| 1. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 2. |
- Isaksson, Hanna, et al.
(författare)
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High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects
- 2013
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Ingår i: Food & Nutrition Research. - Järfälla : Co-Action Publishing. - 1654-6628 .- 1654-661X. ; 57, s. 18519-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. Objective: In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Design: Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. Results: The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.
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| 3. |
- Ollila, Hanna M., et al.
(författare)
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Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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| 4. |
- Alexanderson, Helena, et al.
(författare)
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Coupled luminescence and cosmogenic nuclide dating of postglacial deflation surfaces and sand drift on a raised ice-contact delta at Veinge, SW Sweden
- 2024
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Ingår i: Quaternary Geochronology. - 1871-1014. ; 80
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Tidskriftsartikel (refereegranskat)abstract
- Wind-abraded cobbles (ventifacts) and aeolian sand are known from the sandy-gravelly coastal areas of south-western Sweden, especially in association with raised deltas. Ventifacts are recorded on at least two different stratigraphic levels, at some sites atop glaciofluvial sediment, at other sites atop littoral deposits, and in some places at both levels, while aeolian sand usually forms a surficial cover. The formation of ventifacts has usually been coupled to abrasion due to katabatic winds from the retreating ice sheet or with periglacial climate during the Younger Dryas stadial (12.8–11.7 ka).To determine the timing of these deflation events, we have applied a combination of dating methods to ventifacts and associated sediments on top of an ice-contact delta at Veinge, south-western Sweden. Quartz and feldspar luminescence dating as well as portable luminescence profiling has been used for littoral and aeolian sediments over- and underlying deflation surfaces, while rock surface luminescence burial dating and paired 14C–10Be cosmogenic nuclide dating were conducted on ventifacts. The results show that a first deflation event occurred c. 16.5 ka, just after deglaciation and prior to a regional transgression that peaked around 15.7 ka. At 12.4–11.4 ka, during the Younger Dryas stadial, a new set of ventifacts formed on the surface of the exposed littoral sands and gravels. Some wind abrasion also occurred in the early Holocene, but at c. 8.5 ka the surface was covered by aeolian sand, up to 2.5 m thick.The combination of different dating methods have allowed us to draw more informed conclusions on the timing and duration of these wind abrasion/transport events than would have been possible from the use of only single-method dating. It has also made it possible to infer some environmental conditions during deposition. For example, both glaciofluvial and littoral deposits show evidence of incomplete bleaching of the luminescence signal. This suggests short subaerial transport and brief reworking by waves, respectively, though bleaching conditions improved during shore regression. Rock surface burial luminescence profiles reveal that some ventifacts were repeatedly exposed, but that later event(s) were shorter in duration as indicated by quartz-feldspar age comparisons.
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| 5. |
- Alexanderson, Helena, et al.
(författare)
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Late glacial to Early Holocene deflation events and aeolian deposition on a raised ice-contact delta at Veinge, SW Sweden
- 2024
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Wind-abraded cobbles (ventifacts) and aeolian sand are known from the sandy-gravelly coastal areas of south-western Sweden, especially in association with raised deltas. Ventifacts are recorded on at least two different stratigraphic levels, on top of glaciofluvial sediment and/or on top of littoral deposits, while aeolian sand usually forms a surficial cover. The formation of ventifacts has usually been coupled to abrasion due to katabatic winds from the retreating ice sheet or with periglacial climate during the Younger Dryas stadial (12.8-11.6 ka). However, there are very few absolute ages, and the timing of wind deflation has recently been challenged and proposed to be much older (110-70 ka). To determine the timing of these deflation events, we have applied a combination of dating methods to ventifacts and associated sediments on top of an ice-contact delta at Veinge, south-western Sweden. Quartz and feldspar luminescence dating as well as portable luminescence profiling has been used for the over- and underlying sediments, while rock surface luminescence burial dating and paired 14C10Be cosmogenic nuclide dating were done on ventifacts. The results show that a first deflation event occurred c. 16.5 ka, just after deglaciation and prior to a regional transgression that peaked around 15.7 ka. At 12.4-11.4 ka, during and just after the Younger Dryas stadial, a new set of ventifacts formed on the surface of the exposed littoral sands and gravels. Some wind abrasion also occurred in the early Holocene, but at c. 8.5 ka the surface was covered by aeolian sand, up to 2.5 m thick. The combination of dating methods allowed us to extract more information about the timing and duration of these wind abrasion/transport events than we would have if only a single method had been used, and it is also possible to infer some environmental conditions. For example, both glaciofluvial and littoral deposits show evidence of incomplete bleaching of the luminescence signal. This suggests short subaerial transport and brief reworking by waves, respectively, though bleaching conditions improved during shore regression. Rock surface burial luminescence profiles reveal that some ventifacts were repeatedly exposed, but that later event(s) were shorter in duration as indicated by quartz-feldspar age comparisons.
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| 6. |
- Anjar, Johanna, et al.
(författare)
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Palaeoenvironments in the southern Baltic Sea Basin during Marine Isotope Stage 3 : a multi-proxy reconstruction
- 2012
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 34, s. 81-92
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Tidskriftsartikel (refereegranskat)abstract
- Sediment cores from Kriegers Flak in the southwestern Baltic Sea provide a unique possibility to study the Middle Weichselian history of the Baltic Basin. Three Weichselian interstadial units have been identified and are attributed to Marine Isotope Stage 3 (MIS 3, 60-25 ka). The oldest unit A is characterized by a deglaciation sequence, gradually turning into brackish-water clay. The low-diversity benthic foraminiferal fauna, stable oxygen isotope values and Mg/Ca ratios indicate low temperature and salinity for unit A. A hiatus separates unit A from the overlying unit B, which was deposited in wetlands and shallow lakes between 42 and 36 cal. ka BP. Macrofossil and pollen analyses indicate deposition of unit B in an area dominated by a tree-less open tundra environment, possibly with some birch and pine in sheltered positions. The uppermost unit C is characterized by clay deposition, including redeposition of material from older sediments (unit B). Optically stimulated luminescence (OSL) ages indicate deposition of unit C between 26 and 28.5 ka. Radiocarbon ages of 39 and 40 cal. ka BP for unit C are considered to be too old. The following depositional model is suggested: (I) Isostatic depression of the region after an advance of the Scandinavian Ice Sheet (SIS), most likely the Ristinge ice advance, previously dated to c. 55-50 ka, enabled an inflow of marine waters into the Baltic Basin during the deposition of unit A. (II) Isostatic rebound caused a regression at Kriegers Flak, and a hiatus between units A and B. (III) Wetlands and smaller lakes formed in the uplifted area between 42 and 36 cal. ka BP (unit B). (IV) Deposition of glaciolacustrine clays at Kriegers Flak demonstrates that a growing SIS dammed Kattegat and the Baltic Basin c. 28.5 to 26 ka. The new evidence from Kriegers Flak provides a solid framework for future MIS 3 palaeoenvironmental reconstructions in the circum-Baltic area.
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| 7. |
- Chapman, Elizabeth A., et al.
(författare)
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Perennials as Future Grain Crops : Opportunities and Challenges
- 2022
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Perennial grain crops could make a valuable addition to sustainable agriculture, potentially even as an alternative to their annual counterparts. The ability of perennials to grow year after year significantly reduces the number of agricultural inputs required, in terms of both planting and weed control, while reduced tillage improves soil health and on-farm biodiversity. Presently, perennial grain crops are not grown at large scale, mainly due to their early stages of domestication and current low yields. Narrowing the yield gap between perennial and annual grain crops will depend on characterizing differences in their life cycles, resource allocation, and reproductive strategies and understanding the trade-offs between annualism, perennialism, and yield. The genetic and biochemical pathways controlling plant growth, physiology, and senescence should be analyzed in perennial crop plants. This information could then be used to facilitate tailored genetic improvement of selected perennial grain crops to improve agronomic traits and enhance yield, while maintaining the benefits associated with perennialism.
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| 8. |
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| 9. |
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| 10. |
- Eriksen, Anne Kirstine, et al.
(författare)
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Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: A randomized crossover trial
- 2020
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 111:4, s. 864-876
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Tidskriftsartikel (refereegranskat)abstract
- A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. Objectives: The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. Methods: Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. Results: The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. Conclusions: WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.
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| 11. |
- Gommenginger, Christine, et al.
(författare)
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SEASTAR: A mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUL
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere e.g. freshwater, pollutants. As numerical models continue to evolve towards finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed towards spaceborne implementation within Europe and beyond.
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| 12. |
- Grüning, Björn, et al.
(författare)
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Bioconda: A sustainable and comprehensive software distribution for the life sciences
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
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| 13. |
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| 14. |
- Helgeland, Øyvind, et al.
(författare)
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Characterization of the genetic architecture of infant and early childhood body mass index.
- 2022
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:3, s. 344-358
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Tidskriftsartikel (refereegranskat)abstract
- Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform genome-wide association studies across 12 time points from birth to 8 years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are overrepresented near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1 and KLF14 point towards a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profiles through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth.
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| 15. |
- Helgeland, Øyvind, et al.
(författare)
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Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6-12 months (rs2767486, P6m=2.0×10-21, β6m=0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P1.5y=1.3×10-8, β1.5y=0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.
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| 16. |
- Hjorth, Martin, et al.
(författare)
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Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
- 2012
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Ingår i: European journal of haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:6, s. 485-496
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions: Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
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| 17. |
- Just, Mie Kristine, et al.
(författare)
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Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies
- 2022
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Ingår i: Frontiers in Aging Neuroscience. - : FRONTIERS MEDIA SA. - 1663-4365. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Pathogenic alpha-synuclein (asyn) aggregates are a defining feature of neurodegenerative synucleinopathies, which include Parkinsons disease, Lewy body dementia, pure autonomic failure and multiple system atrophy. Early accurate differentiation between these synucleinopathies is challenging due to the highly heterogeneous clinical profile at early prodromal disease stages. Therefore, diagnosis is often made in late disease stages when a patient presents with a broad range of motor and non-motor symptoms easing the differentiation. Increasing data suggest the clinical heterogeneity seen in patients is explained by the presence of distinct asyn strains, which exhibit variable morphologies and pathological functions. Recently, asyn seed amplification assays (PMCA and RT-QuIC) and conformation-specific ligand assays have made promising progress in differentiating between synucleinopathies in prodromal and advanced disease stages. Importantly, the cellular environment is known to impact strain morphology. And, asyn aggregate pathology can propagate trans-synaptically along the brain-body axis, affecting multiple organs and propagating through multiple cell types. Here, we present our hypothesis that the changing cellular environments, an asyn seed may encounter during its brain-to-body or body-to-brain propagation, may influence the structure and thereby the function of the aggregate strains developing within the different cells. Additionally, we aim to review strain characteristics of the different synucleinopathies in clinical and preclinical studies. Future preclinical animal models of synucleinopathies should investigate if asyn strain morphology is altered during brain-to-body and body-to-brain spreading using these seeding amplification and conformation-specific assays. Such findings would greatly deepen our understanding of synucleinopathies and the potential link between strain and phenotypic variability, which may enable specific diagnosis of different synucleinopathies in the prodromal phase, creating a large therapeutic window with potential future applications in clinical trials and personalized therapeutics.
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| 18. |
- Knudsen, J.F., et al.
(författare)
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The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II
- 2004
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 28:5, s. 285-290
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Tidskriftsartikel (refereegranskat)abstract
- Cyclooxygenase-2 (COX-2) is up-regulated in stromal and inflammatory cells. The inducible COX-2 isoform is expressed during inflammation, in some cancers, and in brain tissue after global and focal ischemia. Tissue acidosis is a dominant factor in inflammation, and contributes to pain and hyperalgesia. Recently, compelling epidemiological and clinical evidence has documented the COX-independent effects of some COX-2 inhibitors (i.e., celecoxib, valdecoxib, and rofecoxib), among these effects are carbonic anhydrase (CA) inhibition. Carbonic anhydrases are zinc metalloenzymes expressed in various cell types, including those of the kidney, where they act as general acid-base catalysts. The kidneys are also known to express the highest concentration of COX-2 messenger ribonucleic acid. Celecoxib, like the prototypic CA inhibitor acetazolamide, is structurally characterized by an unsubstituted sulfonamide moiety. In the present study, we report that celecoxib exhibits the characteristics of a potent CA inhibitor, showing inhibitory human carbonic anhydrase II (hCAII) activity in the nanomolar range. Valdecoxib was relatively less potent. Rofecoxib, which lacks the unsubstituted sulfonamide moiety characteristic of CA inhibitors, showed no significant hCAII inhibitory activity. The current study corroborates our earlier report of structure-activity relationships as predictors of such metabolic events as hyperchloremia, acidosis, and changes in calcium and phosphate disposition, and clinical manifestations associated with CA inhibition reported with celecoxib. These data showing inhibition of hCAII by the unsubstituted sulfonamides celecoxib and valdecoxib, but not by rofecoxib, may have important implications for the elucidation of the mechanisms of action as well as the side effects associated with COX-2 inhibitors. © 2004 Springer Science+Business Media, Inc.
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| 19. |
- Knudsen, Markus Dines, et al.
(författare)
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Self-Reported Whole-Grain Intake and Plasma Alkylresorcinol Concentrations in Combination in Relation to the Incidence of Colorectal Cancer
- 2014
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 179:10, s. 1188-1196
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Tidskriftsartikel (refereegranskat)abstract
- Self-reported food frequency questionnaires (FFQs) have occasionally been used to investigate the association between whole-grain intake and the incidence of colorectal cancer, but the results from those studies have been inconsistent. We investigated this association using intakes of whole grains and whole-grain products measured via FFQs and plasma alkylresorcinol concentrations, a biomarker of whole-grain wheat and rye intake, both separately and in combination (Howe's score with ranks). We conducted a nested case-control study in a cohort from a research project on Nordic health and whole-grain consumption (HELGA, 1992-1998). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression. Plasma alkylresorcinol concentrations alone and Howe's score with ranks were inversely associated with the incidence of distal colon cancer when the highest quartile was compared with the lowest (for alkylresorcinol concentrations, incidence rate ratio = 0.34, 95% confidence interval: 0.13, 0.92; for Howe's score with ranks, incidence rate ratio = 0.35, 95% confidence interval: 0.15, 0.86). No association was observed between whole-grain intake and any colorectal cancer (colon, proximal, distal or rectum cancer) when using an FFQ as the measure/exposure variable for whole-grain intake. The results suggest that assessing whole-grain intake using a combination of FFQs and biomarkers slightly increases the precision in estimating the risk of colon or rectal cancer by reducing the impact of misclassification, thereby increasing the statistical power of the study.
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| 20. |
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| 21. |
- Knudsen, Per Kristian, et al.
(författare)
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Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic fibrosis centres in Denmark, Norway and Sweden
- 2009
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 8:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic Pseudomonas aeruginosa (PA) infection causes increased morbidity and mortality in cystic fibrosis (CF). This study aimed to answer the following questions: Does the prevalence of chronic infection with PA differ between the CF centres in Scandinavia? Which differences exist concerning segregation and treatment of PA? METHODS: 989 patients (86%) from all eight CF-centres in Scandinavia were included. Demographic and clinical data, including PA colonisation status based on cultures and serology, were recorded at inclusion. The patients were followed prospectively for 1 year, recording number of days with anti-PA antibiotic treatment. RESULTS: In all pancreatic insufficient (PI) patients (n=890) the prevalence of chronic PA infection at each centre ranged from 25.8% to 48.9%, but were not significantly different. In PI patients <19 years the prevalence was 14.5% in Copenhagen compared to 30.9% in the Swedish centres pooled (p=0.001). In intermittently colonised PI patients <19 years the median number of days per year on anti-PA antibiotics was almost 6 times higher in Copenhagen (mean 86 (110), median 61 days) compared to the Swedish centres pooled (mean 27 (52), median 11 days) (p=0.037). The pulmonary function was similar. CONCLUSIONS: It is possible to maintain a very low prevalence of chronic PA infection in CF patients <19 years. We speculate that this was most likely due to a very intensive treatment of intermittently colonised patients with inhaled anti-PA antibiotics over prolonged periods of time in some centres. Since lung function was similar in centres with less intensive use of inhaled antibiotics, studies comparing different treatment modalities and other parts of CF care are needed to define the best clinical practice, including how to use antibiotics in the most rational way.
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| 22. |
- Knudsen, TB, et al.
(författare)
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Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients
- 2005
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 11:9, s. 730-735
-
Tidskriftsartikel (refereegranskat)abstract
- Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 mu g/mL). The difference in survival was significant during TB treatment (log rank, p < 0.02) and after long-term follow-up (log rank, p < 0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per mu g of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per mu g of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.
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| 23. |
- Ludewig, Kristin, et al.
(författare)
-
Phenology and morphology of the invasive legume Lupinus polyphyllus along a latitudinal gradient in Europe
- 2022
-
Ingår i: NeoBiota. - : Pensoft Publishers. - 1619-0033 .- 1314-2488. ; 78
-
Tidskriftsartikel (refereegranskat)abstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distributionranges. Temperature is one of the most important drivers of plant phenology together with day length.The adaptation of their phenology may be important for the success of invasive plant species. The presentstudy aims at understanding how the performance and the phenology of the invasive legume Lupinuspolyphyllus vary with latitude. We sampled data across a >2000 km latitudinal gradient from Centralto Northern Europe. We quantified variation in phenology of flowering and fruiting of L. polyphyllususing >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 sites. Theday of the year at which different phenological phases were reached, increased 1.3–1.8 days per degreelatitude, whereas the growing degree days (gdd) required for these phenological phases decreased 5–16 gddper degree latitude. However, this difference disappeared, when the day length of each day included inthe calculation of gdd was considered. The day of the year of the earliest and the latest climatic zone toreach any of the three studied phenological phases differed by 23–30 days and temperature requirementsto reach these stages differed between 62 and 236 gdd. Probably, the invasion of this species will furtherincrease in the northern part of Europe over the next decades due to climate warming. For invasive speciescontrol, our results suggest that in countries with a large latitudinal extent, the mowing date should shiftby ca. one week per 500 km at sites with similar elevations.
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| 24. |
- Ludewig, Kristin, et al.
(författare)
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Phenology of Lupinus polyphyllus from Central to Northern Europe
- 2022
-
Annan publikationabstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distribution ranges. Among the environmental factors, phenology is mostly driven by temperature and day length. Rapid adaptation of their phenology may also be important for the success of invasive plant species. Our main aim was to understand how the performance, timing, and temperature dependence of the phenology of the invasive legume Lupinus polyphyllus varies with latitude. L. polyphyllus is one of the most frequent invasive species in Europe, and the gained information may help to make management more effective by adjustments to latitude and phenology.Methods:We quantified variation in phenology across a >2000 km latitudinal gradient from Central to Northern Europe. We sampled data of flowering and fruiting of L. polyphyllus using >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 locations. We calculated the accumulated growing degree days for each observation date at each site from the temperature data of the meteorological stations, which are listed in the metadata of the dataset.
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| 25. |
- Martin, Natalia, et al.
(författare)
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High-resolution core-level spectroscopy study of the ultrathin aluminum oxide film on NiAl(110)
- 2011
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969 .- 1098-0121. ; 83:12
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the ultrathin aluminum oxide film on NiAl(110) by a combination of high-resolution core-level spectroscopy and density functional theory calculations. Energy-dependent core-level data from the O 1s and Al 2p levels allows for a distinction between oxygen and aluminum atoms residing at the surface or inside the aluminum oxide film. A comparison to calculated core-level binding energies from the recent model by Kresse et al. [Science 308, 1440 (2005)] reveals good agreement with experiment, and the complex spectroscopic signature of the thin Al oxide on NiAl(110) can be explained. Our assignment of a shifted component in the O 1s spectra to oxygen atoms at the surface with a particular Al and oxygen coordination may have implications for the interpretation of photoelectron-diffraction experiments from similar ultrathin aluminum oxide films.
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| 26. |
- Merlo, Domenico Franco, et al.
(författare)
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Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression : The NewGeneris Cohort
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:2, s. 193-200
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.
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| 27. |
- Olesen, Hanne Vebert, et al.
(författare)
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Gender differences in the Scandinavian cystic fibrosis population.
- 2010
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Ingår i: Pediatric pulmonology. - : Wiley. - 1099-0496 .- 8755-6863. ; 45:10, s. 959-65
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Tidskriftsartikel (refereegranskat)abstract
- To explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication.
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| 28. |
- Pedersen, Marie, et al.
(författare)
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Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet : The European Prospective Mother-Child Study (NewGeneris)
- 2012
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:12, s. 1739-1745
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. OBJECTIVES: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother child study. METHODS: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006-2010. Maternal diet was estimated through food-frequency questionnaires. RESULTS: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was -132 g (95% CI: -207, -56); the corresponding difference for head circumference was -0.33 cm (95% CI: -0.61, -0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for Factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. CONCLUSIONS: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. IF confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.
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| 29. |
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| 30. |
- Persson, Lennart, et al.
(författare)
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Density-dependent interactions in an Arctic char - brown trout system : competition, predation, or both?
- 2013
-
Ingår i: Canadian Journal of Fisheries and Aquatic Sciences. - : Canadian Science Publishing. - 0706-652X .- 1205-7533. ; 70:4, s. 610-616
-
Tidskriftsartikel (refereegranskat)abstract
- In the study of mechanisms structuring fish communities, mixed competition-predation interactions where large predators feed on prey fish versus those in which small predators compete with prey fish for a shared prey have been the focus of substantial research. We used a long-term data set from a system inhabited by brown trout (Salmo trutta) (predator) and Arctic char (Salvelinus alpinus) (prey) to evaluate whether mixed interspecific interactions were present in this system as suggested in other studies focusing on this species pair. We found no evidence for a negative interspecific density dependence in individual performance in either Arctic char or brown trout. In contrast, a negative intraspecific density dependence was present, especially in Arctic char. Furthermore, large brown trout condition showed a positive response to encounter rate with Arctic char (related to the density of small Arctic char). The most parsimonious interaction module to explain the Arctic char - brown trout interaction patterns in the studied system does therefore not need to include interspecific competition. We suggest that size-structured mixed competition-predation interactions in different systems are realized as being either mainly structured through interspecific predation or by competition depending on species life history characteristics and environmental conditions.
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| 31. |
- Poutanen, Markku, et al.
(författare)
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The Nordic Geodetic Observing System (NGOS)
- 2007
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Ingår i: International Association of Geodesy Symposia, Dynamic Planet. ; , s. 749-756
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The Nordic Geodetic Observing System (NGOS) integrates fundamental geodetic techniques for the long-term observation of Earth system parameters. The Nordic Geodetic Commission (NKG) established a Task Force with the mission to prepare a document providing the definition and draft for the implementation of the NGOS.The regional system aligns with international efforts such as the Global Earth Observation System of Systems (GEOSS) and Global Observing Systems and adheres to the Integrated Global Observing Strategy (IGOS). Recent developments in the structure and function of the International Association of Geodesy cumulated in the establishment of the Global Geodetic Observing System, GGOS. NGOS is planned as a regional implementation and densification of the GGOS.The NGOS is proposed as a system that will serve a wide range of scientific and practical applications. For the Nordic countries, a main focus will be on crustal motion, dynamics of glaciated areas and sea level. NGOS aims to provide geodetic observations for the Nordic area that are of sufficient quantity and quality to serve most of the needs of global Earth observation as well as practical and scientific applications in the region. In particular, NGOS will contribute to the GGOS and other IAG Services; European activities such as EUREF, ECGN, EUVN, and ESEAS; provide the reference frames for the Nordic countries, as well as contribute to the global ones; support scientific projects related to the geodynamics of the Nordic area and provide ground-truth for satellite missions. In this paper we describe the plans and current status of the NGOS.
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| 32. |
- Pressler, Tacjana, et al.
(författare)
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Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods
- 2009
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1873-5010 .- 1569-1993. ; 8:1, s. 37-42
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate three serological methods for their ability to identify CF patients in different infection status especially those at risk of developing chronic Pseudomonas aeruginosa (Pa) infection. Methods: Two ELISA methods: exotoxin A (ExoA) and CF-IgG-ELISA (CF-IgG) and Crossed Immunoelectrophoresis (CIE) were used for measurement of Pa-antibodies in sera from 791 Scandinavian CF patients. Results: 381 patients were cultured negative for Pa in the year before study start, 129 patients were intermittently colonized and 281 patients were chronically infected. The sensitivity of the investigated assays was 96%, 93% and 97%, specificity 89%, 89% and 83% for CIE, ExoA and CF-IgG respectively. The negative predictive value was for CIE 97%, for ExoA 95% and for CF-IgG 98% and positive predictive values 87%, 86% and 80%. Out of the 381 patients cultured negative for Pa, 11 changed status to chronically infected. Twenty-four out of the 129 patients intermittently colonized became chronically infected. The antibody levels in this latter group of patients were significantly higher already at the study start and increased significantly during the study period (p < 0.05). Elevated levels of specific anti-Pseudomonal antibodies showed to be the risk factor for developing chronic P. aeruginosa infection (OR 4.9 and OR 2.7, p < 0.05 for CF-IgG and ExoA). Conclusion: All three serological assays were equally informative. The very high sensitivity of the assays made it possible to characterize patients with different infection status. Elevated levels of specific anti-Pseudomonas antibodies showed to be the risk factor for developing chronic Pa infection. Due to the specificity of the tests, antibiotic treatment based on serology might be considered in selected cases. There is a window of opportunity for suppression and eradication of initial P aeruginosa infection making measurement of specific anti-Pseudomonas antibodies helpful. (c) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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| 33. |
- Skulason, Skuli, et al.
(författare)
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A way forward with eco evo devo : an extended theory of resource polymorphism with postglacial fishes as model systems
- 2019
-
Ingår i: Biological Reviews. - : John Wiley & Sons. - 1464-7931 .- 1469-185X. ; 94:5, s. 1786-1808
-
Forskningsöversikt (refereegranskat)abstract
- A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well‐suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by (i) the availability of diverse environments promoting divergent natural selection; (ii) dynamic developmental processes sensitive to environmental and genetic signals; and (iii) eco evo and eco devo feedbacks influencing the selective and developmental environments of the phenotype. We highlight empirical examples and present a conceptual model for the generation of resource polymorphism – emphasizing eco evo devo, and identify current gaps in knowledge.
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| 34. |
- Theilgaard-Mönch, Kim, et al.
(författare)
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The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing
- 2004
-
Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 172:12, s. 7684-7693
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing.
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| 35. |
- von Stedingk, Hans, 1978-, et al.
(författare)
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Analysis of hemoglobin adducts from acrylamide, glycidamide and ethylene oxide in paired mother/cordblood samples from Denmark
- 2011
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 24:11, s. 1957-1965
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Tidskriftsartikel (refereegranskat)abstract
- The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography–mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27–0.86) for acrylamide, 0.38 (range 0.20–0.73) for glycidamide, and 0.43 (range 0.17–1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38–0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large population studies.
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| 36. |
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