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[PMID]:27771572
[Au] Autor:Rapee RM; Jones MP; Hudson JL; Malhi GS; Lyneham HJ; Schneider SC
[Ad] Endereço:Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, New South Wales, 2109, Australia. Electronic address: Ron.Rapee@mq.edu.au.
[Ti] Título:d-Cycloserine does not enhance the effects of in vivo exposure among young people with broad-based anxiety disorders.
[So] Source:Behav Res Ther;87:225-231, 2016 12.
[Is] ISSN:1873-622X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Use of the partial NMDA receptor agonist d-Cycloserine (DCS) to increase extinction to feared cues among anxious adults has shown mixed, although overall positive effects. Few studies have extended this effect to youth and none have addressed young people with broad-based anxiety such as separation anxiety, social anxiety, or generalised anxiety. In the current trial 51 children and adolescents with diagnosed anxiety disorders, aged 7-14 years received four sessions of graduated, experimenter-led, in vivo exposure to a hierarchy of feared cues relevant to their primary fear. They were randomly allocated to receive either 50 mg of DCS or a matched placebo capsule in a fully double-blind design. Both groups showed large reductions across sessions in their primary fear according to both parent and child report, but there were no significant differences between conditions at any session. The results are consistent with most studies to date of DCS-augmented exposure in young people.
[Mh] Termos MeSH primário: Transtornos de Ansiedade/tratamento farmacológico
Transtornos de Ansiedade/terapia
Ciclosserina/uso terapêutico
Terapia Implosiva
[Mh] Termos MeSH secundário: Adolescente
Criança
Terapia Combinada
Método Duplo-Cego
Feminino
Seres Humanos
Masculino
Nootrópicos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nootropic Agents); 95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180203
[Lr] Data última revisão:
180203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  2 / 1596 MEDLINE  
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[PMID]:28914444
[Au] Autor:Tremiño L; Forcada-Nadal A; Contreras A; Rubio V
[Ad] Endereço:Instituto de Biomedicina de Valencia (IBV-CSIC), CIBER de Enfermedades Raras (CIBERER-ISCIII), Valencia, Spain.
[Ti] Título:Studies on cyanobacterial protein PipY shed light on structure, potential functions, and vitamin B -dependent epilepsy.
[So] Source:FEBS Lett;591(20):3431-3442, 2017 Oct.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Synechococcus elongatus COG0325 gene pipY functionally interacts with the nitrogen regulatory gene pipX. As a first step toward a molecular understanding of such interactions, we characterized PipY. This 221-residue protein is monomeric and hosts pyridoxal phosphate (PLP), binding it with limited affinity and losing it upon incubation with D-cycloserine. PipY crystal structures with and without PLP reveal a single-domain monomer folded as the TIM barrel of type-III fold PLP enzymes, with PLP highly exposed, fitting a role for PipY in PLP homeostasis. The mobile PLP phosphate-anchoring C-terminal helix might act as a trigger for PLP exchange. Exploiting the universality of COG0325 functions, we used PipY in site-directed mutagenesis studies to shed light on disease causation by epilepsy-associated mutations in the human COG0325 gene PROSC.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Proteínas PII Reguladoras de Nitrogênio/química
Proteínas/química
Fosfato de Piridoxal/química
Synechococcus/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Clonagem Molecular
Cristalografia por Raios X
Ciclosserina/química
Ciclosserina/metabolismo
Epilepsia/metabolismo
Epilepsia/patologia
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Seres Humanos
Cinética
Modelos Moleculares
Mutagênese Sítio-Dirigida
Proteínas PII Reguladoras de Nitrogênio/genética
Proteínas PII Reguladoras de Nitrogênio/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Dobramento de Proteína
Domínios e Motivos de Interação entre Proteínas
Proteínas/genética
Proteínas/metabolismo
Fosfato de Piridoxal/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
Synechococcus/metabolismo
Termodinâmica
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (PII Nitrogen Regulatory Proteins); 0 (PROSC protein, human); 0 (Proteins); 0 (Recombinant Proteins); 5V5IOJ8338 (Pyridoxal Phosphate); 95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12841


  3 / 1596 MEDLINE  
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[PMID]:28813484
[Au] Autor:Na ES; De Jesús-Cortés H; Martinez-Rivera A; Kabir ZD; Wang J; Ramesh V; Onder Y; Rajadhyaksha AM; Monteggia LM; Pieper AA
[Ad] Endereço:Department of Psychology & Philosophy, Texas Woman's University, Denton, TX, United States of America.
[Ti] Título:D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome.
[So] Source:PLoS One;12(8):e0183026, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain. Here, we show that Mecp2tm1.1Jae/y mice display lower presynaptic function as assessed by paired pulse ratio, as well as decreased long term potentiation (LTP) at hippocampal Schaffer-collateral-CA1 synapses. Treatment of Mecp2tm1.1Jae/y mice with D-cycloserine (DCS), an FDA-approved analog of the amino acid D-alanine with antibiotic and glycinergic activity, corrected the presynaptic but not LTP deficit without affecting deficient hippocampal BDNF levels. DCS treatment did, however, partially restore lower BDNF levels in the brain stem and striatum. Thus, treatment with DCS may mitigate the severity of some of the neurobehavioral symptoms experienced by patients with Rett syndrome.
[Mh] Termos MeSH primário: Ciclosserina/farmacologia
Síndrome de Rett/fisiopatologia
Transmissão Sináptica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Apneia
Tronco Encefálico/metabolismo
Tronco Encefálico/fisiopatologia
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Corpo Estriado/metabolismo
Corpo Estriado/fisiopatologia
Ciclosserina/administração & dosagem
Modelos Animais de Doenças
Marcha/efeitos dos fármacos
Hipocampo/efeitos dos fármacos
Hipocampo/fisiopatologia
Locomoção/efeitos dos fármacos
Masculino
Proteína 2 de Ligação a Metil-CpG/genética
Camundongos
Camundongos Transgênicos
Força Muscular/efeitos dos fármacos
Síndrome de Rett/tratamento farmacológico
Síndrome de Rett/genética
Síndrome de Rett/metabolismo
Tremor
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Methyl-CpG-Binding Protein 2); 95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183026


  4 / 1596 MEDLINE  
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[PMID]:28588223
[Au] Autor:Tabuchi F; Matsumoto Y; Ishii M; Tatsuno K; Okazaki M; Sato T; Moriya K; Sekimizu K
[Ad] Endereço:Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
[Ti] Título:D-cycloserine increases the effectiveness of vancomycin against vancomycin-highly resistant Staphylococcus aureus.
[So] Source:J Antibiot (Tokyo);70(8):907-910, 2017 Jul.
[Is] ISSN:0021-8820
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Vancomycin is a widely used clinical drug to treat for infection by methicillin-resistant Staphylococcus aureus. Some patients show a weak response to vancomycin treatment. We previously reported that ß-lactams increase the susceptibility to vancomycin by vancomycin-highly resistant S. aureus (VRSA) strains obtained following repeated in vitro mutagenesis and vancomycin selection. Here we found that the susceptibility of the VRSA strains to vancomycin was remarkably increased by combined treatment with D-cycloserine. On the other hand, VRSA did not show increased susceptibility to vancomycin in combination with bacitracin, fosfomycin, erythromycin, lincomycin, gentamicin, levofloxacin or nisin. Furthermore, in an in vivo infection model with silkworms, combined treatment with vancomycin and D-cycloserine exhibited therapeutic effects, whereas treatment with each compound alone did not. These findings suggest that combined treatment with vancomycin and D-cycloserine could be therapeutically effective against infectious diseases caused by VRSA.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Ciclosserina/farmacologia
Infecções Estafilocócicas/tratamento farmacológico
Staphylococcus aureus/efeitos dos fármacos
Vancomicina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/administração & dosagem
Bombyx
Ciclosserina/administração & dosagem
Modelos Animais de Doenças
Sinergismo Farmacológico
Testes de Sensibilidade Microbiana
Infecções Estafilocócicas/microbiologia
Vancomicina/administração & dosagem
Resistência a Vancomicina
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 6Q205EH1VU (Vancomycin); 95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1038/ja.2017.56


  5 / 1596 MEDLINE  
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[PMID]:28282427
[Au] Autor:Bürkner PC; Bittner N; Holling H; Buhlmann U
[Ad] Endereço:Institute of Psychology, University of Münster, Münster, Germany.
[Ti] Título:D-cycloserine augmentation of behavior therapy for anxiety and obsessive-compulsive disorders: A meta-analysis.
[So] Source:PLoS One;12(3):e0173660, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The present meta-analysis investigates whether the antibiotic D-cycloserine (DCS), a partial agonist at the glutamatergic N-methyl-D-aspartate receptor, can augment the effect of behavior therapy in humans with anxiety and obsessive-compulsive disorders. METHOD: A keyword-based computer search was conducted using common electronic databases. Only studies investigating the effect of DCS in humans with anxiety and obsessive-compulsive disorders were included, resulting in 23 studies with a combined sample size of 1314 patients. Effect sizes were coded as Hedges' g and SMCC, the latter also incorporating differences in pre-treatment values. Bayesian multilevel meta-analysis was applied to take dependencies of effect sizes obtained from the same study into account. RESULTS: While previous meta-analyses found small to moderate improvements, the current results including the most recent research indicate that the overall effect of DCS is very small and almost indistinguishable from zero (g = -0.12, CI = [-0.27, 0.02]; SMCC = -0.10, CI = [-0.29, 0.07]). Slightly larger effects were found for social anxious patients. Further, study quality and year of publication were relevant moderators, with higher quality / more recent studies reported smaller effects of DCS. CONCLUSIONS: These findings raise the question of the usefulness of DCS as an augmentation of exposure therapy for anxiety and obsessive-compulsive disorders. At least, it seems to be less promising than initially thought. The fact that study quality was inversely related to the reported effect sizes underlines the importance of high quality primary research in order to avoid over-estimation of treatment effects in clinical psychology.
[Mh] Termos MeSH primário: Transtornos de Ansiedade/terapia
Ciclosserina/uso terapêutico
Terapia Implosiva/métodos
Transtorno Obsessivo-Compulsivo/terapia
[Mh] Termos MeSH secundário: Transtornos de Ansiedade/tratamento farmacológico
Teorema de Bayes
Seres Humanos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173660


  6 / 1596 MEDLINE  
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[PMID]:28272868
[Au] Autor:Amorim Franco TM; Favrot L; Vergnolle O; Blanchard JS
[Ad] Endereço:Department of Biochemistry, Albert Einstein College of Medicine , 1300 Morris Park Avenue, Bronx, New York 10461, United States.
[Ti] Título:Mechanism-Based Inhibition of the Mycobacterium tuberculosis Branched-Chain Aminotransferase by d- and l-Cycloserine.
[So] Source:ACS Chem Biol;12(5):1235-1244, 2017 May 19.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The branched-chain aminotransferase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme responsible for the final step in the biosynthesis of all three branched-chain amino acids, l-leucine, l-isoleucine, and l-valine, in bacteria. We have investigated the mechanism of inactivation of the branched-chain aminotransferase from Mycobacterium tuberculosis (MtIlvE) by d- and l-cycloserine. d-Cycloserine is currently used only in the treatment of multidrug-drug-resistant tuberculosis. Our results show a time- and concentration-dependent inactivation of MtIlvE by both isomers, with l-cycloserine being a 40-fold better inhibitor of the enzyme. Minimum inhibitory concentration (MIC) studies revealed that l-cycloserine is a 10-fold better inhibitor of Mycobacterium tuberculosis growth than d-cycloserine. In addition, we have crystallized the MtIlvE-d-cycloserine inhibited enzyme, determining the structure to 1.7 Å. The structure of the covalent d-cycloserine-PMP adduct bound to MtIlvE reveals that the d-cycloserine ring is planar and aromatic, as previously observed for other enzyme systems. Mass spectrometry reveals that both the d-cycloserine- and l-cycloserine-PMP complexes have the same mass, and are likely to be the same aromatized, isoxazole product. However, the kinetics of formation of the MtIlvE d-cycloserine-PMP and MtIlvE l-cycloserine-PMP adducts are quite different. While the kinetics of the formation of the MtIlvE d-cycloserine-PMP complex can be fit to a single exponential, the formation of the MtIlvE l-cycloserine-PMP complex occurs in two steps. We propose a chemical mechanism for the inactivation of d- and l-cycloserine which suggests a stereochemically determined structural role for the differing kinetics of inactivation. These results demonstrate that the mechanism of action of d-cycloserine's activity against M. tuberculosis may be more complicated than previously thought and that d-cycloserine may compromise the in vivo activity of multiple PLP-dependent enzymes, including MtIlvE.
[Mh] Termos MeSH primário: Ciclosserina/farmacologia
Mycobacterium tuberculosis/enzimologia
Transaminases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Cristalografia por Raios X
Cinética
Estrutura Molecular
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
95IK5KI84Z (Cycloserine); EC 2.6.1.- (Transaminases); EC 2.6.1.42 (branched-chain-amino-acid transaminase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00142


  7 / 1596 MEDLINE  
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[PMID]:28269783
[Au] Autor:Huang Y; Shen W; Su J; Cheng B; Li D; Liu G; Zhou WX; Zhang YX
[Ad] Endereço:Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
[Ti] Título:Modulating the Balance of Synaptic and Extrasynaptic NMDA Receptors Shows Positive Effects against Amyloid-ß-Induced Neurotoxicity.
[So] Source:J Alzheimers Dis;57(3):885-897, 2017.
[Is] ISSN:1875-8908
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alzheimer's disease (AD) patients suffer a disturbance in the balance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway), and, therefore, restoring the balance of GluN2A and GluN2B should be beneficial for AD. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effect on amyloid-ß (Aß)-induced long-term potentiation deficits. Enhancing the activity of GluN2A had a protective effect against Aß, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect. In Aß ICV-injected animals, the combination of ifenprodil and D-cycloserine (a co-activator of NMDRs similar to D-serine) led to greater improvement in behavior tests (nest building, novel object recognition, and Morris water maze) than ifenprodil (Morris water maze) or D-cycloserine (nest building) alone. Signal pathway analysis showed that Aß disturbed the GluN2A/GluN2B-related pathway. The ratio of GluN2A to GluN2B decreased in Aß-treated animals, and TORC dephosphorylation and ERK1/2 activation, which could be initiated by GluN2A, also decreased in the hippocampal tissues of Aß-treated animals. As a result, the activation of CREB and the content of brain-derived BDNF decreased. The combination of ifenprodil and D-cycloserine reversed the signal pathway more significantly than ifenprodil or D-cycloserine alone, indicating that Aß-induced toxicology was mediated both by functionally inhibiting GluN2A and enhancing GluN2B. These results indicate that enhancing synaptic NMDARs and inhibiting extrasynaptic NMDARs concurrently showed protective effects against Aß-induced neurotoxicity, suggesting that modulation of the balance between GluN2A and GluN2B could be a potential strategy for AD drug development and therapy.
[Mh] Termos MeSH primário: Hipocampo/patologia
Síndromes Neurotóxicas/patologia
Receptores de N-Metil-D-Aspartato/metabolismo
Sinapses/fisiologia
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/toxicidade
Animais
Antimetabólitos/uso terapêutico
Ciclosserina/uso terapêutico
Modelos Animais de Doenças
Antagonistas de Aminoácidos Excitatórios/uso terapêutico
Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos
Locomoção/efeitos dos fármacos
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
N-Metilaspartato/farmacologia
Comportamento de Nidação/efeitos dos fármacos
Síndromes Neurotóxicas/etiologia
Fragmentos de Peptídeos/toxicidade
Piperidinas/uso terapêutico
Ratos
Ratos Wistar
Recognição (Psicologia)/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Sinapses/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Antimetabolites); 0 (Excitatory Amino Acid Antagonists); 0 (Peptide Fragments); 0 (Piperidines); 0 (Receptors, N-Methyl-D-Aspartate); 0 (amyloid beta-protein (1-42)); 6384-92-5 (N-Methylaspartate); 95IK5KI84Z (Cycloserine); R8OE3P6O5S (ifenprodil)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.3233/JAD-161186


  8 / 1596 MEDLINE  
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[PMID]:28231674
[Au] Autor:Li C; Li GL; Luo Q; Li SJ; Wang RB; Lou YL; Lyu JX; Wan KL
[Ad] Endereço:School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
[Ti] Título:[A preliminary study on the molecular characteristics of D-cycloserine resistance of ].
[So] Source:Zhonghua Liu Xing Bing Xue Za Zhi;38(2):240-243, 2017 Feb 10.
[Is] ISSN:0254-6450
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the relationship between D-cycloserine resistance and the gene mutations of , and of ( ) , as well as the association between D-cycloserine resistance and spoligotyping genotyping. A total of 145 strains were selected from the strain bank. D-cycloserine resistant phenotypes of the strains were determined by the proportion method and the minimal inhibitory concentration was determined by resazurin microtiter assay. PCR amplification and DNA direct sequencing methods were used for the analysis of gene mutations. Relationship between the resistance phenotype and genotype was analyzed by -square test. Of the 145 clinically collected strains, 24 (16.6%) of them were D-cycloserine resistant and 121 (83.4%) were sensitive. There were only synonymous mutations noticed on , and in sensitive strains. Of the 24 D-cycloserine resistant strains, 3 (12.5%) isolates' and 1 (4.2%) isolates' happened to be non-synonymous mutations, in which the codes were 188, 318 and 508 of , and 261 of , respectively. Results on drug sensitivity tests confirmed the minimal inhibitory concentration of the mutant strains were all increased to some degrees. The D-cycloserine resistant rates of 88 Beijing genotype and 57 non-Beijing genotype strains were 20.5% and 10.5% , respectively, but with no statistically significant difference ( (2) =2.47, >0.05). The non-synonymous mutations of and might contribute to one of the mechanisms of D-cycloserine resistance. Beijing genotype or non-Beijing genotype was not considered to be associated with the D-cycloserine resistance.
[Mh] Termos MeSH primário: Antibióticos Antituberculose/farmacologia
Ciclosserina/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/genética
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Antibióticos Antituberculose/uso terapêutico
Pequim
Ciclosserina/uso terapêutico
Genótipo
Seres Humanos
Testes de Sensibilidade Microbiana
Mutação
Fenótipo
Tuberculose Resistente a Múltiplos Medicamentos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antitubercular); 95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170224
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0254-6450.2017.02.021


  9 / 1596 MEDLINE  
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[PMID]:28138381
[Au] Autor:Wink LK; Minshawi NF; Shaffer RC; Plawecki MH; Posey DJ; Horn PS; Adams R; Pedapati EV; Schaefer TL; McDougle CJ; Swiezy NB; Erickson CA
[Ad] Endereço:Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, 3333 Burnet Avenue MLC 4002, Cincinnati, OH 45229 USA.
[Ti] Título:d-Cycloserine enhances durability of social skills training in autism spectrum disorder.
[So] Source:Mol Autism;8:2, 2017.
[Is] ISSN:2040-2392
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: d-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability. METHODS: Study participants included 60 outpatient youth with ASD, ages 5-11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22. RESULTS: Analysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group ( = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups. CONCLUSIONS: The findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01086475.
[Mh] Termos MeSH primário: Transtorno do Espectro Autista/tratamento farmacológico
Ciclosserina/administração & dosagem
Aprendizagem/efeitos dos fármacos
[Mh] Termos MeSH secundário: Transtorno do Espectro Autista/psicologia
Criança
Pré-Escolar
Ciclosserina/farmacologia
Método Duplo-Cego
Esquema de Medicação
Feminino
Seres Humanos
Masculino
Índice de Gravidade de Doença
Comportamento Social
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s13229-017-0116-1


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[PMID]:28122091
[Au] Autor:Mataix-Cols D; Fernández de la Cruz L; Monzani B; Rosenfield D; Andersson E; Pérez-Vigil A; Frumento P; de Kleine RA; Difede J; Dunlop BW; Farrell LJ; Geller D; Gerardi M; Guastella AJ; Hofmann SG; Hendriks GJ; Kushner MG; Lee FS; Lenze EJ; Levinson CA; McConnell H; Otto MW; Plag J; Pollack MH; Ressler KJ; Rodebaugh TL; Rothbaum BO; Scheeringa MS; Siewert-Siegmund A; Smits JAJ; Storch EA; Ströhle A; Tart CD; Tolin DF; van Minnen A; Waters AM; Weems CF; Wilhelm S; Wyka K; Davis M; Rück C; Altemus M; Anderson P; Cukor J; Finck C; Geffken GR; Golfels F; Goodman WK; Gutner C; Heyman I; and the DCS Anxiety Consortium
[Ad] Endereço:Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden2Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
[Ti] Título:D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data.
[So] Source:JAMA Psychiatry;74(5):501-510, 2017 May 01.
[Is] ISSN:2168-6238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.
[Mh] Termos MeSH primário: Antidepressivos/uso terapêutico
Transtornos de Ansiedade/terapia
Ciclosserina/farmacologia
Agonistas de Aminoácidos Excitatórios/farmacologia
Terapia Implosiva/métodos
N-Metilaspartato/agonistas
Transtorno Obsessivo-Compulsivo/terapia
Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos
Transtornos de Estresse Pós-Traumáticos/terapia
[Mh] Termos MeSH secundário: Transtornos de Ansiedade/tratamento farmacológico
Terapia Combinada
Sinergismo Farmacológico
Seres Humanos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico
Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Excitatory Amino Acid Agonists); 6384-92-5 (N-Methylaspartate); 95IK5KI84Z (Cycloserine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1001/jamapsychiatry.2016.3955



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