Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model

<p>Abstract</p> <p>Background</p> <p>Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury.</p> <p>Methods</p> <p>Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (V_T) (20 ml/kg) and low V_T(6 ml/kg). Histological evaluation, TLR2, TLR4, <it>IRAK3 </it>gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (IκBα), tumor necrosis factor-alpha (<it>TNF-α</it>) and interleukin-6 (<it>IL6</it>) gene expression in the lungs and TNF-α and IL-6 protein serum concentrations were analyzed.</p> <p>Results</p> <p>High V_Tmechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of <it>IRAK3 </it>lung gene expression and protein levels, a significant decrease of IκBα, and a higher lung expression and serum concentrations of pro-inflammatory cytokines.</p> <p>Conclusions</p> <p>The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections.</p

O trabalho de enfermagem em saúde mental: contradições e potencialidades atuais El trabajo de enfermería en salud mental: contradicciones y potencialidades actuales Mental health nursing work: contradictions and current potentialities

Este estudo teve por objetivo identificar contradições e desafios que se apresentam atualmente no trabalho de enfermagem em saúde mental, no contexto da Reforma Psiquiátrica, tendo por referência a construção histórico-social desse processo de trabalho. A Reforma Psiquiátrica pressupõe um novo desenho de objeto e instrumentos de trabalho, que são ainda pouco visíveis na prática dos enfermeiros, e a possibilidade de se alcançar a condição de sujeito-cidadão para o portador de sofrimento mental - modo de ser e finalidade do trabalho - que está diretamente relacionada à consciência de sujeito-cidadão do trabalhador de enfermagem.<br>Este trabajo tuvo como objetivo identificar las contradicciones y posibilidades que se presentan actualmente en el trabajo de enfermería en salud mental, en el proceso de la Reforma Psiquiátrica, basado en la construcción histórico-social de este proceso de trabajo. Se destaca que la Reforma Psiquiátrica presenta un nuevo diseño de objeto y de instrumento de trabajo que casi no se observa en el quehacer del enfermero. Sostenemos que la posibilidad de alcanzar la condición de sujeto-ciudadano del ser humano en sufrimiento psíquico, se relaciona directamente con la concientización del enfermero, como sujeto-trabajador-ciudadano.<br>This study aimed to identify contradictions and challenges that are present nowadays in mental health nursing work, in the context of the Psychiatric Reform, on the basis of the historical-social construction of this working process. The Psychiatric Reform presupposes a new design of work purpose and instruments, which still have little visibility in nursing practice, and the possibility for the person in mental suffering to achieve the subject-citizen condition - way of being and work purpose - which is directly related with the subject-citizen awareness of the nursing worker

Impact of the {omega}-3 to {omega}-6 Polyunsaturated Fatty Acid Ratio on Cytokine Release in Human Alveolar Cells.

BACKGROUND: ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)-induced cytokine release by human alveolar cells was affected by changes in the ω-3/ω-6 ratio of cell membranes induced by different supplies of PUFAs. METHODS: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. RESULTS: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin-6, and interleukin-8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti-inflammatory interleukin-10 (P < .001). The balance between proinflammatory and anti-inflammatory cytokines showed an anti-inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). CONCLUSIONS: This study showed that proinflammatory cytokine release was dependent on the proportion of ω-3 in the ω-3/ω-6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω-6 to ω-3 in nutrition support of patients with acute lung injury