Plos One
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Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. ⋯ Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection.
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The neuropeptide substance P (SP) is a well-known mediator of neurogenic inflammation following a variety of CNS disorders. Indeed, inhibition of SP through antagonism of its receptor, the tachykinin NK1 receptor, has been shown to be beneficial following both traumatic brain injury and stroke. Such studies demonstrated that administration of an NK1 receptor antagonist reduced blood-brain-barrier permeability, edema development and improved functional outcome. ⋯ Administration of an NK1 receptor antagonist was not effective in reducing BSCB permeability, edema, ITP, or functional deficits following SCI. We conclude that SP mediated neurogenic inflammation does not seem to play a major role in BSCB disruption, edema development and consequential tissue damage seen in acute traumatic SCI. Rather it is likely that the severe primary insult and subsequent hemorrhage may be the key contributing factors to ongoing SCI injury.
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In this work, a lysostaphin-loaded, control-released, self-setting and injectable porous bone cement with efficient protein delivery was prepared by a novel setting method using hydroxyapatite/chitosan (HA/CS) composite scaffold. The cement samples were made through cementitious reactions by mixing solid powder, a mixture of HA/CS composite particles, lysostaphin, Ca(OH)2, CaCO3 and NaHCO3, with setting liquid containing citric acid, acetic acid, NaH2PO4, CaCl2 and poloxamer. The setting parameters of the cement samples were determined. ⋯ Finally the antibacterial activity assay indicated that the loaded lysostaphin had good release ability and strong antibacterial enzymatic activity against methicillin-resistant Staphylococcus aureus. Collectively, all the results suggested that the lysostaphin-loaded self-setting injectable porous bone cement released the protein in a controlled and effective way and the protein activity was well retained during the setting and releasing process. Thus this bone cement can be potentially applied as a combination of artificial bone substitute and controlled-release system for delivery of lysostaphin to treat bone defects and infections.
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The effects of growth hormone on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model and the underlying mechanism was explored. ⋯ rhGH treatment had a positive effect on cognitive function, which was more evident in GH-deficient rats. The increased expression of hippocampal and prefrontal BDNF and TrkB mRNA is implicated in rhGH therapy to improve cognitive function. Changes in the expression of hippocampal SYN mRNA following rhGH therapy may also play a role in improving cognitive function.
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Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. ⋯ When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting.