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1.
Science ; 364(6445)2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-30923171

RESUMO

Saturn's main ring system is associated with a set of small moons that either are embedded within it or interact with the rings to alter their shape and composition. Five close flybys of the moons Pan, Daphnis, Atlas, Pandora, and Epimetheus were performed between December 2016 and April 2017 during the ring-grazing orbits of the Cassini mission. Data on the moons' morphology, structure, particle environment, and composition were returned, along with images in the ultraviolet and thermal infrared. We find that the optical properties of the moons' surfaces are determined by two competing processes: contamination by a red material formed in Saturn's main ring system and accretion of bright icy particles or water vapor from volcanic plumes originating on the moon Enceladus.

2.
Rev Stomatol Chir Maxillofac ; 113(5): 407-10, 2012 Nov.
Artigo em Francês | MEDLINE | ID: mdl-22940377

RESUMO

The PEEK-Optima(®), composite mixture of polyetheretherketon and inert materials, is used in orthopedics, spinal surgery and cranio-facial surgery. It could be used in dental implantology because of its biological and mechanical properties. The results of an experimental and finite element study made on basal implant prototypes, on basal implantology show that PEEK, contrary to titanium, has a compound structure that allows to optimize the distribution of masticatory forces around the implant. These results should be confirmed by a clinical study according to research regulation.


Assuntos
Implantes Dentários , Cetonas/uso terapêutico , Ortopedia/tendências , Polietilenoglicóis/uso terapêutico , Titânio/uso terapêutico , Benzofenonas , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Fenômenos Biomecânicos , Humanos , Teste de Materiais , Ortopedia/métodos , Polímeros , Estresse Mecânico , Titânio/química
5.
Cell Mol Neurobiol ; 29(6-7): 1063-71, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19350381

RESUMO

Evidence suggests that amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Here we investigated the specific effects of Abeta on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes I-IV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble Abeta protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Trifosfato de Adenosina/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Western Blotting , Linhagem Celular Tumoral , Respiração Celular/efeitos dos fármacos , Respiração Celular/fisiologia , Citrato (si)-Sintase/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Técnicas de Transferência de Genes , Humanos , Imuno-Histoquímica , Mitocôndrias/enzimologia , Transfecção
6.
Science ; 319(5868): 1380-4, 2008 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-18323452

RESUMO

Saturn's moon Rhea had been considered massive enough to retain a thin, externally generated atmosphere capable of locally affecting Saturn's magnetosphere. The Cassini spacecraft's in situ observations reveal that energetic electrons are depleted in the moon's vicinity. The absence of a substantial exosphere implies that Rhea's magnetospheric interaction region, rather than being exclusively induced by sputtered gas and its products, likely contains solid material that can absorb magnetospheric particles. Combined observations from several instruments suggest that this material is in the form of grains and boulders up to several decimetres in size and orbits Rhea as an equatorial debris disk. Within this disk may reside denser, discrete rings or arcs of material.

7.
Pharmacopsychiatry ; 39(5): 193-4, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16944412

RESUMO

Neuroacanthocytois is a rare hereditary disease, which causes a degeneration of the striatum. Patients develop a choreatic movement disorder and also complex psychiatric symptoms, such as psychosis or Tourette's syndrome. We report a case of obsessive-compulsive disorder due to neuroacanthocytosis. The striatum plays an important role in the pathophysiology of obsessive-compulsive disorder. In Huntington's disease we also find obsessive-compulsive disorders, due to impairment of the fronto-striatal loop. Encouraged by similar pathophysiology and promising reports of selective serotonin reuptake inhibitors in this disease, we started a treatment with citalopram to which the patient responded very well.


Assuntos
Coreia/complicações , Citalopram/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adulto , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento
8.
J Neural Transm (Vienna) ; 113(11): 1753-61, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16736246

RESUMO

The presumption to suffer from Alzheimer's disease (AD) accelerates with aging. One important risk factor seems to be the isoform epsilon 4 of the apolipoprotein E gene (Apo epsilon 4), which increases the risk to develop AD at an earlier age. Furthermore, convincing evidence is provided that apoptotic cell death mechanisms play an important role in neuronal cell death in AD. In the present study, we investigated whether abnormalities in apoptosis and caspase-3 activity can be found at the level of lymphocytes and a T cell subtype, CD4 T cells, from AD patients compared to aged sex- and ApoE genotype-matched non-demented controls. Under different experimental conditions (at baseline or after in vitro incubation in the presence of proapoptotic stimuli) increased levels of apoptosis and enhanced caspase-3 activity were detected in lymphocytes from AD patients. This difference was most pronounced in the CD4(+) T cell subtype. Notably, we found a significant increase of apoptotic cells and caspase-3 activity in lymphocytes from AD patients bearing one or two alleles of the ApoE4 compared to non-E4 carriers. Again, these effects were strongest in CD4(+) T cells. Circulating amyloid-beta (A beta) levels did not differ between AD patients bearing ApoE4 and non-ApoE4 and age-matched controls. Therefore, it is likely that circulating A beta is not responsible for the observed effects, which might rather reflect an ongoing systemic response in AD, e.g. an increase in CD95 expression.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Apoptose/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Caspase 3/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/sangue , Linfócitos T CD4-Positivos/patologia , Ativação Enzimática/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Reação em Cadeia da Polimerase , Fatores de Risco , Receptor fas/metabolismo
9.
Eur J Histochem ; 50(4): 311-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17213040

RESUMO

The pineal hormone melatonin is involved in physiological transduction of temporal information from the light dark cycle to circadian and seasonal behavioural rhythms, as well as possessing neuroprotective properties. Melatonin and its receptors MT1 and MT2, which belong to the family of G protein-coupled receptors, are impaired in Alzheimer's disease (AD) with severe consequences to neuropathology and clinical symptoms. The present data provides the first immunohistochemical evidence for the cellular localization of the both melatonin receptors in the human pineal gland and occipital cortex, and demonstrates their alterations in AD. We localized MT1 and MT2 in the pineal gland and occipital cortex of 7 elderly controls and 11 AD patients using immunohistochemistry with peroxidase-staining. In the pineal gland both MT1 and MT2 were localized to pinealocytes, whereas in the cortex both receptors were expressed in some pyramidal and non-pyramidal cells. In patients with AD, parallel to degenerative tissue changes, there was an overall decrease in the intensity of receptors in both brain regions. In line with our previous findings, melatonin receptor expression in AD is impaired in two additional brain areas, and may contribute to disease pathology.


Assuntos
Doença de Alzheimer/metabolismo , Lobo Occipital/metabolismo , Glândula Pineal/metabolismo , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Biomarcadores/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade
10.
Fortschr Neurol Psychiatr ; 73 Suppl 1: S103-6, 2005 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-16270254

RESUMO

Paranoid syndromes in the elderly are nosologically unspecific. Delusional disorder is characterized by the presence of delusions, typically persecutory, commonly in their homes. Frequent risk factors are discriminating, insulting or threatening life events, social isolation as well as sensory impairments. Atypical antipsychotics are considered as first line treatment. Delusion of parasitosis and erotomania are presented as subtypes of delusional disorders.


Assuntos
Idoso/psicologia , Transtornos Paranoides/diagnóstico , Transtornos Paranoides/psicologia , Delusões/psicologia , Humanos , Transtornos Paranoides/classificação , Fatores de Risco , Isolamento Social
11.
Neuropsychobiology ; 51(3): 165-72, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15838187

RESUMO

Immersive, stereoscopic virtual reality (VR) systems provide a powerful multimedia tool for a laboratory simulation of distinct scenarios including stressful situations close to reality. Thus far, cortisol secretion as a neuroendocrine parameter of stress has not been evaluated within a VR paradigm. Ninety-four healthy subjects were subjected to a VR paradigm and a cognitive stress task. It was tested (a) if the modification of reality induced by dynamic VR as opposed to static VR can be regarded as a stressor and (b) if it can modify an additional cognitive stress response. In addition, the impact of gender on cortisol responses was assessed. A significant cortisol increase was observed only after the combined application of both conditions, but not after the dynamic VR or the cognitive stress alone. Cortisol reactivity was greater for men than for women. We conclude that dynamic VR does not affect cortisol secretion per se, but increases cortisol responses in a dual task paradigm. This provides the basis for the application of VR in neuroscientific research, which includes the assessment of hypothalamus-pituitary-adrenal axis regulation.


Assuntos
Atenção/fisiologia , Cognição , Hidrocortisona/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio/métodos , Tempo de Reação , Teste de Realidade , Caracteres Sexuais , Interface Usuário-Computador
12.
J Neural Transm (Vienna) ; 112(9): 1165-76, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15614427

RESUMO

Cognitive tasks involving distraction are associated with an early age-related decline in performance. Involuntary shifts in attention to irrelevant stimulus features and subsequent reorientation were studied in young and middle-aged subjects focussing on behavioural and event-related potential (ERP) measures. Subjects were asked to discriminate between equiprobable short and long auditory stimuli. Irrelevant rare frequency deviations prolonged reaction times (RT's), while an age-related effect on RT's was not observed. In contrast, notably after short deviant tones the error rate was considerably increased in the middle-aged subjects. ERP measures after deviant stimuli elicited a sequence of mismatch negativity (MMN), P3a and reorienting negativity (RON). The latency and amplitude of the MMN did not differ between age groups indicating an unchanged deviance detection. However, the consecutive process of attention orientation (P3a) was delayed and the subsequent reorienting (RON) to the primary task was strongly attenuated in the middle-aged subjects. After short deviants the RON was virtually absent in the middle-aged subjects, which might account for the observed decline of accuracy.


Assuntos
Envelhecimento/fisiologia , Atenção/fisiologia , Cognição/fisiologia , Potenciais Evocados Auditivos , Estimulação Acústica , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orientação/fisiologia , Córtex Pré-Frontal/fisiologia , Tempo de Reação/fisiologia
13.
Pol J Pharmacol ; 56(5): 631-4, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15591653

RESUMO

Mitochondrial dysfunction has been identified in a large proportion of neurodegenerative disorders including Alzheimer's disease (AD). In addition, the involvement of nitric oxide (NO) has been implicated in the pathogenesis of AD. Thus, we investigated the effects of the Swedish double mutation (K670M/N671L) in the beta-amyloid precursor protein (APPsw) on NO levels and mitochondrial function in PC12 cells. Interestingly, APPsw PC12 cells showed increased NO levels, decreased cytochrome C oxidase activity and reduced ATP levels compared to wild-type APP bearing cells and empty vector transfected cells. On the basis of our data, we propose a hypothetical sequence of events linking amyloid beta-peptide and NO production with mitochondria failure.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Mitocôndrias/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico/fisiologia , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia
14.
Nervenarzt ; 74(5): 428-35, 2003 May.
Artigo em Alemão | MEDLINE | ID: mdl-12966817

RESUMO

Specific phobias are one of the most frequent mental health problems and can lead to years of personal suffering. The most effective treatment is exposure therapy. Our aim was to proof the feasibility and efficacy of virtual environments in treating acrophobia patients using a manually guided exposure therapy. Our pilot study was designed as a crossover intervention with a waiting list condition as a control group. After treatment, our results show that exposure in virtual environments is a feasible technique, can provoke anxiety, and leads to a therapeutic effect.


Assuntos
Dessensibilização Psicológica/métodos , Transtornos Fóbicos/terapia , Terapia Assistida por Computador/métodos , Interface Usuário-Computador , Adulto , Nível de Alerta , Terapia Cognitivo-Comportamental , Estudos Cross-Over , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Fóbicos/diagnóstico , Transtornos Fóbicos/psicologia , Projetos Piloto , Software , Resultado do Tratamento
15.
Neuroscience ; 120(3): 659-65, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12895507

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in humans and is characterized by neuronal loss, neurofibrillary tangles and beta-amyloid deposition. The interaction between neurotrophins and their tyrosine kinase (trk) receptors is important for cellular differentiation and survival. Interestingly, marked reductions in neurotrophins and receptors have been reported in AD. The cause of the decrease in these molecules remains unclear. However, the role of beta-amyloid (A beta) appears central in understanding the mechanisms controlling neurotrophin/trk expression. In this study we exposed SHSY5Y neuroblastoma cells to A beta or hydrogen peroxide and measured the expression of trk B/truncated trk B, and brain-derived neurotrophic factor (BDNF)/NT4 at the protein and molecular level. We show that A beta or hydrogen peroxide (H(2)O(2)) induces oxidative stress and cell cytotoxicity. The exposure of cells to A beta results in an increased trk B expression with a concurrent reduction in truncated trk B levels. H(2)O(2) exposure decreased both trk B and truncated trk B levels at the cell surface. At the molecular level trk B RNA increased in the presence of A beta and was unaffected by H(2)O(2). Similarly, BDNF and NT4 levels increased in the presence of A beta. Pre-treatment of cells with the anti-oxidant melatonin returns trk receptor expression, mRNA and BDNF/NT4 secretion to normal levels. These results are significant as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Melatonina/metabolismo , Fatores de Crescimento Neural/metabolismo , Receptor trkB/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Antioxidantes/farmacologia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Humanos , Peróxido de Hidrogênio/farmacologia , Melatonina/farmacologia , Neuroblastoma , Estresse Oxidativo , RNA Mensageiro/metabolismo , Receptor trkB/efeitos dos fármacos , Receptor trkB/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células Tumorais Cultivadas
16.
Eur Psychiatry ; 18(2): 82-4, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12711404

RESUMO

In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.


Assuntos
Antipsicóticos/administração & dosagem , Cooperação do Paciente/psicologia , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Antipsicóticos/uso terapêutico , Doença Crônica , Esquema de Medicação , Humanos , Estudos Prospectivos , Resultado do Tratamento
17.
Neurobiol Aging ; 24(1): 85-94, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12493554

RESUMO

We used volumetric MRI and analysis of areas under receiver operating characteristic (ROC) curves to directly compare the extent of hippocampus-amygdala formation (HAF) and corpus callosum atrophy in patients with Alzheimer's disease (AD) in different clinical stages of dementia. Based on neuropathological studies, we hypothesized that HAF atrophy, representing allocortical neuronal degeneration, would precede atrophy of corpus callosum, representing loss of neocortical association neurons, in early AD. HAF and corpus callosum sizes were significantly reduced in 27 AD patients (37% and 16%, respectively) compared to 28 healthy controls. In mildly- and moderately-demented AD patients, the ROC derived index of atrophy was greater for HAF volume than for total corpus callosum area. The index of atrophy of posterior corpus callosum was not significantly different from HAF at mild, moderate or severe stages of dementia. In conclusion, these findings suggest a characteristic regional pattern of allocortical and neocortical neurodegeneraton in AD. Our data indicate that neuronal loss in parietotemporal cortex (represented by atrophy of corpus callosum splenium) may occur simultaneously with allocortical neurodegeneration in mild AD. Moreover, ROC analysis may provide a statistical framework to determine atrophy patterns of different brain structures in neurodegenerative diseases in vivo.


Assuntos
Doença de Alzheimer/patologia , Corpo Caloso/patologia , Hipocampo/patologia , Degeneração Neural/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/patologia , Análise de Variância , Área Sob a Curva , Atrofia/patologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Neocórtex/patologia , Degeneração Neural/patologia , Testes Neuropsicológicos , Curva ROC , Valores de Referência , Índice de Gravidade de Doença
18.
Neuroscience ; 113(4): 849-55, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12182891

RESUMO

The role of estrogen as a neurotrophic/neuroprotective agent in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is increasingly being shown. In this study we examine the neuroprotective effects of beta-estradiol on SHSY5Y neuroblastoma cells which have been exposed to the heavy metals cobalt and mercury. The results show that cobalt and mercury are able to induce oxidative stress and cell cytotoxicity and increase the secretion of beta-amyloid 1-40 and 1-42. These deleterious effects are reversed by the pretreatment of cells with beta-estradiol. It is further shown that beta-estradiol exerts its neuroprotective action through mechanisms which reduce oxidative stress and reduce beta-amyloid secretion. Pre-treatment of the cells with alpha-estradiol did not alleviate the toxic effects of the heavy metals. Our results are significant as they contribute to a better understanding of the mode of action of estrogen with relevance to its use in the treatment of neurodegenerative disorders.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Estradiol/farmacologia , Metais Pesados/toxicidade , Neuroblastoma/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos beta-Amiloides/biossíntese , Cobalto/toxicidade , Relação Dose-Resposta a Droga , Estradiol/fisiologia , Glutationa/biossíntese , Humanos , Mercúrio/toxicidade , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/metabolismo , Células Tumorais Cultivadas
19.
Eur Arch Psychiatry Clin Neurosci ; 252(3): 105-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12192466

RESUMO

During the last decade, the number of patients who consult primary care physicians or psychiatrists for symptoms of depression has doubled. The majority of depressed patients are prescribed oral medication; however, in several European countries antidepressant therapy may be initiated with a daily intravenous infusion. The choice of intravenous antidepressants was previously limited to agents such as dibenzepine, doxepin, clomipramine and viloxazine. More recently, the selective serotonin reuptake inhibitor (SSRI) citalopram has been administered as an intravenous infusion to severely depressed patients. The results from both open and double-blind clinical studies with intravenous citalopram suggest that it is an effective and well-tolerated treatment for depression. Moreover, when treatment is initiated by infusion and continued orally, citalopram is at least as effective as clomipramine, doxepin and viloxazine. As with oral treatment, adverse events experienced by patients are mild to moderate in severity with 50 % of patients reporting no adverse events. The high bioavailability of citalopram indicates that the switch from intravenous to oral citalopram would prevent a deterioration of symptoms as plasma drug concentrations would be maintained. Thus citalopram, the only SSRI available as an intravenous formulation, may be a useful addition for the treatment of severely depressed patients who may benefit from more intensive therapy. The aim of this paper is to review available data detailing the clinical outcome of intravenously administered citalopram in depressed patients.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Citalopram/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Administração Oral , Antidepressivos de Segunda Geração/administração & dosagem , Citalopram/administração & dosagem , Depressão/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Humanos , Infusões Intravenosas , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem
20.
Neurol Clin Neurophysiol ; 2002(2): 2-10, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12028822

RESUMO

The interaction of neurotrophins and their tyrosine kinase receptors (trks) is essential for differentiation and survival of brain cells. In Alzheimer's disease (AD), the number of neurotrophins and receptors is markedly decreased. The cause of this reduction is unclear, but the role of beta-amyloid (Abeta) seems central in understanding the mechanisms controlling neurotrophin and trk expression. In the study reported here, we exposed SHSY5Y neuroblastoma cells to Abeta or hydrogen peroxide (H(2)O(2)) and measured the expression of trk-A and p75 at the protein and molecular levels. Both Abeta and H(2)O(2) induced oxidative stress (measured by a decrease in cellular glutathione), which decreased trk-A levels and increased p75 levels, decreased messenger RNA (mRNA) levels of both receptors, and increased nerve growth factor (NGF) secretion. Pretreatment of cells with the antioxidant melatonin returned levels of protein expression, mRNA, and NGF secretion to normal. These results are significant, as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.


Assuntos
Neuroblastoma/metabolismo , Estresse Oxidativo/fisiologia , Receptor trkA/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Peptídeos beta-Amiloides/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Melatonina/farmacologia , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/antagonistas & inibidores , Fator de Crescimento Neural/biossíntese , Neuroblastoma/tratamento farmacológico , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptor de Fator de Crescimento Neural , Receptor trkA/genética , Receptores de Fator de Crescimento Neural/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
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