Institute Medicina Molecular IMM

Lisbon, Portugal

Institute Medicina Molecular IMM

Lisbon, Portugal
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Martins I.P.,Institute Medicina Molecular IMM | Gil-Gouveia R.,Institute Medicina Molecular IMM | Silva C.,Institute Medicina Molecular IMM | Maruta C.,Institute Medicina Molecular IMM
Headache | Year: 2012

Objectives and Background.-The possible effects of migraine on executive abilities remain controversial; hence, we studied inter-ictal cognitive performance of individuals with migraine and non migraine headaches (NMH) compared with headache free controls. Design and Method.-In a cross-sectional observational study, taking place in primary care, adults aged 50 or above were evaluated by a neurobehavioral battery including several executive measures. Present history of headache was sought, and migraine was diagnosed by the ID-Migraine questionnaire. The effect of headache type on cognitive measures was analyzed with multiple regression with adjustment by diagnosis, age, gender, education, and depressive symptoms. Results.-Among 478 participants, 23.2% reported current headache, of whom 50 were NMH, and 61 were migraine headaches. No group differences were found in the majority of cognitive measures. Compared with controls, migraine subjects performed worse on a test of attention, while NMH participants presented more intrusions and worse discriminability in memory recognition plus a lower performance on semantic memory tests. Conclusion.-The presence of headaches in late adulthood was related to a worse performance on few measures of executive functioning, suggesting that cognitive impact is not specific to migraine but might be associated to headache. © 2012 American Headache Society.


Oliveira S.S.,University of Lisbon | Oliveira S.S.,Institute Medicina Molecular IMM | Da Silva F.A.,Investigacao e Desenvolvimento em Biotecnologia S.A. | Lourenco S.,Investigacao e Desenvolvimento em Biotecnologia S.A. | And 6 more authors.
Biotechnology and Applied Biochemistry | Year: 2012

Single-domain antibodies (SDAs) are among the most studied and interesting antibody fragments. These molecules combine advantages of antibodies and small molecules. However, SDAs present a low efficiency of in vivo targeting because of their low binding avidity and fast clearance from blood circulation. Multimerization of SDA can overcome these drawbacks and increase their therapeutic potency. In this work, we developed and compared three strategies that allow construction of SDA dimers derived from rabbit light chains-PCR overlap, sticky PCR, and restriction/ligation. The restriction/ligation strategy proved to be the most efficient and feasible method to construct a successful library of SDA dimers. To further explore this technique, we constructed different libraries that differed in linker length between the two SDAs, and assessed its efficiency to deliver antigen-specific SDA dimers. We efficiently increased both the molecular size and avidity of antibody fragments, increasing the possibility of these molecules to bind to their antigen. Therefore, this work describes efficient tools for therapeutic development of SDA dimers. © 2012 International Union of Biochemistry and Molecular Biology, Inc.


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 | Year: 2015

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.


Pronto-Laborinho A.C.,University of Lisbon | Pronto-Laborinho A.C.,Institute Medicina Molecular IMM | Pinto S.,University of Lisbon | Pinto S.,Institute Medicina Molecular IMM | And 3 more authors.
BioMed Research International | Year: 2014

Amyotrophic lateral sclerosis (ALS) is a fatal devastating neurodegenerative disorder, involving progressive degeneration of motor neurons in spinal cord, brainstem, and motor cortex. Riluzole is the only drug approved in ALS but it only confers a modest improvement in survival. In spite of a high number of clinical trials no other drug has proved effectiveness. Recent studies support that vascular endothelial growth factor (VEGF), originally described as a key angiogenic factor, also plays a key role in the nervous system, including neurogenesis, neuronal survival, neuronal migration, and axon guidance. VEGF has been used in exploratory clinical studies with promising results in ALS and other neurological disorders. Although VEGF is a very promising compound, translating the basic science breakthroughs into clinical practice is the major challenge ahead. VEGF-B, presenting a single safety profile, protects motor neurons from degeneration in ALS animal models and, therefore, it will be particularly interesting to test its effects in ALS patients. In the present paper the authors make a brief description of the molecular properties of VEGF and its receptors and review its different features and therapeutic potential in the nervous system/neurodegenerative disease, particularly in ALS. © 2014 Ana Catarina Pronto-Laborinho et al.


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 | Year: 2011

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.


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 | Year: 2011

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.


Gil-Gouveia R.,Institute Medicina Molecular IMM | Gil-Gouveia R.,Hospital da Luz
European Neurology | Year: 2014

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.


PubMed | Institute Higiene e Medicina Tropical IHMT, Institute Medicina Molecular IMM, Sabio Institute Investigacion Of Recursos Cinegeticos, Institute Pasteur Of Lille and Academy of Sciences of the Czech Republic
Type: | Journal: Parasites & vectors | Year: 2015

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.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.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).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.

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