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| 2. |
- Alves, Andreia, et al.
(författare)
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Case Study on Screening Emerging Pollutants in Urine and Nails
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:7, s. 4046-4053
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Tidskriftsartikel (refereegranskat)abstract
- Alternative plasticizers and flame retardants (FRs) have been introduced as replacements for banned or restricted chemicals, but much is still unknown about their metabolism and occurrence in humans. We identified the metabolites formed in vitro for four alternative plasticizers (acetyltributyl citrate (ATBC), bis(2-propylheptyl) phthalate (DPHP), bis(2-ethylhexyl) terephthalate (DEHTP), bis(2ethylhexyl) adipate (DEHA)), and one FR (2,2-bis (chloromethyl)-propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate (V6)). Further, these compounds and their metabolites were investigated by LC/ESI-Orbitrap-MS in urine and finger nails collected from a Norwegian cohort. Primary and secondary ATBC metabolites had detection frequencies (% DF) in finger nails ranging from 46 to 95%. V6 was identified for the first time in finger nails, suggesting that this matrix may also indicate past exposure to FRs as well as alternative plasticizers. Two isomeric forms of DEHTP primary metabolite were highly detected in urine (97% DF) and identified in finger nails, while no DPHP metabolites were detected in vivo. Primary and secondary DEHA metabolites were identified in both matrices, and the relative proportion of the secondary metabolites was higher in urine than in finger nails; the opposite was observed for the primary metabolites. As many of the metabolites present in in vitro extracts were further identified in vivo in urine and finger nail samples, this suggests that in vitro assays can reliably mimic the in vivo processes. Finger nails may be a useful noninvasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed.
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| 3. |
- Bennike, Niels H., et al.
(författare)
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Allergic contact dermatitis caused by hydroperoxides of limonene and dose-response relationship-A repeated open application test (ROAT) study
- 2019
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 80:4, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim-OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported. Objectives: To determine the clinical relevance, elicitation threshold and dose-response relationship of Lim-OOHs in individuals with a positive or doubtful patch test reaction to standard Lim-OOHs 0.3% pet. Methods: A multicentre 3-week double-blind vehicle-controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim-OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim-OOHs of 3.0, 0.99 and 0.33 mu g/cm(2), was performed. Results: Among 11 subjects allergic to Lim-OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim-OOHs, two (15%) had positive ROAT reactions to the highest Lim-OOH dose applied (P = 0.36 as compared with controls). Conclusions: Contact allergy to Lim-OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim-OOHs 0.3% pet. can be of clinical relevance.
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| 4. |
- Carlson-Nilsson, Ulrika
(författare)
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Facilitation of introgressive hybridization of wild polyploid mexican potato species using DNA markers of R genes and of different cytoplasmic types
- 2017
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Ingår i: Agricultural biology. - : Sel'skokhozyaistvennaya Biologiya Editorial Office (SBEO), NPO. - 2412-0324. ; 52, s. 964-975
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays potato breeding is targeting to develop genetically divers high yielding varieties with multiple pathogen resistance traits. Interspecific hybridization jointed with marker-Assistantselection (MAS) can effectively combine the R genes from different resistance sources. Additionally to effective pyramiding the target genes, MAS allows to restrict introgression of genetic factors conferring the undesirable traits, for example, male sterility of interspecific hybrids associated with Solanum stoloniferum-derived W/gamma cytoplasm that complicate the traditional breeding. Current study is targeting to search for the opportunities to improve the efficiency of introgressive hybridization between common potato and Mexican polyploid species Solanum. neoantipoviczii (=S. stoloniferum) and S. guerreroense using MAS with DNA markers for different cytoplasmic types and markers associated with major R-genes to the most harmful potato pathogens. DNA-based markers of genes for late blight resistance (R2 like, R3a, Rpi-blb1, Rpi-sto1), for extreme resistance to Potato virus Y (PVY) (Ryadg, Rysto, Ry-fsto) and for H1 gene for resistance to the root cyst nematode (Globodera rostochiensis, pathotype Ro1) were used in this study. Based on the MAS, hybrid genotypes with different combinations of these markers were selected. Among them, there were the clones with high field resistance to late blight and to PVY. Of 29 hybrid clones from different combinations of crossing with polyploid Mexican species used as the maternal forms, 15 had a W/α cytoplasmic type and were male sterile; both these traits were maternally inherited. The remaining hybrids with W/γ cytoplasm produced fertile pollen and were used in interspecific crosses as pollinators. Selection of resistant clones with W/alpha cytoplasm and elimination of genotypes with sterile W/γ cytoplasm among wild species germplasm could increase the probability of obtaining male fertile introgressive lines. This approach allows to obtain the multi-species hybrid genotypes that combine R genes for resistance to pathogens from different Mexican species and to avoid various types of male sterility in breeding. The joint use of two systems of DNA markers, i.e. nuclear markers associated to R genes, and cytoplasmic markers for male sterility factors, could reduce costs and increase efficiency of target gene pyramiding programs.
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| 7. |
- Eriksson, Dennis, et al.
(författare)
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Overview and Breeding Strategies of Table Potato Production in Sweden and the Fennoscandian Region
- 2016
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Ingår i: Potato Research. - : Springer Science and Business Media LLC. - 0014-3065 .- 1871-4528. ; 59, s. 279-294
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Tidskriftsartikel (refereegranskat)abstract
- Recent reductions in the public commitment to potato breeding in Sweden, Norway and Finland call for an evaluation of the current situation regarding the commercial basis for, and structure of, potato breeding in these countries. We here review the extent of cultivation, processing and consumption of table potato in Sweden, as well as provide an overview of the potato breeding tools and programmes in the three countries. We then discuss various strategies to provide long-term stability and increase the impact of public potato breeding, based on the similar overall conditions for potato cultivation across the Fennoscandian region. The conclusions are twofold; first, an increased long-term funding of the public potato breeding programmes is necessary to maintain a minimum level of material, and second, a coordination of the breeding activities in the Fennoscandian region would be of great benefit to all involved stakeholders and allow an enhancement of the current national breeding programmes. In addition, we propose a minimum first field year population size for potato breeding.
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| 8. |
- Gamal Ramzi, Ahmed, 1983-
(författare)
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Analytical methodologies for common skin allergens : Organic thioureas, isothiocyanates and fragrance hydroperoxides in everyday life products
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes analytical methodologies for the determination of important skin-sensitizing chemicals in two types of commercial items: chloroprene rubber and fragrance products which are both well-known to be associated with contact allergy.Chloroprene rubber (neoprene) is widely used in different applications and products, such as bags, gloves, wetsuits, braces, mouse pads et c. Exposure to chloroprene rubber materials has resulted in numerous cases of allergic contact dermatitis. Organic thioureas have been considered the main culprits, even though they at the same time have been classified as weak or non-sensitizers in the murine local lymph node assay (LLNA). Previous findings indicate that a possible reason for sensitization is that organic thioureas are being metabolized in the skin into more reactive electrophiles, such as isothiocyanates and isocyanates, after skin exposure. In this thesis, chemical analyses of a number of chloroprene products from the European open market showed the presence of diethylthiourea in all analyzed items, while other organic thioureas could not be detected. The levels of diethylthiourea varied, with the highest at 158 µg cm-2 in a used back support that had previously caused allergic contact dermatitis in a patient. Furthermore, it was discovered that all the examined items emitted ethyl isothiocyanate. LLNA showed that ethyl isothiocyanate is a strong skin sensitizer, as has been shown earlier for other tested isothiocyanates. Isothiocyanates were shown to be thermally formed from diethyl, diphenyl and dibutylthiourea at a temperature as low as 35 °C, i. e. around skin temperature. Altogether, the results from these experiments, patch tests and chemical analyses revealed that isothiocyanates are important haptens in contact allergy to chloroprene rubber.Fragrances constitute one of the main causes of contact allergy, next to nickel and preservatives. The most widespread fragrances in cosmetics and perfumes on the market are monoterpenes, such as linalool and limonene, which at air exposure easily oxidize to hydroperoxides, which are strongly skin sensitizing compounds and the main haptens. Despite this, there is so far no EU regulation concerning fragrance hydroperoxides in products, which may be due to lack of analytical methods which can reliably measure them in fragrances. Presented in this thesis is a toolbox of different analytical methods, applied on essential oils, shampoo, patch test preparations and different types of perfumes. Furthermore, one of our studies elucidated the first case (to my knowledge) of allergic contact dermatitis as being correlated to a product that contains a fragrance hydroperoxide.Taken together, the thesis shows the importance of developing analytical methods for the identification, measurement and detection of important haptens in contact allergy.
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| 9. |
- Gillen, Michael, et al.
(författare)
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Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort® (budesonide/formoterol) pressurized metered dose inhaler
- 2018
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Ingår i: Pulmonary Pharmacology and Therapeutics. - : Elsevier BV. - 1094-5539 .- 1522-9629. ; 52, s. 7-17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort® (budesonide/formoterol) pMDI 160/4.5 μg/actuation (2 actuations) used with and without a spacer device. In addition, an in vitro study was conducted to characterize performance of the inhaler when used in conjunction with a spacer device. Methods: A Phase I, randomized, open-label, single-dose, single-center, crossover study in 50 healthy volunteers (NCT02934607) assessed the relative bioavailability of single-dose Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) with and without a spacer (AeroChamber Plus® Flow-Vu®). Inhaled doses were administered without or with activated charcoal (taken orally) to estimate total systemic exposure and exposure through the lung, respectively. The in vitro study characterized the effect of the spacer with respect to delivered dose, fine particle dose, and dose during simulated breathing of budesonide and formoterol. Results: In terms of total systemic exposure, use of the spacer increased the relative bioavailability determined by AUC(0-last) and Cmax by 68% (spacer:no spacer treatment ratio, 167.9%; 90% CI, 144.1 to 195.6) and 99% (ratio, 198.7%; 90% CI, 164.4 to 240.2) for budesonide, and 77% (ratio, 176.6%; 90% CI, 145.1 to 215.0) and 124% (ratio, 223.6%; 90% CI, 189.9 to 263.3) for formoterol, respectively, compared with pMDI alone. Similarly, the lung exposure of budesonide and formoterol increased (AUC(0-last) and Cmax by 146% [ratio, 246.0%; 90% CI, 200.7 to 301.6] and 127% [ratio, 226.5%; 90% CI, 186.4 to 275.4] for budesonide, and 173% [ratio, 272.8%; 90% CI, 202.5 to 367.4] and 136% [ratio, 236.2%; 90% CI, 192.6 to 289.6] for formoterol, respectively) when the pMDI was administered through the spacer. When assessed by AUC(0-last) quartile without spacer, subjects in the lowest exposure quartile (indicating poor inhalation technique) with Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) had markedly increased total systemic and lung exposure when the same dose was administered with the spacer. In contrast, for subjects in the highest exposure quartile with pMDI alone, total systemic and lung exposure of formoterol and budesonide was similar with and without the spacer. In the in vitro study, the fine particle dose (<5 μm) of both budesonide and formoterol from the spacer at delay time (i.e. pause period after actuation) = 0 s (instantaneous) after actuation was similar to the fine particle dose when not using the spacer. The delivered doses of budesonide and formoterol from the spacer were both lower compared with the doses administered without the spacer. There was also a decrease in delivered dose with increasing delay time. Conclusions: The clinical study demonstrated that in subjects with poor inhalation technique the use of the AeroChamber Plus® Flow-Vu® spacer increased the bioavailability of Symbicort® pMDI to a level observed in subjects with good inhalation technique without a spacer. The findings from the in vitro study support the fine particle dose characteristics of Symbicort® pMDI with the AeroChamber Plus® Flow-Vu® spacer.
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