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https://www.readbyqxmd.com/read/28640849/motility-in-blastogregarines-apicomplexa-native-and-drug-induced-organisation-of-siedleckia-nematoides-cytoskeletal-elements
#1
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/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28627846/drug-induced-myopathies
#7
Romain Guemara, Ilias Lazarou, Ierre-André Guerne
Drug myopathies are frequent and their identification important because of their potential morbidity. Apart from statins, the drugs most often involved are glucocorticoids, antimalarials, colchicine, and antiretrovirals. These myopathies are largely preventable, particularly those that occur in combinations of treatments or in the presence of comorbidities. Their relatively specific presentation often makes it possible to approach the diagnosis and to target the possible molecule to be interrupted. In general, they are spontaneously and rapidly reversible upon discontinuation of the drug, with the exception of statin-induced autoimmune necrotizing myopathy ; however, the latter is reversible under immunosuppressants, when initiated early enough...
May 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28626034/drug-induced-epigenetic-reprogramming-promotes-drug-resistance
#8
(no author information available yet)
Drug treatment causes resistance in cells with transiently high expression of drug resistance markers.
June 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28625786/drug-induces-depression-like-phenotypes-and-alters-gene-expression-profiles-in-drosophila
#9
Ming-Di Jiang, Ya Zheng, Jia-Lin Wang, Yu-Feng Wang
BACKGROUND: Major depressive disorder (MDD) is a severe mental illness that affects more than 350 million people worldwide. However, the molecular mechanisms of depression are currently unclear. Studies suggest that Drosophila and humans have similar depression-like symptoms under pressure. In this research, we choose Drosophila melanogaster as the animal model to explore the molecular mechanisms that trigger depression. RESULTS: We found that feeding D. melanogaster with the medium containing Levodopa or Chlorpromazine could induce depression-like phenotypes in both behavioral and biochemical biomarkers, including significantly decreased food intake, mating frequency, serotonin (5-HT) concentration, and increased malondialdehyde (MDA) concentration as well as reduced activity of superoxide dismutase (SOD)...
June 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28624960/drug-induced-pyoderma-gangrenosum-a-review
#10
REVIEW
Jane Y Wang, Lars E French, Neil H Shear, Afkham Amiri, Afsaneh Alavi
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be caused by an adverse drug reaction. We discuss the clinical presentation and outcomes of 52 cases of drug-induced PG reported to date in the literature. We conducted our literature search for case reports of drug-induced PG using keywords on PubMed and Medical Subject Heading (MeSH) terms on MEDLINE and EMBASE. To assess the probability that each case of PG was related to drug therapy, we used the Naranjo criteria. We identified 44 studies in the literature, with a total of 52 cases of drug-induced PG...
June 17, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28624112/opposing-roles-of-rapid-dopamine-signaling%C3%A2-across-the-rostral-caudal-axis-of%C3%A2-the%C3%A2-nucleus-accumbens-shell-in-drug-induced-negative-affect
#11
Seth W Hurley, Elizabeth A West, Regina M Carelli
BACKGROUND: Negative reinforcement theories of drug addiction posit that addicts use drugs to alleviate negative mood states. In a preclinical model developed in our laboratory, rats exhibit negative affect to a normally rewarding taste cue when it predicts impending but delayed cocaine. The emergence of this state is accompanied by a reduction in dopamine concentration in the rostral nucleus accumbens shell. However, the rostral and caudal regions of the shell have been implicated in promoting opposing appetitive and aversive states, respectively...
May 11, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28623497/-psychiatric-emergencies
#12
F Schneider, S Weber-Papen
Psychiatric emergencies present a frequent and interdisciplinary challenge. Clinical diagnosis and management are complicated by the acuity, and the patient's compliance is often limited by the illness. Psychiatric emergencies include states of acute agitation, suicidality, delirium, stupor, and drug-induced emergencies. Sometimes interventions such as conversational contact, responding empathically to patients, or "talking down" are sufficient. If pharmacotherapy is necessary, benzodiazepines and antipsychotic drugs are the primary agents of choice...
June 16, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28622161/antipsychotic-use-among-adult-outpatients-and-venous-thromboembolic-disease-a-retrospective-cohort-study
#13
Augusto Ferraris, Alejandro G Szmulewicz, Fernando J Vazquez, William M Vollmer, Federico Angriman
BACKGROUND: Treatment with antipsychotic (AP) agents is associated with incident thromboembolic events. However, the underpinnings of this association remain unknown. We sought to evaluate the effect of AP agents-categorized by their metabolic/sedative and hyperprolactinemia adverse effect profile-on the risk of venous thromboembolic disease during long-term follow-up. METHODS: A retrospective cohort study of adult patients initiating AP treatment for the first time was conducted...
June 15, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28620563/pharmacological-threat-to-lungs-a-case-series-and-literature-review
#14
REVIEW
Omar Irfan, Jaleed A Gilani, Abeel Irshad, Babar Irfan, Javaid A Khan
Drug-induced organ damage stands as a prevalent yet much-neglected issue globally. Keeping in view it's rising frequency, health care providers stand obliged to be well versed with the de-merits of the agents they prescribe. Drug therapies causing damage present with a non-specific clinical presentation, histological findings or radiology, which further elaborates on the necessity of a conscientious diagnosis. Pulmonary architecture ranging from the airways, lung parenchyma, mediastinum, pleura, pulmonary vasculature or the neuromuscular system, all can fall victim to the dreaded outcomes of this menace...
May 9, 2017: Curēus
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#15
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28617228/prediction-models-for-drug-induced-hepatotoxicity-by-using-weighted-molecular-fingerprints
#16
Eunyoung Kim, Hojung Nam
BACKGROUND: Drug-induced liver injury (DILI) is a critical issue in drug development because DILI causes failures in clinical trials and the withdrawal of approved drugs from the market. There have been many attempts to predict the risk of DILI based on in vivo and in silico identification of hepatotoxic compounds. In the current study, we propose the in silico prediction model predicting DILI using weighted molecular fingerprints. RESULTS: In this study, we used 881 bits of molecular fingerprint and used as features describing presence or absence of each substructure of compounds...
May 31, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28616908/-the-correlation-between-micrornas-in-serum-and-the-extent-of-liver-injury
#17
Yi-Nan Zuo, Xue-Ling He, Xue-Ni Shi, Shi-Hang Wei, Hai-Lin Yin
OBJECTIVES: To investigate the correlation between the absolute quantification of the microRNAs (miR-122, miR-451, miR-92a, miR-192) in serum during acute liver injury and the extent of liver injury on rat models of CCl4 induced acute liver injury and mice models of acetaminophen (APAP) induced acute liver injury. Furthermore, to investigate the correlation between the absolute quantification of microRNAs in serum and the drug induced liver injury pathological scoring system (DILI-PSS)...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28616043/angioedema-suppressed-by-a-combination-of-anti-histamine-and-leukotriene-modifier
#18
Brendan N Wong, Peter Vadas
RATIONALE: Angioedema without co-existent urticaria is due to a limited number of causes, including hereditary and acquired C1 esterase inhibitor deficiency, drug-induced angioedema or idiopathic histaminergic or non-histaminergic angioedema. We describe a cohort of patients with recurrent angioedema whose clinical features and response to medications are distinct from the causes above. METHODS: Patients were accrued retrospectively from an academic allergy practice between 2007 and 2014...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28615926/mechanistic-modelling-of-drug-induced-liver-injury-investigating-the-role-of-innate-immune-responses
#19
Lisl Km Shoda, Christina Battista, Scott Q Siler, David S Pisetsky, Paul B Watkins, Brett A Howell
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28615362/drugging-the-catalytically-inactive-state-of-ret-kinase-in-ret-rearranged-tumors
#20
Dennis Plenker, Maximilian Riedel, Johannes Brägelmann, Marcel A Dammert, Rakhee Chauhan, Phillip P Knowles, Carina Lorenz, Marina Keul, Mike Bührmann, Oliver Pagel, Verena Tischler, Andreas H Scheel, Daniel Schütte, Yanrui Song, Justina Stark, Florian Mrugalla, Yannic Alber, André Richters, Julian Engel, Frauke Leenders, Johannes M Heuckmann, Jürgen Wolf, Joachim Diebold, Georg Pall, Martin Peifer, Maarten Aerts, Kris Gevaert, René P Zahedi, Reinhard Buettner, Kevan M Shokat, Neil Q McDonald, Stefan M Kast, Oliver Gautschi, Roman K Thomas, Martin L Sos
Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. We provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors, such as AD80 or ponatinib, that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors...
June 14, 2017: Science Translational Medicine
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