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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/28813206/levamisole-in-illicit-trafficking-cocaine-seized-a-one-year-study
#1
Simona Martello, Massimo Pieri, Cristiano Ialongo, Stefano Pignalosa, Gianluca Noce, Francesca Vernich, Carmelo Russo, Federico Mineo, Sergio Bernardini, Luigi Tonino Marsella
Cocaine use is increasing around the world and its purity is frequently altered through dilution, substitution, contamination, and adulteration. Sugars, talc, starch, and carbonates represent the principal diluents of cocaine, while phenacetin, levamisole, caffeine, and lidocaine are its major adulterants in Europe. Levamisole is used because it is an odorless powder, with physical properties similar to cocaine, and it has reasonable cost and availability, being widely used in veterinary medicine. For this study, we analyzed 88 cocaine samples...
August 16, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28799017/ecotoxicological-risk-assessment-and-seasonal-variation-of-some-pharmaceuticals-and-personal-care-products-in-the-sewage-treatment-plant-and-surface-water-bodies-lakes
#2
G Archana, Rita Dhodapkar, Anupama Kumar
This paper reports the seasonal variation and environmental quality control data for five fingerprint pharmaceuticals and personal care products (PPCPs) (acetaminophen ciprofloxacin, caffeine, irgasan and benzophenone) in the influent and the effluent of the sewage treatment plant (STP) and surface water bodies (six major lakes) in and around Nagpur, one of the "A class city" in the central India over a period of 1 year. The target compounds were analysed using developed offline solid-phase extraction (SPE) coupled with reversed phase high-performance liquid chromatography (RP-HPLC-PDA) method...
August 10, 2017: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/28797958/quantification-of-paracetamol-and-5-oxoproline-in-serum-by-capillary-electrophoresis-implication-for-clinical-toxicology
#3
Tomáš Hložek, Tomáš Křížek, Petr Tůma, Miroslava Bursová, Pavel Coufal, Radomír Čabala
High anion gap metabolic acidosis frequently complicates acute paracetamol overdose and is generally attributed to lactic acidosis or compromised hepatic function. However, metabolic acidosis can also be caused by organic acid 5-oxoproline (pyroglutamic acid). Paracetamol's toxic intermediate, N-acetyl-p-benzoquinoneimine irreversibly binds to glutathione and its depletion leads to subsequent disruption of the gamma glutamyl cycle and an excessive 5-oxoproline generation. This is undoubtedly an underdiagnosed condition because measurement of serum 5-oxoproline level is not readily available...
July 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28795995/toxic-myocarditis-caused-by-acetaminophen-in-a-multidrug-overdose
#4
Maxime Gosselin, Yann Dazé, Pascal Mireault, Marie Crahes
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction...
August 9, 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/28782093/metabolic-acidosis-caused-by-concomitant-use-of-paracetamol-acetaminophen-and-flucloxacillin-a-case-report-and-a-retrospective-study
#5
J K Berbee, L A Lammers, C T P Krediet, J C Fischer, E M Kemper
PURPOSE: A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. METHODS: To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na(+), HCO3(-), Cl(-), albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously...
August 7, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28772250/formation-and-estimated-toxicity-of-trihalomethanes-haloacetonitriles-and-haloacetamides-from-the-chlor-am-ination-of-acetaminophen
#6
Shunke Ding, Wenhai Chu, Tom Bond, Qi Wang, Naiyun Gao, Bin Xu, Erdeng Du
The occurrence of pharmaceuticals and personal care products (PPCPs) in natural waters, which act as drinking water sources, raises concerns. Moreover, those compounds incompletely removed by treatment have the chance to form toxic disinfection byproducts (DBPs) during subsequent disinfection. In this study, acetaminophen (Apap), commonly used to treat pain and fever, was selected as a model PPCP. The formation of carbonaceous and nitrogenous DBPs, namely trihalomethanes, haloacetonitriles, and haloacetamides, during chlor(am)ination of Apap was investigated...
July 25, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28772086/highlights-of-drug-and-herb-induced-liver-injury-in-the-literature-from-2016-how-best-to-translate-new-information-into-clinical-practice
#7
Omar Shahbaz, Sandeep Mahajan, James H Lewis
INTRODUCTION: More than 1500 papers on drug-induced liver injury (DILI) and herb-induced liver injury (HILI) were published in 2016, many of which have the potential to impact clinical practice. AREAS COVERED: Clinical studies and case series that lent themselves to new concepts or directions in diagnosing, preventing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted, including the US DILIN network and Spanish DILI registry...
August 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28766237/the-toxicology-investigators-consortium-case-registry-the-2016-experience
#8
Lynn A Farrugia, Sean H Rhyee, Diane P Calello, Sharan L Campleman, Anne M Riederer, Hannah R Malashock, Anthony Pizon, Timothy Wiegand, Paul M Wax, Jeffrey Brent
The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry contains data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. Currently, 83% of accredited medical toxicology fellowship programs in the USA participate. The Registry continues to grow each year, and as of 31 December 2016, a new milestone was reached, with more than 50,000 cases reported since its inception...
August 1, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28758069/investigating-the-application-of-a-nitroreductase-expressing-transgenic-zebrafish-line-for-high-throughput-toxicity-testing
#9
Anna C Chlebowski, Jane K La Du, Lisa Truong, Staci L Massey Simonich, Robert L Tanguay
Nitroreductase enzymes are responsible for the reduction of nitro functional groups to amino functional groups, and are found in a range of animal models, zebrafish (Danio rerio) excluded. Transgenic zebrafish models have been developed for tissue-specific cell ablation, which use nitroreductase to ablate specific tissues or cell types following exposure to the non-toxic pro-drug metronidazole (MTZ). When metabolized by nitroreductase, MTZ produces a potent cytotoxin, which specifically ablates the tissue in which metabolism occurs...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28734939/public-health-acetaminophen-apap-hepatotoxicity-isn-t-it-time-for-apap-to-go-away
#10
REVIEW
William M Lee
Acetaminophen (APAP) is the most commonly used drug for the treatment of pain and fever around the world. At the same time, APAP is capable of causing dose-related hepatocellular necrosis, responsible for nearly 500 deaths annually in the U.S. alone, as well as 100,000 calls to US Poison Control Centers, 50,000 emergency room visits and 10,000 hospitalizations per year. As an over-the-counter and prescription product (with opioids), APAP toxicity dwarfs all other prescription drugs as a cause for acute liver failure in the United States and Europe, but is not regulated in any significant way...
July 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#11
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
July 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28720398/perinatal-and-neonatal-use-of-paracetamol-for-pain-relief
#12
REVIEW
Karel Allegaert, John N van den Anker
Paracetamol (acetaminophen) is the most widely used drug to treat pain or fever in pregnant women or neonates, but its pharmacokinetics (PK) and pharmacodynamics (PD) warrant a focused analysis. During pregnancy, there is an important increase in paracetamol clearance. Consequently, it is reasonable to anticipate that the analgesic effect of paracetamol will decrease faster, whereas higher doses may result in even higher oxidative toxic metabolites. Therefore, most peripartal PD data relate to multimodal analgesia strategies...
July 15, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28717379/hepatoprotective-effect-of-citral-on-acetaminophen-induced-liver-toxicity-in-mice
#13
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Gabriel Fernando Esteves Cardia, Edivaldo Cremer, Francielli Maria de Souza Silva-Comar, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#14
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D Sharma, Michael Ott, Tobias Cantz
The quest for physiologically-active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC) - derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
July 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28690122/hepatoprotective-effects-of-ethanol-extracts-from-folium-syringae-against-acetaminophen-induced-hepatotoxicity-in%C3%A2-vitro-and-in%C3%A2-vivo
#15
Chen-Xi Shi, Yue-Xia Lin, Fang-Ping Liu, Yi-Cong Chang, Rui Li, Chang-Wen Li, Ying Li, Jing-Shan He, Xin Ma, Zhi Li
BACKGROUND: The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. METHODS: Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively...
July 6, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28680622/a-case-of-reversible-drug-induced-liver-failure
#16
Mohammad Ansari, Sabrina Arshed, Mohammed Islam, Shuvendu Sen, Abdalla Yousif
Acute fulminant liver failure and acute renal failure are devastating complications caused by many drugs. The use of N-acetylcysteine has been well established in acetaminophen toxicity, but it remains controversial in other cases. Dialysis is a very effective method of removing certain drugs from the system. With the invention of new street drugs such as "synthetic marijuana," it may be beneficial in patients whom the substances ingested are unknown. We report a case of a 42-year-old male who developed acute fulminant hepatic failure and acute renal failure, who was cured with dialysis, N-acetylcysteine, and other supportive measures...
July 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28678845/polymerase-free-measurement-of-microrna-122-with-single-base-specificity-using-single-molecule-arrays-detection-of-drug-induced-liver-injury
#17
David M Rissin, Barbara López-Longarela, Salvatore Pernagallo, Hugh Ilyine, A D Bastiaan Vliegenthart, James W Dear, Juan J Díaz-Mochón, David C Duffy
We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity down to a single base, and without the use of amplification by polymerases. An abasic peptide nucleic acid (PNA) probe-containing a reactive amine instead of a nucleotide at a specific position in the sequence-for detecting a microRNA was conjugated to superparamagnetic beads. These beads were incubated with a sample containing microRNA, a biotinylated reactive nucleobase-containing an aldehyde group-that was complementary to the missing base in the probe sequence, and a reducing agent...
2017: PloS One
https://www.readbyqxmd.com/read/28661486/the-role-of-map2-kinases-and-p38-kinase-in-acute-murine-liver-injury-models
#18
Jun Zhang, Robert W M Min, Khanh Le, Sheng Zhou, Mariam Aghajan, Tin A Than, Sanda Win, Neil Kaplowitz
c-Jun N-terminal kinase (JNK) mediates hepatotoxicity through interaction of its phospho-activated form with a mitochondrial outer membrane protein, Sh3bp5 or Sab, leading to dephosphorylation of intermembrane Src and consequent impaired mitochondrial respiration and enhanced ROS release. ROS production from mitochondria activates MAP3 kinases, such as MLK3 and ASK1, which continue to activate a pathway to sustain JNK activation, and amplifies the toxic effect of acetaminophen (APAP) and TNF/galactosamine (TNF/GalN)...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#19
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28599208/occurrence-of-pharmaceutical-recreational-and-psychotropic-drug-residues-in-surface-water-on-the-northern-antarctic-peninsula-region
#20
Silvia González-Alonso, Luis Moreno Merino, Sara Esteban, Miren López de Alda, Damià Barceló, Juan José Durán, Jerónimo López-Martínez, Jaume Aceña, Sandra Pérez, Nicola Mastroianni, Adrián Silva, Myriam Catalá, Yolanda Valcárcel
Human presence in the Antarctic is increasing due to research activities and the rise in tourism. These activities contribute a number of potentially hazardous substances. The aim of this study is to conduct the first characterisation of the pharmaceuticals and recreational drugs present in the northern Antarctic Peninsula region, and to assess the potential environmental risk they pose to the environment. The study consisted of a single sampling of ten water samples from different sources, including streams, ponds, glacier drains, and a wastewater discharge into the sea...
June 6, 2017: Environmental Pollution
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