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https://www.readbyqxmd.com/read/28806140/adherent-invasive-e-coli-enhances-colonic-hypersensitivity-and-p2x-receptors-expression-during-post-infectious-period
#1
Amandine Lashermes, Ludivine Boudieu, Julie Barbier, Benoit Sion, Agathe Gelot, Nicolas Barnich, Denis Ardid, Frédéric Antonio Carvalho
Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are related gastrointestinal disorders characterized by abdominal pain associated with colonic hypersensitivity (CHS). Studies in humans have reported an abnormal colonization of Adherent-Invasive E. coli (AIEC) in the ileum of Crohn's disease (CD) patients associated with overexpression of the bacterial colonizing receptor CEACAM6. The aim of the present study was to investigate whether AIEC reference strain LF82 could induce intestinal impairment during infectious and/or post-infectious periods and subsequently the development of CHS...
August 14, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28797200/the-polymorphism-of-dopamine-receptor-d4-drd4-and-dopamine-transporter-dat-genes-in-the-men-with-antisocial-behavior-and-mixed-martial-arts-fighters
#2
Elena Cherepkova, Vladimir Maksimov, Alexandr Kushnarev, Igor Shakhmatov, Lyubomir I Aftanas
OBJECTIVES: VNTR polymorphisms of DRD4 and DAT genes were studied in the Russian and Chechen men convicted of crimes, and two control groups comprised of the MMA fighters and a sample of general population. A group of MMA fighters included only the subjects without history of antisocial behavior. METHODS: DNA was isolated by phenol-chloroform extraction from the blood. Genotyping VNTR polymorphisms of the DRD4 and DAT genes were performed by PCR on published methods...
August 11, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28630890/drd4-gene-polymorphisms-as-a-risk-factor-for-children-with-attention-deficit-hyperactivity-disorder-in-iranian-population
#3
Seyed Mahmoud Tabatabaei, Shahrokh Amiri, Sara Faghfouri, Seyed Gholamreza Noorazar, Shahin AbdollahiFakhim, Ali Fakhari
BACKGROUND AND OBJECTIVE: Dopamine dysfunction is known to be associated with attention deficit hyperactivity disorder (ADHD). Dopamine D4 receptor gene (DRD4) is one of the important genes in this pathway. This study intended to investigate the variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene in Iranian children and adolescents. MATERIALS AND METHODS: In this study, 130 children with ADHD, aged 6-14 years, and 130 healthy children, within the same age range, were enrolled...
2017: International Scholarly Research Notices
https://www.readbyqxmd.com/read/28592831/genetic-variation-of-dopamine-and-serotonin-function-modulates-the-feedback-related-negativity-during-altruistic-punishment
#4
Sören Enge, Hendrik Mothes, Monika Fleischhauer, Andreas Reif, Alexander Strobel
Why do humans cooperate and often punish norm violations of others? In the present study, we sought to investigate the genetic bases of altruistic punishment (AP), which refers to the costly punishment of norm violations with potential benefit for other individuals. Recent evidence suggests that norm violations and unfairness are indexed by the feedback-related negativity (FRN), an anterior cingulate cortex (ACC) generated neural response to expectancy violations. Given evidence on the role of serotonin and dopamine in AP as well as in FRN-generation, we explored the impact of genetic variation of serotonin and dopamine function on FRN and AP behavior in response to unfair vs...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28559635/asenapine-for-the-control-of-physical-aggression-a-prospective-naturalist-pilot-study
#5
Jin Shi Amon, Sarah B Johnson, Rif S El-Mallakh
It has been previously purported that higher relative affinity to the dopamine D4 receptor compared to D2 (i.e., D4/D2 affinity ratio > 1) may underlie unique antiaggression potency. Asenapine is a newer antipsychotic that also has D4/D2 affinity ratio > 1. It has demonstrated efficacy in reducing acute agitation in a placebo-controlled study. We performed a prospective naturalistic, pilot, proof of concept study on an inpatient psychiatric unit. Among patients with aggression at time of admission (≥ 12 on Refined Aggression Questionnaire [RAQ], or ≥ 2 on Modified Overt Aggression Scale [MOAS]), asenapine treatment was associated with a significant reduction in total aggression as measured by the MOAS (-14...
January 26, 2017: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/28530534/biological-evaluation-of-99mtc-hynic-edda-tricine-ser-3-d4-peptide-for-tumor-targeting
#6
Ziba Kazemi, Mona Haddad Zahmatkesh, Seyed Mohammad Abedi, Seyed Jalal Hosseinimehr
BACKGROUND: D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). OBJECTIVE: The aim of study was to investigate the 99mTc-labeled D4 peptide for non small cell lung tumor targeting. METHOD: HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabebled peptide was evaluated by blocking test on human non small lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice...
May 19, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28495611/hiv-1-tat-protein-enhances-sensitization-to-methamphetamine-by-affecting-dopaminergic-function
#7
James P Kesby, Julia A Najera, Benedetto Romoli, Yiding Fang, Liana Basova, Amanda Birmingham, Maria Cecilia G Marcondes, Davide Dulcis, Svetlana Semenova
Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period...
October 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28489950/the-return-of-d4-dopamine-receptor-antagonists-in-drug-discovery
#8
Craig W Lindsley, Corey R Hopkins
The dopamine D4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Coupled with genetic association of the DRD4 gene with various CNS disorders, multiple companies launched discovery programs to develop selective D4 antagonists. Merck's D4 antagonist L-745,870 was the first to reach the clinic, where it was found to be ineffective in schizophrenia patients, and other groups failed to recapitulate some of the genetic data...
May 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28455126/neurochemical-arguments-for-the-use-of-dopamine-d4-receptor-stimulation-to-improve-cognitive-impairment-associated-with-schizophrenia
#9
Mei Huang, Sunoh Kwon, Wenqi He, Herbert Y Meltzer
BACKGROUND: Dopamine (DA) D4 receptors have been implicated in schizophrenia and the ability of some atypical antipsychotic drugs (APDs) to improve the cognitive impairment associated with schizophrenia (CIAS). Systemic administration of a D4 agonist, PD168077, at a sub-effective dose, together with a sub-effective dose of lurasidone, an atypical APD which is a weak D4 receptor antagonist, reversed the deficit in novel object recognition (NOR) in rats treated subchronically with phencyclidine (PCP), a rodent model of CIAS...
April 25, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28450726/effect-of-drd4-receptor-616-c-g-polymorphism-on-brain-structure-and-functional-connectivity-density-in-pediatric-primary-nocturnal-enuresis-patients
#10
Bing Yu, Na Chang, Yao Lu, Hongwei Ma, Na Liu, Qiyong Guo
The dopamine D4 receptor (DRD4) promoter (-616; rs747302) has been associated with primary nocturnal enuresis (PNE); however, its relationship with neuroimaging has not been investigated. Therefore, we assessed the effects of the DRD4 -616 C/G single nucleotide polymorphism on the gray matter volume (GMV) and functional connectivity density (FCD) during resting-state functional magnetic resonance imaging in children with PNE using voxel-based morphometry and FCD methods. Genomic and imaging data were obtained from 97 children with PNE and 105 healthy controls...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428702/drd4-and-dat1-vntr-genotyping-in-children-with-attention-deficit-hyperactivity-disorder
#11
Ashley Stanley, K Chavda, A Subramanian, S V Prabhu, T F Ashavaid
The dopamine receptor-D4 and the dopamine transporter have been investigated for their role in attention deficit hyperactivity disorder (ADHD) in children. Reports of their genetic association with ADHD have shown mixed results. The aim of the study was to evaluate the association of variable number tandem repeats (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was conducted at a tertiary care centre in Mumbai...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28424758/redox-related-epigenetic-mechanisms-in-glioblastoma-nuclear-factor-erythroid-derived-2-like-2-cobalamin-and-dopamine-receptor-subtype-4
#12
Matthew Scott Schrier, Malav Suchin Trivedi, Richard Carlton Deth
Glioblastoma is an exceptionally difficult cancer to treat. Cancer is universally marked by epigenetic changes, which play key roles in sustaining a malignant phenotype, in addition to disease progression and patient survival. Studies have shown strong links between the cellular redox state and epigenetics. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor that upregulates endogenous antioxidant production, and is aberrantly expressed in many cancers, including glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28420882/the-role-of-the-swi-snf-chromatin-remodeling-complex-in-maintaining-the-stemness-of-glioma-initiating-cells
#13
Hiroaki Hiramatsu, Kazuyoshi Kobayashi, Kyousuke Kobayashi, Takeshi Haraguchi, Yasushi Ino, Tomoki Todo, Hideo Iba
Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373127/rp5063-an-atypical-antipsychotic-drug-with-a-unique-pharmacologic-profile-improves-declarative-memory-and-psychosis-in-mouse-models-of-schizophrenia
#14
Lakshmi Rajagopal, Sunoh Kwon, Mei Huang, Eric Michael, Laxminarayan Bhat, Marc Cantillon, Herbert Y Meltzer
Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4β2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied...
March 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28361337/chronic-stressors-and-adolescents-externalizing-problems-genetic-moderation-by-dopamine-receptor-d4-the-trails-study
#15
Anna Roos E Zandstra, Johan Ormel, Pieter J Hoekstra, Catharina A Hartman
The existing literature does not provide consistent evidence that carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to adverse environmental influences, resulting in enhanced externalizing problems, compared to noncarriers. One explanation is that the adverse influences examined in prior studies were not severe, chronic, or distressing enough to reveal individual differences in sensitivity reflected by DRD4-7R. This study examined whether the 7-repeat allele moderated the association between chronic stressors capturing multiple stressful aspects of individuals' lives and externalizing problems in adolescence...
March 30, 2017: Journal of Abnormal Child Psychology
https://www.readbyqxmd.com/read/28347261/dopamine-d4-receptor-stimulation-contributes-to-novel-object-recognition-relevance-to-cognitive-impairment-in-schizophrenia
#16
Masanori Miyauchi, Nichole M Neugebauer, Herbert Y Meltzer
Several atypical antipsychotic drugs (APDs) have high affinity for the dopamine (DA) D4 receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D4 receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D4 agonist, PD168077, and the D4 antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone...
April 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28341945/translational-value-of-drug-discrimination-with-typical-and-atypical-antipsychotic-drugs
#17
Joseph H Porter, Kevin A Webster, Adam J Prus
This chapter focuses on the translational value of drug discrimination as a preclinical assay for drug development. In particular, the importance of two factors, i.e., training dose and species, for drug discrimination studies with the atypical antipsychotic clozapine is examined. Serotonin receptors appear to be an important pharmacological mechanism mediating clozapine's discriminative cue in both rats and mice, although differences are clearly evident as antagonism of cholinergic muscarinic receptors is important in rats at a higher training dose (5...
March 25, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28336436/induction-of-dopamine-d1-and-d5-receptors-in-r28%C3%A2-cells-by-light-exposures
#18
Yan Ke, Wentao Li, Zhiqun Tan, Zhikuan Yang
Dopamine is known to play an important role in the pathophysiological process of myopia development relevant to the ambient lighting, but it is still poorly understood about how lighting regulates dopamine and its interaction with dopamine receptors to mediate the pathogenic signal transduction leading to alterations of ocular globe and the pathogenesis of myopia. Many studies have highlighted changes of ocular dopamine amount in response to different lighting conditions, but little attention has been paid to the dopamine receptors during these processes...
May 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28329817/early-life-benzo-a-pyrene-exposure-causes-neurodegenerative-syndromes-in-adult-zebrafish-danio-rerio-and-the-mechanism-involved
#19
Dongxu Gao, Chonggang Wang, Zhihui Xi, Yixi Zhou, Yuanchuan Wang, Zhenghong Zuo
There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration...
May 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28327307/discovery-characterization-and-biological-evaluation-of-a-novel-r-4-4-difluoropiperidine-scaffold-as-dopamine-receptor-4-d4r-antagonists
#20
Daniel E Jeffries, Jonathan O Witt, Andrea L McCollum, Kayla J Temple, Miguel A Hurtado, Joel M Harp, Anna L Blobaum, Craig W Lindsley, Corey R Hopkins
Herein, we report the synthesis and structure-activity relationship of a novel series of (R)-4,4-difluoropiperidine core scaffold as dopamine receptor 4 (D4) antagonists. A series of compounds from this scaffold are highly potent against the D4 receptor and selective against the other dopamine receptors. In addition, we were able to confirm the active isomer as the (R)-enantiomer via an X-ray crystal structure.
December 1, 2016: Bioorganic & Medicinal Chemistry Letters
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