Base de dados : MEDLINE
Pesquisa : G02.111.150 [Categoria DeCS]
Referências encontradas : 47878 [refinar]
Mostrando: 1 .. 10   no formato [Longo]

página 1 de 4788 ir para página                         

  1 / 47878 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29396367
Autor:Police A; Shankar VK; Narasimha Murthy S
Endereço:Department of Pharmaceutics and Drug Delivery, University of Mississippi, MS 38677, USA.
Título:RP-HPLC method for simultaneous estimation of vigabatrin, gamma-aminobutyric acid and taurine in biological samples.
Fonte:J Chromatogr B Analyt Technol Biomed Life Sci; 1076:44-53, 2018 Feb 15.
ISSN:1873-376X
País de publicação:Netherlands
Idioma:eng
Resumo:Vigabatrin is used as first line drug in treatment of infantile spasms for its potential benefit overweighing risk of causing permanent peripheral visual field defects and retinal damage. Chronic administration of vigabatrin in rats has demonstrated these ocular events are result of GABA accumulation and depletion of taurine levels in retinal tissues. In vigabatrin clinical studies taurine plasma level is considered as biomarker for studying structure and function of retina. The analytical method is essential to monitor taurine levels along with vigabatrin and GABA. A RP-HPLC method has been developed and validated for simultaneous estimation of vigabatrin, GABA and taurine using surrogate matrix. Analytes were extracted from human plasma, rat plasma, retina and brain by simple protein precipitation method and derivatized by naphthalene 2, 3­dicarboxaldehyde to produce stable fluorescent active isoindole derivatives. The chromatographic analysis was performed on Zorbax Eclipse AAA column using gradient elution profile and eluent was monitored using fluorescence detector. A linear plot of calibration curve was observed in concentration range of 64.6 to 6458, 51.5 to 5150 and 62.5 to 6258 ng/mL for vigabatrin, GABA and taurine, respectively with r ≥ 0.997 for all analytes. The method was successfully applied for estimating levels of vigabatrin and its modulator effect on GABA and taurine levels in rat plasma, brain and retinal tissue. This RP-HPLC method can be applied in clinical and preclinical studies to explore the effect of taurine deficiency and to investigate novel approaches for alleviating vigabatrin induced ocular toxicity.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:1EQV5MLY3D (Taurine); 56-12-2 (gamma-Aminobutyric Acid); GR120KRT6K (Vigabatrin)


  2 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29329091
Autor:Jiang J; Zhang Z; Zou X; Wang R; Bai J; Zhao S; Fan X; Sheng L; Li Y
Endereço:Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Me
Título:Determination of IMM-H004 and its active glucuronide metabolite in rat plasma and Ringer's solution by ultra-performance liquid chromatography-tandem mass spectrometry.
Fonte:J Chromatogr B Analyt Technol Biomed Life Sci; 1074-1075:16-24, 2018 Feb 01.
ISSN:1873-376X
País de publicação:Netherlands
Idioma:eng
Resumo:IMM-H004 is a novel neuroprotective agent and its glucuronide metabolite IMM-H004G has similar protective effects against cerebral ischemic injury in vivo and in vitro. A specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for determination of IMM-H004 and IMM-H004G simultaneously in rat plasma and Ringer's solution. Plasma samples containing IMM-H004, IMM-H004G and internal standard propranolol were prepared by direct protein precipitation in a sample-to-solvent ratio of 1:2:6 (plasma: water: acetonitrile), whereas no protein precipitation was required for Ringer's solution samples. Separation was performed with a gradient mobile phase of methanol/water with 0.5% formic acid (v/v) on Eclipse Plus C18 column (2.1×50mm, 3.5µm) at a flow rate of 0.3mL/min. The detection was operated on a triple quadrupole mass spectrometer in positive ion multiple reaction monitoring (MRM) mode. The monitored transitions were 305.1→248.1 for IMM-H004, 481.3→305.1 for IMM-H004G and 260.1→183.1 for propranolol. The linear ranges of IMM-H004 and IMM-H004G were 5 to 3000ng/mL and 10 to 3000ng/mL for plasma method and 0.5 to 500ng/mL for Ringer's solution method. All the intra-day and inter-day precision and accuracy for the two analytes in rat plasma were below 7.5% and the intra-day precision and accuracy for analytes in Ringer's solution were within ±14.7%. There was no obvious matrix effect and the recoveries of the analytes were higher than 94.2%. IMM-H004 and IMM-H004G were stable during one analytic process. The established method was applied successfully to plasma pharmacokinetic and brain microdialysis studies of IMM-H004 and IMM-H004G in rats after a single intravenous administration of IMM-H004.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Coumarins); 0 (Glucuronides); 0 (IMM-H004); 0 (Isotonic Solutions); 8026-10-6 (Ringer's solution)


  3 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29275172
Autor:Forgacsova A; Galba J; Garruto RM; Majerova P; Katina S; Kovac A
Endereço:Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy of Comenius University, Odbojarov 10, 832 32, Bratislava, Slovak Republic. Electronic address: andrej.kovac@savba.sk.
Título:A novel liquid chromatography/mass spectrometry method for determination of neurotransmitters in brain tissue: Application to human tauopathies.
Fonte:J Chromatogr B Analyt Technol Biomed Life Sci; 1073:154-162, 2018 Jan 15.
ISSN:1873-376X
País de publicação:Netherlands
Idioma:eng
Resumo:Neurotransmitters, small molecules widely distributed in the central nervous system are essential in transmitting electrical signals across neurons via chemical communication. Dysregulation of these chemical signaling molecules is linked to numerous neurological diseases including tauopathies. In this study, a precise and reliable liquid chromatography method was established with tandem mass spectrometry detection for the simultaneous determination of aspartic acid, asparagine, glutamic acid, glutamine, γ-aminobutyric acid, N-acetyl-l-aspartic acid, pyroglutamic acid, acetylcholine and choline in human brain tissue. The method was successfully applied to the analysis of human brain tissues from three different tauopathies; corticobasal degeneration, progressive supranuclear palsy and parkinsonism-dementia complex of Guam. Neurotransmitters were analyzed on ultra-high performance chromatography (UHPLC) using an ethylene bridged hybrid amide column coupled with tandem mass spectrometry (MS/MS). Identification and quantification of neurotransmitters was carried out by ESI+ mass spectrometry detection. We optimized sample preparation to achieve simple and fast extraction of all nine analytes. Our method exhibited an excellent linearity for all analytes (all coefficients of determination >0.99), with inter-day and intra-day precision yielding relative standard deviations 3.2%-11.2% and an accuracy was in range of 92.6%-104.3%. The present study, using the above method, is the first to demonstrate significant alterations of brain neurotransmitters caused by pathological processes in the brain tissues of patient with three different tauopathies.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Neurotransmitter Agents)


  4 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29232607
Autor:Chowdhury EA; Alqahtani F; Bhattacharya R; Mehvar R; Bickel U
Endereço:Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA; Center for Blood-Brain Barrier Research, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
Título:Simultaneous UPLC-MS/MS analysis of two stable isotope labeled versions of sucrose in mouse plasma and brain samples as markers of blood-brain barrier permeability and brain vascular space.
Fonte:J Chromatogr B Analyt Technol Biomed Life Sci; 1073:19-26, 2018 Jan 15.
ISSN:1873-376X
País de publicação:Netherlands
Idioma:eng
Resumo:Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with slow permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labeled [ C ]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling. The purpose of the present study was to develop a UPLC-MS/MS method, which allows simultaneous analysis of two different stable isotope labeled sucrose variants, one of which can be utilized as a vascular marker. The first analyte, [ C ]sucrose, serves to quantify brain uptake clearance as a measure of BBB permeability, while the second analyte, [ C ]sucrose, is administered just before termination of the animal experiment and is considered as the vascular marker. [ H ]sucrose is used as the internal standard for both C labeled compounds. Because the majority of recent studies on CNS diseases employ mice, another objective was to validate the new technique in this species. The UPLC-MS/MS method was linear (r ≥ 0.99) in the tested concentration ranges, from 10 to 1000 ng/mL for both analytes in plasma, from 2 to 400 ng/g [ C ]sucrose in brain and from 10 to 400 ng/g [ C ]sucrose in brain. It was also validated in terms of acceptable intra and inter run accuracy and precision values (n = 5). The dual analyte technique was applied in a study in mice. One group received intravenous bolus injections of 10 mg/kg [ C ]sucrose at time 0, and 10 mg/kg [ C ]sucrose at 14.5 min, and subsequent terminal blood and brain sampling was performed at 15 min. For comparison, another group received an intravenous bolus dose of 10 mg/kg [ C ]sucrose and was submitted to transcardiac perfusion with buffer after 15 min. We demonstrate that the two alternative techniques to correct for intravascular content deliver equivalent values for brain concentration and brain uptake clearance.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Biomarkers); 0 (Carbon Isotopes); 57-50-1 (Sucrose)


  5 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28460583
Autor:Nielsen BS; Larsen EH; Ladefoged O; Lam HR
Endereço:1 Environment and Toxicology, DHI, Hørsholm, Denmark.
Título:Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry.
Fonte:Int J Toxicol; 36(3):239-251, 2017 May/Jun.
ISSN:1092-874X
País de publicação:United States
Idioma:eng
Resumo:Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO )/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl )/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl . Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Chlorides); 0 (Manganese Compounds); 0 (Oxides); 1EQV5MLY3D (Taurine); 333DO1RDJY (Serotonin); 3KX376GY7L (Glutamic Acid); 42Z2K6ZL8P (Manganese); 56-12-2 (gamma-Aminobutyric Acid); 64J2OA7MH3 (manganese oxide); EC 3.1.1.7 (Acetylcholinesterase); QQE170PANO (manganese chloride); VTD58H1Z2X (Dopamine); X4W3ENH1CV (Norepinephrine)


  6 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29236709
Autor:Barrett SP; Parker KR; Horn C; Mata M; Salzman J
Endereço:Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States of America.
Título:ciRS-7 exonic sequence is embedded in a long non-coding RNA locus.
Fonte:PLoS Genet; 13(12):e1007114, 2017 12.
ISSN:1553-7404
País de publicação:United States
Idioma:eng
Resumo:ciRS-7 is an intensely studied, highly expressed and conserved circRNA. Essentially nothing is known about its biogenesis, including the location of its promoter. A prevailing assumption has been that ciRS-7 is an exceptional circRNA because it is transcribed from a locus lacking any mature linear RNA transcripts of the same sense. To study the biogenesis of ciRS-7, we developed an algorithm to define its promoter and predicted that the human ciRS-7 promoter coincides with that of the long non-coding RNA, LINC00632. We validated this prediction using multiple orthogonal experimental assays. We also used computational approaches and experimental validation to establish that ciRS-7 exonic sequence is embedded in linear transcripts that are flanked by cryptic exons in both human and mouse. Together, this experimental and computational evidence generates a new model for regulation of this locus: (a) ciRS-7 is like other circRNAs, as it is spliced into linear transcripts; (b) expression of ciRS-7 is primarily determined by the chromatin state of LINC00632 promoters; (c) transcription and splicing factors sufficient for ciRS-7 biogenesis are expressed in cells that lack detectable ciRS-7 expression. These findings have significant implications for the study of the regulation and function of ciRS-7, and the analytic framework we developed to jointly analyze RNA-seq and ChIP-seq data reveal the potential for genome-wide discovery of important biological regulation missed in current reference annotations.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de substância:0 (RNA, Long Noncoding); 0 (RNA, circular); 63231-63-0 (RNA)


  7 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29339101
Autor:Binesh A; Devaraj SN; Halagowder D
Endereço:Unit of Biochemistry, Department of Zoology, University of Madras, Guindy Campus, Chennai - 600025, TamilNadu, India.
Título:Atherogenic diet induced lipid accumulation induced NFκB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent.
Fonte:Life Sci; 196:28-37, 2018 Mar 01.
ISSN:1879-0631
País de publicação:Netherlands
Idioma:eng
Resumo:Atherogenic Diet (AD) was given to rats to understand the key role of inflammatory mediators in atherosclerotic lesion formation, as a serendipitous study, the diet induced inflammatory mediators in liver and brain, whereas pancreas, kidney and spleen were not affected. The efficacy of diosgenin in ameliorating atherosclerotic progression in heart and suppression of inflammatory mediators in liver and brain of Wistar rat fed on AD diet was investigated. Atherogenic diet triggered inflammatory mediators in heart, liver and brain by upregulating TNF-α, COX-2 and NFkBp65 which are the inflammatory hub, played a key role in pathophysiologic conditions. Endothelial dysfunction, liver tissue with prominent steatosis and the stress evoked in the brain by the atherogenic diet triggered these inflammatory mediators. TNF-α and COX-2 expression was upregulated and its elevation was associated with NFkBp65 activation in heart, liver and brain of atherogenic diet induced rat. Diosgenin downregulated these inflammatory mediators, thereby prevented the atherosclerotic disease progression and concomitant suppression of inflammatory mediators in liver and brain.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Inflammation Mediators); 0 (NF-kappa B); 0 (Transcription Factor RelA); 0 (Tumor Necrosis Factor-alpha); EC 1.14.99.1 (Cyclooxygenase 2); K49P2K8WLX (Diosgenin)


  8 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28453930
Autor:R Cardoso B; Hare DJ; Lind M; McLean CA; Volitakis I; Laws SM; Masters CL; Bush AI; Roberts BR
Endereço:The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
Título:The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease.
Fonte:ACS Chem Neurosci; 8(7):1459-1464, 2017 07 19.
ISSN:1948-7193
País de publicação:United States
Idioma:eng
Resumo:The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer's disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimer's disease and control brain tissue. We found that Alzheimer's disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE ε4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer's disease brain.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Apolipoprotein E4); H6241UJ22B (Selenium)


  9 / 47878 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:27771350
Autor:Tratnjek L; Zivin M; Glavan G
Endereço:University of Ljubljana, Medical Faculty, Institute of Pathophysiology, Brain Research Laboratory, Zaloska 4, 1000, Ljubljana, Slovenia. Electronic address: larisa.tratnjek@mf.uni-lj.si.
Título:Synaptotagmin 7 and SYNCRIP proteins are ubiquitously expressed in the rat brain and co-localize in Purkinje neurons.
Fonte:J Chem Neuroanat; 79:12-21, 2017 Jan.
ISSN:1873-6300
País de publicação:Netherlands
Idioma:eng
Resumo:Synaptotagmin 7 (SYT7) is ubiquitously expressed calcium sensor, involved in neuronal membrane trafficking. Immunoprecipitation experiments demonstrated that SYT7 interacts with Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP). SYNCRIP is a component of mRNA granules, which are transported to dendrites and are prerequisite for synaptic plasticity. Given the potential significance of SYT7 regulation in processes of neurodegeneration, which are characterized by high level of synaptic vulnerability, we aimed to analyse and compare the distribution of SYT7 and SYNCRIP proteins in the adult rat striatum, hippocampus, cerebral and cerebellar cortex. We investigated the degree of SYT7-SYNCRIP co-localization in order to examine possible functional interaction of these two proteins. We found that SYT7 is abundantly distributed in neuropil of all examined anatomical areas of the brain, most prominently in axons. On the contrary, SYNCRIP had cytoplasmic somatodendritic pattern of expression, which was most prominent in the hippocampus and cerebellum. In the striatum, hippocampus and cerebral cortex SYT7 and SYNCRIP immunofluorescent signals were mutually excluded, thus diminishing the probability for their physiological interaction. In somata of Purkinje neurons in the cerebellar cortex, both SYT7 and SYNCRIP were expressed and partially co-localized suggesting possible functional connection between SYT7 and SYNCRIP proteins in Purkinje neurons.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Heterogeneous-Nuclear Ribonucleoproteins); 0 (Syncrip protein, mouse); 0 (Syt7 protein, rat); 134193-27-4 (Synaptotagmins)


  10 / 47878 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:29258552
Autor:Chavushyan VA; Simonyan KV; Simonyan RM; Isoyan AS; Simonyan GM; Babakhanyan MA; Hovhannisyian LE; Nahapetyan KH; Avetisyan LG; Simonyan MA
Endereço:Orbeli Institute of Physiology NAS RA, 22 Orbeli Bros Street, 0028, Yerevan, Armenia.
Título:Effects of stevia on synaptic plasticity and NADPH oxidase level of CNS in conditions of metabolic disorders caused by fructose.
Fonte:BMC Complement Altern Med; 17(1):540, 2017 Dec 19.
ISSN:1472-6882
País de publicação:England
Idioma:eng
Resumo:BACKGROUND: Excess dietary fructose intake associated with metabolic syndrome and insulin resistance and increased risk of developing type 2 diabetes. Previous animal studies have reported that diabetic animals have significantly impaired behavioural and cognitive functions, pathological synaptic function and impaired expression of glutamate receptors. Correction of the antioxidant status of laboratory rodents largely prevents the development of fructose-induced plurimetabolic changes in the nervous system. We suggest a novel concept of efficiency of Stevia leaves for treatment of central diabetic neuropathy. METHODS: By in vivo extracellular studies induced spike activity of hippocampal neurons during high frequency stimulation of entorhinal cortex, as well as neurons of basolateral amygdala to high-frequency stimulation of the hippocampus effects of Stevia rebaudiana Bertoni plant evaluated in synaptic activity in the brain of fructose-enriched diet rats. In the conditions of metabolic disorders caused by fructose, antioxidant activity of Stevia rebaudiana was assessed by measuring the NOX activity of the hippocampus, amygdala and spinal cord. RESULTS: In this study, the characteristic features of the metabolic effects of dietary fructose on synaptic plasticity in hippocampal neurons and basolateral amygdala and the state of the NADPH oxidase (NOX) oxidative system of these brain formations are revealed, as well as the prospects for development of multitarget and polyfunctional phytopreparations (with adaptogenic, antioxidant, antidiabetic, nootropic activity) from native raw material of Stevia rebaudiana. Stevia modulates degree of expressiveness of potentiation/depression (approaches but fails to achieve the norm) by shifting the percentage balance in favor of depressor type of responses during high-frequency stimulation, indicating its adaptogenic role in plasticity of neural networks. Under the action of fructose an increase (3-5 times) in specific quantity of total fraction of NOX isoforms isolated from the central nervous system tissue (amygdala, hippocampus, spinal cord) was revealed. Stevia exhibits an antistress, membrane-stabilizing role reducing the level of total fractions of NOX isoforms from central nervous system tissues and regulates NADPH-dependent O -producing activity. CONCLUSION: Generally, in condition of metabolic disorders caused by intensive consumption of dietary fructose Stevia leaves contributes to the control of neuronal synaptic plasticity possibly influencing the conjugated NOX-specific targets.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Dietary Sugars); 0 (Diterpenes, Kaurane); 0 (Glucosides); 0YON5MXJ9P (stevioside); 30237-26-4 (Fructose); EC 1.6.3.- (NADPH Oxidases)



página 1 de 4788 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde