| 251. |
- Karalija, Nina, 1984-, et al.
(författare)
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Cardiovascular factors are related to dopamine integrity and cognition in aging
- 2019
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley-Blackwell. - 2328-9503. ; 6:11, s. 2291-2303
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.
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| 252. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 253. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
- 2024
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Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine decline is suggested to underlie aging -related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5 -year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5 -year follow-up: n = 129) who underwent positron emission tomography with 11C- raclopride to assess dopamine D2 -like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A datadriven approach (k -means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age -sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide -ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5 -year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.
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| 254. |
- Karalija, Nina, 1984-, et al.
(författare)
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Sex differences in dopamine integrity and brain structure among healthy older adults : Relationships to episodic memory
- 2021
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 105, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Normal brain aging is a multidimensional process that includes deterioration in various brain structures and functions, with large heterogeneity in patterns and rates of decline. Sex differences have been reported for various cognitive and brain parameters, but little is known in relation to neuromodulatory aspects of brain aging. We examined sex differences in dopamine D2-receptor (D2DR) availability in relation to episodic memory, but also, grey-matter volumes, white-matter lesions, and cerebral perfusion in healthy older adults (n = 181, age: 64-68 years) from the Cognition, Brain, and Aging study. Women had higher D2DR availability in midbrain and left caudate and putamen, as well as superior episodic memory performance. Controlling for left caudate D2DR availability attenuated sex differences in memory performance. In men, lower left caudate D2DR levels were associated with lower cortical perfusion and higher burden of white-matter lesions, as well as with episodic memory performance. However, sex was not a significant moderator of the reported links to D2DR levels. Our findings suggest that sex differences in multiple associations among DA receptor availability, vascular factors, and structural connectivity contribute to sex differences in episodic memory. Future longitudinal studies need to corroborate these patterns by lead-lag associations. This manuscript is part of the Special Issue entitled 'Cognitive Neuroscience of Healthy and Pathological Aging' edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza.
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| 255. |
- Karlsson, David, et al.
(författare)
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Electronic speckle pattern interferometry: A tool for determining diffusion and partition coefficients for proteins in gels
- 2002
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Ingår i: Biotechnology Progress. - : Wiley. - 1520-6033 .- 8756-7938. ; 18:6, s. 1423-1430
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to demonstrate electronic speckle pattern interferometry (ESPI) as a powerful tool in determining diffusion coefficients and partition coefficients for proteins in gels. ESPI employs a CCD camera instead of a holographic plate as in conventional holographic interferometry. This gives the advantage of being able to choose the reference state freely. If a hologram at the,reference state is taken and compared to a hologram during the diffusion process, an interferometric picture can be generated that describes the refraction index gradients and thus the concentration gradients in the gel as well as in the liquid. MATLAB is then used to fit Fick's law to the experimental data to obtain the diffusion coefficients in gel and liquid. The partition coefficient is obtained from the same experiment from the flux condition at the interface between gel and liquid. This makes the comparison between the different diffusants more reliable than when the measurements are performed in separate experiments. The diffusion and partitioning coefficients of lysozyme, BSA, and IgG in 4% agarose gel at pH 5.6 and in 0.1 M NaCl have been determined. In the gel the diffusion coefficients were 11.2 +/- 1.6, 4.8 +/- 0.6, and 3.0 +/- 0.3 m(2)/s for lysozyme, BSA, and IgG, respectively. The partition coefficients were determined to be 0.65 +/- 0.04, 0.44 +/- 0.06, and 0.51 +/- 0.04 for lysozyme, BSA, and IgG, respectively. The current study shows that ESPI is easy to use and gives diffusion coefficients and partition coefficients for proteins with sufficient accuracy from the same experiment.
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| 256. |
- Karlsson, David, et al.
(författare)
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Methodologies for model calibration to assist the design of a preparative ion-exchange step for antibody purification
- 2004
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1033:1, s. 71-82
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Tidskriftsartikel (refereegranskat)abstract
- This work proposes methodologies using a model-based approach to gain knowledge on and assist the development of an ion-exchange step in a protein purification process; the separation of IgG from a mixture containing IgG, insulin and transferrin. This approach is suitable for capture and intermediate steps in a process. Both methods involve four consecutive steps. Firstly, the retention of the different protein components is determined giving a retention map of the system. From this the optimal pH and buffer can be determined. Secondly, additional salt gradient experiments are performed at the selected pH. Thirdly, experimental breakthrough curves have to be generated for the protein if the adsorption capacity of the medium for each component is not known. Fourthly, a validation experiment is performed. In method 1, where the capacity for the medium is assumed to be known, the protein adsorption is described by Langmuir kinetics with a mobile phase modulator (MPM). In this description salt is considered to be inert. In method 2 the adsorption behavior is described by steric mass action (SMA), where the salt component competes with the proteins for the available binding sites. Both methods use a dispersion model to describe transport in the mobile phase in the column. The methods are able to predict the separation and loading behavior of the three components. The methods can, with reasonable accuracy, predict the breakthrough of transferrin in a mixture of insulin, IgG and transferrin. Method I requires fewer experiments and predicts the mean volume of breakthrough for the loading step in the validation experiment more accurately than method 2. On the other hand, method 2 has a better accuracy to predict the position of 10% breakthrough and the shape of the breakthrough curve. The methods suggested in this work are shown to be efficient in process development. Some additional experiments have to be performed to obtain the unknown parameters in the models. However, the predictability that is achieved results in less experimental work in the process design as a whole. (C) 2004 Elsevier B.V. All rights reserved.
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| 257. |
- Karlsson, David, et al.
(författare)
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Model-based optimization of a preparative ion-exchange step for antibody purification
- 2004
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1055:1-2, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- A method using a model-based approach to design and optimize an ion-exchange step in a protein purification process is proposed for the separation of IgG from a mixture containing IgG, BSA and myoglobin. The method consists of three steps. In the first step, the model is calibrated against carefully designed experiments. The chromatographic model describes the convective and dispersive flow in the column, the diffusion in the adsorbent particles, and the protein adsorption using Langmuir kinetics with mobile phase modulators (MPM). In the second step, the model is validated against a validation experiment and analyzed. In the third and final step, the operating conditions are optimized. In the optimization step, the loading volume and the elution gradient are optimized with regard to the most important costs: the fixed costs and the feed cost. The optimization is achieved by maximizing the objective functions productivity (i.e. the production rate for a given amount of stationary phase) and product yield (i.e. the fraction of IgG recovered in the product stream). All optimization is conducted under the constraint of 99% purity of the IgG. The model calibration and the analysis show that this purification step is determined mainly by the kinetics. although as large a protein as IgG is used in the study. The two different optima resulting from this study are a productivity of 2.7 g IgG/(s m(3)) stationary phase and a yield of 90%. This model-based approach also gives information of the robustness of the chosen operating conditions. It is shown that the bead diameter could only be increased from 15 mum to 35 mum with maximum productivity and a 99% purity constraint due to increased diffusion hindrance in larger beads. (C) 2004 Elsevier B.V. All rights reserved.
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| 258. |
- Karlsson, Stefan, et al.
(författare)
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Korrosion av planglas inom byggbranschen kopplat till betong
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Ett förekommande problem under byggprocessen är betongrinning. Innebörden av betongrinning är att vatten varit i kontakt med färsk betong och därefter påverkat glasytor till fasader/balkonger/fönster. Påverkan på glaset kan vara fysisk och ibland även kemisk. Resultatet blir droppfläckar, rinnmärken och utfällningar som försämrar glasets ljusgenomsläpplighet och estetiska intryck. Så länge påverkan enbart är fysisk är denna skada relativt lätt att ta bort antingen med hjälp av mekanisk polering eller genom att torka glaset med utspädd syra. Ofta fortskrider dock processen till ett kemiskt angrepp på glaset, vilket är permanent och inte går att avlägsna helt med ovan nämnda metoder. Kemiska reaktioner har då skapat etsningar i glasytan som på sikt blir i storleksordningen mikrometer djupa.I denna förstudie har vi försökt simulera betongrinningsangrepp dels under kontrollerade förhållanden i laboratoriemiljö och dels i utomhusmiljö. Försöksvariablerna var två olika betongvarianter samt glas med respektive utan ett på marknaden befintligt glasskyddande medel. Resultatet av försöken har analyserats genom okulär bedömning, mikroanalys med svepelektronmikroskop och energidispersiv röntgenspektroskopi samt yttopografimätningar med optisk profilometer. Testerna resulterade i utfällningar på glasytan innehållande ämnena svavel, kalium och kalcium, vilka bedöms härstamma från betongen. Efter inomhusförsöken, som pågick i fyra månader, gick utfällningarna att tvätta bort med saltsyralösning, och inga djupgående, permanenta korrosionsskador syntes på glaset. Utomhusförsöken utsträcktes till elva månader, varpå bestående skador kunde konstateras på glasytorna efter att utfällningarna tvättats bort. Djupet på skadorna uppmättes som mest till cirka en halv mikrometer. Varken sänkning av pH i betongen eller skyddsbehandling av glaset bidrog till att hindra uppkomst av fläckighet eller etsningar på glaset. I diskussioner med industrirepresentanter konstaterades att betongrinning är ett ganska vanligt problem, som är oberoende av geografi. Tidigare försök med behandling av både betong och glas varit verkningslösa. I majoriteten av fall handlar problemen om inglasade balkonger alternativt glasräcken i kombination med balkongplatta i betong. Det man vet fungerar är att använda en korrekt konstruktion som hindrar vattnet från att droppa ned på glaset. Regelbunden rengöring av glasen hjälper också och kommer förmodligen hamna som ett underhållskrav mot kunder.
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| 259. |
- Kaunisto, Erik, et al.
(författare)
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A mechanistic modelling approach to polymer dissolution using magnetic resonance microimaging
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 147:2, s. 232-241
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Tidskriftsartikel (refereegranskat)abstract
- In this paper a computationally efficient mathematical model describing the swelling and dissolution of a polyethylene oxide tablet is presented. The model was calibrated against polymer release, front position and water concentration profile data inside the gel layer, using two different diffusion models. The water concentration profiles were obtained from magnetic resonance microimaging data which, in addition to the previously used texture analysis method, can help to validate and discriminate between the mechanisms of swelling, diffusion and erosion in relation to the dissolution process. Critical parameters were identified through a comprehensive sensitivity analysis, and the effect of hydrodynamic shearing was investigated by using two different stirring rates. Good agreement was obtained between the experimental results and the model. (C) 2010 Elsevier B.V. All rights reserved.
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| 260. |
- Kaunisto, Erik, et al.
(författare)
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Dissolution Kinetics or Pure Mass Transfer? A Mechanistic Study of Dissolution
- 2011
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Ingår i: AIChE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 57:10, s. 2610-2617
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Tidskriftsartikel (refereegranskat)abstract
- In many cases, classic in vitro tests are used to investigate dissolution from powders and solids. A problem with these kinds of tests is the frequent use of agitation, leading to a lumped description of the properties at the solid-liquid intetface. The hydrodynamic forces arising from agitation might have a nontrivial impact on the dissolution properties, thus calling for a comparison of results with those stemming from stagnant dissolution with the aim to increase the understanding of the dissolution process. Stagnant dissolution of compressed solid benzoic acid was examined using the noninvasive electronic speckle pattern interferometry technique in this study. The diffusion coefficient for benzoic acid in 37 degrees C water was measured using the same technique, and, by combining the results, the surface kinetics at the solid-liquid intetface were calculated. A comparison with previous dissolution data from a rotating disk suggests that the presence of convection can increase the observed surface kinetics. (C) 2010 American Institute of Chemical Engineers AlChE J, 57: 2610-2617, 2011
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