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https://www.readbyqxmd.com/read/28110399/safinamide-a-review-in-parkinson-s-disease
#1
Hannah A Blair, Sohita Dhillon
Safinamide (Xadago(®)) is an orally active, selective, reversible monoamine oxidase-B inhibitor with both dopaminergic and non-dopaminergic (glutamatergic) properties. In the EU, safinamide is approved for the treatment of mid- to late-stage fluctuating Parkinson's disease (PD) as add-on therapy to a stable dose of levodopa alone or in combination with other PD medications. Safinamide 50-100 mg/day administered as a fixed or flexible dose significantly increased daily 'on' time without dyskinesia (primary endpoint) in patients with mid- to late-stage PD with motor fluctuations in 24-week, placebo-controlled clinical trials...
January 21, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28109835/gut-microbiota-a-player-in-aging-and-a-target-for-anti-aging-intervention
#2
REVIEW
Alexander M Vaiserman, Alexander K Koliada, Francesco Marotta
Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance...
January 18, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28109809/potent-inhibition-of-monoamine-oxidase-a-by-decursin-from-angelica-gigas-nakai-and-by-wogonin-from-scutellaria-baicalensis-georgi
#3
Hyun Woo Lee, Hyung Won Ryu, Myung-Gyun Kang, Daeui Park, Hanna Lee, Heung Mook Shin, Sei-Ryang Oh, Hoon Kim
During the ongoing search for new monoamine oxidase (MAO) inhibitors, five coumarin derivatives and eight flavonoids were isolated from the roots of Angelica gigas Nakai and Scutellaria baicalensis Georgi, respectively. Of the phytochemicals, decursin (4) was found to potently and selectively inhibit human MAO-A (IC50=1.89μM). The IC50 value of 4 for MAO-A belonged to the lowest group in herbal sources and was similar to that of toloxatone (1.78μM), a marketed drug. Wogonin (11) effectively inhibited MAO-A and MAO-B (IC50=6...
January 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28109723/octogenarian-parkinsonism-clinicopathological-observations
#4
Ali H Rajput, Emma F Rajput
BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder for which old age is the best known risk. The proportion of elderly in the world is increasing, resulting in larger pool of people at risk for Parkinson's disease. Several other neurodegenerative disorders also produce Parkinson syndrome. Distinguishing between those variants is only possible with pathological examination of brain. No autopsy confirmed study of 80 years and older onset in parkinsonism cases has been reported...
January 12, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28109635/impact-of-high-cholesterol-in-a-parkinson-s-disease-model-prevention-of-lysosomal-leakage-versus-stimulation-of-%C3%AE-synuclein-aggregation
#5
Ida Eriksson, Sangeeta Nath, Per Bornefall, Ana Maria Villamil Giraldo, Karin Öllinger
Parkinson's disease is characterized by accumulation of intraneuronal cytoplasmic inclusions, Lewy bodies, which mainly consist of aggregated α-synuclein. Controversies exist as to whether high blood cholesterol is a risk factor for the development of the disease and whether statin treatment could have a protective effect. Using a model system of BE(2)-M17 neuroblastoma cells treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), we found that MPP(+)-induced cell death was accompanied by cholesterol accumulation in a lysosomal-like pattern in pre-apoptotic cells...
January 16, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28108911/traditional-chinese-medicine-for-modern-treatment-of-parkinson-s-disease
#6
REVIEW
Lu Han, Yuan-Hong Xie, Rong Wu, Chen Chen, Yan Zhang, Xiao-Ping Wang
Parkinson's disease (PD) is a chronic and progressive degenerative disorder of brain commonly seen among the elderly. As conventionally medical therapy is of limited relief and potential side effects, complementary and alternative medicine (CAM) has attracted growing public and professional attention. Therapies such as acupuncture, musical/rhythmic therapy and deep brain stimulation have been gradually proved positively in clinic. In this review, we retrospected the scientific or evidence-based-medicine advances of application and research for modern treatment of PD by CAM, especially traditional Chinese medicine in categories...
January 20, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28108849/toll-like-receptor-4-affects-the-cerebral-biochemical-changes-induced-by-mptp-treatment
#7
Carmela Conte, Luca Roscini, Roccaldo Sardella, Giuseppina Mariucci, Stefania Scorzoni, Tommaso Beccari, Laura Corte
The etiology and pathogenesis of Parkinson's disease (PD) are still unclear. However, multiple lines of evidence suggest a critical role of the toll like receptor 4 (TLR4) in inflammatory response and neuronal death. Neuroinflammation may be associated with the misfolding and aggregation of proteins accompanied by a change in their secondary structure. Recent findings also suggest that biochemical perturbations in cerebral lipid content could contribute to the pathogenesis of central nervous system (CNS) disorders, including PD...
January 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28107736/crystal-structures-binding-interactions-and-adme-evaluation-of-brain-penetrant-n-substituted-indazole-5-carboxamides-as-subnanomolar-selective-monoamine-oxidase-b-and-dual-mao-a-b-inhibitors
#8
Nikolay T Tzvetkov, Hans-Georg Stammler, Beate Neumann, Silvia Hristova, Liudmil Antonov, Marcus Gastreich
The pharmacological and physicochemical analysis of structurally optimized N-alkyl-substituted indazole-5-carboxamides, developed as potential drug and radioligand candidates for the treatment and diagnosis of Parkinson's disease (PD) and other neurological disorders, is reported. Recent efforts have been focused on the development of subnanomolar potent, selective MAO-B (N1-alkyl-substituted compounds 12a-14a and 15) and dual active MAO-A/B (N2-methylated compounds 12b-14b) inhibitors with nanomolar potency towards MAO-B and moderately active against MAO-A enzyme, respectively...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28107119/olfaction-new-understandings-diagnostic-applications
#9
Gabrielle F Ruggiero, Jeannette Y Wick
Estimates indicate that 14 million Americans have olfactory dysfunction. As with other senses, such as sight and hearing, olfaction frequently declines with age. Impaired olfaction can be a warning sign of Parkinson's disease, sometimes occurring before motor symptoms develop. It's also an initial symptom of Alzheimer's dementia (AD); the amyloid plaques and tangles characterizing AD invade the olfactory bulb and hippocampus early in its course, hampering odor identification. Olfactory dysfunction is associated with some serious problems, including inability to smell warning odors (fire, gas) and impaired ability to taste food...
November 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#10
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106568/physical-therapy-versus-a-general-exercise-programme-in-patients-with-hoehn-yahr-stage-ii-parkinson-s-disease-a%C3%A2-randomized-controlled-trial
#11
Savina Dipasquale, Roberto Meroni, Francesco Sasanelli, Ivan Messineo, Daniele Piscitelli, Cecilia Perin, Cesare Maria Cornaggia, Cesare G Cerri
BACKGROUND AND OBJECTIVE: Several studies suggest that general exercise (GE) and physical therapy programmes (PT) improve the outcomes of Parkinson's disease (PD) patients; however, the available data do not allow a determination of which treatment is more effective. Our study aims to compare the effects of physiotherapy and general exercise in Parkinson's disease. METHODS: Design and setting: Randomized controlled trial -general hospital outpatient clinic. The participants were patients with Hoehn Yahr stage II PD...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106066/the-psychosis-spectrum-in-parkinson-disease
#12
REVIEW
Dominic H Ffytche, Byron Creese, Marios Politis, K Ray Chaudhuri, Daniel Weintraub, Clive Ballard, Dag Aarsland
In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication...
January 20, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28105978/simultaneous-transplantation-of-fetal-ventral-mesencephalic-tissue-and-encapsulated-genetically-modified-cells-releasing-gdnf-in-a-hemi-parkinsonian-rat-model-of-parkinson-s-disease
#13
Alberto Perez-Bouza, Stefano Di, Stefanie Seiler, Morten Meyer, Lukas Andereggen, Alexander Huber, Raphael Guzman, Hans R
Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor or mocktransfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior and 2, 4, 6 and 9 weeks post-transplantation...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28105331/opioid-system-in-l-dopa-induced-dyskinesia
#14
REVIEW
Jing Pan, Huaibin Cai
L-3, 4-Dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) is a major clinical complication in the treatment of Parkinson's disease (PD). This debilitating side effect likely reflects aberrant compensatory responses for a combination of dopaminergic neuron denervation and repeated L-DOPA administration. Abnormal endogenous opioid signal transduction pathways in basal ganglia have been well documented in LID. Opioid receptors have been targeted to alleviate the dyskinesia. However, the exact role of this altered opioid activity is remains under active investigation...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28104279/effect-of-inhibition-of-fatty-acid-amide-hydrolase-on-mptp-induced-dopaminergic-neuronal-damage
#15
J M Viveros-Paredes, R E Gonzalez-Castañeda, A Escalante-Castañeda, A R Tejeda-Martínez, F Castañeda-Achutiguí, M E Flores-Soto
INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterised by balance problems, muscle rigidity, and slow movement due to low dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The endocannabinoid system is known to modulate the nigrostriatal pathway through endogenous ligands such as anandamide (AEA), which is hydrolysed by fatty acid amide hydrolase (FAAH). The purpose of this study was to increase AEA levels using FAAH inhibitor URB597 to evaluate the modulatory effect of AEA on dopaminergic neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
January 16, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28104232/dopamine-agonist-withdrawal-syndrome-a-comprehensive-review
#16
REVIEW
Xin Xin Yu, Hubert H Fernandez
Dopamine agonists are effective and widely used treatments for Parkinson disease (PD). However, patients on dopamine agonists may experience significant side effects which necessitate dose tapering or discontinuation. Dopamine agonist withdrawal syndrome (DAWS) is a complication that affects up to 19% of PD patients who undergo a dopamine agonist taper. It was initially described in 2010 as a severe stereotypical cluster of psychiatric and physical symptoms occurring with dopamine agonist withdrawal. Identified risk factors for DAWS include impulse control behavior disorders (ICD) and higher dopamine agonist dosage...
January 2, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28103749/clinical-practice-with-anti-dementia-drugs-a-revised-third-consensus-statement-from-the-british-association-for-psychopharmacology
#17
John T O'Brien, Clive Holmes, Matthew Jones, Roy Jones, Gill Livingston, Ian McKeith, Peter Mittler, Peter Passmore, Craig Ritchie, Louise Robinson, Elizabeth L Sampson, John-Paul Taylor, Alan Thomas, Alistair Burns
The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B)...
December 1, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28101657/levodopa-carbidopa-microtablets-in-parkinson-s-disease-a-study-of-pharmacokinetics-and-blinded-motor-assessment
#18
Marina Senek, Sten-Magnus Aquilonius, Håkan Askmark, Filip Bergquist, Radu Constantinescu, Anders Ericsson, Sara Lycke, Alexander Medvedev, Mevludin Memedi, Fredrik Ohlsson, Jack Spira, Jerker Westin, Dag Nyholm
BACKGROUND: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments. OBJECTIVES: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson's disease. METHODS: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations...
January 18, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28101650/speech-disorders-in-parkinson-s-disease-early-diagnostics-and-effects-of-medication-and-brain-stimulation
#19
REVIEW
L Brabenec, J Mekyska, Z Galaz, Irena Rektorova
Hypokinetic dysarthria (HD) occurs in 90% of Parkinson's disease (PD) patients. It manifests specifically in the areas of articulation, phonation, prosody, speech fluency, and faciokinesis. We aimed to systematically review papers on HD in PD with a special focus on (1) early PD diagnosis and monitoring of the disease progression using acoustic voice and speech analysis, and (2) functional imaging studies exploring neural correlates of HD in PD, and (3) clinical studies using acoustic analysis to evaluate effects of dopaminergic medication and brain stimulation...
January 18, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28101525/untangling-basal-ganglia-network-dynamics-and-function-role-of-dopamine-depletion-and-inhibition-investigated-in-a-spiking-network-model
#20
Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
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