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- O envelhecimento do sistema sensorial: implicações na funcionalidade e qualidade de vidaPublication . Lamas, Maria Céu; Paúl, ConstançaA maioria das pessoas, à medida que envelhece, vai sofrendo modificações estruturais e funcionais no sistema sensorial, que mediante a sua gravidade, podem limitar a independência e desempenho na realização das atividades de vida diária e participação social. O objetivo desta revisão consiste em analisar as principais disfunções do sistema sensorial, focando sucintamente as alterações mais comuns de cada sentido e suas implicações na vida dos idosos. Procedeu-se à pesquisa da bibliografia, durante o mês de dezembro de 2011 e janeiro de 2012, na base de dados PubMed, Lilacs, Google Schoolar e livros de medicina, para textos e estudos transversais e longitudinais, sobre o envelhecimento sensorial na globalidade ou em parte. O envelhecimento sensorial, pode assumir, importantes consequências psicológicas e sociais, com repercussões no funcionamento das atividades intelectuais. Por isso, os estudos tendem a explorar as alterações da função sensorial no tempo e nos padrões de conduta dos idosos.
- Role of the DHH1 Gene in the Regulation of Monocarboxylic Acids Transporters Expression in Saccharomyces cerevisiaePublication . Mota, Sandra; Vieira, Neide; Barbosa, Sónia; Delaveau, Thierry; Torchet, Claire; Saux, Agnès Le; Garcia, Mathilde; Pereira, Ana; Lemoine, Sophie; Coulpier, Fanny; Darzacq, Xavier; Benard, Lionel; Casal, Margarida; Devaux, Frédéric; Paiva, SandraPrevious experiments revealed that DHH1, a RNA helicase involved in the regulation of mRNA stability and translation, complemented the phenotype of a Saccharomyces cerevisiae mutant affected in the expression of genes coding for monocarboxylic-acids transporters, JEN1 and ADY2 (Paiva S, Althoff S, Casal M, Leao C. FEMS Microbiol Lett, 1999, 170∶301–306). In wild type cells, JEN1 expression had been shown to be undetectable in the presence of glucose or formic acid, and induced in the presence of lactate. In this work, we show that JEN1 mRNA accumulates in a dhh1 mutant, when formic acid was used as sole carbon source. Dhh1 interacts with the decapping activator Dcp1 and with the deadenylase complex. This led to the hypothesis that JEN1 expression is post-transcriptionally regulated by Dhh1 in formic acid. Analyses of JEN1 mRNAs decay in wild-type and dhh1 mutant strains confirmed this hypothesis. In these conditions, the stabilized JEN1 mRNA was associated to polysomes but no Jen1 protein could be detected, either by measurable lactate carrier activity, Jen1-GFP fluorescence detection or western blots. These results revealed the complexity of the expression regulation of JEN1 in S. cerevisiae and evidenced the importance of DHH1 in this process. Additionally, microarray analyses of dhh1 mutant indicated that Dhh1 plays a large role in metabolic adaptation, suggesting that carbon source changes triggers a complex interplay between transcriptional and post-transcriptional effects.
- Prevalência de perfis lipídico e glicémico alterados em pacientes com esquizofreniaPublication . Amorim, Manuela; Moreira, Anabela; Monteiro, Pedro; Curral, Rosário; Marques, AntónioOs pacientes com esquizofrenia (SCZ) apresentam anomalias importantes no metabolismo lipídico e da glicose, que podem ser induzidas pela terapia antipsicótica (AP) e pelo estilo de vida associado. O risco de doenças cardiovasculares, diabetes mellitus e síndrome metabólica está aumentado nestes pacientes, que apresentam taxa de mortalidade por doenças cardiovasculares duas vezes mais elevada do que a população geral. Analisar a prevalência de alterações nos perfis lipídicos e glicémicos e a terapêutica AP numa amostra de pacientes SCZ. Realizou-se um estudo retrospetivo aos registos de perfis lipídico e glicémico e da terapia AP de pacientes SCZ de uma unidade de dia de cuidados de saúde mental, de 2009 a 2011. Selecionámos para estudo individualizado os casos que cumpriam os seguintes critérios: presença de fatores de risco cardiovascular, hiperglicemia ou fatores indicadores de síndrome metabólica. A amostra foi constituída por 51 pacientes SCZ, dos quais registámos 5 casos com fatores de risco cardiovascular, 6 com hiperglicemia indicadora de diabetes e 7 com fatores laboratoriais indicadores de síndrome metabólica. Para estes casos, analisámos o agente antipsicótico prescrito. Os dados mostram a necessidade de monitorização dos efeitos secundários metabólicos da terapia AP e do estabelecimento de medidas corretivas (alimentares, estilo de vida e terapêuticas).
- Construção e validação de um instrumento para avaliar a satisfação e importância atribuída aos serviços de enfermagem prestados na área da saúde mentalPublication . Mota, Sandra; Araújo, Maria José; Trigueiro, Maria João; Leuchner, António; Amorim, ManuelaA avaliação da satisfação dos utentes é um indicador da qualidade e eficácia dos cuidados de saúde prestados, pelo que é da maior importância ter instrumentos válidos para a recolha desta informação. Na existência de poucos instrumentos que cumpram esses requisitos, procedemos à construção e validação de um que permitisse avaliar a satisfação dos utentes e a importância que estes atribuem aos cuidados prestados numa instituição de saúde mental. Avaliou-se as propriedades psicométricas do instrumento, através dos testes α de Cronbach, Ró de Spearman e análise fatorial, numa amostra de 95 utentes. Verificou-se que o instrumento cumpriu os critérios intermédios necessários para ser considerado um instrumento validado para os utentes de consulta externa de cuidados de enfermagem de uma instituição de saúde mental. Verificou-se ainda que os utentes se encontram satisfeitos com os cuidados prestados e consideram estes cuidados importantes.
- Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetatePublication . Mota, Sandra; Alves, Rosana; Carneiro, Catarina; Silva, Sónia; Brown, Alistair J.; Istel, Fabian; Kuchler, Karl; Sampaio, Paula; Casal, Margarida; Henriques, Mariana; Paiva, SandraCandida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analyzing biofilm formation, antifungal drug resistance, and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2, and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis.
- Acute effects of physical exercise with microcurrent in the adipose tissue of the abdominal region: A randomized controlled trialPublication . Noites, Andreia; Moreira, Anabela; Melo, Cristina; Faria, Miriam; Vilarinho, Rui; Freitas, Carla; Monteiro, Pedro; Carvalho, Paulo; Adubeiro, Nuno; Sousa, Maria; Santos, Rubim; Nogueira, LuisaIncreased abdominal fat and sedentary lifestyles contribute to cardiovascular disease risk. Low-intensity electrical current (microcurrent) on the abdominal region, associated with physical exercise, appears to be an innovative method to increase the lipolytic rate of abdominal adipocytes, in order to reduce abdominal fat. This study aimed to analyze the acute effects of microcurrent associated with an aerobic exercise program in healthy subjects in lipolysis. A double-blinded, randomized controlled trial was developed and conducted in a higher education school. Eighty-three healthy subjects, aged between 18 and 30 years old and with a 18.5 to 29.9 kg/m2 body mass index were randomly assigned either to an experimental or to a placebo group. Subjects received a trans-abdominal microcurrent stimulation for 40 min with (experimental group) or without (placebo group) electrical current, followed by a single aerobic exercise session (60 min at 45–55% VO2max intensity). Lipolytic activity (serum glycerol), abdominal fat (waist circumference, abdominal skinfold, ultrasonography), and serum lipid profile (serum triglyceride, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol) were evaluated in all subjects. Physical activity (International Physical Activity Questionnaire) and dietary intake (food-frequency questionnaire) questionnaires were applied. After the intervention, lipolytic rate was significantly higher (p = 0.003) in the experimental group (mean = 0.15) than in the placebo group (mean = 0.09). Glycerol results showed a statistically significant increase between baseline and after the intervention for both experimental group (p = 0.001) and the placebo group (p = 0.001). Combined use of microcurrent and physical aerobic exercise had an acute effect enhancing lipolytic rate comparing to exercise alone, in young healthy subjects.
- The carboxylic acid transporters Jen1 and Jen2 affect the architecture and fluconazole susceptibility of Candida albicans biofilm in the presence of lactatePublication . Alves, Rosana; Mota, Sandra; Silva, Sónia; F. Rodrigues, Célia; P. Brown, Alistair J.; Henriques, Mariana; Casal, Margarida; Paiva, SandraCandida albicans has the ability to adapt to different host niches, often glucose-limited but rich in alternative carbon sources. In these glucose-poor microenvironments, this pathogen expresses JEN1 and JEN2 genes, encoding carboxylate transporters, which are important in the early stages of infection. This work investigated how host microenvironments, in particular acidic containing lactic acid, affect C. albicans biofilm formation and antifungal drug resistance. Multiple components of the extracellular matrix were also analysed, including their impact on antifungal drug resistance, and the involvement of both Jen1 and Jen2 in this process. The results show that growth on lactate affects biofilm formation, morphology and susceptibility to fluconazole and that both Jen1 and Jen2 might play a role in these processes. These results support the view that the adaptation of Candida cells to the carbon source present in the host niches affects their pathogenicity.
- Clinical and metabolic implications of obesity in prostate cancer: is testosterone a missing link?Publication . Duarte, Fernanda; Luís, C.; Baylina, Pilar; Faria, Isabel; Fernandes, Rúben; La Fuente, J. M.Objectives: To assess sex hormones in men with obesity and prostate cancer (PCa) and to study association between androgens and the pathogenesis biology of PCa in vitro. Subjects and methods: One hundred and eighty-one men older than 45 years selected from of a population attending to Urology departments screening for PCa, (78 participants without PCa and 103 patients with PCa). All participants were assessed for body mass index (BMI), age, Gleason score, and PSA. Endocrine profile was determined for LH, total testosterone (TT), 17β-estradiol (E2), prolactin and leptin. Biochemical profile (HbA1c, triacylglycerols and lipoproteins) was also determined. In vitro experiments were also performed, involving the study of 5α-dihydrotestosterone (DHT) and E2 in the presence of adipocyte-conditioned medium (aCM). Results: All variables were continuous and described a Gaussian distribution unless mentioned. To determine the relation of aggressiveness, variable were transformed into categories. Thus, PCa aggressiveness is associated with the increase of age and BMI (p < .0001) but with is decreased with TT and E2 (p < .05). Moreover, adipocyte-secreted molecules increase aggressiveness of PCa cells in vitro. Lastly, DTH but not E2 enables invasiveness in vitro. Conclusions: It was observed a coexistence of hormone axis profile alteration with sex hormones and BMI in PCa patients, in accordance with the new perspective of PCa pathogenesis.
- Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthoodPublication . Amorim, Manuela; Bravo, Joana; Silva, Ana Isabel; Alves, Cecília Juliana; Monteiro, Pedro; Magalhãess, Ana; Summavielle, TeresaAdolescent development of the prefrontal cortex (PFC) is accompanied by important changes in glutamatergic, GABAergic and dopaminergic circuitries, susceptible to modulation by N-methyl-D-aspartate receptors (NMDAR) antagonists. Repeated ketamine was associated with social and memory deficits, but other relevant factors, such as anxiety, were not sufficiently addressed. The present study aimed to examine the behavioral and molecular consequences of repeated exposure to ketamine with a particular focus in anxiety. Methods. We treated male adolescent Wistar rats, starting postnatal day (PND) 35, with ketamine (30 mg/kg, i.p, 7 days). Behavioral evaluation was conducted in the adulthood (PND 60). The elevated plus maze (EPM) and open field tests were used to evaluate anxiety and locomotion, while sociability and novelty recognition were assessed through the novel object recognition (NOR) and the sociability and social novelty tests. At the end of the behavioral evaluation, brains were dissected and the prefrontal cortex used for biochemical evaluation. Results. Analysis of the elevated plus maze (EPM) data revealed a ketamine-induced anxiety-like profile, corroborated by the open field data. Ketaminetreated rats also failed to increase contact time with a conspecific in the social affiliation test and with an unknown rat in the novelty preference test. At the molecular level, frontal expression levels of tyrosine hydroxylase were found decreased. Conclusion. Altogether, these results show that repeated ketamine-exposure in the adolescent may result in long-term anxiety
- Warburg Effect Inversion: Adiposity shifts central primary metabolism in MCF-7 breast cancer cellsPublication . Luís, Carla; Duarte, Fernanda; Faria, Isabel; Jarak, Ivana; Oliveira, Pedro F.; Alves, Marco G.; Soares, Raquel; Fernandes, RúbenObesity is a complex health disorder and a trigger to many diseases like Diabetes mellitus (DM) and breast cancer (BrCa), both leading causes of morbidity and mortality worldwide. Also evidence demonstrates that abnormal glucose metabolism termed ‘the Warburg effect’ in cancer cell is closely associated with malignant phenotypes and promote the aggressiveness of several types of cancer, including BrCa. In this study, we evaluated the breast cancer cell metabolism in normoglycemia, hyperglycemia and in an obesity condition in order to clarify the potential underlined mechanisms that link these disorders. Materials and methods MCF-7 cells were exposed to low and high glucose levels, the latter either in the presence of 3T3-L1 adipocyte conditioned medium (CM), thus mimicking the adiposity observed in obese patients. Cell viability, migration, proliferation, cytotoxicity and cell death assays were performed under the different culture conditions. Hormonal and lipid profile were also characterized by biochemical assays and primary metabolism was determined by Nuclear Magnetic Resonance (NMR)-based metabolomics. Results Our results show an increased aggressiveness in the condition mimicking diabetogenic obesity with an altered energy/lipid metabolism. Interestingly in the experimental obesity-mimicking status, lipids and amino acids were expended while glucose was produced by tumor cells from lactate. These findings reveal a shift on tumor cells metabolism that is opposite to ‘the Warburg effect’. Conclusions Overall, this experimentally obesity-mimicking condition not only revealed an increased tumor proliferation and aggressiveness but also disclosed a new mechanism of cancer metabolism, the ‘Warburg Effect Inversion’.
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