Browsing by Author "Alves, J."
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- Group B Streptococcus Hijacks the Host Plasminogen System to Promote Brain Endothelial Cell InvasionPublication . Magalhães, V.; Andrade, E.; Alves, J.; Ribeiro, A:; Kim, K.; Lima, M.; Trieu-Cuot, P.; Ferreira, P.Group B Streptococcus (GBS) is the leading cause of meningitis in neonates. We have previously shown that plasminogen, once recruited to the GBS cell surface and converted into plasmin by host-derived activators, leads to an enhancement of bacterial virulence. Here, we investigated whether plasmin(ogen) bound at the GBS surface contributes to blood-brain barrier penetration and invasion of the central nervous system. For that purpose, GBS strain NEM316 preincubated with or without plasminogen plus tissue type plasminogen activator was analyzed for the capacity to adhere to, invade and transmigrate the human brain microvascular endothelial cell (hBMEC) monolayer, and to penetrate the central nervous system using a neonatal mouse model. At earlier times of infection, plasmin(ogen)-treated GBS exhibited a significant increase in adherence to and invasion of hBMECs. Later, injury of hBMECs were observed with plasmin(ogen)-treated GBS that displayed a plasmin-like activity. The same results were obtained when hBMECs were incubated with whole human plasma and infected with untreated GBS. To confirm that the observed effects were due to the recruitment and activation of plasminogen on GBS surface, the bacteria were first incubated with epsilon-aminocaproic acid (εACA), an inhibitor of plasminogen binding, and thereafter with plasmin(ogen). A significant decrease in the hBMECs injury that was correlated with a decrease of the GBS surface proteolytic activity was observed. Furthermore, plasmin(ogen)-treated GBS infected more efficiently the brain of neonatal mice than the untreated bacteria, indicating that plasmin(ogen) bound to GBS surface may facilitate the traversal of the blood-brain barrier. A higher survival rate was observed in offspring born from εACA-treated mothers, compared to untreated mice, and no brain infection was detected in these neonates. Our findings suggest that capture of the host plasmin(ogen) by the GBS surface promotes the crossing of the blood-brain barrier and contributes to the establishment of meningitis.
- Mechanical thrombectomy in patients with acute basilar occlusion using stent retrieversPublication . Carneiro, A.; Rodrigues, J.; Pereira, J.; Alves, J.; Xavier, J.Early arterial recanalisation with stent retrievers (SR) has been recently demonstrated to improve clinical outcome of patients with large-vessel occlusion of the anterior circulation. However, the benefit of SR thrombectomy in the setting of acute basilar artery occlusion (BAO) has not been proven yet. This study evaluated a series of consecutive patients with BAO treated with SR, focusing on the efficacy, safety and clinical results.
- Recomendações para o Diagnóstico da Forma Tardia da Doença de PompePublication . Brito-Avô, L.; Alves, J.; Costa, J.; Valverde, A.; Santos, L.; Araújo, F.; Marinho, A.; Oliveira, A.; Gomes, D.INTRODUCTION: Pompe disease is a progressive and debilitating autossomal recessive myopathy due to mutations in lysossomal acid-α-glucosidase. Its late-onset form has a heterogeneous presentation mimicking other neuromuscular diseases, leading to diagnostic challenge. OBJECTIVE: To develop consensus based recommendations for the diagnosis of late-onset Pompe Disease. MATERIAL AND METHODS: Bibliographic review and analysis of an opinion questionnaire applied to a group of specialists with expertise in the diagnosis of several myopathies and lysossomal storage disorders. Discussed in consensus meeting. RECOMMENDATIONS: Patients with a progressive limb-girdle weakness, fatigue, cramps and muscle pain should be evaluated with CK levels, electromyography, dynamic spirometry and muscle biopsy in inconclusive cases. Suspected cases and those in which muscle biopsy could not allow other diagnosis should be screened for lysossomal acid-α-glucosidase deficiency with DBS (dried blood spot). The diagnosis should be confirmed by determination of lysossomal acid-α-glucosidase activity in a second sample and lysossomal acid-α-glucosidase gene sequencing.
- Reliability of CT perfusion in the evaluation of the ischaemic penumbraPublication . Alves, J.; Carneiro, A.; Xavier, J.CT perfusion (CTP) is part of the initial evaluation of stroke patients, allowing differentiation between infarcted tissue and the ischaemic penumbra and helping in the selection of patients for endovascular treatment. This study assessed the reliability of the qualitative evaluation CTP maps in defining the ischemic penumbra and identified potential pitfalls associated with this technique. We reviewed CTP scans of 45 consecutive patients admitted to our institution with anterior circulation acute ischaemic stroke. Two neuroradiologists performed qualitative evaluations of cerebral blood volume (CBV) and mean transit time (MTT) maps, using 24h follow-up non-contrast CT as surrogate marker for the area of definitive infarct. For each slice analyzed, the area of qualitative alteration in the CBV and MTT maps was classified as either being inferior, equal or superior to the area of infarct on the follow-up CT. Three out of 45 (7%) patients had admission CT CBV abnormalities larger than follow-up lesions; 34/45 (76%) patients had infarct areas smaller than initial MTT prolongation. In the group of patients with no recanalization 12/19 (63%) had infarct areas smaller than initial MTT lesion. CBV abnormality is a reliable marker for an irreversible ischaemic lesion, although rarely it may overestimate the ischaemic "core", possibly due to delay in contrast arrival to the brain. In the majority of patients without recanalization, MTT overestimated final infarct areas, probably because it does not differentiate true "at risk" penumbra from benign oligaemia. Qualitative evaluation of CBV and MTT maps may overestimate the real ischaemic penumbra.
- Response to letter to the editor. "CT angiography source-images and CT perfusion: are they complementary tools for ischemic stroke evaluation?"Publication . Alves, J.; Carneiro, A.; Xavier, J.