Toxicity screening of Diclofenac, Propranolol, Sertraline and Simvastatin using Danio rerio and Paracentrotus lividus embryo bioassays

Early life-stage bioassays have been used as an alternative to short-term adult toxicity tests since they are cost-effective. A single couple can produce hundreds or thousands of embryos and hence can be used as a simple high-throughput approach in toxicity studies. In the present study, zebrafish and sea urchin embryo bioassays were used to test the toxicity of four pharmaceuticals belonging to different therapeutic classes: diclofenac, propranolol, simvastatin and sertraline. Simvastatin was the most toxic tested compound for zebrafish embryo, followed by diclofenac. Sertraline was the most toxic drug to sea urchin embryos, inducing development abnormalities at the ng/L range. Overall, our results highlight the potential of sea urchin embryo bioassay as a promising and sensitive approach for the high-throughput methods to test the toxicity of new chemicals, including pharmaceuticals, and identify several drugs that should go through more detailed toxicity assays.

Caracterização dos estilos de vida dos sem-abrigo da cidade do Porto

O fenómeno dos sem-abrigo está em constante crescimento nos centros urbanos, na cidade no Porto o mesmo acontece, sendo esta uma realidade ainda pouco conhecida. Têm sido realizados alguns estudos sobre esta problemática, no entanto poucos incidem sobre a população portuguesa, pouco se sabe sobre como vivem estes indivíduos e sobre o que define o seu estilo de vida. Os estilos de vida têm vindo a ser uma área de crescente interesse para estudo, visto que afecta a nossa saúde e a longo prazo tem influência nos padrões de morbilidade e mortalidade. Com este estudo procurou-se caracterizar os sem-abrigo da cidade do Porto e os comportamentos que tipificam o seu estilo de vida, bem como verificar se existem variáveis dos estilos de vida que se encontram correlacionadas com a presença de sintomatologia psicopatológica. Para este efeito, foi realizado um inquérito por questionário a 30 pessoas que vivem na condição de sem-abrigo na cidade do Porto, através da administração de um questionário de estilos de vida e da Brief Psychiatric Rating Scale (BPRS). Concluímos que os sem-abrigo se caracterizam por ser do sexo masculino, solteiros de nacionalidade portuguesa e baixa escolaridade. Constatamos que a maioria apresenta comportamentos pouco saudáveis como fumar e não praticar exercício físico, contudo têm cuidado com a higiene pessoal, apresentam uma boa higiene do sono e manifestam poucos comportamentos sexuais de risco. Verificamos que a ansiedade se encontra correlacionada negativamente com o stress, higiene do sono, insight e alimentação. As perturbações somáticas mostraram uma correlação com a higiene do sono, o humor depressivo com a higiene do sono e insight, o retraimento emocional com a socialização e falta de cooperação com a socialização, sendo todas estas correlações negativas. Encontramos ainda uma correlação positiva entre a lentificação e o consumo de substâncias e uma correlação negativa entre a lentificação e higiene do sono. Considerando os resultados obtidos pensamos ser fundamental prosseguir com estudos de investigação nesta área, para que de futuro as intervenções junto desta população consigam dar uma melhor resposta ao seu estado de saúde.

Primary screening of the bioactivity of brackishwater cyanobacteria: toxicity of crude extracts to artemia salina larvae and paracentrotus lividus embryos

Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against vertebrates, invertebrates, plants, microalgae, fungi, bacteria, viruses and cell lines. The aim of this study was to assess the toxic effects of aqueous, methanolic and hexane crude extracts of benthic and picoplanktonic cyanobacteria isolated from estuarine environments, towards the nauplii of the brine shrimp Artemia salina and embryos of the sea urchin Paracentrotus lividus. The A. salina lethality test was used as a frontline screen and then complemented by the more specific sea urchin embryo-larval assay. Eighteen cyanobacterial isolates, belonging to the genera Cyanobium, Leptolyngbya, Microcoleus, Phormidium, Nodularia, Nostoc and Synechocystis, were tested. Aqueous extracts of cyanobacteria strains showed potent toxicity against A. salina, whereas in P. lividus, methanolic and aqueous extracts showed embryo toxicity, with clear effects on development during early stages. The results suggest that the brackishwater cyanobacteria are producers of bioactive compounds with toxicological effects that may interfere with the dynamics of invertebrate populations.

Frequency of TERT promoter mutations in human cancers

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs)

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.