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Drug induced parkinsonism

Rodolfo Savica, Brandon R Grossardt, James H Bower, J Eric Ahlskog, Michelle M Mielke, Walter A Rocca
BACKGROUND: Epidemiological studies of drug-induced parkinsonism remain limited. OBJECTIVES: To investigate the incidence and time trends of drug-induced parkinsonism over 30 years in a geographically defined American population. METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project to identify all persons in Olmsted County, Minnesota, who received a screening diagnostic code for parkinsonism from 1976 through 2005...
October 25, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
M Rieck, A F Schumacher-Schuh, V Altmann, S M Callegari-Jacques, C R M Rieder, M H Hutz
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated...
October 25, 2016: Pharmacogenomics Journal
Ranjit Singh, Ranju Bansal
Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1β) might contribute neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models...
October 24, 2016: ACS Chemical Neuroscience
Jyotiska Chaudhuri, Neelanjan Bose, Jianke Gong, David Hall, Alexander Rifkind, Dipa Bhaumik, T Harshani Peiris, Manish Chamoli, Catherine H Le, Jianfeng Liu, Gordon J Lithgow, Arvind Ramanathan, X Z Shawn Xu, Pankaj Kapahi
Reactive α-dicarbonyls (α-DCs), like methylglyoxal (MGO), accumulate with age and have been implicated in aging and various age-associated pathologies, such as diabetic complications and neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Evolutionarily conserved glyoxalases are responsible for α-DC detoxification; however, their core biochemical regulation has remained unclear. We have established a Caenorhabditis elegans model, based on an impaired glyoxalase (glod-4/GLO1), to broadly study α-DC-related stress...
October 12, 2016: Current Biology: CB
Roberto De Marzi, Werner Poewe, Elke R Gizewski, Philipp Mahlknecht, Klaus Seppi
No abstract text is available yet for this article.
November 2016: Radiology
Pil Sung Gu, Minho Moon, Jin Gyu Choi, Myung Sook Oh
Mulberry fruit, which has been long used in traditional oriental medicine, was reported to ameliorate motor dysfunction and dopaminergic neuronal degeneration via antioxidant and antiapoptotic effects in an animal model of Parkinson's disease (PD). More than 95% of PD patients exhibit nonmotor problems such as olfactory dysfunction and gastrointestinal constipation, which are generally considered to be early symptoms of PD. However, few studies have actually examined potential drugs to treat early PD symptoms...
September 22, 2016: Journal of Nutritional Biochemistry
Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Danya Ben-Hail, Racheli Begas-Shvartz, Moran Shalev, Anna Shteinfer-Kuzmine, Arie Gruzman, Simona Reina, Vito De Pinto, Varda Shoshan-Barmatz
Apoptosis is thought to play a critical role in several pathological processes, such as neurodegenerative diseases (i.e., Parkinson's and Alzheimer's diseases) and various cardiovascular diseases. Despite the fact that apoptotic mechanisms are well defined, there is still no substantial therapeutic strategy to stop or even slow this process. Thus, there is an unmet need for therapeutic agents that are able to block or slow apoptosis in neurodegenerative and cardiovascular diseases. The outer mitochondrial membrane protein voltage-dependent anion channel 1 (VDAC1) is a convergence point for a variety of cell survival and death signals, including apoptosis...
October 13, 2016: Journal of Biological Chemistry
Matthias Schmitz, Maria Cramm, Franc Llorens, Dominik Müller-Cramm, Steven Collins, Ryuichiro Atarashi, Katsuya Satoh, Christina D Orrù, Bradley R Groveman, Saima Zafar, Walter J Schulz-Schaeffer, Byron Caughey, Inga Zerr
The development and adaption of in vitro misfolded protein amplification systems has been a major innovation in the detection of abnormally folded prion protein scrapie (PrP(Sc)) in human brain and cerebrospinal fluid (CSF) samples. Herein, we describe a fast and efficient protein amplification technique, real-time quaking-induced conversion (RT-QuIC), for the detection of a PrP(Sc) seed in human brain and CSF. In contrast to other in vitro misfolded protein amplification assays-such as protein misfolding cyclic amplification (PMCA)-which are based on sonication, the RT-QuIC technique is based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate, accelerated by alternating cycles of shaking and rest in fluorescence plate readers...
November 2016: Nature Protocols
Prahlad V Raninga, Giovanna Di Trapani, Slavica Vuckovic, Kathryn F Tonissen
Multiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson's disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shorter overall survival and poor prognosis in MM patients...
October 12, 2016: Apoptosis: An International Journal on Programmed Cell Death
Joong Seok Kim, Dong Woo Ryu, Ju Hee Oh, Yang Hyun Lee, Sung Jin Park, Kipyung Jeon, Jong Yun Lee, Seong Hee Ho, Jungmin So, Jin Hee Im, Kwang Soo Lee
BACKGROUND AND PURPOSE: Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. METHODS: This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring...
October 7, 2016: Journal of Clinical Neurology
O A Gan'kina, E E Vasenina, O S Levin, E Yu Fedotova, S N Illarioshkin
Parkinson's disease (PD) is a common neurodegenerative disease. Literature sources indicate the association of PD and mutations in the glucocerebrosidase A (GBA) gene. According to our study, the frequency of the two most common mutations in the GBA gene, N370S and L444P, is 1.85%. Mutation carriers have slower progression of motor symptoms, but are more likely to develop drug-induced motor fluctuations and dyskinesia. In carriers of GBA mutations, the severity of cognitive impairment corresponds to age-matched patients without mutations...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
E Carlino, A Piedimonte, F Benedetti
Placebos have long been considered a nuisance in clinical research, for they have always been used as comparators for the validation of new treatments. By contrast, today they represent an active field of research, and, due to the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. There is not a single placebo effect, but many, with different mechanisms across different medical conditions and therapeutic interventions...
2017: Handbook of Clinical Neurology
Lianggong Ding, Ye Lei, Yanping Han, Yuhong Li, Xunming Ji, Lei Liu
As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission and transport are regulated by several core components, including Miro. As an atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchange factor (GEF). However, the GEF for Miro has not been identified. While studying mitochondrial morphology in Drosophila, we incidentally observed that the loss of vimar, a gene encoding an atypical GEF, enhanced mitochondrial fission under normal physiological conditions...
October 2016: PLoS Genetics
Koki Fujimori, Toshiki Tezuka, Hiroyuki Ishiura, Jun Mitsui, Koichiro Doi, Jun Yoshimura, Hirobumi Tada, Takuya Matsumoto, Miho Isoda, Ryota Hashimoto, Nubutaka Hattori, Takuya Takahashi, Shinichi Morishita, Shoji Tsuji, Wado Akamatsu, Hideyuki Okano
Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs...
October 3, 2016: Molecular Brain
Sameer Hassamal, Susan Waller, Kimberly Reese, Claudia Testa
Valproic acid (VPA) is approved by the Food and Drug Administration (FDA) for the treatment of manic or mixed episodes associated with bipolar disorder. VPA is also used off-label to treat other conditions in psychiatry such as impulse control disorders, major depression, and posttraumatic stress disorder (PTSD). Although VPA is mostly well-tolerated, common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea), neurological symptoms (sedation, ataxia, tremor), weight gain, and alopecia...
2016: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
Elisa Garbayo, Eduardo Ansorena, Hugo Lana, María Del Mar Carmona-Abellan, Irene Marcilla, José Luis Lanciego, María Rosario Luquin, María José Blanco-Prieto
Glial cell line-derived neurotrophic factor (GDNF) remains the most potent neurotrophic factor for dopamine neurons. Despite its potential as treatment for Parkinson's disease (PD), its clinical application has been hampered by safety and efficacy concerns associated with GDNF's short in vivo half-life and with significant brain delivery obstacles. Drug formulation systems such as microparticles (MPs) may overcome these issues providing protein protection from degradation and sustained drug release over time...
December 2016: Biomaterials
Giovanna Mulas, Elena Espa, Sandro Fenu, Saturnino Spiga, Giovanni Cossu, Elisabetta Pillai, Ezio Carboni, Gabriella Simbula, Dragana Jadžić, Fabrizio Angius, Stefano Spolittu, Barbara Batetta, Daniela Lecca, Andrea Giuffrida, Anna R Carta
Neuroinflammation is associated with l-DOPA treatment in Parkinson's disease (PD), suggesting a role in l-DOPA-induced dyskinesia (LID), however it is unclear whether increased inflammation is specifically related to the dyskinetic outcome of l-DOPA treatment. Diversely from oral l-DOPA, continuous intrajejunal l-DOPA infusion is associated with very low dyskinetic outcome in PD patients. We reproduced these regimens of administration in 6-OHDA-lesioned hemiparkinsonian rats, where dyskinetic responses and striatal neuroinflammation induced by chronic pulsatile (DOPAp) or continuous (DOPAc) l-DOPA were compared...
September 30, 2016: Experimental Neurology
Zhimin Wang, Jiajia Wu, Xuelian Yang, Pei Cai, Qiaohong Liu, Kelvin D G Wang, Lingyi Kong, Xiaobing Wang
The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins...
September 21, 2016: Bioorganic & Medicinal Chemistry
Thi Thu Ha Nguyen, Antoine Pariente, Jean-Louis Montastruc, Maryse Lapeyre-Mestre, Vanessa Rousseau, Olivier Rascol, Bernard Bégaud, François Montastruc
AIMS: Pharmacovigilance databases are usually used to detect new potential signals relevant for drug safety. They are seldom used for explanatory purposes, e.g. to understand the mechanisms of adverse drug reactions (ADRs). The aim of the present study was to combine pharmacovigilance and pharmacodynamic data to investigate the association between D2, 5HT2A, and M1 receptor occupancy and the risks of antipsychotic (AP)-induced movement disorders. METHODS: First, we performed a case non-case analysis using spontaneous reports from the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database, VigiBase®...
September 30, 2016: British Journal of Clinical Pharmacology
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