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- Andõn, F. T., et al.
(författare)
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Biodegradation of Single-Walled Carbon Nanotubes by Eosinophil Peroxidase
- 2013
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Ingår i: Small. - : Wiley-VCH Verlagsgesellschaft. - 1613-6810 .- 1613-6829. ; 9:16, s. 2721-2729
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O 2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. Human eosinophil peroxidase (EPO) is able to degrade SWCNTs in vitro in the presence of H2O2. EPO is one of the major oxidant-generating enzymes present in human lungs during inflammatory states. The biodegradation of SWCNTs is evidenced also in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. These results are relevant to potential respiratory exposure to carbon nanotubes.
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- Ungvari, Zoltan, et al.
(författare)
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Resistance to Genotoxic Stresses in Arctica islandica, the Longest Living Noncolonial Animal : Is Extreme Longevity Associated With a Multistress Resistance Phenotype?
- 2013
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 68:5, s. 521-529
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Tidskriftsartikel (refereegranskat)abstract
- Bivalve molluscs are newly discovered models of successful aging. Here, we test the hypothesis that extremely long-lived bivalves are not uniquely resistant to oxidative stressors (eg, tert-butyl hydroperoxide, as demonstrated in previous studies) but exhibit a multistress resistance phenotype. We contrasted resistance (in terms of organismal mortality) to genotoxic stresses (including topoisomerase inhibitors, agents that cross-link DNA or impair genomic integrity through DNA alkylation or methylation) and to mitochondrial oxidative stressors in three bivalve mollusc species with dramatically differing life spans: Arctica islandica (ocean quahog), Mercenaria mercenaria (northern quahog), and the Atlantic bay scallop, Argopecten irradians irradians (maximum species life spans: >500, >100, and ~2 years, respectively). With all stressors, the short-lived A i irradians were significantly less resistant than the two longer lived species. Arctica islandica were consistently more resistant than M mercenaria to mortality induced by oxidative stressors as well as DNA methylating agent nitrogen mustard and the DNA alkylating agent methyl methanesulfonate. The same trend was not observed for genotoxic agents that act through cross-linking DNA. In contrast, M mercenaria tended to be more resistant to epirubicin and genotoxic stressors, which cause DNA damage by inhibiting topoisomerases. To our knowledge, this is the first study comparing resistance to genotoxic stressors in bivalve mollusc species with disparate longevities. In line with previous studies of comparative stress resistance and longevity, our data extends, at least in part, the evidence for the hypothesis that an association exists between longevity and a general resistance to multiplex stressors, not solely oxidative stress. This work also provides justification for further investigation into the interspecies differences in stress response signatures induced by a diverse array of stressors in short-lived and long-lived bivalves, including pharmacological agents that elicit endoplasmic reticulum stress and cellular stress caused by activation of innate immunity.
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- Bhattacharya, Kunal, et al.
(författare)
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Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
- 2014
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 6:24, s. 14686-14690
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Tidskriftsartikel (refereegranskat)abstract
- Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising-and degradable-nanomedicine vector.
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- Star, Kristina, et al.
(författare)
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Pneumonia following antipsychotic prescriptions in electronic health records : a patient safety concern?
- 2010
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Ingår i: British Journal of General Practice. - 0960-1643 .- 1478-5242. ; 60:579, s. 749-755
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Tidskriftsartikel (refereegranskat)abstract
- Background In screening the Intercontinental Medical Statistics (IMS) Health Disease Analyzer database of GP records from the UK, an increased registration of pneumonia subsequent to the prescription of some antipsychotic medicines was identified. Aim To investigate the temporal pattern between antipsychotic prescriptions and pneumonia with respect to age, type of pneumonia and other chest infections, and antipsychotic class. Design of study Self-controlled cohort analysis. Setting Electronic health records from the UK IMS Health Disease Analyzer database. Method Three groups of pneumonia-related International Classification of Diseases (ICD)-10 terms and prescriptions of atypical and conventional antipsychotic medicines were studied. Separate analyses were carried out for patients aged >= 65 years. The observed rate of pneumonia terms registered in different time periods in connection to antipsychotic prescriptions was contrasted to the overall rate of pneumonia terms relative to prescriptions of other drugs in the same dataset. Results In patients aged >= 65 years, an increased registration of a group of terms defined as 'acute chest infections', after atypical antipsychotic prescriptions, was identified. The corresponding increase after conventional antipsychotic prescriptions was much smaller. Bronchopneumonia had a striking increase after both atypical and conventional antipsychotic prescriptions, and was commonly recorded with fatal outcome. Few registrations of hypostatic. pneumonia were noted. Patients aged <65 years did not have a higher rate of acute chest infections after receiving antipsychotic prescriptions. Conclusion The consistent pattern of an increased rate of chest infections after atypical antipsychotic prescriptions in older people seen in this outpatient study, together with the higher risk shown in a previous study on hospitalised patients, suggests a causal relationship. This is of importance since bronchopneumonia seems highly linked to fatal outcome. In the absence of a mechanism, further investigation of the role of antipsychotics in older people is needed.
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