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https://www.readbyqxmd.com/read/28441487/the-isomeric-preference-of-an-atypical-dopamine-transporter-inhibitor-contributes-to-its-selection-of-the-transporter-conformation
#1
Ara M Abramyan, Sebastian Stolzenberg, Zheng Li, Claus J Loland, Frank Noé, Lei Shi
Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT) by trapping the protein in an outward-open conformation, whereas atypical DAT inhibitors such as benztropine have low abuse liability and prefer less outward-open conformations. Here, we use a spectrum of computational modeling and simulation approaches to obtain the underlying molecular mechanism in atomistic detail. Interestingly, our quantum mechanical calculations and molecular dynamics (MD) simulations suggest that a benztropine derivative JHW007 prefers a different stereoisomeric conformation of tropane in binding to DAT compared to that of a cocaine derivative, CFT...
April 25, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28440392/suppressive-role-of-diallyl-trisul%C3%AF-de-in-the-activated-platelet-mediated-hematogenous-metastasis-of-mda-mb-231-human-breast-cancer-cells
#2
Yuping Liu, Yang Zhao, Yingyu Wang, Pingting Zhu, Zhonghong Wei, Siliang Wang, Li Tao, Zhaoguo Liu, Hongyan Wu, Xiaobo Sheng, Yin Lu
Accumulating evidence has indicated that garlic consumption may reduce the risk of developing several types of cancer, and extensive studies have revealed the effects of its bioactive component, diallyl trisulfide (DATS), on the proliferation and apoptosis of tumor cells. The present study was undertaken to examine whether DATS affects hematogenous metastasis. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we attempted to demonstrate the role of DATS in the metastatic behavior of MDA-MB-231 human breast cancer cells, which were co-incubated with activated platelets...
April 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28440074/applications-of-synthetic-organic-tetrasulfides-as-h2s-donors
#3
Matthew M Cerda, Matthew D Hammers, Mary S Earp, Lev N Zakharov, Michael D Pluth
In an effort to expand the availability of simple polysulfides for H2S donation, we report here the synthesis and H2S release profiles of bis(aryl) and bis(alkyl) tetrasulfides. The tetrasulfide donors release H2S in a first-order dependence on reduced glutathione (GSH) and release more H2S than the commonly used trisulfide DATS.
April 25, 2017: Organic Letters
https://www.readbyqxmd.com/read/28437017/determination-of-the-enantiomeric-purity-of-the-selective-dopamine-transporter-inhibitor-r-r-4-2-benzhydryloxyethyl-1-4-fluorobenzyl-piperidin-3-ol
#4
Patrick Neiens, Georg Höfner, Klaus T Wanner
(+)-R,R-D-84 ((+)-R,R-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol) is a promising pharmacological tool for the dopamine transporter (DAT), due to its high affinity and selectivity for this target. In this study, an analytical method to ascertain the enantiomeric purity of this compound was established. For this purpose, a high-performance liquid chromatographic (HPLC) method, based on a cellulose derived chiral stationary phase (CSP) was developed. The method was characterized concerning its specificity, linearity, and range...
April 24, 2017: Chirality
https://www.readbyqxmd.com/read/28428472/examination-of-a-method-to-determine-the-reference-region-for-calculating-the-specific-binding-ratio-in-dopamine-transporter-imaging
#5
Ayumi Watanabe, Yusuke Inoue, Yuji Asano, Kei Kikuchi, Hiroki Miyatake, Takanobu Tokushige
The specific binding ratio (SBR) was first reported by Tossici-Bolt et al. for quantitative indicators for dopamine transporter (DAT) imaging. It is defined as the ratio of the specific binding concentration of the striatum to the non-specific binding concentration of the whole brain other than the striatum. The non-specific binding concentration is calculated based on the region of interest (ROI), which is set 20 mm inside the outer contour, defined by a threshold technique. Tossici-Bolt et al. used a 50% threshold, but sometimes we couldn't define the ROI of non-specific binding concentration (reference region) and calculate SBR appropriately with a 50% threshold...
2017: Nihon Hoshasen Gijutsu Gakkai Zasshi
https://www.readbyqxmd.com/read/28426941/behavioral-deficits-and-neural-damage-of-caenorhabditis-elegans-induced-by-three-rare-earth-elements
#6
Tiantian Xu, Manke Zhang, Jiani Hu, Zihan Li, Taipu Wu, Jianing Bao, Siyu Wu, Lili Lei, Defu He
Rare earth elements (REEs) are widely used in industry, agriculture, medicine and daily life in recent years. However, environmental and health risks of REEs are still poorly understood. In this study, neurotoxicity of trichloride neodymium, praseodymium and scandium were evaluated using nematode Caenorhabditis elegans as the assay system. Median lethal concentrations (48 h) were 99.9, 157.2 and 106.4 mg/L for NdCl3, PrCl3 and ScCl3, respectively. Sublethal dose (10-30 mg/L) of these trichloride salts significantly inhibited body length of nematodes...
April 17, 2017: Chemosphere
https://www.readbyqxmd.com/read/28426083/energetic-isomers-of-1-2-4-5-tetrazine-bis-1-2-4-triazoles-with-low-toxicity
#7
A Shlomovich, T Pechersky, A Cohen, Q L Yan, M Kosa, N Petrutik, N Tal, A Aizikovich, M Gozin
A series of nitrogen-rich "green" Energetic Materials (EMs), some with improved sensitivity, thermostability, and very low toxicity, were synthesized on the basis of 3,5-diamino-1,2,4-triazole (DAT) and 1,2,4,5-tetrazine building blocks. Since DAT contains several nucleophilic reactive sites, obtaining selective reactivity and specific isomeric products with 1,2,4,5-tetrazine precursors is a challenging task. We developed reaction conditions under which specific isomers could be prepared. On evaluating these compounds for their energetic properties, we found that N(5),N(5)'-(1,2,4,5-tetrazine-3,6-diyl)-bis(1H-1,2,4-triazole-3,5-diamine) 1 has very high thermostability (onset of decomposition temperature at 357 °C) and it is insensitive to impact (Im > 98 J), friction (>360 N) and electrostatic discharge (2512 mJ)...
April 20, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28418992/initiation-of-antiretroviral-therapy-containing-integrase-inhibitors-increases-the-risk-of-iris-requiring-hospitalization
#8
Marine Dutertre, Lise Cuzin, Elisa Demonchy, Pascal Puglièse, Véronique Joly, Marc-Antoine Valantin, Laurent Cotte, Thomas Huleux, Pierre Delobel, Guillaume Martin-Blondel
No abstract text is available yet for this article.
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28418899/an-exploration-of-the-role-of-a-fish-oriented-diet-in-cognitive-decline-a-systematic-review-of-the-literature
#9
REVIEW
Ling-Feng Zeng, Ye Cao, Wei-Xiong Liang, Wen-Hu Bao, Jian-Ke Pan, Qi Wang, Jun Liu, Hao-Dong Liang, Hui Xie, Yan-Ting Chai, Zi-Tong Guan, Qian Cao, Xiao-Yan Li, Lei Yang, Wei-Hua Xu, Sui-Qing Mi, Ning-Sheng Wang
Epidemiological studies have presented inconsistent evidence of the correlation between a fish-oriented dietary intake (FDI) and the risk of cognitive decline. To address these controversies, we performed this systematic review of prospective studies published in December 2016 and earlier using PubMed, Embase, and Web of Science. Two independent researchers conducted the eligibility assessment and data extraction; all discrepancies were solved by discussion with a third researcher. The pooled relative risks (RRs) focused on the incidence of events were estimated with 95% confidence intervals (CIs)...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418071/chronic-exposure-to-graphene-based-nanomaterials-induces-behavioral-deficits-and-neural-damage-in-caenorhabditis-elegans
#10
Ping Li, Tiantian Xu, Siyu Wu, Lili Lei, Defu He
Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C...
April 18, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28417953/recombinant-adeno-associated-virus-mediated-rescue-of-function-in-a-mouse-model-of-dopamine-transporter-deficiency-syndrome
#11
P Illiano, C E Bass, L Fichera, L Mus, E A Budygin, T D Sotnikova, D Leo, S Espinoza, R R Gainetdinov
Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416295/depressive-symptoms-in-schizophrenia-and-dopamine-and-serotonin-gene-polymorphisms
#12
Vjekoslav Peitl, Mario Štefanović, Dalibor Karlović
Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores...
April 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28410288/the-utility-of-the-combination-of-a-spect-study-with-123i-fp-cit-of-dopamine-transporters-and-123i-mibg-myocardial-scintigraphy-in-differentiating-parkinson-disease-from-other-degenerative-parkinsonian-syndromes
#13
Naoto Uyama, Hideki Otsuka, Takayoshi Shinya, Yoichi Otomi, Masafumi Harada, Wataru Sako, Yuishin Izumi, Ryuji Kaji, Yuya Watanabe, Satoru Takashi, Yamato Kunikane
OBJECTIVE: Molecular imaging of nigrostriatal dopamine transporters (DAT) and sympathetic cardiac innervation with single-photon emission computed tomography (SPECT) are useful tools for differentiating idiopathic Parkinson disease (PD) from other degenerative parkinsonian syndromes (non-PD). Nevertheless, these modalities are often insufficient for achieving a definite diagnosis. The aims of this study were to evaluate the diagnostic accuracy of the combination of these tools. MATERIALS AND METHODS: The SPECT radiotracers [I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) and meta-[I]-iodobenzylguanidine (MIBG) were used to research presynaptic dopaminergic projections (DAT SPECT) and myocardial adrenergic innervation (MIBG scintigraphy), respectively...
April 13, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28409113/axonal-damage-and-loss-of-connectivity-in-nigrostriatal-and-mesolimbic-dopamine-pathways-in-early-parkinson-s-disease
#14
Silvia Paola Caminiti, Luca Presotto, Damiano Baroncini, Valentina Garibotto, Rosa Maria Moresco, Luigi Gianolli, Maria Antonietta Volonté, Angelo Antonini, Daniela Perani
A progressive loss of dopamine neurons in the substantia nigra (SN) is considered the main feature of idiopathic Parkinson's disease (PD). Recent neuropathological evidence however suggests that the axons of the nigrostriatal dopaminergic system are the earliest target of α-synuclein accumulation in PD, thus the principal site for vulnerability. Whether this applies to in vivo PD, and also to the mesolimbic system has not been investigated yet. We used [(11)C]FeCIT PET to measure presynaptic dopamine transporter (DAT) activity in both nigrostriatal and mesolimbic systems, in 36 early PD patients (mean disease duration in months ± SD 21...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28408289/dopaminergic-control-of-anxiety-in-young-and-aged-zebrafish
#15
Victoria Kacprzak, Neil A Patel, Elizabeth Riley, Lili Yu, Jing-Ruey J Yeh, Irina V Zhdanova
Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wildtype (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed...
April 10, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28407307/adenosine-a1-receptors-measured-with-11-c-mpdx-pet-in-early-parkinson-s-disease
#16
Masahiro Mishina, Kenji Ishii, Yuichi Kimura, Masahiko Suzuki, Shin Kitamura, Kenji Ishibashi, Muneyuki Sakata, Keiichi Oda, Shiro Kobayashi, Kazumi Kimura, Kiichi Ishiwata
Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1 Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-(11) C-methyl-3-propylxanthine ((11) C-MPDX). We studied 10 drug-naïve patients with early PD...
April 13, 2017: Synapse
https://www.readbyqxmd.com/read/28406934/dat-spect-assessment-depicts-dopamine-depletion-among-asymptomatic-g2019s-lrrk2-mutation-carriers
#17
Moran Artzi, Einat Even-Sapir, Hedva Lerman Shacham, Avner Thaler, Avi Orr Urterger, Susan Bressman, Karen Marder, Talma Hendler, Nir Giladi, Dafna Ben Bashat, Anat Mirelman
Identification of early changes in Dopamine-Transporter (DaT) SPECT imaging expected in the prodromal phase of Parkinson's disease (PD), are usually overlooked. Carriers of the G2019S LRRK2 mutation are known to be at high risk for developing PD, compared to non-carriers. In this work we aimed to study early changes in Dopamine uptake in non-manifesting PD carriers (NMC) of the G2019S LRRK2 mutation using quantitative DaT-SPECT analysis and to examine the potential for early prediction of PD. Eighty Ashkenazi-Jewish subjects were included in this study: eighteen patients with PD; thirty-one NMC and thirty-one non-manifesting non-carriers (NMNC)...
2017: PloS One
https://www.readbyqxmd.com/read/28406545/diagnosing-nocturnal-paroxysmal-hemoglobinuria-a-single-center-4-year-experience
#18
T Mercier, T Devos, M Mukovnikova, N Boeckx
INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease and can present as a wide range of signs and symptoms. As such, the indication for diagnostic testing for PNH is not always straightforward. Therefore, we analyzed all first-time samples tested over a 56-month period to determine the clinical settings with a high probability of detecting a PNH clone. METHODS: We retrospectively analyzed 323 first-time PNH flow cytometry tests, including LDH, cytopenias, direct antiglobulin test (DAT), and clinical indication for testing as available at the time of testing...
April 13, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28405636/when-transporters-fail-to-be-transported-how-to-rescue-folding-deficient-slc6-transporters
#19
Sonja Sucic, Ameya Kasture, H M Mazhar Asjad, Carina Kern, Ali El-Kasaby, Michael Freissmuth
The human dopamine transporter (hDAT) belongs to the solute carrier 6 (SLC6) gene family. Point mutations in hDAT (SLC6A3) have been linked to a syndrome of dopamine transporter deficiency or infantile dystonia/parkinsonism. The mutations impair DAT folding, causing retention of variant DATs in the endoplasmic reticulum and subsequently impair transport activity. The folding trajectory of DAT itself is not understood, though many insights have been gained from studies of folding-deficient mutants of the closely related serotonin transporter (SERT); i...
December 30, 2016: Journal of Neurology & Neuromedicine
https://www.readbyqxmd.com/read/28403780/synthesis-of-novel-benzothiazole-piperazine-derivatives-and-their-biological-evaluation-as-acetylcholinesterase-inhibitors-and-cytotoxic-agents
#20
Enise Ece Gurdal, Bengisu Turgutalp, Hayrettin Ozan Gulcan, Tugba Erçetin, Mustafa Fethi Sahin, Irem Durmaz, Rengul Cetin Atalay, Quoc Dat Nguyen, Wolfgang Sippl, Mine Yarim
A new series of benzothiazole-piperazine derivatives were synthesized and a complete chemical characterization of the novel compounds was provided. In vitro cytotoxic activities were screened against colorectal (HCT-116), breast (MCF-7) and hepatocellular (Huh7) cancer cell lines by Sulforhodamine B assay. All compounds showed cytotoxic activity against hepatocellular (Huh7) and breast (MCF-7) cancer cell lines. Dihalo substituted benzylpiperazine derivatives (2a, 2e) had the highest cytotoxic activities in all tested cell lines...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
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