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991.
Anna Murphy Kate Sheehy Alan Casey Gordon Chambers 《Journal of applied toxicology : JAT》2015,35(6):665-680
Establishing realistic exposure scenarios is critical for cytotoxic investigation of silver nanoparticles (AgNP) in the gastrointestinal tract. This study investigated the potential interaction with and effect of biofluid components, namely cholic acid, deoxycholic acid and ursodeoxycholic acid, on AgNP toxicity. Two cell lines corresponding to organs related to the biofluid components were employed. These were HepG‐2 a hepatocellular carcinoma derived from liver tissue and Hep2 an epithelial cell line. Physiochemical and cytotoxic screening was performed and the ability of biofluid components to modify AgNP cytotoxicity was explored. No alteration to the physiochemical characteristics of AgNP by biofluid components was demonstrated. However, biofluid component addition resulted in alteration of AgNP toxicity. Greater reactive oxygen species induction was noted in the presence of cholic acid and deoxycholic acid. Ursodeoxycholic acid demonstrated no modification of toxicity in HepG‐2 cells; however, significant modification was noted in Hep2 cells. It is concluded that biofluid components can modify AgNP toxicity but this is dependent on the biofluid component itself and the location where it acts. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
992.
Investigation on cobalt‐oxide nanoparticles cyto‐genotoxicity and inflammatory response in two types of respiratory cells
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Delia Cavallo Aureliano Ciervo Anna Maria Fresegna Raffaele Maiello Paola Tassone Giuliana Buresti Stefano Casciardi Sergio Iavicoli Cinzia Lucia Ursini 《Journal of applied toxicology : JAT》2015,35(10):1102-1113
The increasing use of cobalt oxide (Co3O4) nanoparticles (NPs) in several applications and the suggested genotoxic potential of Co‐oxide highlight the importance of evaluating Co3O4 NPs toxicity. Cyto‐genotoxic and inflammatory effects induced by Co3O4 NPs were investigated in human alveolar (A549), and bronchial (BEAS‐2B) cells exposed to 1–40 µg ml–1. The physicochemical properties of tested NPs were analysed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cytotoxicity was studied to analyze cell viability (WST1 test) and membrane damage (LDH assay), direct/oxidative DNA damage was assessed by the Formamido‐pyrimidine glycosylase (Fpg)‐modified comet assay and inflammation by interleukin (IL)‐6, IL‐8 and tumor necrosis factor‐alpha (TNF‐α) release (ELISA). In A549 cells, no cytotoxicity was found, whereas BEAS‐2B cells showed a viability reduction at 40 µg ml–1 and early membrane damage at 1, 5 and 40 µg ml–1. In A549 cells, direct and oxidative DNA damage at 20 and 40 µg ml–1 were detected without any effects on cytokine release. In BEAS‐2B cells, significant direct DNA damage at 40 µg ml–1 and significant oxidative DNA damage with a peak at 5 µg ml–1, that was associated with increased TNF‐α release at 1 µg ml–1 after 2 h and increased IL‐8 release at 20 µg ml–1 after 24 h, were detected. The findings show in the transformed alveolar cells no cytotoxicity and genotoxic/oxidative effects at 20 and 40 µg ml–1. In normal bronchial cells, moderate cytotoxicity, direct DNA damage only at the highest concentration and significant oxidative‐inflammatory effects at lower concentrations were detected. The findings confirm the genotoxic‐oxidative potential of Co3O4 NPs and show greater sensitivity of BEAS‐2B cells to cytotoxic and oxidative‐inflammatory effects suggesting the use of different cell lines and multiple end‐points to elucidate Co3O4 NPs toxicity. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
993.
Laura Rabinovich-Guilatt Anna Elgart Lavi Erisson Sandra K Willsie Shoshi Tessler Ofra Barnett-Griness Amitkumar Pande Ofer Spiegelstein 《British journal of clinical pharmacology》2015,80(3):436-445
Aims
Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects.Methods
Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated.Results
AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration–effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience.Conclusion
Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen. 相似文献994.
Anna M. de Haan Albert E. Boon Robert R. J. M. Vermeiren Machteld Hoeve Joop T. V. M. de Jong 《Child & youth care forum》2015,44(1):1-16
Background
Dropout from child and adolescent psychotherapy is a common phenomenon which can have negative consequences for the individual later in life. It is therefore important to gain insight on dropout risk factors.Objective
Several potential risk factors [ethnic minority status, a lower socioeconomic status (SES), and higher problem severity] were analyzed in present study. Innovations are that these risk factors were examined for children and adolescents separately, and a distinction was made in termination status between referred patients, dropouts and completers.Methods
For ethnic majority and minority outpatient children (age 5–11, n = 399) and adolescents (age 12–20, n = 352) problem severity, ethnic background, SES, and treatment termination status (completer, dropout, referral) were specified. Multinomial logistic regression models were used as main method of analysis.Results
For children, a Moroccan/Turkish ethnicity and higher externalizing scores were risk factors for being referred. For adolescents, a Surinamese/Antillean ethnicity, being female, being older, and lower parental SES occupation levels were risk factors for dropout.Conclusions
Different dropout risk profiles emerged for children versus adolescents, and for dropouts versus referrals. Also, it depended on the specific ethnic background whether ethnic minority status was a predictor for dropout, and the relationship between SES and termination status differed by whether parental SES occupation or parental SES education were used as SES indicator. Professionals should thus be aware of these potential risk factors for dropout or referral when treating children and adolescents.995.
The perceived impact of public involvement in palliative care in a provincial palliative care network in the Netherlands: a qualitative study
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996.
997.
Great ‘app‐eal’ but not there yet: A review of iPhone nutrition applications relevant to child weight management
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998.
999.
Justyna Kalinowska-Tucik Jakub Staro Anna Krawczuk Stefan Mordalski Dawid Warszycki Grzegorz Sataa Adam S. Hogendorf Andrzej J. Bojarski 《RSC advances》2018,8(33):18672
The development of compounds with enhanced activity and selectivity by a conserved spatial orientation of the pharmacophore elements has a long history in medicinal chemistry. Rigidified compounds are an example of this concept. However, the intramolecular interactions were seldom used as a basis for conformational restraints. Here, we show the weak intramolecular interactions that contribute to the relatively well-conserved geometry of N1-arylsulfonyl indole derivatives. The structure analysis along with quantum mechanics calculations revealed a crucial impact of the sulfonyl group on the compound geometry. The weak intramolecular C–H⋯O interaction stabilizes the mutual "facing" orientation of two aromatic fragments. These findings extend the pharmacological interpretation of the sulfonyl group role from the double hydrogen bond acceptor to the conformational scaffold based on intramolecular forces. This feature has, to date, been omitted in in silico drug discovery. Our results should increase the awareness of researchers to consider the conformational preference when designing new compounds or improving computational methods.The impact of weak intramolecular C–H⋯O interactions on the conformational stability of bis-arylsulfones is discussed, suggesting different role of sulfonyl group in the ligand – 5HT6 receptor interaction. 相似文献
1000.
Do patients’ information requirements for choice in health care vary with their socio‐demographic characteristics?
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Anthony A. Laverty MSc Anna Dixon PhD Christopher Millett PhD 《Health expectations》2015,18(5):1127-1138