Plos One
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Microvascular inflammation occurs during sepsis and the endogenous opioid-like peptide nociceptin/orphanin FQ (N/OFQ) is known to regulate inflammation. This study aimed to determine the inflammatory role of N/OFQ and its receptor NOP (ORL1) within the microcirculation, along with anti-inflammatory effects of the NOP antagonist UFP-101 (University of Ferrara Peptide-101) in an animal model of sepsis (endotoxemia). Male Wistar rats (220 to 300 g) were administered lipopolysaccharide (LPS) for 24 h (-24 h, 1 mg kg(-1); -2 h, 1 mg kg(-1) i.v., tail vein). ⋯ Firstly, the rat mesenteric microcirculation expresses NOP receptors and secondly, NOP function (ability to induce dilation) is enhanced with LPS. UFP-101 also reduced microvascular inflammation to endotoxemia in vivo. Hence inhibition of the microvascular N/OFQ-NOP pathway may have therapeutic potential during sepsis and warrants further investigation.
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Neuropeptide kisspeptin has been suggested to be an essential central regulator of reproduction in response to changes in serum gonadal steroid concentrations. However, in spite of wide kisspeptin receptor distribution in the brain, especially in the preoptic area and hypothalamus, the research focus has mostly been confined to the kisspeptin regulation on GnRH neurons. Here, by using medaka whose kisspeptin (kiss1) neurons have been clearly demonstrated to be regulated by sex steroids, we analyzed the anatomical distribution of kisspeptin receptors Gpr54-1 and Gpr54-2. ⋯ In contrast, there was no gpr54-expressing cell in the vicinities of neuromodulatory GnRH2 or GnRH3 neurons. From these results, we suggest that medaka kisspeptin neurons directly regulate some behavioral and neuroendocrine functions via vasotocin/isotocin neurons, whereas they do not regulate hypophysiotropic GnRH1 neurons at least in a direct manner. Thus, direct kisspeptin regulation of GnRH1 neurons proposed in mammals may not be the universal feature of vertebrate kisspeptin system in general.
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Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone. ⋯ Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.
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Following fear conditioning (FC), ex vivo evidence suggests that early dynamics of cellular and molecular plasticity in amygdala and hippocampal circuits mediate responses to fear. Such altered dynamics in fear circuits are thought to be etiologically related to anxiety disorders including posttraumatic stress disorder (PTSD). Consistent with this, neuroimaging studies of individuals with established PTSD in the months after trauma have revealed changes in brain regions responsible for processing fear. However, whether early changes in fear circuits can be captured in vivo is not known. ⋯ Our results indicate that DTI can detect rapid microstructural changes in brain regions known to mediate fear conditioning in vivo. DTI indices could be explored as a translational tool to capture potential early biological changes in individuals at risk for developing PTSD.
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Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. ⋯ Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.