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  1. Article ; Online: Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    Detrait, Eric R / Carr, Greg V / Weinberger, Daniel R / Lamberty, Yves

    Behavioural pharmacology

    2016  Volume 27, Issue 5, Page(s) 415–421

    Abstract: The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, ... ...

    Abstract The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.
    MeSH term(s) Animals ; Benzophenones/administration & dosage ; Benzophenones/pharmacology ; Blood-Brain Barrier/metabolism ; Brain/metabolism ; Catechol O-Methyltransferase/drug effects ; Catechol O-Methyltransferase/genetics ; Catechol O-Methyltransferase Inhibitors/administration & dosage ; Catechol O-Methyltransferase Inhibitors/pharmacology ; Catechols/pharmacology ; Cognition Disorders/drug therapy ; Cognition Disorders/physiopathology ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Male ; Memory Disorders/drug therapy ; Mice ; Mice, Transgenic ; Nitriles/pharmacology ; Nitrophenols/administration & dosage ; Nitrophenols/pharmacology ; Phencyclidine/administration & dosage ; Phencyclidine/toxicity ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Recognition (Psychology)/drug effects ; Tolcapone
    Chemical Substances Benzophenones ; Catechol O-Methyltransferase Inhibitors ; Catechols ; Nitriles ; Nitrophenols ; entacapone (4975G9NM6T) ; Tolcapone (CIF6334OLY) ; Catechol O-Methyltransferase (EC 2.1.1.6) ; Phencyclidine (J1DOI7UV76) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2016-03-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 1027374-8
    ISSN 1473-5849 ; 0955-8810
    ISSN (online) 1473-5849
    ISSN 0955-8810
    DOI 10.1097/FBP.0000000000000208
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Using Bayesian analysis in repeated preclinical in vivo studies for a more effective use of animals.

    Walley, Rosalind / Sherington, John / Rastrick, Joe / Detrait, Eric / Hanon, Etienne / Watt, Gillian

    Pharmaceutical statistics

    2016  Volume 15, Issue 3, Page(s) 277–285

    Abstract: Whilst innovative Bayesian approaches are increasingly used in clinical studies, in the preclinical area Bayesian methods appear to be rarely used in the reporting of pharmacology data. This is particularly surprising in the context of regularly repeated ...

    Abstract Whilst innovative Bayesian approaches are increasingly used in clinical studies, in the preclinical area Bayesian methods appear to be rarely used in the reporting of pharmacology data. This is particularly surprising in the context of regularly repeated in vivo studies where there is a considerable amount of data from historical control groups, which has potential value. This paper describes our experience with introducing Bayesian analysis for such studies using a Bayesian meta-analytic predictive approach. This leads naturally either to an informative prior for a control group as part of a full Bayesian analysis of the next study or using a predictive distribution to replace a control group entirely. We use quality control charts to illustrate study-to-study variation to the scientists and describe informative priors in terms of their approximate effective numbers of animals. We describe two case studies of animal models: the lipopolysaccharide-induced cytokine release model used in inflammation and the novel object recognition model used to screen cognitive enhancers, both of which show the advantage of a Bayesian approach over the standard frequentist analysis. We conclude that using Bayesian methods in stable repeated in vivo studies can result in a more effective use of animals, either by reducing the total number of animals used or by increasing the precision of key treatment differences. This will lead to clearer results and supports the "3Rs initiative" to Refine, Reduce and Replace animals in research. Copyright © 2016 John Wiley & Sons, Ltd.
    MeSH term(s) Animals ; Bayes Theorem ; Cytokines/metabolism ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods ; Inflammation/pathology ; Lipopolysaccharides/pharmacology ; Models, Animal ; Nootropic Agents/pharmacology ; Research Design
    Chemical Substances Cytokines ; Lipopolysaccharides ; Nootropic Agents
    Language English
    Publishing date 2016-05
    Publishing country England
    Document type Comparative Study ; Journal Article
    ZDB-ID 2083706-9
    ISSN 1539-1612 ; 1539-1604
    ISSN (online) 1539-1612
    ISSN 1539-1604
    DOI 10.1002/pst.1748
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The inhibitory avoidance test optimized for discovery of cognitive enhancers.

    Detrait, Eric R A Y / Hanon, Etienne / Dardenne, Bertrand / Lamberty, Yves

    Behavior research methods

    2009  Volume 41, Issue 3, Page(s) 805–811

    Abstract: In the present article, we describe a new protocol for the inhibitory avoidance test, with a dual purpose: (1) to provide a less variable and more reliable assessment of the efficacy of potential cognitive enhancers in antagonizing scopolamine-induced ... ...

    Abstract In the present article, we describe a new protocol for the inhibitory avoidance test, with a dual purpose: (1) to provide a less variable and more reliable assessment of the efficacy of potential cognitive enhancers in antagonizing scopolamine-induced long-term-memory deficits, and (2) to secure a high throughput for pharmacological screening of cognitive enhancers. The new protocol consists of two acquisition trials that are followed 24 h later by a single retention trial. In the present study, this protocol clearly dissociated the frequency distributions of retention latencies between scopolamine- and vehicle-treated groups and allowed validation by means of two acetylcholinesterase inhibitors-tacrine and donepezil-that proved to be active in counteracting the scopolamine-induced memory deficit. This protocol also produced stability of the behavioral response to pharmacological agents over a 3-year period. A statistical power analysis indicated that, depending on the efficacy of the drug/dose, a sample size of 5-12 mice was required in order to show a reversal of the scopolamine-induced memory deficit. The double-trial acquisition protocol is suitable for testing cognitive enhancers, while also providing a clearly enhanced throughput.
    MeSH term(s) Animals ; Avoidance Learning/drug effects ; Drug Evaluation, Preclinical/instrumentation ; Drug Evaluation, Preclinical/methods ; Drug Interactions ; Indans/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Nootropic Agents/pharmacology ; Piperidines/pharmacology ; Scopolamine Hydrobromide/pharmacology ; Tacrine/pharmacology
    Chemical Substances Indans ; Nootropic Agents ; Piperidines ; Scopolamine Hydrobromide (451IFR0GXB) ; Tacrine (4VX7YNB537) ; donepezil (8SSC91326P)
    Language English
    Publishing date 2009-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 231560-9
    ISSN 1554-3528 ; 1554-351X ; 0743-3808
    ISSN (online) 1554-3528
    ISSN 1554-351X ; 0743-3808
    DOI 10.3758/BRM.41.3.805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Extracorporeal photopheresis for GVHD prophylaxis after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation: a prospective multicenter phase 2 study.

    Michallet, Mauricette / Sobh, Mohamad / Garban, Frederic / Bulabois, Claude Eric / Yakoub-Agha, Ibrahim / Coiteux, Valerie / Dulery, Remy / Rohrlich, Pierre-Simon / Legrand, Faezeh / Clement, Laurence / Praire, Aline / Detrait, Marie / Barraco, Fiorenza / Nicolini, Franck Emmanuel / Hequet, Olivier

    Leukemia & lymphoma

    2017  Volume 59, Issue 2, Page(s) 372–380

    Abstract: We performed a prospective multicenter phase 2 study to evaluate the safety and efficacy of prophylactic Extracorporeal Photopheresis (ECP) in adult patients with hematological malignancies early after RIC allo-HSCT on day 21 twice per week during the ... ...

    Abstract We performed a prospective multicenter phase 2 study to evaluate the safety and efficacy of prophylactic Extracorporeal Photopheresis (ECP) in adult patients with hematological malignancies early after RIC allo-HSCT on day 21 twice per week during the first two weeks and then once per week for the next four weeks for a total of eight ECP courses. A total of 20 patients were included; 10 were males, median age was 60 years. All patients engrafted, 17 (85%) received the total eight ECP courses. There were no adverse effects related to ECP. Seven patients developed acute graft-versus-host disease (GVHD), with 15% grade ≥ II cumulative incidence at day 100. The cumulative incidence of chronic GVHD at 2 years was 22%. The 2 years probability of overall survival (OS) and progression-free survival (PFS) were 84 and 74%, respectively. This study shows encouraging results with low acute and chronic GVHD incidence and no interference with graft-versus-leukemia (GVL) effect.
    MeSH term(s) Acute Disease ; Aged ; Biomarkers ; Chronic Disease ; Female ; Graft vs Host Disease/etiology ; Graft vs Host Disease/mortality ; Graft vs Host Disease/prevention & control ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/mortality ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunosuppressive Agents/therapeutic use ; Incidence ; Male ; Middle Aged ; Photopheresis/methods ; Survival Analysis ; Transplantation Chimera ; Transplantation Conditioning/adverse effects ; Transplantation Conditioning/methods ; Transplantation, Homologous ; Treatment Outcome
    Chemical Substances Biomarkers ; Immunosuppressive Agents
    Language English
    Publishing date 2017-06-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2017.1334120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Human neural tube defects: developmental biology, epidemiology, and genetics.

    Detrait, Eric R / George, Timothy M / Etchevers, Heather C / Gilbert, John R / Vekemans, Michel / Speer, Marcy C

    Neurotoxicology and teratology

    2005  Volume 27, Issue 3, Page(s) 515–524

    Abstract: Birth defects (congenital anomalies) are the leading cause of death in babies under 1 year of age. Neural tube defects (NTD), with a birth incidence of approximately 1/1000 in American Caucasians, are the second most common type of birth defect after ... ...

    Abstract Birth defects (congenital anomalies) are the leading cause of death in babies under 1 year of age. Neural tube defects (NTD), with a birth incidence of approximately 1/1000 in American Caucasians, are the second most common type of birth defect after congenital heart defects. The most common presentations of NTD are spina bifida and anencephaly. The etiologies of NTDs are complex, with both genetic and environmental factors implicated. In this manuscript, we review the evidence for genetic etiology and for environmental influences, and we present current views on the developmental processes involved in human neural tube closure.
    MeSH term(s) Animals ; Environment ; Female ; Humans ; Mice ; Nervous System/embryology ; Neural Tube Defects/epidemiology ; Neural Tube Defects/genetics ; Neural Tube Defects/pathology ; Pregnancy
    Language English
    Publishing date 2005-03-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639165-5
    ISSN 1872-9738 ; 0892-0362
    ISSN (online) 1872-9738
    ISSN 0892-0362
    DOI 10.1016/j.ntt.2004.12.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Reporter gene transfer induces apoptosis in primary cortical neurons.

    Detrait, Eric R / Bowers, William J / Halterman, Marc W / Giuliano, Rita E / Bennice, Lisa / Federoff, Howard J / Richfield, Eric K

    Molecular therapy : the journal of the American Society of Gene Therapy

    2002  Volume 5, Issue 6, Page(s) 723–730

    Abstract: Modern cell biologists typically use reporter genes either alone or co-expressed with a protein of interest to facilitate the localization or quantification of protein expression. Our work demonstrates that reporter genes should be used cautiously, as ... ...

    Abstract Modern cell biologists typically use reporter genes either alone or co-expressed with a protein of interest to facilitate the localization or quantification of protein expression. Our work demonstrates that reporter genes should be used cautiously, as several common reporter gene products are toxic to primary cortical neuronal cultures. We used the herpes simplex virus-based viral amplicon vector to transduce cortical neurons with three different reporter genes and assessed whether any reporter gene products were toxic over time, by monitoring neurite disintegration and apoptosis. Toxicity varied as a function of the reporter gene, the gene product localization, and the level of reporter gene expression. Transduction of enhanced green fluorescent protein or nuclear-localized beta-galactosidase was more toxic than non-nuclear localized beta-galactosidase. This work underscores the need for careful design of gene expression constructs. Moreover, in studies where cell injury or toxicity is being evaluated, their use should be carefully considered.
    MeSH term(s) Animals ; Apoptosis ; Cells, Cultured ; Dose-Response Relationship, Drug ; Gene Transfer Techniques ; Genes, Reporter ; Genetic Vectors/metabolism ; Green Fluorescent Proteins ; Luminescent Proteins/genetics ; Luminescent Proteins/toxicity ; Mice ; Neurons/cytology ; Neurons/pathology ; Simplexvirus/metabolism ; Transgenes ; beta-Galactosidase/genetics ; beta-Galactosidase/toxicity
    Chemical Substances Luminescent Proteins ; Green Fluorescent Proteins (147336-22-9) ; beta-Galactosidase (EC 3.2.1.23)
    Language English
    Publishing date 2002-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1006/mthe.2002.0609
    Database MEDical Literature Analysis and Retrieval System OnLINE

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