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Pinheiro-Silva R.,Institute Higiene e Medicina Tropical IHMT | Borges L.,Institute Higiene e Medicina Tropical IHMT | Borges L.,Institute of Tropical Medicine | Coelho L.P.,Institute Medicina Molecular IMM | And 8 more authors.
Parasites and Vectors

Background: Malaria is a devastating infectious disease caused by Plasmodium parasites transmitted through the bites of infected Anopheles mosquitoes. Salivary glands are the only mosquito tissue invaded by Plasmodium sporozoites, being a key stage for the effective parasite transmission, making the study of Anopheles sialome highly relevant. Methods: RNA-sequencing was used to compare differential gene expression in salivary glands of uninfected and Plasmodium berghei-infected Anopheles coluzzii mosquitoes. RNA-seq results were validated by quantitative RT-PCR. The transmembrane glucose transporter gene AGAP007752 was selected for functional analysis by RNA interference. The effect of gene silencing on infection level was evaluated. The putative function and tertiary structure of the protein was assessed. Results: RNA-seq data showed that 2588 genes were differentially expressed in mosquitoes salivary glands in response to P. berghei infection, being 1578 upregulated and 1010 downregulated. Metabolism, Immunity, Replication/Transcription/Translation, Proteolysis and Transport were the mosquito gene functional classes more affected by parasite infection. Endopeptidase coding genes were the most abundant within the differentially expressed genes in infected salivary glands (P∈<∈0.001). Based on its putative function and expression level, the transmembrane glucose transporter gene, AGAP007752, was selected for functional analysis by RNA interference. The results demonstrated that the number of sporozoites was 44.3 % lower in mosquitoes fed on infected mice after AGAPP007752 gene knockdown when compared to control (P∈<∈0.01). Conclusions: Our hypothesis is that the protein encoded by the gene AGAPP007752 may play a role on An. coluzzii salivary glands infection by Plasmodium parasite, working as a sporozoite receptor and/or promoting a favorable environment for the capacity of sporozoites. © 2015 Pinheiro-Silva et al. Source

Gil-Gouveia R.,Institute Medicina Molecular IMM | Gil-Gouveia R.,Headache Center
European Neurology

Background: General practitioners (GPs) and neurologists are involved in treating headache patients in Portugal. Having migraine themselves might influence the way they perceive and treat migraine patients. Objective: To identify clinicians' perceptions about migraine, their own headache status and management of their own migraine. Methods: An observational cross-sectional survey of GPs and neurologists using anonymous questionnaires including demographic data, headache and migraine status and migraine perception questions. Results: Of 348 respondent physicians, 20% were neurologists and 53% were females with an average age of 48 years. The majority had an interest in migraine and considered it disabling (93%), although 65-85% reported management difficulties, GPs more often than neurologists. Satisfaction with current treatment options was high (69-79%). 63 physicians suffered from migraine and 81% felt it influenced their perception of the disease. Portuguese physicians preferentially treat their own migraines with NSAIDs (33%), analgesics (29%) and triptans (20%). Conclusion: Portuguese physicians treating migraine patients have realistic perceptions about the disease and those with migraine feel their perception is influenced by their experience. Although reporting management difficulties, the majority of physicians are satisfied with current treatment options for migraine. © 2014 S. Karger AG, Basel. Source

MacHado M.V.,Hospital Universitario Of Santa Maria | MacHado M.V.,Institute Medicina Molecular IMM | Cortez-Pinto H.,Hospital Universitario Of Santa Maria | Cortez-Pinto H.,Institute Medicina Molecular IMM | Cortez-Pinto H.,Servio
Journal of Hepatology

It has been recognized that some lean individuals unexpectedly present with non-alcoholic steatohepatitis (NASH) [1] and in contrast, morbidly obese individuals present NASH in only about 14-37% of cases [2]. Although this situation is seemingly paradoxical, the discrepancy has been mostly attributed to the pattern of obesity being predominantly visceral/truncal, or peripheral/subcutaneous. Obesity, and particularly visceral fat (VF), is considered a key player in the development of the metabolic syndrome and its complications, namely cardiovascular risk and non-alcoholic fatty liver disease (NAFLD). Indeed, waist circumference, considered an indirect measurement of VF, is one criterion in the metabolic syndrome definition. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

Martins I.P.,Institute Medicina Molecular IMM | Goucha T.,Max Planck Institute for Human Cognitive and Brain Sciences | Mares I.,Institute Medicina Molecular IMM | Antunes A.F.,GAPIC
Journal of Headache and Pain

Late onset aura (LOA) is usually considered benign but raises diagnostic uncertainties. We compared individuals with LOA (≥45 years of age at aura onset) with those of early onset (EOA) in clinical features, vascular risk factors and imaging, in a retrospective study design including patients with migraine aura and age >44 years at first visit. In 77 cases (51 EOA and 26 LOA), no differences were found in gender distribution, family or personal history of migraine without aura, type of aura symptoms or imaging findings. LOA patients' were more likely to not fulfil all ICHD-II aura criteria and to lack headache. This data suggest that LOA and EOA are overall identical but there are differences in presentation that deserve a better characterization by a prospective study. © The Author(s) 2012. Source

MacHado M.V.,Hospital Universitario Of Santa Maria | MacHado M.V.,Institute Medicina Molecular IMM | Cortez-Pinto H.,Hospital Universitario Of Santa Maria | Cortez-Pinto H.,Institute Medicina Molecular IMM
Expert Review of Gastroenterology and Hepatology

Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the Western world. Progression to more aggressive forms of liver injury, such as nonalcoholic steatohepatitis (NASH) and cirrhosis, occurs in less than a third of affected subjects. Human data and both in vivo and in vitro models demonstrate that cell death, particularly apoptosis, is increased in NAFLD and NASH patients, suggesting that it is crucial in disease progression. Indeed, fatty acids-more specifically, saturated fatty acids-strongly induce hepatocyte apoptosis. In addition, hepatic steatosis renders hepatocytes more susceptible to apoptotic injury. Ballooned hepatocytes and Mallory-Denk bodies are important hallmarks of NASH and correlate with disease progression. There are complex correlations between ballooning, Mallory-Denk bodies and apoptosis through keratin metabolism and depletion, as well as through the endoplasmic reticulum stress response. Whether apoptosis may promote hepatocellular ballooning, or vice versa, will be discussed in this article. © 2011 Expert Reviews Ltd. Source

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