Cancer risk evaluation: Preliminary analysis of inflammatory biomarkers in farmers exposed to zoonotic agents

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Notes on fauna associated with an opportunistic artificial reef near cold-water corals

This short communication provides a sporadic insight on the importance of a hard three-dimensional structure for deepwater fish near CWC. Fish size and behaviour inside the structure and in the surrounding area are described. Additionally, a list of biofouling macroorganisms found on the structure after one year of deployment is presented

Cytotoxicity of spermine oxidation products to multidrug resistant melanoma M14 ADR2 cells: Sensitization by the MDL 72527 lysosomotropic compound

It has been confirmed that multidrug resistant (MDR) human melanoma cells are more sensitive than their wild-type counterparts to H(2)O(2) and aldehydes, the products of bovine serum amine oxidase (BSAO)-catalyzed oxidation of spermine. The metabolites formed by BSAO and spermine are more toxic than exogenous H(2)O(2) and acrolein, even thou-h their concentration is lower during the initial phase of incubation due to their more gradual release than the exogenous products. Both wild-type and MDR cells, after pre-treatment with MDL 72527, an inactivator of polyamine oxidase and a lysosomotropic compound, show to be sensitized to subsequent exposure to BSAO/spermine. Evidence of ultrastructural aberrations and acridine orange release from lysosomes is presented in this work that is in favor of the permeabilization of the lysosomal membrane as the major cause of sensitization by MDL 72527. Owing to its lysosomotropic effect, pre-treatment with MDL 72527 amplifies the ability of the metabolites formed from spermine by oxidative deamination to induce cell death. Since it is conceivable that combined treatment with a lysosomotropic compound and BSAO/spermine would be effective against tumor cells, it is of interest to search for such novel compounds, which might be promising for application in a therapeutic setting

Anticancer drugs and hyperthermia enhance cytotoxicity induced by polyamine enzymatic oxidation products

A correlation between regulation of cell proliferation and polyamine metabolism is described. The latter can enter protein synthesis through the modification of eukaryotic initiation factor 5A (eIF5A) and the formation of the peculiar amino acid hypusine. Specific inhibitors of hypusine formation induce apoptosis that can be potentiated by the combination with cytokines such as interferon alpha (IFN alpha) that itself decreases hypusine synthesis. We have also demonstrated that the concomitant treatment of cancer cells with IFNa and the protein synthesis inhibitor fusion protein TGF alpha/Pseudomonas Aeruginosa toxin synergize in inducing cancer cell growth inhibition. Another way used by polyamines to induce apoptosis is the generation of intracellular oxidative stress through the interaction with bovine serum amine oxidase (BSAO). This enzyme used simultaneously to spermine induces apoptosis, necrosis, inhibition of cell proliferation and inhibition of DNA and protein synthesis in several cell types. The enzymatic oxidation products of polyamine, H2O2 and aldehyde(s) cause these effects. We have recently found that the cytotoxicity of anti-cancer agents, either etoposide or docetaxel, in cancer cells is potentiated in the presence of BSAO/Spermine. In conclusion, polyamine metabolites could be useful in the design of new therapeutic strategies

Effect of peroxides on spermine transport in rat brain and liver mitochondria.

The polyamine spermine is transported into the matrix of various types of mitochondria by a specific uniporter system identified as a protein channel. This mechanism is regulated by the membrane potential; other regulatory effectors are unknown. This study analyzes the transport of spermine in the presence of peroxides in both isolated rat liver and brain mitochondria, in order to evaluate the involvement of the redox state in this mechanism, and to compare its effect in both types of mitochondria. In liver mitochondria peroxides are able to inhibit spermine transport. This effect is indicative of redox regulation by the transporter, probably due to the presence of critical thiol groups along the transport pathway, or in close association with it, with different accessibility for the peroxides and performing different functions. In brain mitochondria, peroxides have several effects, supporting the hypothesis of a different regulation of spermine transport. The fact that peroxovanadate can inhibit tyrosine phosphatases in brain mitochondria suggests that mitochondrial spermine transport is regulated by tyrosine phosphorylation in this organ. In this regard, the evaluation of spermine transport in the presence of Src inhibitors suggests the involvement of Src family kinases in this process. It is possible that phosphorylation sites for Src kinases are present in the channel pathway and have an inhibitory effect on spermine transport under regulation by Src kinases. The results of this study suggest that the activity of the spermine transporter probably depends on the redox and/or tyrosine phosphorylation state of mitochondria, and that its regulation may be different in distinct organs

O conhecimento matemático dos estudantes no início da Licenciatura em Educação Básica: um projeto envolvendo três Escolas superiores de educação

O novo modelo de formação inicial (Decreto-Lei 43/2007) exige que os futuros professores do 1.º e 2.º ciclos do ensino básico e os futuros educadores de infância façam pelo menos 30 ECTS de formação em Matemática na Licenciatura em Educação Básica (LEB), mas a forma e o conteúdo desta formação é da responsabilidade de cada instituição, que define as unidades curriculares, o seu conteúdo e a forma como são lecionadas. Sabe-se que, para além do conteúdo, a forma como o professor aprende tem uma forte influência na forma como vai ensinar. Assim, todos estes aspetos precisam de ser discutidos, tendo por base a investigação já realizada em Portugal e noutros países. Partindo da assunção de que o conhecimento do professor constitui um fator decisivo na interpretação e implementação do currículo e da necessidade de uma discussão alargada de qual deverá ser o conteúdo da formação em Matemática na LEB, as Escolas Superiores de Educação de Lisboa, de Viana do Castelo e de Viseu iniciaram um projeto de investigação que tem como principal objetivo compreender de que modo a formação inicial contribui para o desenvolvimento do conhecimento do professor em Matemática e em Ensino da Matemática e como pode este ser promovido. Uma das questões que o projeto visa investigar é que conhecimento de conteúdo matemático têm os estudantes quando iniciam o curso da LEB. Para caracterizar o conhecimento matemático dos estudantes da LEB, à entrada no curso, foi elaborado um teste diagnóstico, que foi aplicado nas três Escolas Superiores de Educação, em outubro de 2011, a todos os alunos a iniciar o 1.º ano, num total de 268: 143 em Lisboa, 51 em Viseu e 74 em Viana do Castelo. Neste artigo é apresentada uma análise dos principais resultados deste teste bem como as questões e dilemas que aqueles resultados nos colocam

PARP-1 modulates amyloid beta peptide-induced neuronal damage.

Amyloid beta peptide (A beta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with A beta(25-35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. A beta(25-35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following A beta(25-35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that A beta(25-35) induces DNA damage which in turn activates PARP-1. Challenge with A beta(25-35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, A beta(25-35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by A beta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed

Anticancer drugs and hyperthermia enhance cytotoxicity induced by polyamine enzymatic oxidation products Review Article

Summary. A correlation between regulation of cell proliferation and polyamine metabolism is described. The latter can enter protein synthesis through the modification of eukaryotic initiation factor 5A (eIF5A) and the formation of the peculiar amino acid hypusine. Specific inhibitors of hypusine formation induce apoptosis that can be potentiated by the combination with cytokines such as interferona (IFNa) that itself decreases hypusine synthesis. We have also demonstrated that the concomitant treatment of cancer cells with IFNa and the protein synthesis inhibitor fusion protein TGFa=Pseudomonas Aeruginosa toxin synergize in inducing cancer cell growth inhibition. Another way used by polyamines to induce apoptosis is the generation of intracellular oxidative stress through the interaction with bovine serum amine oxidase (BSAO). This enzyme used simultaneously to spermine induces apoptosis, necrosis, inhibition of cell proliferation and inhibition of DNA and protein synthesis in several cell types. The enzymatic oxidation products of polyamine, H 2 O 2 and aldehyde(s) cause these effects. We have recently found that the cytotoxicity of anti-cancer agents, either etoposide or docetaxel, in cancer cells is potentiated in the presence of BSAO=Spermine. In conclusion, polyamine metabolites could be useful in the design of new therapeutic strategies

Polyketone polymer: a new support for direct enzyme immobilization.

Polyketone polymer -[-CO-CH2CH2-](n)-, obtained by copolymerization of ethene and carbon monoxide, is utilized for immobilization of three different enzymes, one peroxidase from horseradish (HRP) and two amine oxidases, from bovine serum (BSAO) and lentil seedlings (LSAO). The easy immobilization procedure is carried out in diluted buffer, at pH 7.0 and 3 degrees C, gently mixing the proteins with the polymer. No bifunctional reagents and spacer arms are required for the immobilization, which occurs exclusively via a large number of hydrogen bonds between the carbonyl groups of the polymer and the -NH groups of the polypeptidic chain. Experiments demonstrate a high linking capacity of polymer for BSAO and an extraordinary strong linkage for LSAO. Moreover, activity measurements demonstrate that immobilized LSAO totally retains the catalytic characteristics of the free enzyme, where only a limited increase of K-M value is observed. Finally, the HRP-activated polymer is successfully used as active packed bed of an enzymatic reactor for continuous flow conversion and flow injection analysis of hydrogen peroxide containing solutions. (c) 2006 Elsevier B.V. All rights reserved