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hyperbilirubinemia physiology

Kyunghee Yang, Christina Battista, Jeffrey L Woodhead, Simone H Stahl, Jerome T Mettetal, Paul B Watkins, Scott Q Siler, Brett A Howell
Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure. However, drugs also can increase serum bilirubin in the absence of hepatic injury by inhibiting specific enzymes/transporters. We constructed a mechanistic model of bilirubin disposition based on known functional polymorphisms in bilirubin metabolism/transport. Using physiologically-based pharmacokinetic model-predicted drug exposure and enzyme/transporter inhibition constants determined in vitro, our model correctly predicted indinavir-mediated hyperbilirubinemia in humans and rats...
January 11, 2017: Clinical Pharmacology and Therapeutics
T Malla, B Sathian, K Karmacharya Malla, S Adhikari
Background Urine culture is usually not a part of work-up for neonatal unconjugated hyperbilirubinemia; hence its prevalence remains unknown. Objective This study was done to determine the incidence of urinary tract infection (UTI) in asymptomatic newborns with prolonged unconjugated hyperbilirubinemia and to evaluate which other laboratory parameters are associated with UTIs. Method A prospective observational study where jaundiced newborns otherwise clinically well, were evaluated for UTI. The study was carried out in neonatal intensive care unit of Manipal Teaching Hospital, Pokhara from June 2012 -April 2013...
January 2016: Kathmandu University Medical Journal (KUMJ)
Marie-Laure Specq, Mélisande Bourgoin-Heck, Nathalie Samson, François Corbin, Christian Gestreau, Maxime Richer, Hazim Kadhim, Jean-Paul Praud
Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150-250 μmol/L) was induced during 17 h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia...
2016: Frontiers in Physiology
Ziba Mosayebi, Maral Rahmani, Shahin Behjati Ardakani, Mahdi Sheikh, Mamak Shariat, Golnaz Rezaeizadeh
BACKGROUND: The existing therapeutic methods for neonatal jaundice are costly, time-consuming and potentially risky. Zinc salts can reduce phototherapy duration by precipitating unconjugated bilirubin in the intestine (bilirubin and zinc can form a complex in physiologic pH); however, zinc toxicity is an issue that must be considered since theoretically bilirubin reduction by phototherapy may increase serum zinc levels, making additional zinc supplementation the potential cause of zinc toxicity...
June 2016: Iranian Journal of Pediatrics
Jaymon Patel, Saqib Walayat, Nikhil Kalva, Sidney Palmer-Hill, Sonu Dhillon
Bile cast nephropathy is a condition of renal dysfunction in the setting of hyperbilirubinemia. There are very few cases of this condition reported in the last decade and a lack of established treatment guidelines. While the exact etiology remains unknown, bile cast nephropathy is presumed to be secondary to multiple concurrent insults to the kidney including direct toxicity from bile acids, obstructive physiology from bile casts, and systemic hypoperfusion from vasodilation. Therapy directed at bilirubin reduction may improve renal function, but will likely need dialysis or plasmapheresis as well...
July 21, 2016: World Journal of Gastroenterology: WJG
Sana Ullah, Khaista Rahman, Mehdi Hedayati
BACKGROUND: Hyperbilirubinemia, or jaundice, is a life threatening disorder in newborns. It is a multifactorial disorder with many symptoms. Generally, the physiological jaundice is the most prevalent type however in some regions pathological jaundice is also common. This review article focuses on a brief introduction to jaundice, its types and causes, measuring the bilirubin level, clinical approaches towards hyperbilirubinemia, different precautionary measures for the parents of babies suffering from hyperbilirubinemia and different remedial therapeutic measures for its treatment...
May 2016: Iranian Journal of Public Health
Zahida Khan, Veena L Venkat, Kyle A Soltys, Donna B Stolz, Sarangarajan Ranganathan
Jaundice in the newborn period can be physiologic and is often due to benign causes. Jaundice due to conjugated hyperbilirubinemia extending beyond the second week of life may be an early sign of several cholestatic or metabolic liver diseases, and it requires logical and timely analysis so that specific treatments can be initiated. A1AT deficiency is the most common genetic cause of pediatric liver disease and transplantation, and it must be considered when evaluating cholestatic infants. Here, we present an unusual case of A1AT deficiency with severe infantile cholestasis and rapid decompensation in the first 4 months of life, where in-depth but timely diagnosis was crucial for the appropriate intervention to take place...
February 8, 2016: Pediatric and Developmental Pathology
K Bauerova, F Drafi, V Kuncirova, S Ponist, D Mihalova, P Babal, T Sykora
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration...
2015: Physiological Research
T Malla, S Singh, P Poudyal, B Sathian, G Bk, K K Malla
BACKGROUND: An exchange transfusion involves replacing patient's blood with donor blood in order to remove abnormal blood components and circulating toxins while maintaining adequate circulating blood volume. OBJECTIVE: To observe the incidence, causes of jaundice requiring Exchange and any adverse event of exchange transfusion in newborns with unconjugated hyperbilirubinemia. METHOD: Prospective study undertaken at Neonatal Intensive Care Unit (NICU) of Manipal Teaching Hospital, Pokhara, Nepal from March 2014 to April 2015...
April 2015: Kathmandu University Medical Journal (KUMJ)
Ryoichi Fujiwara, Yoshihiro Maruo, Shujuan Chen, Robert H Tukey
Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ...
November 15, 2015: Toxicology and Applied Pharmacology
Eduardo Flores-Villalba, Carlos Rodriguez-Montalvo, Francisco Bosques-Padilla, Gabriela Arredondo-Saldaña, Tania Zertuche-Maldonado, Landy Torre-Flores
Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dL in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases...
April 2016: Revista Española de Enfermedades Digestivas
Hye Seon Kang, Chin Kook Rhee, Hea Yon Lee, Young Kyoon Kim, Soon Seog Kwon, Seok Chan Kim, Jong Wook Lee
BACKGROUND/AIMS: The clinical outcomes of patients with hematologic malignancies who were treated with extracorporeal membrane oxygenation (ECMO) after the failu re of optimal conventional therapy were determined. METHODS: The medical records of all patients administered ECMO during their stay in a medical intensive care unit of Seoul St. Mary's Hospital between February 2010 and July 2013 were reviewed retrospectively. RESULTS: In total, 15 patients with hematologic malignancies were compared to 33 immunocompetent patients with documented cardiorespiratory failure...
July 2015: Korean Journal of Internal Medicine
Hüseyin Altunhan, Ali Annagür, Nuriye Tarakçi, Murat Konak, Sabahattin Ertuğrul, Rahmi Örs
OBJECTIVES: The purpose of this study was to compare the efficacy and safety of two different catheterization techniques of exchange transfusion (ET) used in the therapy of newborn jaundice: fully automated two-way ET technique and the classical one-way ET. PATIENTS AND METHODS: The study included babies at gestational age of >34 weeks. In total, 107 ETs were performed on 86 babies. Totally, the umbilical vein (UV) group included 54 babies having undergone 69 ETs and the UV/UA group included 32 babies having undergone 38 ETs...
2016: Journal of Maternal-fetal & Neonatal Medicine
Michael Schleibinger, Cathérine L Steinbach, Christoph Töpper, Alexander Kratzer, Uwe Liebchen, Frieder Kees, Bernd Salzberger, Martin G Kees
AIMS: The aim of the present study was to assess the pharmacokinetics of total and unbound ceftriaxone in intensive care unit (ICU) patients and its protein binding characteristics. METHODS: Twenty patients (m/f 15/5, age 25-86 years, body weight 60-121 kg, APACHE II 7-40, estimated glomerular filtration rate 19-157 ml min(-1) , albumin 11.7-30.1 g l(-1) , total bilirubin <0.1-36.1 mg dl(-1) ) treated with intravenous ceftriaxone were recruited from two ICUs...
September 2015: British Journal of Clinical Pharmacology
I Azkárate, G Choperena, E Salas, R Sebastián, G Lara, I Elósegui, L Barrutia, I Eguibar, R Salaberria
OBJECTIVE: To determine the clinical characteristics and prognostic factors of patients with severe sepsis/septic shock admitted to the Intensive Care Unit of Donostia University Hospital (Guipuzcoa, Spain). DESIGN: A prospective, observational study was carried out during a consecutive 6-year period (1st February 2008-31st December 2013). SETTING: The Intensive Care Unit of Donostia University Hospital, the only third level hospital in the province of Guipuzcoa, with a recruitment population of 700,000 inhabitants...
January 2016: Medicina Intensiva
Patricia Mena N, Jorge León Del P, Daniela Sandino P, Pamela Ralmolfo B, Debora Sabatelli, Adolfo Llanos M, Beatriz Milet L
INTRODUCTION: It has been reported that feeding tolerance in preterm infants is associated with an early passage of meconium. Prospective, randomized or historical control studies that stimulate meconium evacuation have reported varied results. This study was intented to evaluate the use of enemas to speed up meconium evacuation, facilitating feeding tolerance. PATIENTS AND METHOD: A controlled multicenter randomized trial that evaluated the use of physiological saline enemas with glycerol (0...
June 2014: Revista Chilena de Pediatría
N N Sazhina, V N Titov, I N Popov, S A Solonin, M A Godkov
The antioxidant activity is implemented in human blood serum by ascorbic acid, uric acid, amino acids, glucose, mono unsaturated fatty acids (in the first instance Ω-9 oleic acid), essential polyenoic fatty acids, thiol groups of albumins and proteins, tripeptide and pigment of bilirubin. The antioxidant activity of blood serum of donors and recipients before liver transplantation was determined The input of particular biochemical analytes into liver transplantation was determined too. The antioxidant parameters were detected using technique of termo-induced chemiluminescence under application of set of corresponding reagents...
August 2014: Klinicheskaia Laboratornaia Diagnostika
Hiroko Sato, Toshihiko Uchida, Kentaro Toyota, Tomohiro Nakamura, Gen Tamiya, Miyako Kanno, Taeko Hashimoto, Masashi Watanabe, Kuraaki Aoki, Kiyoshi Hayasaka
Neonates have physiologically increased bilirubin production and immature bilirubin metabolism, and present hyperbilirubinemia in association with genetic and or epigenetic factors. We previously reported that maximal body weight loss (inadequate feeding) is an independent risk factor for the development of hyperbilirubinemia in breast-fed Japanese neonates, and the UGT1A1 211G>A genotype becomes a risk factor under conditions of inadequate feeding. We extended the study to the association of other genetic factors, the UGT1A1 (TA)7 and solute-carrier organic anion transporters (SLCOs) polymorphisms with neonatal hyperbilirubinemia...
January 2015: Journal of Human Genetics
Lori W E van der Schoor, Henkjan J Verkade, Folkert Kuipers, Johan W Jonker
INTRODUCTION: For the elimination of environmental chemicals and metabolic waste products, the body is equipped with a range of broad specificity transporters that are present in excretory organs as well as in several epithelial blood-tissue barriers. AREAS COVERED: ABCC2 and ABCC3 (also known as MRP2 and MRP3) mediate the transport of various conjugated organic anions, including many drugs, toxicants and endogenous compounds. This review focuses on the physiology of these transporters, their roles in drug disposition and how they affect drug sensitivity and toxicity...
February 2015: Expert Opinion on Drug Metabolism & Toxicology
Ingrid F Metzger, Troy C Quigg, Noam Epstein, Abdulateef O Aregbe, Nancy Thong, John T Callaghan, David A Flockhart, Anne T Nguyen, Colleen K Stevens, Samir K Gupta, Zeruesenay Desta
BACKGROUND: Efavirenz exhibits multiple interactions with drug-metabolizing enzymes and transporters, and for this reason efavirenz-based HIV therapy is associated with altered pharmacokinetics of coadministered drugs. Probably by the same mechanism, efavirenz-based HIV therapy affects the disposition of endogenous compounds, but this effect is difficult to directly link with efavirenz because it is used in combination with other drugs. OBJECTIVES: To explore the effect of efavirenz monotherapy on biochemical laboratory values in a clinical trial of healthy volunteers...
December 2014: Current Therapeutic Research, Clinical and Experimental
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