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Xinxin Yang, Zhongfang Zhu, Xiqing Ding, Xiaoying Wang, Guiyun Cui, Fang Hua, Jie Xiang
Levodopa (L-dopa) remains the best treatment for Parkinson's disease (PD). However, long-term L-dopa treatment induces dyskinesia. The mechanism of L-dopa-induced dyskinesia (LID) is not fully understood. Enhanced activity of protein kinase A (PKA) and pulsatile dopamine (DA) stimulation plays an important role in LID. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for DA synthesis. Decreased TH activity causes reduced pulsatile DA stimulation, which in turn reduces LID. Moreover, TH is a substrate of CaMKII...
February 14, 2018: Brain Research
Natália Drumond Lopes, Otávio Augusto Chaves, Márcia C C de Oliveira, Carlos Mauricio R Sant'Anna, Danilo Sousa-Pereira, José Carlos Netto-Ferreira, Aurea Echevarria
A novel series of piperonal mesoionic derivatives (PMI 1-6) was synthesized. Tyrosinase inhibition in the presence of PMI-1, -2, -3, -4, -5 and -6 as well as human serum albumin (HSA) binding studies with PMI-5 and PMI-6 were done by spectroscopic and theoretical methods. The mesoionic compound PMI-5 is the most promising tyrosinase inhibitor with a noncompetitive inhibitory mechanism and an IC 50 = 124 μmol L -1 . In accordance with the kinetic profile, molecular docking results show that PMI-5 is able to interact favorably with the tyrosinase active site containing the substrate molecule, L-DOPA, interacting with Val-247, Phe-263 and Val-282 residues...
February 12, 2018: International Journal of Biological Macromolecules
Luigi Bartolomei, Andrea Pastore, Lucia Meligrana, Elena Sanson, Nicola Bonetto, Giacomo Maria Minicuci, Sandro Zambito Marsala, Tiziana Mesiano, Lorenzo Bragagnolo, Angelo Antonini
Parkinson's disease (PD) is a neurodegenerative disorder which affects the quality of life of patient and their family. Sleep disorders appear in 80-90% of PD patients and have a great impact on the PD well-being. We examined the relationship of patients' sleep quality and depression on burden, mood, quality of life, and quality of sleep of their caregivers. A multicenter, regional (Veneto), observational, cross-sectional study that included 55 patient-caregiver pairs was conducted. Patients were assessed using Parkinson's Disease Sleep Scale (PDSS) and Epworth Sleepiness Scale (ESS) for sleep disorders, Beck Depression Inventory (BDI) as a measure of depression, and Parkinson's Disease Questionnaire (PDQ-39) as a measure of quality of life...
February 14, 2018: Neurological Sciences
Jerome R Lechien, Serge Blecic, Kathy Huet, Véronique Delvaux, Myriam Piccaluga, Virginie Roland, Bernard Harmegnies, Sven Saussez
INTRODUCTION: To investigate voice quality (VQ) impairments in idiopathic Parkinson's disease (IPD) and to explore the impact of medical treatments and L-Dopa challenge testing on voice. METHODS: Relevant studies published between January 1980 and June 2017 describing VQ evaluations in IPD were retrieved using PubMed, Scopus, Biological Abstracts, BioMed Central, and Cochrane databases. Issues of clinical relevance, including IPD treatment efficiency and voice quality outcomes, were evaluated for each study...
February 14, 2018: Clinical Otolaryngology
Hendrik Woehlk, Jan Steinkoenig, Christiane Lang, Lukas Michalek, Vanessa Trouillet, Peter Krolla-Sidenstein, Anja S Goldmann, Leonie Barner, James P Blinco, Christopher Barner-Kowollik, Kathryn E Fairfull-Smith
We pioneer a versatile surface modification strategy based on mussel inspired oxidative catecholamine polymerization for the design of nitroxide containing thin polymer films. A 3,4-dihydroxy-L-phenylalanine (L-DOPA) monomer equipped with a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) derived oxidation-labile hydroxylamine functional group is employed as a universal coating agent to generate polymer scaffolds with persistent radical character. Various types of materials including silicon, titanium, ceramic alumina and inert poly(tetrafluoroethylene) (PTFE) were successfully coated with poly(DOPA-TEMPO) thin films in a one-step dip-coating procedure under aerobic, slightly alkaline (pH 8...
February 14, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Sonam Sinha, Sonal Sharma, Jaykant Vora, Heta Shah, Anshu Srivastava, Neeta Shrivastava
ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens (L.) DC (MP) is an ancient Indian medicinal plant traditionally used to treat Parkinson's disease. L-Dopa (LD), precursor of dopamine is abundantly found in the seeds of MP. L-dopa is a natural inhibitor of prolactin (PRL) hormone which is required to maintain lactation in women but it's over production (hyperprolactinemia) plays critical role in advancement of breast cancer. AIM OF THE STUDY: We aim to examine the pharmacological effect of LD and MP on this hyperprolactinemia associated breast cancer and related signaling for effective management of the disease...
February 7, 2018: Journal of Ethnopharmacology
Antti Huotarinen, Martin Reich, Jens Volkmann, Eero Pekkonen
Background: STB DBS (deep brain stimulation of the subthalamic nucleus) is commonly used to treat advanced Parkinson disease (PD) while posterior hypothalamic DBS for cluster headache (CH) remains experimental. Methods: We present a case where a middle-aged man was diagnosed with both CH and PD and received medical treatment for both. The patient was treated with bilateral STN DBS after developing side effects related to L-dopa. Findings: STN DBS not only alleviated PD symptoms but also the CH, and hence the CH treatment could be withdrawn...
September 2017: Case Reports in Neurology
Oscar Solís, Rosario Moratalla
The current standard treatment for Parkinson disease focuses on restoring striatal dopamine levels using L-3,4-dihydroxyphenylalanine (L-DOPA). However, disease progression and chronic treatment are associated with motor side effects such as L-DOPA-induced dyskinesia (LID). Dopamine receptor function is strongly associated with the mechanisms underlying LID. In fact, increased D1R signaling is associated with this motor side effect. Compelling evidence demonstrates that dopamine receptors in the striatum can form heteromeric complexes, and heteromerization can lead to changes in the functional and pharmacological properties of receptors compared to their monomeric subtypes...
February 7, 2018: Journal of Neural Transmission
Larissa C Esteves, Amanda C Pinheiro, Renan M Pioli, Tatiana C Penna, Wilhelm J Baader, Thiago C Correra, Erick L Bastos
Betanin (betanidin 5-O-β-D-glucoside) is a water-soluble plant pigment used as a color additive in food, drugs and cosmetic products. Despite its sensitivity to light and heat, betanin maintains appreciable tinctorial strength in low acidic and neutral conditions, where the color of other plant pigments, such as anthocyanins, quickly fades. However, betanin is an iminium natural product that experience acid- and base-catalyzed hydrolysis to form the fairly stable betalamic acid and cyclo-DOPA-5-O-β-D-glucoside...
February 7, 2018: Photochemistry and Photobiology
Mohsen Alavash, Sung-Joo Lim, Christiane Thiel, Bernhard Sehm, Lorenz Deserno, Jonas Obleser
Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in l-dopa-induced behavioral benefits...
February 2, 2018: NeuroImage
Ahmed M Kabel, Mohamed S Omar, Abdulrahman Alhadhrami, Salman S Alharthi, Majed M Alrobaian
OBJECTIVE: Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. METHODS: Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day...
January 30, 2018: Physiology & Behavior
Yong Mao, Xuan Wu, Li An, Xiao Li, Ze Li, Guiyu Zhu
Estrogen is the primary sex hormone responsible for the development and modulation of the female reproductive system in all vertebrates including avian species. The actions of estrogen are mediated by the estrogen receptor, which could be modulated by the selective estrogen receptor modulator tamoxifen (TAM). In this study, we administered TAM into the actively laying chicken to investigate the ovarian and hypothalamic responses to the estrogen action blockage. The laying was disrupted and the development of the pre-ovulatory hierarchical follicles was arrested...
February 1, 2018: Biochemical and Biophysical Research Communications
Francisco Velasco, Mauricio Esqueda-Liquidano, Ana Luisa Velasco, Maria Guadalupe García-Gomar
BACKGROUND: Selective improvement of symptoms may be required when treating Parkinson disease (PD) patients with a predominantly monosymptomatic clinical picture. OBJECTIVE: To define a target in prelemniscal radiation fibers (Raprl) related to the physiopathology of tremor evidenced by tractography. CASE REPORT: We report a patient with predominant unilateral rest and postural tremor, diagnosed as PD based on 80% improvement induced by the administration of L-DOPA/carbidopa, subsequently complicated by motor fluctuations, L-DOPA dyskinesia, and a reduced ON period...
February 6, 2018: Stereotactic and Functional Neurosurgery
Giada Spigolon, Gilberto Fisone
A large number of signaling abnormalities have been implicated in the emergence and expression of L-DOPA-induced dyskinesia (LID). The primary cause for many of these changes is the development of sensitization at dopamine receptors located on striatal projection neurons (SPN). This initial priming, which is particularly evident at the level of dopamine D1 receptors (D1R), can be viewed as a homeostatic response to dopamine depletion and is further exacerbated by chronic administration of L-DOPA, through a variety of mechanisms affecting various components of the G-protein-coupled receptor machinery...
February 2, 2018: Journal of Neural Transmission
Mohammed Jamil Asha, Benjamin Fisher, Jamilla Kausar, Hayley Garratt, Hari Krovvidi, Colin Shirley, Anwen White, Ramesh Chelvarajah, Ismail Ughratdar, James A Hodson, Hardev Pall, Rosalind D Mitchell
OBJECTIVES: The authors have previously reported on the technical feasibility of subthalamic nucleus deep brain stimulation (STN DBS) under general anesthesia (GA) with microelectrode recording (MER) guidance in Parkinsonian patients who continued dopaminergic therapy until surgery. This paper presents the results of a prospective cohort analysis to verify the outcome of the initial study, and report on wider aspects of clinical outcome and postoperative recovery. METHODS: All patients in the study group continued dopaminergic therapy until GA was administered...
February 2, 2018: Acta Neurochirurgica
Manuela Mellone, Fabrizio Gardoni
Overactivation of the glutamatergic synapse leading to maladaptive synaptic plasticity in the basal ganglia is a well-demonstrated process involved in the onset of L-DOPA-induced dyskinesia (LID). Changes in glutamate release are paralleled by compensatory modifications of the expression and/or synaptic localization of both ionotropic and metabotropic glutamate receptors (mGluRs). Accordingly, compounds targeting N-methyl-D-aspartate glutamate receptors (NMDARs) and specific subtypes of metabotropic glutamate receptors (mGluR4 and mGluR5) have been tested both in preclinical and clinical studies...
January 31, 2018: Journal of Neural Transmission
Vineeta Gautam, Karan P Singh, Vijay L Yadav
Nanocomposite materials are potentially revolutionizing many technologies, including sensors. In this paper, we described the application of "PANI/MWCNTs/Starch" modified carbon paste electrode (PCS-CPE) as a simple and highly sensitive cholesterol sensor. This novel nano-composite material has integrated nano-morphology, where polyaniline could interact effectively with the additives; pi-pi stacking "MWCNTs," and covalently bonded with starch. Specific binding sites (sugar chains), better electro-catalytic properties and fast electron transfer facilitated the oxidation of cholesterol...
January 31, 2018: Analytical and Bioanalytical Chemistry
Qi Li, Hongyu Yang, Jun Mo, Yao Chen, Yue Wu, Chen Kang, Yuan Sun, Haopeng Sun
Targeting tyrosinase is considered to be an effective way to control the production of melanin. Tyrosinase inhibitor is anticipated to provide new therapy to prevent skin pigmentation, melanoma and neurodegenerative diseases. Herein, we report our results in identifying new tyrosinase inhibitors. The shape-based virtual screening was performed to discover new tyrosinase inhibitors. Thirteen potential hits derived from virtual screening were tested by biological determinations. Compound 5186-0429 exhibited the most potent inhibitory activity...
2018: PeerJ
Mehdi Yoosefian, Elham Rahmanifar, Nazanin Etminan
Loss of dopamine-secreting neurons in the midbrain causes Parkinson's disease. L-DOPA, the precursor to the neurotransmitters dopamine, crosses vast majority of physiological and biochemical barriers that dopamine cannot. But most levodopa is decarboxylated to dopamine before it reaches the brain. This causes to little therapeutic gain with strong peripheral side effects. Benserazide is an irreversible inhibitor of peripheral aromatic L-amino acid decarboxylase that prevents the breakdown of levodopa in the bloodstream...
January 29, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Moon K Kim, Moe H Aung, Lukas Mees, Darin E Olson, Nikita Pozdeyev, P Michael Iuvone, Peter M Thule, Machelle T Pardue
Purpose: Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysfunction. In the current study, we examined whether oscillatory potentials (OPs) could serve as a potential marker for detecting early inner retinal dysfunction due to retinal DA deficiency...
January 1, 2018: Investigative Ophthalmology & Visual Science
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