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https://www.readbyqxmd.com/read/28820004/drug-induced-liver-injury-in-children-clinical-observations-animal-models-and-regulatory-status
#1
Qiang Shi, Xi Yang, James J Greenhaw, Alec Thomas Salminen, Gary M Russotti, William F Salminen
Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28812385/increased-acetaminophen-related-calls-to-finnish-pic-better-reflect-acetaminophen-sales-than-serious-poisonings
#2
Mikko J Parry, Helena Isoniemi, Anna-Maria Koivusalo, Kalle Hoppu
OBJECTIVE: Acetaminophen (APAP) or paracetamol is a commonly encountered medicine in poisonings. We studied the changes in APAP related calls to the Finnish poison information centre (FPIC), and serious intoxications, involving hepatotoxicity or death in 2001-2014. These data were compared with paracetamol sales in Finland. METHODS: This is a retrospective analysis of the FPIC database calls, national cause of death registry, registries of liver transplantations and molecular adsorbent recycling system (MARS)-treated patients from Helsinki University Hospital together with the National Institute of Health and Welfare registry of patients hospitalized...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28809737/acute-liver-failure-due-to-etodolac-a-selective-cycloxygenase-2-cox-2-inhibitor-non-steroidal-anti-inflammatory-drug-established-by-rucam-based-causality-assessment
#3
Sunil Taneja, Pramod Kumar, Sahaj Rathi, Ajay Duseja, Virendra Singh, Radha Krishan Dhiman, Yogesh Kumar Chawla
Drug induced liver injury is a common cause of acute liver failure (ALF). While most of these cases are due to dose dependent hepatotoxicity with acetaminophen, idiosyncratic drug-induced liver injury (DILI) is responsible for about 15% cases of ALF. Antibiotics are the most common cause of idiosyncratic DILI as well as DILI induced ALF. Etodolac is a selective cycloxygenase- 2 (COX -2) inhibitor non-steroidal anti-inflammatory drug used as an analgesic and anti-inflammatory in musculoskeletal diseases. Severe liver impairment is extremely rare...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#4
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807032/liquid-chromatography-mass-spectrometry-based-profiling-of-phosphatidylcholine-and-phosphatidylethanolamine-in-the-plasma-and-liver-of-acetaminophen-induced-liver-injured-mice
#5
Ya-Nan Ming, Jing-Yi Zhang, Xiao-Lin Wang, Chun-Min Li, Si-Cong Ma, Zheng-Yang Wang, Xiao-Lin Liu, Xiao-Bo Li, Yi-Min Mao
BACKGROUND: Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. METHODS: A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver...
August 14, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28795995/toxic-myocarditis-caused-by-acetaminophen-in-a-multidrug-overdose
#6
Maxime Gosselin, Yann Dazé, Pascal Mireault, Marie Crahes
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction...
August 9, 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/28772086/highlights-of-drug-and-herb-induced-liver-injury-in-the-literature-from-2016-how-best-to-translate-new-information-into-clinical-practice
#7
Omar Shahbaz, Sandeep Mahajan, James H Lewis
INTRODUCTION: More than 1500 papers on drug-induced liver injury (DILI) and herb-induced liver injury (HILI) were published in 2016, many of which have the potential to impact clinical practice. AREAS COVERED: Clinical studies and case series that lent themselves to new concepts or directions in diagnosing, preventing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted, including the US DILIN network and Spanish DILI registry...
August 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28770975/paracetamol-acetaminophen-for-chronic-non-cancer-pain-in-children-and-adolescents
#8
REVIEW
Tess E Cooper, Emma Fisher, Brian Anderson, Nick Mr Wilkinson, David G Williams, Christopher Eccleston
BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important...
August 2, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28765016/a-novel-biomarker-and-hepato-protector-for-acetaminophen-induced-liver-injury
#9
EDITORIAL
Yi-Shin Huang
No abstract text is available yet for this article.
July 29, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28758069/investigating-the-application-of-a-nitroreductase-expressing-transgenic-zebrafish-line-for-high-throughput-toxicity-testing
#10
Anna C Chlebowski, Jane K La Du, Lisa Truong, Staci L Massey Simonich, Robert L Tanguay
Nitroreductase enzymes are responsible for the reduction of nitro functional groups to amino functional groups, and are found in a range of animal models, zebrafish (Danio rerio) excluded. Transgenic zebrafish models have been developed for tissue-specific cell ablation, which use nitroreductase to ablate specific tissues or cell types following exposure to the non-toxic pro-drug metronidazole (MTZ). When metabolized by nitroreductase, MTZ produces a potent cytotoxin, which specifically ablates the tissue in which metabolism occurs...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28755860/dynamic-and-accurate-assessment-of-acetaminophen-induced-hepatotoxicity-by-integrated-photoacoustic-imaging-and-mechanistic-biomarkers-in-vivo
#11
Nathalie Brillant, Mohamed Elmasry, Neal C Burton, Josep Monne Rodriguez, Jack W Sharkey, Stephen Fenwick, Harish Poptani, Neil R Kitteringham, Christopher E Goldring, Anja Kipar, B Kevin Park, Daniel J Antoine
The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention...
July 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28740338/localization-and-role-of-metabotropic-glutamate-receptors-subtype-5-in-the-gastrointestinal-tract
#12
REVIEW
Andrea Ferrigno, Clarissa Berardo, Laura G Di Pasqua, Veronica Siciliano, Plinio Richelmi, Mariapia Vairetti
Metabotropic glutamate receptor subtype 5 (mGluR5) is a Group I mGlu subfamily of receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like other mGluR subtypes, mGluR5s contain a phylogenetically conserved, extracellular orthosteric binding site and a more variable allosteric binding site, located on the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key pharmacological target in conditions affecting the central nervous system (CNS) but its presence outside the CNS underscores its potential role in pathologies affecting peripheral organs such as the gastrointestinal (GI) tract and accessory digestive organs such as the tongue, liver and pancreas...
July 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28734939/public-health-acetaminophen-apap-hepatotoxicity-isn-t-it-time-for-apap-to-go-away
#13
REVIEW
William M Lee
Acetaminophen (APAP) is the most commonly used drug for the treatment of pain and fever around the world. At the same time, APAP is capable of causing dose-related hepatocellular necrosis, responsible for nearly 500 deaths annually in the U.S. alone, as well as 100,000 calls to US Poison Control Centers, 50,000 emergency room visits and 10,000 hospitalizations per year. As an over-the-counter and prescription product (with opioids), APAP toxicity dwarfs all other prescription drugs as a cause for acute liver failure in the United States and Europe, but is not regulated in any significant way...
July 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#14
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
July 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28717379/hepatoprotective-effect-of-citral-on-acetaminophen-induced-liver-toxicity-in-mice
#15
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Gabriel Fernando Esteves Cardia, Edivaldo Cremer, Francielli Maria de Souza Silva-Comar, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28717103/metabolomics-of-an-in-vitro-liver-model-containing-primary-hepatocytes-assembling-around-an-endothelial-cell-network-comparative-study-on-the-metabolic-stability-and-the-effect-of-acetaminophen-treatment
#16
Yu Toyoda, Kasumi Kashikura, Tomoyoshi Soga, Yoh-Ichi Tagawa
Recently, a novel culture system consisting of primary hepatocytes structured over a network of endothelial cells on the Engelbreth-Holm-Swarm (EHS) gel has been reported. This in vitro liver model on the EHS gel (IVLEHS) has been shown to maintain the expression of hepatic genes and their functional activity. Moreover, the IVLEHS was more sensitive to xenobiotics than hepatocyte monocultures, suggesting the potential utility of this culture system for compound hepatotoxicity screening. However, the effect of this three-dimensional structure formation on the cellular metabolic profile of hepatocytes in the IVLEHS is not well understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#17
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D Sharma, Michael Ott, Tobias Cantz
The quest for physiologically-active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC) - derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
July 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28692292/discovery-of-potent-and-selective-inhibitors-of-cdc2-like-kinase-1-clk1-as-a-new-class-of-autophagy-inducers
#18
Qi-Zheng Sun, Gui-Feng Lin, Lin-Li Li, Xi-Ting Jin, Lu-Yi Huang, Guo Zhang, Wei Yang, Kai Chen, Rong Xiang, Chong Chen, Yu-Quan Wei, Guang-Wen Lu, Sheng-Yong Yang
Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1...
July 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#19
Julie Massart, Karima Begriche, Caroline Moreau, Bernard Fromenty
BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28687253/connexin-hemichannel-inhibition-reduces-acetaminophen-induced-liver-injury-in-mice
#20
Michaël Maes, Sara Crespo Yanguas, Joost Willebrords, James L Weemhoff, Tereza Cristina da Silva, Elke Decrock, Margitta Lebofsky, Isabel Veloso Alves Pereira, Luc Leybaert, Anwar Farhood, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen...
July 4, 2017: Toxicology Letters
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