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https://www.readbyqxmd.com/read/28816033/selection-of-12-hour-sustained-release-acetaminophen-paracetamol-formulation-through-comparison-of-pharmacokinetic-profiles-of-4-sustained-release-prototype-formulations-and-standard-acetaminophen-formulation-an-open-label-randomized-proof-of-principle-pharmacokinetic
#1
Yong Yue, Dongzhou J Liu
Acetaminophen (APAP; paracetamol), a widely used analgesic and antipyretic, is available in modified-release and immediate-release (IR) formulations requiring 3- or 4-times-daily dosing. This phase 1 open-label crossover study compared pharmacokinetic profiles of single 2000-mg doses of 4 different sustained-release (SR) formulations of APAP (designed to allow twice-daily dosing) against two 1000-mg doses (taken 6 hours apart) of standard IR APAP in 14 healthy volunteers. The primary end point was duration of time that plasma APAP concentration exceeded a plasma concentration (TC ) of 4 μg/mL...
August 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28812385/increased-acetaminophen-related-calls-to-finnish-pic-better-reflect-acetaminophen-sales-than-serious-poisonings
#2
Mikko J Parry, Helena Isoniemi, Anna-Maria Koivusalo, Kalle Hoppu
OBJECTIVE: Acetaminophen (APAP) or paracetamol is a commonly encountered medicine in poisonings. We studied the changes in APAP related calls to the Finnish poison information centre (FPIC), and serious intoxications, involving hepatotoxicity or death in 2001-2014. These data were compared with paracetamol sales in Finland. METHODS: This is a retrospective analysis of the FPIC database calls, national cause of death registry, registries of liver transplantations and molecular adsorbent recycling system (MARS)-treated patients from Helsinki University Hospital together with the National Institute of Health and Welfare registry of patients hospitalized...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#3
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807032/liquid-chromatography-mass-spectrometry-based-profiling-of-phosphatidylcholine-and-phosphatidylethanolamine-in-the-plasma-and-liver-of-acetaminophen-induced-liver-injured-mice
#4
Ya-Nan Ming, Jing-Yi Zhang, Xiao-Lin Wang, Chun-Min Li, Si-Cong Ma, Zheng-Yang Wang, Xiao-Lin Liu, Xiao-Bo Li, Yi-Min Mao
BACKGROUND: Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. METHODS: A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver...
August 14, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28802595/variability-in-opioid-prescribing-for-children-undergoing-ambulatory-surgery-in-the-united-states
#5
William C Van Cleve, Eliot B Grigg
STUDY OBJECTIVE: We attempted to describe the opioid prescribing patterns for ambulatory pediatric surgery in the United States from 2007 to 2014. DESIGN: Retrospective database review. SETTING: Operating room ambulatory encounters as determined by the Truven Health Marketscan Commercial Claims and Encounters database. PATIENTS: A total of 929,874 ambulatory surgical encounters were identified in patients <18years of age and, of these, 439,286 encounters generated an analgesic prescription...
September 2017: Journal of Clinical Anesthesia
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/28766385/paracetamol-overdose-induced-oxidative-stress-toxicity-metabolism-and-protective-effects-of-various-compounds-in-vivo-and-in-vitro
#7
Xu Wang, Qinghua Wu, Aimei Liu, Arturo Anadón, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, María-Aránzazu Martínez
Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress...
August 16, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28755860/dynamic-and-accurate-assessment-of-acetaminophen-induced-hepatotoxicity-by-integrated-photoacoustic-imaging-and-mechanistic-biomarkers-in-vivo
#8
Nathalie Brillant, Mohamed Elmasry, Neal C Burton, Josep Monne Rodriguez, Jack W Sharkey, Stephen Fenwick, Harish Poptani, Neil R Kitteringham, Christopher E Goldring, Anja Kipar, B Kevin Park, Daniel J Antoine
The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention...
July 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28748093/pathological-features-of-explant-lungs-with-fibrosis-in-autoimmune-pulmonary-alveolar-proteinosis
#9
Manabu Ono, Ryoko Saito, Junya Tominaga, Yoshinori Okada, Shinya Ohkouchi, Tamiko Takemura
Association of fibrosis with autoimmune pulmonary alveolar proteinosis (aPAP) is rare. However, prognoses of such cases are poor and the process of the formation of fibrosis is still unknown. In this study, we report a case of aPAP with progressive fibrosis occurring in a 46-year-old woman. She had undergone several repetitions of whole lung lavage (WLL) for 7 years and granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation for 3 months; however, the progression of fibrosis was not hindered...
September 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28735193/fabrication-of-in2s3-zn2geo4-composite-photocatalyst-for-degradation-of-acetaminophen-under-visible-light
#10
Tao Yan, Tingting Wu, Yaru Zhang, Meng Sun, Xiaodong Wang, Qin Wei, Bin Du
A novel indium trisulfide/zinc germinate (In2S3/Zn2GeO4) composite was developed via a co-precipitation hydrothermal method. The as-prepared composite was characterized in detail by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV-vis diffuse reflectance spectroscopy (DRS). Zn2GeO4 nanorods work as the main photocatalyst while In2S3 nanoparticles deposited on them acts as the photosensitizer. The resulting In2S3/Zn2GeO4 heterogeneous photocatalyst not only has enhanced visible light absorption, but also improved photo-generated charge transfer efficiency with remarkably high efficiency in decomposing acetaminophen (APAP)...
June 23, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28734939/public-health-acetaminophen-apap-hepatotoxicity-isn-t-it-time-for-apap-to-go-away
#11
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
#12
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/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/28701992/verifying-the-relative-efficacy-between-continuous-positive-airway-pressure-therapy-and-its-alternatives-for-obstructive-sleep-apnea-a-network-meta-analysis
#14
Tingwei Liu, Wenyang Li, Hui Zhou, Zanfeng Wang
Obstructive sleep apnea (OSA) is a common breathing disorder, and continuous positive airway pressure (CPAP) therapy together with its alternatives has been developed to treat this disease. This network meta-analysis (NMA) was aimed to compare the efficacy of treatments for OSA. Cochrane Library, MEDLINE, and Embase were searched for eligible studies. A conventional and NMA was carried out to compare all therapies. Sleeping characteristics, including Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), arterial oxygen saturation, and arousal index (AI), and changes of blood pressure were selected as outcomes...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28692292/discovery-of-potent-and-selective-inhibitors-of-cdc2-like-kinase-1-clk1-as-a-new-class-of-autophagy-inducers
#15
Qi-Zheng Sun, Gui-Feng Lin, Lin-Li Li, Xi-Ting Jin, Lu-Yi Huang, Guo Zhang, Wei Yang, Kai Chen, Rong Xiang, Chong Chen, Yu-Quan Wei, Guang-Wen Lu, Sheng-Yong Yang
Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1...
July 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28677736/glutathione-peroxidase-3-is-a-protective-factor-against-acetaminophen%C3%A2-induced-hepatotoxicity-in-vivo-and-in-vitro
#16
Syu-Ichi Kanno, Ayako Tomizawa, Shin Yomogida, Akiyoshi Hara
Acetaminophen (APAP) is a widely available antipyretic and analgesic; however, overdose of the drug inflicts severe damage to the liver. It is well established that the hepatotoxicity of APAP is initiated by formation of a reactive metabolite, N‑acetyl‑p‑benzoquinone imine (NAPQI), which can be detoxified by conjugation with reduced glutathione (GSH), a typical antioxidant. We recently found that the blood mRNA expression level of glutathione peroxidase 3 (Gpx3), which catalyzes the oxidation of GSH, is associated with the extent of APAP‑induced hepatotoxicity in mice...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28670625/mechanisms-of-acetaminophen-hepatotoxicity-and-their-translation-to-the-human-pathophysiology
#17
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and mechanisms of liver injury induced by APAP overdose have been the focus of extensive investigation. Studies in the mouse model, which closely reproduces the human condition, have shown that hepatotoxicity is initiated by formation of a reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which depletes cellular glutathione and forms protein adducts on mitochondrial proteins. This leads to mitochondrial oxidative and nitrosative stress, accompanied by activation of c-jun N-terminal kinase (JNK) and its translocation to the mitochondria...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28668488/glycyrrhetinic-acid-prevents-acetaminophen-induced-acute-liver-injury-via-the-inhibition-of-cyp2e1-expression-and-hmgb1-tlr4-signal-activation-in-mice
#18
Genling Yang, Li Zhang, Li Ma, Rong Jiang, Ge Kuang, Ke Li, Hongtao Tie, Bin Wang, Xinyu Chen, Tianjun Xie, Xia Gong, Jingyuan Wan
Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, which is safe and effective at the therapeutic dose. Unfortunately, excessive dosage of APAP could cause severe liver injury due to lack of effective therapy. Successful therapeutic strategies are urgently requested in clinic. Glycyrrhetinic acid (GA), derived from a traditional medicine licorice, has been shown to exert anti-inflammatory and antioxidant actions. In this study, the effect and the underlying mechanism of GA on APAP-induced hepatotoxicity were explored...
June 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28661486/the-role-of-map2-kinases-and-p38-kinase-in-acute-murine-liver-injury-models
#19
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/28654297/eriodictyol-not-its-glucuronide-metabolites-attenuates-acetaminophen-induced-hepatotoxicity
#20
Ling Ye, Zhaoyu Wang, Yao Lan, Minghao Chen, Cailing Wen, Yanxian Hu, Zhong Qiu Liu
Acetaminophen (APAP) is one of the most commonly used oral analgesics and antipyretics, but hepatotoxicity including liver failure may occur after overdose. The therapeutic options for treating APAP hepatotoxicity are limited. Eriodictyol, a dietary flavonoid with anti-inflammatory and antioxidant properties, was used here to determine its protective effects against APAP-induced hepatotoxicity in mice. Various administration routes and pharmacokinetics-pharmacodynamics (PK-PD) analyses were used to determine these effects...
June 27, 2017: Molecular Pharmaceutics
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