Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis

Chemical composition similarity between the essential oils isolated from male and female specimens of each five Baccharis species

In the few studies published on essential oils from female and male specimens of Baccharis species, strong differences between the compositions of both samples were always found. The experiments conducted in this study make use of strategies to minimize the interference from genetic and environmental factors. Essential oils from leaves of female and male specimens of five Baccharis species were investigated by gas chromatography-mass spectrometry plus flame ionization detector (GC-MS-FID): B. caprariaefolia and B. dracunculifolia, which have been previously studied with similar aims; and B. coridifolia, B. semiserrata var. elaegnoides and B. pentaptera, the latter two not yet mentioned in the literature. The results were followed by hierarchical cluster analysis, verifying the formation of groups indicative of the great similarity of essential oils from male and female specimens of all five species. The study reinforces the value of field observation in natural product research and points genetic and ecological factors as main responsible for differences in the secondary metabolites of the studied plants._________________________________________________________________________________________ RESUMO: Nos poucos estudos publicados comparando óleos essenciais de espécimes femininos e masculinos de espécies Baccharis, fortes diferenças entre as composições de ambas as amostras foram sempre encontradas. Os experimentos realizados nesta pesquisa utilizam estratégias para minimizar a interferência de fatores genéticos e ecológicos. Os óleos essenciais das folhas de espécimes femininos e masculinos de cinco espécies Baccharis foram pesquisados com uso de um cromatógrafo gasoso acoplado a um espectrômetro de massas e a um detector de ionização de chama (CG-EM-DIC): B. caprariaefolia e B. dracunculifolia, já pesquisadas anteriormente com objetivos similares; e B. coridifolia, B. semiserrata var. elaegnoides e B. pentaptera, as duas últimas ainda não mencionadas na literatura química. Os resultados foram acompanhados por análise hierárquica de grupos, verificando-se a formação de grupos indicativos da grande similaridade entre óleos essenciais dos espécimes masculinos e femininos de todas as cinco espécies. O estudo reafirma o valor das observações de campo na pesquisa de produtos naturais, e aponta fatores genéticos e ecológicos como principais responsáveis por diferenças no metabolismo secundário das plantas estudadas

ESTUDO DA QUALIDADE DAS ÁGUAS DO RIO MAROMBAS (SC/BRASIL), UTILIZANDO PARÂMETROS FÍSICO-QUÍMICOS E BIOENSAIOS.

O presente trabalho propôs realizar estudos preliminares de avaliação da qualidade das águas do Rio Marombas (SC-Brasil), utilizando parâmetros físico-químicos e bioensaios. Amostras de águas do Rio Marombas foram coletadas em 3 pontos e realizada a determinação de pH, oxigênio dissolvido (OD), análise de agroquímicos, hidrocarbonetos policíclicos aromáticos (HPA’s), compostos orgânicos voláteis (COV’s) e bifenilas policloradas (PCB’s). Foram executados ensaios de toxicidade aguda (CL50) em microcrustáceos Artemia sp. e de fitotoxicidade em Allium cepa L. avaliada pela inibição de crescimento e peso de raízes e pelos biomarcadores de estresse oxidativo glutationa reduzida (GSH) e peroxidação lipídica. Os resultados dos parâmetros físico-químicos indicaram que os valores de pHestiveram compatíveis com padrões previstos pela legislação. Foi constatada a presença dos agroquímicos metomil nos Pontos 1 e 2 e metconazol no Ponto 1. Os bioensaios revelaram que não houve toxicidade em Artemia sp. e ausência de inibição de crescimento e peso de raízes em Allium cepa L. A concentração de GSH estava significativamente aumentada no Ponto 3 quando comparada ao Ponto 1 e ao controle negativo. Não foi observada diferença significativa na avaliação de peroxidação lipídica entre os diferentes grupos. Esses resultados indicam que as águas do Rio Marombas podem estar sendo contaminadas por agroquímicos, sugerindo a necessidade de implementação de sistema de monitoramento periódico de sua qualidade.Palavras-chave: rio Marombas; parâmetros físico-químicos; bioensaiosSTUDY OF WATER QUALITY FROM THE MAROMBAS RIVER (SC/BRAZIL) USING THE PHYSICOCHEMICAL PARAMETERS AND BIOASSAYS.ABSTRACTThe present study proposed preliminary studies assessing the quality of water from the river Marombas (SCBrazil) using the physicochemical parameters and bioassays. Samples of water from Marombas river were collected at three points and it was determined the pH, dissolved oxygen (DO), concentration of agrochemicals, polycyclic aromatic hydrocarbons (PAH’s), volatile organic compounds (VOC`s) and polychlorinated biphenyls (PCB´s). Acute toxicity tests (LC50) were carried out in microcrustaceans Artemia sp. and phytotoxicity tests in Allium cepa L. assessed through theinhibition of growth and weight of roots and by biomarkers of oxidative stress reduced glutathione (GSH) and lipid peroxidation. The results of physicochemical parameters indicated that the pH values were consistent with standards established by the legislation. It could be observed the presence of the agrochemicals methomyl in Points 1 and 2 and metconazole in Point 1. The bioassays showed absence of the acute toxicity in Artemia sp. and there was no inhibition of growth and weight of roots in Allium cepa L. The concentration of GSH was significantly increased (P<0.05) in Point 3 when compared to Point 1 and the negative control. No significant difference could be observed in the evaluation of lipid peroxidation between different groups. These results demonstrate that the water of the Marombas river is contaminated by agrochemicals, suggesting the necessity of implementing a system of monitoring its quality.Key words: Marombas river, physicochemical parameters, bioassay

How knowledge flows in university-industry relations: An overview from two economic sectors in Brazil

Purpose – The purpose of this paper is to characterize the knowledge flow between companies and universities based on national and sectoral systems of innovation perspective. It is argued here that high-tech sectors can describe a knowledge flow mainly based on scientific research, while sectors with lower technological impact may establish relations based on technical needs. Design/methodology/approach – A case study research was conducted in the horticulture and aerospace sectors in Brazil. Thirteen interviews were performed with chief executive officer’s and academic researchers from both fields. Findings – Results demonstrated differences in technology development and knowledge infrastructure when comparing both sectors, reflecting the impacts of national and sectoral systems of innovation. The horticulture sector presented technological limitations due to restricted eating habits, logistics, knowledge development at universities and difficulties on the establishment of partnerships between local companies and Embrapa, the main public research centre. Such restrictions limit academic activities while companies look for research partnerships abroad. Space industry also has limited technological development due to international embargoes and lack of research alignment between companies and universities. Companies end up developing research activities internally, usually funded by governmental tenders. Research limitations/implications – The horticulture sector has limitations, as it is not the main agriculture area in science and technology applications. Future studies may analyse areas like soy beans, sugar cane and coffee, which may present differences specially regarding sectoral systems of innovation. Originality/value – The finding of this paper may influence the review of sectoral innovation policies, improving the development of local research activities which may be a source of valuable knowledge to companies. It also demonstrates the importance of the knowledge flow to improve sector’s technology level