| 231. |
- Nord, Maria, et al.
(författare)
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The Effect of Peripheral Enzyme Inhibitors on Levodopa Concentrations in Blood and CSF
- 2010
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 25:3, s. 363-367
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Tidskriftsartikel (refereegranskat)abstract
- Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa. shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day I; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg bid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C-max of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C-max in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.
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| 232. |
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| 233. |
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| 234. |
- Nyholm, Dag, et al.
(författare)
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Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson's disease
- 2004
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 19:4, s. 446-451
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Tidskriftsartikel (refereegranskat)abstract
- AbstractFrequent assessment of the symptoms in Parkinson's disease (PD) is important in both clinical and experimental settings, especially when motor fluctuations are present. Patient diaries are increasingly used in studies, allowing patients to stay in their home environments. However, traditional paper diaries may not reflect reality because of a lack in compliance or retrospective data entries. This study presents a comparison between paper diaries and a new method, real-time data capture with a hand-held computer (electronic diary). Twenty patients with PD diagnosed at least 5 years previously were randomly assigned to use either a paper diary or an electronic diary on 8 days during 1 month. Questions were answered every 2 hours over a 12-hour period on each day. Median compliance was 88% with the electronic diary and 98% with the paper diary, although strict compliance to the scheduled times by patients using the paper diary was 78%. Neither age nor earlier experience with computers affected the patient's ability to use the electronic diary. Electronic diaries can be used for self-assessment of PD symptoms. The real-time feature provides fast access to clean data with knowledge of true compliance.
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| 235. |
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| 236. |
- Ogaki, Kotaro, et al.
(författare)
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Multiple system atrophy and apolipoprotein E
- 2018
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 33:4, s. 647-650
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. Objective: This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and -synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect -synuclein uptake in a oligodendrocyte cell.Methods: One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with -synuclein and recombinant human apolipoprotein E, with internalized -synuclein imaged by confocal microscopy and cells analyzed by flow cytometry.Results: No significant association with risk of MSA or was observed for either Apolipoprotein E 2 or 4. -Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E 4 significantly reduced -synuclein uptake in the oligodendrocytic cell line.Conclusions: Despite differential effects of apolipoprotein E isoforms on -synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or -synuclein pathology.
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| 237. |
- Olanow, C. Warren, et al.
(författare)
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Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:1, s. 31-40
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Forskningsöversikt (refereegranskat)abstract
- Altered protein handling is thought to play a key role in the etiopathogenesis of Parkinson's disease (PD), as the disorder is characterized neuropathologically by the accumulation of intraneuronal protein aggregates (Lewy bodies and Lewy neurites). Attention has particularly focused on the alpha-synuclein protein, as it is the principal component of Lewy pathology. Moreover, point mutations in the alpha-synuclein gene cause rare familial forms of PD. Importantly, duplication/triplication of the wild type alpha-synuclein gene also cause a form of PD, indicating that increased levels of the normal alpha-synuclein protein is sufficient to cause the disease. Further, single nucleotide polymorphisms in the alpha-synuclein gene are associated with an increased risk of developing sporadic PD. Recent evidence now suggests the possibility that alpha-synuclein is a prion-like protein and that PD is a prion-like disease. Within cells, alpha-synuclein normally adopts an alpha-helical conformation. However, under certain circumstances, the protein can undergo a profound conformational transition to a beta-sheet-rich structure that polymerizes to form toxic oligomers and amyloid plaques. Recent autopsy studies of patients with advanced PD who received transplantation of fetal nigral mesencephalic cells more than a decade earlier demonstrated that typical Lewy pathology had developed within grafted neurons. This suggests that alpha-synuclein in an aberrantly folded, beta-sheet-rich form had migrated from affected to unaffected neurons. Laboratory studies confirm that alpha-synuclein can transfer from affected to unaffected nerve cells, where it appears that the misfolded protein can act as a template to promote misfolding of host alpha-synuclein. This leads to the formation of larger aggregates, neuronal dysfunction, and neurodegeneration. Indeed, recent reports demonstrate that a single intracerebral inoculation of misfolded alpha-synuclein can induce Lewy-like pathology in cells that can spread from affected to unaffected regions and can induce neurodegeneration with motor disturbances in both transgenic and normal mice. Further, inoculates derived from the brains of elderly alpha-synuclein-overexpressing transgenic mice have now been shown to accelerate the disease process when injected into the brains of young transgenic animals. Collectively, these findings support the hypothesis that alpha-synuclein is a prion-like protein that can adopt a self-propagating conformation that causes neurodegeneration. We propose that this mechanism plays an important role in the development of PD and provides novel targets for candidate neuroprotective therapies. (C) 2013 Movement Disorder Society
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| 238. |
- Olsson, Bob, 1969, et al.
(författare)
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The glial marker YKL-40 is decreased in synucleinopathies.
- 2013
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 28:14, s. 1882-1885
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Tidskriftsartikel (refereegranskat)abstract
- Microglia are resident immunosurveillant cells in the central nervous system, and astrocytes are important for blood flow, plasticity, and neurotransmitter regulation. The aim of this study was to investigate whether astrocyte and microglial activation, estimated through markers in cerebrospinal fluid and serum, differed between synucleinopathies, tauopathies, and controls.
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| 239. |
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| 240. |
- Outeiro, Tiago F., et al.
(författare)
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From iPS Cells to Rodents and Nonhuman Primates : Filling Gaps in Modeling Parkinson's Disease
- 2021
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:4, s. 832-841
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is primarily known as a movement disorder because of typical clinical manifestations associated with the loss of dopaminergic neurons in the substantia nigra. However, it is now widely recognized that PD is a much more complex condition, with multiple and severe nonmotor features implicating additional brain areas and organs in the disease process. Pathologically, typical forms of PD are characterized by the accumulation of α-synuclein-rich protein inclusions known as Lewy bodies and Lewy neurites, although other types of protein inclusions are also often present in the brain. Familial forms of PD have provided a wealth of information about molecular pathways leading to neurodegeneration, but only to add to the complexity of the problem and uncover new knowledge gaps. Therefore, modeling PD in the laboratory has become increasingly challenging. Here, we discuss knowledge gaps and challenges in the use of laboratory models for the study of a disease that is clinically heterogeneous and multifactorial. We propose that the combined use of patient-derived cells and animal models, along with current technological tools, will not only expand our molecular and pathophysiological understanding of PD, but also assist in the identification of therapeutic strategies targeting relevant pathogenic pathways.
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