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acetaminophen and acute hepatic failure

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https://www.readbyqxmd.com/read/27862262/different-effects-of-selective-%C3%AE-1-adrenoceptor-antagonists-nebivolol-or-atenolol-in-acetaminophen-induced-heptatotoxicity-of-rats
#1
Remon R Rofaeil, Maha Yehia Kamel, Walaa Yehia Abdelzaher
Acetaminophen (APAP) overdose is a common cause of acute liver failure and beta blockers are commonly used drugs in clinical practice. This study aims to evaluate the effect of two different beta blockers agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg /day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27761495/gene-expression-data-from-acetaminophen-induced-toxicity-in-human-hepatic-in-vitro-systems-and-clinical-liver-samples
#2
Robim M Rodrigues, Olivier Govaere, Tania Roskams, Tamara Vanhaecke, Vera Rogiers, Joery De Kock
This data set is composed of transcriptomics analyses of (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF) and (ii) hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Data from primary human hepatocytes was also added to the data set "Open TG-GATEs: a large-scale toxicogenomics database" (Igarashi et al...
June 2016: Data in Brief
https://www.readbyqxmd.com/read/27531059/transcriptome-association-analysis-identifies-mir-375-as-a-major-determinant-of-variable-acetaminophen-glucuronidation-by-human-liver
#3
Ioannis Papageorgiou, Marina Freytsis, Michael H Court
Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression...
October 1, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27350943/acetaminophen-induced-hepatotoxicity-a-comprehensive-update
#4
REVIEW
Eric Yoon, Arooj Babar, Moaz Choudhary, Matthew Kutner, Nikolaos Pyrsopoulos
Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur...
June 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/27275268/fulminate-hepatic-failure-in-a-5-year-old-female-after-inappropriate-acetaminophen-treatment
#5
Irena Kasmi, Sashenka Sallabanda, Gentian Kasmi
BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day...
September 15, 2015: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/27235652/-good-use-and-knowledge-of-paracetamol-acetaminophen-among-self-medicated-patients-prospective-study-in-community-pharmacies
#6
Anne-Elise Severin, Nadine Petitpain, Julien Scala-Bertola, Clotilde Latarche, Melissa Yelehe-Okouma, Paolo Di Patrizio, Pierre Gillet
Acetaminophen (paracetamol), the highest over-the-counter (OTC) selling drug in France, is also the first cause of acute hepatic failure. We aimed to assess the good use and the knowledge of acetaminophen in a setting of urban self-medicated patients. We conducted a prospective observational study in randomly selected community pharmacies of Metz (France) agglomeration. Patients coming to buy OTC acetaminophen for themselves or their family had to answer to an anonymous autoquestionnaire. Responses were individually and concomitantly analyzed through 3 scores: good use, knowledge and overdosage...
June 2016: Thérapie
https://www.readbyqxmd.com/read/27215797/the-role-of-hepatitis-e-virus-infection-in-adult-americans-with-acute-liver-failure
#7
Robert John Fontana, Ronald E Engle, Steven Scaglione, Victor Araya, Obaid Shaikh, Holly Tillman, Nahid Attar, Robert H Purcell, William M Lee
: Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27211843/role-of-nicotinamide-vitamin-b3-in-acetaminophen-induced-changes-in-rat-liver-nicotinamide-effect-in-acetaminophen-damged-liver
#8
Yomna I Mahmoud, Asmaa A Mahmoud
Acetaminophen is a widely used analgesic and antipyretic agent, which is safe at therapeutic doses. However, overdoses of acetaminophen induce severe oxidative stress, which leads to acute liver failure. Nicotinamide has proven effective in ameliorating many pathological conditions that occur due to oxidative stress. This study verifies the prophylactic and therapeutic effects of nicotinamide against the hepatic pathophysiological and ultrastructural alterations induced by acetaminophen. Wistar rats intoxicated with an acute overdose of acetaminophen (5g/kg b...
June 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27171266/chitohexaose-protects-against-acetaminophen-induced-hepatotoxicity-in-mice
#9
P K Barman, R Mukherjee, B K Prusty, S Suklabaidya, S Senapati, B Ravindran
Acetaminophen (N-acetyl-para-aminophenol (APAP)) toxicity causes acute liver failure by inducing centrilobular hepatic damage as a consequence of mitochondrial oxidative stress. Sterile inflammation, triggered by hepatic damage, facilitates gut bacterial translocation leading to systemic inflammation; TLR4-mediated activation by LPS has been shown to have a critical role in APAP-mediated hepatotoxicity. In this study, we demonstrate significant protection mediated by chitohexaose (Chtx) in mice challenged with a lethal dose of APAP (400 mg/kg b...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27170397/acute-liver-failure-it-s-just-a-matter-of-cell-death
#10
Jan-Peter Sowa, Guido Gerken, Ali Canbay
BACKGROUND: Acute liver failure (ALF) is characterized by a sudden loss of hepatic function due to hepatocyte cell death and dysfunction in previously healthy individuals. The clinical presentation of ALF is associated with coagulopathy (international normalized ratio ≥1.5) and hepatic encephalopathy, although the latter may be less pronounced. Without appropriate and timely intensive care or liver transplantation (LTx), ALF will result in multi-organ failure and death. Various causes may induce ALF, with acetaminophen (APAP) intoxication and acute hepatitis B infection as most common causes in industrialized countries...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27144271/attenuating-oxidative-stress-by-paeonol-protected-against-acetaminophen-induced-hepatotoxicity-in-mice
#11
Yi Ding, Qing Li, Yuan Xu, Yuning Chen, Yue Deng, Feng Zhi, Ke Qian
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. The purpose of this study was to investigate whether paeonol protected against APAP-induced hepatotoxicity. Mice treated with paeonol (25, 50, 100 mg/kg) received 400 mg/kg acetaminophen intraperitoneally (i.p.) and hepatotoxicity was assessed. Pre-treatment with paeonol for 6 and 24 h ameliorated APAP-induced hepatic necrosis and significantly reduced the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in a dose-dependent manner...
2016: PloS One
https://www.readbyqxmd.com/read/27142208/drug-induced-liver-injury-highlights-from-a-review-of-the-2015-literature
#12
REVIEW
Philip Sarges, Joshua M Steinberg, James H Lewis
Numerous publications contributed to the expanding knowledge base about drug-induced liver injury (DILI) in 2015. New findings from the US Drug Induced Liver Injury Network (DILIN) in their most recently updated registry include a 1- to 3-week delay in the appearance of acute DILI from short-course antibiotics such as cefazolin. They corroborated the finding that acute DILI in patients with underlying liver disease was far more severe and potentially fatal than in patients without liver disease. The only drug that seemed to have an increased risk of hepatotoxicity in these patients was azithromycin...
September 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/27085756/development-of-a-model-to-predict-transplant-free-survival%C3%A2-of%C3%A2-patients-with-acute-liver-failure
#13
David G Koch, Holly Tillman, Valerie Durkalski, William M Lee, Adrian Reuben
BACKGROUND & AIMS: Patients with acute liver failure (ALF) have a high risk of death that can be substantially reduced with liver transplantation. It is a challenge to predict which patients with ALF will survive without liver transplant because available prognostic scoring systems are inadequate. We devised a mathematical model, using a large dataset collected by the Acute Liver Failure Study Group, which can predict transplant-free survival in patients with ALF. METHODS: We performed a retrospective analysis of data from 1974 subjects who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) enrolled in the Acute Liver Failure Study Group database from January 1, 1998 through June 11, 2013...
August 2016: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27058243/the-pathology-of-acute-liver-failure
#14
Jay H Lefkowitch
Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells...
May 2016: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/27057357/therapeutic-potential-of-hgf-expressing-human-umbilical-cord-mesenchymal-stem-cells-in-mice-with-acute-liver-failure
#15
Yunxia Tang, Qiongshu Li, Fanwei Meng, Xingyu Huang, Chan Li, Xin Zhou, Xiaoping Zeng, Yixin He, Jia Liu, Xiang Hu, Ji-Fan Hu, Tao Li
Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival...
2016: International Journal of Hepatology
https://www.readbyqxmd.com/read/27043883/outcomes-in-adults-with-acute-liver-failure-between-1998-and-2013-an-observational-cohort-study
#16
Adrian Reuben, Holly Tillman, Robert J Fontana, Timothy Davern, Brendan McGuire, R Todd Stravitz, Valerie Durkalski, Anne M Larson, Iris Liou, Oren Fix, Michael Schilsky, Timothy McCashland, J Eileen Hay, Natalie Murray, Obaid S Shaikh, Daniel Ganger, Atif Zaman, Steven B Han, Raymond T Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, M Edwyn Harrison, David Koch, Santiago Munoz, K Rajender Reddy, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein, A James Hanje, Jody Olson, Ram Subramanian, Constantine Karvellas, Bilal Hameed, Averell H Sherker, Patricia Robuck, William M Lee
BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers...
June 7, 2016: Annals of Internal Medicine
https://www.readbyqxmd.com/read/27043544/the-honolulu-liver-disease-cluster-at-the-medical-center-its-mysteries-and-challenges
#17
REVIEW
Rolf Teschke, Axel Eickhoff
In 2013, physicians at the Honolulu Queen's Medical Center (QMC) noticed that seven liver disease patients reported the use of OxyELITE Pro (OEP), a widely consumed dietary supplement (DS). Assuming a temporal association between OEP use and disease, they argued that OEP was the cause of this mysterious cluster. Subsequent reexamination, however, has revealed that this QMC cohort is heterogeneous and not a cluster with a single agent causing a single disease. It is heterogeneous because patients used multiple DS's and drugs and because patients appeared to have suffered from multiple liver diseases: liver cirrhosis, liver failure by acetaminophen, hepatotoxicity by non-steroidal antiinflammatory drugs (NSAIDs), resolving acute viral hepatitis by hepatitis B virus (HBV), herpes simplex virus (HSV), and varicella zoster virus (VZV), and suspected hepatitis E virus (HEV)...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26998396/new-strategies-for-acute-liver-failure-focus-on-xenotransplantation-therapy
#18
Luiz Anastácio Alves, André Bonavita, Kátia Quaresma, Elenilde Torres, Paulo Anastácio Furtado Pacheco, Vinícius Cotta-de-Almeida, Roberto Magalhães Saraiva
Acute liver failure (ALF) has a poor prognosis and, despite intensive care support, reported average survival is only 10-40%. The most common causes responsible for ALF are viral hepatitis (mainly hepatitis A and B) and acetaminophen poisoning. Hepatic transplantation is the only appropriate treatment for patients with unlikely survival with supportive care alone. Survival rates after transplantation can be as high as 80-90% at the end of the first year. However, there is a shortage of donors and is not uncommon that no appropriate donor matches with the patient in time to avoid death...
2010: Cell Medicine
https://www.readbyqxmd.com/read/26990366/remote-ischemic-conditioning-protects-against-acetaminophen-induced-acute-liver-injury-in-mice
#19
Wei Zheng, Zhiyong Zhang, Sushun Liu, Jianbin Bi, Jingyao Zhang, Lixue Du, Xiaoming Ding, Chang Liu
Acetaminophen (APAP) overdose is a major cause of drug acute liver failure. Studies have shown that remote ischemic pre- and post-conditioning (R-IPC and R-IPOST) can protect the liver against ischemia-reperfusion (I/R) and LPS induced injuries. The aim of this study was to investigate the effect of R-IPC and R-IPOST on APAP-induced hepatotoxicity in mice. Mice were randomized (n = 6 per group) to seven major groups that were treated as follows: (1) the normal control group; (2) the sham operated group; (3) the APAP group; (4) R-IPC + APAP group; (5) R-IPC + APAP + ZnPP group; (6) R-IPOST + APAP group; and (7) R-IPOST + APAP + ZnPP group...
March 17, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/26983031/a-proof-of-concept-phase-ii-randomized-european-trial-on-the-efficacy-of-alf-5755-a-novel-extracellular-matrix-targeted-antioxidant-in-patients-with-acute-liver-diseases
#20
RANDOMIZED CONTROLLED TRIAL
Bertrand Nalpas, Philippe Ichaï, Laure Jamot, Nicolas Carbonell, Marika Rudler, Philippe Mathurin, François Durand, Guido Gerken, Michael Manns, Christian Trautwein, Dominique Larrey, Sylvie Radenne, Christophe Duvoux, Vincent Leroy, Jacques Bernuau, Jamila Faivre, Nicolas Moniaux, Christian Bréchot, Gilles Amouyal, Paul Amouyal, Didier Samuel
OBJECTIVE: No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. DESIGN: double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72)...
2016: PloS One
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