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https://www.readbyqxmd.com/read/28528369/effect-of-physical-stress-on-drug-induced-sleep-endoscopy-for-obstructive-sleep-apnea
#1
Sang Min Park, Dong-Kyu Kim
Drug-induced sleep endoscopy (DISE) is a reliable upper airway evaluation tool, widely used to improve surgical results in patients with obstructive sleep apnea (OSA). Several factors, including sleeping position and depth of sedation, affect DISE findings. This study aimed to evaluate the impact of physical stress on DISE findings. Eighty-five patients with OSA underwent two DISE examinations at the same level of sedation. The "first DISE" (control group) was performed after polysomnography, while the "second DISE" (test group) performed immediately after a treadmill stress test...
May 20, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28527921/drug-induced-fatal-arrhythmias-acquired-long-qt-and-brugada-syndromes
#2
REVIEW
Isik Turker, Tomohiko Ai, Hideki Itoh, Minoru Horie
Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527154/structure-based-classification-for-bile-salt-export-pump-bsep-inhibitors-using-comparative-structural-modeling-of-human-bsep
#3
Sankalp Jain, Melanie Grandits, Lars Richter, Gerhard F Ecker
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline...
May 19, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#4
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28527032/methylone-and-mdpv-activate-autophagy-in-human-dopaminergic-sh-sy5y-cells-a-new-insight-into-the-context-of-%C3%AE-keto-amphetamines-related-neurotoxicity
#5
Maria João Valente, Cristina Amaral, Georgina Correia-da-Silva, José Alberto Duarte, Maria de Lourdes Bastos, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells...
May 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28526605/microevolutionary-response-of-a-gut-nematode-to-intestinal-inflammation
#6
Cédric Lippens, Bruno Faivre, Gabriele Sorci
Parasitic helminths interfere with the immune responses of their hosts to establish long-lasting, chronic infections. While favorable to the parasite, the capacity to dampen the immune response can also provide a benefit to the host in terms of reduced risk of immune disorders and immunopathology. The immunomodulatory role of nematodes has been exploited in clinical trials to treat a number of inflammatory and immune diseases. However, how parasites adapt to an inflammatory environment remains a poorly explored question...
May 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28525920/torsade-de-pointes-arrhythmias-arise-at-the-site-of-maximal-heterogeneity-of-repolarization-in-the-chronic-complete-atrioventricular-block-dog
#7
Albert Dunnink, Thom R G Stams, Alexandre Bossu, Veronique M F Meijborg, Jet D M Beekman, Sofieke C Wijers, Jacques M T De Bakker, Marc A Vos
Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP. Methods and results: In 8 CAVB animals, 56 needles, each containing 4 electrodes, were inserted in the ventricles...
May 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28525371/arsenic-trioxide-and-angiotensin-ii-have-inhibitory-effects-on-herg-protein-expression-evidence-for-the-role-of-pml-sumoylation
#8
Yu Liu, Duo Li, Dan Nie, Shang-Kun Liu, Fang Qiu, Mei-Tong Liu, Yuan-Yuan Li, Jia-Xin Wang, Yan-Xin Liu, Chang-Jiang Dong, Di Wu, Wei Tian, Jia Yang, Wei Mu, Jia-Tong Li, Dan Zhao, Xiao-Feng Wang, Wen-Feng Chu, Bao-Feng Yang
The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525267/the-supernatant-from-hepatocyte-cultures-with-drugs-that-cause-idiosyncratic-liver-injury-activates-macrophage-inflammasomes
#9
Ryuji Kato, Jack Uetrecht
There is increasing evidence that most idiosyncratic drug-induced liver injury (IDILI) is immune mediated, and in most cases reactive metabolites appear to be responsible for induction of this immune response. Reactive metabolites can cause cell damage with the release of damage-associated molecular patterns (DAMPs), which is thought to be involved in immune activation. Presumably the reason that the liver is a common target of idiosyncratic drug reactions is because it is the major site of drug metabolism and reactive metabolite formation...
May 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28524847/an-in-vivo-strategy-to-counteract-post-administration-anticoagulant-activity-of-azido-warfarin
#10
Sylvain Ursuegui, Marion Recher, Wojciech Krężel, Alain Wagner
Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent...
May 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28524363/donor-transmitted-mutation-of-the-abcb11-gene-and-ensuing-intra-hepatic-cholestasis-of-pregnancy-in-a-liver-transplant-recipient
#11
Tiong Yeng Lim, Iona Coltart, Pierre Foskett, Richard Thompson, Sandra Strautnieks, Leonie Penna, Catherine Williamson, Rosa Miquel, Michael A Heneghan
In liver transplant (LT) recipients, the cause of graft dysfunction in pregnancy is often difficult to ascertain. Moreover, a liver biopsy in late pregnancy is often avoided as a consequence of patient and physician factors. Management of graft dysfunction can be difficult in this setting. We report a 30-year-old female LT recipient who developed acutely deranged liver biochemistry during the third trimester of her first pregnancy. At 29 weeks gestation, her liver function test (LFT) became abnormal; AST peaked at 978 IU/L (normal range 10-50), GGT 25 IU/L (normal range 1-55), bilirubin 1...
May 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28524116/inhibition-of-autophagy-promotes-salinomycin-induced-apoptosis-via-reactive-oxygen-species-mediated-pi3k-akt-mtor-and-erk-p38-mapk-dependent-signaling-in-human-prostate-cancer-cells
#12
Kwang-Youn Kim, Kwang-Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Sul-Gi Park, Young Woo Kim, Young-Kyo Seo, Jin-Yeul Ma, Soon-Cheol Ahn
Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28524079/assembly-of-hepatocyte-spheroids-using-magnetic-3d-cell-culture-for-cyp450-inhibition-induction
#13
Pujan K Desai, Hubert Tseng, Glauco R Souza
There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28523543/drug-addiction-and-dna-modifications
#14
Amber N Brown, Jian Feng
Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523534/idiosyncratic-drug-induced-liver-injury-linked-to-polygonum-multiflorum-a-case-study-by-pharmacognosy
#15
Chun-Yu Li, Qin He, Dan Gao, Rui-Yu Li, Yun Zhu, Hui-Fang Li, Wu-Wen Feng, Mei-Hua Yang, Xiao-He Xiao, Jia-Bo Wang
No abstract text is available yet for this article.
May 18, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28522677/synergistic-effect-of-dofetilide-and-mexiletine-on-prevention-of-atrial-fibrillation
#16
Guizhi Liu, Xiaolin Xue, Chuanyu Gao, Jiaqi Huang, Datun Qi, Yanzhou Zhang, Jian-Zeng Dong, Chang-Sheng Ma, Gan-Xin Yan
BACKGROUND: Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias. METHODS AND RESULTS: The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28521790/unintentional-drowning-role-of-medicinal-drugs-and-alcohol
#17
Tuulia Pajunen, Erkki Vuori, Frank F Vincenzi, Pirjo Lillsunde, Gordon Smith, Philippe Lunetta
BACKGROUND: Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates. METHODS: Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75...
May 19, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28521333/drugging-the-cancers-addicted-to-dna-repair
#18
Jac A Nickoloff, Dennie Jones, Suk-Hee Lee, Elizabeth A Williamson, Robert Hromas
Defects in DNA repair can result in oncogenic genomic instability. Cancers occurring from DNA repair defects were once thought to be limited to rare inherited mutations (such as BRCA1 or 2). It now appears that a clinically significant fraction of cancers have acquired DNA repair defects. DNA repair pathways operate in related networks, and cancers arising from loss of one DNA repair component typically become addicted to other repair pathways to survive and proliferate. Drug inhibition of the rescue repair pathway prevents the repair-deficient cancer cell from replicating, causing apoptosis (termed synthetic lethality)...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28521054/in-silico-prediction-of-drug-induced-liver-injury-based-on-adverse-drug-reaction-reports
#19
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/28520417/correction-to-evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#20
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
No abstract text is available yet for this article.
May 18, 2017: Chemical Research in Toxicology
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