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https://www.readbyqxmd.com/read/28795997/celecoxib-induced-liver-injury-analysis-of-published-case-reports-and-cases-reported-to-the-food-and-drug-administration
#1
Pavan K Mukthinuthalapati, Robert J Fontana, Raj Vuppalanchi, Naga Chalasani, Marwan Ghabril
BACKGROUND: Celecoxib is a widely prescribed nonsteroidal anti-inflammatory drug, and has been associated with rare instances of idiosyncratic drug-induced liver injury (DILI). The aim of this study is to describe and analyze the salient features of published cases of celecoxib DILI. MATERIALS AND METHODS: A literature search using common terms for liver injury cross-referenced with celecoxib was undertaken from the year 2000 through June 2016. Identified cases were analyzed with respect to reported demographic and clinical data with descriptive...
August 8, 2017: Journal of Clinical Gastroenterology
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
#2
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/28770534/antidepressant-induced-acute-liver-injury-a-case-control-study-in-an-italian-inpatient-population
#3
Carmen Ferrajolo, Cristina Scavone, Monia Donati, Oscar Bortolami, Giovanna Stoppa, Domenico Motola, Alfredo Vannacci, Alessandro Mugelli, Roberto Leone, Annalisa Capuano
INTRODUCTION: Pre-marketing clinical trials show that antidepressant-induced liver injury seems to be a rare adverse event. Because of short follow-up trial duration, the incidence of liver injury due to antidepressant use could be underestimated. OBJECTIVES: We aimed to quantify the risk of acute liver injury associated with antidepressant use through a case-control analysis among an inpatient population. METHODS: A multicenter study was carried out in nine Italian hospitals from October 2010 to January 2014, within the DILI-IT (Drug-Induced Liver Injury in Italy) study project...
August 2, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28762471/clinical-presentation-of-terbinafine-induced-severe-liver-injury-and-the-value-of-laboratory-monitoring-a-critically-appraised-topic
#4
REVIEW
O N Kramer, J Albrecht
CONTEXT: Many physicians monitor liver function tests during terbinafine therapy. OBJECTIVE: Evaluate the symptoms of published cases of terbinafine associated severe DILI (Drug Induced Liver Injury) to assess the utility of laboratory monitoring. DATA SOURCES: We based our search on the Liver Tox database of the National Institute of Health, but searched PUBMED as well as EMBASE. In addition, we hand-searched the references of the papers we found...
August 1, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28762375/idiosyncratic-drug-induced-liver-injury-in-african-americans-is-associated-with-greater-morbidity-and-mortality-compared-to-caucasians
#5
Naga Chalasani, K Rajender K Reddy, Robert J Fontana, Huiman Barnhart, Jiezhun Gu, Paul H Hayashi, Jawad Ahmad, Andrew Stolz, Victor Navarro, Jay H Hoofnagle
OBJECTIVES: Idiosyncratic drug induced liver injury (DILI) is a rare but potentially serious liver disorder and a major cause of significant liver injury. Limited data exist on racial differences in DILI incidence, presentation, and course. METHODS: We compared the causative agents, clinical features, and outcomes of DILI among self-described African-Americans and non-Hispanic whites (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite, highly likely, or probable DILI enrolled between September 2004 and February 2016 were included in this analysis...
August 1, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28762043/customised-in-vitro-model-to-detect-human-metabolism-dependent-idiosyncratic-drug-induced-liver-injury
#6
Laia Tolosa, Nuria Jiménez, Gabriela Pérez, José V Castell, M José Gómez-Lechón, M Teresa Donato
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI...
July 31, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28754111/care-of-the-mother-infant-dyad-a-novel-approach-to-conducting-and-evaluating-neonatal-resuscitation-simulation-training-in-bihar-india
#7
Brennan Vail, Hilary Spindler, Melissa C Morgan, Susanna R Cohen, Amelia Christmas, Pramod Sah, Malay B Shah, Aritra Das, Dilys M Walker
BACKGROUND: As the global under-five mortality rate declines, an increasing percentage is attributable to early neonatal mortality. A quarter of early neonatal deaths are due to perinatal asphyxia. However, neonatal resuscitation (NR) simulation training in low-resource settings, where the majority of neonatal deaths occur, has achieved variable success. In Bihar, India, the poorest region in South Asia, there is tremendous need for a new approach to reducing neonatal morality. METHODS: This analysis aims to assess the impact of a novel in-situ simulation training program, developed by PRONTO International and implemented in collaboration with CARE India, on NR skills of nurses in Bihar...
July 28, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#8
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28743512/inferring-transcription-factor-activity-from-microarray-data-reveals-novel-targets-for-toxicological-investigations
#9
T M Souza, T van den Beucken, J C S Kleinjans, D G J Jennen
Transcription factors (TFs) are important modulators of the inducible portion of the transcriptome, and therefore relevant in the context of exposure to exogenous compounds. Current approaches to predict the activity of TFs in biological systems are usually restricted to a few entities at a time due to low-throughput techniques targeting a limited fraction of annotated human TFs. Therefore, high-throughput alternatives may help to identify new targets of mechanistic and predictive value in toxicological investigations...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28732258/areca-catechu-palm-tree-nut-chewing-and-seizures-an-observational-study
#10
Farrah J Mateen, Marco Carone, Lhab Tshering, Chencho Dorji, Ugyen Dema, Sara J Grundy, Dili Ram Pokhrel, Damber K Nirola
OBJECTIVE: The objective of this study was to report the impact of chronic abuse of Areca catechu nut wrapped in leaf (also known as doma, quid, paan), the fourth most commonly abused psychoactive substance worldwide, on the frequency of seizures among people with epilepsy. METHODS: People with clinically diagnosed epilepsy (>14years old) residing in the Kingdom of Bhutan were surveyed for self-reported Areca catechu use, demographic variables, epilepsy characteristics, and seizure frequency...
July 18, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#11
Takuo Ogihara, Hiroshi Arakawa, Tomoko Jomura, Yoko Idota, Satoshi Koyama, Kentaro Yano, Hajime Kojima
We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717101/mechanism-based-risk-assessment-strategy-for-drug-induced-cholestasis-using-the-transcriptional-benchmark-dose-derived-by-toxicogenomics
#12
Taisuke Kawamoto, Yuichi Ito, Osamu Morita, Hiroshi Honda
Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28713494/caspase-3-role-and-immunohistochemical-expression-in-assessment-of-apoptosis-as-a-feature-of-h1n1-vaccine-caused-drug-induced-liver-injury-dili
#13
Abir Khalil Mohamed, Mona Magdy
BACKGROUND: Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. AIM: To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. METHODS: This 2014's experimental study was conducted on 70 albino rats. They were given Arepanrix(TM) H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1(st) and 2(nd) doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2(nd) dose, mix2 and mix4 injected with 1(st) and 2(nd) doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2(nd) dose...
May 2017: Electronic Physician
https://www.readbyqxmd.com/read/28702139/ramipril-associated-cholestasis-in-the-setting-of-recurrent-drug-induced-liver-injury
#14
David Forner, Tasha Kulai, Thomas Arnason, Steven E Gruchy, Magnus MacLeod
Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat hypertension. Although generally well tolerated, the adverse effects of ACEIs include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of ACEI-induced hepatotoxicity have been described, most notably a cholestatic pattern of injury related to captopril. A 67-year-old male presented to the emergency department with a three-week history of jaundice, pruritis and weakness. Eight weeks before, he began taking ramipril and clopidogrel...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28694671/substantial-hepatic-necrosis-is-prognostic-in-fulminant-liver-failure
#15
Paul Ndekwe, Marwan S Ghabril, Yong Zang, Steven A Mann, Oscar W Cummings, Jingmei Lin
AIM: To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival. METHODS: Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#16
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/28688954/rifampicin-induced-injury-in-hepg2-cells-is-alleviated-by-tudca-via-increasing-bile-acid-transporters-expression-and-enhancing-the-nrf2-mediated-adaptive-response
#17
Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner...
July 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28675685/challenges-and-difficulties-in-pathological-diagnosis-of-autoimmune-hepatitis
#18
REVIEW
Kenichi Harada, Nguyen Canh Hiep, Hiromasa Ohira
Autoimmune hepatitis (AIH) with acute presentation is widely recognized as a distinct clinical entity, and its clinicopathology has been extensively studied. In most cases, AIH with acute presentation is merely acute exacerbation of classical chronic AIH, but pure acute-onset AIH without previous symptoms of chronic liver disease is also encountered. Rapid diagnosis and initiation of immunosuppressive treatment are necessary for both acute exacerbation and acute-onset to prevent fatal liver failure. The diagnostic criteria commonly used for classical AIH are generally applicable to acute exacerbation, but acute-onset AIH may present with additional pathological features...
July 3, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28675031/efficient-two-photon-fluorescent-probe-for-glutathione-s-transferase-detection-and-imaging-in-drug-induced-liver-injury-sample
#19
Jing Zhang, Zhen Jin, Xiao-Xiao Hu, Hong-Min Meng, Jin Li, Xiao-Bing Zhang, Hong-Wen Liu, Tanggang Deng, Shan Yao, Lili Feng
Drug-induced liver injury (DILI) is a potential complication of any prescribed medication. So far, the diagnosis of DILI is still a clinical challenge due to the lack of efficient diagnosis method. Glutathione S-transferase (GST), with a high concentration in liver cytosol, can reduce toxicity and facilitate urinary excretion by catalyzing the conjugation of glutathione (GSH) with reactive metabolites in liver. When liver is seriously damaged, GST and GSH will be released into plasma from liver cytosol, which caused a lower GST activity in liver cytosol...
July 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28674261/preliminary-evaluation-of-three-dimensional-primary-human-hepatocyte-culture-system-for-assay-of-drug-metabolizing-enzyme-inducing-potential
#20
Hiroshi Arakawa, Hiroki Kamioka, Tomoko Jomura, Satoshi Koyama, Yoko Idota, Kentaro Yano, Hajime Kojima, Takuo Ogihara
Drug-induced liver injury (DILI) is a common reason for withdrawal of candidate drugs from clinical trials, or of approved drugs from the market. DILI may be induced not only by intact parental drugs, but also by metabolites or intermediates, and therefore should be evaluated in the enzyme-induced state. Here, we present a protocol for assay of drug-metabolizing enzyme-inducing potential using three-dimensional (3D) primary cultures of human hepatocytes (hepatocyte spheroids). Hepatocyte spheroids could be used up to 21 d after seeding (pre-culture for 7 d and exposure to inducer for up to 14 d), based on preliminary evaluation of basal activities of CYP subtypes and mRNA expression of the corresponding transcription factor and xenobiotic receptors (aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X receptor (PXR))...
2017: Biological & Pharmaceutical Bulletin
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