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https://www.readbyqxmd.com/read/28405636/when-transporters-fail-to-be-transported-how-to-rescue-folding-deficient-slc6-transporters
#1
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/28404997/novel-fitc-labeled-igy-antibody-fluorescence-imaging-toxoplasma-gondii-in-vitro
#2
Mehtap Sert, Rabia Cakir Koc, Yasemin Budama Kilinc
Toxoplasmosis is caused by T. gondii and can create serious health problems in humans and also worldwide economic harm. Because of the clinical and veterinary importance of toxoplasmosis, its timely and accurate diagnosis has a major impact on disease-fighting strategies. T. gondii surface antigen 1 (SAG1), an immunodominant-specific antigen, is often used as a diagnostic tool. Therefore, the aim of this study was the optimization of novel fluorescein isothiocyanate (FITC) labeling of the SAG1-specific IgY antibody to show the potential for immunofluorescence imaging of T...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404880/serotonergic-system-antagonists-target-breast-tumor-initiating-cells-and-synergize-with-chemotherapy-to-shrink-human-breast-tumor-xenografts
#3
William D Gwynne, Robin M Hallett, Adele Girgis-Gabardo, Bojana Bojovic, Anna Dvorkin-Gheva, Craig Aarts, Kay Dias, Anita Bane, John A Hassell
Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396142/atypical-binding-at-dopamine-and-serotonin-transporters-contribute-to-the-discriminative-stimulus-effects-of-mephedrone
#4
Alyssa F DeLarge, Laura L Erwin, Peter J Winsauer
Mephedrone (4-methylmethcathinone), a constituent of the recreational substances known as "bath salts", is a synthetic cathinone that can produce auditory and visual hallucinations, as well as problematic cardiovascular effects. This study compared the discriminative stimulus effects of mephedrone (0.32-10 mg/kg) with other prototypical drugs of abuse: cocaine (0.56-32 mg/kg), d-amphetamine (0.18-3.2 mg/kg), ketamine (1.8-18 mg/kg), phencyclidine (PCP, 1-5.6 mg/kg), heroin (1-10 mg/kg), 2,5-dimethoxy-4-iodoamphetamine (R-DOI, 0...
April 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342338/antidepressants-and-risk-of-cataract-development-a-population-based-nested-case-control-study
#5
Po-Han Chou, Che-Sheng Chu, Yi-Huei Chen, Min-Yen Hsu, Min-Wei Huang, Tsuo-Hung Lan, Ching-Heng Lin
BACKGROUND: Previous studies demonstrated increased risk of cataract development among users of selective serotonin reuptake inhibitors (SSRIs). However, it remains unknown whether this risk also prevails with the use of other types of antidepressants. The aim of this study was to investigate whether use of antidepressants is associated with an increased risk of cataract development. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of antidepressant and the risk of cataracts is examined...
March 18, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28331735/metaplastic-breast-carcinoma-analysis-of-clinical-and-pathologic-characteristics-a-case-series
#6
Semra Salimoğlu, İsmail Sert, Mustafa Emiroğlu, Cem Karaali, Dilek Kuzukıran, Yasemin Akyüz Kırmızı, Gülden Diniz, Cengiz Aydın
OBJECTIVE: Metaplastic breast cancer (MBC) is a rare type of breast cancer that is considered to be clinically aggressive. The clinical significance and prognostic risk factors of MBC are limited. This study comprises a retrospective analysis of the clinical and pathologic findings of a series of patients treated for MBC. MATERIALS AND METHODS: The files of 657 patients who underwent surgery because of breast cancer at our clinic were examined and the data found on 11 patients who were diagnosed as having MBC were analyzed...
April 2016: Journal of Breast Health (2013)
https://www.readbyqxmd.com/read/28284954/peri-adolescent-asthma-symptoms-cause-adult-anxiety-related-behavior-and-neurobiological-processes-in-mice
#7
Jasmine I Caulfield, Michael J Caruso, Kerry C Michael, Rebecca A Bourne, Nicole R Chirichella, Laura C Klein, Timothy Craig, Robert H Bonneau, Avery August, Sonia A Cavigelli
Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28266501/the-novel-modafinil-analog-jjc8-016-as-a-potential-cocaine-abuse-pharmacotherapeutic
#8
Hai-Ying Zhang, Guo-Hua Bi, Hong-Ju Yang, Yi He, Gilbert Xue, Jiajing Cao, Gianluigi Tanda, Eliot L Gardner, Amy Hauck Newman, Zheng-Xiong Xi
(±)Modafinil ((±)MOD) and its R-enantiomer (R-modafinil; R-MOD) have been investigated for their potential as treatments for psychostimulant addiction. We recently reported a series of (±)MOD analogs, of which JJC8-016 (N-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)-3-phenylpropan-1-amine) was selected for further development. JJC8-016 and R-MOD were evaluated for binding across ~70 receptors, transporters, and enzymes. Although at a concentration of 10 μM, there were many hits for JJC8-016, binding affinities in the range of its DAT affinity were only observed at the serotonin transporter (SERT), dopamine D2-like, and sigma1 receptors...
March 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28220701/deconstructed-analogs-of-bupropion-reveal-structural-requirements-for-transporter-inhibition-versus-substrate-induced-neurotransmitter-release
#9
Abdelrahman R Shalabi, Donna Walther, Michael H Baumann, Richard A Glennon
Bupropion (1), an α-aminophenone uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET), is a widely prescribed antidepressant and smoking cessation aid. Cathinone (2), a structurally simpler α-aminophenone, is a substrate-type releasing agent at the same transporters and a recognized drug of abuse. Our goal was to identify the structural features of α-aminophenones that govern the mechanistic transition from uptake inhibition to substrate-induced release. Deconstructed analogs of 1 were synthesized and compared for their ability to interact with DAT, NET, and the serotonin transporter (SERT) using in vitro assay methods...
February 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28220069/effects-of-selective-serotonin-reuptake-inhibitors-on-interregional-relation-of-serotonin-transporter-availability-in-major-depression
#10
Gregory M James, Pia Baldinger-Melich, Cecile Philippe, Georg S Kranz, Thomas Vanicek, Andreas Hahn, Gregor Gryglewski, Marius Hienert, Marie Spies, Tatjana Traub-Weidinger, Markus Mitterhauser, Wolfgang Wadsak, Marcus Hacker, Siegfried Kasper, Rupert Lanzenberger
Selective serotonin reuptake inhibitors (SSRIs) modulate serotonergic neurotransmission by blocking reuptake of serotonin from the extracellular space. Up to now, it remains unclear how SSRIs achieve their antidepressant effect. However, task-based and resting state functional magnetic resonance imaging studies, have demonstrated connectivity changes between brain regions. Here, we use positron emission tomography (PET) to quantify SSRI's main target, the serotonin transporter (SERT), and assess treatment-induced molecular changes in the interregional relation of SERT binding potential (BPND)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28198447/the-tnf-%C3%AE-antagonist-etanercept-reverses-age-related-decreases-in-colonic-sert-expression-and-faecal-output-in-mice
#11
Bhavik Anil Patel, Sara Fidalgo, Chunfang Wang, Leena Parmar, Kasonde Mandona, Annabelle Panossian, Melanie S Flint, Richard N Ranson, M Jill Saffrey, Mark S Yeoman
Treatment for chronic constipation in older people is challenging and the condition has a major impact on quality of life. A lack of understanding about the causes of this condition has hampered the development of effective treatments. 5-HT is an important pro-kinetic agent in the colon. We examined whether alterations in colonic 5-HT signalling underlie age-related changes in faecal output in mice and whether these changes were due to an increase in TNF-α. Components of the 5-HT signalling system (5-HT, 5-HIAA, SERT) and TNF-α expression were examined in the distal colon of 3, 12, 18 and 24-month old mice and faecal output and water content monitored under control conditions and following the administration of etanercept (TNF-α inhibitor; 1 mg Kg(-1))...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28182708/comparison-of-brain-serotonin-transporter-using-i-123-adam-between-obese-and-non-obese-young-adults-without-an-eating-disorder
#12
Chih-Hsing Wu, Chin-Sung Chang, Yen Kuang Yang, Lie-Hang Shen, Wei-Jen Yao
Cerebral serotonin metabolism has an important but controversial role in obesity. However, it is not given enough attention in morbidly obese young adults. We used single photon emission computed tomography (SPECT) with [I-123]-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) to investigate changes in serotonin transporter (SERT) availability in 10 morbidly obese young adults without an eating disorder (M/F = 5/5, body mass index (BMI): 40.3 ± 4.1 kg/m2, percentage of body fat (BF%): 46...
2017: PloS One
https://www.readbyqxmd.com/read/28132172/evaluation-of-benign-afebrile-convulsions-in-16-children-with-rotavirus-gastroenteritis
#13
Alaaddin Yorulmaz, Sadiye Sert, Fatma Hilal Yilmaz
In this study, we aimed to investigate the demographic, clinical, and laboratory findings of the patients hospitalized with rotavirus gastroenteritis-related afebrile seizure, retrospectively. The study population consisted of 16 patients (9 girls and 7 boys) with a mean age of 13.81 ± 5.98 months (age range 6-26). The male/female ratio was 0.77. None of the patients had any psychomotor developmental retardation. Neurological examinations of all the patients were normal. There were 7 patients with generalized tonic (43...
January 28, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28097008/preclinical-findings-predicting-efficacy-and-side-effect-profile-of-ly2940094-an-antagonist-of-nociceptin-receptors
#14
Jeffrey M Witkin, Linda M Rorick-Kehn, Mark J Benvenga, Benjamin L Adams, Scott D Gleason, Karen M Knitowski, Xia Li, Steven Chaney, Julie F Falcone, Janice W Smith, Julie Foss, Kirsti Lloyd, John T Catlow, David L McKinzie, Kjell A Svensson, Vanessa N Barth, Miguel A Toledo, Nuria Diaz, Celia Lafuente, Alma Jiménez, Alfonso Benito, Conception Pedregal, Maria A Martínez-Grau, Anke Post, Michael A Ansonoff, John E Pintar, Michael A Statnick
Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide whose receptor is designated ORL1 or nociceptin receptor (NOP). We utilized a potent, selective, and orally bioavailable antagonist with documented engagement with NOP receptors in vivo to assess antidepressant- and anxiolytic-related pharmacological effects of NOP receptor blockade along with measures of cognitive and motor impingement. LY2940094 ([2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol) displayed antidepressant-like behavioral effects in the forced-swim test in mice, an effect absent in NOP (-/-) mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28094186/nardonaphthalenones-a-and-b-from-the-roots-and-rhizomes-of-nardostachys-chinensis-batal
#15
Xu Deng, Yi-Jing Wu, Ying-Peng Chen, Hong-Hong Zheng, Zhong-Ping Wang, Yan Zhu, Xiu-Mei Gao, Yan-Tong Xu, Hong-Hua Wu
Nardonaphthalenones A and B (1-2), one new apo-α-carotenone (3) and four new monoterpenoids (4, 8-9 and 11), along with six known compounds (5-7, 10, 12-13) were isolated from the dried roots and rhizomes of Nardostachys chinensis Batal. Their structures were elucidated by analysis of the spectroscopic data including NMR, HRESIMS and circular dichroism data. Furthermore, the serotonin transporter (SERT)-regulating activities of these isolates were evaluated, among them compound 3 showed the strongest enhancement activity while compound 12 showed a moderate inhibition activity on SERT...
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28068779/norepinephrine-transporter-gene-variants-and-remission-from-depression-with-venlafaxine-treatment-in-older-adults
#16
Victoria S Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K Tiwari, Etienne Sibille, Daniel M Blumberger, Jordan F Karp, Eric J Lenze, Charles F Reynolds, James L Kennedy, Benoit H Mulsant, Daniel J Müller
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine. METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
January 10, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28066808/effect-of-mr-imaging-contrast-thresholds-on-prediction-of-neoadjuvant-chemotherapy-response-in-breast-cancer-subtypes-a-subgroup-analysis-of-the-acrin-6657-i-spy-1-trial
#17
Wen Li, Vignesh Arasu, David C Newitt, Ella F Jones, Lisa Wilmes, Jessica Gibbs, John Kornak, Bonnie N Joe, Laura J Esserman, Nola M Hylton
Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery...
December 2016: Tomography: a Journal for Imaging Research
https://www.readbyqxmd.com/read/28043073/a-comparative-qsar-analysis-and-molecular-docking-studies-of-phenyl-piperidine-derivatives-as-potent-dual-nk1r-antagonists-serotonin-transporter-sert-inhibitors
#18
Somayeh Zare, Masood Fereidoonnezhad, Davoud Afshar, Zahra Ramezani
Depression is a critical mood disorder that affects millions of patients. Available therapeutic antidepressant agents are associated with several undesirable side effects. Recently, it has been shown that Neurokinin 1 receptor (NK1R) antagonists can potentiate the antidepressant effects of serotonin-selective reuptake inhibitors (SSRIs). In this study, a series of phenyl piperidine derivatives as potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors were applied to quantitative structure-activity relationship (QSAR) analysis...
December 23, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28035393/fluoxetine-protects-against-methamphetamine%C3%A2-induced-lung-inflammation-by-suppressing-oxidative-stress-through-the-sert-p38-mapk-nrf2-pathway-in-rats
#19
Yun Wang, Yu-Han Gu, Ming Liu, Yang Bai, Huai-Liang Wang
Methamphetamine (MA) abuse is a major public health and safety concern throughout the world and a growing burden on healthcare costs. The purpose of the present study was to investigate the protective effect of fluoxetine against MA‑induced chronic pulmonary inflammation and to evaluate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidative stress. Wistar rats were divided into control, MA and two fluoxetine‑treated groups. Rats in the MA and the two fluoxetine‑treated groups were treated daily with intraperitoneal injection of 10 mg/kg MA twice daily...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27993209/enhanced-serotonin-signaling-stimulates-ordered-intestinal-mucosal-growth
#20
John J Tackett, Neeru Gandotra, Michaela C Bamdad, Eleanor D Muise, Robert A Cowles
BACKGROUND: Significant quantities of serotonin (5-hydroxytryptamine; 5-HT) are found in the intestine, and studies have demonstrated that 5-HT can stimulate enterocyte cell division, suggesting regulatory roles in mucosal homeostasis and intestinal adaptation. We hypothesized that excess enteric 5-HT signaling enhances mucosal growth without changing intestinal villous cellular makeup. METHODS: Mice lacking the serotonin reuptake transporter (SERT) and wild-type littermates (WTLM) were euthanized and their ileum analyzed...
February 2017: Journal of Surgical Research
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