| 51. |
- Almandoz-Gil, Leire, et al.
(författare)
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In situ proximity ligation assay reveals co-localization of alpha-synuclein and SNARE proteins in murine primary neurons
- 2018
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of alpha-synuclein (alpha Syn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of aSyn is to promote the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between aSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human aSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human aSyn, a PLA signal indicating close proximity between aSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human aSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of aSyn and the SNARE proteins in primary neuronal cultures
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| 52. |
- Almemark, Mats, et al.
(författare)
-
Aktiva badhus
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Projektet syftar till att ta fram ett underlag som kan ligga till grund för de val man gör som anläggningsägare då en simhall med all kringutrustning skall utformas och byggas, i syfte att såväl byggnation som drift av badhusen ska genomföras på ett så miljö- och hälsomässigt samt ekonomiskt hållbart sätt som möjligt. De aspekter som behandlas är energianvändning, vattenrening, ventilation och innemiljö, driftsoptimering genom simulering av driften med en simuleringsmodell som har tagits fram inom ramen för projektet samt städmetoder. Den övervägande delen av befintliga badhus är utrustade med reningsanläggningar bestående av sandfilter med flockningssteg. I stort sett alla badhus använder klor för att desinficera badvattnet. I och med att problemen med bildning av desinfektionsbiprodukter uppmärksammats i en allt större utsträckning på senare tid så har kompletterande reningssteg tillförts. Membranfiltrering för rening av badvatten har länge varit en allt för energikrävande teknik och därför inte setts som ett gångbart alternativ till sandfilter. Det finns dock en potential för att använda membranteknik i större utsträckning framöver då tekniken utvecklats och idag inte är lika energikrävande som förr. Rent teoretiskt så är energibehovet för membranfiltrering i samma storleksordning som för sandfilter. De badhus som studerats i detta projekt har använt klor för att desinficera bassängvattnet. Inom ramen för projektet har energianvändningen i tre badhus kartlagts, och förslag till energieffektiviseringsåtgärder har tagits fram. Resultatet visar att det är möjligt effektivisera energianvändningen i badhus med i storleksordningen 70 procent jämfört med dagens nivåer, vilket avsevärt förbättrar såväl miljöprestanda som den ekonomiska bärkraften för anläggningarna.
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| 53. |
- Alvebratt, Caroline
(författare)
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Advanced Methods for Evaluation of the Performance of Complex Drug Delivery System
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low oral bioavailability of drugs originating from poor aqueous solubility is a common issue in drug development. Various enabling formulations have been presented to circumvent this limitation, many making use of supersaturation. In these, the drug is delivered to the gastro-intestinal lumen in a high energy state e.g. in amorphous form or a liquid lipid vehicle. Concentrations surpassing the equilibrium solubility of the crystalline drug are achieved, which facilitate increased absorption for dissolution-rate limited compounds. Meanwhile the use of the enabling formulation can be beneficial to increase the bioavailability of poorly water-soluble drugs, in vitro evaluation of these systems remain challenging. Limited methods have also evaluated several different types of enabling formulation in the same experimental setup. The overall aim of this thesis was therefore to develop assays to study the performance of various complex drug delivery systems. In the first part, a small scale dissolution apparatus, the µDiss Profiler, was used to study drug release from drug-loaded mesoporous magnesium carbonate (MMC). A protective filter was developed to minimize particle interference on the UV-measurements, enabling studies of supersaturation from the amorphous carrier. In the second paper, lipids were adsorbed onto the MMC. A modified in vitro lipolysis setup was established and the samples were analyzed with nuclear magnetic resonance spectroscopy. A stability study of the lipid-loaded MMC was also performed. The methods developed in the first two projects provided an insight to events occurring in the intestinal lumen. The intestinal absorption has however been shown to be a complex interplay between dissolution-digestion and permeation. In the final two projects, two devices comprising of a donor (luminal) chamber and a receiver (serosal) chamber were studied (the µFLUX and the enabling absorption, ENA, device). The two chambers were separated by a semipermeable membrane (cell-based and/or phospholipid-based). A wide range of enabling formulations were evaluated in the two assays. As the exposure in the donor correlated poorly with the exposure in the receiver compartment, this emphasizes the importance of in vitro methods taking both the dissolution-digestion and permeation into account. The ENA results also predicted the in vivo performance in rats well. To conclude, several models have been established in the thesis to study the in vitro performance of enabling formulations, which will be valuable for screening of appropriate drug delivery systems.
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| 54. |
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| 55. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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| 56. |
- Andersson, Irene, 1978, et al.
(författare)
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Increased atherosclerotic lesion area in apoE deficient mice overexpressing bovine growth hormone
- 2006
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 188:2, s. 331-40
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Tidskriftsartikel (refereegranskat)abstract
- Human growth hormone (GH) excess is linked to increased cardiovascular morbidity and mortality. However, little is known about the effect of GH excess on atherosclerosis. We developed a new mouse model to assess the hypothesis that GH overexpression accelerates atherosclerotic lesion formation. apoE(-/-) mice were crossed with bovine GH (bGH) transgenic mice to yield apoE(-/-) mice overexpressing bGH (apoE(-/-)/bGH). The mice were fed either standard or Western diet. At 22 weeks, atherosclerotic lesion area of thoracic aorta was larger in apoE(-/-)/bGH mice compared with littermate apoE(-/-) mice fed either diet (standard: +161+/-50%, Western: +430+/-134%). Aortic sinus lesions were more severe in apoE(-/-)/bGH mice fed standard diet compared with littermate apoE(-/-) mice. apoE(-/-)/bGH mice had lower (VLDL+LDL)/HDL ratios compared with littermate apoE(-/-) mice, while systolic blood pressure was higher in apoE(-/-)/bGH mice, irrespective of diet. The levels of serum amyloid A and hepatic CRP mRNA were higher in apoE(-/-)/bGH mice than in littermate apoE(-/-) mice. In conclusion, this study shows that excess GH augments the development of atherosclerosis in apoE(-/-) mice. The mechanisms could be direct effects of GH on cellular processes in the vessel wall or the result of concomitant processes such as hypertension or a general inflammatory state.
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| 57. |
- Andersson, Jan, et al.
(författare)
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Biologisk recipientkontroll vid Oskarshamns kärnkraftverk : Sammanställning av undersökningar till och med 2008
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Påverkan på fisk och bottenfauna av kylvattenutsläpp från ett kärnkraftverk vid svenska östersjökusten har övervakats under mer än 40 år. Positiva effekter på beståndsstorlek och tillväxt hos abborre har observerats och få fiskarter har påverkats i negativ riktning av kraftverkets drift. Stora och långsiktiga förändringar hos marina fiskarter som torsk, strömming och bottenlevande evertebrater har inte kunnat kopplas till kraftverkets drift utan antas spegla storskaliga förändringar hos Östersjöns ekosystem
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| 58. |
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| 59. |
- Andren, Peter, et al.
(författare)
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FUD rörande gång- och cykelvägar : en beskrivning av VTI:s kompetens och resurser
- 2006
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The present report presents, partly, the collected VTI research on the "functional properties" of pedestrian and bicycle roads, and partly a survey of what has been done in this field outside of VTI. The term "functional property" has been interpreted in a broad sense, and basically everything connected with bicycle roads and bicycle traffic is included in the VTI literature review, which is the major part of the report. The operating environment analysis is made on the basis of the discussions from a seminar held at VTI, December 12, 2005, and complemented with literature reviews. The possibilities to build an instrumented vehicle for measuring bicycle roads, and the relevant properties of an evenness index, were discussed at the seminar. In the literature review, the research of VTI has been divided into five parts: traffic safety, maintenance and operation, mode choice, measurement of cycle flow, and the umbrella part "others". The research concerning traffic safety dominates, both at VTI and elsewhere. One of the conclusions from the project is that VTI should try to get funding to develop a measuring vehicle for cycleway surfaces. There is also a need to develop the unreliable methods used today (elastic tube and induction coil) to count bicycle traffic.
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| 60. |
- Andresen Bergström, Moa, 1978, et al.
(författare)
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A skin-like cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites.
- 2007
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 127:5, s. 1145-53
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis is a complex syndrome representing immunological responses to cutaneous exposure to protein-reactive chemicals. Although many contact sensitizers directly can elicit this disorder, others (prohaptens) require activation. Knowledge regarding the activating mechanisms remains limited, but one possibility is metabolic activation by cytochrome P450 (CYP) enzymes in the skin. We have, after quantitative reverse transcriptase-PCR studies of the CYP content in 18 human skin samples, developed an enriched skin-like recombinant human (rh) CYP cocktail using CYP1A1, 1B1, 2B6, 2E1, and 3A5. To validate the rhCYP cocktail, a prohaptenic conjugated diene ((5R)-5-isopropenyl-2-methyl-1-methylene-2-cyclohexene) was investigated using: the skin-like rhCYP cocktail, a liver-like rhCYP cocktail, single rhCYP enzymes, liver microsomes, keratinocytes, and a dendritic cell (DC) assay. The diene was activated to sensitizing epoxides in all non-cell-based incubations including the skin-like rhCYP cocktail. An exocyclic epoxide metabolite ((7R)-7-isopropenyl-4-methyl-1-oxaspiro[2.5]oct-4-ene) was found to be mainly responsible for the allergenic activity of the diene. This epoxide also induced pronounced DC activation indicated by upregulation of IL-8. The skin-like rhCYP cocktail provides a simplified alternative to using skin tissue preparations in mechanistic studies of CYP-mediated skin metabolism of prohaptens and offers the future possibility of designing in vitro predictive assays for assessment of allergenic activity of prohaptens.
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