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DILI

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https://www.readbyqxmd.com/read/28448553/a-computational-toxicogenomics-approach-identifies-a-list-of-highly-hepatotoxic-compounds-from-a-large-microarray-database
#1
Héctor A Rueda-Zárate, Iván Imaz-Rosshandler, Roberto A Cárdenas-Ovando, Juan E Castillo-Fernández, Julieta Noguez-Monroy, Claudia Rangel-Escareño
The liver and the kidney are the most common targets of chemical toxicity, due to their major metabolic and excretory functions. However, since the liver is directly involved in biotransformation, compounds in many currently and normally used drugs could affect it adversely. Most chemical compounds are already labeled according to FDA-approved labels using DILI-concern scale. Drug Induced Liver Injury (DILI) scale refers to an adverse drug reaction. Many compounds do not exhibit hepatotoxicity at early stages of development, so it is important to detect anomalies at gene expression level that could predict adverse reactions in later stages...
2017: PloS One
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#2
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28443154/drug-induced-liver-injury-do-we-know-everything
#3
REVIEW
Tamara Alempijevic, Simon Zec, Tomica Milosavljevic
Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged...
April 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28437842/autoimmune-like-chronic-hepatitis-induced-by-olmesartan
#4
Sandrine Barge, Marianne Ziol, Jean-Charles Nault
Drug liver-induced injury (DILI) due to minocyclin, alpha methyldopa or nitrofurantoin may be responsible for chronic liver damage that mimic the biological and/or histological features of chronic autoimmune hepatitis and, in rare cases, progresses to cirrhosis(1). Olmesartan medoxomil is an antihypertensive drug that acts by blocking the angiotensin II receptor and is metabolized into its pharmacologically active form, olmesartan, in the intestine and in the liver before being released into the systemic circulation...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#5
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28436314/metabolomic-approaches-in-the-discovery-of-potential-urinary-biomarkers-of-drug-induced-liver-injury-dili
#6
Ana Margarida Araújo, Márcia Carvalho, Félix Carvalho, Maria de Lourdes Bastos, Paula Guedes de Pinho
Drug-induced liver injury (DILI) is a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The identification of DILI biomarkers is a labor-intensive area. Conventional biomarkers are not specific and often only appear at significant levels when liver damage is substantial. Therefore, new biomarkers for early identification of hepatotoxicity during the drug discovery process are needed, thus resulting in lower development costs and safer drugs...
April 24, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28425415/drug-induced-liver-injury-at-a-tertiary-hospital-in-india-etiology-clinical-features-and-predictors-of-mortality
#7
Chetan Rathi, Nirav Pipaliya, Ruchir Patel, Meghraj Ingle, Aniruddha Phadke, Prabha Sawant
INTRODUCTION AND AIMS: Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. MATERIAL AND METHODS: Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. RESULTS: We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years)...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28425398/prospective-indian-study-of-dili-with-confirmed-causality-using-the-roussel-uclaf-causality-assessment-method-rucam-a-report-of-excellence
#8
Rolf Teschke, Gaby Danan
No abstract text is available yet for this article.
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28417920/evaluation-of-the-potential-risk-of-drugs-to-induce-hepatotoxicity-in-human-relationships-between-hepatic-steatosis-observed-in-non-clinical-toxicity-study-and-hepatotoxicity-in-humans
#9
Keisuke Goda, Akio Kobayashi, Akemi Takahashi, Tadakazu Takahashi, Kosuke Saito, Keiko Maekawa, Yoshiro Saito, Shoichiro Sugai
In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28405790/csh-guidelines-for-the-diagnosis-and-treatment-of-drug-induced-liver-injury
#10
EDITORIAL
Yue-Cheng Yu, Yi-Min Mao, Cheng-Wei Chen, Jin-Jun Chen, Jun Chen, Wen-Ming Cong, Yang Ding, Zhong-Ping Duan, Qing-Chun Fu, Xiao-Yan Guo, Peng Hu, Xi-Qi Hu, Ji-Dong Jia, Rong-Tao Lai, Dong-Liang Li, Ying-Xia Liu, Lun-Gen Lu, Shi-Wu Ma, Xiong Ma, Yue-Min Nan, Hong Ren, Tao Shen, Hao Wang, Ji-Yao Wang, Tai-Ling Wang, Xiao-Jin Wang, Lai Wei, Qing Xie, Wen Xie, Chang-Qing Yang, Dong-Liang Yang, Yan-Yan Yu, Min-de Zeng, Li Zhang, Xin-Yan Zhao, Hui Zhuang
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells...
April 12, 2017: Hepatology International
https://www.readbyqxmd.com/read/28398242/drug-induced-liver-injury-can-biomarkers-assist-rucam-in-causality-assessment
#11
REVIEW
Rolf Teschke, Johannes Schulze, Axel Eickhoff, Gaby Danan
Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28391356/rat-precision-cut-liver-slices-predict-drug-induced-cholestatic-injury
#12
Viktoriia Starokozhko, Rick Greupink, Petra van de Broek, Nashwa Soliman, Samiksha Ghimire, Inge A M de Graaf, Geny M M Groothuis
Drug-induced cholestasis (DIC) is one of the leading manifestations of drug-induced liver injury (DILI). As the underlying mechanisms for DIC are not fully known and specific and predictive biomarkers and pre-clinical models are lacking, the occurrence of DIC is often only reported when the drug has been approved for registration. Therefore, appropriate models that predict the cholestatic potential of drug candidates and/or provide insight into the mechanism of DIC are highly needed. We investigated the application of rat precision-cut liver slices (PCLS) to predict DIC, using several biomarkers of cholestasis: hepatocyte viability, intracellular accumulation of total as well as individual bile acids and changes in the expression of genes known to play a role in cholestasis...
April 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28386997/the-transformation-in-biomarker-detection-and-management-of-drug-induced-liver-injury
#13
REVIEW
Rachel J Church, Paul B Watkins
Drug-induced liver injury (DILI) is a major concern for patients, care givers and the pharmaceutical industry. Interpretation of the serum biomarkers routinely used to detect and monitor DILI, which have not changed in almost 50 years, can be improved with recently proposed models employing quantitative systems pharmacology. In addition, several newer serum biomarkers are showing great promise. Studies in rodents indicate that the ratio of the caspase cleaved fragment of cytokeratin 18 to total K18 in serum (termed the "apoptotic index") estimates the relative proportions of apoptosis vs necrosis during drug-induced liver injury...
April 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28383671/drug-induced-liver-injury-in-oncology
#14
A D Ricart
Liver regeneration has been an adaptation of vertebrates through evolutionary events to protect them from environmental pressures (e.g. ingested toxins). Elevated serum levels of aminotransferases generally indicate liver injury, but do not necessarily reflect or predict hepatotoxicity. Drug-induced liver injury (DILI) is first classified as predictable or unpredictable (idiosyncratic). Predictable DILI is dose-related and occurs shortly after exposure (e.g. high dose alkylating agents). Unpredictable reactions result from a succession of unlikely events, a "multihit" process (e...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28379592/severe-hepatocytotoxicity-linked-to-denosumab
#15
S Malnick, Y Maor, E Melzer, N N Ziv-Sokolowskaia, M G Neuman
OBJECTIVE: Denosumab (Prolia, Amgen, Thousand Oaks, CA, USA) is a fully human antibody to the receptor activator of nuclear factor-KB ligand (RANKL). We present a case of submassive hepatic necrosis with evidence implicating cytokine induction resulting from an immune reaction to denosumab. CASE REPORT: A 72-year-old lady presented with elevated liver enzymes. One month previously, she received a s/c administration of 60 mg of denosumab. Viral hepatitis A, B and C and human herpes viruses 6-7 were negative as were routine autoimmune serology...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28379591/fatty-liver-and-drugs-the-two-sides-of-the-same-coin
#16
L Miele, A Liguori, G Marrone, M Biolato, C Araneo, F G Vaccaro, A Gasbarrini, A Grieco
Drug-induced liver injury (DILI) is a common and underestimated cause of liver disease. Several drugs and other xenobiotics can be the cause of different clinicopathologic patterns of liver disease. Steatosis and steatohepatitis are rare but well-documented types of DILI. Over the past decades commonly used drugs like amiodarone, tamoxifen, irinotecan, methotrexate, valproic acid and glucocorticoids have been recognized to be associated with steatosis. Even though the pathophysiological pathways are still only partially understood, inhibition of mitochondrial beta-oxidation, reduced very low-density lipoprotein secretion, insulin resistance induction and increased de novo synthesis or increased liver uptake of fatty acids are considered the main pathogenic mechanisms through which drugs can lead to hepatic steatosis...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28379588/a-focus-on-epidemiology-of-drug-induced-liver-injury-analysis-of-a-prospective-cohort
#17
A Licata, M G Minissale, V Calvaruso, A Craxì
OBJECTIVE: Drug-induced liver injury (DILI) is more often a challenge even for expert clinicians. Presently, there are limited data about the epidemiology, because the real incidence and prevalence of the disorder are underestimated, and further, sometimes the pharmacovigilance chain is unsuccessful as cases are largely underreported. We review available literature data and discuss our clinical experience regarding a prospective cohort of 185 patients with a diagnosis of DILI. MATERIALS AND METHODS: Significant papers were identified by literature search, and selected based on content including the epidemiology of DILI...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28379587/drug-induced-liver-injury-2017-the-diagnosis-is-not-easy-but-always-to-keep-in-mind
#18
G Marrone, F G Vaccaro, M Biolato, L Miele, A Liguori, C Araneo, F R Ponziani, N Mores, A Gasbarrini, A Grieco
A drug-induced liver injury (DILI) is defined as a liver injury caused by exposure to a drug or a non-infectious toxic agent with a variable degree of organ dysfunction. A better understanding of DILI epidemiology has been obtained in recent years with the institution of international registries in the United States and Europe. Despite the advances in the understanding and characterization of the phenomenon, DILI remains an exclusion diagnosis so, probability scores and the analysis of literature reports are useful tools in dealing with a suspected DILI...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28373338/prevalence-disparities-and-determinants-of-primary-cesarean-births-among-first-time-mothers-in-mexico
#19
Sylvia Guendelman, Alison Gemmill, Dorothy Thornton, Dilys Walker, Michael Harvey, Julia Walsh, Ricardo Perez-Cuevas
Mexico has the second-highest prevalence of cesarean deliveries in the Americas, behind Brazil. Having had a previous cesarean delivery is highly predictive of having subsequent cesarean deliveries, yet evidence on the drivers of primary (that is, first-time) cesarean deliveries is sparse. Using 2014 Mexican birth certificate data and performing population-level analyses of data on 600,124 first-time mothers giving birth after at least thirty-seven weeks of gestation, we examined the prevalence and determinants of primary cesarean deliveries...
April 1, 2017: Health Affairs
https://www.readbyqxmd.com/read/28369588/in-vitro-drug-induced-liver-injury-prediction-criteria-optimization-of-efflux-transporter-ic50-and-physicochemical-properties
#20
Robert W Yucha, Kan He, Qin Shi, Lining Cai, Yukie Nakashita, Cindy Q Xia, Mingxiang Liao
Drug-induced liver injury (DILI) is a severe drug adverse response, which cannot always be reliably predicted in preclinical or clinical studies. Lack of observation of DILI during preclinical and clinical drug development has led to DILI being a leading cause of drug withdrawal from the market. As DILI is potentially fatal, pharmaceutical companies have been developing in vitro tools to screen for potential liver injury. Screens for physicochemical properties, mitochondrial function, and transport protein inhibition have all been employed to varying degrees of success...
March 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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