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| 2. |
- Johansson, Henrik, et al.
(författare)
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Genomic Allergen Rapid Detection In-House Validation—A Proof of Concept
- 2014
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-0929 .- 1096-6080. ; 139:2, s. 362-370
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Tidskriftsartikel (refereegranskat)abstract
- Chemical sensitization is an adverse immunologic response to chemical substances, inducing hypersensitivity in exposed individuals. Identifying chemical sensitizers is of great importance for chemical, pharmaceutical and cosmetic industry, in order to prevent the use of sensitizers in consumer products. Historically, chemical sensitizers have been assessed mainly by in vivo methods, however, recently enforced European legislations urge and promote the development of animal-free test methods able to predict chemical sensitizers. Recently, we presented a predictive biomarker signature in the myeloid cell line MUTZ-3, for assessment of skin sensitizers. The identified genomic biomarkers were found to be involved in immunologically relevant pathways, induced by recognition of foreign substances and regulating dendritic cell maturation and cytoprotective mechanisms. We have developed the usage of this biomarker signature into a novel in vitro assay for assessment of chemical sensitizers, called Genomic Allergen Rapid Detection, GARD. The assay is based on chemical stimulation of MUTZ-3 cultures, using the compounds to be assayed as stimulatory agents. The readout of the assay is a transcriptional quantification of the genomic predictors, collectively termed the GARD Prediction Signature, using a complete genome expression array. Compounds are predicted as either sensitizers or non-sensitizers by a Support Vector Machine model. In this report, we provide a proof of concept for the functionality of the GARD assay by describing the classification of 26 blinded and 11 non-blinded chemicals as sensitizers or non-sensitizers. Based on these classifications, the accuracy, sensitivity and specificity of the assay was estimated to 89%, 89% and 88%, respectively.
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| 3. |
- Kronstrand, Robert, et al.
(författare)
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Fatal intoxications associated with the designer opioid AH-7921
- 2014
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 38:8, s. 599-604
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Tidskriftsartikel (refereegranskat)abstract
- AH-7921 (3,4-dichloro-N-[(1-dimethylamino) cyclohexylmethyl] benzamide) is a designer opioid with similar to 80% of morphines m-agonist activity. Over a 6-month period, we encountered nine deaths where AH-7921 was involved and detected in blood from the deceased. Shortly after the last death, on August 1 2013, AH-7921 was scheduled as a narcotic and largely disappeared from the illicit market in Sweden. AH-7921 was measured by a selective liquid chromatography- MS-MS method and the concentrations of AH-7921 ranged from 0.03 to 0.99 mu g/g blood. Six of our cases had other drugs of abuse on board and most had other medications such as benzodiazepines, antidepressants and analgesics. However, the other medicinal drugs encountered were present in postmortem therapeutic concentrations and unlikely to have contributed to death. In addition to the parent compound, we identified six possible metabolites where two N-demethylated dominated and four mono-hydroxylated were found in trace amounts in the blood. In conclusion, deaths with AH-7921 seem to occur both at low and high concentrations, probably a result of different tolerance to the drug. Hence, it is reasonable to assume that no sharp dividing line exists between lethal and non-lethal concentrations. Further, poly-drug use did not seem to be a major contributing factor for the fatal outcome.
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- Lindstedt, B A, et al.
(författare)
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Use of multilocus variable-number tandem repeat analysis (MLVA) in eight European countries, 2012
- 2013
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Genotyping of important medical or veterinary prokaryotes has become a very important tool during the last decades. Rapid development of fragment-separation and sequencing technologies has made many new genotyping strategies possible. Among these new methods is multilocus variable-number tandem repeat analysis (MLVA). Here we present an update on the use of MLVA in eight European countries (Denmark, France, Germany, Ireland, Italy, the Netherlands, Norway and Sweden). Researchers in Europe have been active in developing and implementing a large array of different assays. MLVA has been used as a typing tool in several contexts, from aiding in resolving outbreaks of foodborne bacteria to typing organisms that may pose a bioterrorist threat, as well as in scientific studies.
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