P465L-PPARγ mutation confers partial resistance to the hypolipidaemic action of fibrates

Familial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPAR. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated to this mutation using a humanised mouse model that recapitulated most of the clinical symptoms observed in human patients under different experimental conditions. One of the key clinical manifestations observed both in humans and mouse models is the ectopic accumulation of fat in the liver. Here, we dissect the molecular mechanisms that contribute to the excessive accumulation of lipids in the liver and characterise the negative effect of this PPAR mutation on the activity of PPAR in vivo when activated by fibrates. P465L mice have increased levels of insulin and free fatty acids (FFA), exhibit decreased levels of Very Low Density Lipoproteins (VLDL) when fed high fat diet (HFD) and partial impaired response to the hypolipidemic action of WY14643. This indicates that the deleterious effects of P465L-PPAR mutation may be augmented by their collateral negative effect on PPAR function.Wellcome Trust, MRC MDU (MC_UU_12012/2), FP7-MITIN (Integration of the System Models of Mitochondrial Function and Insulin Signaling and its Application in the Study of Complex Diseases) (Grant Agreement 223450) and H2020 EPoS (Elucidating Pathways of Steatohepatitis) (Grant Agreement 634413). Disease Model Core, Biochemistry Assay Lab and the Histology Core are funded by MRC_MC_UU_12012/5 and a Wellcome Trust Strategic Award [100574/Z/12/Z

Micronucleus frequency in children exposed to biomass burning in the Brazilian Legal Amazon region: a control case study

<p>Abstract</p> <p>Background</p> <p>The Amazon represents an area of 61% of Brazilian territory and is undergoing major changes resulting from disorderly economic development, especially the advance of agribusiness. Composition of the atmosphere is controlled by several natural and anthropogenic processes, and emission from biomass burning is one with the major impact on human health. The aim of this study was to evaluate genotoxic potential of air pollutants generated by biomass burning through micronucleus assay in exfoliated buccal cells of schoolchildren in the Brazilian Amazon region.</p> <p>Methods</p> <p>The study was conducted during the dry seasons in two regions of the Brazilian Amazon. The assay was carried out on buccal epithelial cells of 574 schoolchildren between 6-16 years old.</p> <p>Results</p> <p>The results show a significant difference between micronucleus frequencies in children exposed to biomass burning compared to those in a control area.</p> <p>Conclusions</p> <p>The present study demonstrated that in situ biomonitoring using a sensitive and low cost assay (buccal micronucleus assay) may be an important tool for monitoring air quality in remote regions. It is difficult to attribute the increase in micronuclei frequency observed in our study to any specific toxic element integrated in the particulate matters. However, the contribution of the present study lies in the evidence that increased exposure to fine particulate matter generates an increased micronuclei frequency in oral epithelial cells of schoolchildren.</p

Genotoxic potential generated by biomass burning in the Brazilian Legal Amazon by Tradescantia micronucleus bioassay: a toxicity assessment study

<p>Abstract</p> <p>Background</p> <p>The Brazilian Amazon has suffered impacts from non-sustainable economic development, especially owing to the expansion of agricultural commodities into forest areas. The Tangará da Serra region, located in the southern of the Legal Amazon, is characterized by non-mechanized sugar cane production. In addition, it lies on the dispersion path of the pollution plume generated by biomass burning. The aim of this study was to assess the genotoxic potential of the atmosphere in the Tangará da Serra region, using <it>Tradescantia pallida </it>as <it>in situ </it>bioindicator.</p> <p>Methods</p> <p>The study was conducted during the dry and rainy seasons, where the plants were exposed to two types of exposure, active and passive.</p> <p>Results</p> <p>The results showed that in all the sampling seasons, irrespective of exposure type, there was an increase in micronucleus frequency, compared to control and that it was statistically significant in the dry season. A strong and significant relationship was also observed between the increase in micronucleus incidence and the rise in fine particulate matter, and hospital morbidity from respiratory diseases in children.</p> <p>Conclusions</p> <p>Based on the results, we demonstrated that pollutants generated by biomass burning in the Brazilian Amazon can induce genetic damage in test plants that was more prominent during dry season, and correlated with the level of particulates and elevated respiratory morbidity.</p

Probing the mechanism of the Ugi four-component reaction with charge-tagged reagents by ESI-MS(/MS)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The mechanism of the Ugi four-component reaction has been investigated by electrospray ionization (tandem) mass spectrometry using charge-tagged reagents (a carboxylic acid or an amine) to favour detection. Key intermediates were transferred directly via ESI(+) from the reaction solution to the gas phase and characterized by MS measurements and MS/MS collision induced dissociation. The Mumm rearrangement (final step) was also investigated by both travelling wave ion mobility mass spectrometry and DFT calculations. The data seem to consolidate the amazingly selective mechanism of this intricate four-component reaction.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.503338340FAPDFCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FINATECDPP-UnBCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Resiliência na área da Enfermagem em Oncologia Resiliencia en el área de Enfermería en Oncologia Resilience and oncology nursing

Este estudo objetivou mapear a produção científica, nacional e internacional, sobre a resiliência na Enfermagem em Oncologia e discutir sua aplicabilidade na assistência. Resiliência origina-se do latim resiliens e significa saltar para trás, voltar, ser impelido, recuar, encolher-se, romper. Trata-se de revisão sistemática sem meta análise nas bases de dados Public Medical (PubMed), Literatura Internacional em Ciências da Saúde (Medline), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Base de Dados de Enfermagem (BDENF) e nos sites da Oncology Nursing Society e da International Society of Nurses in Cancer Care. Os descritores foram: resilience e nursing; resilience, cancer e oncology; resilience, nursing, cancer e oncology; resiliência e enfermagem; resiliência, câncer e oncologia; resiliência, enfermagem, câncer e oncologia. Foram encontrados 116 artigos e selecionados cinco artigos que abordam a resiliência vinculada à Enfermagem em Oncologia. Verifica-se uma lacuna na utilização do conceito na Enfermagem em Oncologia na América Latina, e incipiência nas produções internacionais. Há necessidade do incremento da abordagem da resiliência nessa área e ampliação da discussão na temática.<br>En este estudio se tuvo como objetivo listar la producción científica nacional e internacional, sobre la resiliencia en el área de Enfermería en Oncología y discutir su aplicabilidad en la asistencia. La resiliencia se origina del latin resiliens y significa saltar hacia atrás, volver, ser impelido, retroceder, encogerse, romper. Se trata de una revisión sistemática sin meta análisis realizada en las bases de datos Public Medical (PubMed), Literatura Internacional en Ciencias de la Salud (Medline), Literatura Latino-Americana y del Caribe en Ciencias de la Salud (LILACS) y Base de Datos de Enfermería (BDENF) y en los sites de la Oncology Nursing Society y de la International Society of Nurses in Cancer Care. Los descriptores fueron: resilience y nursing; resilience, cancer e oncology; resilience, nursing, cancer y oncology; resiliencia y enfermería; resiliencia, cáncer y oncología; resiliencia, enfermería, cáncer y oncología. Fueron encontrados 116 artículos y seleccionados cinco artículos que abordaban la resiliencia vinculada a la Enfermería en Oncología. Se verifica una laguna en la utilización del concepto en la enfermería en oncología en América Latina, e incipiencia en las producciones internacionales. Hay necesidad de incremento del abordaje de la resiliencia en esa área así como la ampliación de la discusión en la temática.<br>The objectives of this study were to synthesize the national and international scientific publications on resilience and oncology nursing and to discuss the application of resilience in nursing practice. Resilience has its origin in the Latin "resilience" meaning recover from or adjust to, change, to be pushed back, recover its size and shape, and to break. A systematic literature review was conducted in the PubMed (Public Medical), MEDLINE (Medical Literature Analysis and Retrieval System Online), LILACS (Latin American and Caribbean Health Sciences Literature), BDENF (Base de Dados de Enfermagem "Nursing Database"), and the web sites of the Oncology Nursing Society and the International Society of Nurses in Cancer Care. Key words in English and in Portuguese included "Resilience AND Nursing," "Resilience AND Cancer AND Oncology," "Resilience AND Nursing AND Cancer AND Oncology." From the 116 publications retrieved, only 5 publications were on oncology nursing. There was a gap in the use of the concept of resilience in oncology nursing in Latin American publications. In addition, the study and use of the concept resilience in the international publications continue in incipient phase. Thus, there is a need for discussions regarding the use of resilience in oncology nursing