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1.
BMJ Case Rep ; 16(11)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38035679

RESUMO

Skene's gland duct cysts are benign, asymptomatic bulging interlabial masses that are rarely identified in female newborns. The aetiology is unknown, but it is commonly associated with in utero maternal oestrogen exposure or obstruction or stenosis of the gland duct. We report three unrelated cases of neonatal Skene's gland duct cysts that resolved spontaneously without the need for surgical intervention.


Assuntos
Cistos , Neoplasias Cutâneas , Doenças Uretrais , Humanos , Recém-Nascido , Feminino , Doenças Uretrais/cirurgia , Cistos/diagnóstico por imagem , Cistos/cirurgia
2.
Acta Ortop Bras ; 27(5): 273-275, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839738

RESUMO

OBJECTIVE: Non-union and persistence of infection at a fracture site for long periods are always described as a challenge to orthopedists, especially in cases of severe compound fractures with comminution and segmental bone loss. This is a case series of septic non-unions, using S53P4 bioactive glass for adjunctive treatment, using internal syntheses or external fixators. The objective is to retrospectively evaluate the results of the use of S53P4 bioglass for the adjunctive treatment of septic non-unions. METHODS: We reviewed 18 patients with septic non-unions. The patients were preoperatively classified using the Non-union Scoring System (NUSS) and union outcomes were assessed by the modified radiographic union scale in tibial (RUST) fractures. Of the 18 patients treated, six underwent internal osteosynthesis and 12 were treated with external fixators in combination with bioactive glass grafting. RESULTS: The patients had a mean NUSS score of 56.6 (standard deviation of 7.6) and fracture union was achieved according to the RUST score in 17 of 18 cases (94.4%), with a mean value of 10.2 (standard deviation of 1.0). One patient was lost to follow-up. Reevaluation using the modified RUST score was 12.3 (SD = 1.0), maintaining union of 17/18. CONCLUSION: The fracture union rate was high, according to the literature, as was control of infection. Level of Evidence IV, Case series.


OBJETIVO: A não união e a persistência de infecção no local de uma fratura por períodos prolongados são sempre descritas como desafios para os ortopedistas, especialmente em casos de fraturas expostas graves, com cominuição e perdas de segmentos ósseos. Esta é uma série de casos de não consolidações infectadas, utilizando o vidro bioativo S53P4 como adjuvante no tratamento, utilizando-se sínteses internas ou fixadores externos. O objetivo é avaliar retrospectivamente os resultados do uso do biovidro S53P4 como adjuvante no tratamento de não uniões infectadas. MÉTODOS: Foram revistos 18 pacientes com não consolidações infectadas. Os pacientes foram classificados antes da cirurgia pelo Non-Union Severity Score (NUSS), e os resultados quanto à consolidação foram avaliados pelo escore de RUST modificado (escala radiográfica de consolidação da tíbia). Dos 18 pacientes tratados, seis foram submetidos à osteossíntese interna e 12 foram tratados com fixadores externos, associados à enxertia com vidro bioativo. RESULTADOS: Os pacientes tinham resultado NUSS médio de 56,6 (desvio padrão de 7,6) e a consolidação foi obtida segundo o escore de RUST em 17 de 18 casos (94,4%), com valor médio de 10,2 (desvio padrão de 1.0). Um paciente abandonou o seguimento. A reavaliação pelo escore de RUST modificado foi de 12,3 (PF=1,0), mantendo a consolidação de 17/18. CONCLUSÃO: O índice de consolidação foi elevado, segundo a literatura, bem como controle infeccioso. Nível de evidência IV, série de casos.

3.
Injury ; 50(2): 386-391, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30558805

RESUMO

OBJECTIVES: The purpose of this study was to compare the pain scores and the rates and doses of opioid use in patients undergoing volar locked plate fixation of intra-articular distal radius fractures using or not postoperative immobilization. METHODS: This was a prospective randomized controlled trial. Thirty-nine patients with distal radius fractures scheduled to receive volar plate fixation were randomly assigned to receive a short forearm splint for two weeks postoperatively or conventional bandage with early wrist mobilization. Thirty-six patients completed the follow-up. The outcome measurements included pain scores (0-10 points); rates and doses of tramadol use; DASH score; wrist range of motion; patient satisfaction; and complication rates. The last follow-up assessment was performed at 6 months. RESULTS: The pain scores were similar between the groups during hospital stay, as well as after hospital discharge within the first week and in subsequent assessments up to six months. The rates of tramadol use were greater in the No splint group during hospital stay, but this difference was not statistically significant (No splint = 65%; Splint = 47%; p = 0.296). Likewise, the doses of tramadol intake were higher in the No splint group during hospital stay (No splint = 218 mg; Splint = 167 mg; p = 0.273) and after discharge (2nd day: No splint = 112 mg; Splint = 75 mg; p = 0.286), with no statistically significant differences. The functional results and complication rates were similar between the groups. CONCLUSIONS: In this study, there was a trend to a greater use of tramadol in patients who did not use immobilization and started early wrist mobilization after volar locked plating of distal radius fracture, compared with patients who were immobilized for two weeks. The pain scores were similar but may have been influenced by the unbalanced use of opioids between the groups. The functional results and complication rates were not influenced by the use of immobilization. LEVEL OF EVIDENCE: Therapeutic Level I.


Assuntos
Analgésicos Opioides/uso terapêutico , Fixação Interna de Fraturas/métodos , Manejo da Dor/estatística & dados numéricos , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular/fisiologia , Articulação do Punho/fisiopatologia , Adulto , Idoso , Placas Ósseas , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Fraturas do Rádio/fisiopatologia , Fraturas do Rádio/reabilitação , Resultado do Tratamento
4.
Injury ; 48 Suppl 4: S2-S5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29145963

RESUMO

INTRODUCTION: According to Fraser's description, ipsilateral femoral and tibial diaphyseal fractures are characterised as type I floating knee and have a better prognosis than fractures with joint involvement (type II). There are few reports of functional and muscle strength in these patients. The objective of this study was to evaluate the functional and isokinetic muscle strength of patients with type I floating knee undergoing femoral and tibial internal fixation. METHODS: Patients with type I floating knee undergoing concomitant femoral and tibial internal fixation were invited for clinical evaluation. The parameters evaluated included the following: Karlstrom and Olerud score; Lysholm score; isokinetic thigh and hip muscle evaluation; knee range of motion; pain level; investigation of associated knee injuries by clinical evaluation and MRI; and types of complications. RESULTS: Twenty-one patients were included in the study; 11 of these were clinically evaluated, with a mean follow-up of 23.9 months. Six patients had an acceptable result according to the Karlstrom criteria, whereas eight patients had a poor result based on the Lysholm scale. The peak torque deficit was 61% for knee extensors, 37% for flexors and -9% for hip abductors. The mean pain level was 5.9. Three patients had a partial anterior cruciate ligament (ACL) injury; one patient had a posterior cruciate ligament (PCL) injury; and three patients had a meniscal injury. There were four cases of tibial or femoral nonunion at one year and two cases of chronic osteomyelitis. CONCLUSION: Patients with type I floating knee had unsatisfactory functional results, significant knee extensor and flexor muscle strength deficits and a significant rate of complications at the two-year follow-up.


Assuntos
Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas , Instabilidade Articular/cirurgia , Articulação do Joelho/fisiopatologia , Força Muscular/fisiologia , Fraturas da Tíbia/cirurgia , Adulto , Feminino , Fraturas do Fêmur/fisiopatologia , Fraturas do Fêmur/reabilitação , Seguimentos , Humanos , Instabilidade Articular/fisiopatologia , Instabilidade Articular/reabilitação , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos , Fraturas da Tíbia/fisiopatologia , Fraturas da Tíbia/radioterapia , Torque , Resultado do Tratamento , Adulto Jovem
5.
Acta Ortop Bras ; 25(2): 107-109, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28642662

RESUMO

OBJECTIVE: To evaluate the rate of deviation in the lateral radiographic incidence in patients with femoral neck fracture classified as non-diverted in the anteroposterior view (Garden I and II). METHODS: Nineteen selected patients with femoral neck fractures classified as Garden I and II were retrospectively evaluated, estimating the degree of deviation in the lateral view. RESULTS: Fifteen cases (79%) presented deviations in lateral view, with a mean of 18.6 degrees (±15.5). CONCLUSION: Most fractures of the femoral neck classified as Garden I and II present some degree of posterior deviation in the X-ray lateral view. Level of Evidence III, Retrospective Comparative Study.


OBJETIVO: Avaliar a taxa de desvio na incidência radiográfica lateral em pacientes com fratura do colo femoral classificadas como não desviadas na incidência anteroposterior (Garden I e II). MÉTODOS: foram avaliados retrospectivamente 19 pacientes selecionados com fraturas do colo do fêmur classificadas como Garden I e II, estimando-se o grau de desvio na incidência radiográfica lateral. RESULTADOS: Quinze casos (79%) apresentaram desvio no perfil, com média de 18,6 (± 15,5). CONCLUSÃO: A maioria das fraturas do colo femoral classificadas como Garden I e II apresenta algum grau de desvio posterior na incidência radiográfica lateral. Nível de Evidência III, Estudo Retrospectivo Comparativo .

6.
Acta ortop. bras ; 25(2): 107-109, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-837752

RESUMO

ABSTRACT Objective: To evaluate the rate of deviation in the lateral radiographic incidence in patients with femoral neck fracture classified as non-diverted in the anteroposterior view (Garden I and II). Methods: Nineteen selected patients with femoral neck fractures classified as Garden I and II were retrospectively evaluated, estimating the degree of deviation in the lateral view. Results: Fifteen cases (79%) presented deviations in lateral view, with a mean of 18.6 degrees (±15.5). Conclusion: Most fractures of the femoral neck classified as Garden I and II present some degree of posterior deviation in the X-ray lateral view. Level of Evidence III, Retrospective Comparative Study.


RESUMO Objetivo: Avaliar a taxa de desvio na incidência radiográfica lateral em pacientes com fratura do colo femoral classificadas como não desviadas na incidência anteroposterior (Garden I e II). Métodos: foram avaliados retrospectivamente 19 pacientes selecionados com fraturas do colo do fêmur classificadas como Garden I e II, estimando-se o grau de desvio na incidência radiográfica lateral. Resultados: Quinze casos (79%) apresentaram desvio no perfil, com média de 18,6 (± 15,5). Conclusão: A maioria das fraturas do colo femoral classificadas como Garden I e II apresenta algum grau de desvio posterior na incidência radiográfica lateral. Nível de Evidência III, Estudo Retrospectivo Comparativo .

7.
Drug Alcohol Depend ; 162: 199-205, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27036936

RESUMO

BACKGROUND: Earlier studies have already identified that a greater proportion of injured drivers are under the effects of illicit drugs than alcohol in Brazil, but the crash risk attributable to each substance is still unknown. METHODS: Injured motorcycle drivers who were involved in traffic accidents in the West Zone of the city of Sao Paulo were recruited for a cross-sectional study based on crash culpability analysis. Alcohol and drug positivity among drivers was evaluated according to their responsibility for the crash. Culpability ratios were generated based on the proportion of drivers who were deemed culpable in relation to those considered not culpable according to the use of drugs and alcohol. RESULTS: Of the 273 drivers recruited, 10.6% tested positive for alcohol. Among those who were also tested for drugs (n=232), 20.3% had consumed either alcohol and/or other drugs, 15.5% of whom were positive only for drugs other than alcohol, specifically cannabis and cocaine. Drivers who tested positive for alcohol were significantly less likely to possess a valid driver's license and to report driving professionally, whereas those who had consumed only drugs were more likely to drive professionally. The culpability ratio estimated for alcohol-positive drivers was three times higher than that for alcohol-free drivers, showing a superior ratio than drivers who had consumed only drugs other than alcohol, who presented a 1.7 times higher culpability ratio than drug-free drivers. CONCLUSION: Substance use was overrepresented among culpable motorcycle drivers, with alcohol showing a greater contribution to crash culpability than other drugs.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Consumo de Bebidas Alcoólicas/epidemiologia , Condução de Veículo/estatística & dados numéricos , Drogas Ilícitas/análise , Motocicletas , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Brasil/epidemiologia , Cannabis , Cocaína/análise , Estudos Transversais , Humanos , Drogas Ilícitas/efeitos adversos , Masculino , Transtornos Relacionados ao Uso de Substâncias
8.
PLoS One ; 7(1): e29086, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22242157

RESUMO

The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA) has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function.


Assuntos
Sensação/fisiologia , Vias Visuais/crescimento & desenvolvimento , Vias Visuais/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Neurônios GABAérgicos/metabolismo , Larva/citologia , Larva/metabolismo , Estimulação Luminosa , Retina/citologia , Retina/crescimento & desenvolvimento , Retina/metabolismo , Colículos Superiores/crescimento & desenvolvimento , Colículos Superiores/metabolismo , Vias Visuais/citologia , Xenopus laevis/crescimento & desenvolvimento , Xenopus laevis/metabolismo
9.
Rev. bras. ortop ; 46(supl.1): 9-12, 2011. ilus, tab
Artigo em Português | LILACS | ID: lil-596370

RESUMO

OBJETIVO: Apresentar os resultados de pesquisa Datafolha, realizada no período de 23 de setembro a 18 de outubro de 2010, sobre as condições existentes para o exercício profissional na área do trauma ortopédico no Brasil. MÉTODOS: pesquisa quantitativa, com abordagem telefônica dos entrevistados, por meio de sorteio aleatório de membros da Sociedade Brasileira de Ortopedia e Traumatologia, em cadastro contendo mais de 7.000 nomes. As entrevistas foram realizadas mediante aplicação de questionário estruturado, com aproximadamente 25 minutos de duração. RESULTADOS: 97 por cento dos entrevistados dedica parte do seu tempo ao trauma ortopédico. 87 por cento dos entrevistados exercem outra sub-especialidade, que não o trauma ortopédico. Na média dos atendimentos no país, 43 por cento dos pacientes pertencem à rede pública de saúde e 41 por cento pertencem à rede de convênios. O uso de implantes importados ocorre na minoria das situações (36 por cento) e 83 por cento dos médicos que utilizam ambos os tipos de implantes julga que os nacionais apresentam qualidade inferior. 61 por cento dos entrevistados julga a qualidade do atendimento em serviços públicos regular, ruim ou péssima. Metade dos entrevistados declara ter problemas para a liberação de suas solicitações de procedimentos junto aos planos de saúde em pelo menos 25 por cento das vezes em que encaminham tais pedidos. CONCLUSÃO: O trauma ortopédico é uma especialidade exercida pela grande maioria dos ortopedistas brasileiros. A estrutura dos serviços públicos é considerada insatisfatória pela maioria dos ortopedistas entrevistados. A maioria dos ortopedista deseja uma reformulação nos honorários médicos e na infra-estrutura de serviços.


OBJECTIVES: The aim of this article is to present the data collected by Datafolha institute, from September 23rd. through October 18th. 2010 about orthopedic trauma care in Brazil. METHOD: A quantitative analysis based on telephonic interviews has been performed. From Brazilian Orthopedic Society database containing more than 7000 records. A structured query has been applied and the interview lasted around 25 minutes. RESULTS: 97 percent of interviewees dedicate part of his/her time to orthopedic trauma. 87 percent of all interviewees dedicate his/her time to more than one sub-specialty. The majority of orthopedic trauma patients comes from government insurance system (43 percent), while 41 percent of patients come from private insurance. 61 percent of all interviewees think that the quality of public health system could be rated as unsatisfactory. Northeast of Brazil is the place where the majority of patients are from public health system and where we have highest rates of dissatisfaction (85 percent) related to available infrastructure for orthopedic trauma care. Half of all interviewed individuals have problems for getting private insurance authorization previously to a surgery. CONCLUSIONS: Orthopedic trauma is a specialty practiced by the vast majority of orthopedic surgeons in our country. Neither the infrastructure nor the salaries satisfy the majority or orthopedic surgeons dedicated to trauma care.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Serviços Médicos de Emergência , Avaliação de Eficácia-Efetividade de Intervenções , Primeiros Socorros , Traumatismo Múltiplo , Avaliação de Processos e Resultados em Cuidados de Saúde , Satisfação do Paciente , Ferimentos e Lesões , Pesquisa sobre Serviços de Saúde
11.
J Neurosci ; 29(15): 5032-43, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19369572

RESUMO

The emergence of dendritic arbor structure in vivo depends on synaptic inputs. We tested whether inhibitory GABAergic synaptic transmission regulates Xenopus optic tectal cell dendritic arbor development in vivo by expressing a peptide corresponding to an intracellular loop (ICL) of the gamma2 subunit of type A GABA receptors (GABA(A)R), which is required to anchor GABA(A) receptors to the postsynaptic scaffold. Enhanced green fluorescent protein (EGFP)-tagged ICL (EGFP-ICL) was distributed in a punctate pattern at putative inhibitory synapses, identified by vesicular GABA transporter immunoreactive puncta. ICL expression completely blocked GABA(A)R-mediated transmission in 36% of transfected neurons and significantly reduced GABA(A)R-mediated synaptic currents relative to AMPA receptor-mediated synaptic currents in the remaining transfected neurons without altering release probability or neuronal excitability. Further analysis of ICL-expressing neurons with residual GABA(A)R-mediated inputs showed that the capacity of benzodiazepine to enhance GABAergic synaptic responses was reduced in ICL-expressing neurons, indicating that they were likely depleted of gamma2 subunit-containing GABA(A)R. Neurons expressing a mutant form of ICL were comparable to controls. In vivo time-lapse images showed that ICL-expressing neurons have more sparsely branched dendritic arbors, which expand over larger neuropil areas than EGFP-expressing control neurons. Analysis of branch dynamics indicated that ICL expression affected arbor growth by reducing rates of branch addition. Furthermore, we found that decreasing GABAergic synaptic transmission with ICL expression blocked visual experience dependent dendritic arbor structural plasticity. Our findings establish an essential role for inhibitory GABAergic synaptic transmission in the regulation of dendritic structural plasticity in Xenopus in vivo.


Assuntos
Dendritos/fisiologia , Dendritos/ultraestrutura , Receptores de GABA-A/fisiologia , Transmissão Sináptica/fisiologia , Sequência de Aminoácidos , Animais , Larva/fisiologia , Camundongos , Dados de Sequência Molecular , Xenopus laevis
12.
J Cell Biol ; 172(3): 453-67, 2006 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16449195

RESUMO

Actin is the major cytoskeletal source of dendritic spines, which are highly specialized protuberances on the neuronal surface where excitatory synaptic transmission occurs (Harris, K.M., and S.B. Kater. 1994. Annu. Rev. Neurosci. 17:341-371; Yuste, R., and D.W. Tank. 1996. Neuron. 16:701-716). Stimulation of excitatory synapses induces changes in spine shape via localized rearrangements of the actin cytoskeleton (Matus, A. 2000. Science. 290:754-758; Nagerl, U.V., N. Eberhorn, S.B. Cambridge, and T. Bonhoeffer. 2004. Neuron. 44:759-767). However, what remains elusive are the precise molecular mechanisms by which different neurotransmitter receptors forward information to the underlying actin cytoskeleton. We show that in cultured hippocampal neurons as well as in whole brain synaptosomal fractions, RhoA associates with glutamate receptors (GluRs) at the spine plasma membrane. Activation of ionotropic GluRs leads to the detachment of RhoA from these receptors and its recruitment to metabotropic GluRs. Concomitantly, this triggers a local reduction of RhoA activity, which, in turn, inactivates downstream kinase RhoA-specific kinase, resulting in restricted actin instability and dendritic spine collapse. These data provide a direct mechanistic link between neurotransmitter receptor activity and the changes in spine shape that are thought to play a crucial role in synaptic strength.


Assuntos
Espinhas Dendríticas/fisiologia , Receptores de Glutamato/metabolismo , Proteína rhoA de Ligação ao GTP/fisiologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Actinas/metabolismo , Amidas/farmacologia , Animais , Proteínas de Transporte/metabolismo , Células Cultivadas , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Proteína 4 Homóloga a Disks-Large , Maleato de Dizocilpina/farmacologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/citologia , Hipocampo/embriologia , Peptídeos e Proteínas de Sinalização Intracelular/análise , Proteínas de Membrana/análise , Modelos Biológicos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Cloreto de Potássio/farmacologia , Profilinas/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Piridinas/farmacologia , Ratos , Receptores de AMPA/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Frações Subcelulares/química , Sinaptossomos/química , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/metabolismo
13.
Nature ; 436(7051): 704-8, 2005 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-16079847

RESUMO

Neuronal polarization occurs shortly after mitosis. In neurons differentiating in vitro, axon formation follows the segregation of growth-promoting activities to only one of the multiple neurites that form after mitosis. It is unresolved whether such spatial restriction makes use of an intrinsic program, like during C. elegans embryo polarization, or is extrinsic and cue-mediated, as in migratory cells. Here we show that in hippocampal neurons in vitro, the axon consistently arises from the neurite that develops first after mitosis. Centrosomes, the Golgi apparatus and endosomes cluster together close to the area where the first neurite will form, which is in turn opposite from the plane of the last mitotic division. We show that the polarized activities of these organelles are necessary and sufficient for neuronal polarization: (1) polarized microtubule polymerization and membrane transport precedes first neurite formation, (2) neurons with more than one centrosome sprout more than one axon and (3) suppression of centrosome-mediated functions precludes polarization. We conclude that asymmetric centrosome-mediated dynamics in the early post-mitotic stage instruct neuronal polarity, implying that pre-mitotic mechanisms with a role in division orientation may in turn participate in this event.


Assuntos
Polaridade Celular , Centrossomo/metabolismo , Neurônios/citologia , Animais , Axônios/metabolismo , Transporte Biológico , Diferenciação Celular , Movimento Celular , Células Cultivadas , Sinais (Psicologia) , Endossomos/metabolismo , Complexo de Golgi/metabolismo , Hipocampo/citologia , Microtúbulos/metabolismo , Mitose , Neuritos/metabolismo , Ratos
14.
Nat Neurosci ; 8(5): 606-15, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15834419

RESUMO

Axon specification triggers the polarization of neurons and requires the localized destabilization of filamentous actin. Here we show that plasma membrane ganglioside sialidase (PMGS) asymmetrically accumulates at the tip of one neurite of the unpolarized rat neuron, inducing actin instability. Suppressing PMGS activity blocks axonal generation, whereas stimulating it accelerates the formation of a single (not several) axon. PMGS induces axon specification by enhancing TrkA activity locally, which triggers phosphatidylinositol-3-kinase (PI3K)- and Rac1-dependent inhibition of RhoA signaling and the consequent actin depolymerization in one neurite only. Thus, spatial restriction of an actin-regulating molecular machinery, in this case a membrane enzymatic activity, before polarization is enough to determine axonal fate.


Assuntos
Diferenciação Celular/fisiologia , Polaridade Celular/fisiologia , Sistema Nervoso Central/embriologia , Dendritos/metabolismo , Cones de Crescimento/metabolismo , Neuraminidase/metabolismo , Actinas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Células Cultivadas , Sistema Nervoso Central/citologia , Sistema Nervoso Central/metabolismo , Dendritos/efeitos dos fármacos , Dendritos/ultraestrutura , Inibidores Enzimáticos/farmacologia , Cones de Crescimento/efeitos dos fármacos , Cones de Crescimento/ultraestrutura , Neuraminidase/antagonistas & inibidores , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neuritos/ultraestrutura , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Receptor trkA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
15.
Nat Cell Biol ; 5(12): 1071-8, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14595335

RESUMO

The actin cytoskeleton is best known for its role during cellular morphogenesis. However, other evidence suggests that actin is also crucial for the organization and dynamics of membrane organelles such as endosomes and the Golgi complex. As in morphogenesis, the Rho family of small GTPases are key mediators of organelle actin-driven events, although it is unclear how these ubiquitously distributed proteins are activated to regulate actin dynamics in an organelle-specific manner. Here we show that the brain-specific Rho-binding protein Citron-N is enriched at, and associates with, the Golgi apparatus of hippocampal neurons in culture. Suppression of the whole protein or expression of a mutant form lacking the Rho-binding activity results in dispersion of the Golgi apparatus. In contrast, high intracellular levels induce localized accumulation of RhoA and filamentous actin, protecting the Golgi from the rupture normally produced by actin depolymerization. Biochemical and functional analyses indicate that Citron-N controls actin locally by assembling together the Rho effector ROCK-II and the actin-binding, neuron-specific, protein Profilin-IIa (PIIa). Together with recent data on endosomal dynamics, our results highlight the importance of organelle-specific Rho modulators for actin-dependent organelle organization and dynamics.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas de Ciclo Celular , Diferenciação Celular/fisiologia , Proteínas Contráteis , Complexo de Golgi/metabolismo , Neurônios/metabolismo , Proteínas/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Actinas/metabolismo , Animais , Sítios de Ligação/genética , Células Cultivadas , Feto , Hipocampo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas dos Microfilamentos/metabolismo , Neurônios/ultraestrutura , Profilinas , Ligação Proteica/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas/genética , Ratos , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP/metabolismo
17.
J Cell Biol ; 162(7): 1267-79, 2003 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-14517206

RESUMO

Neuritogenesis, the first step of neuronal differentiation, takes place as nascent neurites bud from the immediate postmitotic neuronal soma. Little is known about the mechanisms underlying the dramatic morphological changes that characterize this event. Here, we show that RhoA activity plays a decisive role during neuritogenesis of cultured hippocampal neurons by recruiting and activating its specific kinase ROCK, which, in turn, complexes with profilin IIa. We establish that this previously uncharacterized brain-specific actin-binding protein controls neurite sprouting by modifying actin stability, a function regulated by ROCK-mediated phosphorylation. Furthermore, we determine that this novel cascade is switched on or off by physiological stimuli. We propose that RhoA/ROCK/PIIa-mediated regulation of actin stability, shown to be essential for neuritogenesis, may constitute a central mechanism throughout neuronal differentiation.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas Contráteis , Proteínas dos Microfilamentos/metabolismo , Neurônios/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Tamanho Celular/fisiologia , Células Cultivadas , Hipocampo/citologia , Peptídeos e Proteínas de Sinalização Intracelular , Fatores de Crescimento Neural/farmacologia , Neuritos/enzimologia , Neurônios/ultraestrutura , Profilinas , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Estimulação Química , Quinases Associadas a rho
18.
Brain Res ; 987(1): 107-16, 2003 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-14499952

RESUMO

Sorting of certain membrane proteins requires a mechanism involving rafts, protein-lipid complexes enriched in glycosphingolipids and cholesterol. These microdomains remain at the plasma membrane of different cell types and play a role in signal transduction. Although recent reports have begun to describe molecules associated with rafts, their protein composition remains largely unknown, especially in neuronal cells. To address this question, we have purified detergent-insoluble raft fractions (DRMs) from primary cultures of hippocampal neurons. Bidimensional gel analysis and pharmacological raft lipid manipulation allowed the identification of neuronal raft proteins and their characterisation by MALDI-TOF analysis. Enolases were found among the proteins identified and functional studies demonstrate their participation in plasminogen binding. We also show the specific enrichment in rafts of several other plasminogen binding molecules and the exclusive activation of plasminogen to the protease plasmin in these microdomains. These observations suggest that neuronal rafts may play, in addition to intracellular signaling, a role in extracellular/membrane protein proteolysis.


Assuntos
Microdomínios da Membrana/química , Proteínas de Membrana/isolamento & purificação , Neurônios/química , Plasminogênio/metabolismo , Animais , Western Blotting , Técnicas de Cultura de Células , Colesterol/metabolismo , Imunofluorescência , Microdomínios da Membrana/metabolismo , Neurônios/metabolismo , Ratos , Esfingolipídeos/metabolismo
19.
Nat Rev Neurosci ; 3(9): 694-704, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12209118

RESUMO

The sprouting of neurites, which will later become axons and dendrites, is an important event in early neuronal differentiation. Studies in living neurons indicate that neuritogenesis begins immediately after neuronal commitment, with the activation of membrane receptors by extracellular cues. These receptors activate intracellular cascades that trigger changes in the actin cytoskeleton, which promote the initial breakdown of symmetry. Then, through the regulation of gene transcription, and of microtubule and membrane dynamics, the newly formed neurite becomes stabilized. A key challenge is to define the molecular machinery that regulates the actin cytoskeleton during initial neurite sprouting. We propose that analysing the molecules involved in actin-dependent mechanisms in non-neuronal systems, such as budding yeast and migrating fibroblasts, could help to uncover the secrets of neuritogenesis.


Assuntos
Actinas/metabolismo , Diferenciação Celular/fisiologia , Membrana Celular/metabolismo , Sistema Nervoso Central/embriologia , Citoesqueleto/metabolismo , Neuritos/metabolismo , Receptores de Superfície Celular/metabolismo , Actinas/ultraestrutura , Animais , Membrana Celular/ultraestrutura , Movimento Celular/fisiologia , Sistema Nervoso Central/citologia , Sistema Nervoso Central/metabolismo , Citoesqueleto/ultraestrutura , Humanos , Neuritos/ultraestrutura , Transdução de Sinais/fisiologia , Proteínas rho de Ligação ao GTP/metabolismo
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