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Unconjugated bilirubin

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https://www.readbyqxmd.com/read/29137095/differences-in-ugt1a1-gene-mutations-and-pathological-liver-changes-between-chinese-patients-with-gilbert-syndrome-and-crigler-najjar-syndrome-type-ii
#1
Lei Sun, Man Li, Liang Zhang, Xiaoying Teng, Xiangmei Chen, Xingang Zhou, Zhiyuan Ma, Liming Qi, Peng Wang
Diagnosis of Crigler-Najjar syndrome type II (CNS-II) and Gilbert syndrome (GS) based on the serum bilirubin concentration is difficult, because this parameter can fluctuate under certain conditions. The aim of this study was to explore differences in UGT1A1 gene mutations, which cause both CNS and GS, and pathological changes between CNS-II and GS.Ninety-five Chinese patients with hereditary unconjugated hyperbilirubinemia were enrolled in this study. Peripheral blood samples obtained from patients were used to evaluate bilirubin levels and for UGT1A1 gene testing...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29132818/bilirubin-albumin-binding-and-unbound-unconjugated-hyperbilirubinemia-in-premature-infants
#2
Sanjiv B Amin, Hongyue Wang
OBJECTIVE: To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. STUDY DESIGN: In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day...
November 10, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29117957/nocturnal-oxyhemoglobin-desaturation-and-arteriopathy-in-a-pediatric-sickle-cell-disease-cohort
#3
Nomazulu Dlamini, Dawn E Saunders, Michael Bynevelt, Sara Trompeter, Timothy C Cox, Romola S Bucks, Fenella J Kirkham
OBJECTIVE: The purpose of this study of sickle cell disease (SCD) was to determine whether arteriopathy, measurable as intracranial vessel signal loss on magnetic resonance angiography (MRA), was associated with low nocturnal hemoglobin oxygen saturation (SpO2) or hemolytic rate, measurable as reticulocytosis or unconjugated hyperbilirubinemia. METHODS: Ninety-five East London children with SCD without prior stroke had overnight pulse oximetry, of whom 47 (26 boys, 39 hemoglobin SS; mean age 9...
November 8, 2017: Neurology
https://www.readbyqxmd.com/read/29096561/in-silico-modeling-to-optimize-interpretation-of-liver-safety-biomarkers-in-clinical-trials
#4
Rachel J Church, Paul B Watkins
Current strategies to delineate the risk of serious drug-induced liver injury associated with drugs rely on assessment of serum biomarkers that have been utilized for many decades. In particular, serum alanine aminotransferase and total bilirubin levels are typically used to assess hepatic integrity and function, respectively. Parallel measurement of these biomarkers is utilized to identify patients with drug-induced hepatocellular jaundice ("Hy's Law" cases) which carries at least a 10% risk of death or liver transplant...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29079291/mechanisms-of-redox-interactions-of-bilirubin-with-copper-and-the-effects-of-penicillamine
#5
Bojana Božić, Jelena Korać, Dalibor M Stanković, Marina Stanić, Ana Popović-Bijelić, Jelena Bogdanović Pristov, Ivan Spasojević, Milica Bajčetić
Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu(2+). However, the development and mechanisms of such interactions at physiological pH have not been resolved. This study shows that BR reduces Cu(2+) to Cu(1+) in 1:1 stoichiometry. Apparently, BR undergoes degradation, i.e. BR and Cu(2+) do not form stable complexes. The binding of Cu(2+) to inorganic phosphates, liposomal phosphate groups, or to chelating drug penicillamine, impedes redox interactions with BR...
October 26, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28968925/restoration-of-plasma-markers-of-liver-and-kidney-functions-integrity-in-alloxan-induced-diabetic-rabbits-by-aqueous-extract-of-pleurotus-tuberregium-sclerotia
#6
Catherine Chidinma Ikewuchi, Jude Chigozie Ikewuchi, Mercy Onuekwuzu Ifeanacho
The effect of aqueous extract of the sclerotia of Pleurotus tuberregium on the plasma electrolytes, and markers of liver and kidney functions/integrity of normal and alloxan-induced rabbits was investigated. Diabetes mellitus was induced by injection of alloxan (120mg/kg body weight), via the marginal ear vein. The extract was administered orally at 100, 200 and 300mg/kg (both to normal and diabetic rabbits), and metformin at 50mg/kg. Gas chromatographic-flame ionization detector analysis of the extract revealed the presence of twelve known phenolic acids, consisting mainly of caffeic acid (80...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28965934/the-activation-of-autophagy-protects-neurons-and-astrocytes-against-bilirubin-induced-cytotoxicity
#7
Mohammed Qaisiya, Paula Mardešić, Beatrice Pastore, Claudio Tiribelli, Cristina Bellarosa
Unconjugated bilirubin (UCB) neurotoxicity involves oxidative stress, calcium signaling and ER-stress. The same insults can also induce autophagy, a process of "self-eating", with both a pro-survival or a pro-apoptotic role. Our aim was to study the outcome of autophagy activation by UCB in the highly sensitive neuronal SH-SY5Y cells and in the resistant astrocytoma U87 cells. Upon treatment with a toxic dose of UCB, the conversion of LC3-I to LC3-II was detected in both cell lines. Inhibition of autophagy by E64d before UCB treatment increased SH-SY5Y cell mortality and made U87 cells sensitive to UCB...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28954873/chronic-auditory-toxicity-in-late-preterm-and-term-infants-with-significant-hyperbilirubinemia
#8
MULTICENTER STUDY
Sanjiv B Amin, Satish Saluja, Arvind Saili, Mark Orlando, Hongyue Wang, Nirupama Laroia, Asha Agarwal
BACKGROUND AND OBJECTIVES: Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion)...
October 2017: Pediatrics
https://www.readbyqxmd.com/read/28948382/association-of-serum-bilirubin-with-oxidant-damage-of-human-atherosclerotic-plaques-and-the-severity-of-atherosclerosis
#9
Domenico Lapenna, Giuliano Ciofani, Sante Donato Pierdomenico, Maria Adele Giamberardino, Sante Ucchino, Giovanni Davì
Bilirubin has protective effects against atherosclerotic cardiovascular diseases hypothetically due to its antioxidant-antilipoperoxidative properties. Thus, we investigated whether serum bilirubin is associated with oxidant damage, namely lipid peroxidation, of human atherosclerotic plaques and the severity of atherosclerosis. In this regard, we correlated the levels of serum total bilirubin (STB), direct (conjugated) bilirubin (SDB) and indirect (unconjugated) bilirubin (SIB) with those of fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH) of 32 endarterectomy-derived carotid atherosclerotic plaques...
September 25, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28892962/crigler-najjar-syndrome-type-2-cns-type-2-an-unwonted-cause-of-jaundice-in-adults
#10
Prabhat Kumar, Gargi Sasmal, Shreya Gupta, Renu Saxena, Sudha Kohli
Crigler Najjar Syndrome (CNS) Type 2 is an uncommon genetic disorder characterised by non-haemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase- 1, required for the conjugation and further excretion of bilirubin from the body. Affected individuals are usually asymptomatic apart from the jaundice and investigations reveal isolated indirect hyperbilirubinemia. It can be conveniently diagnosed by evaluating the response to phenobarbitone in terms of fall in bilirubin levels...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28892712/relationship-between-serum-total-bilirubin-levels-and-mortality-in-uremia-patients-undergoing-long-term-hemodialysis-a-nationwide-cohort-study
#11
Hui-Hsien Su, Chia-Man Kao, Yi-Chun Lin, Yen-Chung Lin, Chih-Chin Kao, Hsi-Hsien Chen, Chih-Cheng Hsu, Kuan-Chou Chen, Chiung-Chi Peng, Mai-Szu Wu
BACKGROUND AND AIMS: Previous studies show that serum bilirubin has potent antioxidant effect and is associated with protection from kidney damage and reduce cardiovascular events. The aim of this study was to examine the association of serum total bilirubin level and mortality in uremia patients who underwent hemodialysis. METHODS: This is a nationwide retrospective long-term cohort study. Patients were registered in the Taiwan Renal Registry Data System (TWRDS) from 2005 to 2012...
September 4, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28888563/bilirubin-uridine-diphosphate-glucuronosyltransferase-polymorphism-as-a-risk-factor-for-prolonged-hyperbilirubinemia-in-japanese-preterm-infants
#12
Takahide Yanagi, Sayuri Nakahara, Yoshihiro Maruo
OBJECTIVE: To determine whether a variant of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1*6) is a risk factor for prolonged hyperbilirubinemia in preterm infants. STUDY DESIGN: UGT1A1 genotypes in 46 Japanese preterm infants (<37 weeks of gestation) were compared with UGT1A1 genotypes in 38 control infants, using polymerase chain reaction-direct sequencing. Prolonged unconjugated hyperbilirubinemia was defined as serum total bilirubin concentration of >150 µmol/L (8...
September 6, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28856221/analytical-performance-evaluation-of-the-elecsys%C3%A2-cyclosporine-and-elecsys%C3%A2-tacrolimus-assays-on-the-cobas-e411-analyzer
#13
Maki Sasano, Shigeki Kimura, Ikuhiro Maeda, Yoh Hidaka
BACKGROUND: Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs that are often used to treat autoimmune diseases and as transplantation therapy; therefore, their concentrations need to be monitored carefully. We herein evaluated the analytical performance of the Elecsys® Cyclosporine and Elecsys® Tacrolimus assay kits, which have been newly developed to measure CsA and TAC concentrations in the whole blood. METHODS: We used residual whole blood samples from autoimmune disease and transplantation patients who were being treated with CsA or TAC...
August 2017: Pract Lab Med
https://www.readbyqxmd.com/read/28815739/kernicterus-in-a-boy-with-ornithine-transcarbamylase-deficiency-a-case-report
#14
Eduardo López-Corella, Isabel Ibarra-González, Cynthia Fernández-Lainez, Miguel Á Rodríguez-Weber, Sara Guillén-Lopez, Leticia Belmont-Martínez, David Agüero-Linares, Marcela Vela-Amieva
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle defect associated with severe and usually fatal hyperammonemia. This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11.55 mg/dL). The patient was a full-term male with a family history of two previous male siblings who died as newborns after acute neurologic deterioration...
August 16, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28805798/repeated-aav-mediated-gene-transfer-by-serotype-switching-enables-long-lasting-therapeutic-levels-of-hugt1a1-enzyme-in-a-mouse-model-of-crigler-najjar-syndrome-type-i
#15
L Bočkor, G Bortolussi, A Iaconcig, G Chiaruttini, C Tiribelli, M Giacca, F Benvenuti, L Zentilin, A F Muro
Adeno-associated virus (AAV) -mediated gene therapy is a promising strategy to treat liver-based monogenic diseases. However, two major obstacles limit its success: first, vector dilution in actively dividing cells, such as hepatocytes in neonates/children, due to the non-integrating nature of the vector; second, development of an immune response against the transgene and/or viral vector. Crigler-Najjar Syndrome Type I is a rare monogenic disease with neonatal onset, caused by mutations in the liver-specific UGT1 gene, with toxic accumulation of unconjugated bilirubin in plasma, tissues and brain...
October 2017: Gene Therapy
https://www.readbyqxmd.com/read/28805483/tet1-mediated-dna-demethylation-involves-in-neuron-damage-induced-by-bilirubin-in-vitro
#16
Panhong Gou, Xiaoling Qi, Rui Yuan, Haojie Li, Xiaoling Gao, Junling Wang, Benzhong Zhang
The aim of this study is to identify the role of Tet1-mediated DNA demethylation in the neurotoxicity caused by unconjugated bilirubin (UCB) in vitro. Primary neuronal cells after cultured for 72 h were exposed to UCB (0-100 μmol/L) for 24 h. Following exposure to UCB cytotoxicity was determined with the methyl tetrazolium (MTT) assay, reactive oxygen species (ROS) and caspase-3 activity in neuron cells were measured with the corresponding assay kits. The expression of Tet1 and Klotho was determined with RT-PCR at mRNA level and western blot at protein level...
August 25, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28782473/the-importance-of-hemolysis-and-its-clinical-detection-in-neonates-with-hyperbilirubinemia
#17
Ronald J Wong, Vinod K Bhutani, David K Stevenson
Background: Hyperbilirubinemia is a benign transitional phenomenon that occurs in 60% to 80% of all term infants. The degree of hyperbilirubinemia and hence risk for developing bilirubin-induced neurologic dysfunction or BIND is dependent upon two major processes: (i) bilirubin production and its elimination. Objective: The aim of this review is to address the importance of hemolysis and its clinical detection in neonates with hyperbilirubinemia. Results: In newborns, an increased bilirubin production rate due to hemolysis is often the primary cause of hyperbilirubinemia during the first week of life...
August 7, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28776730/effect-of-feed-deprivation-on-selected-parameters-of-lipid-mobilisation-and-hepatic-function-in-healthy-akhal-teke-horses
#18
B Tóth, A Auth, L Rompos, Z Bakos
BACKGROUND: Gastrointestinal and other systemic diseases of Equidae are often characterised by partial or complete inappetence. The catabolic processes may lead to lipid mobilisation and other metabolic disturbances. Evidence from earlier studies has revealed that during feed deprivation/inappetence, the conjugation of bilirubin is reduced causing a substantial rise of the total bilirubin and its unconjugated fraction. OBJECTIVES: We hypothesised that during feed deprivation, the serum concentration of free fatty acids (FFA), triglycerides (TG), blood urea nitrogen (BUN), total bilirubin (tBIL) total bile acids (tBA) and activity of GGT and GLDH increase, while the concentration of insulin and direct bilirubin (dBIL) decrease...
August 4, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28762235/fluid-supplementation-for-neonatal-unconjugated-hyperbilirubinaemia
#19
REVIEW
Nai Ming Lai, Azanna Ahmad Kamar, Yao Mun Choo, Juin Yee Kong, Chin Fang Ngim
BACKGROUND: Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation...
August 1, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28751579/promoterless-gene-targeting-without-nucleases-rescues-lethality-of-a-crigler-najjar-syndrome-mouse-model
#20
Fabiola Porro, Giulia Bortolussi, Adi Barzel, Alessia De Caneva, Alessandra Iaconcig, Simone Vodret, Lorena Zentilin, Mark A Kay, Andrés F Muro
Crigler-Najjar syndrome type I (CNSI) is a rare monogenic disease characterized by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of neurological damage and death. Liver transplantation is the only curative option, which has several limitations and risks. We applied an in vivo gene targeting approach based on the insertion, without the use of nucleases, of a promoterless therapeutic cDNA into the albumin locus of a mouse model reproducing all major features of CNSI Neonatal transduction with the donor vector resulted in the complete rescue from neonatal lethality, with a therapeutic reduction in plasma bilirubin lasting for at least 12 months, the latest time point analyzed...
October 2017: EMBO Molecular Medicine
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