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https://www.readbyqxmd.com/read/28521054/in-silico-prediction-of-drug-induced-liver-injury-based-on-adverse-drug-reaction-reports
#1
Xiang-Wei Zhu, Shao-Jing Li
Drug-induced liver injury (DILI) is a major cause of drug attrition. Currently existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for DILI. Furthermore, their practical applications were limited by lack of new hepatotoxicity data. In this study, we first collected and curated a novel set of 122 DILI-positive and 932 DILI-negative drugs from online adverse drug reports using proportional reporting ratios as the signal detection method. Second, three strategies (under-sampling the majority class, synthetic minority over-sampling technique, and adjusting decision threshold approach) were employed to develop predictive classification models to cope with the unbalanced dataset...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28511055/professional-midwifery-in-guatemala-a-qualitative-exploration-of-perceptions-attitudes-and-expectations-among-stakeholders
#2
Anna Summer, Sylvia Guendelman, Edgar Kestler, Dilys Walker
BACKGROUND: Despite recommendations that women give birth with a skilled birth attendant (SBA), 70% of births in Guatemala occur outside health facilities with informally trained traditional birth attendants (TBAs). To increase SBA in rural, indigenous communities, a professional midwifery school accredited by the government is scheduled to open in 2017. Drawing from Filby's model on barriers to the successful integration of professional midwifery into health systems, this paper aims to identify threats - and facilitators-toward professional midwifery's re-introduction in Guatemala...
May 4, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28508325/preliminary-results-of-a-novel-algorithmic-method-aiming-to-support-initial-causality-assessment-of-routine-pharmacovigilance-case-reports-for-medication-induced-liver-injury-the-pv-rucam
#3
Erik Scalfaro, Henk Johan Streefkerk, Michael Merz, Christoph Meier, David Lewis
INTRODUCTION: Data incompleteness in pharmacovigilance (PV) health records limits the use of current causality assessment methods for drug-induced liver injury (DILI). In addition to the inherent complexity of this adverse event, identifying cases of high causal probability is difficult. OBJECTIVE: The aim was to evaluate the performance of an improved, algorithmic and standardised method called the Pharmacovigilance-Roussel Uclaf Causality Assessment Method (PV-RUCAM), to support assessment of suspected DILI...
May 15, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28506365/drug-induced-liver-injury-the-hepatic-pathologist-s-approach
#4
REVIEW
David E Kleiner
The evaluation of liver biopsies in suspected drug-induced liver injury (DILI) can be complex. The biopsy may be approached systematically, by identification of histologic lesions and then identification of the overall pattern of injury. Potential DILI must be separated from concomitant non-DILI liver disease. The findings can be analyzed with respect to the various prescription and nonprescription medications and dietary supplements under suspicion to provide a complete interpretation of the findings. The pathologic findings, the histologic differential diagnosis, and expert interpretation are part of a complete biopsy assessment and provide information that is of greatest value in patient management...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28494844/west-nile-virus-surveillance-in-europe-moving-towards-an-integrated-animal-human-vector-approach
#5
Céline M Gossner, Laurence Marrama, Marianne Carson, Franz Allerberger, Paolo Calistri, Dimitrios Dilaveris, Sylvie Lecollinet, Dilys Morgan, Norbert Nowotny, Marie-Claire Paty, Danai Pervanidou, Caterina Rizzo, Helen Roberts, Friedrich Schmoll, Wim Van Bortel, Andrea Gervelmeyer
This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures...
May 4, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28490012/is-the-prophylactic-use-of-hepatoprotectants-necessary-in-anti-tuberculosis-treatment
#6
Li Xu, Fei Zhang, Chen Xu, Kai-Ge Liu, Wei Wu, Ying-Xuan Tian
BACKGROUND: Liver injury is one of the serious side effects of anti-tuberculosis (TB) drugs. It is controversial whether hepatoprotectant prophylaxis is efficient and safe in anti-TB treatment, so we aimed to assess the efficacy and safety of hepatoprotectant prophylaxis in patients who had received anti-TB treatment. METHODS: PubMed, the Cochrane library, Embase, Ovid, Springer link, Wiley, Elsevier, Web of Science, and the Karger Online Journal were systematically searched prior to April 2016 for articles related to hepatoprotectant prophylaxis in the treatment of TB...
May 11, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28486401/drug-induced-liver-injury-cascade-of-events-leading-to-cell-death-apoptosis-or-necrosis
#7
REVIEW
Andrea Iorga, Lily Dara, Neil Kaplowitz
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR)...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473992/hepatotoxicity-of-antimycotics-used-for-invasive-fungal-infections-in-vitro-results
#8
Sandra Doß, Heike Potschka, Fanny Doß, Steffen Mitzner, Martin Sauer
Purpose. Drug-induced liver injury (DILI) is the most common cause of liver injury and a serious clinical problem; antimycotics are involved in approximately 3% of all DILI cases. The hepatotoxicity of many drugs, including the antimycotics, is poorly screened in human models. Methods. In a standardized assay the cytotoxicity on hepatocytes of different concentrations (Cmax, 5x Cmax, and 10x Cmax) of the antimycotics used for systemic infections was tested. Anidulafungin (ANI), liposomal amphotericerin B (L-AmB), caspofungin (CASPO), fluconazole (FLUCO), and voriconazole (VORI) were incubated with HepG2/C3A cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28448553/a-computational-toxicogenomics-approach-identifies-a-list-of-highly-hepatotoxic-compounds-from-a-large-microarray-database
#9
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
#10
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
#11
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
#12
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
#13
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-DILI-concern and 55 of No-DILI-concern)...
May 4, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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