scholarly journals The effect of steady‐state ropinirole on plasma concentrations of digoxin in patients with Parkinson’s disease

1999 ◽  
Vol 47 (2) ◽  
pp. 219-222 ◽  
Author(s):  
Taylor ◽  
Beerahee ◽  
Citerone ◽  
Davy ◽  
Fitzpatrick ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Steady State ◽  
Plasma Concentrations

scholarly journals Levodopa and executive performance in Parkinson's disease: A randomized study

2008 ◽  
Vol 14 (5) ◽  
pp. 832-841 ◽  
Author(s):  
BERTA PASCUAL-SEDANO ◽  
JAIME KULISEVSKY ◽  
MANEL BARBANOJ ◽  
CARMEN GARCÍA-SÁNCHEZ ◽  
ANTONIA CAMPOLONGO ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Wisconsin Card Sorting Test ◽  
Cognitive Changes ◽  
Executive Performance ◽  
Tower Of Hanoi

Parkinson's disease (PD) patients may experience fluctuations in executive performance after oral levodopa (LD). Their relationship with the pharmacokinetic profile of LD and with distinct cognitive processes associated with frontal-basal ganglia circuits is not well understood. In this randomized, double-blind, crossover study we plotted acute cognitive changes in 14 PD patients challenged with faster (immediate-release, IR) versus slower (controlled-release, CR) increases in LD plasma concentrations. We monitored motor status, LD plasma levels, and performance on four tasks of executive function (Wisconsin Card Sorting Test—WCST, Sternberg test, Stroop and Tower of Hanoi), 1 hr before and over +6 hr after IR and CR-LD dose. Analysis of variance demonstrated significant but divergent changes in the Sternberg (6-digit but not 2- and 4-digit) test: improvement after CR-LD and worsening after IR-LD. Marginal improvement (p = .085) was observed with CR-LD in the WCST, while no significant differences were seen for the Stroop or Tower of Hanoi tests. Executive-related performance after LD challenge may differ depending on the LD time-to-peak plasma concentration and specific task demands. A slower rise in LD levels appears to have a more favorable impact on more difficult working memory tests. These results require replication to determine their generalization. (JINS, 2008, 14, 832–841.)

scholarly journals The G2385R risk factor for Parkinson's disease enhances CHIP-dependent intracellular degradation of LRRK2

2017 ◽  
Vol 474 (9) ◽  
pp. 1547-1558 ◽  
Author(s):  
Iakov N. Rudenko ◽  
Alice Kaganovich ◽  
Rebekah G. Langston ◽  
Aleksandra Beilina ◽  
Kelechi Ndukwe ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Steady State ◽  
Proteasomal Degradation ◽  
Wild Type ◽  
Intracellular Protein ◽  
Protein Levels ◽  
Intracellular Degradation

Autosomal dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease (PD). Most pathogenic LRRK2 mutations result in amino acid substitutions in the central ROC (Ras of complex proteins)–C-terminus of ROC–kinase triple domain and affect enzymatic functions of the protein. However, there are several variants in LRRK2, including the risk factor G2385R, that affect PD pathogenesis by unknown mechanisms. Previously, we have shown that G2385R LRRK2 has decreased kinase activity in vitro and altered affinity to LRRK2 interactors. Specifically, we found an increased binding to the chaperone Hsp90 (heat shock protein 90 kDa) that is known to stabilize LRRK2, suggesting that G2385R may have structural effects on LRRK2. In the present study, we further explored the effects of G2385R on LRRK2 in cells. We found that G2385R LRRK2 has lower steady-state intracellular protein levels compared with wild-type LRRK2 due to increased protein turnover of the mutant protein. Mechanistically, this is a consequence of a higher affinity of G2385R compared with the wild-type protein for two proteins involved in proteasomal degradation, Hsc70 and carboxyl-terminus of Hsc70-interacting protein (CHIP). Overexpression of CHIP decreased intracellular protein levels of both G2385R mutant and wild-type LRRK2, while short interfering RNA CHIP knockdown had the opposite effect. We suggest that the G2385R substitution tilts the equilibrium between refolding and proteasomal degradation toward intracellular degradation. The observation of lower steady-state protein levels may explain why G2385R is a risk factor rather than a penetrant variant for inherited PD.

scholarly journals Longevity factor klotho and resistance to cognitive deficits in a transgenic mouse model and in individuals with Parkinson’s disease

2020 ◽  
Author(s):  
Arturo Moreno ◽  
Nijee Luthra ◽  
Luke Bonham ◽  
Jonathan Lin ◽  
Lauren Broestl ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Steady State ◽  
Cognitive Deficits ◽  
Genetic Variant ◽  
Transgenic Mouse Model ◽  
Primary Risk Factor ◽  
Related Mortality

Abstract Aging is the primary risk factor for Parkinson’s disease (PD) and cognitive impairment from PD is a major and unmet biomedical challenge. Klotho, a pleiotropic protein, extends lifespan and enhances cognition. Whether longevity factors such as klotho can counteract PD-related mortality and deficits in mice or associate with resistance to PD in humans is unknown. Here we show that transgenic elevation of klotho increased lifespan, improved synaptic and cognitive, but not motor, functions in mice, and decreased steady state α-synuclein levels in the brains of mice that express wildtype human α-synuclein. In humans, a genetic variant of KLOTHO that increases circulating klotho levels associated with better executive cognition and less CSF abnormalities of α-synuclein in individuals with PD. Thus, klotho can counteract cognitive deficits related to PD, possibly modulating α-synuclein levels – and these findings may be relevant to new therapeutic pathways for human PD.

scholarly journals Tranylcypromine Isomers and Parkinson's Disease: New Aspects of an Old Drug

1981 ◽  
Vol 74 (9) ◽  
pp. 649-652 ◽  
Author(s):  
G P Reynolds ◽  
P Riederer ◽  
M Sandler
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Concentrations ◽  
Depressive Illness ◽  
Low Doses ◽  
Mao Activity ◽  
Platelet Monoamine Oxidase ◽  
Hypertensive Reaction ◽  
Antiparkinsonian Therapy ◽  
Comparative Trials

The tranylcypromine stereoisomers have been investigated in a series of comparative trials in Parkinson's disease and the results indicate that doses below 3 mg/day, of the (+)-isomer in particular, are effective as adjuvant antiparkinsonian therapy. Biochemical results, monitoring platelet monoamine oxidase (MAO) activity and plasma concentrations of drugs and phenylethylamine, an MAO substrate, showed such low doses of the (+)-isomer to inhibit MAO without inducing the hypertensive reaction sometimes observed at higher dosage. These findings, along with the observation of substantial pharmacokinetic differences between the two isomers are discussed, particularly in relation to reports on their efficacy in depressive illness.

scholarly journals Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Natália Pessoa Rocha ◽  
Paula Luciana Scalzo ◽  
Izabela Guimarães Barbosa ◽  
Mariana Soares Souza ◽  
Isabela Boechat Morato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Depressive Symptoms ◽  
Cognitive Performance ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Cognitive Status ◽  
Enzyme Linked Immunosorbent Assay ◽  
Significant Difference ◽  
And Control

Cognitive impairment and depressive symptoms are of great interest in Parkinson’s disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD.

scholarly journals Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Wolfram Eisenreich ◽  
Bernd Sommer ◽  
Sebastian Hartter ◽  
Wolfgang H. Jost
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Agonist ◽  
Extended Release ◽  
Plasma Concentrations ◽  
Safety Data ◽  
Immediate Release ◽  
Efficacy And Safety ◽  
Release Formulation ◽  
Extended Release Formulation

Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.

scholarly journals An Activity Recognition Framework for Monitoring Non-Steady-State Locomotion of Individuals with Parkinson’s Disease

2021 ◽  
Author(s):  
Mahdieh Kazemimoghadam ◽  
Nicholas Fey
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Steady State ◽  
Activity Recognition ◽  
Short Term Memory ◽  
Upper Body ◽  
Linear Discriminant ◽  
Healthcare Monitoring ◽  
Task Recognition ◽  
Improved Performance

Abstract Background: Fundamental knowledge in activity recognition of individuals with motor disorders such as Parkinson’s disease (PD) has been primarily limited to detection of steady-state/static tasks (e.g., sitting, standing, walking), and identification of non-steady-state locomotion on uneven terrains (stairs, ramps) has not received much attention. Furthermore, previous research has mainly relied on data from a large number of locations which could adversely affect user convenience and system performance. Methods: Here, individuals with mild stages of PD and healthy subjects performed non-steady-state circuit trials comprising stairs, ramp, and changes of direction. An offline analysis using a linear discriminant analysis (LDA) classifier and a Long-Short Term Memory (LSTM) neural network was performed for task recognition. The performance of accelerographic and gyroscopic information from varied lower/upper-body segments were tested across a set of user-independent and user-dependent training paradigms. Results: Comparing the F1 score of a given segment across classifiers showed improved performance using LSTM compared to LDA. Using LSTM, even a subset of information (e.g., feet data) in subject-independent paradigms appeared to provide F1 score > 0.8. However, employing LDA was shown to be at the expense of being limited to using a subject-dependent paradigm and/or biomechanical data from multiple body locations. Conclusion: The findings could inform a number of applications in the field of healthcare monitoring and developing advanced lower-limb assistive devices by providing insights into classification schemes capable of handling non-steady-state and unstructured locomotion in individuals with mild Parkinson’s disease.

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