| 1. |
- Scholz, Birger, et al.
(författare)
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Neuropeptidomic analysis of the embryonic Japanese quail diencephalon
- 2010
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 10, s. 30-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17), sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon.Results: We identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2 exposure and sex effects were neuropeptide K (downregulated by EE2 in males and females), gastrin-releasing peptide (more highly expressed in control and EE2 exposed males) and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex). We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide.Conclusions: This study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model.
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| 2. |
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| 3. |
- Andersson, Ingemar, 1950-
(författare)
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Rehabilitering vid långvarig smärta
- 2010. - 2
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Ingår i: Smärta och smärtbehandling. - Stockholm : Liber. - 9789147084135 ; , s. 401-409
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Larsson, Åke, 1944, et al.
(författare)
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Kustfisk - hälsa
- 2012
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Ingår i: HAVET 2012 - Om miljötillståndet i svenska havsområden. - 1654-6741. ; år 2012
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Forskningsöversikt (refereegranskat)
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| 5. |
- Qvarnström, Miriam, et al.
(författare)
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Persistence to antihypertensive drug treatment in Swedish primary healthcare
- 2013
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 69:11, s. 1955-1964
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Tidskriftsartikel (refereegranskat)abstract
- To determine factors associated with low persistence in patients initiated on drug treatment for hypertension. Cohort study using medical records for patients with hypertension in 48 Swedish primary healthcare centres. Data were linked to national registers on dispensed drugs, hospitalizations, outpatient hospital consultations, deaths, migration, and socioeconomy. We identified 5225 patients (55 % women, mean age 61 years) initiated on antihypertensive drug treatment during 2006-2007. Persistence was measured for two years by the dispensed drugs. Patients with a gap of > 30 days between end of dispensed supply and the next dispensed prescription were classified as non-persistent. This was calculated by Kaplan-Meier analysis. Cox proportional hazard regression was used to estimate hazard ratios for discontinuation. Potential predictors included age, gender, blood pressure before initiation of therapy, cardiovascular comorbidity, educational level, country of birth, and income. Among patients with a dispensed first prescription, 26 % discontinued treatment during the first year, and a further 9 % discontinued during the second year. Discontinuation (all adjusted) was more common in men (P = 0.002) and in younger patients (30-49 years, P < 0.001). Systolic (P < 0.001) but not diastolic blood pressure was positively associated with persistence. Native-born Swedish citizens and patients born in the other Nordic countries had lower discontinuation rates than those born outside the Nordic countries (P < 0.001). Major determinants of discontinuation of antihypertensive drug treatment are male sex, young age, mild-to-moderate systolic blood pressure elevation, and birth outside of Sweden.
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| 6. |
- Gustafsson, Kerstin, et al.
(författare)
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Direct and indirect effects of the fungicide azoxystrobin in outdoor brackish water microcosms
- 2010
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Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 19:2, s. 431-444
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Tidskriftsartikel (refereegranskat)abstract
- The effects of the strobilurin fungicide azoxystrobin were studied in brackish water microcosms, with natural plankton communities and sediment. Two experiments were conducted: Experiment 1 (nominal conc. 0, 15 and 60 mu g/L, 24-L outdoor microcosms for 21 days) and a second, follow-up, Experiment 2 (nominal conc. 0, 3, 7.5, 15 mu g/L, 4-L indoor microcosms for 12 days). The microcosms represent a simplified brackish water community found in shallow semi-enclosed coastal areas in agricultural districts in the Baltic Sea region. Measured water concentrations of the fungicide (Experiment 1) were, on average, 83 and 62% of nominal concentrations directly after application, and 25 and 30% after 21 days, for the low and high dose treatments, respectively, corresponding to mean DT50-values of 15.1 and 25.8 days, for low and high dose treatments, respectively. In Experiment 1, direct toxic effects on calanoid copepods at both test concentrations were observed. Similarly, in Experiment 2, the copepod abundance was significantly reduced at all tested concentrations. There were also significant secondary effects on zooplankton and phytoplankton community structure, standing stocks and primary production. Very few ecotoxicological studies have investigated effects of plant protection products on Baltic organisms in general and effects on community structure and function specifically. Our results show that azoxystrobin is toxic to brackish water copepods at considerably lower concentrations than previously reported from single species tests on freshwater crustaceans, and that direct toxic effects on this ecologically important group may lead to cascade effects altering lower food webs and ecosystem functioning.
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| 7. |
- Rekić, Dinko, 1984, et al.
(författare)
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External Validation of the Bilirubin-Atazanavir Nomogram for Assessment of Atazanavir Plasma Exposure in HIV-1-Infected Patients.
- 2013
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Ingår i: The AAPS journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 15:2, s. 308-15
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Tidskriftsartikel (refereegranskat)abstract
- Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on a ritonavir-boosted regimen. In addition, the nomogram was evaluated in 56 Italian patients on an unboosted regimen. The predictive properties of the nomogram were validated against observed atazanavir plasma concentrations. The use of the nomogram to detect non-adherence was also investigated by simulation. The bilirubin nomogram predicted suboptimal exposure in the patient populations on a ritonavir-boosted regimen with a negative predictive value of 97% (95% CI 95-100). The bilirubin nomogram and monitoring of atazanavir concentrations had similar predictive properties for detecting non-adherence based on simulations. Although both methods performed adequately during a period of non-adherence, they had lower predictive power to detect past non-adherence episodes. Using the bilirubin nomogram for detection of suboptimal atazanavir exposure in patients on a ritonavir-boosted regimen is a rapid and cost-effective alternative to routine measurements of the actual atazanavir exposure in plasma. Its application may be useful in clinical settings if atazanavir concentrations are not available.
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| 8. |
- Ekman, Elisabet, et al.
(författare)
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Awareness among nurses about reporting of adverse drug reactions in Sweden
- 2012
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Ingår i: Drug, Healthcare and Patient Safety. - 1179-1365. ; 4, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to investigate awareness among nurses regarding their new role as reporters of adverse drug reactions in Sweden and factors that may influence reporting by nurses.Methods: In 2007, all nurses were included in the adverse drug reaction reporting scheme in Sweden. A questionnaire was sent to 753 randomly selected nurses in September 2010.Results: Of the 453 (60%) responding nurses, 265 (58%) were aware that nurses were included in the reporting of adverse drug reactions. Sixty-one nurses (14%) stated that they had reported an adverse drug reaction. Fifteen percent (n = 70) of the respondents had received training about reporting of adverse drug reactions. Almost one third of these (n = 21, 30%) had reported an adverse drug reaction on at least one occasion. Among nurses without training, a smaller proportion (n = 40, 11%, P < 0.05) had reported an adverse drug reaction on at least one occasion. The two factors considered most important by nurses for reporting were the severity of the adverse drug reaction and if the reaction was to a newly approved drug. A majority of the nurses (n = 397, 88%) were interested in a training course in pharmacology as part of their ongoing professional development. One third (32%) of all nurses stated that one reason for not reporting a suspected adverse drug reaction was that the physician responsible did not regard the reaction necessary to report.Conclusion: We found that more than half of the study population of nurses in Sweden were aware of their new role as reporters of adverse drug reactions, but few of the responding nurses had reported an adverse drug reaction. Given that training seems to be associated with high reporting frequency, we suggest more training in pharmacovigilance for nurses.
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| 9. |
- Nilsson, Mats F., et al.
(författare)
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Improved methodology for identifying the teratogenic potential in early drug development of hERG channel blocking drugs
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 29:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Drugs blocking the potassium current IKr of the heart (via hERG channel-inhibition) have the potential to cause hypoxia-related teratogenic effects. However, this activity may be missed in conventional teratology studies because repeat dosing may cause resorptions. The aim of the present study was to investigate an alternative protocol to reveal the teratogenic potential of IKr-blocking drugs. The IKr blocker astemizole, given as a single dose (80mg/kg) on gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart rate at 20nM, and arrhythmias at 200-400nM. Cetirizine, without IKr-blocking properties, did not affect the rat embryonic heart in vitro. The present study shows that single dose testing on sensitive days of development, together with whole embryo culture, can be a useful methodology to better characterize the teratogenic potential of IKr-blocking drugs.
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| 10. |
- Motwani, Hitesh V., et al.
(författare)
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Cob(I)alamin Reacts with Sucralose to Afford an Alkylcobalamin : Relevance to In Vivo Cobalamin and Sucralose Interaction
- 2011
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Ingår i: Food and Chemical Toxicology. - : Springer. - 0278-6915 .- 1873-6351. ; 49:4, s. 750-757
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin B12, viz., cyano- or hydroxo-cobalamin, can be chemically or enzymatically converted into the derivatives methyl- and adenosyl-cobalamin, which are complex organometallic cofactors associated with several cobalamin-dependent enzymes. The reduced form of vitamin B12, cob(I)alamin {Cbl(I)}, obtained by reduction of hydroxocobalamin (OH-Cbl) with e.g. sodium borohydride, is one of the most powerful nucleophiles known. Cbl(I) was shown to react readily with the synthetic sweetener sucralose (1,6-dichloro-1,6-dideoxy-β-d-fructofuranosyl-4-chloro-4-deoxy-α-d-galactopyranoside) in an aqueous system to form an alkylcobalamin (Suc-Cbl). This occurred by replacement of one of the three chlorine atoms of sucralose with a cobalamin moiety. The efficiency of trapping sucralose in presence of excess Cbl(I) was estimated to be >90%. Furthermore, in an in vitro study using human liver S9 with NADPH regeneration, in presence of OH-Cbl and sucralose, Suc-Cbl was shown to be formed. The Suc-Cbl was characterized primarily by LC-ESI+-MS/MS. Given the human consumption of sucralose from food and beverages, such a reaction between the sweetener and reduced vitamin B12 could occur in vivo.
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