3,971 results match your criteria Toxicity Acetaminophen


Core Entrustable Professional Activities in Clinical Pharmacology for Entering Residency: Common Problem Drugs and How to Prescribe Them.

J Clin Pharmacol 2019 Feb 15. Epub 2019 Feb 15.

The American College of Clinical Pharmacology, Ashburn, VA, USA.

Although the medical profession strives for safe prescribing, most medications are unique challenges even when prescribed by an experienced provider. In this article we discuss the pitfalls associated with drug interactions between commonly used antibiotics and anticoagulants, the complexities associated with the administration of novel reversible anticoagulants, the often-overlooked severe adverse drug reactions from commonly used classes of medications such as corticosteroids, the nuances of managing an acetaminophen overdose, and uncommon yet serious adverse events associated with the use of contraceptive hormone drugs. Read More

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http://dx.doi.org/10.1002/jcph.1389DOI Listing
February 2019

Effects of acetaminophen in oxidative stress and neurotoxicity biomarkers of the gastropod Phorcus lineatus.

Environ Sci Pollut Res Int 2019 Feb 8. Epub 2019 Feb 8.

Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.

The growing use of pharmaceutical drugs has become a major environmental issue considering that these substances (or their metabolites) end up inevitably in sewage waters after excretion. In the wild, these chemicals may affect non-target organisms, and their potential toxicity is not sufficiently studied, a reality that is particularly true for marine organisms. Acetaminophen (also known as paracetamol) is known to be toxic in high dosages, namely, by triggering oxidative effects. Read More

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http://dx.doi.org/10.1007/s11356-019-04349-1DOI Listing
February 2019
1 Read

Acetaminophen is Undetectable in Plasma From More Than Half of Patients Believed to Have Acute Liver Failure Due to Overdose.

Clin Gastroenterol Hepatol 2019 Feb 4. Epub 2019 Feb 4.

Division of Digestive and Liver Diseases, The University of Texas Southwestern Medical Center, Dallas, TX, United States; Grant Support-This study was supported by a grant from the National Institute for Diabetes and Digestive and Kidney Diseases (U01-DK-58369 ) to the University of Texas Southwestern Medical Center at Dallas.

Background Aims: Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity. Read More

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http://dx.doi.org/10.1016/j.cgh.2019.01.040DOI Listing
February 2019
1 Read

Comparison of RNA-Seq and Microarray Gene Expression Platforms for the Toxicogenomic Evaluation of Liver From Short-Term Rat Toxicity Studies.

Front Genet 2018 22;9:636. Epub 2019 Jan 22.

Investigative Toxicology and Pathology, Global Preclinical Safety, AbbVie, North Chicago, IL, United States.

Gene expression profiling is a useful tool to predict and interrogate mechanisms of toxicity. RNA-Seq technology has emerged as an attractive alternative to traditional microarray platforms for conducting transcriptional profiling. The objective of this work was to compare both transcriptomic platforms to determine whether RNA-Seq offered significant advantages over microarrays for toxicogenomic studies. Read More

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http://dx.doi.org/10.3389/fgene.2018.00636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349826PMC
January 2019
3 Reads

Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen.

Sci Rep 2019 Feb 4;9(1):1396. Epub 2019 Feb 4.

Division of Experimental and Translational Genetics, University of Missouri Kansas City School of Medicine, Kansas City, USA.

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. Read More

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http://dx.doi.org/10.1038/s41598-018-37940-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362041PMC
February 2019
1 Read

Mannan-binding lectin attenuates acetaminophen-induced hepatotoxicity by regulating CYP2E1 expression via ROS-dependent JNK/SP1 pathway.

Eur J Immunol 2019 Feb 1. Epub 2019 Feb 1.

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Mannan-binding lectin (MBL) acts as a soluble pattern recognition molecule in the innate immune system, which is primarily produced by the liver. MBL deficiency occurs with high frequency in the population and is reported to be associated with susceptibility to several liver diseases. In the present study, we investigated the pathophysiological role of MBL in acetaminophen (APAP)-induced hepatotoxicity. Read More

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http://dx.doi.org/10.1002/eji.201847830DOI Listing
February 2019
1 Read

Can acetaminophen/dimethyl sulfoxide formulation prevent accidental and intentional acetaminophen hepatotoxicity?

Drug Dev Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.

An overdose of acetaminophen (APAP) causes liver injury in experimental animals and humans. The activation step (formation of reactive metabolite, N-acetyl-p-benzoquinone imine by cytochrome P450 system) and the consequent downstream pathway of oxidative stress, nitrosative stress, and inflammation play an important role in APAP-induced hepatotoxicity. Formulation of APAP with an inhibitor of the activation step would be ideal to prevent accidental and intentional APAP toxicity. Read More

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http://dx.doi.org/10.1002/ddr.21520DOI Listing
January 2019
2 Reads
0.734 Impact Factor

Evaluation of pharmaceutical toxic effects of non-standard endpoints on the macrophyte species Lemna minor and Lemna gibba.

Sci Total Environ 2019 Mar 2;657:926-937. Epub 2018 Dec 2.

Department of Biology, Aveiro University, Campus de Santiago, 3810-193 Aveiro, Portugal; Centre for Environmental and Marine Studies (CESAM), Campus de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

In the last years the environmental presence of pharmaceuticals has gained increasing attention. Research data show that these compounds can cause toxicological effects in different species of fish, mollusks and macroinvertebrates. However, the literature is scarce in terms of ecotoxicity data especially focusing on plants as test organisms. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.12.002DOI Listing

Transformation of endocrine disrupting chemicals, pharmaceutical and personal care products during drinking water disinfection.

Sci Total Environ 2019 Mar 11;657:1480-1490. Epub 2018 Dec 11.

Australian Rivers Institute, School of Environment and Science, Griffith University, Southport, Qld 4222, Australia; The University of Queensland, Queensland Alliance for Environmental Health Sciences (QAEHS), Woolloongabba, Qld 4102, Australia; UFZ - Helmholtz Centre for Environmental Research, Cell Toxicology, 04318 Leipzig, Germany.

Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds (EDCs) are frequently detected in drinking water sources. This raises concerns about the formation of potentially more toxic transformation products (TPs) after drinking water disinfection. This study applied a combination of computational and experimental methods to investigate the biological activity of eight EDCs and PPCPs commonly detected in source waters (acetaminophen, bisphenol A, carbamazepine, estrone, 17α-ethinylestradiol, gemfibrozil, naproxen and triclosan) before and after disinfection. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.12.106DOI Listing
March 2019
4.099 Impact Factor

Green synthesized selenium nanoparticles using Spermacoce hispida as carrier of s-allyl glutathione: to accomplish hepatoprotective and nephroprotective activity against acetaminophen toxicity.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):56-63

a Department of Biochemistry, Molecular Therapeutics Laboratory , Periyar University , Salem , India.

s-allyl glutathione (SAG) an analogue of glutathione is explored for its antioxidative and liver protection property in recent years. Selenium nanoparticles (Sh-SeNPs) were synthesized using medicinal plant Spermacoce hispida and conjugated with SAG (SAG-Sh-SeNPs). SAG-Sh-SeNPs and Sh-SeNPs were characterized using by Fourier transform infrared spectroscopy, Transmission electron microscopy, Energy dispersive X-ray analysis, X-ray diffraction analysis and zeta potential analysis. Read More

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http://dx.doi.org/10.1080/21691401.2018.1543192DOI Listing
December 2019
1 Read

The inhibitor of glycerol 3-phosphate acyltransferase FSG67 blunts liver regeneration after acetaminophen overdose by altering GSK3β and Wnt/β-catenin signaling.

Food Chem Toxicol 2019 Jan 14;125:279-288. Epub 2019 Jan 14.

Dept. of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Dept. of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address:

Repair mechanisms after acetaminophen (APAP) hepatotoxicity are poorly understood. We recently discovered that phosphatidic acid (PA) increases in mice and humans after APAP overdose, and is critical for liver regeneration. Here, we hypothesized that PA inhibits glycogen synthase kinase-3β (GSK3β), a component of canonical Wnt/β-catenin signaling, after APAP overdose. Read More

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http://dx.doi.org/10.1016/j.fct.2019.01.014DOI Listing
January 2019
2 Reads

"Safety issues of pharmacological acute pain treatment in children".

Clin Pharmacol Ther 2019 Jan 16. Epub 2019 Jan 16.

Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive care and Emergency medicine, Geneva University Hospitals, Switzerland.

Acute nociceptive pain management in children is a major public health concern. Effective and safe pain treatment is essential, but safety data cannot be simply extrapolated from adults to children due to pharmacokinetic and pharmacodynamic specificities. In addition, the frequent absence of child-specific data, the difficulty to assess drug tolerability and the infants' inability to communicate properly and voluntarily report adverse drug reactions, make children more vulnerable to safety issues. Read More

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http://dx.doi.org/10.1002/cpt.1358DOI Listing
January 2019
5 Reads

Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats.

Int Urol Nephrol 2019 Jan 2. Epub 2019 Jan 2.

Department of Biology, Faculty of Science and Literature, Kutahya Dumlupinar University, Kutahya, Turkey.

Introduction And Aim: Hydrogen sulfide (HS) is an endogenously produced gas-structure mediator. It is proposed to have antioxidant, anti-inflammatory and antiapoptotic effects. Acetaminophen (N-acetyl-P-aminophenol; APAP) is an antipyretic and analgesic medication known as paracetamol. Read More

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http://dx.doi.org/10.1007/s11255-018-2053-0DOI Listing
January 2019
2 Reads

Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling.

Molecules 2018 Dec 29;24(1). Epub 2018 Dec 29.

Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Acetaminophen (APAP) overdose-induced acute liver damage is mostly due to overwhelmingly increased oxidative stress. Nuclear factor-erythroid 2-related factor2 (Nrf2) plays an important role in alleviating APAP hepatic toxicity. Shikonin (SHK) enhances Nrf2 in multiple lines of normal cells. Read More

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http://dx.doi.org/10.3390/molecules24010110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337349PMC
December 2018
1 Read
2.416 Impact Factor

Increased susceptibility to oxidative stress-induced toxicological evaluation by genetically modified nrf2a-deficient zebrafish.

J Pharmacol Toxicol Methods 2018 Dec 27;96:34-45. Epub 2018 Dec 27.

Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan; Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan; Mie University Medical Zebrafish Research Center, Mie, Japan; Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Mie, Japan.

Introduction: Oxidative stress plays an important role in drug-induced toxicity. Oxidative stress-mediated toxicities can be detected using conventional animal models but their sensitivity is insufficient, and novel models to improve susceptibility to oxidative stress have been researched. In recent years, gene targeting methods in zebrafish have been developed, making it possible to generate homozygous null mutants. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10568719173055
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http://dx.doi.org/10.1016/j.vascn.2018.12.006DOI Listing
December 2018
6 Reads

Victims of chemical terrorism, a family of four who were exposed to sulfur mustard.

Toxicol Lett 2019 Mar 17;303:9-15. Epub 2018 Dec 17.

University of Health Sciences, Dept. of Medical CBRN Defense, 06010, Etlik, Ankara, Turkey.

Sulfur mustard (SM) was responsible for more than 80% of all documented chemical casualties during the Great War. Recent literature on clinic picture of SM exposure remained so limited with the sporadic cases who were accidentally exposed to SM especially either in Western Europe or China. We reported a Syrian family of four who became victims of chemical terrorism due to SM exposure and we described the detailed clinical course of the family including the medical history, initial symptomatology, clinical examination, hematological data, and initial treatment in the first 48 hours after exposure at Kilis State Hospital, Turkey. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.12.006DOI Listing
March 2019
2 Reads

Small Heterodimer Partner Regulates Circadian Cytochromes p450 and Drug-Induced Hepatotoxicity.

Theranostics 2018 22;8(19):5246-5258. Epub 2018 Oct 22.

Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, China.

The role of small heterodimer partner (SHP) in regulation of xenobiotic detoxification remains elusive. Here, we uncover a critical role for SHP in circadian regulation of cytochromes P450 (CYPs) and drug-induced hepatotoxicity. The mRNA and protein levels of CYPs in the livers of wild-type and SHP mice were measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. Read More

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http://www.thno.org/v08p5246.htm
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http://dx.doi.org/10.7150/thno.28676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276094PMC
October 2018
10 Reads

Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism.

Arch Toxicol 2019 Feb 14;93(2):341-353. Epub 2018 Dec 14.

Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.

Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and mitochondrial dysfunction. Hepatoma cell lines typically lack the CYP450 activity to generate the reactive metabolite of APAP observed in vivo, but are still subject to APAP cytotoxicity. In this study, we employed metabolic profiling and isotope labelling approaches to investigate the metabolic impact of acute exposure to cytotoxic doses of APAP on the widely used HepG2 cell model. Read More

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http://dx.doi.org/10.1007/s00204-018-2371-0DOI Listing
February 2019
5 Reads

Dimethyl fumarate ameliorates acetaminophen-induced hepatic injury in mice dependent of Nrf-2/HO-1 pathway.

Life Sci 2019 Jan 11;217:251-260. Epub 2018 Dec 11.

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address:

Drug-induced liver toxicity is the most frequent cause of acute liver failure worldwide. Hepatotoxicity caused by acetaminophen (ACT) overdose is mediated by its metabolic product promoting oxidative stress and activation of inflammatory mediators. Nuclear factor erythroid-related factor-2 (Nrf-2) induces the release of cytoprotective enzymes in response to electrophilic or oxidative stress and is considered a promising therapeutic target. Read More

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http://dx.doi.org/10.1016/j.lfs.2018.12.013DOI Listing
January 2019
1 Read

The diagnostic role of miR-122 in drug-induced liver injury: A systematic review and meta-analysis.

Medicine (Baltimore) 2018 Dec;97(49):e13478

School of Graduates, Tianjin Medical University.

Background: Drug-induced liver injury (DILI) is a potentially severe adverse drug reaction especially in susceptible patients. But there are no sensitive or specific parameters to detecting DILI. The specific expression of miR-122 in the liver has been a hotspot in the evaluation of hepatic toxicity due to its high stability and sensitivity. Read More

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http://dx.doi.org/10.1097/MD.0000000000013478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310488PMC
December 2018

Pharmacotherapy for patent ductus arteriosus closure.

Authors:
John M Ferguson

Congenit Heart Dis 2018 Dec 11. Epub 2018 Dec 11.

Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.

Even though up to 60% of premature infants less than 28 weeks gestation develop persistent patent ductus arteriosus (PDA), there remains controversy regarding if, when, and how to close the PDA. Failure to close the PDA has been associated with significant morbidity but no cause-and-effect has been proven for short-term or long-term outcomes in modern times. Surgical closure has the advantage of eliminating the PDA, but short-term complications and long-term adverse outcomes are worrisome. Read More

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http://dx.doi.org/10.1111/chd.12715DOI Listing
December 2018
4 Reads

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://dx.doi.org/10.18053/jctres.04.201801.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261533PMC
May 2018
4 Reads

Acetaminophen absorption and metabolism in an intestine/liver microphysiological system.

Chem Biol Interact 2019 Feb 26;299:59-76. Epub 2018 Nov 26.

Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Zip Code 13083-970, Campinas, São Paulo, Brazil.

This study describes the characterization of pharmacokinetic (PK) properties of acetaminophen (APAP) in the Two-Organ-Chip platform (2-OC), a two-chamber device able to cultivate 3D tissues under flow. The APAP intestinal absorption and hepatic metabolism were emulated by human intestine and liver equivalents respectively. The intestinal barrier was produced using Caco-2 and HT-29 cells. Read More

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http://dx.doi.org/10.1016/j.cbi.2018.11.010DOI Listing
February 2019
8 Reads

Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury.

Int J Mol Sci 2018 Nov 28;19(12). Epub 2018 Nov 28.

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, PO Box # 17666, United Arab Emirates University, Al Ain 17666, UAE.

Acetaminophen (APAP), which is also known as paracetamol or -acetyl--aminophenol is a safe and potent drug for fever, pain and inflammation when used at its normal therapeutic doses. It is available as over-the-counter drug and used by all the age groups. The overdose results in acute liver failure that often requires liver transplantation. Read More

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http://dx.doi.org/10.3390/ijms19123776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321362PMC
November 2018
1 Read
2.862 Impact Factor

Detection of Cutting Agents in Drug-Positive Seized Exhibits within the United States.

J Forensic Sci 2018 Nov 28. Epub 2018 Nov 28.

The Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, PA, 19090.

The following report summarizes a study performed on seized drug exhibits collected in two U.S. states to evaluate the presence and identification of cutting agents. Read More

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http://doi.wiley.com/10.1111/1556-4029.13968
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http://dx.doi.org/10.1111/1556-4029.13968DOI Listing
November 2018
8 Reads

DAMPs and sterile inflammation in drug hepatotoxicity.

Hepatol Int 2019 Jan 24;13(1):42-50. Epub 2018 Nov 24.

Department of Emergencies and Critical Care, Oslo University Hospital, Nydalen, PO Box 4950, 0424, Oslo, Norway.

Drug hepatotoxicity is the leading cause of acute liver failure (ALF) in the developed countries. The early diagnosis and treatment are still problematic, and one important reason is the lack of reliable mechanistic biomarkers and therapeutic targets; therefore, searching for new biomarkers and therapeutic targets is urgent. Drug hepatotoxicity induces severe liver cells damage and death. Read More

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http://dx.doi.org/10.1007/s12072-018-9911-9DOI Listing
January 2019
1 Read

Prevention of acetaminophen-induced liver injury by alginate.

Toxicol Appl Pharmacol 2019 Jan 20;363:72-78. Epub 2018 Nov 20.

Liver Unit, Hebrew University- Hadassah Medical Center, Jerusalem, Israel.

Introduction: Acetaminophen (APAP) intoxication is a major cause of acute liver failure. Alginate, an anionic polysaccharide, was previously shown as a macroporous scaffold, to reduce liver inflammation and sustain hepatic synthetic function, when implanted on liver remnant after extended partial hepatectomy. In the recent study we wanted to examine in a model of APAP intoxication the potential of a specially formulated alginate solution to prevent APAP toxicity. Read More

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http://dx.doi.org/10.1016/j.taap.2018.11.008DOI Listing
January 2019
17 Reads
3.705 Impact Factor

Safety and Efficacy of Bupivacaine HCl Collagen-Matrix Implant (INL-001) in Open Inguinal Hernia Repair: Results from Two Randomized Controlled Trials.

Adv Ther 2019 Jan 22;36(1):200-216. Epub 2018 Nov 22.

Innocoll, Newtown Square, PA, USA.

Introduction: Surgical site infiltration with bupivacaine results in short-lived analgesia. The MATRIX-1 and MATRIX-2 studies examined the efficacy and safety of the bioresorbable bupivacaine HCl collagen-matrix implant (INL-001) for postsurgical pain after open inguinal hernia repair. INL-001, designed to provide early and extended delivery of bupivacaine, provides prolonged duration of perioperative analgesia. Read More

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http://dx.doi.org/10.1007/s12325-018-0836-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318344PMC
January 2019
12 Reads

Improved protective effects of American ginseng berry against acetaminophen-induced liver toxicity through TNF-α-mediated caspase-3/-8/-9 signaling pathways.

Phytomedicine 2018 Dec 2;51:128-138. Epub 2018 Oct 2.

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; National & Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China. Electronic address:

Background: Similar to the leaves of P. Quinquefolius, American ginseng berry (AGB) is another important part of P. Quinquefolius with alternative therapeutic potential. Read More

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http://dx.doi.org/10.1016/j.phymed.2018.09.234DOI Listing
December 2018
2 Reads
3.126 Impact Factor

Chemical profile, liver protective effects and analgesic properties of a Solanum paniculatum leaf extract.

Biomed Pharmacother 2019 Feb 20;110:129-138. Epub 2018 Nov 20.

Institute for Research on Natural Products, Federal University of Rio de Janeiro, RJ, 21941-902, Brazil.

Background/aim: Solanum paniculatum L. (Solanaceae) is a plant native to South America where it is used in traditional medicine for different therapeutic indications. This study evaluated the chemical composition and the hepatoprotective and analgesic activities of S. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.11.036DOI Listing
February 2019
10 Reads

Cytotoxicity of new psychoactive substances and other drugs of abuse studied in human HepG2 cells using an adopted high content screening assay.

Toxicol Lett 2019 Feb 19;301:79-89. Epub 2018 Nov 19.

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany. Electronic address:

New psychoactive substances (NPS) are still an emerging issue in clinical and forensic toxicology. Information about their cytotoxic potential is limited or even unavailable before distribution and thus their intake can be of high risk for consumers. The aim of the presented study was to develop a strategy to identify cytotoxic potential of NPS based on a high content screening assay (HCSA) using HepG2 cell line and four fluorescent dyes, namely Hoechst33342, TMRM, CAL-520, and TOTO-3. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.11.007DOI Listing
February 2019
9 Reads

Organic semiconducting nanoprobe with redox-activatable NIR-II fluorescence for in vivo real-time monitoring of drug toxicity.

Chem Commun (Camb) 2018 Dec;55(1):27-30

Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications (NUPT), Nanjing 210023, China.

An activatable organic semiconducting nanoprobe that specifically turns on its second near-infrared window fluorescence upon being exposed to nitric oxide stimuli was developed for in vivo, in situ, real-time and high-spatial-resolution mapping of drug-induced hepatotoxicity. Read More

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http://dx.doi.org/10.1039/c8cc08413kDOI Listing
December 2018
9 Reads
6.834 Impact Factor

Role of extracellular vesicles in release of protein adducts after acetaminophen-induced liver injury in mice and humans.

Toxicol Lett 2019 Feb 15;301:125-132. Epub 2018 Nov 15.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address:

Formation of acetaminophen (APAP) protein adducts are a critical feature of APAP hepatotoxicity, and circulating protein adducts have recently been utilized in bioassays for identification of APAP overdose in humans. Despite their clinical significance, mechanisms of adduct release into the circulation are not well understood. Extracellular vesicles (EVs) are discrete membrane bound vesicles, which package cellular cargo and function in extracellular transport. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03784274183200
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http://dx.doi.org/10.1016/j.toxlet.2018.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338225PMC
February 2019
17 Reads

Isoform-specific therapeutic control of sulfonation in humans.

Biochem Pharmacol 2019 Jan 10;159:25-31. Epub 2018 Nov 10.

Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461-1926, United States. Electronic address:

The activities of hundreds, perhaps thousands, of metabolites are regulated by human cytosolic sulfotransferases (SULTs) - a 13-member family of disease relevant enzymes that catalyze transfer of the sulfuryl moiety (-SO) from PAPS (3'-phosphoadenosine 5'-phosphosulfonate) to the hydroxyls and amines of acceptors. SULTs harbor two independent allosteric sites, one of which, the focus of this work, binds non-steroidal anti-inflammatory drugs (NSAIDs). The structure of the first NSAID-binding site - that of SULT1A1 - was elucidated recently and homology modeling suggest that variants of the site are present in all SULT isoforms. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952183047
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http://dx.doi.org/10.1016/j.bcp.2018.11.010DOI Listing
January 2019
32 Reads

Acute liver failure: A review for emergency physicians.

Am J Emerg Med 2019 Feb 22;37(2):329-337. Epub 2018 Oct 22.

Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States. Electronic address:

Introduction: Acute liver failure (ALF) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization.

Objective: This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of ALF.

Discussion: While ALF remains a rare clinical presentation, surveillance data suggest an overall incidence between 1 and 6 cases per million people every year, accounting for 6% of liver-related deaths and 7% of orthotopic liver transplants (OLT) in the U. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07356757183084
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http://dx.doi.org/10.1016/j.ajem.2018.10.032DOI Listing
February 2019
14 Reads

Protective effects and possible molecular mechanism of Thunb. extract on acetaminophen-induced hepatotoxicity.

Pharmazie 2018 11;73(11):666-670

Thunb. is a traditional hepatoprotective Chinese medicine, and in research, much effort has been focused on the protection against alcoholic liver injury. In this study, the protective effects of a fruit ethanol extract of (FE) against APAP-induced acute hepatotoxicity in mice and the possibly involved molecular mechanisms were investigated. Read More

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http://dx.doi.org/10.1691/ph.2018.8650DOI Listing
November 2018
8 Reads

Effects of food restriction on the expression of genes related to acetaminophen-induced liver toxicity in rats.

J Toxicol Pathol 2018 Oct 16;31(4):267-274. Epub 2018 Jun 16.

Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.

It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the expression of drug-metabolizing enzyme genes and total glutathione content in the liver, which are related to toxicity induced by overdose of the hepatotoxic drug acetaminophen (-acetyl--aminophenol; APAP), were examined in rats reared under different feeding conditions: feeding, 16-h fasting, and food restriction (fed 70% of the average intake of feeding for 10 days) conditions. Read More

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http://dx.doi.org/10.1293/tox.2018-0009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206280PMC
October 2018
3 Reads

Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue.

Environ Sci Pollut Res Int 2019 Jan 3;26(1):240-249. Epub 2018 Nov 3.

Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.

Acetaminophen, APAP, is a common over-the-counter drug with antipyretic-analgesic action. When APAP is used in large doses, it causes hepatotoxicity and nephrotoxicity but safe at therapeutic doses. Cinnamon (Cinnamomum zeylanicum) is extensively used in folk medicine due to its high content of natural antioxidants. Read More

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http://link.springer.com/10.1007/s11356-018-3553-2
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http://dx.doi.org/10.1007/s11356-018-3553-2DOI Listing
January 2019
9 Reads
2.830 Impact Factor

Alogliptin abates memory injuries of hepatic encephalopathy induced by acute paracetamol intoxication via switching-off autophagy-related apoptosis.

Life Sci 2018 Dec 1;215:11-21. Epub 2018 Nov 1.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address:

Aims: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome. Paracetamol (APAP) causes, in high doses, a hepatic injury. Alogliptin (ALO), with its 100% oral bioavailability, may be able to reverse the acute hepatic injury and memory impairments. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00243205183070
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http://dx.doi.org/10.1016/j.lfs.2018.10.069DOI Listing
December 2018
8 Reads

Pharmaceuticals as chemical markers of wastewater contamination in the vulnerable area of the Ebro Delta (Spain).

Sci Total Environ 2019 Feb 22;652:952-963. Epub 2018 Oct 22.

Catalan Institute for Water Research (ICRA), C/Emili Grahit 101, 17003 Girona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Company 23, 08010 Barcelona, Spain.

This study evaluated the occurrence and distribution of 81 pharmaceutically active compounds (PhACs) in the vulnerable area of the Ebro Delta region (Catalonia, Spain), to assess the environmental impact of wastewater treatment plants discharge to coastal environments. The occurrence of PhACs was followed along the wastewater-recipient water-sediment chain until they reach estuaries and the Mediterranean Sea. Water and sediment samples were collected in an integrated way at different sampling points covering three different seasons in reaches of the Ebro River located upstream and downstream from wastewater treatment plants (WWTPs), surrounding channels, estuaries, and the associated receiving seawater. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00489697183418
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http://dx.doi.org/10.1016/j.scitotenv.2018.10.290DOI Listing
February 2019
4 Reads

Light to moderate drinking and therapeutic doses of acetaminophen: An assessment of risks for renal dysfunction.

Prev Med Rep 2018 Dec 24;12:253-258. Epub 2018 Oct 24.

Department of Epidemiology and Biostatistics, School of Community and Rural Health, University of Texas Health Science Center, 11937 US Hwy 271, Tyler, TX 75708, United States of America.

This study investigated the potential effect of therapeutic doses of acetaminophen (APAP) in combination with light-moderate amounts of alcohol on kidney functions controlling for factors such as hypertension, diabetes and obesity that may predispose the kidney to APAP and/or alcohol toxicity. Secondary analysis of the 2003-2004 National Health and Nutrition Examination Survey data was performed using SAS 9.4. Read More

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https://www.sciencedirect.com/science/article/pii/S221133551
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https://www.sciencedirect.com/journal/preventive-medicine-re
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https://linkinghub.elsevier.com/retrieve/pii/S22113355183025
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http://dx.doi.org/10.1016/j.pmedr.2018.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205325PMC
December 2018
10 Reads

A spatial-temporal model for zonal hepatotoxicity of acetaminophen.

Drug Metab Pharmacokinet 2019 Feb 8;34(1):71-77. Epub 2018 Oct 8.

Auckland Bioengineering Institute, The University of Auckland, New Zealand. Electronic address:

The metabolism zonation in liver lobules is well known yet its incorporation into the mathematical models of acetaminophen (APAP) metabolism is still primitive - only the oxidation pathway via reaction with the cytochrome P450 (CYP450) has been considered, yet the zonal heterogeneity exhibits in all three pathways including sulphation, glucuronidation and oxidation. In this paper we present a novel computational method where an intracellular APAP metabolism model is integrated into a Finite Element Model (FEM) of sinusoids, and the zonal heterogeneity in three metabolism pathways are all incorporated. We demonstrate that the degradation of APAP, detoxification via glutathione (GSH) and the formation of hepatotoxicity, are all affected profoundly by the zonal difference. Read More

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http://dx.doi.org/10.1016/j.dmpk.2018.09.266DOI Listing
February 2019
2 Reads

Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice.

Sci Rep 2018 Oct 30;8(1):16070. Epub 2018 Oct 30.

Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.

Exosomes are small extracellular membrane vesicles released from endosomes of various cells and could be found in most body fluids. The main functions of exosomes have been recognized as important mediators of intercellular communication and as potential biomarkers of various disease states. This study investigated whether exogenous exosomes from mice with acetaminophen (APAP)-induced liver injury can damage the recipient hepatic cells or promote hepatotoxicity in mice. Read More

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http://www.nature.com/articles/s41598-018-34309-7
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http://dx.doi.org/10.1038/s41598-018-34309-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207703PMC
October 2018
26 Reads

Environmentally-relevant mixture of pharmaceutical drugs stimulates sex-steroid hormone production and modulates the expression of candidate genes in the ovary of juvenile female rainbow trout.

Aquat Toxicol 2018 Dec 13;205:89-99. Epub 2018 Oct 13.

University of Namur, Institute of Life, Earth & Environment, Research Unit in Environmental and Evolutionary Biology, 61 rue de Bruxelles, B-5000 Namur, Belgium. Electronic address:

Because of their intrinsic biological activity and ubiquitous environmental occurrence, human pharmaceutical compounds have received increasing attention from health and environmental agencies. In the present study, all-female juvenile rainbow trout (Oncorhynchus mykiss) were exposed to environmentally-realistic concentrations of a mixture of nonsteroidal pharmaceuticals for 42 days, and the effects on plasma levels of sex-steroids and the expression of genes encoding key proteins involved in ovarian development were assessed. Paracetamol, carbamazepine, diclofenac, irbesartan and naproxen were selected, as these have been detected in the Meuse River in Belgium. Read More

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http://dx.doi.org/10.1016/j.aquatox.2018.10.006DOI Listing
December 2018
2 Reads

Mito-tempo protects against acute liver injury but induces limited secondary apoptosis during the late phase of acetaminophen hepatotoxicity.

Arch Toxicol 2019 Jan 15;93(1):163-178. Epub 2018 Oct 15.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 1018, Kansas City, KS, 66160, USA.

We previously reported that delayed treatment with Mito-tempo (MT), a mitochondria-targeted superoxide dismutase mimetic, protects against the early phase of acetaminophen (APAP) hepatotoxicity by inhibiting peroxynitrite formation. However, whether this protection is sustained to the late phase of toxicity is unknown. To investigate the late protection, C57Bl/6J mice were treated with 300 mg/kg APAP followed by 20 mg/kg MT 1. Read More

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http://link.springer.com/10.1007/s00204-018-2331-8
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http://dx.doi.org/10.1007/s00204-018-2331-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344320PMC
January 2019
16 Reads

Biomarkers associated with binaprofen‑induced liver injury.

Mol Med Rep 2018 Dec 10;18(6):5076-5086. Epub 2018 Oct 10.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong 510990, P.R. China.

Drug‑induced liver injury (DILI) is a common hepatic disease. The identification of biomarkers for DILI prediction is critical for rational drug use. The aim of the present study was to investigate liver injury caused by binaprofen and identify proteins that may serve as early biomarkers to predict DILI. Read More

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http://dx.doi.org/10.3892/mmr.2018.9549DOI Listing
December 2018
2 Reads

Protective effects of on acetaminophen-induced liver and kidney toxicity in rats.

Food Sci Biotechnol 2018 Oct 15;27(5):1445-1454. Epub 2018 May 15.

1Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University, Seongnam-si, Gyunggi-do 13135 Republic of Korea.

An overdose of acetaminophen (AAP) causes hepatic and renal toxicity. This study examined the protective effects of (GEB) on hepatic and renal injury induced by AAP. Rats were orally administered distilled water or GEB for 14 days and injected with AAP 1 h after the oral last administration; control rats were administered water without AAP injection. Read More

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http://link.springer.com/10.1007/s10068-018-0374-5
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http://dx.doi.org/10.1007/s10068-018-0374-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170282PMC
October 2018
10 Reads

Relevance of the incubation period in cytotoxicity testing with primary human hepatocytes.

Arch Toxicol 2018 Dec 13;92(12):3505-3515. Epub 2018 Oct 13.

Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), 44139, Dortmund, Germany.

Primary human hepatocytes (PHHs) remain the gold standard for in vitro testing in the field of pharmacology and toxicology. One crucial parameter influencing the results of in vitro tests is the incubation period with test compounds. It has been suggested that longer incubation periods may be critical for the prediction of repeated dose toxicity. Read More

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http://link.springer.com/10.1007/s00204-018-2302-0
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http://dx.doi.org/10.1007/s00204-018-2302-0DOI Listing
December 2018
2 Reads

Effect of Ocimum basilicum leaves extract on acetaminophen-induced nephrotoxicity in BALB/c mice.

J Complement Integr Med 2018 Oct 12. Epub 2018 Oct 12.

Department of Biological Sciences, Faculty of Science, Beirut Arab University, Debbieh, Lebanon.

Background Acetaminophen (APAP) is one of the most widely used drugs to treat pain. Its overdose is lethal causing liver and kidney failure. Nephrotoxicity and hepatotoxicity are mostly due to the overproduction of reactive oxygen species. Read More

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http://www.degruyter.com/view/j/jcim.ahead-of-print/jcim-201
Publisher Site
http://dx.doi.org/10.1515/jcim-2018-0111DOI Listing
October 2018
15 Reads