilirubin neurotoxicity in especially hemolytic conditions. The study aimed to elucidate the potential neuroprotective effects of erythropoietin (EPO) in hemolysis-induced hyperbilirubinemia. In newborn rats, hyperbilirubinemia secondary to hemolysis was induced by injecting with phenylhydrazine hydrochloride (PHZ) and rats were injected with either vehicle or EPO. At 54th hour of the PHZ injection, rats were decapitated. Serum levels of TNF-α, IL-1β, IL-10, brain-derived neurotrophic factor (BDNF) and S100-B and brain malondialdehyde, glutathione levels and myeloperoxidase activities were measured...
December 19, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27980881/obstetric-obesity-is-associated-with-neonatal-hyperbilirubinemia-with-high-prevalence-in-native-hawaiians-and-pacific-island-women
#17
Luc Ra Rougée, Shogo J Miyagi, Abby C Collier
Obesity and pregnancy both place the liver under metabolic stress, but interactions between obstetric obesity and bilirubin metabolism have not been studied. We determined associations between obesity, maternal/neonatal bilirubin levels, and uridine 5'diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme that eliminates bilirubin. Adult livers were analyzed for UGT1A1 expression, activity, and bilirubin clearance by pharmacokinetic modeling. Then, matched maternal and neonatal sera (N = 450) were assayed for total and unconjugated bilirubin...
December 2016: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/27979672/-neonatal-expression-of-beta-thalassemia-trait-associated-with-hereditary-spherocytosis-in-two-monozygotic-twins
#18
H Ben Hamouda, B Mahjoub, H Soua, S Laradi, A Miled, M T Sfar
The beta-thalassemia trait is a heterozygous beta-thalassemia characterized by a partial deficiency of the synthesis of beta-globin chains of hemoglobin. It is usually asymptomatic and the diagnosis is often made on the occasion of the completion of a systematic blood count or a family survey. Clinical expression during the neonatal period is impossible and its association with hereditary spherocytosis is common. We report two monozygotic twins who, on the 3rd day of life, presented intense jaundice, unconjugated bilirubin associated with anemia, without hepatosplenomegaly...
February 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/27968820/mortality-outcomes-after-busulfan-containing-conditioning-treatment-and-haemopoietic-cell-transplantation-in-patients-with-gilbert-s-syndrome-a-retrospective-cohort-study
#19
George B McDonald, Ashley T Evans, Jeannine S McCune, Gary Schoch, J Donald Ostrow, Ted A Gooley
BACKGROUND: Gilbert's syndrome is a common inherited disorder of bilirubin metabolism, characterised by mild, unconjugated hyperbilirubinaemia. However, the effect of Gilbert's syndrome on the disposition of some drugs can lead to unexpected toxicity. We tested the hypothesis that patients undergoing myeloablative conditioning and haemopoietic cell transplantation would have different mortality outcomes depending on whether or not they had laboratory evidence of Gilbert's syndrome. METHODS: In this retrospective cohort study, we used clinical and laboratory data of patients who had haemopoietic cell transplantation from Jan 1, 1991, to Dec 31, 2011...
November 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27943244/genetic-variations-in-bilirubin-metabolism-genes-and-their-association-with-unconjugated-hyperbilirubinemia-in-adults
#20
Ashish S Chiddarwar, Selma Z D'Silva, Roshan B Colah, Kanjaksha Ghosh, Malay B Mukherjee
OBJECTIVE: The present study was undertaken to investigate the genotype and allele frequencies of the variants in the four bilirubin metabolism genes (UGT1A1, OATP2, HMOX1, and BLVRA) and their association with hyperbilirubinemia. MATERIAL AND METHODS: Genotyping of 17 genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR-RFLP, GeneScan analysis, and direct DNA sequencing. RESULTS: Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital-responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1, and BLVRA genes, were significantly higher among the cases than the controls...
December 12, 2016: Annals of Human Genetics
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