| 1. |
- Kristiansen, Oscar, et al.
(författare)
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Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side-effects : a randomized, double-blinded crossover trial
- 2021
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 7:6, s. 507-516
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites.METHODS AND RESULTS: A randomized multi-center trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-weeks double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference [statin-placebo] was 0.31 (95% CI -0.24-0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearmans rho ≤0.40, for all variables).CONCLUSION: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.
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| 2. |
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| 3. |
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| 4. |
- Lindberg, Julia, et al.
(författare)
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Selection for tameness modulates the expression of heme related genes in silver foxes
- 2007
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Ingår i: Behavioral and Brain Functions. - : Springer Science and Business Media LLC. - 1744-9081. ; 3, s. 18-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The genetic and molecular mechanisms of tameness are largely unknown. A line of silver foxes (Vulpes vulpes) selected for non-aggressive behavior has been used in Russia since the 1960's to study the effect of domestication. We have previously compared descendants of these selected (S) animals with a group of non-selected (NS) silver foxes kept under identical conditions, and showed that changes in the brain transcriptome between the two groups are small. Unexpectedly, many of the genes showing evidence of differential expression between groups were related to hemoproteins. RESULTS: In this study, we use quantitative RT-PCR to demonstrate that the activity of heme related genes differ between S and NS foxes in three regions of the brain. Furthermore, our analyses also indicate that changes in mRNA levels of heme related genes can be well described by an additive polygenic effect. We also show that the difference in genetic background between the two lines of foxes is limited, as estimated by mitochondrial DNA divergence. CONCLUSION: Our results indicate that selection for tameness can modify the expression of heme related genes in canid brain regions known to modulate emotions and behavior. The possible involvement of heme related genes in behavior is surprising. It is possible that hemoglobin modulates the behavior of canids by interaction with CO and NO signaling. Another possibility is that hemorphins, known to be produced after enzymatic cleavage of hemoglobin, are responsible for behavioral alterations. Thus, we hypothesize that hemoglobin metabolism can be a functionally relevant aspect of the domestic phenotype in foxes selected for tameness.
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| 5. |
- Lindberg, Ulf, et al.
(författare)
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Simon Frith : Crossover Critic
- 2014
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Ingår i: Popular Music Matters: Essays in Honour of Simon Frith. - : Ashgate. - 9781472421807 - 9781472421791 ; , s. 129-143
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Linnebjerg, Jannie Fries, et al.
(författare)
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Non-breeding areas of three sympatric auk species breeding in three Icelandic colonies
- 2018
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Ingår i: Polar Biology. - : Springer Science and Business Media LLC. - 0722-4060 .- 1432-2056. ; 41:10, s. 1951-1961
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Tidskriftsartikel (refereegranskat)abstract
- Like many seabirds, auks spend most of the year in offshore areas. Information on which oceanic areas they rely on throughout the winter is therefore important in understanding their population dynamics and establishing appropriate conservation measures. The breeding populations of Thick-billed Murres (Uria lomvia), Common Murres (Uria aalge) and Razorbills (Alca torda) in Iceland have been reported declining for the last 30 years. Thick-billed Murres have shown the most alarming rate of decrease, while Razorbills have declined the least. To help understand these changes, we collected information about the non-breeding distribution of these three species by using light-based geolocation. Geolocators were deployed on breeding adults in three different colonies in Iceland in 2013 and 2014. Data showed that the three species’ wintering areas differed substantially. Thick-billed Murres wintered off the west coast of Greenland and East Greenland/Northern Iceland, Common Murres favoured areas around Iceland/East Greenland and to the southwest along the Mid-Atlantic Ridge, and Razorbills were mostly distributed around Iceland. Although some intraspecific variation was evident, we conclude that the population development of Thick-billed Murres in Iceland is likely to be largely influenced by environmental conditions in west Greenland, while Common Murres and Razorbills are more dependent on the oceanic area around Iceland. The results may therefore prove to be an important platform for understanding the population dynamics of these three species in Iceland and informing conservation actions.
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| 7. |
- Ljungblad, Ulf Wike, et al.
(författare)
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A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
- 2022
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Ingår i: International Journal of Neonatal Screening. - : MDPI AG. - 2409-515X. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The sensitivity of newborn screening (NBS) in detecting infants that later develop symptomatic vitamin B12 deficiency is unknown. We evaluated the predictive value using NBS algorithms in detecting infants that later were clinically diagnosed with symptomatic B12 deficiency. Furthermore, we investigated whether being born in a hospital using nitrous oxide (N2O) as pain relief in labor may have had an impact on total homocysteine at NBS. Methods: We retrospectively retrieved NBS data and analyzed total homocysteine, methylmalonic acid and methyl citrate on stored NBS dried blood spots (DBS) of 70 infants diagnosed with symptomatic B12 deficiency and compared them to 646 matched and 434 unmatched DBS controls to evaluate the Austrian and Heidelberg B12 NBS algorithms. Results: The sensitivity of NBS in detecting infants later diagnosed with symptomatic B12 deficiency at median age 10.9 weeks was ≤10%. Total homocysteine was higher in DBS for the unmatched controls who were born in hospitals providing N2O compared to in hospitals not providing N2O, with median total homocysteine 4.0 µmol/L compared to 3.5 µmol/L (n = 434, 95% CI 0.04–0.87, p = 0.03). Conclusion: NBS algorithms were unable to identify most infants diagnosed with symptomatic B12 deficiency after the neonatal period. Being born in hospitals providing N2O may impact total homocysteine at NBS.
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| 8. |
- Ljungblad, Ulf Wike, et al.
(författare)
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Breastfed Infants With Spells, Tremor, or Irritability : Rule Out Vitamin B12 Deficiency
- 2022
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Ingår i: Pediatric Neurology. - : Elsevier BV. - 0887-8994. ; 131, s. 4-12
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Norway, 5-10% of neonates and infants have biomarkers suggesting vitamin B12 deficiency from newborn screening tests and unselected clinical screening, respectively. Aims: The aims were to identify risk factors and describe presenting symptoms and biochemical profiles in infants diagnosed with vitamin B12 deficiency. Methods: In this case-control study, we searched hospital medical records for infants younger than one year born in 2011-2018, diagnosed with vitamin B12 deficiency. We compared 85 cases with a control group of 252 infants aged 3-7 months. Parents completed questionnaires. Results: Of the 85 cases with vitamin B12 deficiency, 80% presented with spells (37%) of apneas, motor seizures, or absences within the first two months of life. Tremor (29%) and irritability (18%) were the most common findings at the first examination. Serum total homocysteine ≥10 μmol/L was found in 77% of cases compared to 28% of controls (P < 0.001). None of the mothers were vegetarians, but 25% reported a previous history of vitamin B12 deficiency and 7% had celiac disease. The dose of nitrous oxide given during labor was significantly associated with infant serum total homocysteine level at diagnosis (r = 0.37, 95% confidence interval = 0.16-0.55, P < 0.001) for cases, but not for controls. Conclusion: Spells, tremor, and irritability are common findings in early infant vitamin B12 deficiency. Nitrous oxide given during labor is proposed as a contributing risk factor to the development of early infant vitamin B12 deficiency.
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| 9. |
- Ljungblad, Ulf Wike, et al.
(författare)
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Nitrous oxide in labour predicted newborn screening total homocysteine and is a potential risk factor for infant vitamin B12 deficiency
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253. ; 111:12, s. 2315-2321
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Risk factors for vitamin B12 deficiency in infants are not fully understood. The aim of the study was to assess predictors of total homocysteine and methylmalonic acid analysed in newborn screening dried blood spots. Methods: In a Norwegian case control study, we analysed total homocysteine and methylmalonic acid in newborn screening dried blood spots of 86 infants clinically diagnosed with vitamin B12 deficiency during 2012–2018. Results were compared to 252 healthy infants and 400 dried blood spot controls. Medical records were reviewed, and mothers completed questionnaires. Results: Both total homocysteine and methylmalonic acid were significantly higher on newborn screening dried blood spots in infants later clinically diagnosed with vitamin B12 deficiency than controls. Multiple regression analysis showed that the dose of nitrous oxide during labour was the strongest predictor for total homocysteine level in newborn screening dried blood spots for all infants, with larger effect in infants later clinically diagnosed with vitamin B12 deficiency than controls. Conclusion: Nitrous oxide dose during labour was a predictor for total homocysteine and may impact the interpretation of total homocysteine analysis in newborn screening. Nitrous oxide is suggested as a contributing risk factor for infants prone to develop vitamin B12 deficiency.
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| 10. |
- Ljungblad, Ulf Wike, et al.
(författare)
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The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants
- 2021
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Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798. ; 35, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. Aims: To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. Methods: In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Results: Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. Conclusion: We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.
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| 11. |
- Luo, Dan, et al.
(författare)
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Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L.
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:34, s. E5082-E5089
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Tidskriftsartikel (refereegranskat)abstract
- The seed oil of Euphorbia lathyris L. contains a series of macrocyclic diterpenoids known as Euphorbia factors. They are the current industrial source of ingenol mebutate, which is approved for the treatment of actinic keratosis, a precancerous skin condition. Here, we report an alcohol dehydrogenase-mediated cyclization step in the biosynthetic pathway of Euphorbia factors, illustrating the origin of the intramolecular carbon-carbon bonds present in lathyrane and ingenane diterpenoids. This unconventional cyclization describes the ring closure of the macrocyclic diterpene casbene. Through transcriptomic analysis of E. lathyris L. mature seeds and in planta functional characterization, we identified three enzymes involved in the cyclization route from casbene to jolkinol C, a lathyrane diterpene. These enzymes include two cytochromes P450 from the CYP71 clan and an alcohol dehydrogenase (ADH). CYP71D445 and CYP726A27 catalyze regio-specific 9-oxidation and 5-oxidation of casbene, respectively. When coupled with these P450-catalyzed monooxygenations, E. lathyris ADH1 catalyzes dehydrogenation of the hydroxyl groups, leading to the subsequent rearrangement and cyclization. The discovery of this nonconventional cyclization may provide the key link to complete elucidation of the biosynthetic pathways of ingenol mebutate and other bioactive macrocyclic diterpenoids.
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| 12. |
- Muheim, Claudio, et al.
(författare)
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Increasing the permeability of Escherichia coli using MAC13243
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The outer membrane of gram-negative bacteria is a permeability barrier that prevents the efficient uptake of molecules with large scaffolds. As a consequence, a number of antibiotic classes are ineffective against gram-negative strains. Herein we carried out a high throughput screen for small molecules that make the outer membrane of Escherichia coli more permeable. We identified MAC13243, an inhibitor of the periplasmic chaperone LolA that traffics lipoproteins from the inner to the outer membrane. We observed that cells were (1) more permeable to the fluorescent probe 1-N-phenylnapthylamine, and (2) more susceptible to large-scaffold antibiotics when sub-inhibitory concentrations of MAC13243 were used. To exclude the possibility that the permeability was caused by an off-target effect, we genetically reconstructed the MAC13243-phenotype by depleting LolA levels using the CRISPRi system.
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| 13. |
- Muheim, Claudio, et al.
(författare)
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Increasing the permeability of Escherichia coli using MAC13243
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The outer membrane of gram-negative bacteria is a permeability barrier that prevents the efficient uptake of molecules with large scaffolds. As a consequence, a number of antibiotic classes are ineffective against gram-negative strains. Herein we carried out a high throughput screen for small molecules that make the outer membrane of Escherichia coli more permeable. We identified MAC13243, an inhibitor of the periplasmic chaperone LolA that traffics lipoproteins from the inner to the outer membrane. We observed that cells were (1) more permeable to the fluorescent probe 1-N-phenylnapthylamine, and (2) more susceptible to large-scaffold antibiotics when sub-inhibitory concentrations of MAC13243 were used. To exclude the possibility that the permeability was caused by an off-target effect, we genetically reconstructed the MAC13243-phenotype by depleting LolA levels using the CRISPRi system.
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| 14. |
- Patterson, Allison, et al.
(författare)
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Foraging range scales with colony size in high-latitude seabirds
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:17, s. 3800-3807
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Tidskriftsartikel (refereegranskat)abstract
- Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1, 2, 3, 4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world’s most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole’s halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole’s version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.
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| 15. |
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