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https://www.readbyqxmd.com/read/29165069/predicting-hepatotoxicity-of-drug-metabolites-via-an-ensemble-approach-based-on-support-cector-machine
#1
Yin Lu, Lili Liu, Dong Lu, Yudong Cai, Mingyue Zheng, Xiaomin Luo, Hualiang Jiang, Kaixian Chen
OBJECTIVE: Drug-induced liver injury (DILI) is a major cause of drug withdrawal. The chemical properties of the drug, especially drug metabolites, play key roles in DILI. Our goal is to construct a QSAR model to predict drug hepatotoxicity based on drug metabolites. MATERIALS AND METHODS: 64 hepatotoxic drug metabolites and 3,339 non-hepatotoxic drug metabolites were gathered from MDL Metabolite Database. Considering the imbalance of the dataset, we randomly split the negative samples and combined each portion with all the positive samples to construct individually balanced datasets for constructing independent classifiers...
November 20, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29146462/individual-serum-bile-acid-profiling-in-rats-aids-in-human-risk-assessment-of-drug-induced-liver-injury-due-to-bsep-inhibition
#2
Steven Cepa, David Potter, Lisa Wong, Leah Schutt, Jacqueline Tarrant, Jodie Pang, Xiaolin Zhang, Roxanne Andaya, Laurent Salphati, Yingqing Ran, Le An, Ryan Morgan, Jonathan Maher
Drug-induced liver injury (DILI) has been the most frequent cause of post-marketing drug withdrawals in the last 50years. The multifactorial nature of events that precede severe liver injury in human patients is difficult to model in rodents due to a variety of confounding or contributing factors that include disease state, concurrent medications, and translational species differences. In retrospective analyses, a consistent risk factor for DILI has been the inhibition of the Bile Salt Export Pump (BSEP). One compound known for potent BSEP inhibition and severe DILI is troglitazone...
November 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29145837/molecular-network-based-analysis-of-the-mechanism-of-liver-injury-induced-by-volatile-oils-from-artemisiae-argyi-folium
#3
Hongjie Liu, Sha Zhan, Yan Zhang, Yan Ma, Liang Chen, Lingxiu Chen, Hanqiu Dong, Min Ma, Zhe Zhang
BACKGROUND: Volatile oils from Artemisiae argyi folium (VOAAF) is reported with hepatotoxicity, but the underlying mechanism is still unclear. METHODS: In the present study this molecular mechanism was explored with the Ingenuity Pathway Analysis (IPA). The chemical components of the VOAAF were searched in the database, and their target proteins were all identified in the PubChem, while drug-induced liver injury (DILI) genes were searched in the PubMed gene databases...
November 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29132028/dna-methylation-and-genetic-variation-of-the-angiotensin-converting-enzyme-ace-in-depression
#4
Dilys Lam, Marie-Laure Ancelin, Karen Ritchie, Richard Saffery, Joanne Ryan
BACKGROUND: Depression is one of the most prevalent psychiatric disorders, and in older persons is associated with high levels of comorbidity and under-treatment. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) stress axis is consistently observed in the older population as well as depressed patients, with the angiotensin converting enzyme (ACE) a key regulator of the stress response. Epigenetic regulation of ACE may play an important role in HPA axis (dys)regulation. OBJECTIVE: To investigate ACE promoter methylation as a biomarker of late-life depression, and its association with genetic variation and cortisol secretion...
November 8, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29119413/identification-and-characterization-of-fenofibrate-induced-liver-injury
#5
Jawad Ahmad, Joseph A Odin, Paul H Hayashi, Naga Chalasani, Robert J Fontana, Huiman Barnhart, Elizabeth T Cirulli, David E Kleiner, Jay H Hoofnagle
BACKGROUND: Fenofibrate is a commonly used hypolipidemic associated with rare instances of hepatotoxicity, and routine liver biochemistry monitoring is recommended. AIMS: The aim of this study is to describe the presenting clinical features, liver histopathology, and outcomes of 7 cases of acute liver injury associated with fenofibrate. METHODS: All cases of definite, very likely, and probable drug-induced liver injury (DILI) attributed to fenofibrate enrolled in the DILI Network study between 2004 and 2015 were reviewed...
December 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29108197/-advances-in-clinical-differentiation-between-immunological-and-drug-induced-liver-injury
#6
Y Wang, Y N Li, J Zhang, B M Wang, L Zhou
The differentiation between autoimmune hepatitis (AIH) and drug-induced liver injury (DILI) is a difficult task in clinical practice. Some AIH patients had a medication history before disease onset, and some DILI patients may have positive serum antibody. In addition, these two groups of patients have similar clinical symptoms, serological examination results, and liver histopathology, which lead to the difficulties in differentiation. However, correct differential diagnosis is of great significance in making clinical treatment decisions and preventing liver cirrhosis...
September 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#7
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches (Olson et al. 2000) necessitates the development of alternative testing approaches. Body of evidence associates DILI with the induction of stress-response genes in the liver cells (Yuan and Kaplowitz 2013). Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29096561/in-silico-modeling-to-optimize-interpretation-of-liver-safety-biomarkers-in-clinical-trials
#8
Rachel J Church, Paul B Watkins
Current strategies to delineate the risk of serious drug-induced liver injury associated with drugs rely on assessment of serum biomarkers that have been utilized for many decades. In particular, serum alanine aminotransferase and total bilirubin levels are typically used to assess hepatic integrity and function, respectively. Parallel measurement of these biomarkers is utilized to identify patients with drug-induced hepatocellular jaundice ("Hy's Law" cases) which carries at least a 10% risk of death or liver transplant...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29090021/liver-injury-and-glatiramer-acetate-an-uncommon-association-case-report-and-literature-review
#9
REVIEW
Javier Almeida, Nuria Solà-Valls, Elisa Pose, Yolanda Blanco, María Sepúlveda, Sara Llufriu, Pere Gines, Albert Saiz
We report the case of a 65-year-old woman who presented with a 1-month history of progressive paraparesia associated with a thoracic lesion with irregular ring-like gadolinium enhancement. Biopsy of the lesion confirmed the demyelinating origin and brain magnetic resonance imaging showed additional lesions demonstrative of dissemination in space. Immunomodulatory therapy with glatiramer acetate (GA) was started after having a second relapse 2 months later. Shortly after initiation, the patient developed acute hepatitis...
November 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29056687/the-epidemiology-of-q-fever-in-england-and-wales-2000-2015
#10
Kate D Halsby, Hilary Kirkbride, Amanda L Walsh, Ebere Okereke, Timothy Brooks, Matthew Donati, Dilys Morgan
Between 2000 and 2015, 904 cases of acute Q fever were reported in England and Wales. The case dataset had a male to female ratio of 2.5:1, and a median age of 45 years. Two outbreaks were recognised during this time period, and the incidence of sporadic cases was highest across the southwest of England, and Wales. There are limitations in the surveillance system for Q fever, including possible geographical differences in reporting and limited epidemiological data collection. The surveillance system needs to be strengthened in order to improve the quality and completeness of the epidemiological dataset...
May 19, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/29048533/parallel-sequencing-lives-or-what-makes-large-sequencing-projects-successful
#11
Javier Quilez, Enrique Vidal, François Le Dily, François Serra, Yasmina Cuartero, Ralph Stadhouders, Thomas Graf, Marc A Marti-Renom, Miguel Beato, Guillaume Filion
T47D_rep2 and b1913e6c1_51720e9cf were 2 Hi-C samples. They were born and processed at the same time, yet their fates were very different. The life of b1913e6c1_51720e9cf was simple and fruitful, while that of T47D_rep2 was full of accidents and sorrow. At the heart of these differences lies the fact that b1913e6c1_51720e9cf was born under a lab culture of Documentation, Automation, Traceability, and Autonomy and compliance with the FAIR Principles. Their lives are a lesson for those who wish to embark on the journey of managing high-throughput sequencing data...
November 1, 2017: GigaScience
https://www.readbyqxmd.com/read/29040982/clinicopathological-study-of-autoimmune-hepatitis-cases-that-were-difficult-to-differentiate-from-drug-induced-liver-injury
#12
Akemi Tsutsui, Kenichi Harada, Koichi Tsuneyama, Tomonori Senoh, Takuya Nagano, Koichi Takaguchi, Midori Ando, Satoko Nakamura, Koichi Mizobuchi, Masatoshi Kudo
AIM: Acute-onset autoimmune hepatitis (AIH) histopathologically presents with features of acute hepatitis and lacks a specific diagnostic method. Also, AIH is often difficult to differentiate from drug-induced liver injury (DILI). We aimed to investigate the final clinical diagnosis of these cases, and compare the clinical, biochemical, and histological characteristics of AIH vs. DILI. METHODS: We examined the Digestive Disease Week Japan 2004 (DDW-J) scale scores, AIH scores, clinical data, and pathological findings in 20 patients in whom it was difficult to differentiate autoimmune liver disease from DILI...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29036176/association-and-clinical-utility-of-nat2-in-the-prediction-of-isoniazid-induced-liver-injury-in-singaporean-patients
#13
Sze Ling Chan, Angeline Poh Gek Chua, Folefac Aminkeng, Cynthia Bin Eng Chee, Shengnan Jin, Marie Loh, Suay Hong Gan, Yee Tang Wang, Liam R Brunham
BACKGROUND AND AIMS: Isoniazid (INH) is part of the first-line-therapy for tuberculosis (TB) but can cause drug-induced liver injury (DILI). Several candidate single nucleotide polymorphisms (SNPs) have been previously identified but the clinical utility of these SNPs in the prediction of INH-DILI remains uncertain. The aim of this study was to assess the association between selected candidate SNPs and the risk of INH-DILI and to assess the clinical validity of associated variants in a Singaporean population...
2017: PloS One
https://www.readbyqxmd.com/read/29035890/biocharacterization-of-heat-shock-protein-90-in-acetaminophen-treated-livers-without-conspicuous-drug-induced-liver-injury
#14
Ka Wu, Chao Guo, Min Su, Xinmou Wu, Rong Li
BACKGROUND/AIMS: Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during various stresses, such as wound healing and tissue remodeling. Recently, it is discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to clinical references of liver damage, this study was designed to assess the potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug induced liver injury (DILI)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29033486/topiramate-induced-acute-liver-injury-a-rare-adverse-effect
#15
Archish Khivsara, Jeffrey Pradeep Raj, Divya Hegde, Mangala Rao
Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures...
May 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29032512/il-33-signalling-in-liver-immune-cells-enhances-drug-induced-liver-injury-and-inflammation
#16
Maísa Mota Antunes, Alan Moreira Araújo, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Débora Moreira Alvarenga, Bruna Araújo David, Renata Monti Rocha, Maria Alice Freitas Lopes, Sarah Cozzer Marchesi, Brenda Naemi Nakagaki, Érika Carvalho, Pedro Elias Marques, Bernhard Ryffel, Valérie Quesniaux, Rodrigo Guabiraba Brito, José Carlos Alves Filho, Denise Carmona Cara, Rafael Machado Rezende, Gustavo Batista Menezes
OBJECTIVE AND DESIGN: The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). MATERIAL AND TREATMENTS: DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL)...
October 14, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29021781/cross-talk-between-adipose-tissue-and-placenta-in-obese-and-gestational-diabetes-mellitus-pregnancies-via-exosomes
#17
REVIEW
Nanthini Jayabalan, Soumyalekshmi Nair, Zarin Nuzhat, Gregory E Rice, Felipe A Zuñiga, Luis Sobrevia, Andrea Leiva, Carlos Sanhueza, Jaime Agustín Gutiérrez, Martha Lappas, Dilys Jane Freeman, Carlos Salomon
Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body's major energy reservoir...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28974930/induction-of-mkp-1-and-nuclear-translocation-of-nrf2-by-limonoids-from-khaya-grandifoliola-c-dc-protect-l-02-hepatocytes-against-acetaminophen-induced-hepatotoxicity
#18
Arnaud F Kouam, Fei Yuan, Frédéric N Njayou, Hongtao He, Roméo F Tsayem, Babayemi O Oladejo, Fuhang Song, Paul F Moundipa, George F Gao
Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports showing the hepatoprotective molecular mechanism of the plant are lacking. The aim of this study was therefore to identify compounds from the plant bearing hepatoprotective activity and the related molecular mechanism by assessing their effects against acetaminophen (APAP)-induced hepatotoxicity in normal human liver L-02 cells line...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28970715/norethisterone-related-drug-induced-liver-injury-a-series-of-3-cases
#19
Narendra S Choudhary, Vijay Bodh, Shraddha Chaudhari, Neeraj Saraf, Sanjiv Saigal
Drug induced liver injury (DILI) is uncommon and severe forms are associated with significant morbidity and mortality. Female sex hormones (estrogens and progestogens) related DILI generally occur with estrogen component. Progesterone component related DILI are infrequently reported. Norethisterone is commonly used drug in gynecologic practice to prevent excess per vaginal bleeding. We report 3 cases of Norethisterone related DILI manifesting as significant rise of transaminases. All of these patients took Norethisterone for prolonged periods and improved completely after withdrawal of drug...
September 2017: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/28968354/marked-decrease-in-urgent-listing-for-liver-transplantation-over-time-evolution-of-characteristics-and-outcomes-of-status-1-liver-transplantation
#20
Linda L Wong, Hung P Truong, Todd Seto, Lea Lacar, Willscott E Naugler
BACKGROUND: Approximately 5% of liver transplants annually are performed urgently with "status-1" designation. This study aims to determine if the demand, characteristics and outcome for status-1 liver transplantation has changed over time. METHODS: We utilized the Scientific Registry of Transplant Patients (2003-2015) to characterize 2352 adult patients who underwent 2408 status-1 liver transplants and compared them between Era1 (2003-6/2009) and Era2 (7/2009 -2015)...
September 29, 2017: Transplantation
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