Dysfunction of Nrf-2 in CF Epithelia Leads to Excess Intracellular H2O2 and Inflammatory Cytokine Production

Cystic fibrosis is characterized by recurring pulmonary exacerbations that lead to the deterioration of lung function and eventual lung failure. Excessive inflammatory responses by airway epithelia have been linked to the overproduction of the inflammatory cytokine IL-6 and IL-8. The mechanism by which this occurs is not fully understood, but normal IL-1β mediated activation of the production of these cytokines occurs via H2O2 dependent signaling. Therefore, we speculated that CFTR dysfunction causes alterations in the regulation of steady state H2O2. We found significantly elevated levels of H2O2 in three cultured epithelial cell models of CF, one primary and two immortalized. Increases in H2O2 heavily contributed to the excessive IL-6 and IL-8 production in CF epithelia. Proteomic analysis of three in vitro and two in vivo models revealed a decrease in antioxidant proteins that regulate H2O2 processing, by ≥2 fold in CF vs. matched normal controls. When cells are stimulated, differential expression in CF versus normal is enhanced; corresponding to an increase in H2O2 mediated production of IL-6 and IL-8. The cause of this redox imbalance is a decrease by ∼70% in CF cells versus normal in the expression and activity of the transcription factor Nrf-2. Inhibition of CFTR function in normal cells produced this phenotype, while N-acetyl cysteine, selenium, an activator of Nrf-2, and the overexpression of Nrf-2 all normalized H2O2 processing and decreased IL-6 and IL-8 to normal levels, in CF cells. We conclude that a paradoxical decrease in Nrf-2 driven antioxidant responses in CF epithelia results in an increase in steady state H2O2, which in turn contributes to the overproduction of the pro-inflammatory cytokines IL-6 and IL-8. Treatment with antioxidants can ameliorate exaggerated cytokine production without affecting normal responses

Conhecimento vocal e a importância da voz como recurso pedagógico na perspectiva de professores universitários

OBJETIVO: investigar o conhecimento vocal e sua importância como recurso pedagógico em professores universitários. MÉTODOS: participaram 112 docentes, média de 46,60 anos, 35,7% do sexo masculino e 64,3% do feminino, 66,1% doutores. Utilizou-se o questionário Condições de Produção Vocal-Professor, adaptado pela pesquisadora, além da inserção de novas questões abertas e fechadas de interesse para o estudo, as quais foram assinaladas em uma escala analógica de zero a dez. Foram coletadas amostras de voz dos professores e analisadas por avaliação fonoaudiológica. As questões fechadas receberam tratamento estatístico, considerando-se a média das notas autorreferidas, em cada variável pesquisada. Os resultados foram correlacionados a partir das variáveis: sexo e presença/ausência de alteração vocal. Organizaram-se as respostas das questões abertas por similaridade de conteúdo e frequência de ocorrência. RESULTADOS: constatou-se associação significante entre sexo feminino e voz fina, fadiga e perda da voz; presença de distúrbio de voz e autorreferência à voz fraca, rouquidão, voz insuficiente para o trabalho e fadiga vocal. Os professores participaram da pesquisa para colaborar e melhorar a voz na docência; mudariam suas vozes nos aspectos de intensidade, tom e modulação; os recursos vocais mais utilizados em sala de aula foram variação de tom e intensidade, modulação e pausas; e quando a voz está alterada, recorrem ao repouso vocal e à hidratação. Atribuiu-se a média de 9,42 para a voz como recurso pedagógico. CONCLUSÃO: o conhecimento vocal dos participantes foi apropriado e eles avaliaram a voz como recurso pedagógico essencial

'Statins in retinal disease'

Statins are known for their blood cholesterol-lowering effect and are widely used in patients with cardiovascular and metabolic diseases. Research over the past three decades shows that statins have diverse effects on different pathophysiological pathways involved in angiogenesis, inflammation, apoptosis, and anti-oxidation, leading to new therapeutic options. Recently, statins have attracted considerable attention for their immunomodulatory effect. Since immune reactivity has been implicated in a number of retinal diseases, such as uveitis, age-related macular degeneration (AMD) and diabetic retinopathy, there is now a growing body of evidence supporting the beneficial effects of statins in these retinopathies. This review evaluates the relationship between statins and the pathophysiological basis of these diseases, focusing on their potential role in treatment. A PubMed database search and literature review was conducted. Among AMD patients, there is inconsistent evidence regarding protection against development of early AMD or delaying disease progression; though they have been found to reduce the risk of developing choroidal neovascular membranes (CNV). In patients with retinal vein occlusion, there was no evidence to support a therapeutic benefit or a protective role with statins. In patients with diabetic retinopathy, statins demonstrate a reduction in disease progression and improved resolution of diabetic macular oedema (DMO). Among patients with uveitis, statins have a protective effect by reducing the likelihood of uveitis development