Browsing by Author "Rosa, J"
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- Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF SignallingPublication . Miranda-Lourenço, C; Duarte, ST; Palminha, C; Gaspar, C; Rodrigues, TM; Magalhães-Cardoso, T; Rei, N; Colino-Oliveira, M; Gomes, R; Ferreira, S; Rosa, J; Xapelli, S; Armstrong, J; García-Cazorla, A; Correia-de-Sá, P; Sebastião, AM; Diógenes, MJRett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.
- Nariz. Subunidades e Pontos de ReferênciaPublication . Goulão, J; Ponte, P; Rosa, JA cirurgia tumoral com localização no nariz é muito frequente, pelo que nos deparamos muitas vezes com a necessidade de intervir nesta estrutura. Em muitos casos há necessidade de excisar mais que um tumor na mesma subunidade anatómica e há zonas de alto risco de progressão local, como a columela, junção nasolabial, junção nasocantal interna e junção nasofacial. Daqui advém a importância de uma boa identificação das zonas anatómicas do nariz. Torna-se assim necessário procurar uniformizar a terminologia dos vários pontos do nariz, para que as lesões sejam correctamente identificadas no que respeita à sua localização.
- Radix Nasi Transposition Flap for Medial Canthus and Nasal Sidewall DefectsPublication . Carvalho, R; Casal, D; Zagalo, C; Rosa, J
- Retalho em Ilha com Pedículo Lateral. Um Refinamento da Técnica TradicionalPublication . Trindade, F; Rosa, JOs retalhos em ilha são uma boa opção a ter em conta quando se pretende reparar um defeito da pálpebra ou da região periorbitária. Podem ser executados segundo o método original, com pedículo subdérmico (central e inferior), com deslizamento limitado. No entanto, se o pedículo for lateral, obtém-se maior mobilidade do retalho, tornando-se muito útil para reparações na face. Apresentam-se 3 casos clínicos de doentes com tumores localizados nas pálpebras e região periorbitária, nos quais foram efectuados retalhos em ilha com pedículo lateral, com resultados funcionais e cosméticos muito aceitáveis.
- Retalho Triangular de Avanço Geniano para Reconstrução de Defeitos Cirúrgicos da Parede Lateral do NarizPublication . Goulão, J; Ponte, P; Rosa, JA reconstrução de defeitos cirúrgicos do nariz constitui sempre um desafio para o cirurgião. Os autores descrevem, com alguns casos ilustrativos, um retalho de avanço muito útil na reconstrução de médicos e grandes defeitos da parede lateral do nariz.
- Upper Eyelid Reconstruction With a Horizontal V-Y Myotarsocutaneous Advancement FlapPublication . Rosa, J; Casal, D; Moniz, PUpper eyelid tumours, particularly basal cell carcinomas, are relatively frequent. Surgical ablation of these lesions creates defects of variable complexity. Although several options are available for lower eyelid reconstruction, fewer surgical alternatives exist for upper eyelid reconstruction. Large defects of this region are usually reconstructed with two-step procedures. In 1997, Okada et al. described a horizontal V-Y myotarsocutaneous advancement flap for reconstruction of a large upper eyelid defect in a single operative time. However, no further studies were published regarding the use of this particular flap in upper eyelid reconstruction. In addition, this flap is not described in most plastic surgery textbooks. The authors report here their experience of 16 cases of horizontal V-Y myotarsocutaneous advancement flaps used to reconstruct full-thickness defects of the upper eyelid after tumour excision. The tumour histological types were as follows: 12 basal cell carcinomas, 2 cases of squamous cell carcinomas, 1 case of sebaceous cell carcinoma and 1 of malignant melanoma. This technique allowed closure of defects of up to 60% of the eyelid width. None of the flaps suffered necrosis. The mean operative time was 30 min. No additional procedures were necessary as good functional and cosmetic results were achieved in all cases. No recurrences were noted. In this series, the horizontal V-Y myotarsocutaneous advancement flap proved to be a technically simple, reliable and expeditious option for reconstruction of full-thickness upper eyelid defects (as wide as 60% of the eyelid width) in a single operative procedure. In the future this technique may become the preferential option for such defects.