Intrathecal Injection of Spironolactone Attenuates Radicular Pain by Inhibition of Spinal Microglia Activation in a Rat Model

Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation.Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn't affected.These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects

IPACK2009-89408 A Novel Approach to Optimizing Solder Reflow Process in Assembling PQFN Packages

ABSTRACT Solder void is a common defect during assembling Power Quad Flat No-lead (PQFN) packages. It is detrimental to the packages' feature of good power management and reliability performance and needs to be controlled within certain specification. Reflow process is well considered as critical to the solder void formation for a given solder paste. The transport index of reflow oven, which determines how solder paste are reflowed through solder reflowing process within the reflow oven, has therefore been optimized by a novel approach in this study. The underlying principle of the optimization is to find such a transport index that solder paste have a best possibility to experience homogeneous heat transfer during reflow phase of the whole reflow process. Different from the traditionally experimental trial and error, the present approach first predicts the optimal transport index by calculating the relative locations of lead frame (solder paste are dispensed on it) to the heating blocks of the reflow oven and the amount of heat input at different locations on the lead frame during the reflow phase. Then only necessary experiments are conducted to validate the prediction. As the theoretic calculations already screen out part of experiments that have to be conducted in the traditional trial and error, the present approach saves time and cost in practice

A Novel Nuclear Function for the Interleukin-17 Signaling Adaptor Protein Act1

<div><p>In the context of the human airway, interleukin-17A (IL-17A) signaling is associated with severe inflammation, as well as protection against pathogenic infection, particularly at mucosal surfaces such as the airway. The intracellular molecule Act1 has been demonstrated to be an essential mediator of IL-17A signaling. In the cytoplasm, it serves as an adaptor protein, binding to both the intracellular domain of the IL-17 receptor as well as members of the canonical nuclear factor kappa B (NF-κB) pathway. It also has enzymatic activity, and serves as an E3 ubiquitin ligase. In the context of airway epithelial cells, we demonstrate for the first time that Act1 is also present in the nucleus, especially after IL-17A stimulation. Ectopic Act1 expression can also increase the nuclear localization of Act1. Act1 can up-regulate the expression and promoter activity of a subset of IL-17A target genes in the absence of IL-17A signaling in a manner that is dependent on its N- and C-terminal domains, but is NF-κB independent. Finally, we show that nuclear Act1 can bind to both distal and proximal promoter regions of <i>DEFB4</i>, one of the IL-17A responsive genes. This transcriptional regulatory activity represents a novel function for Act1. Taken together, this is the first report to describe a non-adaptor function of Act1 by directly binding to the promoter region of IL-17A responsive genes and directly regulate their transcription.</p></div

IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction

Emerging evidence suggests that the T(H)17 subset of αβ T cells contributes to the development of allergic asthma. In this study we found that mice lacking αvβ8 on dendritic cells failed to generate T(H)17 cells in the lung and were protected from AHR in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. IL-17A enhanced contractile force generation through a NF-κB/RhoA/ROCK2 signaling cascade. Mice lacking integrin αvβ8 on dendritic cells showed impaired activation of this pathway after OVA sensitization and challenge, and the diminished contraction of tracheal rings from these mice was reversed by IL-17A. These data indicate that IL-17A produced by T(H)17 cells contributes to allergen-induced AHR through direct effects on airway smooth muscle