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[PMID]:29303006
[Au] Autor:Papaseit E; Torrens M; Pérez-Mañá C; Muga R; Farré M
[Ad] Endereço:a Departments of Clinical Pharmacology and Internal Medicine , Hospital Universitari Germans Trias I Pujol-IGTP , Badalona , Spain.
[Ti] Título:Key interindividual determinants in MDMA pharmacodynamics.
[So] Source:Expert Opin Drug Metab Toxicol;14(2):183-195, 2018 Feb.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: MDMA, 3,4-methylenedioxymethamphetamine, is a synthetic phenethylamine derivative with structural and pharmacological similarities to both amphetamines and mescaline. MDMA produces characteristic amphetamine-like actions (euphoria, well-being), increases empathy, and induces pro-social effects that seem to motivate its recreational consumption and provide a basis for its potential therapeutic use. Areas covered: The aim of this review is to present the main interindividual determinants in MDMA pharmacodynamics. The principal sources of pharmacodynamic variability are reviewed, with special emphasis on sex-gender, race-ethnicity, genetic differences, interactions, and MDMA acute toxicity, as well as possible therapeutic use. Expert opinion: Acute MDMA effects are more pronounced in women than they are in men. Very limited data on the relationship between race-ethnicity and MDMA effects are available. MDMA metabolism includes some polymorphic enzymes that can slightly modify plasma concentrations and effects. Although a considerable number of studies exist about the acute effects of MDMA, the small number of subjects in each trial limits evaluation of the different interindividual factors and does not permit a clear conclusion about their influence. These issues should be considered when studying possible MDMA therapeutic use.
[Mh] Termos MeSH primário: Alucinógenos/administração & dosagem
N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem
Serotoninérgicos/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Grupos de Populações Continentais
Interações Medicamentosas
Grupos Étnicos
Feminino
Alucinógenos/efeitos adversos
Alucinógenos/farmacologia
Seres Humanos
Masculino
N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos
N-Metil-3,4-Metilenodioxianfetamina/farmacologia
Serotoninérgicos/efeitos adversos
Serotoninérgicos/farmacologia
Fatores Sexuais
Transtornos Relacionados ao Uso de Substâncias/psicologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Hallucinogens); 0 (Serotonin Agents); KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1424832


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[PMID]:27773601
[Au] Autor:Huff CL; Morano RL; Herman JP; Yamamoto BK; Gudelsky GA
[Ad] Endereço:Division of Pharmaceutical Sciences, University of Cincinnati-James Winkle College of Pharmacy, Cincinnati, OH 45267, United States.
[Ti] Título:MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.
[So] Source:Neurotoxicology;57:282-290, 2016 12.
[Is] ISSN:1872-9711
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Glutamato Descarboxilase/metabolismo
Alucinógenos/farmacologia
Hipocampo/citologia
N-Metil-3,4-Metilenodioxianfetamina/farmacologia
Neurônios/efeitos dos fármacos
Neurônios/enzimologia
[Mh] Termos MeSH secundário: Animais
Temperatura Corporal/efeitos dos fármacos
Modelos Animais de Doenças
Maleato de Dizocilpina/uso terapêutico
Agonistas de Aminoácidos Excitatórios/toxicidade
Ácido Glutâmico/metabolismo
Ácido Caínico/toxicidade
Masculino
Microdiálise
Ratos
Ratos Sprague-Dawley
Convulsões/induzido quimicamente
Convulsões/tratamento farmacológico
Convulsões/metabolismo
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Excitatory Amino Acid Agonists); 0 (Hallucinogens); 3KX376GY7L (Glutamic Acid); 6LR8C1B66Q (Dizocilpine Maleate); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1); KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine); SIV03811UC (Kainic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE


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[PMID]:28457570
[Au] Autor:Ponté C; Lapeyre-Mestre M
[Ad] Endereço:Service de pharmacologie médicale et clinique, Centre d'évaluation et d'information sur la pharmacodépendance-addictovigilance, faculté de médecine, CHU de Toulouse, 37, allées Jules-Guesde, 31000 Toulouse, France. Electronic address: ponte.c@chu-toulouse.fr.
[Ti] Título:[Psychoactive effects of 'legal high': About lysergic acid amide (LSA)].
[Ti] Título:Effets psychoactifs des « legal high ¼ : à propos de l'acide lysergique amide (LSA)..
[So] Source:Therapie;72(5):605-608, 2017 Oct.
[Is] ISSN:0040-5957
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:Lysergic acid amide (LSA) is a natural psychoactive substance consumed as a psychedelic drug. In 2016, 4 cases were reported to the Toulouse Addictovigilance Centre, resulting in unintended psychic effects and led to a hospitalisation in 2 cases. Other cases of serious LSA intoxication are published, including a death. It is important to inform about the risks related to LSA consumption, a substance which is freely available and sometimes hidden behind various plant names.
[Mh] Termos MeSH primário: Alucinógenos/efeitos adversos
Dietilamida do Ácido Lisérgico/análogos & derivados
Transtornos Relacionados ao Uso de Substâncias/complicações
[Mh] Termos MeSH secundário: Adulto
Feminino
França
Seres Humanos
Dietilamida do Ácido Lisérgico/efeitos adversos
Masculino
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hallucinogens); 073830XH10 (lysergamide); 8NA5SWF92O (Lysergic Acid Diethylamide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28459969
[Au] Autor:Logan BK; Mohr ALA; Friscia M; Krotulski AJ; Papsun DM; Kacinko SL; Ropero-Miller JD; Huestis MA
[Ad] Endereço:Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, PA 19090, USA.
[Ti] Título:Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2013-2016: A Review.
[So] Source:J Anal Toxicol;41(7):573-610, 2017 Sep 01.
[Is] ISSN:1945-2403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Novel psychoactive substances (NPS) represent significant analytical and interpretive challenges to forensic and clinical toxicologists. Timely access to case reports and reports of adverse incidents of impairment or toxicity is imperative to clinical diagnosis and treatment, as well as to interpretation of forensic results. Delays in identifying the presence of a novel intoxicating agent have significant consequences for public health and public safety. Adverse effects of intoxications with novel cannabinoids, stimulants, hallucinogens, benzodiazepines and opioids spanning January 2013 through December 2016 as reported in emergency departments, death investigations, impaired driving cases and other forensic contexts are the subject of this review. Discussion of the chemistry, pharmacology and adverse events associated with novel drug classes is summarized and described within. Adverse effects or symptoms associated with ingestion of more than 45 NPS have been abstracted and summarized in tables, including demographics, case history, clinical or behavioral symptoms, autopsy findings and drug confirmations with quantitative results when provided. Based on these findings and gaps in the available data, we provide recommendations for future toxicological testing of these evolving substances. These include development and management of a national monitoring program to provide real-time clinical and toxicological data, confirmed analytically, on emerging drugs and their known toxidromes and side effect profiles. Increased efforts should be made to analytically confirm the agents responsible for clinical intoxications involving adverse events in emergency department admissions or hospitalizations. Evidence-based community preparedness among analytical laboratories gained through active communication and sharing of toxicological findings and trends in NPS is imperative to assist in enabling early detection of new drugs in forensic and clinical populations.
[Mh] Termos MeSH primário: Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
Psicotrópicos/efeitos adversos
[Mh] Termos MeSH secundário: Analgésicos Opioides
Benzodiazepinas
Canabinoides
Estimulantes do Sistema Nervoso Central
Alucinógenos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Cannabinoids); 0 (Central Nervous System Stimulants); 0 (Hallucinogens); 0 (Psychotropic Drugs); 12794-10-4 (Benzodiazepines)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/jat/bkx031


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[PMID]:28678861
[Au] Autor:de Bragança AC; Moreau RLM; de Brito T; Shimizu MHM; Canale D; de Jesus DA; Silva AMG; Gois PH; Seguro AC; Magaldi AJ
[Ad] Endereço:Clinical Hospital, School of Medicine-Department of Nephrology- Basic Research Laboratory-LIM12, University of Sâo Paulo, SP, Brazil.
[Ti] Título:Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage.
[So] Source:PLoS One;12(7):e0179199, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used. METHODS: Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.). RESULTS: Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo. CONCLUSION: Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia.
[Mh] Termos MeSH primário: Depuradores de Radicais Livres/farmacologia
Rim/efeitos dos fármacos
Fibras Musculares Esqueléticas/efeitos dos fármacos
N-Metil-3,4-Metilenodioxianfetamina/toxicidade
Estresse Oxidativo/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Rabdomiólise/induzido quimicamente
[Mh] Termos MeSH secundário: Acetilcisteína/farmacologia
Alopurinol/farmacologia
Animais
Aquaporina 2/metabolismo
Western Blotting
Canais Epiteliais de Sódio/metabolismo
Glutationa/metabolismo
Alucinógenos/toxicidade
Rim/metabolismo
Túbulos Renais Coletores/efeitos dos fármacos
Túbulos Renais Coletores/metabolismo
Masculino
Fibras Musculares Esqueléticas/metabolismo
Fibras Musculares Esqueléticas/patologia
Ratos Wistar
Rabdomiólise/prevenção & controle
Membro 1 da Família 12 de Carreador de Soluto/metabolismo
Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
Água/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aquaporin 2); 0 (Epithelial Sodium Channels); 0 (Free Radical Scavengers); 0 (Hallucinogens); 0 (Reactive Oxygen Species); 0 (Solute Carrier Family 12, Member 1); 0 (Thiobarbituric Acid Reactive Substances); 059QF0KO0R (Water); 63CZ7GJN5I (Allopurinol); GAN16C9B8O (Glutathione); KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine); WYQ7N0BPYC (Acetylcysteine)
[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:170706
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179199


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[PMID]:28548221
[Au] Autor:Sellers EM
[Ad] Endereço:Departments of Pharmacology and Toxicology, Medicine and Psychiatry, University of Toronto, Ontario, Canada.
[Ti] Título:Psilocybin: Good Trip or Bad Trip.
[So] Source:Clin Pharmacol Ther;102(4):580-584, 2017 Oct.
[Is] ISSN:1532-6535
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Much of the history of pharmacology and therapeutics involves finding new uses for old drugs. The latest rediscovery is that of psychedelic drugs. Since they can cause profound distortions of perception and were once used as part of religious ceremonies, such research may seem unusual at this time.
[Mh] Termos MeSH primário: Reposicionamento de Medicamentos
Alucinógenos/administração & dosagem
Psilocibina/administração & dosagem
[Mh] Termos MeSH secundário: Alucinógenos/efeitos adversos
Alucinógenos/farmacologia
Seres Humanos
Psilocibina/efeitos adversos
Psilocibina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hallucinogens); 2RV7212BP0 (Psilocybin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1002/cpt.697


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[PMID]:28342897
[Au] Autor:Paasonen J; Salo RA; Ihalainen J; Leikas JV; Savolainen K; Lehtonen M; Forsberg MM; Gröhn O
[Ad] Endereço:A.I.V. Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
[Ti] Título:Dose-response effect of acute phencyclidine on functional connectivity and dopamine levels, and their association with schizophrenia-like symptom classes in rat.
[So] Source:Neuropharmacology;119:15-25, 2017 Jun.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Current drug treatments for schizophrenia (SCZ) can alleviate positive symptoms, but have little effect on the negative symptoms and cognitive deficits that are difficult to translate into preclinical models for drug development. Therefore, we aimed to determine the dose-response effects of acute phencyclidine (PCP, 1.0-5.0 mg/kg) on rat brain connectivity and detect markers for different SCZ-like symptoms. Pharmacological functional magnetic resonance imaging (phMRI) and microdialysis were used to investigate PCP-induced effects on functional connectivity (FC) and dopamine levels, respectively. Next, we evaluated the association between PCP-induced changes in imaging parameters and behavior. PCP at doses of 3.0-5.0 mg/kg induced fMRI signal changes in several brain regions associated with SCZ. Additionally, the FC was globally disturbed, dopamine levels increased, and locomotor activity increased, reflecting the manifestation of SCZ-like positive symptoms. A distinct pattern in the measures was observed at lower PCP doses (1.0-2.0 mg/kg); PCP induced fMRI signal changes in the fronto-cortical regions, and increased dopamine levels in the medial prefrontal cortex. In addition to the dysconnectivity of these regions, the hippocampal FC was disrupted. These observations are consistent with the induction of SCZ-like cognitive deficits and negative symptoms, which were observed as impaired novel object recognition and decreased social interaction. No indicators for positive symptoms were observed at lower PCP doses. We conclude that acute PCP induces SCZ-like symptom classes in a dose-dependent manner; PCP doses of 1.0-2.0 mg/kg are more suitable for modeling SCZ-like negative symptoms and cognitive deficits, while SCZ-like positive symptoms dominate at doses of 3.0-5.0 mg/kg.
[Mh] Termos MeSH primário: Encéfalo
Dopamina/metabolismo
Alucinógenos/toxicidade
Fenciclidina/toxicidade
Esquizofrenia/induzido quimicamente
Esquizofrenia/patologia
[Mh] Termos MeSH secundário: Animais
Encéfalo/diagnóstico por imagem
Encéfalo/metabolismo
Encéfalo/patologia
Mapeamento Encefálico
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Processamento de Imagem Assistida por Computador
Relações Interpessoais
Locomoção/efeitos dos fármacos
Imagem por Ressonância Magnética
Masculino
Microdiálise
Oxigênio/sangue
Ratos
Ratos Wistar
Recognição (Psicologia)/efeitos dos fármacos
Esquizofrenia/diagnóstico por imagem
Psicologia do Esquizofrênico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hallucinogens); J1DOI7UV76 (Phencyclidine); S88TT14065 (Oxygen); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170327
[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]:28322979
[Au] Autor:Pérez-Hernández M; Fernández-Valle ME; Rubio-Araiz A; Vidal R; Gutiérrez-López MD; O'Shea E; Colado MI
[Ad] Endereço:Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre, 28041 Madrid, Spain; Red de Trastornos Adictivos del Instituto de Salud Carlos III, 28029 Madrid, Spain.
[Ti] Título:3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.
[So] Source:Neuropharmacology;118:157-166, 2017 May 15.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/fisiopatologia
Edema Encefálico/induzido quimicamente
Regulação da Expressão Gênica/efeitos dos fármacos
Alucinógenos/toxicidade
Metaloproteinase 9 da Matriz/metabolismo
N-Metil-3,4-Metilenodioxianfetamina/toxicidade
[Mh] Termos MeSH secundário: Animais
Aquaporina 4/metabolismo
Barreira Hematoencefálica/diagnóstico por imagem
Barreira Hematoencefálica/efeitos dos fármacos
Edema Encefálico/diagnóstico por imagem
Edema Encefálico/patologia
Claudina-5/metabolismo
Modelos Animais de Doenças
Inibidores Enzimáticos/farmacologia
Proteína Glial Fibrilar Ácida/metabolismo
Compostos Heterocíclicos com 1 Anel/farmacologia
Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo
Imagem por Ressonância Magnética
Masculino
Permeabilidade/efeitos dos fármacos
Plasminogênio/metabolismo
Ratos
Sulfonas/farmacologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aqp4 protein, rat); 0 (Aquaporin 4); 0 (Claudin-5); 0 (Enzyme Inhibitors); 0 (Glial Fibrillary Acidic Protein); 0 (Hallucinogens); 0 (Heterocyclic Compounds, 1-Ring); 0 (Low Density Lipoprotein Receptor-Related Protein-1); 0 (SB 3CT compound); 0 (Sulfones); 9001-91-6 (Plasminogen); EC 3.4.24.35 (Matrix Metalloproteinase 9); KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE


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[PMID]:28249943
[Au] Autor:Nour MM; Carhart-Harris RL
[Ad] Endereço:Matthew M. Nour, BA, BM BCh, Institute of Psychiatry Psychology & Neuroscience, King's College London, London and South London and Maudsley NHS Foundation Trust, London; Robin L. Carhart-Harris, BSc, MA, PhD, Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK matthew.nour@kcl.ac.uk.
[Ti] Título:Psychedelics and the science of self-experience.
[So] Source:Br J Psychiatry;210(3):177-179, 2017 Mar.
[Is] ISSN:1472-1465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Altered self-experiences arise in certain psychiatric conditions, and may be induced by psychoactive drugs and spiritual/religious practices. Recently, a neuroscience of self-experience has begun to crystallise, drawing upon findings from functional neuroimaging and altered states of consciousness occasioned by psychedelic drugs. This advance may be of great importance for psychiatry.
[Mh] Termos MeSH primário: Estado de Consciência/efeitos dos fármacos
Alucinógenos/farmacologia
[Mh] Termos MeSH secundário: Seres Humanos
Neurociências/métodos
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Hallucinogens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170303
[St] Status:MEDLINE
[do] DOI:10.1192/bjp.bp.116.194738



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