Reactive Intermediates and Bioactivation Pathways Characterization of Avitinib by LC-MS/MS: In vitro Metabolic Investigation
Publication date: Available online 17 November 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Mohamed W. Attwa, Adnan A. Kadi, Ali S. AbdelhameedAbstractAvitinib (AC0010) is a third generation inhibitor of the EGFR (epidermal growth factor receptor) that was permitted parallel phase I clinical trials in the US and in 2014. It is estimated to enter in market within two years. In the current study, eight in vitro metabolites were detected and their chemical structures were postulated. The main in vitro phase-I metabolic reaction was N-oxidation in piperazine moiety. The generation of reactive metabolites in avitinib metabolism was investigated using rat liver microsomes while adding capturing agents, viz potassium cyanide for reactive iminium intermediates, GSH for iminoquinones and methoxylamine for aldehyde forming stable adducts which are identifiable by LC-MS/MS. Ten reactive intermediates (four iminoquinones, three iminium and three aldehydes) were characterized. The three capturing agents used resulted in proposing four different bioactivation pathways. Upon literature examination, no former articles were found for avitinib metabolism including the produced reactive metabolites.Graphical abstract
Publication date: Available online 16 November 2019Source: Journal of Health EconomicsAuthor(s): Dimitris Christelis, Dimitris Georgarakos, Anna Sanz-de-GaldeanoAbstractEconomic theory predicts that a reduction in background risk should induce financial risk-taking, particularly for individuals with low stock market participation costs. Hence, health insurance coverage could affect financial risk-taking by offsetting health-related background risk. We use a regression discontinuity design to examine whether Medicare eligibility at age 65 increases stockholding in the US and find that it does so for those with college educa...
In this study, serum IL6 was measured by ELISA, and the HSD11B1rs12086634(T/G) polymorphism was analyzed using a TaqMan allelic discrimination assay technique. There were statistically significant differences between the two studied groups concerning the serum IL-6 level and HSD11B1rs12086634(T/G) genotype distribution, with increased serum IL6 and increased frequencies of the GG and TG genotypes in patients with PCO. The GG genotype of HSD11B1 rs12086634(T/G) and its associated high level of serum IL-6 may represent genetic risk factors for PCOS.
Publication date: Available online 17 November 2019Source: European UrologyAuthor(s): Tom Marcelissen, Kevin Rademakers
Publication date: Available online 17 November 2019Source: European UrologyAuthor(s): Zhengzheng Xu, Guangzhe Ge, Bao Guan, Zhentao Lei, Xueyu Hao, Yuanyuan Zhou, Yue Shi, Huan Lu, Jilu Wang, Ding Peng, XiKang Wu, Huiying He, Bao Zhang, Xuesong Li, Liqun Zhou, Weimin Ci
Publication date: Available online 16 November 2019Source: European UrologyAuthor(s): Pirus Ghadjar, Thomas Wiegel
Publication date: Available online 16 November 2019Source: European UrologyAuthor(s): Elise De Bleser, Piet Ost
ConclusionThe CFQL-2 is a brief, reliable scale that effectively measures psychosocial aspects of QoL and is sensitive to changes in QoL in families of children with ASD or related neurodevelopmental disorders. Child externalizing behavior is strongly associated with reductions in multiple aspects of child and family psychosocial QoL.
ConclusionThis meta-analysis suggested a significant association between MTHFR gene polymorphism (C677T and A1298C) and ASD risk.
ConclusionGiven that obtaining negative margins is important in reducing the risk of recurrence, the method of surgical resection utilized is based on the amount of future functional residual hepatic parenchyma.
ConclusionsTattooing of axillary LNs is safe and easily performed. Tattooing was helpful in identifying the marked LN in the majority of cases. This technique helps to ensure that metastatic LNs are identified and removed at surgery after NAT.