| 61. |
- Huttunen, Henri J., et al.
(författare)
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Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial
- 2023
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:7, s. 1209-1222
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE-PE2I. Results: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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| 62. |
- Jaars, Kerneels, et al.
(författare)
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Measurements of biogenic volatile organic compounds at a grazed savannah grassland agricultural landscape in South Africa
- 2016
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:24, s. 15665-15688
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Tidskriftsartikel (refereegranskat)abstract
- Biogenic volatile organic compounds (BVOCs) play an important role in the chemistry of the troposphere, especially in the formation of tropospheric ozone (O3) and secondary organic aerosols (SOA). Ecosystems produce and emit a large number of BVOCs. It is estimated on a global scale that approximately 90% of annual BVOC emissions are from terrestrial sources. In this study, measurements of BVOCs were conducted at the Welgegund measurement station (South Africa), which is considered to be a regionally representative background site situated in savannah grasslands. Very few BVOC measurements exist for savannah grasslands and results presented in this study are the most extensive for this type of landscape. Samples were collected twice a week for 2h during the daytime and 2h during the night-time through two long-term sampling campaigns from February 2011 to February 2012 and from December 2013 to February 2015, respectively. Individual BVOCs were identified and quantified using a thermal desorption instrument, which was connected to a gas chromatograph and a mass selective detector. The annual median concentrations of isoprene, 2-methyl-3-butene-2-ol (MBO), monoterpene and sesquiterpene (SQT) during the first campaign were 14, 7, 120 and 8pptv, respectively, and 14, 4, 83 and 4pptv, respectively, during the second campaign. The sum of the concentrations of the monoterpenes were at least an order of magnitude higher than the concentrations of other BVOC species during both sampling campaigns, with α-pinene being the most abundant species. The highest BVOC concentrations were observed during the wet season and elevated soil moisture was associated with increased BVOC concentrations. However, comparisons with measurements conducted at other landscapes in southern Africa and the rest of the world that have more woody vegetation indicated that BVOC concentrations were, in general, significantly lower for savannah grasslands. Furthermore, BVOC concentrations were an order of magnitude lower compared to total aromatic concentrations measured at Welgegund. An analysis of concentrations by wind direction indicated that isoprene concentrations were higher from the western sector that is considered to be a relatively clean regional background region with no large anthropogenic point sources, while wind direction did not indicate any significant differences in the concentrations of the other BVOC species. Statistical analysis indicated that soil moisture had the most significant impact on atmospheric levels of MBO, monoterpene and SQT concentrations, whereas temperature had the greatest influence on isoprene levels. The combined O3 formation potentials of all the BVOCs measured calculated with maximum incremental reactivity (MIR) coefficients during the first and second campaign were 1162 and 1022pptv, respectively. α-Pinene and limonene had the highest reaction rates with O3, whereas isoprene exhibited relatively small contributions to O3 depletion. Limonene, α-pinene and terpinolene had the largest contributions to the OH reactivity of BVOCs measured at Welgegund for all of the months during both sampling campaigns.
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| 63. |
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| 64. |
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| 65. |
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| 66. |
- Kajos, M. K., et al.
(författare)
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Terpenoid emissions from fully grown east Siberian Larix cajanderi trees
- 2013
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 10:7, s. 4705-4719
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Tidskriftsartikel (refereegranskat)abstract
- While emissions of many biogenic volatile organic compounds (BVOCs), such as terpenoids, have been studied quite intensively in North American and Scandinavian boreal forests, the vast Siberian boreal forests have remained largely unexplored by experimental emission studies. In this study the shoot-scale terpenoid emission rates from two mature Larix cajanderi trees growing in their natural habitat in eastern Siberia were measured at the Spasskaya Pad flux measurement site (62 degrees 15'18.4 '' N, 129 degrees 37'07.9 '' E) located on the western bank of the Lena river. The measurements were conducted during three campaigns: 3-24 June, 8-26 July, and 14-30 August, in the summer of 2009. A dynamic flow-through enclosure technique was applied for adsorbent sampling, and the samples were analysed offline with a gas chromatograph. Between 29 and 45 samples were taken from each shoot during all three campaigns. Seven different monoterpenes, six different sesquiterpenes, linalool isoprene, and 2-methyl-3-buten-2-ol (MBO) were identified. The monthly median value of the total terpenoid emissions varied between 0.006 and 10.6 mu g g(dw)(-1)h(-1). The emissions were dominated by monoterpenes, which constituted between 61 and 92% of the total emissions. About half of the monoterpene emissions were comprised of Delta(3)-carene; alpha- and beta-pinene had significant emissions as well. Linalool emissions were also substantial, comprising 3-37% of the total emissions, especially in June. Sesquiterpenes accounted for less than 3% and isoprene less than 1% of the total emissions. Based on the measured emission rates, the relative atmospheric concentration of each compound was estimated. Monoterpenes were the species with the highest relative concentration, while linalool and sesquiterpenes had a notably smaller contribution to the estimated atmospheric concentration than to the emission rates. A temperature-dependent pool algorithm with a constant beta (0.09 degrees C-1 for monoterpenes and 0.143 degrees C-1 for sesquiterpenes) was used to normalize the measured emission data. For monoterpenes the emission potential varied between 0.5 and 18.5 mu g g(dw)(-1)h(-1) and for sesquiterpenes between 0.02 and 0.4 mu g g(dw)(-1)h(-1).
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| 67. |
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| 68. |
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| 69. |
- Konki, Mikko, et al.
(författare)
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Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer's disease.
- 2019
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Ingår i: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs.RESULTS: Comparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset.CONCLUSIONS: DNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.
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