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[PMID]:29185593
[Au] Autor:Conceição CQ; Engi SA; Cruz FC; Planeta CS
[Ad] Endereço:Laboratório de Neuropsicofarmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP, Brasil.
[Ti] Título:Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats.
[So] Source:Braz J Med Biol Res;51(1):e6388, 2017 Nov 17.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.
[Mh] Termos MeSH primário: Anfetaminas/farmacologia
Anabolizantes/farmacologia
Androgênios/farmacologia
Locomoção/efeitos dos fármacos
Testosterona/farmacologia
[Mh] Termos MeSH secundário: Fatores Etários
Anfetaminas/efeitos adversos
Anabolizantes/efeitos adversos
Androgênios/efeitos adversos
Animais
Comportamento Animal/efeitos dos fármacos
Interações Medicamentosas
Injeções Subcutâneas
Masculino
Atividade Motora/efeitos dos fármacos
Psicotrópicos/efeitos adversos
Psicotrópicos/farmacologia
Ratos Wistar
Testosterona/efeitos adversos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Anabolic Agents); 0 (Androgens); 0 (Psychotropic Drugs); 3XMK78S47O (Testosterone); W0194S5FOA (fenproporex)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE


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[PMID]:28762862
[Au] Autor:Mattingly GW; Wilson J; Rostain AL
[Ad] Endereço:a Washington University School of Medicine , Department of Psychiatry and Behavioral Neurosciences , St. Charles , MO , USA.
[Ti] Título:A clinician's guide to ADHD treatment options.
[So] Source:Postgrad Med;129(7):657-666, 2017 Sep.
[Is] ISSN:1941-9260
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Attention deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition of children and adolescents that often persists into adulthood. Primary care physicians are commonly the first to diagnosis ADHD and initiate a treatment plan with the patient. Guidelines recommend psychostimulant treatment as a first-line therapy in the management plan because it has a substantial impact on alleviating the core symptoms of ADHD. The recent development of a variety of methylphenidate and amphetamine formulations provides many options to meet individual patient lifestyle needs. Liquid, chewable, sprinkled capsule, wearable patch, and orally disintegrating tablet formulations are currently available for patients who may be noncompliant with or have difficulty swallowing traditional pills. This review provides a resource for physicians to identify the stimulant delivery formulation that best suits the patient. Formulations in development are also discussed.
[Mh] Termos MeSH primário: Anfetaminas/uso terapêutico
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico
Estimulantes do Sistema Nervoso Central/uso terapêutico
Metilfenidato/uso terapêutico
Guias de Prática Clínica como Assunto
[Mh] Termos MeSH secundário: Adolescente
Criança
Feminino
Seres Humanos
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amphetamines); 0 (Central Nervous System Stimulants); 207ZZ9QZ49 (Methylphenidate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1080/00325481.2017.1354648


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[PMID]:28672699
[Au] Autor:Causanilles A; Kinyua J; Ruttkies C; van Nuijs ALN; Emke E; Covaci A; de Voogt P
[Ad] Endereço:KWR Watercycle Research Institute, Chemical Water Quality and Health, P.O. Box 1072, 3430 BB, Nieuwegein, The Netherlands; Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, P.O. Box 94248, 1090 GE, Amsterdam, The Netherlands.
[Ti] Título:Qualitative screening for new psychoactive substances in wastewater collected during a city festival using liquid chromatography coupled to high-resolution mass spectrometry.
[So] Source:Chemosphere;184:1186-1193, 2017 Oct.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The inclusion of new psychoactive substances (NPS) in the wastewater-based epidemiology approach presents challenges, such as the reduced number of users that translates into low concentrations of residues and the limited pharmacokinetics information available, which renders the choice of target biomarker difficult. The sampling during special social settings, the analysis with improved analytical techniques, and data processing with specific workflow to narrow the search, are required approaches for a successful monitoring. This work presents the application of a qualitative screening technique to wastewater samples collected during a city festival, where likely users of recreational substances gather and consequently higher residual concentrations of used NPS are expected. The analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. Data were processed using an algorithm that involves the extraction of accurate masses (calculated based on molecular formula) of expected m/z from an in-house database containing about 2,000 entries, including NPS and transformation products. We positively identified eight NPS belonging to the classes of synthetic cathinones, phenethylamines and opioids. In addition, the presence of benzodiazepine analogues, classical drugs and other licit substances with potential for abuse was confirmed. The screening workflow based on a database search was useful in the identification of NPS biomarkers in wastewater. The findings highlight the specific classical drugs and low NPS use in the Netherlands. Additionally, meta-chlorophenylpiperazine (mCPP), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 4-fluoroamphetamine (FA) were identified in wastewater for the first time.
[Mh] Termos MeSH primário: Psicotrópicos/análise
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Anfetaminas/análise
Cromatografia Líquida/métodos
Cidades
Monitoramento Ambiental/métodos
Férias e Feriados
Países Baixos
Piperazinas/análise
Detecção do Abuso de Substâncias/métodos
Espectrometria de Massas em Tandem/métodos
Águas Residuais/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Piperazines); 0 (Psychotropic Drugs); 0 (Waste Water); 0 (Water Pollutants, Chemical); REY0CNO998 (1-(3-chlorophenyl)piperazine); S5744XYR1Z (4-fluoroamphetamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE


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[PMID]:28489121
[Au] Autor:Lucchetta RC; Riveros BS; Pontarolo R; Radominski RB; Otuki MF; Fernandez-Llimos F; Correr CJ
[Ad] Endereço:Laboratory of Clinical Services and Evidence in Health, Pharmacy Department, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
[Ti] Título:Diethylpropion and mazindol: An end to the discussion?
[So] Source:Rev Assoc Med Bras (1992);63(3):203-206, 2017 Mar.
[Is] ISSN:1806-9282
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Antiobesity pharmacotherapy remains the main point of disagreement among both scientists and regulators. This is probably due to small sample sizes, high levels of heterogeneity, and low methodological quality. For many years, Brazil was one of the largest consumers of appetite suppressants worldwide, with evidence of irrational use of this drug class. Therefore, the country was the scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa - Agência Nacional de Vigilância Sanitária) and medical societies over the maintenance record of diethylpropion, mazindol and fenproporex. In this context, this commentary presents new arguments to contribute to the discussion, as well as recommendations for future studies.
[Mh] Termos MeSH primário: Depressores do Apetite/uso terapêutico
Dietilpropiona/uso terapêutico
Mazindol/uso terapêutico
Obesidade/tratamento farmacológico
[Mh] Termos MeSH secundário: Anfetaminas/uso terapêutico
Brasil
Ciclobutanos/uso terapêutico
Aprovação de Drogas
Seres Humanos
Medição de Risco/tendências
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Appetite Depressants); 0 (Cyclobutanes); C56709M5NH (Mazindol); Q94YYU22B8 (Diethylpropion); W0194S5FOA (fenproporex); WV5EC51866 (sibutramine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE


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[PMID]:28329719
[Au] Autor:Allen HK; Caldeira KM; Bugbee BA; Vincent KB; O'Grady KE; Arria AM
[Ad] Endereço:Center on Young Adult Health and Development, University of Maryland School of Public Health, Department of Behavioral and Community Health, 2387 School of Public Health Building, College Park, MD 20742, USA. Electronic address: hallen@umd.edu.
[Ti] Título:Drug involvement during and after college: Estimates of opportunity and use given opportunity.
[So] Source:Drug Alcohol Depend;174:150-157, 2017 May 01.
[Is] ISSN:1879-0046
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: College students perceive widespread availability of drugs and prescription medications for non-medical use on campus, but less is known about the relationship between opportunity to use, use, and use given opportunity of these drugs during and after college. The current study describes annual trends in (1) opportunity to use, (2) use, and (3) use given opportunity of eight drugs and three prescription medications used non-medically over seven years. METHODS: Data were derived from a longitudinal cohort study of 1253 first-year college students (52% female, 72% non-Hispanic white) at one large, public university. Annually, past-year opportunity to use and use were assessed for marijuana, hallucinogens, inhalants, cocaine, ecstasy, amphetamines, methamphetamine, heroin, and non-medical use of prescription stimulants, analgesics, and tranquilizers. Binary variables were created to represent opportunity to use, use, and use given opportunity for each drug. RESULTS: Participants had the greatest opportunity to use marijuana compared with other drugs during the study period, but there was a significant decline in the opportunity to use marijuana over time. Notably, opportunity for both drugs other than marijuana and prescription medications used non-medically consistently declined, while use given opportunity remained relatively stable over time. CONCLUSIONS: These findings suggest that changes in drug use are driven by changes in opportunity to use, even during the post-college years. Greater opportunity to use and use of all drugs during the college years in comparison with the post-college years confirms the high-risk nature of the college environment.
[Mh] Termos MeSH primário: Anfetaminas
Estimulantes do Sistema Nervoso Central
Usuários de Drogas/psicologia
Alucinógenos
Fumar Maconha/psicologia
Psicotrópicos
Estudantes
Transtornos Relacionados ao Uso de Substâncias/psicologia
Universidades
[Mh] Termos MeSH secundário: Adolescente
Estudos de Coortes
Feminino
Seres Humanos
Estudos Longitudinais
Masculino
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Central Nervous System Stimulants); 0 (Hallucinogens); 0 (Psychotropic Drugs)
[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:170323
[St] Status:MEDLINE


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[PMID]:28262446
[Au] Autor:Maas A; Sydow K; Madea B; Hess C
[Ad] Endereço:University Bonn, Institute of Forensic Medicine, Department of Forensic Toxicology, Stiftsplatz 12, 53111 Bonn, Germany. Electronic address: alexandramaas@uni-bonn.de.
[Ti] Título:Separation of ortho, meta and para isomers of methylmethcathinone (MMC) and methylethcathinone (MEC) using LC-ESI-MS/MS: Application to forensic serum samples.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1051:118-125, 2017 Apr 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Separation and identification of positional isomers is an important issue in forensic toxicology, particularly in the context of new psychoactive substances (NPS). Despite the structural similarity, positional isomers often show different pharmacological properties and thus can exhibit dramatic differences with respect to their toxicity. Additionally, besides these pharmacological and toxicological effects, the legal status is also of great importance. We present a sensitive and selective LC-MS/MS method to separate the ortho, meta and para isomers of methylmethcathinone (MMC) and methylethcathinone (MEC) using a core-shell biphenyl analytical column. Reliability of the method was confirmed under consideration of the validation parameters selectivity, linearity, accuracy and precision, analytical limits, processed sample stability, matrix effects and recovery. Linearity was demonstrated over the entire calibration range from 5 to 250ng/ml with the use of a 1/x weighting. Appropriate quantification and detection limits (LLOQ=5ng/ml, LOD<2ng/ml) could be achieved. Application of the method to real serum samples collected between June 2014 and August 2016 revealed the proof of a recent MMC or MEC consumption, respectively, in eight cases. Isomers of MMC could be detected in three of these eight cases, of which two were positive for 3-MMC and one was positive for 2-MMC. The other samples were tested positively for 3-MEC. In none of the samples 4-MMC, 2-MEC or 4-MEC could be detected. Only substances that were not governmentally controlled at that time could be detected, reflecting the rapid response of the recreational drug market to newly enacting drug laws.
[Mh] Termos MeSH primário: Anfetaminas/isolamento & purificação
Estimulantes do Sistema Nervoso Central/isolamento & purificação
Cromatografia Líquida de Alta Pressão/métodos
Metanfetamina/análogos & derivados
Propiofenonas/isolamento & purificação
Espectrometria de Massas por Ionização por Electrospray/métodos
Drogas Ilícitas/isolamento & purificação
[Mh] Termos MeSH secundário: Anfetaminas/análise
Anfetaminas/sangue
Estimulantes do Sistema Nervoso Central/análise
Estimulantes do Sistema Nervoso Central/sangue
Seres Humanos
Isomerismo
Limite de Detecção
Metanfetamina/análise
Metanfetamina/sangue
Metanfetamina/isolamento & purificação
Propiofenonas/análise
Propiofenonas/sangue
Drogas Ilícitas/análise
Drogas Ilícitas/sangue
Espectrometria de Massas em Tandem/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (3-methylmethcathinone); 0 (Amphetamines); 0 (Central Nervous System Stimulants); 0 (Propiophenones); 0 (Street Drugs); 44RAL3456C (Methamphetamine); 9665W17SH3 (4-methylethcathinone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE


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[PMID]:28230564
[Au] Autor:Odell AP; Reynolds GL; Fisher DG; Huckabay LM; Pedersen WC; Xandre P; Miocevic M
[Ad] Endereço:*School of Nursing, †Center for Behavioral Research and Services, and ‡Department of Psychology, California State University, Long Beach, CA; and §Department of Psychology, Arizona State University, Tempe, AZ.
[Ti] Título:Attention Deficit Hyperactivity Disorder, Aggression, and Illicit Stimulant Use: Is This Self-Medication?
[So] Source:J Nerv Ment Dis;205(5):372-379, 2017 May.
[Is] ISSN:1539-736X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study compares adults with and without attention deficit hyperactivity disorder (ADHD) on measures of direct and displaced aggression and illicit drug use. Three hundred ninety-six adults were administered the Wender Utah Rating Scale, the Risk Behavior Assessment, the Aggression Questionnaire (AQ), and the Displaced Aggression Questionnaire (DAQ). Those with ADHD were higher on all scales of the AQ and DAQ, were younger at first use of amphetamines, and were more likely to have ever used crack and amphetamines. A Structural Equation Model found a significant interaction in that for those with medium and high levels of verbal aggression, ADHD predicts crack and amphetamine. Follow-up logistic regression models suggest that blacks self-medicate with crack and whites and Hispanics self-medicate with amphetamine when they have ADHD and verbal aggression.
[Mh] Termos MeSH primário: Agressão/fisiologia
Anfetaminas/uso terapêutico
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia
Cocaína Crack/uso terapêutico
Automedicação
Transtornos Relacionados ao Uso de Substâncias/etiologia
[Mh] Termos MeSH secundário: Adulto
Grupo com Ancestrais do Continente Africano/etnologia
Agressão/efeitos dos fármacos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico
Transtorno do Deficit de Atenção com Hiperatividade/etnologia
Grupo com Ancestrais do Continente Europeu/etnologia
Feminino
Hispano-Americanos/estatística & dados numéricos
Seres Humanos
Los Angeles/etnologia
Masculino
Meia-Idade
Transtornos Relacionados ao Uso de Substâncias/etnologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Crack Cocaine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170524
[Lr] Data última revisão:
170524
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170224
[St] Status:MEDLINE
[do] DOI:10.1097/NMD.0000000000000668


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[PMID]:28161375
[Au] Autor:Mi Z; Si T; Kapadia K; Li Q; Muma NA
[Ad] Endereço:Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, United States.
[Ti] Título:Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines.
[So] Source:Neuropharmacology;117:93-105, 2017 May 01.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Regulation of dendritic spines is an important component of synaptic function and plasticity whereas dendritic spine dysregulation is related to several psychiatric and neurological diseases. In the present study, we tested the hypothesis that serotonin (5-HT)2A/2C receptor-induced Rho family transamidation and activation regulates dendritic spine morphology and that activation of multiple types of receptors can induce transglutaminase (TGase)-catalyzed transamidation of small G proteins. We previously reported a novel 5-HT2A receptor downstream effector, TGase-catalyzed serotonylation of the small G protein Rac1 in A1A1v cells, a rat embryonic cortical cell line. We now extend these findings to rat primary cortical cultures which develop dendritic spines; stimulation of 5-HT2A/2C receptors increased transamidation of Rac1 and Cdc42, but not RhoA. Inhibition of TGases significantly decreased transamidation and activation of Rac1 and Cdc42, suggesting that transamidation led to their activation. In primary cortical cultures, stimulation of 5-HT2A/2C receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) caused a transient dendritic spine enlargement, which was blocked by TGase inhibition. Stimulation of both 5-HT2A and 5-HT2C receptors contributed to DOI-induced Rac1 transamidation in primary cortical cultures as demonstrated by selective antagonists. Furthermore, stimulation of muscarinic acetylcholine receptors and NMDA receptors also increased TGase-catalyzed Rac1 activation in SH-SY5Y cells and N2a cells, respectively. Receptor-stimulated TGase-catalyzed transamidation of Rac1 occurs at Q61, a site previously reported to be important in the inactivation of Rac1. These studies demonstrate that TGase-catalyzed transamidation and activation of small G proteins results from stimulation of multiple types of receptors and this novel signaling pathway can regulate dendritic spine morphology and plasticity.
[Mh] Termos MeSH primário: Espinhas Dendríticas/fisiologia
Receptor 5-HT2A de Serotonina/fisiologia
Transglutaminases/fisiologia
Proteína cdc42 de Ligação ao GTP/metabolismo
Proteínas rac1 de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Anfetaminas/farmacologia
Animais
Seres Humanos
Camundongos
Cultura Primária de Células
Agonistas de Receptores 5-HT2 de Serotonina/farmacologia
Transglutaminases/metabolismo
Proteína rhoA de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Receptor, Serotonin, 5-HT2A); 0 (Serotonin 5-HT2 Receptor Agonists); EC 2.3.2.13 (Transglutaminases); EC 3.6.5.2 (cdc42 GTP-Binding Protein); EC 3.6.5.2 (rac1 GTP-Binding Protein); EC 3.6.5.2 (rhoA GTP-Binding Protein); OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170206
[St] Status:MEDLINE


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[PMID]:28104804
[Au] Autor:Kern C; Erdem FA; El-Kasaby A; Sandtner W; Freissmuth M; Sucic S
[Ad] Endereço:From the Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria.
[Ti] Título:The N Terminus Specifies the Switch between Transport Modes of the Human Serotonin Transporter.
[So] Source:J Biol Chem;292(9):3603-3613, 2017 Mar 03.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The serotonin transporter (SERT) and other monoamine transporters operate in either a forward transport mode where the transporter undergoes a full transport cycle or an exchange mode where the transporter seesaws through half-cycles. Amphetamines trigger the exchange mode, leading to substrate efflux. This efflux was proposed to rely on the N terminus, which was suggested to adopt different conformations in the inward facing, outward facing and amphetamine-bound states. This prediction was verified by tryptic digestion of SERT-expressing membranes: in the absence of Na , the N terminus was rapidly digested. Amphetamine conferred protection against cleavage, suggesting a relay between the conformational states of the hydrophobic core and the N terminus. We searched for a candidate segment that supported the conformational switch by serial truncation removing 22 (ΔN22), 32 (ΔN32), or 42 (ΔN42) N-terminal residues. This did not affect surface expression, inhibitor binding, and substrate influx. However, amphetamine-induced efflux by SERT-ΔN32 or SERT-ΔN42 (but not by SERT-ΔN22) was markedly diminished. We examined the individual steps in the transport cycle by recording transporter-associated currents: the recovery rate of capacitive peak, but not of steady state, currents was significantly lower for SERT-ΔN32 than that of wild type SERT and SERT-ΔN22. Thus, the exchange mode of SERT-ΔN32 was selectively impaired. Our observations show that the N terminus affords the switch between transport modes. The findings are consistent with a model where the N terminus acts as a lever to support amphetamine-induced efflux by SERT.
[Mh] Termos MeSH primário: Anfetaminas/química
Proteínas da Membrana Plasmática de Transporte de Serotonina/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Biotinilação
Células HEK293
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Concentração Inibidora 50
Proteínas Luminescentes/química
Microscopia Confocal
Neurotransmissores/química
Técnicas de Patch-Clamp
Conformação Proteica
Domínios Proteicos
Serotonina/química
Sódio/química
Tripsina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Bacterial Proteins); 0 (Luminescent Proteins); 0 (Neurotransmitter Agents); 0 (Serotonin Plasma Membrane Transport Proteins); 0 (yellow fluorescent protein, Bacteria); 333DO1RDJY (Serotonin); 9NEZ333N27 (Sodium); EC 3.4.21.4 (Trypsin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.771360


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[PMID]:28098590
[Au] Autor:Kram B; Kram SJ; Sharpe ML; James ML; Kuchibhatla M; Shapiro ML
[Ad] Endereço:Departments of *Pharmacy, †Anesthesiology, ‡Biostatistics and Bioinfor matics, and §Surgery, Duke University Hospital, Durham, North Carolina.
[Ti] Título:Analgesia and Sedation Requirements in Mechanically Ventilated Trauma Patients With Acute, Preinjury Use of Cocaine and/or Amphetamines.
[So] Source:Anesth Analg;124(3):782-788, 2017 Mar.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The purpose of this study was to determine whether mechanically ventilated trauma patients with a positive urine drug screen (UDS) for cocaine and/or amphetamines have different opioid analgesic and sedative requirements compared with similar patients with a negative drug screen for these stimulants. METHODS: This retrospective, single-center cohort study at a tertiary care, academic medical and level 1 trauma center in the United States included patients ≥16 years of age who were admitted to an adult intensive care unit with a diagnosis of trauma between 2009 and 2013 with a UDS documented within 24 hours of admission, and were mechanically ventilated for >24 hours. The primary end point was the daily dose of opioid received during mechanical ventilation, expressed as morphine equivalents, for patients presenting with a positive UDS for cocaine and/or amphetamines compared with patients with a negative UDS for these stimulants. Secondary end points included the daily benzodiazepine dose and median infusion rates of propofol and dexmedetomidine received during mechanical ventilation, duration of mechanical ventilation, intensive care unit and hospital length of stay, and in-hospital mortality. Analgesic and sedative goals were similar for the duration of the study period, and both intermittent and continuous infusions of opioids and sedatives were administered to achieve these targets, although a standardized approach was not used. A multivariate logistic regression analysis and a propensity-adjusted model evaluated patient characteristics predictive of a higher median opioid requirement. RESULTS: A total of 150 patients were included in the final analysis. In a univariate analysis, opioid and sedative requirements were similar for patients presenting with a positive UDS for cocaine and/or amphetamines compared with patients with a negative UDS for these stimulants. In the multivariate regression analysis, increasing age and Abbreviated Injury Scale (head and neck) were associated with decreased daily opioid requirements (odds ratio [OR], .95, 95% confidence interval [CI], .93-.97 and OR, .71, 95% CI, .65-.77, respectively), whereas preinjury stimulant use was not predictive of opioid requirements (OR, .88, 95% CI, .40-1.90). In a propensity score--adjusted model, preinjury stimulant use was similarly not predictive of opioid requirements during mechanical ventilation (OR, .97, 95% CI, .44-2.11). CONCLUSIONS: For trauma patients presenting with acute, preinjury use of cocaine and/or amphetamines, analgesic and sedative requirements are variables and may not be greater than those patients presenting with a stimulant-negative UDS to achieve desirable pain control and depth of sedation, although this observation should be interpreted cautiously in light of the wide CI observed in the propensity score--adjusted model. Although unexpected, these findings indicate that empirically increasing analgesic and sedative doses based on positive UDS results for these stimulants may not be necessary.
[Mh] Termos MeSH primário: Anfetaminas/administração & dosagem
Analgesia/métodos
Cocaína/administração & dosagem
Hipnóticos e Sedativos/administração & dosagem
Respiração Artificial
Ferimentos e Lesões/tratamento farmacológico
[Mh] Termos MeSH secundário: Anfetaminas/efeitos adversos
Analgesia/tendências
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Unidades de Terapia Intensiva/tendências
Tempo de Internação/tendências
Masculino
Respiração Artificial/efeitos adversos
Respiração Artificial/tendências
Estudos Retrospectivos
Centros de Traumatologia/tendências
Ferimentos e Lesões/diagnóstico
Ferimentos e Lesões/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amphetamines); 0 (Hypnotics and Sedatives); I5Y540LHVR (Cocaine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE
[do] DOI:10.1213/ANE.0000000000001740



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