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1.
Biochim Biophys Acta Mol Basis Dis ; 1863(6): 1666-1677, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28392418

RESUMO

Alteration of axonal transport has emerged as a common precipitating factor in several neurodegenerative disorders including Human Spastic Paraplegia (HSP). Mutations of the SPAST (SPG4) gene coding for the spastin protein account for 40% of all autosomal dominant uncomplicated HSP. By cleaving microtubules, spastin regulates several cellular processes depending on microtubule dynamics including intracellular membrane trafficking. Axonal transport is fundamental for the viability of motor neurons which often have very long axons and thus require efficient communication between the cell body and its periphery. Here we found that the anterograde velocity of VAMP7 vesicles, but not that of VAMP2, two vesicular-SNARE proteins implicated in neuronal development, is enhanced in SPG4-KO neurons. We showed that this effect is associated with a slight increase of the level of acetylated tubulin in SPG4-KO neurons and correlates with an enhanced activity of kinesin-1 motors. Interestingly, we demonstrated that an artificial increase of acetylated tubulin by drugs reproduces the effect of Spastin KO on VAMP7 axonal dynamics but also increased its retrograde velocity. Finally, we investigated the effect of microtubule targeting agents which rescue axonal swellings, on VAMP7 and microtubule dynamics. Our results suggest that microtubule stabilizing agents, such as taxol, may prevent the morphological defects observed in SPG4-KO neurons not simply by restoring the altered anterograde transport to basal levels but rather by increasing the retrograde velocity of axonal cargoes.


Assuntos
Córtex Cerebral/metabolismo , Neurônios/metabolismo , Proteínas R-SNARE/metabolismo , Vesículas Secretórias/metabolismo , Espastina/metabolismo , Animais , Transporte Biológico Ativo/genética , Células Cultivadas , Córtex Cerebral/citologia , Camundongos , Camundongos Knockout , Proteínas R-SNARE/genética , Vesículas Secretórias/genética , Espastina/genética
3.
Neurología (Barc., Ed. impr.) ; 22(5): 292-300, jun. 2007. ilus
Artigo em Es | IBECS | ID: ibc-054731

RESUMO

Introducción. Benito Pérez Galdós fue un escritor realista dedicado a representar la realidad en toda su complejidad. Comparte los rasgos de la medicina experimental de Claude Bernard (Introduction à l'étude de la médicine expérimentale). El escritor fue muy amigo de prominentes médicos (Gregorio Marañón, Manuel Tolosa Latour), poseía libros de contenido neurológico y sabía de Charcot. Métodos. Con esos datos son previsibles descripciones neurológicas, esto es lo que nos proponemos hallar. Revisamos las novelas Fortunata y Jacinta, La de Bringas y Tormento. Resultados. Hallamos: a) migraña con y sin aura, con descripción de desencadenantes y herencia. El propio escritor sufrió migrañas graves; b) trastornos del movimiento: síndrome parkinsoniano y espasmo hemifacial; c) epilepsia en una niña, convulsiva y no convulsiva; también síncopes y pérdidas de conciencia psicógenas; d) sífilis congénita, con rasgos físicos típicos. Se trata de un personaje con esquizofrenia paranoide; es probable que se deba la asociación sífilis-demencia tan aceptada en la época; e) alcoholismo: intoxicación aguda, privación, trastornos de conducta, encefalopatía hepática y una probable pelagra; f) trastornos del sueño: parasomnias (sonambulismo, somniloquia) y parálisis de sueño, y g) «ictus» y metamorfopsia invertida de origen psicógeno. Conclusión. Las deformidades físicas y las enfermedades eran parte de la vida cotidiana en el siglo XIX. Los trastornos neurológicos eran prevalentes y están plenamente integrados en el realismo narrativo de Galdós. Muchos de ellos se adaptan a las teorías de degeneración de la época. No obstante, el escritor aporta rasgos humanitarios que elevan a sus personajes sobre su destino trágico. Algunos datos biográficos, sobre todo su rica vida amorosa y su implicación como político liberal, pueden haber contribuido a la riqueza y precisión de las descripciones


Introduction. Benito Pérez Galdós was a realistic writer. As such, he was devoted to displaying reality in its full complexity. He shared the traits of experimental medicine of Claude Bernard (Introduction à l'étude de la médecine expérimentale). The writer was a close friend of famous contemporary doctors (Gregorio Marañón, Manuel Tolosa Latour), had textbooks with neurological content, and was familiar with Charcot. Methods. With this background, we have foreseen neurological descriptions in his works. To search for them, we have reviewed three paramount novels: Fortunata y Jacinta, La de Bringas and Tormento. Results. We found: a) headache, usually migraine with and without aura; common precipitants and inheritance are present. The novelist himself suffered from severe migraine; b) movement disorders: Parkinson syndrome and hemifacial spasm; c) convulsive and non-convulsive epilepsy in a girl as well as syncope and psychogenic loss of consciousness; d) congenital syphilis, based on a typical physical appearance in a character with madness (paranoid schizophrenia); the reason was probably that syphilis was regarded as the most common cause of «dementia praecox»; e) alcoholism: acute intoxication, deprivation, behavior disorders, hepatic encephalopathy and a likely pellagra; f) sleep disorders: parasomnias (somnambulism, somniloquy) and sleep paralysis, and g) stroke and also inverted metamorphopsia of psychogenic origin. Conclusion. Ailments and disease pervaded life in the 19th century. Neurological disorders were highly prevalent and are fully integrated into Galdos realistic works. Many of them fulfill criteria of disorders contemplated according to degeneration theories. Nevertheless, humanitarian features raise the characters above their tragic destiny. Biographical factors, particularly his many love affairs and his political implication as a liberal, could have contributed to the plethora of precise descriptions


Assuntos
Humanos , Medicina na Literatura , Doenças do Sistema Nervoso , Pessoas Famosas , Epilepsia , Doença de Parkinson , Transtornos de Enxaqueca
4.
Neurologia ; 22(5): 292-300, 2007 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-17508303

RESUMO

INTRODUCTION: Benito Pérez Galdós was a realistic writer. As such, he was devoted to displaying reality in its full complexity. He shared the traits of experimental medicine of Claude Bernard (Introduction à l'étude de la médecine expérimentale). The writer was a close friend of famous contemporary doctors (Gregorio Marañón, Manuel Tolosa Latour), had textbooks with neurological content, and was familiar with Charcot. METHODS: With this background, we have foreseen neurological descriptions in his works. To search for them, we have reviewed three paramount novels: Fortunata y Jacinta, La de Bringas and Tormento. RESULTS: We found: a) headache, usually migraine with and without aura; common precipitants and inheritance are present. The novelist himself suffered from severe migraine; b) movement disorders: Parkinson syndrome and hemifacial spasm; c) convulsive and non-convulsive epilepsy in a girl as well as syncope and psychogenic loss of consciousness; d) congenital syphilis, based on a typical physical appearance in a character with madness (paranoid schizophrenia); the reason was probably that syphilis was regarded as the most common cause of "dementia praecox"; e) alcoholism: acute intoxication, deprivation, behavior disorders, hepatic encephalopathy and a likely pellagra; f) sleep disorders: parasomnias (somnambulism, somniloquy) and sleep paralysis, and g) stroke and also inverted metamorphopsia of psychogenic origin. CONCLUSION: Ailments and disease pervaded life in the 19th century. Neurological disorders were highly prevalent and are fully integrated into Galdos realistic works. Many of them fulfill criteria of disorders contemplated according to degeneration theories. Nevertheless, humanitarian features raise the characters above their tragic destiny. Biographical factors, particularly his many love affairs and his political implication as a liberal, could have contributed to the plethora of precise descriptions.


Assuntos
Literatura Moderna , Doenças do Sistema Nervoso , Pessoas Famosas , Feminino , História do Século XIX , Humanos , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/história
5.
Neurologia ; 17(3): 151-5, 2002 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-11927104

RESUMO

The turn of the screw is one of the most celebrated stories by Henry James. It is also a top writing within the so-called fantastic literature, whose narrative strength comes from the intermittent visions suffered by the main character. The vividness and dramatic content that represent the firstly unidentified human figures, that moreover recur as brief, stereotyped and fragmentary images, are constitutive of complex visual hallucinations. These characteristics, alongside acute premonitory symptoms such as emotional changes (fear, anxiety) or altered thinking (forced, "dejà vu", "jamais vu"), and the final altered awareness or loss of consciousness, allow us to infer an epileptic nature of the ten episodes described. Postictal psychosis, that follows a lucid interval and may last up to the several weeks encompassed by the story, would account for the paranoia featured, in the setting of a temporal lobe epilepsy. The accurate descriptions prompted us to search for autobiographical, scientific or literary influences: The alcoholism and visual hallucinations suffered by his father, the knowledge on hallucinations provided by his brother Williams on his paramount and former The Principles of Psychology, and an early devotion to Poe's writings, an epileptic himself with excellent descriptions of seizures in his writings, might have enabled the author to perform his story with such a hallmark of neurological details.


Assuntos
Epilepsia do Lobo Temporal/história , Alucinações , Literatura Moderna/história , Medicina na Literatura , Epilepsia do Lobo Temporal/fisiopatologia , História do Século XIX , Humanos
6.
Neurología (Barc., Ed. impr.) ; 17(3): 151-155, mar. 2002.
Artigo em Es | IBECS | ID: ibc-11265

RESUMO

Otra vuelta de tuerca es una de las novelas más famosas de Henry James. Es a la vez una obra cumbre de la literatura fantástica, cuya fuerza narrativa es consecuencia de las visiones intermitentes del personaje principal. La viveza y el contenido dramático que representan las figuras humanas de la alucinación, no identificadas inicialmente, que recurren además como imágenes breves, estereotipadas y fragmentarias, son constitutivas de alucinaciones visuales complejas. Estas características, junto con cambios premonitorios emocionales (miedo o ansiedad) o del pensamiento (forzado, "déjà vu", "jamais vu") y una alteración o pérdida de conciencia final, nos permiten inferir un origen epiléptico de los 10 episodios descritos. La psicosis postictal, que sigue a un intervalo lúcido y que puede durar las semanas que abarca la historia, puede explicar la paranoia que narra, en el contexto de una epilepsia del lóbulo temporal. La precisión de las descripciones nos ha llevado a buscar influencias autobiográficas, científicas o literarias: la historia de alcoholismo con alucinaciones visuales de su padre, el conocimiento de alucinaciones que le proporcionó la obra capital y previa Principios de psicología, de su hermano Williams, y la fascinación temprana que profesó por la obra de Poe, epiléptico con una obra que alberga excelentes descripciones de crisis, pueden haber facilitado al autor la aportación a su novela de detalles neurológicos tan destacados. (AU)


Assuntos
História do Século XIX , Humanos , Medicina na Literatura , Alucinações , Literatura Moderna , Epilepsia do Lobo Temporal
7.
J Neurochem ; 79(1): 98-109, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11595762

RESUMO

Capacitative calcium entry (CCE) has been described in a variety of cell types. To date, little is known about its role in the CNS, and in particular in the cross-talk between glia and neurons. We have first analyzed the properties of CCE of astrocytes in culture, in comparison with that of the rat basophilic leukemia cell line (RBL-2H3), a model where calcium release-activated Ca2+ (CRAC) channels have been unambiguously correlated with CCE. We here show that (i) in astrocytes CCE activated by store depletion and Ca2+ influx induced by glutamate share the same pharmacological profile of CCE in RBL-2H3 cells and (ii) glutamate-induced Ca2+ influx in astrocytes plays a primary role in glutamate-dependent intracellular Ca2+ concentration ([Ca2+]i) oscillations, being these latter reduced in frequency and amplitude by micromolar concentrations of La3+. Finally, we compared the expression of various mammalian transient receptor potential genes (TRP) in astrocytes and RBL-2H3 cells. Despite the similar pharmacological properties of CCE in these cells, the pattern of TRP expression is very different. The involvement of CCE and TRPs in glutamate dependent activation of astrocytes is discussed.


Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Cálcio/metabolismo , Córtex Cerebral/citologia , Ácido Glutâmico/farmacologia , Animais , Animais Recém-Nascidos , Transporte Biológico/efeitos dos fármacos , Canais de Cálcio/genética , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Células Cultivadas , Quelantes/farmacologia , Ácido Egtázico/farmacologia , Inibidores Enzimáticos/farmacologia , Corantes Fluorescentes , Indóis/farmacologia , Lantânio/farmacologia , Leucemia Basofílica Aguda , RNA Mensageiro/análise , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPC , Tapsigargina/farmacologia , Células Tumorais Cultivadas
8.
Rev. Finlay ; 4(4): 60-6, 1990. tab
Artigo em Espanhol | LILACS | ID: lil-267417

RESUMO

Se evaluan los resultados obtenidos en el tratamiento de las disfunciones temporomandibulares en nuestro medio en un año de trabajo en una consulta creada al efecto, donde se estudiaron 52 pacientes entre 15 y 60 años y se analizaron las caracteristicas clinicas de estos enfermos: edad, posibles alteraciones psiquicas, así como las terapeuticas mas utilizadas. Los datos obtenidos se computaron y analizaron mediante por ciento y prueba de x2, para los cual se propuso aceptar un nivel de significación igual o menor a 0.05 se observó que los pacientes mas aquejados estaban entre los 15 y los 30 años, con predominio del sexo femenino. El síntoma fundamental fue dolor articular y la limitación de la apertura bucal entre otros, aplicandose a todos estos pacientes el protocolo de tratamiento escogido para este estudio


Assuntos
Síndrome da Disfunção da Articulação Temporomandibular/terapia , Transtornos da Articulação Temporomandibular/terapia
9.
Rev. Finlay ; 4(4): 60-6, 1990. tab
Artigo em Espanhol | CUMED | ID: cum-17152

RESUMO

Se evaluan los resultados obtenidos en el tratamiento de las disfunciones temporomandibulares en nuestro medio en un año de trabajo en una consulta creada al efecto, donde se estudiaron 52 pacientes entre 15 y 60 años y se analizaron las caracteristicas clinicas de estos enfermos: edad, posibles alteraciones psiquicas, así como las terapeuticas mas utilizadas. Los datos obtenidos se computaron y analizaron mediante por ciento y prueba de x2, para los cual se propuso aceptar un nivel de significación igual o menor a 0.05 se observó que los pacientes mas aquejados estaban entre los 15 y los 30 años, con predominio del sexo femenino. El síntoma fundamental fue dolor articular y la limitación de la apertura bucal entre otros, aplicandose a todos estos pacientes el protocolo de tratamiento escogido para este estudio (AU)


Assuntos
Transtornos da Articulação Temporomandibular/terapia , Síndrome da Disfunção da Articulação Temporomandibular/terapia
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