| 1. |
- Lillethorup, Thea Pinholt, et al.
(författare)
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In vivo quantification of glial activation in minipigs overexpressing human α-synuclein
- 2018
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Ingår i: Synapse. - : Wiley. - 0887-4476. ; 72:12
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11C](R)PK11195, to image brain microglial activation and (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.
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| 2. |
- Nielsen, Roni Ranghøj, et al.
(författare)
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Quantitative estimation of extravascular lung water volume and preload by dynamic 15O-water positron emission tomography
- 2019
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press. - 2047-2404 .- 2047-2412. ; 20:10, s. 1120-1128
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Left ventricular filling pressure (preload) can be assessed by pulmonary capillary wedge pressure (PCWP) during pulmonary arterial catheterization (PAC). An emerging method [pulse indexed contour cardiac output (PICCO)] can estimate preload by global end-diastolic volume (GEDV) and congestion as extravascular lung water (EVLW) content. However, no reliable quantitative non-invasive methods are available. Hence, in a porcine model of pulmonary congestion, we evaluated EVLW and GEDV by positron emission tomography (PET). The method was applied in 35 heart failure (HF) patients and 9 healthy volunteers.METHODS AND RESULTS: Eight pigs were studied. Pulmonary congestion was induced by a combination of beta-blockers, angiotensin-2 agonist and saline infusion. PAC, PICCO, computerized tomography, and 15O-H2O-PET were performed. EVLW increased from 521 ± 76 to 973 ± 325 mL (P < 0.001) and GEDV from 1068 ± 170 to 1254 ± 85 mL (P < 0.001). 15O-H2O-PET measures of EVLW increased from 566 ± 151 to 797 ± 231 mL (P < 0.001) and GEDV from 364 ± 60 to 524 ± 92 mL (P < 0.001). Both EVLW and GEDV measured with PICCO and 15O-H2O-PET correlated (r2 = 0.40, P < 0.001; r2 = 0.40, P < 0.001, respectively). EVLW correlated with Hounsfield units (HU; PICCO: r2 = 0.36, P < 0.001, PET: r2 = 0.46, P < 0.001) and GEDV with PCWP (PICCO: r2 = 0.20, P = 0.01, PET: r2 = 0.29, P = 0.002). In human subjects, measurements were indexed (I) for body surface area. Neither EVLWI nor HU differed between chronic stable HF patients and healthy volunteers (P = 0.11, P = 0.29) whereas GEDVI was increased in HF patients (336 ± 66 mL/m2 vs. 276 ± 44 mL/m2, P = 0.01).CONCLUSION: The present study demonstrates that 15O-H2O-PET can assess pulmonary congestion and preload quantitatively. Hence, prognostic information from 15O-H2O-PET examinations should be evaluated in clinical trials.
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| 3. |
- O'Regan, Matt, et al.
(författare)
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The Holocene dynamics of Ryder Glacier and ice tongue in north Greenland
- 2021
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 15:8, s. 4073-4097
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Tidskriftsartikel (refereegranskat)abstract
- The northern sector of the Greenland Ice Sheet is considered to be particularly susceptible to ice mass loss arising from increased glacier discharge in the coming decades. However, the past extent and dynamics of outlet glaciers in this region, and hence their vulnerability to climate change, are poorly documented. In the summer of 2019, the Swedish icebreaker Oden entered the previously unchartered waters of Sherard Osborn Fjord, where Ryder Glacier drains approximately 2 % of Greenland's ice sheet into the Lincoln Sea. Here we reconstruct the Holocene dynamics of Ryder Glacier and its ice tongue by combining radiocarbon dating with sedimentary facies analyses along a 45 km transect of marine sediment cores collected between the modern ice tongue margin and the mouth of the fjord. The results illustrate that Ryder Glacier retreated from a grounded position at the fjord mouth during the Early Holocene (> 10.7±0.4 ka cal BP) and receded more than 120 km to the end of Sherard Osborn Fjord by the Middle Holocene (6.3±0.3 ka cal BP), likely becoming completely land-based. A re-advance of Ryder Glacier occurred in the Late Holocene, becoming marine-based around 3.9±0.4 ka cal BP. An ice tongue, similar in extent to its current position was established in the Late Holocene (between 3.6±0.4 and 2.9±0.4 ka cal BP) and extended to its maximum historical position near the fjord mouth around 0.9±0.3 ka cal BP. Laminated, clast-poor sediments were deposited during the entire retreat and regrowth phases, suggesting the persistence of an ice tongue that only collapsed when the glacier retreated behind a prominent topographic high at the landward end of the fjord. Sherard Osborn Fjord narrows inland, is constrained by steep-sided cliffs, contains a number of bathymetric pinning points that also shield the modern ice tongue and grounding zone from warm Atlantic waters, and has a shallowing inland sub-ice topography. These features are conducive to glacier stability and can explain the persistence of Ryder's ice tongue while the glacier remained marine-based. However, the physiography of the fjord did not halt the dramatic retreat of Ryder Glacier under the relatively mild changes in climate forcing during the Holocene. Presently, Ryder Glacier is grounded more than 40 km seaward of its inferred position during the Middle Holocene, highlighting the potential for substantial retreat in response to ongoing climate change.
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| 4. |
- Pertold, Cino, et al.
(författare)
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Prevalence of skull pathologies in European harbor seals (Phoca vitulina) during 1981–2014
- 2018
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Ingår i: Mammal Research. - : Springer Science and Business Media LLC. - 2199-2401 .- 2199-241X. ; 63:1, s. 55-63
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Tidskriftsartikel (refereegranskat)abstract
- Harbor seals (Phoca vitulina) inhabit the seas surrounding Denmark and are an important top predator in the marine food chain. This trophic position exposes them to environmental contaminants with disease epi- demics and hunting being additional threats to this popu- lation. It is therefore important to study how environmen- tal pollution at the current order of magnitude affects the health of the population. Earlier studies have shown that occurrence of periodontitis could be linked to the amount of pollution the seals were subjected to. In order to inves- tigate this further, 380 skulls and 141 mandibles of harbor seals (Phoca vitulina) from the Wadden Sea, the Limfjord, and Kattegat collected during the period 1970–2014 were examined. The skulls were examined for pathological le- sions. The Hounsfield Units (HU) which are correlated to the bone mineral density (BMD) were measured in a sub- sample (n= 34) using CT scans. The macroscopic examination revealed (with the exception of the Swedish part of Kattegat) a significant increase of pathological lesions over the study period of 1981–2014. The exami- nation of HU showed that median HU measured at mul- tiple sites was highest in the healthy skulls compared to the skulls with one or more of the lesions. A discriminant analysis allowed high discriminatory capacity to separate healthy skulls from the skulls with pathologies, simply by the utilization of the HU data. Former studies of BMD in marine mammals have shown that exposure to environ- mental chemicals alter BMD and cause periodontitis. The present study, based on temporal and spatial trends in BMD, confirms the results of previous studies Prevalence of skull pathologies in European harbor seals (Phoca vitulina) during 1981–2014 (PDF Download Available). Available from: https://www.researchgate.net/publication/320586176_Prevalence_of_skull_pathologies_in_European_harbor_seals_Phoca_vitulina_during_1981-2014 [accessed Dec 15 2017].
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| 5. |
- Thomassen, Sisse Anette, et al.
(författare)
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Cerebral blood flow measured by positron emission tomography during normothermic cardiopulmonary bypass : an experimental porcine study
- 2018
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Ingår i: Perfusion. - : SAGE Publications. - 0267-6591 .- 1477-111X. ; 33:5, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mean arterial blood pressure (MAP) and/or pump flow during normothermic cardiopulmonary bypass (CPB) are the most important factors of cerebral perfusion. The aim of this study was to explore the influence of CPB blood flow on cerebral blood flow (CBF) measured by dynamic positron emission tomography (PET) using O-15-labelled water with no pharmacological interventions to maintain the MAP.Methods: Eight pigs (69-71 kg) were connected to normothermic CPB. After 60 minutes (min) with a CPB pump flow of 60 mL/kg/min, the pigs were changed to either 35 mL/kg/min or 47.5 mL/kg/min for 60 min and, thereafter, all the pigs returned to 60 mL/kg/min for another 60 min. The MAP was measured continuously and the CBF was measured by positron emission tomography (PET) during spontaneous circulation and at each CPB pump flow after 30 min of steady state.Results: Two pigs were excluded due to complications. CBF increased from spontaneous circulation to a CPB pump flow of 60 mL/kg/min. A reduction in CPB pump flow to 47.5 mL/kg/min (n=3) resulted in only minor changes in CBF while a reduction to 35 mL/kg/min (n=3) caused a pronounced change (correlation coefficient (R-2) 0.56). A return of CPB pump flow to 60 mL/kg/min was followed by an increase in CBF, except in the one pig with the lowest CBF during low flow (R-2=0.44). CBF and MAP were not correlated (R-2=0.20).Conclusion: In this experimental porcine study, a relationship was observed between pump flow and CBF under normothermic low-flow CPB. The effect of low pump flow on MAP showed substantial variations, with no correlation between CBF and MAP.
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| 6. |
- Thomassen, Sisse Anette, et al.
(författare)
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Muscle Tissue Saturation Compared With Muscle Tissue Perfusion During Low Blood Flows : An Experimental Study.
- 2017
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 31:6, s. 2065-2071
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model.DESIGN: A prospective, randomized study.SETTING: Research laboratory, single institution.PARTICIPANTS: Eight pigs (69-71 kg).INTERVENTIONS: In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with (15)O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels.MEASUREMENTS AND MAIN RESULTS: The results showed profound systemic ischemia during low CPB blood flow. StO2 remained high until muscle tissue perfusion decreased to about 50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion.CONCLUSION: In an experimental CPB animal model, StO2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO2 and muscle tissue perfusion.
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