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- Devos, David, et al.
(författare)
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Trial of Deferiprone in Parkinson’s Disease
- 2022
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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| 2. |
- Fuzzi, Sandro, et al.
(författare)
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Overview of the inorganic and organic composition of size-segregated aerosol in Rondonia, Brazil, from the biomass-burning period to the onset of the wet season
- 2007
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Ingår i: Journal of Geophysical Research. - 2156-2202. ; 112:D1
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Tidskriftsartikel (refereegranskat)abstract
- The aerosol characterization experiment performed within the Large-Scale Biosphere-Atmosphere Experiment in Amazonia-Smoke, Aerosols, Clouds, Rainfall and Climate (LBA-SMOCC) field experiment carried out in Rondonia, Brazil, in the period from September to November 2002 provides a unique data set of size-resolved chemical composition of boundary layer aerosol over the Amazon Basin from the intense biomass-burning period to the onset of the wet season. Three main periods were clearly distinguished on the basis of the PM10 concentration trend during the experiment: (1) dry period, with average PM10 well above 50 mu g m(-3); (2) transition period, during which the 24-hour-averaged PM10 never exceeded 40 mu g m(-3) and never dropped below 10 mg m(-3); (3) and wet period, characterized by 48-hour-averaged concentrations of PM10 below 12 mu g m(-3) and sometimes as low as 2 mu g m(-3). The trend of PM10 reflects that of CO concentration and can be directly linked to the decreasing intensity of the biomass- burning activities from September through November, because of the progressive onset of the wet season. Two prominent aerosol modes, in the submicron and supermicron size ranges, were detected throughout the experiment. Dry period size distributions are dominated by the fine mode, while the fine and coarse modes show almost the same concentrations during the wet period. The supermicron fraction of the aerosol is composed mainly of primary particles of crustal or biological origin, whereas submicron particles are produced in high concentrations only during the biomass-burning periods and are mainly composed of organic material, mostly water-soluble, and similar to 10% of soluble inorganic salts, with sulphate as the major anion. Size-resolved average aerosol chemical compositions are reported for the dry, transition, and wet periods. However, significant variations in the aerosol composition and concentrations were observed within each period, which can be classified into two categories: (1) diurnal oscillations, caused by the diurnal cycle of the boundary layer and the different combustion phase active during day (flaming) or night (smouldering); and (2) day-to-day variations, due to alternating phases of relatively wet and dry conditions. In a second part of the study, three subperiods representative of the conditions occurring in the dry, transition, and wet periods were isolated to follow the evolution of the aerosol chemical composition as a function of changes in rainfall rate and in the strength of the sources of particulate matter. The chemical data set provided by the SMOCC field experiment will be useful to characterize the aerosol hygroscopic properties and the ability of the particles to act as cloud condensation nuclei.
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| 3. |
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| 4. |
- Schmid, Otmar, et al.
(författare)
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Derivation of the Density and Refractive Index of Organic Matter and Elemental Carbon from Closure between Physical and Chemical Aerosol Properties
- 2009
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 43:4, s. 1166-1172
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Tidskriftsartikel (refereegranskat)abstract
- Information on the density (p) and refractive index m(=n-ik) of elemental carbon (ECa) and organic matter (OMa), the main carbon components of atmospheric aerosols, has frequently been obtained from closure calculations between physical and chemical aerosol properties. However, this approach has suffered from large uncertainties since there were more unknown (or poorly known) parameters than defining equations. In this study, we propose a method that avoids this ambiguity mainly by considering both optical and mass closure and by expressing the three ECa parameters (p(Eca), n(Eca), k(ECa)) by a single (unknown) parameter. This allows mathematically rigorous determination of p(Eca), m(Eca), p(OMa) and m(OMa) from standard physico-chemical aerosol data and rigorous error analysis. The results are unambiguous and self-consistent, i.e., there is no difference between the chemically and physically derived p and m values of the atmospheric aerosol. Application of this method to our previously published data on biomass burning particles from Amazonia yields p(Eca) = 1.8(+/- 0.2) g/cm(3), m(ECa) = 1.9(+/- 0.1)-i0.20(-0.04/+0.02), p(OMa) = 1.39(+/- 0.13) g/cm(3) and m(OMa)=1.46(+/- 0.02), where the 1 sigma uncertainty limits given in parenthesis are based on the principles of error propagation. The relatively low imaginary part of mEca indicates the presence of only partially graphitized elemental carbon, which is consistent with biomass burning aerosol dominated bysmoldering combustion conditions.
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