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https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#1
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28643999/dexmedetomidine-and-general-anesthesia-a-narrative-literature-review-of-its-major-indications-for-use-in-adults-undergoing-non-cardiac-surgery
#2
Arthur Davy, Julien Fessler, Marc Fischler, Morgan le Guen
BACKGROUND: In Europe, dexmedetomidine has marketing approval only for sedation in intensive care units. However, its use during general anesthesia has been widely reported. The aim of this narrative review is to draw a picture of potential indications in anesthesia. METHODS: We searched in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials using the keywords "Dexmedetomidine, Dexdor, Precedex and Dexdomitor". The research ended in December 2016...
June 22, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28643552/drug-induced-physeal-abnormalities-in-preclinical-toxicity-studies
#3
Kendall S Frazier
Most toxic physeal changes are characterized microscopically by altered chondrocyte development, proliferation, or maturation in the growth plate and eventually result in disordered appositional bone growth. Many therapeutic drugs directly or indirectly target proteins involved in chondrocytic differentiation and maturation pathways, so toxic physeal injury has become increasingly common in preclinical toxicologic pathology. While physeal dysplasia has been associated with several different drug classes including bisphosphonates, vascular endothelial growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, transforming growth factor beta receptor inhibitors, and vascular targeting agents, physeal changes often share similar morphologic features including thickening and disorganization of the hypertrophic layer, increased numbers of hypertrophic chondrocytes, altered mineralization of endochondral ossification, and/or increased thickness of subphyseal bone...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28643108/integrated-tk-td-modeling-for-drug-induced-concurrent-tachycardia-and-qt-changes-in-beagle-dogs
#4
Fan Wu, Tycho Heimbach, Panos Hatsis, Hai-Ming Tang, Raviprakash Dugyala, Qin Yue, Tao Wang, Handan He
Drug-induced cardiotoxicity, including tachycardia and QT prolongation, remains a major safety concern that needs to be identified and its risk mitigated in early stages of drug development. In the present study, an integrated toxicokinetic-toxicodynamic (TK-TD) modeling approach within a nonlinear mixed-effect modeling framework is applied to investigate concurrent abnormal heart rate and QT changes in three beagle dogs, using a Novartis internal compound (NVS001) as the case example. By accounting for saturable drug absorption, circadian rhythms, drug-effect tolerance, and nonlinear rate-dependency of QT interval, the dynamic TK-TD model captures the experimentally observed drug effects on heart rate and QT interval across a wide dosing range of NVS001 in beagle dogs...
June 22, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28642210/rationale-and-design-for-a-randomized-comparison-of-efficacy-and-safety-between-aspirin-and-clopidogrel-in-atrial-fibrillation-patients-with-low-stroke-risk-cesac-af-trial
#5
Sang Min Park, Haemin Jeong, Mi-Hyang Jung, Kyung Soon Hong, Myeong-Ki Hong, Chang Seok Bang, Christopher Y Kim
BACKGROUND: Atrial fibrillation (AF) increases the risk of thromboembolic stroke. An oral anticoagulant should be administrated to prevent stroke in patients with moderate stroke risk (ie, CHA2DS2-VASc score>2). If the stroke risk is low (i.e. the score=1), however, antiplatelet agent such as aspirin is widely used. Aspirin can cause peptic ulcer disease (PUD) while its alternative, clopidogrel, theoretically does not. OBJECTIVE: To elucidate the efficacy and safety between aspirin and clopidogrel, a multicenter randomized controlled trial was designed in AF patients with low stroke risk...
June 19, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28642068/chloramphenicol-decreases-cb1-receptor-expression-in-the-nucleus-accumbens-and-prefrontal-cortex-and-prevents-amphetamine-induced-conditioned-place-preference-in-rats
#6
Octavio Amancio-Belmont, Diego Pérez-Vázquez, Alejandra E Ruiz-Contreras, Miguel Pérez de la Mora, Pavel E Rueda-Orozco, Mónica Méndez-Díaz, Oscar E Prospero-Garcia
Drug dependence seems to involve a learning and memory process. Since learning and memory depend on protein synthesis, drug dependence may depend on protein synthesis, too. Drug-induced reward is a crucial effect for the development of drug-dependence. We used chloramphenicol (CAP, a protein synthesis inhibitor), to evaluate its effects on amphetamine (amph)-seeking behavior, on CB1R expression and on protein synthesis in general, in specific areas of the brain. Two groups of Wistar adult male rats were subjected to amph-induced conditioned place preference (CPP)...
June 19, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28641965/animal-models-of-psychoactive-drug-use-and-addiction-present-problems-and-future-needs-for-translational-approaches
#7
REVIEW
Christian P Müller
Drug addiction is a psychiatric disorder based on a dysfunction of the brain. It frequently develops from a controlled drug consumption and drug instrumentalization (DI). Thereby, DI is the use of a drug to improve specific non-drug related behaviors, beyond the drug's direct positive or negative reinforcing effects. Currently available pharmacotherapies for drug addiction show low effect size and rather limited long-term efficacy, which suggests that current theories on addiction are still insufficient in how they capture the phenomenon and how they allow predictions for highly efficient treatments...
June 19, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28641484/protective-effect-of-hesperetin-against-haloperidol-induced-orofacial-dyskinesia-and-catalepsy-in-rats
#8
Dinesh Dhingra, Shikha Goswami, Nidhi Gahalain
OBJECTIVES: The present study was designed to evaluate the effect of hesperetin on haloperidol-induced orofacial dyskinesia and catalepsy in Wistar male albino rats. METHODS: Haloperidol (1 mg/kg, ip) was administered for 21 successive days to induce orofacial dyskinesia and catalepsy. Hesperetin (50 and 100 mg/kg, po) was administered 10 min prior to the injection of haloperidol for 21 successive days. Vacuous chewing movements (VCMs), tongue protrusions, catalepsy, and locomotor activity scores were recorded on 7th, 14th, and 22nd day of drug treatment...
June 22, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28640849/motility-in-blastogregarines-apicomplexa-native-and-drug-induced-organisation-of-siedleckia-nematoides-cytoskeletal-elements
#9
Andrea Valigurová, Naděžda Vaškovicová, Andrei Diakin, Gita G Paskerova, Timur G Simdyanov, Magdaléna Kováčiková
Recent studies on motility of Apicomplexa concur with the so-called glideosome concept applied for apicomplexan zoites, describing a unique mechanism of substrate-dependent gliding motility facilitated by a conserved form of actomyosin motor and subpellicular microtubules. In contrast, the gregarines and blastogregarines exhibit different modes and mechanisms of motility, correlating with diverse modifications of their cortex. This study focuses on the motility and cytoskeleton of the blastogregarine Siedleckia nematoides Caullery et Mesnil, 1898 parasitising the polychaete Scoloplos cf...
2017: PloS One
https://www.readbyqxmd.com/read/28640208/associations-of-drug-lipophilicity-and-extent-of-metabolism-with-drug-induced-liver-injury
#10
Kristin McEuen, Jürgen Borlak, Weida Tong, Minjun Chen
Drug-induced liver injury (DILI), although rare, is a frequent cause of adverse drug reactions resulting in warnings and withdrawals of numerous medications. Despite the research community's best efforts, current testing strategies aimed at identifying hepatotoxic drugs prior to human trials are not sufficiently powered to predict the complex mechanisms leading to DILI. In our previous studies, we demonstrated lipophilicity and dose to be associated with increased DILI risk and, and in our latest work, we factored reactive metabolites into the algorithm to predict DILI...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28639964/drug-induced-necrotizing-pancreatitis-with-a-focus-on-canagliflozin
#11
Kinner M Patel, Erik Pikas, Tanya George
No abstract text is available yet for this article.
February 14, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28639492/clinical-commentary-on-recurrent-natalizumab-related-aseptic-meningitis-in-a-patient-with-multiple-sclerosis-by-foley-et-al
#12
Andrew Chan
This clinical commentary discusses the occurrence of drug-induced aseptic meningitis in patients undergoing natalizumab treatment and other immunotherapies.
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28638678/detailed-features-of-hematological-involvement-and-medication-induced-cytopenia-in-systemic-lupus-erythematosus-patients-single-center-results-of-221-patients
#13
Hava Üsküdar Teke, Döndü Üsküdar Cansu, Cengiz Korkmaz
OBJECTIVE: Systemic lupus erythematosus (SLE) may affect a number of systems, with the hematological system being one of the most common. Our aim is to determine the existence of cytopenia at diagnosis or during follow-up of our SLE patients as well as the associated factors. MATERIAL AND METHODS: A cohort of SLE patients that had been followed-up in the Department of Rheumotology from 1998 to 2015 was retrospectively assessed. Clinical and laboratory findings about the patients were recorded...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28638234/ischemic-or-toxic-injury-a-challenging-diagnosis-and-treatment-of-drug-induced-stenosis-of-the-sigmoid-colon
#14
Zong-Ming Zhang, Xiang-Chun Lin, Li Ma, An-Qin Jin, Fang-Cai Lin, Zhuo Liu, Li-Min Liu, Chong Zhang, Na Zhang, Li-Juan Huo, Xue-Liang Jiang, Feng Kang, Hong-Jun Qin, Qiu-Yang Li, Hong-Wei Yu, Hai Deng, Ming-Wen Zhu, Zi-Xu Liu, Bai-Jiang Wan, Hai-Yan Yang, Jia-Hong Liao, Xu Luo, You-Wei Li, Wen-Ping Wei, Meng-Meng Song, Yue Zhao, Xue-Ying Shi, Zhao-Hui Lu
A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28638211/psychogenic-blepharospasm-a-diagnostic-dilemma
#15
Soumitra DAS, Roopchand Pandrantil Sreedharan, Prasanth Sudhakaran Remadevi, Cheruvallil Velayudhan Saji
Blepharospasm is an uncontrolled spasmodic contraction of the orbicularis muscles of the eye resulting in an abnormal tic or twitch of eyes. It usually lasts for seconds to minutes but in severe cases eyes may be closed for hours. It may be essentially benign or secondary due to a lesion in basal ganglia, pyramidal tract, and trauma, local pathology in the eyes or drug induced. Here we are presenting a case of psychogenic blepharospasm. A 65 year old woman presented with a history of episodic inability of opening her eyes for the past 6 months...
December 25, 2016: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#16
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/28635225/-modification-factors-associated-with-maternally-inherited-non-syndromic-hearing-loss
#17
W J Hong, B J Zheng, J F Qian, H Wu, H Jin, Y T Zhu
Mutations in the mitochondrial DNA have been certified to be one of the most important causes of maternally inherited sensorineural hearing loss. Among these, mitochondrial 12S rRNA1555A>G, 1494C>T and other mutations are associated with both nonsyndromic and drug induced hearing loss caused by aminoglycosides. Individuals carrying 1555A>G or 1494C>T mutation have a variety of clinical manifestations, which implies that the 1555A>G or 1494C>T mutation is a chief factor underlying the development of deafness but insufficient to produce the clinical phenotype...
June 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28634147/csahi-study-2-validation-of-multi-electrode-array-systems-mea60-2100-for-prediction-of-drug-induced-proarrhythmia-using-human-ips-cell-derived-cardiomyocytes-assessment-of-reference-compounds-and-comparison-with-non-clinical-studies-and-clinical-information
#18
Yumiko Nozaki, Yayoi Honda, Hitoshi Watanabe, Shota Saiki, Kiyotaka Koyabu, Tetsuji Itoh, Chiho Nagasawa, Chiaki Nakamori, Chiaki Nakayama, Hiroshi Iwasaki, Shinobu Suzuki, Kohji Tanaka, Etsushi Takahashi, Kaori Miyamoto, Kaoru Morimura, Atsuhiro Yamanishi, Hiroko Endo, Junko Shinozaki, Hisashi Nogawa, Tadahiro Shinozawa, Fumiyo Saito, Takeshi Kunimatsu
With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period...
June 17, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28632695/serum-ceruloplasmin-and-striatal-dopamine-transporter-density-in-parkinson-disease-comparison-with-123i-fp-cit-spect
#19
Yoo Sung Song, Jong-Min Kim, Kyeong Joon Kim, Ji Young Yun, Sang Eun Kim
PURPOSE: In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin-along with its related serum markers- and striatal presynaptic dopaminergic denervation measured with I-FP-CIT SPECT. METHODS: We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism)...
June 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28627888/investigation-of-drug-induced-hepatotoxicity-and-its-remediation-pathway-with-reaction-based-fluorescent-probes
#20
Dan Cheng, Wang Xu, Lin Yuan, Xiao-Bing Zhang
Drug-induced liver injury (DILI) is considered a serious problem related to public health, due to its unpredictability and acute response. The level of peroxynitrite (ONOO-) generated in liver has long been regarded as a biomarker for the prediction and measurement of DILI. Herein we present two reaction based fluorescent probes (Naph-ONOO- and Rhod-ONOO-) for ONOO- through a novel and universally applicable mechanism: ONOO- mediated deprotection of -keto caged fluorophores. Among them, Rhod-ONOO- can selectively accumulate and react in mitochondria, one of the main sources of ONOO-, with a substantial lower nano-molar sensitivity of 43 nM...
June 19, 2017: Analytical Chemistry
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