Comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine

Cancer is still one of the most challenging diseases to treat, making the pursuit for novel molecules with potential anticancer activity an important research topic. Herein, we have performed a comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine. The former is a well-known bioluminescent substrate, while the latter is a metabolic product of the resulting bioluminescent reaction. While both types of analogs showed anticancer activity toward lung and gastric cancer cell lines, we have obtained data that highlight relevant differences between the activity of these two types of compounds. More specifically, we observed relevant differences in structure-activity relationships between these types of compounds. Also, coelenteramine analogs showed time-dependent activity, while coelenterazine-based compounds usually present time-independent activity. Coelenterazine analogs also appear to be relatively safer toward noncancer cells than coelenteramine analogs. There was also seen a correlation between the activity of the coelenterazine-based compounds and their light-emission properties. Thus, these results further indicate the potential of the marine coelenterazine chemi-/bioluminescent system as a source of new molecules with anticancer activity, while providing more insight into their modes of action

Formação em serviço: impacto de novas estratégias

A formação em enfermagem contribui para o desenvolvimento de competências cognitivas e técnicas, mas também relacionais que possam ser transferíveis para o contexto de trabalho pelo que se deve privilegiar a formação em serviço como forma de manter actualizados, aprofundar e desenvolver os conhecimentos adquiridos. Faz parte do descritivo de funções do enfermeiro e consta dos seus princípios orientadores da prática, a constante actualização através da formação. (ver OE ….) Identificada a irregular e reduzida formação interna que ocorre no serviço (obrigatória ou não), a par de identificação de lacunas em temas fulcrais, foi implementada no serviço de Cardiologia do Hospital Fernando Fonseca E.P.E. múltiplas estratégias de intervenção que visem o desenvolvimento profissional dos enfermeiros e auxiliares de acção médica através do aumento da formação na sua globalidade. A diversas estratégias preconizadas consistem na contabilização das horas de formação como horas de serviço, inscrição dos formandos para as formações com disponibilização do dia expresso em horário, possibilidade de negociação de objectivos para as avaliações de desempenho anuais, existência de um cronograma anual, de um Manual do Formador como guia orientador à prática formativa, abordagem de diferentes áreas focado nas necessidades de serviço e também no interesse individual, com apresentações frequentes e que abranja todos os profissionais, formações semanais de curta duração a decorrer em passagem de turno, formações mensais de uma hora em sala de formação, trabalhos disponibilizados a toda a equipa. Esta etapa formativa decorreu ao longo de todo o ano de 2014, cabendo em fase posterior, a sua análise e avaliação, com base em indicadores de formação em serviço, como sendo indicadores de execução como a taxa de número de horas de formação e taxa de número de acções de formação, acrescida da avaliação de satisfação individual dos participantes e suas opiniões face às estratégias implementadas, através da realização de questionários aos mesmos. Acresce a avaliação da variação de adesão à formação não obrigatória face às formações disponibilizadas, comparativamente com as obrigatórias realizadas face à totalidade de formação obrigatórias. A análise dos referidos dados, revelam-nos uma percentagem significativa de acções de formação ocorridas, assim como elevado número de horas formativas, pelo que sugere um método eficaz de acção. Uma análise preliminar revela satisfação e interesse equiparados às taxas formativas. Daqui se poderá depreender que o conjunto de estratégias implementadas veio ao encontro dos objectivos estabelecidos. Cabe, em fase posterior, a análise do impacto formativo na melhoria das práticas, eventualmente com base em indicadores adequados a cada formação, complementada com os dados trimestrais das auditorias aos cuidados de enfermagem do HFF

Langerhans cell histiocytosis involving the liver of a male smoker: a case report

<p>Abstract</p> <p>Introduction</p> <p>Langerhans' cell histiocytosis is a proliferative histiocytic disorder of unknown cause originating from dendritic cells.</p> <p>Case presentation</p> <p>The authors report a case of Langerhans' cell histiocytosis in a 48-year-old man with multisystemic disease presentation, including liver involvement.</p> <p>Conclusion</p> <p>Hepatic involvement is an uncommon feature in this rare disease and there is no consensus on the most effective therapeutic approach.</p

Content of Lipids, Fatty Acids, Carbohydrates, and Proteins in Continental Cyanobacteria: A Systematic Analysis and Database Application

The lipid, fatty acid, protein, and carbohydrate contents in cyanobacterial strains and biomass can vary by orders of magnitude. Many publications (thousands of peer-reviewed articles) require more work to extract their precise concentration values (i.e., different units, inaccurate data), which makes them not easily exploitable. For this purpose, tables have been compiled from the literature data, including lipids, fatty acids, proteins, and carbohydrates composition and quantities in cyanobacteria. A lot of data (323) were collected after careful a literature search, according to selected criteria in order to distinguish separately cyanobacteria, and according to categories of genus and species and generate average values of the contents of these cell components. These data are exploited in a first systematic analysis of the content in types of strains. Our database can be a powerful tool for biologists, chemists, and environmental agencies to determine the potential concentration of high-value chemical building blocks directly from low-value bloom biomass, cell cultures, or debris in the sediment, offering the potential to minimize environmental waste and add value to the agro-industrial residues. The database can also support strategies for food manufacturers to develop new products with optimized properties for veterinarian applications

Structure of Extreme Correlated Equilibria: a Zero-Sum Example and its Implications

We exhibit the rich structure of the set of correlated equilibria by analyzing the simplest of polynomial games: the mixed extension of matching pennies. We show that while the correlated equilibrium set is convex and compact, the structure of its extreme points can be quite complicated. In finite games the ratio of extreme correlated to extreme Nash equilibria can be greater than exponential in the size of the strategy spaces. In polynomial games there can exist extreme correlated equilibria which are not finitely supported; we construct a large family of examples using techniques from ergodic theory. We show that in general the set of correlated equilibrium distributions of a polynomial game cannot be described by conditions on finitely many moments (means, covariances, etc.), in marked contrast to the set of Nash equilibria which is always expressible in terms of finitely many moments

Synchrotron-based FTIR evaluation of biochemical changes in cancer and noncancer cells induced by brominated marine coelenteramine

The mode of action toward gastric cancer cells of brominated Coelenteramine, an analogue of a metabolic product of a marine bioluminescent reaction, was investigated by synchrotron radiation-based Fourier Transform Infrared spectrocopy (FTIR). This method revealed that the anticancer activity of brominated Coelenteramine is closely connected with cellular lipids, by affecting their organization and composition. More specifically, there is an increasing extent of oxidative stress, which results in changes in membrane polarity, lipid chain packing and lipid composition. However, this effect was not observed in a noncancer cell line, helping to explain its selectivity profile. Thus, synchrotron radiation-based FTIR helped to identify the potential of this Coelenteramine analogue in targeting membrane lipids, while proving to be a powerful technique to probe the mechanism of anticancer drugs

Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals

Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction

Low temperature scattering with the R-matrix method: the Morse potential

Experiments are starting to probe collisions and chemical reactions between atoms and molecules at ultra-low temperatures. We have developed a new theoretical procedure for studying these collisions using the R-matrix method. Here this method is tested for the atom -- atom collisions described by a Morse potential. Analytic solutions for continuum states of the Morse potential are derived and compared with numerical results computed using an R-matrix method where the inner region wavefunctions are obtained using a standard nuclear motion algorithm. Results are given for eigenphases and scattering lengths. Excellent agreement is obtained in all cases. Progress in developing a general procedure for treating ultra-low energy reactive and non-reactive collisions is discussed.Comment: 18 pages, 6 figures, 3 tables, conferenc