“Barnabé e sua aventura”: um projeto de educação para a saúde em disfonia infantil

"Os nódulos vocais, associados etiologicamente a um comportamento disfuncional de mau uso e abuso vocal, são os principais responsáveis pela disfonia crônica em crianças de ambos os gêneros. A disfonia infantil pode influenciar a sedimentação das relações sociais da criança disfônica e conduzir a processos de estigmatização e constrangimento por parte de seus pares. O presente instrumento de Educação para a Saúde tem como principal objetivo consciencializar a criança disfônica para o uso correto da sua voz, diminuindo o impacto biopsicossocial inerente à patologia vocal. Este instrumento, destinado essencialmente a crianças de ambos os sexos entre os sete e os nove anos de idade, e simultaneamente aos seus pais e professores/educadores de infância, consiste num livro de literatura infantil que aborda a problemática da voz e da patologia nodular infantil, tendo sido concretizado em dois formatos: impresso em formato A5 e em formato digital, com narração áudio incluída. O instrumento elaborado, ideal para a população-alvo pré-definida, consiste num excelente veículo de consciencialização da importância da voz e da promoção de hábitos vocais salutogênicos, podendo ser usado em diversos contextos de vida da criança (terapêutico, familiar e escolar)."

Utilização de murganhos no estudo de novos alvos da terapia oncológica anti-angiogénica

Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas

Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice

AIMS: Cognitive decline in Alzheimer's disease (AD) patients has been linked to synaptic damage and neuronal loss. Hyperphosphorylation of tau protein destabilizes microtubules leading to the accumulation of autophagy/vesicular material and the generation of dystrophic neurites, thus contributing to axonal/synaptic dysfunction. In this study, we analyzed the effect of a microtubule-stabilizing compound in the progression of the disease in the hippocampus of APP751SL/PS1M146L transgenic model. METHODS: APP/PS1 mice (3 month-old) were treated with a weekly intraperitoneal injection of 2 mg/kg epothilone-D (Epo-D) for 3 months. Vehicle-injected animals were used as controls. Mice were tested on the Morris water maze, Y-maze and object-recognition tasks for memory performance. Abeta, AT8, ubiquitin and synaptic markers levels were analyzed by Western-blots. Hippocampal plaque, synaptic and dystrophic loadings were quantified by image analysis after immunohistochemical stainings. RESULTS: Epo-D treated mice exhibited a significant improvement in the memory tests compared to controls. The rescue of cognitive deficits was associated to a significant reduction in the AD-like hippocampal pathology. Levels of Abeta, APP and ubiquitin were significantly reduced in treated animals. This was paralleled by a decrease in the amyloid burden, and more importantly, in the plaque-associated axonal dystrophy pathology. Finally, synaptic levels were significantly restored in treated animals compared to controls. CONCLUSION: Epo-D treatment promotes synaptic and spatial memory recovery, reduces the accumulation of extracellular Abeta and the associated neuritic pathology in the hippocampus of APP/PS1 model. Therefore, microtubule stabilizing drugs could be considered therapeutical candidates to slow down AD progression. Supported by FIS-PI12/01431 and PI15/00796 (AG),FIS-PI12/01439 and PI15/00957(JV)

Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei

The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases

Clínica de animais de companhia

O presente relatório apresenta as atividades desenvolvidas no estágio decorrido no Hospital Ars Veterinaria. A primeira parte do relatório refere-se ao relatório de casuística com apresentação de casos e procedimentos acompanhados. A segunda refere-se à monografia com o tema “Opções terapêuticas em hemangiossarcoma canino” e encontra-se ilustrada por três casos clínicos. O hemangiossarcoma é uma neoplasia descrita com origem endotelial, devido à aparência histológica, no entanto descobertas recentes sugerem que provém de células progenitoras hematopoiéticas. Os sinais clínicos são inespecíficos e variáveis. A localização mais comum é o baço, embora ocorra noutras localizações. O diagnóstico requer o estadiamento tumoral e para ser completo deve incluir hematologia e bioquímica sérica, provas de coagulação, exames imagiológicos e confirmação histopatológica. O tratamento base é cirúrgico associado a protocolos quimioterápicos baseados em doxorrubicina. Novas terapias começam a ser investigadas de forma a melhorar os tempos de sobrevivência desta neoplasia de prognóstico reservado; Abstract: Small animal medicine This report was elaborated following a traineeship at the Ars Veterinaria Hospital. The first part concerns about cases report and includes presentation of cases and followed procedures. The second part is the monography under the theme “therapeutical options in canine hemangiosarcoma” and it presents three clinical cases seen during the internship. The hemangiossarcoma is a cancer described to have endothelial origin, because of its histological appearance, but recent discoveries suggest that it originates from hematopoietic progenitor cells. The clinical signs are variable and unspecific. The most common location is the spleen, but others might exist. The diagnosis demands tumoral staging, which to be complete must include hematology and biochemical analysis, coagulation tests, imagiologic tests and histopathologic confirmation. The basic treatment is surgical, associated with chemotherapy based on doxorubicin. New therapies are beginning to be investigated, aiming improve survival times of this cancer with reserved prognosis.

Obstructive sleep apneas naturally occur in mice during REM sleep and are more prevalent in a mouse model of Down syndrome

Study Objectives. The use of mouse models in sleep apnea research is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. With this study we wanted to develop a protocol to look for the presence of OSAs in wild-type mice and, then, to apply it to a mouse model of Down Syndrome (DS), a human pathology characterized by a high incidence of OSAs. Methods. Nine C57Bl/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), diaphragmatic activity (DIA) and then placed in a whole-body-plethysmographic (WBP) chamber for 8h during the resting (light) phase to simultaneously record sleep and breathing activity. The concomitant analysis of WBP and DIA signals allowed the discrimination between CSA and OSA. The same protocol was then applied to 12 Ts65Dn mice (a validated model of DS) and 14 euploid controls. Results. OSAs represented about half of the apneic events recorded during rapid-eye-movement sleep (REMS) in each experimental group while almost only CSAs were found during non-REMS. Ts65Dn mice had similar rate of apneic events than euploid controls but a significantly higher occurrence of OSAs during REMS. Conclusions. We demonstrated for the first time that mice physiologically exhibit both CSAs and OSAs and that the latter are more prevalent in the Ts65Dn mouse model of DS. These findings indicate that mice can be used as a valid tool to accelerate the comprehension of the pathophysiology of all kind of sleep apnea and for the development of new therapeutical approaches to contrast these respiratory disorders.

Longitudinal Micro CT-driven biomarkers as a tool to evaluate lung fibrosis progression and antifibrotic efficacy in a refined Bleomycin mouse model

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with no curative pharmacological treatment. Animal models play an essential role in revealing molecular mechanisms involved in the pathogenesis of the disease. Bleomycin (BLM)-induced lung fibrosis is the most widely used and characterized model for anti-fibrotic drugs screening. However, several issues have been reported, such as the identification of an optimal BLM dose and administration scheme as well as gender-specificity. Moreover, the balance between disease resolution, an appropriate time window for therapeutic intervention and animal welfare remains critical aspects yet to be fully elucidated. In this thesis, Micro CT imaging has been used as a tool to identify the ideal BLM dose regimen to induce sustained lung fibrosis in mice as well as to assess the anti-fibrotic effect of Nintedanib (NINT) treatment upon this BLM administration regimen. In order to select the optimal BLM dose scheme, C57bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA), following either double or triple BLM administration. The triple BLM administration resulted in the most promising scheme, able to balance disease resolution, appropriate time-window for therapeutic intervention and animal welfare. The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 5 weeks after BLM administration and 5 animals were sacrificed at each timepoint for the BALF and histological evaluation. The antifibrotic effect of NINT was assessed following different treatment regimens in this model. Herein, we have developed an optimized mouse model of pulmonary fibrosis, enabling three weeks of the therapeutic window to screen putative anti-fibrotic drugs. micro-CT scanning, allowed us to monitor the progression of lung fibrosis and the therapeutical response longitudinally in the same subject, drastically reducing the number of animals involved in the experiment.