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Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
A Abellán-Llobregat, C González-Gaitán, L Vidal, A Canals, E Morallón
A new portable electrochemical sensor based on 4-aminobenzoic acid-modified herringbone carbon nanotubes (hCNTs-4ABA/Au-IDA) has been developed for the simultaneous determination of ascorbic acid (AA) and uric acid (UA) in physiological fluids. AA and UA were quantified by chronoamperometry at 0.1 and 0.32 V, respectively, in phosphate buffer solution (PBS 0.25 M, pH 7.0). Significant results were obtained for the separate quantification of AA and UA, with a limit of detection (LOD) of 0.65 μM for both analytes, and sensitivities of (9...
February 23, 2018: Biosensors & Bioelectronics
Ivana Glavina Jelaš, Ivan Dević, Dalibor Karlović
BACKGROUND: the objective of this study was to examine the associations between Cloninger temperament and character dimensions with the DAT1 VNTR and COMT Val158Met polymorphisms. SUBJECTS AND METHODS: The study was conducted on 101 subjects, consisting of students of the Police College in Zagreb and staff of the Sestre Milosrdnice University Hospital in Zagreb. The Cloninger Temperament and Character Inventory (TCI) was used to test personality traits. RESULTS: A main effect of the DAT1 VNTR polymorphism was found on the subscale self-directedness - SD2 (F=5...
March 2018: Psychiatria Danubina
Sunao Mizumura, Kazuhiro Nishikawa, Akihiro Murata, Kosei Yoshimura, Nobutomo Ishii, Tadashi Kokubo, Miyako Morooka, Akiko Kajiyama, Atsuro Terahara
OBJECTIVE: In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs...
March 15, 2018: Annals of Nuclear Medicine
Carolina Ribeiro, Rosa Quinta, Ana Raposo, Ana Valentim, José Albuquerque, Manuela Grazina
Objective: Prospective observational study to analyze CYP2D6 pharmacogenetics in 55 Portuguese adult parturients undergoing elective cesarean section and to investigate the association between CYP2D6 alleles and pain score. Methods: DNA was extracted from peripheral blood by standard methods. Genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number determination with TaqMan probes by real-time polymerase chain reaction (PCR)...
March 12, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
Paola Imbriani, Tommaso Schirinzi, Maria Meringolo, Nicola B Mercuri, Antonio Pisani
Significant advances have been made in the understanding of the numerous mechanisms involved in Parkinson's disease (PD) pathogenesis. The identification of PD pathogenic mutations and the use of different animal models have contributed to better elucidate the processes underlying the disease. Here, we report a brief survey of some relevant cellular mechanisms, including autophagic-lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level, mainly consisting in a decrease in dopamine release at nigrostriatal terminals and loss of synaptic plasticity at corticostriatal synapses...
2018: Frontiers in Neurology
Xiaoqun Zhang, Ioannis Mantas, Alexandra Alvarsson, Takashi Yoshitake, Mohammadreza Shariatgorji, Marcela Pereira, Anna Nilsson, Jan Kehr, Per E Andrén, Mark J Millan, Karima Chergui, Per Svenningsson
The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (β-PEA) compared to 3-iodothyronamine (T1 AM). Immunoblotting and amperometry were performed in dorsal striatal slices from wild-type (WT) and TAAR1 knockout (KO) mice. T1 AM increased TH phosphorylation at both Ser19 and Ser40 , actions that should promote functional activity of TH...
2018: Frontiers in Pharmacology
Magdalena Kolasa, Joanna Solich, Agata Faron-Górecka, Dariusz Żurawek, Paulina Pabian, Sylwia Łukasiewicz, Maciej Kuśmider, Kinga Szafran-Pilch, Marta Szlachta, Marta Dziedzicka-Wasylewska
Recently, it has been shown that serotonin 5-HT1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2)...
March 12, 2018: Neuroscience
Damiano Terenzi, Raffaella I Rumiati, Mauro Catalan, Lucia Antonutti, Giovanni Furlanis, Paolo Garlasco, Paola Polverino, Claudio Bertolotti, Paolo Manganotti, Marilena Aiello
BACKGROUND: Parkinson's disease (PD) patients who are treated with dopamine replacement therapy are at risk of developing impulse control disorders (ICDs) (such as gambling, binge eating, and others). According to recent evidence, compulsive reward seeking in ICDs may arise from an excessive attribution of incentive salience (or 'wanting') to rewards. OBJECTIVES: In this study, we tested this hypothesis in patients with PD who developed binge eating (BE). METHODS: Patients with BE, patients without BE, and healthy controls performed different experimental tasks assessing food liking and wanting...
March 9, 2018: Parkinsonism & related Disorders
Julia E Gerson, Kathleen M Farmer, Natalie Henson, Diana L Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett, Rakez Kayed
BACKGROUND: We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target...
March 15, 2018: Molecular Neurodegeneration
Laura J Mosher, Sean C Godar, Marc Morissette, Kenneth M McFarlin, Simona Scheggi, Carla Gambarana, Stephen C Fowler, Thérèse Di Paolo, Marco Bortolato
The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses...
February 16, 2018: Psychoneuroendocrinology
Stefano Magni, François Gagné, Chantale André, Camilla Della Torre, Joëlle Auclair, Houda Hanana, Camilla Carla Parenti, Francesco Bonasoro, Andrea Binelli
Microplastics (MPs), plastic debris smaller than 5mm, are widely found in both marine and freshwater ecosystems. However, few studies regarding their hazardous effects on inland water organisms, have been conducted. For this reason, the aim of our research was the evaluation of uptake and chronic toxicity of two mixtures (MIXs) of virgin polystyrene microbeads (PMs) of 10μm and 1μm in size (MIX 1, with 5×105 of 1μmsizePMs/L and 5×105 of 10μmsizePMs/L, and MIX 2 with 2×106 of 1μmsizePMs/L and 2×106 of 10μmsizePMs/L) on freshwater zebra mussel Dreissena polymorpha (Mollusca: Bivalvia) during 6 exposure days...
March 12, 2018: Science of the Total Environment
Cheng-Han Wu, Bang-Hung Yang, Yuan-Hwa Chou, Shyh-Jen Wang, Jyh-Cheng Chen
99mTc-TRODAT-1 is a type of drug that can bind to dopamine transporters in living organisms and is often used in SPCT imaging for observation of changes in the activity uptake of dopamine in the striatum. Therefore, it is currently widely used in studies on clinical diagnosis of Parkinson's disease (PD) and movement-related disorders. In conventional 99mTc-TRODAT-1 SPECT image evaluation, visual inspection or manual selection of ROI for semiquantitative analysis is mainly used to observe and evaluate the degree of striatal defects...
2018: PloS One
Pontus Plavén-Sigray, Granville James Matheson, Petter Gustavsson, Per Stenkrona, Christer Halldin, Lars Farde, Simon Cervenka
BACKGROUND: Associations between dopamine receptor levels and pro- and antisocial behavior have previously been demonstrated in human subjects using positron emission tomography (PET) and self-rated measures of personality traits. So far, only one study has focused on the dopamine D1-receptor (D1-R), finding a positive correlation with the trait social desirability, which is characterized by low dominant and high affiliative behavior, while physical aggression showed a negative correlation...
2018: PloS One
Peter Kranke, Sergio D Bergese, Harold S Minkowitz, Timothy I Melson, David G Leiman, Keith A Candiotti, Ngai Liu, Leopold Eberhart, Ashraf S Habib, Jan Wallenborn, Anthony L Kovac, Pierre Diemunsch, Gabriel Fox, Tong J Gan
BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors...
March 15, 2018: Anesthesiology
Farzad Jalali, Seyedeh Fatemeh Hashemi
BACKGROUND: From one hand, depression is one of the symptoms that occur after abstinence from methamphetamine. On the other people living with HIV/AIDS are in isolation due to the nature of their illness and depression is one of the most common mental health problems they experience. OBJECTIVES: This study was aimed at determining the effectiveness of saffron on reducing depression among recovered consumers of methamphetamine living with HIV/AIDS. METHODS: The design of this study was semi-experimental with pre-test, post-test and control (placebo) groups...
March 15, 2018: Substance Use & Misuse
Prama Pallavi, Marc Pretze, Julio Caballero, Yingchun Li, Björn B Hofmann, Eleni Stamellou, Sarah Klotz, Carmen Wängler, Björn Wängler, Ralf Loesel, Steffen Roth, Bastian Theisinger, Handan Moerz, Uta Binzen, Wolfgang Greffrath, Rolf-Detlef Treede, Martin C Harmsen, Bernhard K Krämer, Mathias Hafner, Benito A Yard, Anna-Isabelle Kälsch
We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) activation and inhibition of inflammation. The efficacy of NOD to activate TRPV1 was significantly higher compared to variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted (N-octanoyl tyramine) or the ester functionality consisted of a bulky fatty acid (N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its efficacy which further increased by interchanging the carbonyl and amide groups (ΔNODR)...
March 15, 2018: Journal of Medicinal Chemistry
Bruno Romeo, Lisa Blecha, Katia Locatelli, Amine Benyamina, Catherine Martelli
The objective of this meta-analysis is to assess the efficacy and safety of partial and complete dopamine agonists in the treatment of acute mood disorder episodes. Randomized, double-blind and placebo-controlled trials of dopamine agonists in the treatment of acute mood disorder episodes were identified in the MEDLINE and PsycINFO databases and included in the meta-analysis. In monotherapy of mania, improved remission rates were found for cariprazine (odds ratio (OR): 2.08, P < 0.01) and for high-dose aripiprazole (OR: 3...
March 1, 2018: Journal of Psychopharmacology
Augusta Pisanu, Laura Boi, Giovanna Mulas, Saturnino Spiga, Sandro Fenu, Anna R Carta
Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration...
March 14, 2018: Journal of Neural Transmission
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