Aterosclerose e doença cardiovascular : o problema do colesterol elevado

A secção Biologia é coordenada pelo Professor Universitário Armindo Rodrigues.A aterosclerose é a principal causa de patologia cardiovascular. A Hipercolesterolemia Familiar é uma doença genética, e um factor de risco para a aterosclerose

Trace metals and over-expression of metallothioneins in bladder tumoral lesions: a case-control study

<p>Abstract</p> <p>Background</p> <p>Previous studies have provided some evidence of a possible association between cancer and metallothioneins. Whether this relates to an exposure to carcinogenic metals remains unclear.</p> <p>Methods</p> <p>In order to examine the association between the expression of metallothioneins and bladder tumors, and to compare the levels of arsenic, cadmium, chromium, lead and nickel in animals with bladder tumors and animals without bladder tumors, 37 cases of bovine bladder tumors and 17 controls were collected. The detection and quantification of metallothioneins in bladder tissue of both cases and controls was performed by immunohistochemistry. And the quantification of metals in tissue and hair was assessed by inductively coupled plasma – mass spectrometry.</p> <p>Results</p> <p>Increased expression of metallothioneins was associated with bladder tumors when compared with non-tumoral bladder tissue (OR = 9.3, 95% CI: 1.0 – 480). The concentrations of cadmium, chromium, lead and nickel in hair of cases were significantly higher than those of controls. However, as for the concentration of metals in bladder tissue, the differences were not significant.</p> <p>Conclusion</p> <p>Though the sample size was small, the present study shows an association between bladder tumors and metallothioneins. Moreover, it shows that concentrations of metals such as cadmium, chromium, lead and nickel in hair may be used as a biomarker of exposure.</p

Patterns of mitochondrial DNA damage in blood and brain tissues of a transgenic mouse model of Machado-Joseph disease

BACKGROUND: Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia caused by a CAG tract expansions in the ATXN3 gene. Patterns of mitochondrial damage associated with pathological findings of brain tissues could provide molecular biomarkers of this disorder. OBJECTIVE: The potential of mitochondrial DNA (mtDNA) damage as a biomarker of MJD progression was investigated using a transgenic mouse model. METHODS: DNA was obtained from affected (pontine nuclei) and nonaffected tissues (hippocampus and blood) of transgenic animals of three distinct age groups: 8 weeks, before onset of the phenotype; 16 weeks, at onset, and 24 weeks, at well-established phenotype. Wild-type littermate mice, serving as controls, were analyzed for the same tissues and age groups. mtDNA damage was studied by fluorescence-based quantitative PCR in 84 transgenic and 93 wild-type samples. RESULTS: A clear pattern of decrease in mtDNA copy number with age and accumulation of 3,867-bp deletions at the initial stages (both being more pronounced in transgenic mice) was observed. Pontine nuclei, the affected tissue in transgenic mice, displayed 1.5 times less copies of mtDNA than nonaffected brain tissue hippocampus (odds ratio = 1.21). Pontine nuclei displayed the highest percentage of mtDNA deletions (6.05% more in transgenic mice). CONCLUSION: These results suggest that mtDNA damage is related to the initiation of the phenotype in transgenic mice; mtDNA 3,867-bp deletions may be a biomarker of the initial stages of the disease.This study was supported by the following grants: DRCT Postdoctoral fellowship to N.K. (M3.1.7/F/002/2008), FCT Postdoctoral fellowship to T.C. (SFRH/BPD/38659/2007) and C.B. (SFRH/BPD/63121/2009), FCT research grants to S.S. (PTDC/SAU-GMG/64076/2006) and A.S.F. (PIC/IC/83013/2007)

The APOE ε2 allele increases the risk of Earlier Age at onset in Machado-Joseph disease

Background. Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder of late onset, caused by a (CAG)n expansion at the ATXN3 gene (14q32.1). Variation in age-at-onset is partially explained by the size of the (CAG)n tract in expanded alleles. The remaining variation should be the product of other factors, namely modifier genes. The genotype at the APOE locus has been described as a possible modifier in different neurological disorders, namely Parkinson (PD) and Huntington disease (HD). In the CNS, apolipoprotein E constitutes an important mediator of cholesterol transport/metabolism, which is essential for synaptic integrity and neuronal function. Objective. To investigate a modulating effect of the APOE polymorphism on age-at-onset of MJD. Design and Subjects. The APOE polymorphism was typed in a series of 192 MJD patients. Results. Cases with the ε2/ε3 genotype presented an earlier onset, when compared with those with ε3/ε3 or ε3/ε4. In this series of patients, the presence of an APOE ε2 allele implies a decrease of nearly 5 years in the age-at-onset. When combining, in a general linear model, several other predictors, namely the presence/absence of the APOE ε2 allele, with the size of the (CAG)n in expanded alleles, the model was significantly improved and the explanation of onset variance was raised from 59.8% to 66.5%. Furthermore, the presence of the ε2 allele was associated with an onset below 39 years (OR=5.00; 95% CI: 1.18-21.14). Conclusions. These findings indicate that the polymorphism at the APOE gene plays a role as a genetic modifier of MJD phenotype.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/63121/2009, SFRH/BPD/38659/2007, M3.1.3/F/004/2009, “Secretaria Regional da Ciência, Tecnologia e Equipamentos”.Fundação para a Ciência e a Tecnologia (FCT) - “Transcriptional variation of the ATXN3 gene as modulator of the clinical heterogeneity in Machado-Joseph disease (MJD)” (PIC/IC/83074/2007)Institute of Biotechnology and Biomedicine (IBBA) - “High prevalence diseases in the Azores Islands” (M2.1.2/I/026/2008

Relationship of the APOE polymorphism and lipid profile: A population-based study in the Azores Islands (Portugal)

European Human Genetics Conference 2009: Abstract P17.18 em Livro de Resumos. Austria Center Vienna, Vienna, Austria, Saturday, May 23 – Tuesday, May 26, 2009.The factors leading to a two-fold mortality rate from coronary artery disease (CAD) in the Azores, as compared to Mainland Portugal, have not been elucidated. Previous studies reported a population tendency for hypercholesterolemia, one of the main factors contributing to the development of atherosclerosis (AT), considered the primary cause of CAD. Apolipoprotein E has a key role in plasma lipid metabolism, given its function as a ligand for cell-surface receptor mediated uptake of lipoproteins. Polymorphism in the apolipoprotein gene (APOE) results in three major isoforms encoded by three codominant alleles (E2, E3 and E4). With the purpose of establishing the pattern of variation at the APOE locus and determining its association with lipid profile, we studied a random sample of 298 unrelated, apparently healthy individuals of Azorean origin. In nearly 50% of the sample total cholesterol (TC) was above 200mg/dl; in 25% of the individuals LDL-cholesterol (LDL-C) was higher than 130 mg/dl. Allele frequencies were 0.0833, 0.8317 and 0.0850 for E2, E3 and E4, respectively. Genotype frequencies were higher for E3*E3 genotype (66.1%); genotype distribution displayed conformity with Hardy-Weinberg expectations. No differences in allelic frequencies were found in comparison with other Caucasian populations, namely with mainland Portugal. E3*E4 individuals presented the highest cholesterol levels. Analysis of variance performed with the most represented genotypes (E2*E3, E3*E3 and E3*E4) revealed a clear association between the genotypic composition and TC, as well as LDL-C, thus confirming in this population, the role of APOE as one of the genetic determinants of AT

Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report

Background: Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C). Case presentation: Patient 1 is a 40 year-old female (onset at 30 years of age), initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother). Patient 2 is a 38 year-old male (onset at 33 years of age), presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father). Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions: The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD

transferências culturais e intertextualidade no teatro musical de Francisco de Sá Noronha

UID/EAT/00693/2013From the 1840s until his death in 1881, Portuguese composer Francisco de Sá Noronha wrote music for the theatre on texts in Portuguese, mostly translated from the French. Looking at this repertory, this article has as its object the study of vaudevilles, comédies mêlées de musique, opéras comiques and opérettes that migrated from Paris to the stages of the theatres of Portuguese-speaking cities, located in different countries and continents, between the forties and the eighties of the nineteenth century. The migration of the above-mentioned repertoires leads to the establishment of processes of 'cultural transfer', which are often carried out through more or less complex intertextual relations. As a case study, special attention will be paid to “Les deux pigeons”, the successive adaptations of La Fontaine’s fable which was dramatized and set to music by Noronha and other composers both in Brazil and Portugal.publishersversionpublishe

Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3): a two-case report

Abstract Background Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C). Case presentation Patient 1 is a 40 year-old female (onset at 30 years of age), initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother). Patient 2 is a 38 year-old male (onset at 33 years of age), presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father). Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD.</p

Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3) : a two-case report

Background: Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity), namely on what concerns genetic variation in Parkinson's disease (PD) associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C). Case presentation: Patient 1 is a 40 year-old female (onset at 30 years of age), initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother). Patient 2 is a 38 year-old male (onset at 33 years of age), presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father). Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions: The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD