Evaluation of 99mTc-Sestamibi as a potential tool to investigate PgP activity in inflammation

Introduction: In the XXI Century ’s Society the scientific investigation process has been growing steadily , and the field of the pharmaceutical research is one of the most enthusiastic and relevant . Here, it is very important to correlate observed functional alterations with possibly modified drug bio distribution patterns . Cancer, inflammation and inf ection are processes that induce many molecular intermediates like cytokines, chemokines and other chemical complexes that can alter the pharmacokinetics of many drugs. One cause of such changes is thought to be the modulator action of these complexes in t he P - Glyco p rotein activity, because they can act like inducers/inhibitors of MDR - 1 expression. This protein results from the expression of MDR - 1 gene, and acts as an ATP energy - dependent efflux pump, with their substrates including many drugs , like antiretrovirals, anticancers, anti - infectives, immunosuppressants, steroids or opioids . Objectives: Because of the lack of methods to provide helpful information in the investigation of in vivo molecular changes in Pgp activity during infection/infl ammation processes, and its value in the explanation of the altered drug pharmacokinetic, this paper want to evaluate the potential utility of 99m Tc - Sestamibi scintigraphy during this kind of health sciences investigation. Although the a im is indeed to create a technique to the in vivo study of Pgp activity, this preliminary Project only reaches the in vitro study phase, assumed as the first step in a n evaluation period for a new tool development. Materials and Methods: For that reason , we are performing in vitro studies of influx and efflux of 99m Tc - Sestamibi ( that is a substrate of Pgp) in hepatocytes cell line (HepG2). We are interested in clarify the cellular behavior of this radiopharmaceutical in Lipopolysaccharide(LPS) stimulated cells ( well known in vitro model of inflammation) to possibly approve this methodology. To validate the results, the Pgp expression will be finally evaluated using Western Blot technique. Results: Up to this moment , we still don’t have the final results, but we have already enough data to let us believe that LPS stimulation induce a downregulation of MDR - 1, and consequently Pgp, which could conduce to a prolonged retention of 99m Tc - Sestamibi in the inflamed cells . Conclusions: If and when this methodology demonstrate the promising results we expect, one will be able to con clude that Nuclear Medicine is an important tool to help evidence based research also on this specific field .

Q192R polymorphism of the paraoxonase-1 gene as a risk factor for obesity in Portuguese women

Introduction - Obesity became a major public health problem as a result of its increasing prevalence worldwide. Paraoxonase-1 (PON1) is an esterase able to protect membranes and lipoproteins from oxidative modifications. At the PON1 gene, several polymorphisms in the promoter and coding regions have been identified. The aims of this study were i) to assess PON1 L55M and Q192R polymorphisms as a risk factor for obesity in women; ii) to compare PON1 activity according to the expression of each allele in L55M and Q192R polymorphisms; iii) to compare PON1 activity between obese and normal-weight women. Materials and methods - We studied 75 healthy (35.9±8.2 years) and 81 obese women (34.3±8.2 years). Inclusion criteria for obese subjects were body mass index ≥30 kg/m2 and absence of inflammatory/neoplasic conditions or kidney/hepatic dysfunction. The two PON1 polymorphisms were assessed by real-time PCR with TaqMan probes. PON1 enzymatic activity was assessed by spectrophotometric methods, using paraoxon as a substrate. Results - No significant differences were found for PON1 activity between normal and obese women. Nevertheless, PON1 activity was greater (P<0.01) for the RR genotype (in Q192R polymorphism) and for the LL genotype (in L55M polymorphism). The frequency of allele R of Q192R polymorphism was significantly higher in obese women (P<0.05) and was associated with an increased risk of obesity (odds ratio=2.0 – 95% confidence interval (1.04; 3.87)). Conclusion - 55M and Q192R polymorphisms influence PON1 activity. The allele R of the Q192R polymorphism is associated with an increased risk for development of obesity among Portuguese Caucasian premenopausal women.

Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis

Introduction and Objectives - Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression. Methods - We investigated the association between PON1 55 and 192 single nucleotide polymorphisms (SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67 consecutive patients with moderate CAVS and 251 healthy controls. Results - PON1 paraoxonase activity was higher in CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein (P=0.24) or low-density lipoprotein cholesterol (P=0.52). Conclusion - The PON1 genotype Q192R SNP has an important effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique population.

eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.

Studying the development of an online course on Curriculum : implications for the students' workload in light of the Bologna principles

ECER 2014 "The Past, the Present and Future of Educational Research in Europe" will take place at the University of Porto from 1 - 5 September 2014.

Contributo do iPad® para o desenvolvimento de crianças com necessidades educativas especiais

Dissertação apresentada à Escola Superior de Educação de Lisboa para obtenção do grau de Mestre em Ciências da Educação, Especialidade Intervenção Precoce

Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strains

Cyanobacteria are widely recognized as a valuable source of bioactive metabolites. The majority of such compounds have been isolated from so-called complex cyanobacteria, such as filamentous or colonial forms, which usually display a larger number of biosynthetic gene clusters in their genomes, when compared to free-living unicellular forms. Nevertheless, picocyanobacteria are also known to have potential to produce bioactive natural products. Here, we report the isolation of hierridin B from the marine picocyanobacterium Cyanobium sp. LEGE 06113. This compound had previously been isolated from the filamentous epiphytic cyanobacterium Phormidium ectocarpi SAG 60.90, and had been shown to possess antiplasmodial activity. A phylogenetic analysis of the 16S rRNA gene from both strains confirmed that these cyanobacteria derive from different evolutionary lineages. We further investigated the biological activity of hierridin B, and tested its cytotoxicity towards a panel of human cancer cell lines; it showed selective cytotoxicity towards HT-29 colon adenocarcinoma cells.

Research practice development for nuclear medicine technologists: an innovative experience

Introduction - European nuclear medicine technologist’s education is delivered by Higher Education Institutions and students obtain a grade of Bachelor of Sciences (BSc), during which they are initiated to research during their studies. Once BSc nuclear medicine technologists are in professional practice, they have very few opportunities to develop a real research experience and they rather become passive users than active contributors the growth of scientific knowledge in nuclear medicine. Aim - To describe and discuss an innovative educational and professional experience aimed in strengthen research knowledge, skills and competencies of former nuclear medicine technologists student in the context of an international mobility stay.

Estudo económico das energias renováveis: o caso português

Dissertação de Mestrado apresentado ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Empreendedorismo e Internacionalização, sob orientação de Maria Clara Dias Pinto Ribeiro

Food consumption, physical activity and socio-economic status related to BMI, waist circumference and waist-to-height ratio in adolescents

Objective: To examine the association between obesity and food group intakes, physical activity and socio-economic status in adolescents. Design: A cross-sectional study was carried out in 2008. Cole’s cut-off points were used to categorize BMI. Abdominal obesity was defined by a waist circumference at or above the 90th percentile, as well as a waist-to-height ratio at or above 0?500. Diet was evaluated using an FFQ, and the food group consumption was categorized using sex-specific tertiles of each food group amount. Physical activity was assessed via a self-report questionnaire. Socio-economic status was assessed referring to parental education and employment status. Data were analysed separately for girls and boys and the associations among food consumption, physical activity, socio-economic status and BMI, waist circumference and waist-to-height ratio were evaluated using logistic regression analysis, adjusting the results for potential confounders. Setting: Public schools in the Azorean Archipelago, Portugal. Subjects: Adolescents (n 1209) aged 15–18 years. Results: After adjustment, in boys, higher intake of ready-to-eat cereals was a negative predictor while vegetables were a positive predictor of overweight/ obesity and abdominal obesity. Active boys had lower odds of abdominal obesity compared with inactive boys. Boys whose mother showed a low education level had higher odds of abdominal obesity compared with boys whose mother presented a high education level. Concerning girls, higher intake of sweets and pastries was a negative predictor of overweight/obesity and abdominal obesity. Girls in tertile 2 of milk intake had lower odds of abdominal obesity than those in tertile 1. Girls whose father had no relationship with employment displayed higher odds of abdominal obesity compared with girls whose father had high employment status. Conclusions: We have found that different measures of obesity have distinct associations with food group intakes, physical activity and socio-economic status.

Relationship of milk intake and physical activity to abdominal obesity among adolescents

Background: Diet and physical activity (PA) are recognized as important factors to prevent abdominal obesity (AO), which is strongly associated with chronic diseases. Some studies have reported an inverse association between milk consumption and AO. Objective: This study examined the association between milk intake, PA and AO in adolescents. Methods: A cross-sectional study was conducted with 1209 adolescents, aged 15–18 from the Azorean Archipelago, Portugal in 2008. AO was defined by a waist circumference at or above the 90th percentile. Adolescent food intake was measured using a semi-quantitative food frequency questionnaire, and milk intake was categorized as ‘low milk intake’ (<2 servings per day) or ‘high milk intake’ ( 2 servings per day). PA was assessed via a self-report questionnaire, and participants were divided into active (>10 points) and low-active groups ( 10 points) on the basis of their reported PA. They were then divided into four smaller groups, according to milk intake and PA: (i) low milk intake/low active; (ii) low milk intake/active; (iii) high milk intake/low active and (iv) high milk intake/active. The association between milk intake, PA and AO was evaluated using logistic regression analysis, and the results were adjusted for demographic, body mass index, pubertal stage and dietary confounders. Results: In this study, the majority of adolescents consumed semi-skimmed or skimmed milk (92.3%). The group of adolescents with high level of milk intake and active had a lower proportion of AO than did other groups (low milk intake/low active: 34.2%; low milk intake/active: 26.9%; high milk intake/low active: 25.7%; high milk intake/active: 21.9%, P = 0.008). After adjusting for confounders, low-active and active adolescents with high levels of milk intake were less likely to have AO, compared with low-active adolescents with low milk intake (high milk intake/low active, odds ratio [OR] = 0.412, 95% confidence intervals [CI]: 0.201– 0.845; high milk intake/active adolescents, OR = 0.445, 95% CI: 0.235–0.845).Conclusion: High milk intake seems to have a protective effect on AO, regardless of PA level

Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strains

Cyanobacteria are widely recognized as a valuable source of bioactive metabolites. The majority of such compounds have been isolated from so-called complex cyanobacteria, such as filamentous or colonial forms, which usually display a larger number of biosynthetic gene clusters in their genomes, when compared to free-living unicellular forms. Nevertheless, picocyanobacteria are also known to have potential to produce bioactive natural products. Here, we report the isolation of hierridin B from the marine picocyanobacterium Cyanobium sp. LEGE 06113. This compound had previously been isolated from the filamentous epiphytic cyanobacterium Phormidium ectocarpi SAG 60.90, and had been shown to possess antiplasmodial activity. A phylogenetic analysis of the 16S rRNA gene from both strains confirmed that these cyanobacteria derive from different evolutionary lineages. We further investigated the biological activity of hierridin B, and tested its cytotoxicity towards a panel of human cancer cell lines; it showed selective cytotoxicity towards HT-29 colon adenocarcinoma cells.

Exploring nature profits: development of novel and potent lipophilic antioxidants based on galloylecinnamic hybrids

Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neurodegenerative disorders. However, until now, most of natural antioxidants have limited therapeutic success a fact that could be related with their limited distribution throughout the body and with the inherent difficulties to attain the target sites. The development of phenolic antioxidants based on a hybrid concept and structurally based on natural hydroxybenzoic (gallic acid) and hydroxycinnamic (caffeic acid) scaffolds seems to be a suitable solution to surpass the mentioned drawbacks. Galloylecinnamic hybrids were synthesized and their antioxidant activity as well as partition coefficients and redox potentials evaluated. The structureepropertyeactivity relationship (SPAR) study revealed the existence of a correlation between the redox potentials and antioxidant activity. The galloylecinnamic acid hybrid stands out as the best antioxidant supplementing the effect of a blend of gallic acid plus caffeic acid endorsing the hypothesis that the whole is greater than the sum of the parts. In addition, some hybrid compounds possess an appropriate lipophilicity allowing their application as chain-breaking antioxidant in biomembranes or other type of lipidic systems. Their predicted ADME properties are also in accordance with the general requirements for drug-like compounds. Accordingly, these phenolic hybrids can be seen as potential antioxidants for tackling the oxidative status linked to the neurodegenerative, inflammatory or cancer processes.

Association between Schistosomiasis mansoni and hepatitis C: systematic review

OBJECTIVE: To perform a systematic review of the prevalence of the HCV/ S. mansoni co-infection and associated factors in Schistosoma mansoni -infected populations. METHODS: The bibliographic search was carried out using the Medline, Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the studies' selection and the extraction data were based on systematic review methods. Forty five studies were found, with nine being excluded in a first screening. Thirteen articles were used for data extraction. RESULTS: The HCV infection rates in schistosomiasis populations range from 1% in Ethiopia to 50% in Egypt. Several studies had poorly defined methodologies, even in areas characterized by an association between hepatitis C and schistosomiasis, such as Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates in schistosomotic populations were heterogeneous and risk factors for acquiring the virus varied widely. CONCLUSIONS: Despite the limitations, this review may help to identify regions with higher rates of hepatitis C and schistosomiasis association. However, more studies are necessary for the development of public health policies on prevention and control of both diseases.

Boas práticas de igualdade de género e sua relação nos domínios da satisfação laboral e clima organizacional

A Igualdade entre Homens e Mulheres e a não discriminação constituem princípios fundamentais da Constituição da Republica Portuguesa e do Tratado que institui a União Europeia – Tratado de Lisboa. A desigualdade entre Homens e Mulheres constitui uma violação dos direitos fundamentais, e impõe um pesado custo à economia na medida em que se desaproveitam talentos em função do género. A promoção de uma efetiva igualdade entre Homens e Mulheres constitui um dever fundamental do Estado. A promoção da participação ativa de Homens e Mulheres na vida política, ao nível da administração central, regional e local, é também um forte indicador da qualidade da democracia de um estado. Tomando por base a temática da Igualdade de Género, o Roteiro para a Igualdade entre Homens e Mulheres (2006-2010), o pacto Europeu para a Igualdade entre os Sexos (2006), a Estratégia para a Igualdade entre Homens e Mulheres 2010-2015 que elencam ações consideradas prioritárias – igualdade na independência económica; igualdade na remuneração por trabalho igual e por trabalho de igual valor; igualdade na tomada de decisões; promoção da dignidade e a integridade, pôr fim à violência de género; e questões horizontais – papéis desempenhados por Homens e Mulheres, legislação, governação e instrumentos no domínio da igualdade entre Homens e Mulheres, o objeto deste estudo centra-se na atividade do Estado Português, mais concretamente ao nível local. Procurou-se enquadrar esta temática na Gestão dos Recursos Humanos, na busca de um conhecimento mais aprofundado sobre a implementação de Boas Práticas de Igualdade de Género e a sua relação nos domínios da Satisfação Laboral assim como no Clima Organizacional. O presente estudo expõe uma abordagem quantitativa, de carácter descritivo, exploratório, correlacional e preditivo. O tratamento estatístico realizou-se com recurso ao programa IBM SPSS Statistics, versão 21. Os resultados encontrados apontam para uma associação positiva entre a existência de boas práticas de igualdade de género e a satisfação laboral dos trabalhadores, assim como do clima organizacional. São apresentadas pistas para a intervenção no domínio da função da gestão e desenvolvimento dos recursos humanos.