| 1. |
- Aad, G., et al.
(författare)
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- 2016
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Ingår i: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 93:1
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; :12
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review D. Particles and fields. - : American Physics Society. - 0556-2821 .- 1089-4918. ; 92:11
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Aaseth, Jan, et al.
(författare)
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Treatment strategies in Alzheimers disease: a review with focus on selenium supplementation
- 2016
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Ingår i: Biometals. - : SPRINGER. - 0966-0844 .- 1572-8773. ; 29:5, s. 827-839
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.
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| 6. |
- Dahlgren, David, et al.
(författare)
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Regional Intestinal Permeability of Three Model Drugs in Human
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3013-3021
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Tidskriftsartikel (refereegranskat)abstract
- Currently there are only a limited number of determinations of human P-eff in the distal small intestine and none in the large intestine. This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms. To meet this demand, three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers. The P-eff of each model drug was then calculated using a validated deconvolution method. The median P-eff of atenolol in the jejunum, ileum, and colon was 0.45, 0.15, and 0.013 X 10(-4) cm/s, respectively. The corresponding values for metoprolol were 1.72, 0.72, and 1.30 X 10(-4) cm/s, and for ketoprofen 8.85, 6.53, and 3.37 X 10(-4) cm/s, respectively. This is the first study where the human Peff of model drugs has been determined in all parts of the human intestinal tract in the same subjects. The jejunal values were similar to directly determined values using intestinal single-pass perfusion, indicating that the deconvolution method is a valid approach for determining regional P-eff. The values from this study will be highly useful in the validation of preclinical regional absorption models and in silico tools.
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| 7. |
- Kjaer, Per, et al.
(författare)
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GLA:D-(R) Back group-based patient education integrated with exercises to support self-management of back pain- development, theories and scientific evidence-
- 2018
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Ingår i: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundClinical guidelines recommend that people with back pain be given information and education about their back pain, advice to remain active and at work, and exercises to improve mobility and physical activity. Guidelines, however, rarely describe how this is best delivered. The aim of this paper is to present the development, theories, and underlying evidence for GLA:D Back - a group education and exercise program that translates guideline recommendations into a clinician-delivered program for the promotion of self-management in people with persistent/recurrent back pain.MethodsGLA:D Back, which included a rationale and objectives for the program, theory and evidence for the interventions, and program materials, was developed using an iterative process. The content of patient education and exercise programs tested in randomised trials was extracted and a multidisciplinary team of expert researchers and clinicians prioritised common elements hypothesised to improve back pain beliefs and management skills. The program was tested on eight people with persistent back pain in a university clinic and 152 patients from nine primary care physiotherapy and chiropractic clinics. Following feedback from the clinicians and patients involved, the working version of the program was created.ResultsEducational components included pain mechanisms, pain modulation, active coping strategies, imaging, physical activity, and exercise that emphasised a balance between the sum of demands and the individuals capacity. These were operationalised in PowerPoint presentations with supporting text to aid clinicians in delivering two one-hour patient education lectures.The exercise program included 16 supervised one-hour sessions over 8weeks, each comprising a warm-up section and eight types of exercises for general flexibility and strengthening of six different muscle groups at four levels of difficulty. The aims of the exercises were to improve overall back fitness and, at the same time, encourage patients to explore variations in movement by incorporating education content into the exercise sessions.ConclusionFrom current best evidence about prognostic factors in back pain and effective treatments for back pain, research and clinical experts developed a ready-to-use structured program - GLA:D (R) Back - to support self-management for people with persistent/recurrent back pain.
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| 8. |
- Wallin, Cecilia, et al.
(författare)
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Alzheimer's disease and cigarette smoke components : effects of nicotine, PAHs, and Cd(II), Cr(III), Pb(II), Pb(IV) ions on amyloid-beta peptide aggregation
- 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
- Cigarette smoking is a significant risk factor for Alzheimer’s disease (AD), which is associated with extracellular brain deposits of amyloid plaques containing aggregated amyloid-β (Aβ) peptides. Aβ aggregation occurs via multiple pathways that can be influenced by various compounds. Here, we used AFM imaging and NMR, fluorescence, and mass spectrometry to monitor in vitro how Aβ aggregation is affected by the cigarette-related compounds nicotine, polycyclic aromatic hydrocarbons (PAHs) with one to five aromatic rings, and the metal ions Cd(II), Cr(III), Pb(II), and Pb(IV). All PAHs and metal ions modulated the Aβ aggregation process. Cd(II), Cr(III), and Pb(II) ions displayed general electrostatic interactions with Aβ, whereas Pb(IV) ions showed specific transient binding coordination to the N-terminal Aβ segment. Thus, Pb(IV) ions are especially prone to interact with Aβ and affect its aggregation. While Pb(IV) ions affected mainly Aβ dimer and trimer formation, hydrophobic toluene mainly affected formation of larger aggregates such as tetramers. The uncharged and hydrophilic nicotine molecule showed no direct interactions with Aβ, nor did it affect Aβ aggregation. Our Aβ interaction results suggest a molecular rationale for the higher AD prevalence among smokers, and indicate that certain forms of lead in particular may constitute an environmental risk factor for AD.
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| 9. |
- Wallin, Cecilia, et al.
(författare)
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Characterization of Mn(II) ion binding to the amyloid-beta peptide in Alzheimer's disease
- 2016
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Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 38, s. 183-193
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-beta (A beta) peptides. Previous studies have shown that A beta displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate A beta aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the A beta(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to A beta may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying A beta binding reveals more complex AD metal chemistry than has been previously considered in the literature.
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