Browsing by Author "Sousa, N."
Now showing 1 - 4 of 4
Results Per Page
Sort Options
- Anafilaxia induzida por fármacos: Registo Nacional 2007-2010Publication . Faria, E.; Rodrigues-Cernadas, J.; Gaspar, A.; Botelho, C.; Castro, E.; Lopes, A.; Gomes, E.; Malheiro, D.; Cadinha, S.; Campina-Costa, S.; Neto, M.; Sousa, N.; Rodrigues-Alves, R.; Romeira, A.; Caiado, J.; Morais-Almeida, M.Introdução: A anafilaxia a fármacos constitui uma situação potencialmente fatal e imprevisível, desconhecendo-se a real prevalência em diferentes grupos populacionais e os factores de risco relacionados.Objectivo: Contribuir para o melhor conhecimento epidemiológico da anafilaxia induzida por fármacos no nosso país. Métodos: Durante um período de 4 anos (Janeiro de 2007 a Dezembro de 2010) foi implementado um sistema de notificação nacional de anafilaxia, focalizado na notificação voluntária por clínicos com diferenciação em patologia imunoalérgica. Foram recebidas e analisadas notificações de anafilaxia a fármacos de 313 doentes. No estudo estatístico foram aplicados testes de distribuição e análise de regressão logística múltipla para obter significância e coeficientes de regressão e efeitos marginais. Resultados: A média de idade foi de 43,8 ±17,4 anos, sendo 8% de idade inferior a 18 anos. A relação género feminino/masculino foi de 2/1. A média de idade do primeiro episódio foi de 39 ±18,2 anos. Nove doentes apresentaram mais que uma causa de anafilaxia, correspondendo a um total de 322 notificações de grupos de fármacos envolvidos. As principais causas da anafilaxia a fármacos foram os anti-inflamatórios não esteróides (AINEs), os antibióticos e os agentes anestésicos, com respectivamente 48%, 36% e 6% dos casos. Outros fármacos implicados foram citostáticos, corticosteróides, inibidores da bomba de protões e meios de contraste iodados, entre outros. Houve predomínio de manifestações mucocutâneas (92%), seguido de respiratórias (81%) e de cardiovasculares (49%). Os doentes com anafilaxia a AINEs apresentaram aumento significativo da associação de manifestações mucocutâneas e respiratórias. Não foram observadas diferenças significativas em idade, género ou antecedentes de atopia entre os diferentes grupos de fármacos envolvidos. As reacções ocorreram em ambiente hospitalar em 45% dos casos. Em 53% nos 15 minutos após a administração do fármaco e 35% motivaram internamento. A recorrência da anafilaxia foi observada em 26% e o risco foi significativamente mais elevado nos casos de anafilaxia a AINEs. Apenas 48% dos doentes receberam tratamento com adrenalina e somente em 9% dos casos foi prescrito dispositivo para auto-administração de adrenalina. Conclusões: Neste estudo os AINEs foram os fármacos mais frequentes e os mais associados a recorrência de anafilaxia. Destaca -se o sub-tratamento com adrenalina e a necessidade de serem tomadas medidas no sentido do tratamento eficaz e da prevenção da recorrência de anafilaxia a fármacos.
- Morphological correlates of corticosteroid-induced changes in prefrontal cortex-dependent behaviorsPublication . Cerqueira, J.; Pêgo, J.; Taipa, R.; Bessa, J.; Almeida, O.; Sousa, N.Imbalances in the corticosteroid milieu have been implicated in several neuropsychiatric disorders, including depression and schizophrenia. Prefrontal cortex (PFC) dysfunction is also a hallmark of these conditions, causing impairments in executive functions such as behavioral flexibility and working memory. Recent studies have suggested that the PFC might be influenced by corticosteroids released during stress. To test this possibility, we assessed spatial working memory and behavioral flexibility in rats submitted to chronic adrenalectomy or treatment with corticosterone (25 mg/kg) or the synthetic glucocorticoid dexamethasone (300 g/kg); the behavioral analysis was complemented by stereological evaluation of the PFC (prelimbic, infralimbic, and anterior cingulate regions), the adjacent retrosplenial and motor cortices, and the hippocampal formation. Dexamethasone treatment resulted in a pronounced impairment in working memory and behavioral flexibility, effects that correlated with neuronal loss and atrophy of layer II of the infralimbic, prelimbic, and cingulate cortices. Exposure to corticosterone produced milder impairments in behavioral flexibility, but not in working memory, and reduced the volume of layer II of all prefrontal areas. Interestingly, adrenalectomy-induced deleterious effects only became apparent on the reverse learning task and were not associated with structural alterations in the PFC. None of the experimental procedures influenced the morphology of retrosplenial or motor cortices, but stereological measurements confirmed previously observed effects of corticosteroids on hippocampal structure. Our results describe, for the first time, that imbalances in the corticosteroid environment can induce degeneration of specific layers of the PFC; these changes appear to be the morphological correlate of corticosteroid-induced impairment of PFC-dependent behavior(s)
- Specific configuration of dendritic degeneration in pyramidal neurons of the medial prefrontal cortex induced by differing corticosteroid regimensPublication . Cerqueira, J.; Taipa, R.; Uylings, R.; Osborne, F.; Almeida, F.; Sousa, N.We previously demonstrated that hypercorticalism induces pronounced volumetric reductions in the rat medial prefrontal cortex (mPFC) and that these structural changes correlate with deficits in executive function. By applying 3-dimensional analysis of Golgi- Cox--stained material, we now demonstrate that corticosteroids can exert differential effects on dendritic arborizations of pyramidal neurons in lamina II/III of the mPFC. Treatment with the glucocorticoid receptor--selective agonist dexamethasone and with the natural adrenosteroid, corticosterone (CORT), results in significant reductions in the total length of apical dendrites in the pyramidal neurons in lamina II/III of the anterior cingulate/prelimbic and infralimbic cortices. Interestingly, although these treatments do not affect the number of dendritic branches, they are associated with impoverished arborizations in their distal portions and, in CORTtreated animals, with increased branching in the middle portions of the apical dendritic tree. Deprivation of corticosteroids by adrenalectomy leads to decreases in total apical dendritic length and spine number, but in this case, dendritic impoverishment was restricted to the middle/proximal segments of the dendritic trees. None of the treatments influenced the architecture of the basal dendrites. These results add to our knowledge of the morphological substrates through which corticosteroids may disrupt mPFC-dependent behaviors.
- WNT6 is a novel oncogenic prognostic biomarker in human glioblastomaPublication . Gonçalves, C.; Vieira de Castro, J.; Pojo, M.; Martins, E.; Queirós, S.; Chautard, E.; Taipa, Ricardo; Pires, M.; Pinto, A.; Pardal, F.; Custódia, C.; Faria, C.; Clara, C.; Reis, R.; Sousa, N.; Costa, B.Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. Methods: WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects in vitro and in vivo. Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect. Results: We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typical oncogenic activities in GBM cells, including viability, proliferation, glioma stem cell capacity, invasion, migration, and resistance to temozolomide chemotherapy. Concordantly, in in vivo orthotopic GBM mice models, using both overexpressing and silencing models, WNT6 expression was associated with shorter overall survival, and increased features of tumor aggressiveness. Mechanistically, WNT6 contributes to activate typical oncogenic pathways, including Src and STAT, which intertwined with the WNT pathway may be critical effectors of WNT6-associated aggressiveness in GBM. Clinically, we establish WNT6 as an independent prognostic biomarker of shorter survival in GBM patients from several independent cohorts. Conclusion: Our findings establish WNT6 as a novel oncogene in GBM, opening opportunities to develop more rational therapies to treat this highly aggressive tumor.