Consulta: subjectFacets:"Alzheimer's disease"
Registros recuperados: 20
Data/hora: 08/06/2024 15:22:27

Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer's Disease patients: a pilot study
Provedor de dados: 74
Autores: González-Castañeda,Rocío E.; Sánchez-González,Víctor J.; Flores-Soto,Mario; Vázquez-Camacho,Gonzalo; Macías-Islas,Miguel A.; Ortiz,Genaro G.
Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer's Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Neural restrictive silencer factor; Choline acetyltransferase; Alzheimer's disease; Protein expression; Brain.
Ano: 2013
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572013000100005

Apolipoprotein E polymorphism as a predictor for cognitive decline and dementia in the Saudi general population over 65 years
Provedor de dados: 74
Autores: Al-Khedhairy,Abdulaziz Ali A.
Specific Apolipoprotein E (ApoE) genotypes are thought to be associated with risk for Alzheimer's disease (AD). It is essential to understand how this genetic factor affects cognitive decline and dementia in the general population. One hundred and fifty elderly persons residing at social nursing centers in different provinces of Saudi Arabia were tested for ApoE genotypes, using PCR amplification of genomic DNA followed by DNA digestion with Cfo I. All subjects were diagnosed with regard to cognitive decline and dementia. In the general Saudi population, the ApoE4 allele was found to be a weaker predictor for dementia than for AD. This may be a result of non-AD pathological processes and/or of most prevalent dementia at an age when the ApoE4 effect on the...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: ApoE; Alzheimer's disease; Dementia; Saudi population.
Ano: 2004
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572004000300004

Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells
Provedor de dados: 42
Autores: LAGUNES,TERESA; HERRERA-RIVERO,MARISOL; HERNÁNDEZ-AGUILAR,MARÍA ELENA; ARANDA-ABREU,GONZALO E.
Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease, where its hyperphos-phorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing which generates six isoforms in the human brain, due to inclusion/exclusion of exons 2, 3 and 10. Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing of other exons is less studied. We studied the effects of beta-amyloid(42) in the alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to retract in differentiated cells and altered the expression of exons...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; Amyloid peptide; Splicing regulation; Tau isoforms.
Ano: 2014
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652014000401927

Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology
Provedor de dados: 42
Autores: HERRERA-RIVERO,MARISOL; SOTO-CID,ABRAHAM; HERNáNDEZ,MARíA E.; ARANDA-ABREU,GONZALO E.
Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure,...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; APP; BACE1; Nicastrin; Normal ageing; Risk factors.
Ano: 2013
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652013000401489

Alzheimer´s Disease associated with Psychiatric Comorbidities
Provedor de dados: 42
Autores: Garcez,Michelle L.; Falchetti,Ana Carolina B.; Mina,Francielle; Budni,Josiane.
Alzheimer's disease (AD) is the most common cause of dementia and has become a severe public health issue. It is estimated that globally, 35.6% of people have some form of dementia. This number is expected to double by 2030, and possibly even triple by 2050. The disease is associated with deficits in cognition/memory and a reduced ability in coping with everyday life. Moreover, patients can experience behavioral alterations such as mood swings, depression and hallucinations. Therefore, it is common to find the presence of neuropsychiatric comorbidities such as depression, schizophrenia and bipolar disorder during the course or development of AD. These disorders can become severe enough to interfere with the patients daily functioning, and can worsen the...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; Bipolar disorder; Depression; Schizophrenia.
Ano: 2015
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652015000301461

Physiopathological modulators of amyloid aggregation and novel pharmacological approaches in Alzheimer's disease
Provedor de dados: 42
Autores: DEFELICE,FERNANDA G.; FERREIRA,SÉRGIO T.
The biological mechanisms underlying the neuropathology of Alzheimer's disease (AD) are complex, as several factors likely contribute to the development of the disease. Therefore, it is not surprising that a number of different possible therapeutic approaches addressing distinct aspects of this disease are currently being investigated. Among these are ways to prevent amyloid aggregation and/or deposition, to prevent neuronal degeneration, and to increase brain neurotransmitter levels. Here, we discuss possible roles of endogenous modulators of Abeta aggregation in the physiopathology of AD and some of the strategies currently under consideration to interfere with brain levels of beta-amyloid, its aggregation and neurotoxicity.
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; Abeta peptide; Aggregation; Neurotoxicity; Physiopathological modulators.
Ano: 2002
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652002000200006

Amyloid-β peptide absence in short term effects on kinase activity of energy metabolism in mice hippocampus and cerebral cortex
Provedor de dados: 42
Autores: IANISKI,FRANCINE R.; RECH,VIRGINIA C.; NISHIHIRA,VIVIAN S.K.; ALVES,CATIANE B.; BALDISSERA,MATHEUS D.; WILHELM,ETHEL A.; LUCHESE,CRISTIANE.
ABSTRACT Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-β or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam-loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol. In the fourteenth day, kinases activities were performed. Amyloid-β did not change the kinases activity in the hippocampus and cerebral cortex of mice. However, free meloxicam decrease the creatine kinase...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; Nanoparticles; Meloxicam; Energetic metabolism; Phosphoryltransfer network.
Ano: 2016
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652016000501829

Small-molecule aggregation inhibitors reduce excess amyloid in a trisomy 16 mouse cortical cell line
Provedor de dados: 48
Autores: LIMA,ANDRÉA C PAULA; ARRIAGADA,CHRISTIAN; TORO,RODRIGO; CÁRDENAS,ANA MARÍA; CAVIEDES,RAÚL; FERREIRA,SERGIO T; CAVIEDES,PABLO.
We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the &amp;#946;-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP) accumulation in the CTb immortalized cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down's syndrome. Compared to a non-trisomic cortical cell line (CNh), CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca2+ levéis ([Ca2+]¡). Here, we show that the compounds 2,4-dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and...
Tipo: Journal article
Palavras-chave: Alzheimer's disease; Down syndrome; Intracellular amyloid; Murine trisomy 16; Small molecule inhibitors.
Ano: 2008
URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602008000200001

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology
Provedor de dados: 48
Autores: Nualart,Francisco; Salazar,Katterine; Oyarce,Karina; Cisternas,Pedro; Jara,Nery; Silva-Álvarez,Carmen; Pastor,Patricia; Martínez,Fernando; García,Andrea; García-Robles,María de los Ángeles; Tapia,Juan Carlos.
Stem cells are considered a valuable cellular resource for tissue replacement therapies in most brain disorders. Stem cells have the ability to self-replicate and differentiate into numerous cell types, including neurons, oligodendrocytes and astrocytes. As a result, stem cells have been considered the "holy grail" of modern medical neuroscience. Despite their tremendous therapeutic potential, little is known about the mechanisms that regulate their differentiation. In this review, we analyze stem cells in embryonic and adult brains, and illustrate the differentiation pathways that give origin to most brain cells. We also evaluate the emergent role of the well known anti-oxidant, vitamin C, in stem cell differentiation. We believe that a complete...
Tipo: Journal article
Palavras-chave: Stem cells; Radial glia; Vitamin C; SVCT2; Brain development; Tanycytes; Bergmann glia; Neurogenic niche; Type B cells; Neuroblast; Parkinson's disease; Alzheimer's disease; Amyotrophic lateral sclerosis.
Ano: 2012
URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602012000300006

Histidines 13 and 14 in the A&amp;#946; sequence are targets for inhibition of Alzheimer's disease A&amp;#946; ion channel and cytotoxicity
Provedor de dados: 48
Autores: DÍAZ,JUAN CARLOS; LINNEHAN,JOHN; POLLARD,HARVEY; ARISPE,NELSON.
The fact that Alzheimer's beta amyloid (A&amp;#946;) peptides forms cation channels in lipid bilayers was discovered during the course of our experiments in the laboratory of "Guayo" Rojas at NIH in Bethesda, Maryland (USA). Recently, we found that the A&amp;#946; ion channel could be blocked selectively with small peptides that copy the amino acid sequence of the predicted mouth region of the A&amp;#946; channel pore. We now have searched for the essential amino acid residues required for this blocking effect by mutations. We found that the ability of peptides to block A&amp;#946; channel activity could be lost by replacement of histidines 13 and 14 by alanine or lysine. The amino acid substitution also resulted in the loss of the capacity of the peptides...
Tipo: Journal article
Palavras-chave: Alzheimer's disease; Beta amyloid; Ion channel blockers; Peptides; Histidine; Toxicity.
Ano: 2006
URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000300007

On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae)
Provedor de dados: 48
Autores: Rivera,Daniela S.; Inestrosa,Nibaldo C.; Bozinovic,Francisco.
Cognitive ecologist posits that the more efficiently an animal uses information from the biotic and abiotic environment, the more adaptive are its cognitive abilities. Nevertheless, this approach does not test for natural neurodegenerative processes under field or experimental conditions, which may recover animals information processing and decision making and may explain, mechanistically, maladaptive behaviors. Here, we call for integrative approaches to explain the relationship between ultimate and proximate mechanisms behind social behavior. We highlight the importance of using the endemic caviomorph rodent Octodon degus as a valuable natural model for mechanistic studies of social behavior and to explain how physical environments can shape social...
Tipo: Journal article
Palavras-chave: Cognitive ecology; Octodon degus; Social behavior; Stress; Aging; Alzheimer's disease.
Ano: 2016
URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100010

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
Provedor de dados: 48
Autores: TSUJITA,MIKI; SAKURABA,SHIGEKI; KURIBAYASHI,JUNYA; HOSOKAWA,YUKI; HATORI,EIKI; OKADA,YASUMASA; KASHIWAGI,MASANORI; TAKEDA,JUNZO; KUWANA,SHUN-ICHI.
Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the...
Tipo: Journal article
Palavras-chave: Morphine; Donepezil; Rabbit; Respiratory depression; Alzheimer's disease; Cholinesterase inhibitor.
Ano: 2007
URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602007000400008

Risk of Dementia and Alcohol and Wine Consumption: a Review of Recent Results
Provedor de dados: 48
Autores: LETENNEUR,LUC.
The term dementia refers to a clinical syndrome of acquired intellectual disturbances produced by brain dysfunction. Dementia may result from a wide variety of disorders, including degenerative (e.g. Alzheimer's disease, AD), vascular (e.g. multi-infarct dementia), and traumatic (e.g. head injury). Long-term abuse of alcohol is related to the development of the Wernicke-Korsakoff's syndrome or alcohol dementia. However, light to moderate alcohol intake might also reduce the risk of dementia and AD. In Bordeaux (France), a population-based prospective study found that subjects drinking 3 to 4 standard glasses of wine per day (&gt; 250 and up to 500 ml), categorized as moderate drinkers, the crude odds ratio (OR) was 0.18 for incident dementia (p &lt; 0.01)...
Tipo: Journal article
Palavras-chave: Alcohol; Alzheimer's disease; Dementia; Wine.
Ano: 2004
URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000200003

The cognitive subscale of the "Alzheimer's Disease Assessment Scale" in a Brazilian sample
Provedor de dados: 56
Autores: Schultz,R.R.; Siviero,M.O.; Bertolucci,P.H.F.
The cognitive subscale of the "Alzheimer's Disease Assessment Scale" (ADAS-Cog) is widely used for the evaluation of dementia and is very popular in dementia drug trials because of the characteristics of the scale. The objective of the present study was to adapt the ADAS-Cog for use for the Brazilian population. A major problem is that education is variable, a fact that may influence performance in cognitive evaluation. This study was conducted on a control group (CG) of 96 subjects (25 males and 71 females aged 68 ± 8.6 years) and on 44 Alzheimer's disease (AD) patients (19 males and 25 females aged 72 ± 6.4 years) with mild dementia (Clinical Dementia Rating score 1). For statistical analysis groups were divided into three educational levels: I, 0-4...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Dementia; Alzheimer's disease; Neuropsychological evaluation; Education.
Ano: 2001
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001001000009

Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians
Provedor de dados: 56
Autores: Souza,D.R.S.; De Godoy,M.R.; Hotta,J.; Tajara,E.H.; Brandão,A.C.; Pinheiro Júnior,S.; Tognola,W.A.; Dos Santos,J.E.
The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE) gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68), other late-life dementias (N = 39), and in cognitively normal controls (N = 58) was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2...
Tipo: Info:eu-repo/semantics/other
Palavras-chave: Alzheimer's disease; Vascular dementia; Dementia; Apolipoprotein E; Aging; Genetic polymorphisms.
Ano: 2003
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2003000700013

A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects
Provedor de dados: 56
Autores: Carvalho,K.M.; França,M.S.F.; Camarão,G.C.; Ruchon,A.F.
A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human brain using successive steps of chromatography on DEAE-Trisacryl, hydroxylapatite and Sephacryl S-200. The purified enzyme cleaved the Gly33-Leu34 bond of the 25-35 neurotoxic sequence of the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects. This enzyme activity was only inhibited by divalent cation chelators such as EDTA, EGTA and o-phenanthroline (1 mM) and was insensitive to phosphoramidon and captopril (1 µM concentration), specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. The high affinity of this human brain endopeptidase for ß-amyloid 1-40...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Brain metalloendopeptidase; Alzheimer ß-amyloid 1-40 peptide; Alzheimer's disease.
Ano: 1997
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997001000002

Alzheimer's disease: is a vaccine possible?
Provedor de dados: 56
Autores: Alves,R.P.S.; Yang,M.J.; Batista,M.T.; Ferreira,L.C.S.
The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected...
Palavras-chave: Alzheimer's disease; Β-amyloid; Vaccine; Active immunization.
Ano: 2014
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2014000600438

Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population
Provedor de dados: 56
Autores: de-Andrade,F.M.; Larrandaburu,M.; Callegari-Jacques,S.M.; Gastaldo,G.; Hutz,M.H.
Apolipoprotein E (protein: apo E; gene: APOE) plays an important role in the multifactorial etiology of both Alzheimer's disease (AD) and lipid level concentrations. The polymerase chain reaction (PCR) was used to investigate the APOE gene polymorphism in 446 unrelated Caucasians, among them 23 AD patients, and 100 Afro-Brazilians living in Porto Alegre, Brazil. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.075, 0.810 and 0.115 in Caucasians and 0.075, 0.700 and 0.225 in Afro-Brazilians, respectively (c2 = 8.72, P = 0.013). A highly significant association was observed between the APOE*4 allele and AD in this population-based sample. The APOE*4 frequency in AD patients (39%) was about four times higher than in the general Caucasian...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Polymorphism; APOE; Lipoproteins; Apoprotein; Alzheimer's disease.
Ano: 2000
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2000000500007

The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder
Provedor de dados: 56
Autores: Oliveira,J.R.M.; Zatz,M.
Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD), the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the &lt;FONT FACE="Symbol"&gt;e&lt;/font&gt;4 allele of the apolipoprotein E (APOE) gene (on chromosome 19) is the major susceptibility locus for the most common late onset AD (LOAD). Serotonin (5-hydroxytryptamine or 5-HT) is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT) gene has been studied in several psychiatric diseases and...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; Allelic association; Serotonin polymorphisms.
Ano: 1999
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1999000400014

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease
Provedor de dados: 60
Autores: Yar,Muhammad; Arshad,Muhammad; Farooq,Ariba; Gilani,Mazhar Amjad; Ayub,Khurshid; Ejaz,Asma; Kumar,Anupriya; Ninomiya,Ichiya.
Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into...
Tipo: Info:eu-repo/semantics/article
Palavras-chave: Alzheimer's disease; Antioxidant compounds; Chronic diseases; Density Functional Theory; Molecular docking; Computational studies; DPPH assay; Indole derivatives; Acetylcholinesterase (AChE); Butyrylcholinesterase (BChE).
Ano: 2015
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502015000100053