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https://www.readbyqxmd.com/read/28725874/metabolites-of-alectinib-in-human-their-identification-and-pharmacological-activity
#1
Mika Sato-Nakai, Kosuke Kawashima, Toshito Nakagawa, Yukako Tachibana, Miyuki Yoshida, Kenji Takanashi, Peter N Morcos, Martin Binder, David J Moore, Li Yu
Two metabolites (M4 and M1b) in plasma and four metabolites (M4, M6, M1a and M1b) in faeces were detected through the human ADME study following a single oral administration of [(14)C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28721082/effectiveness-evaluation-of-two-volumizing-hyaluronic-acid-dermal-fillers-in-a-controlled-randomized-double-blind-split-face-clinical-study
#2
Martina Kerscher, Karla Agsten, Maria Kravtsov, Welf Prager
BACKGROUND: Enhancement of the midface can be achieved with volumizing hyaluronic acid (HA) fillers. OBJECTIVE: The objective of this study was to compare the safety and effectiveness of Cohesive Polydensified Matrix(®) 26 mg/mL HA gel (CPM-26) and Vycross(®) 20 mg/ml HA gel (VYC-20) in a controlled, randomized, evaluator-blind, split-face clinical study. PATIENTS AND METHODS: Subjects with moderate-to-severe malar volume loss on the Merz Aesthetics Scale (MAS) received CPM-26 on one side and VYC-20 on the contralateral side of the face...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28711188/plan-delivery-quality-assurance-for-cyberknife-statistical-process-control-analysis-of-350-film-based-patient-specific-qas
#3
J Bellec, N Delaby, F Jouyaux, M Perdrieux, J Bouvier, S Sorel, O Henry, C Lafond
PURPOSE: Robotic radiosurgery requires plan delivery quality assurance (DQA) but there has never been a published comprehensive analysis of a patient-specific DQA process in a clinic. We proposed to evaluate 350 consecutive film-based patient-specific DQAs using statistical process control. We evaluated the performance of the process to propose achievable tolerance criteria for DQA validation and we sought to identify suboptimal DQA using control charts. METHODS AND MATERIAL: DQAs were performed on a CyberKnife-M6 using Gafchromic-EBT3 films...
July 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28710455/retrieving-precise-three-dimensional-deformation-on-the-2014-m6-0-south-napa-earthquake-by-joint-inversion-of-multi-sensor-sar
#4
Min-Jeong Jo, Hyung-Sup Jung, Sang-Ho Yun
We reconstructed the three-dimensional (3D) surface displacement field of the 24 August 2014 M6.0 South Napa earthquake using SAR data from the Italian Space Agency's COSMO-SkyMed and the European Space Agency's Sentinel-1A satellites. Along-track and cross-track displacements produced with conventional SAR interferometry (InSAR) and multiple-aperture SAR interferometry (MAI) techniques were integrated to retrieve the east, north, and up components of surface deformation. The resulting 3D displacement maps clearly delineated the right-lateral shear motion of the fault rupture with a maximum surface displacement of approximately 45 cm along the fault's strike, showing the east and north components of the trace particularly clearly...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28671745/specially-treated-aramid-fiber-stabilized-gel-emulsions-preparation-of-porous-polymeric-monoliths-and-highly-efficient-removing-of-airborne-hcho
#5
Jianfei Liu, Xiangli Chen, Pei Wang, Xuwei Fu, Kaiqiang Liu, Yu Fang
Porous polymeric monoliths with densities as low as ≈0.060 g cm(-3) are prepared in a gel-emulsion template way, of which the stabilizer employed is a newly discovered acidified aramid fiber that is so efficient that 0.05% (w/v, accounts for continuous phase) is enough to gel the system. The porous monoliths as obtained can be dried at ambient conditions, avoiding energy-consuming processes. Importantly, the monoliths show selective adsorption to HCHO, and the corresponding adsorption capacity (M6) is ≈2700 mg g(-1) , the best result that is reported until now...
July 3, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28669319/serum-inflammatory-molecules-and-markers-of-neuronal-damage-in-alcohol-dependent-subjects-after-withdrawal
#6
Murielle Girard, Dominique Malauzat, Philippe Nubukpo
OBJECTIVES: Our aim is to describe changes in serum concentration for the proinflammatory factors TNF-α, IFN-gamma, IL-1beta, IL-8, IL-6, IL-10, IL-12, and MCP-1, for the satiety factor leptin and for factors associated with neuronal changes, neuron-specific enolase (NSE) and glial activation S100-beta protein (S100-β), and explore their association with abstinence in alcohol dependent subjects after withdrawal. METHODS: Serum sampling and clinical assessments from 115 alcohol-dependent subjects admitted to a psychiatric hospital for alcohol were repeated during the first 48 hours of withdrawal (M0) and 1, 2, 4 and 6 months (M1, M2, M4, M6) after...
July 3, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28657423/in-vitro-metabolism-of-alectinib-a-novel-potent-alk-inhibitor-in-human-contribution-of-cyp3a-enzymes
#7
Toshito Nakagawa, Stephen Fowler, Kenji Takanashi, Kuresh Youdim, Tsuyoshi Yamauchi, Kosuke Kawashima, Mika Sato-Nakai, Li Yu, Masaki Ishigai
1. The in vitro metabolism of alectinib, a potent and highly selective oral anaplastic lymphoma kinase inhibitor, was investigated. 2. The main metabolite (M4) in primary human hepatocytes was identified, which is produced by deethylation at the morpholine ring. Three minor metabolites (M6, M1a, and M1b) were also identified, and a minor peak of hydroxylated alectinib (M5) was detected as a possible precursor of M4, M1a, and M1b. 3. M4, an important active major metabolite, was produced and further metabolized to M6 by CYP3A, indicating that CYP3A enzymes were the principal contributors to this route...
June 28, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28657157/cyberknife-with-integrated-ct-on-rails-system-description-and-first-clinical-application-for-pancreas-sbrt
#8
Chrysi Papalazarou, Gijsbert J Klop, Maaike T W Milder, Johannes P A Marijnissen, Vikas Gupta, Ben J M Heijmen, Joost J M E Nuyttens, Mischa S Hoogeman
PURPOSE: This paper reports on the integration of a sliding-gantry CT-on-rails with a robotic linear accelerator. METHODS: The system consists of a SOMATOM Definition AS CT scanner (Siemens Healthcare, Forchheim, Germany) and a CyberKnife M6 FIM (Accuray, Inc., Sunnyvale, CA, USA). Additional movement programs were implemented in the robotic treatment table (RoboCouch, Accuray Inc.) to move between CT and treatment position. Acceptance testing was performed on the CT scanner according to AAPM83 guidelines, as well as safety tests for collision avoidance and electromagnetic (EM) compatibility...
June 28, 2017: Medical Physics
https://www.readbyqxmd.com/read/28641617/-biological-characteristics-and-therapeutic-efficacy-of-103-patients-with-acute-erythroleukemia
#9
Yue Yin, Wen-Qi Zhan, Hui-Fang Huang, Chen-Qing Zhang, Dang-Hui Fu, Shu-Juan Xu, Jian-Da Hu, Xin-Ji Chen
OBJECTIVE: To investigate the biological characteristics and therapeutic efficacyt of acute erythroleukemia (AEL,AML-M6). METHODS: Blood cell count, liver function, lactate dehydrogenase level, coagulation, morphology, immunology, cell genetics and molecular biology were retrospectively analyzed in 103 cases of acute erythroleukemia patients admitted in our department from May 2016 to June 2009. The therapeutic efficacy was observed by means of remission rate, relapse rate, relapse-free survival and overall survival...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641005/electron-crystallography-reveals-atomic-structures-of-metal-organic-nanoplates-with-m12-%C3%AE-3-o-8-%C3%AE-3-oh-8-%C3%AE-2-oh-6-m-zr-hf-secondary-building-units
#10
Ruihan Dai, Fei Peng, Pengfei Ji, Kuangda Lu, Cheng Wang, Junliang Sun, Wenbin Lin
Nanoscale metal-organic frameworks (nMOFs) have shown tremendous potential in cancer therapy and biomedical imaging. However, their small dimensions present a significant challenge in structure determination by single-crystal X-ray crystallography. We report here the structural determination of nMOFs by rotation electron diffraction (RED). Two isostructural Zr- and Hf-based nMOFs with linear biphenyldicarboxylate (BPDC) or bipyridinedicarboxylate (BPYDC) linkers are stable under intense electron beams to allow the collection of high-quality RED data, which reveal a MOF structure with M12(μ3-O)8(μ3-OH)8(μ2-OH)6 (M = Zr, Hf) secondary building units (SBUs)...
July 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28627966/further-evidence-of-cucurbit-host-specificity-among-acidovorax-citrulli-groups-based-on-a-detached-melon-fruit-pathogenicity-assay
#11
Lichun Yan, Hu Baishi, Gong Chen, Mei Zhao, Ron Ricardo Walcott
Bacterial fruit blotch (BFB), caused by the gram-negative bacterium Acidovorax citrulli, is a serious economic threat to cucurbit crop production worldwide. A. citrulli strains can be divided into two genetically distinct groups with group I strains infecting a range of cucurbit species, and group II strains being predominantly associated with watermelon. Group I and II A. citrulli strains differ in their arsenal of type III secreted (T3S) effector proteins and we hypothesize that these effectors are critical for cucurbit host preference...
June 19, 2017: Phytopathology
https://www.readbyqxmd.com/read/28619503/clinical-pharmacokinetics-of-levornidazole-in-elderly-subjects-and-dosing-regimen-evaluation-using-pharmacokinetic-pharmacodynamic-analysis
#12
Beining Guo, Gaoli He, Xiaojie Wu, Jicheng Yu, Guoying Cao, Yi Li, Yaxin Fan, Yuancheng Chen, Yaoguo Shi, Yingyuan Zhang, Jing Zhang
PURPOSE: Levornidazole, the levo-isomer of ornidazole, is a third-generation nitroimidazole derivative newly developed after metronidazole, tinidazole, and ornidazole. An open-label, parallel-controlled, single-dose study was conducted for the investigation of the pharmacokinetic (PK) profile of levornidazole and its metabolites in healthy elderly Chinese subjects, and for the evaluation of 2 dosing regimens in the elderly. METHODS: Levornidazole was intravenously administered at 500 mg to healthy elderly (aged 60-80 years) or young subjects (aged 19-45 years)...
June 12, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28619437/fatigue-evaluation-in-fingolimod-treated-patients-an-observational-study
#13
Marion Masingue, Rabab Debs, Elisabeth Maillart, Valérie Delvaux, Catherine Lubetzki, Jean-Sébastien Vidal, Caroline Papeix
BACKGROUND: Fatigue is one of the most disabling symptoms in Multiple Sclerosis (MS) patients and is associated with a low quality of life. Fingolimod (Fg), a sphingosine 1-phosphate receptor modulator, is the first oral MS disease modifying treatment. Little is known about its effect on fatigue. To assess the impact of Fg on fatigue within the first 6 months of treatment in MS patients, we conducted a prospective, open label study, in real life setting. METHODS: Change of Modified Fatigue Impact Scale (MFIS) between Fg treatment start and at 6 months was used as a first outcome...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28616979/proposed-biotransformation-pathways-for-new-metabolites-of-paralytic-shellfish-toxins-based-on-field-and-experimental-mussel-samples
#14
Ling Ding, Jiangbing Qiu, Aifeng Li
A seafood poisoning event occurred in Qinhuangdao, China, in April 2016. Subsequently, the causative mussels (Mytilus galloprovincialis) were harvested and analyzed to reveal a high concentration [∼10 758 μg of saxitoxin (STX) equiv kg(-1)] of paralytic shellfish toxins (PSTs), including gonyautoxin (GTX)1/4 and GTX2/3, as well as new metabolites 11-hydroxy-STX (M2), 11,11-dihydroxy-STX (M4), open-ring 11,11-dihydroxy-STX (M6), 11-hydroxy-neosaxitoxin (NEO) (M8), and 11,11-dihydroxy-NEO (M10). To understand the origin and biotransformation pathways of these new metabolites, uncontaminated mussels (M...
July 12, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28611092/altering-metabolic-profiles-of-drugs-by-precision-deuteration-2-discovery-of-a-deuterated-analog-of-ivacaftor-with-differentiated-pharmacokinetics-for-clinical-development
#15
Scott L Harbeson, Adam J Morgan, Julie F Liu, Ara M Aslanian, Sophia Nguyen, Gary W Bridson, Christopher L Brummel, Lijun Wu, Roger D Tung, Lana Pilja, Virginia Braman, Vinita Uttamsingh
Ivacaftor is currently used for the treatment of cystic fibrosis as both monotherapy (Kalydeco®) and combination therapy with lumacaftor (Orkambi®). Each therapy targets specific patient populations: Kalydeco treats patients carrying one of nine gating mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR), while Orkambi treats patients homozygous for the F508del CFTR mutation. In this study, we explored the pharmacological and metabolic effects of precision deuteration chemistry on ivacaftor by synthesizing two novel deuterated ivacaftor analogs, CTP-656 (d9-ivacaftor) and d18-ivacaftor...
June 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28607829/adaptive-hypofractionated-gamma-knife-radiosurgery-in-the-acute-management-of-large-thymic-carcinoma-brain-metastases
#16
Georges Sinclair, Heather Martin, Michael Fagerlund, Amir Samadi, Hamza Benmakhlouf, Ernest Doodo
BACKGROUND: Brain metastases often lead to serious neurological impairment and life threatening states. Their acute management remains complex, particularly in the case of rare malignancies with aggressive evolution. In large single lesions, open surgery followed by radiation to the surgical cavity is widely regarded as the best approach; yet in many cases, microsurgery is not feasible due to the lesion's critical location and/or the number of brain metastases present. We report the effects of adaptive hypofractionated gamma knife radiosurgery in the acute management of critically located thymic carcinoma metastases...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28598126/-flt3-gene-expression-and-its-clinical-significance-in-acute-myeloid-leukemia
#17
Si-Shi Tang, Yuan-Xin Ye, Yan-Hong Zhou, Yi Zhou, Juan Zhou, Jiang Yu, Man-Ying Guo, Xiao-Jun Lu, Bin-Wu Ying
OBJECTIVES: To determine the correlation between fms-like tyrosine kinase 3 gene (FLT3) expression and FLT3-internal tandem duplication (ITD) mutations in acute myeloid leukemia patients,and the association between expression of FLT3 gene and clinical and laboratory features of patients. METHODS: The expression of FLT3 mRNA in bone marrow (BM) leukemic cells of 128 acute myeloid leukemia (AML) patients was measured by real-time PCR.The patients were divided into two groups using the 35% FLT3 expression as a cut-off point...
November 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28579219/-visual-outcomes-after-descemet-s-membrane-endothelial-keratoplasty
#18
A S Gauthier, M Castelbou, M Saleh, B Delbosc
OBJECTIVES: Evaluation and monitoring at 6 months after Descemet's membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy and study of factors influencing visual rehabilitation and postoperative quality of life. METHODS: Prospective, consecutive, interventional study of 35 eyes of 32 patients with Fuchs endothelial dystrophy who underwent surgery from February 2015 to February 2016 by DMEK. Measurement at D10, M1, M3, M6 of visual acuity, graft endothelial cell density, pachymetry, and intraocular pressure, and performance at M6 of aberrometry, macular OCT and a quality of life survey (NEI-VFQ-25)...
May 31, 2017: Journal Français D'ophtalmologie
https://www.readbyqxmd.com/read/28538261/physical-activity-and-sleep-quality-in-breast-cancer-survivors-a-randomized-trial
#19
Laura Q Rogers, Kerry S Courneya, Robert A Oster, Philip M Anton, Randall S Robbs, Andres Forero, Edward McAuley
PURPOSE: Data from large randomized controlled trials confirming sleep quality improvements with aerobic physical activity have heretofore been lacking for post-primary treatment breast cancer survivors. Our primary purpose for this report was to determine the effects of a physical activity behavior change intervention, previously reported to significantly increase physical activity behavior, on sleep quality in post-primary treatment breast cancer survivors. METHODS: Post-primary treatment breast cancer survivors (n=222) were randomized to a 3-month physical activity behavior change intervention (BEAT Cancer) or usual care...
May 20, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28535920/cyberknife%C3%A2-m6%C3%A2-peripheral-dose-evaluation-for-brain-treatments
#20
N Delaby, J Bellec, J Bouvier, F Jouyaux, M Perdrieux, J Castelli, I Lecouillard, J P Manens, C Lafond
PURPOSE: This study evaluates the peripheral dose (PD) delivered to healthy tissues for brain stereotactic radiotherapy treatments (SRT) performed with a CyberKnife M6™ Robotic Radiosurgery System and proposes a model to estimate PD before treatment. METHOD: PD was measured with thermoluminescent dosimeters. Measurements were performed to evaluate the influence of distance, collimator type (fixed or Iris™) and aperture size on PD for typical brain treatment plans simulated on an anthropomorphic phantom...
May 2017: Physica Medica: PM
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