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Rui Kang, Ling Zeng, Yangchun Xie, Zhengwen Yan, Borong Zhou, Lizhi Cao, Daniel J Klionsky, Kevin J Tracey, Jianhua Li, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Although the PINK1-PARK2 pathway contributes to the pathogenesis of Parkinson disease, its roles in sepsis (a major challenge for critical care) were previously unknown. Here, we show that pink1(-/-) and park2(-/-) mice are more sensitive to polymicrobial sepsis-induced multiple organ failure and death. The decrease in the circulating level of the neurotransmitter dopamine in pink1(-/-) and park2(-/-) mice accelerates the release of a late sepsis mediator, HMGB1, via HIF1A-dependent anaerobic glycolysis and subsequent NLRP3-dependent inflammasome activation...
October 18, 2016: Autophagy
Youngsin Jung, Erik K St Louis
REM sleep behavior disorder (RBD) is a common parasomnia disorder affecting between 1 and 7 % of community-dwelling adults, most frequently older adults. RBD is characterized by nocturnal complex motor behavior and polysomnographic REM sleep without atonia. RBD is strongly associated with synucleinopathy neurodegeneration. The approach to RBD management is currently twofold: symptomatic treatment to prevent injury and prognostic counseling and longitudinal follow-up surveillance for phenoconversion toward overt neurodegenerative disorders...
November 2016: Current Treatment Options in Neurology
Jennifer L Schroeck, James Ford, Erin L Conway, Kari E Kurtzhalts, Megan E Gee, Krista A Vollmer, Kari A Mergenhagen
PURPOSE: Insomnia is problematic for older adults. After behavioral modifications fail to show adequate response, pharmacologic options are used. The pharmacokinetics of agents used to treat insomnia may be altered. This review focuses on the safety and efficacy of medications used to treat insomnia. METHODS: A literature search of Medline, PubMed, and Embase was conducted (January 1966-June 2016). It included systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on insomnia in an older population...
October 14, 2016: Clinical Therapeutics
David Maltête, Floriane Le Goff, Gulden Ozel, Romain Lefaucheur
No abstract text is available yet for this article.
October 4, 2016: Journal of Clinical Psychopharmacology
Lei-Fang Cao, Xiao-Yan Peng, Ya Huang, Bing Wang, Feng-Ming Zhou, Ruo-Xiao Cheng, Li-Hua Chen, Wei-Feng Luo, Tong Liu
In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats...
2016: Neural Plasticity
Ken Ikeda, Takehisa Hirayama, Takanori Takazawa, Kiyokazu Kawabe, Yasuo Iwasaki
Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients...
2016: Internal Medicine
Alireza Sarkaki, Yaghoob Farbood, Mojtaba Dolatshahi, Seyed Mohammad Taqhi Mansouri, Ali Khodadadi
Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection...
August 2016: Acta Medica Iranica
Maju Mathew Koola, Jan Fawcett
No abstract text is available yet for this article.
August 2016: Psychiatric Annals
Simon Loiodice, Poppy Winlow, Sarah Dremier, Etienne Hanon, David Dardou, Omar Ouachikh, Aziz Hafidi, Andre Nogueira da Costa, Franck Durif
RATIONALE: Impulsive-compulsive disorders (ICD) in patients with Parkinson's disease (PD) have been described as behavioral or substance addictions including hypersexuality, gambling, or compulsive medication use of the dopamine replacement therapy (DRT). OBJECTIVES: A remaining challenge is to understand the neuroadaptations leading to reward bias in PD patients under DRT. METHODS: To this end, the appetitive effect of the D2/D3 agonist pramipexole was assessed after chronic exposure to L-dopa in an alpha-synuclein PD rat model...
September 10, 2016: Psychopharmacology
Haley Gallant, Andrew Vo, Ken N Seergobin, Penny A MacDonald
Dopaminergic therapy has paradoxical effects on cognition in Parkinson's disease (PD) patients, with some functions worsened and others improved. The dopamine overdose hypothesis is proposed as an explanation for these opposing effects of medication taking into account the varying levels of dopamine within different brain regions in PD. The detrimental effects of medication on cognition have been attributed to exogenous dopamine overdose in brain regions with spared dopamine levels in PD. It has been demonstrated that learning is most commonly worsened by dopaminergic medication...
2016: Frontiers in Neuroscience
Dan Luo, Horrick Sharma, Deepthi Yedlapudi, Tamara Antonio, Maarten E A Reith, Aloke K Dutta
Our ongoing drug development endeavor to design compounds for symptomatic and neuroprotective treatment of Parkinson's disease (PD) led us to carry out a structure activity relationship study based on dopamine agonists pramipexole and 5-OHDPAT. Our goal was to incorporate structural elements in these agonists in a way to preserve their agonist activity while producing inhibitory activity against aggregation of α-synuclein protein. In our design we appended various catechol and related phenol derivatives to the parent agonists via different linker lengths...
November 1, 2016: Bioorganic & Medicinal Chemistry
He-Ting Luo, Jin-Pei Zhang, Feng Miao
Advances approaches in the treatment of Parkinson's disease are needed. The study was aimed to evaluate the therapeutic value of the new dopamine receptor agonist pramipexole. The effects of pramipexole on serum exosomes were investigated, and the possible mechanisms of action of the drug were explored. Initially, 68 patients were included in the study, of whom 3 cases did not complete the study. The remaining 65 patients were administered pramipexole at increasing doses starting at 0.25 mg twice a day for the 1st week, and reaching 1...
September 2016: Experimental and Therapeutic Medicine
Wolfgang Oertel, Jörg B Schulz
Over a period of more than 50 years, the symptomatic treatment of the motor symptoms of Parkinson disease (PD) has been optimized using pharmacotherapy, deep brain stimulation, and physiotherapy. The arsenal of pharmacotherapies includes L-Dopa, several dopamine agonists, inhibitors of monoamine oxidase (MAO)-B and catechol-o-methyltransferase (COMT), and amantadine. In the later course of the disease, motor complications occur, at which stage different oral formulations of L-Dopa or dopamine agonists with long half-life, a transdermal application or parenteral pumps for continuous drug supply can be subscribed...
October 2016: Journal of Neurochemistry
Francesco Porta, Alberto Ponzone, Marco Spada
Tetrahydrobiopterin (BH4) deficiencies are inherited neuro-metabolic disorders leading to monoamine neurotransmitters deficiency. An individualized replacement therapy with neurotransmitters precursors is necessary to restore dopaminergic and serotoninergic homeostasis. The correction of dopaminergic tone is complicated, like in Parkinson disease, by l-dopa short half-life and adverse effects. To improve this picture, since 2009 we introduced the non-ergot dopamine agonist pramipexole as an adjunct to l-dopa therapy in the treatment of the most common causes of BH4 deficiency, 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and dihydropteridine reductase (DHPR) deficiency...
November 2016: European Journal of Paediatric Neurology: EJPN
Doreen Reichelt, Khaled Salman Radad, Rudolf Moldzio, Wolf-Dieter Rausch, Heinz Reichmann, Gabriele Gille
BACKGROUND: Dopamine agonists are utilized clinically as an initial treatment in younger Parkinson's disease patients to delay the side effects associated with commencement of levodopa medication. These agonists also serveas adjunctive therapeutics with levodopa to lower the incidence of adverse motor symptoms in advanced stages of the disease. OBJECTIVES: To compare the neuroprotective effects of the dopamine agonists pergolide and pramipexole on ferrous sulfate-induced neurotoxicity in dopaminergic neurons from primary mesencephalic cell culture...
August 1, 2016: CNS & Neurological Disorders Drug Targets
Mi Eun Kim, Joo Yeon Lee, Kyung Moon Lee, Hee Ra Park, Eunjin Lee, Yujeong Lee, Jun Sik Lee, Jaewon Lee
Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease next to Alzheimer's disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation...
August 2016: Archives of Pharmacal Research
Lars Michels, Sigrid Scherpiet, Philipp Stämpfli, Uwe Herwig, Annette B Brühl
BACKGROUND: The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known. METHODS: In this randomized cross-over, placebo-controlled and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the non-ergoline class) 1 hour before the experiment...
July 27, 2016: International Journal of Neuropsychopharmacology
Burak Yulug, Lutfu Hanoglu
BACKGROUND: There is still speculative data regarding the role spinal dopaminergic neurotransmission in restless leg syndrome (RLS). METHODS: We have evaluated the therapeutic role of pramipexole in a patient with cervical disc prolapsus who was exceptionally presented with neck restlessness Results: We have found that pramipexole leads to a significant improvement in restlessness symptoms in the neck region. DISCUSSION: The therapeutic role of pramipexole may not only suggest secondary deficits due to spinal pathologies but also indicate that specialized spinal dopaminergic neurons may play an important role in the pathogenesis of region specific restlessness symptomatology...
July 19, 2016: Current Clinical Pharmacology
Shian Ming Tan, Yi Min Wan
While widely accepted as a first-line treatment for rapid eye movement sleep (REM) behaviour disorder, clonazepam (CNZP) has side effects that limit its applicability. Pramipexole is a possible alternative, but limited literature on its effectiveness exists. This review aims to summarize the available data on the use of pramipexole in REM sleep behaviour disorder. A systematic search of major databases was conducted to look for published and on-going trials. This search yielded a total of five articles, all of which are observational in nature...
September 30, 2016: Psychiatry Research
Birgitta Johansson Cahlin, Jan Hedner, Lars Dahlström
Sleep bruxism bears several similarities to restless legs syndrome, and a link to changes in central dopamine activity has been considered in both conditions. The dopamine agonist pramipexole is currently indicated for the symptomatic treatment of restless legs. The effect of pramipexole on sleep bruxism was investigated in subjects with 'probable bruxism' recruited at the Orofacial Pain Clinic. Thirteen patients underwent polysomnographic recordings, including bilateral masseter electromyographic activity...
July 17, 2016: Journal of Sleep Research
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