Browsing by Author "Martins, M."
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- Alterações fenotípicas e genéticas do metabolismo do ferro numa população portuguesa com doença de Alzheimer: potenciais implicações no conhecimento da fisiopatologia e no diagnóstico desta demênciaPublication . Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.; Verdelho, A.; Porto, G.; Guerreiro, M.; Herrero, A.; Costa, C.; Mendonça, A.; Martins, M.; Costa, L.
- Association of the alpha4 integrin subunit gene (ITGA4) with autismPublication . Correia, C.; Coutinho, A.M.; Almeida, J.; Lontro, R.; Lobo, C.; Miguel, T.S.; Martins, M.; Gallagher, L.; Conroy, J.; Gill, M.; Oliveira, G.; Vicente, A.M.In the present work, we provide further evidence for the involvement of the integrin alpha-4 precursor gene (ITGA4) in the etiology of autism, by replicating previous findings of a genetic association with autism in various independent populations. The ITGA4 gene maps to the autism linkage region on 2q31-33 and is therefore a plausible positional candidate. We tested eight single nucleotide polymorphisms (SNPs) in the ITGA4 gene region for association with autism in a sample of 164 nuclear families. Evidence for association was found for the rs155100 marker (P = 0.019) and for a number of specific marker haplotypes containing this SNP (0.00053 < P < 0.022). alpha4 integrins are known to play a key role in neuroinflammatory processes, which are hypothesized to contribute to autism. In this study, an association was found between the ITGA4 rs1449263 marker and levels of a serum autoantibody directed to brain tissue, which was previously shown to be significantly more frequent in autistic patients than in age-matched controls in our population. This result suggests that the ITGA4 gene could be involved in a neuroimmune process thought to occur in autistic patients and, together with previous findings, offers a new perspective on the role of integrins in the etiology of autism to which little attention has been paid so far.
- Diabetes hinders community-acquired pneumonia outcomes in hospitalized patientsPublication . Martins, M.; Boavida, J.M.; Raposo, J.F.; Froes, F.; Nunes, Baltazar; Ribeiro, R.T.; Macedo, M.P.; Penha-Gonçalves, C.Objectives: This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and inhospital mortality. Research design and methods: We carried out a retrospective, nationwide register analysis of CAP in adult patients admitted to Portuguese hospitals between 2009 and 2012. Anonymous data from 157 291 adult patients with CAP were extracted from the National Hospital Discharge Database and we performed a DM-conditioned analysis stratified by age, sex and year of hospitalization. Results: The 74 175 CAP episodes that matched the inclusion criteria showed a high burden of DM that tended to increase over time, from 23.7% in 2009 to 28.1% in 2012. Interestingly, patients with CAP had high DM prevalence in the context of the national DM prevalence. Episodes of CAP in patients with DM had on average 0.8 days longer hospital stay as compared to patients without DM ( p<0.0001), totaling a surplus of 15 370 days of stay attributable to DM in 19 212 admissions. In-hospital mortality was also significantly higher in patients with CAP who have DM (15.2%) versus those who have DM (13.5%) ( p=0.002). Conclusions: Our analysis revealed that DM prevalence was significantly increased within CAP hospital admissions, reinforcing other studies’ findings that suggest that DM is a risk factor for CAP. Since patients with CAP who have DM have longer hospitalization time and higher mortality rates, these results hold informative value for patient guidance and healthcare strategies.
- Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levelsPublication . Coutinho, A.M.; Sousa, I.; Martins, M.; Correia, C.; Morgadinho, T.; Bento, C.; Marques, C.; Ataíde, A.; Miguel, T.S.; Moore, J.H.; Oliveira, G.; Vicente, A.M.Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism.
- Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulationPublication . Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.; Verdelho, A.; Porto, G.; Guerreiro, M.; Herrero, A.; Costa, C.; de Mendonça, A.; Costa, L.; Martins, M.Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.
- The occurrence of inorganic contaminants in ‘tronchuda’ cabbage (Brassica oleracea L. var. costata DC.) after large forest fires in PortugalPublication . Ventura, Marta; Cavaco, H.; Delgado, Inês; Coelho, Inês; Gueifão, Sandra; Martins, M.; Costa, M.H.; Matos, A.; Castanheira, IsabelEuropean Mediterranean countries have been affected by unhealthy pollutants released by wildfire smoke. This work aims to determine the inorganic elements, present in the vegetable widely consumed by the rural population, provided by burned areas. Two groups composed the sampling plan; group one before forest fires and group two after forest fires under three campaigns: 1) immediately after forest fires; 2) after rainfall; 3) during springtime. ICP-MS analysed all the samples to evaluate the contents of As, Br, Cd, Co, Cr, Pb, Se, Sr, and Zn. The amounts of trace elements founded were the following Pb < Cd < Co < As < Cr < Se < Zn < Br < Sr. Hierarchical Cluster Analysis evidenced 4 clusters; the first with the highest contents of Cr and Pb, the second cluster was marked by the highest amounts of As, and Br, higher values of Se characterised the third cluster, and the fourth cluster presented the highest values of Zn and Cd. The contents of contaminants in group one is not a matter of concern. The results obtained in group two identified a hazard, decreasing one year after the fires and maintaining these patterns afterwards. Occurrence data from local foods is a pioneer to study the impact of forest fires on human health through food consumption.