Role of myosin light chain kinase in intestinal epithelial barrier defects in a rat model of bowel obstruction

<p>Abstract</p> <p>Background</p> <p>Bowel obstruction is a common cause of abdominal emergency, since the patients are at increased risk of septicemia resulting in high mortality rate. While the compartmentalized changes in enteric microfloral population and augmentation of bacterial translocation (BT) have already been reported using experimental obstruction models, alterations in epithelial permeability of the obstructed guts has not been studied in detail. Myosin light chain kinase (MLCK) is actively involved in the contraction of epithelial perijunctional actinomyosin ring and thereby increases paracellular permeability. In the current study we attempt to investigate the role of MLCK in epithelial barrier defects using a rat model of simple mechanical obstruction.</p> <p>Methods</p> <p>Wistar rats received intraperitoneal injection of ML-7 (a MLCK inhibitor) or vehicle at 24, 12 and 1 hrs before and 12 hrs after intestinal obstruction (IO). The distal small intestine was obstructed with a single ligature placed 10 cm proximal to the ileocecal junction in IO rats for 24 hrs. Sham-operated rats served as controls.</p> <p>Results</p> <p>Mucosal injury, such as villous blunting and increased crypt/villus ratio, was observed in the distal small intestine of IO rats. Despite massive enterocyte shedding, intestinal villi were covered with a contiguous epithelial layer without cell apoptosis. Increased transmural macromolecular flux was noticed in the distal small intestine and the proximal colon after IO. The bacterial colony forming units in the spleen and liver of IO rats were significantly higher than those of sham controls. Addition of ML-7 ameliorated the IO-triggered epithelial MLC phosphorylation, mucosal injury and macromolecular flux, but not the level of BT.</p> <p>Conclusions</p> <p>The results suggest that IO-induced premature enterocytic sloughing and enhanced paracellular antigenic flux were mediated by epithelial MLCK activation. In addition, enteric bacteria may undergo transcytotic routes other than paracellular paths to cross the epithelium.</p

Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

<p>Abstract</p> <p>Background</p> <p>Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β). Matrix metalloprotease-9 (MMP-9) has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs) and up-regulation of IL-1β in dorsal root ganglia (DRGs), and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes.</p> <p>Results</p> <p>Subcutaneous morphine injection (10 mg/kg) induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after <it>Mmp9 </it>deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia.</p> <p>Conclusions</p> <p>Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.</p

Separation, characterization and leaching behaviors of heavy metals in contaminated river sediments

In this research, the sequential extraction test was conducted to understand the characteristic of heavy metals in the sediment. Subsequently, the pH-dependent leaching test, percolation test were subjected to explore the possible leaching of heavy metals and stabilizing mechanism. Finally, based on the resuts of pH dependent test,the acid/chemical washing were applied to predict long-term, leaching characteristics. The results from the sediment characteristic analyses showed that the concentrations of heavy metals (such as Cu, Pb, Zn, Ni, and Cr) in river sediments exceeded the upper limit of Sediment Quality Standard of Taiwan, implying further decontamination works should be addressed. Results from the chemical washing (extraction) showed that the heavy metal removal efficiency was good when washed with 2N HCl for 120 minutes; the order of removal efficiency was Ni 90% &gt; Zn 87% &gt; Pb 85% &gt; Cu 83% &gt; Cr 70%. For chelation extraction, the suitable operating condition was achieved with 0.5M Citric Acid after 120 minutes contact; the order of heavy metal ion capturing efficiency was Zn 61% &gt; Ni 54% &gt; Pb 40% &gt; Cu 36% &gt; Cr 24%. Comparing the heavy metal bonding types before and after chemical washing (extraction) showed that some metal ions exist in residual forms in the sediments (Ni, Zn, Cu); however, after the washing process, the heavy metal ions became more exchangeable forms with higher bioavailability. Keywords: sediment, heavy metal, leaching test, chemical washing

Photobiomodulation with 670 nm light ameliorates Müller cell-mediated activation of microglia and macrophages in retinal degeneration

Müller cells, the supporting cells of the retina, play a key role in responding to retinal stress by releasing chemokines, including CCL2, to recruit microglia and macrophages (MG/MΦ) into the damaged retina. Photobiomodulation (PBM) with 670 nm light has been shown to reduce inflammation in models of retinal degeneration. In this study, we aimed to investigate whether 670 nm light had an effect on Müller cell-initiated inflammation under retinal photo-oxidative damage (PD) in vivo and in vitro. Sprague-Dawley rats were pre-treated with 670 nm light (9J/cm2) once daily over 5 days prior to PD. The expression of inflammatory genes including CCL2 and IL-1β was analysed in retinas. In vitro, primary Müller cells dissociated from neonatal rat retinas were co-cultured with 661W photoreceptor cells. Co-cultures were exposed to PD, followed by 670 nm light treatment to the Müller cells only, and Müller cell stress and inflammation were assessed. Primary MG/MΦ were incubated with supernatant from the co-cultures, and collected for analysis of inflammatory activation. To further understand the mechanism of 670 nm light, the expression of COX5a and mitochondrial membrane potential (ΔΨm) were measured in Müller cells. Following PD, 670 nm light-treated Müller cells had a reduced inflammatory activation, with lower levels of CCL2, IL-1β and IL-6. Supernatant from 670 nm light-treated co-cultures reduced activation of primary MG/MΦ, and lowered the expression of pro-inflammatory cytokines, compared to untreated PD controls. Additionally, 670 nm light-treated Müller cells had an increased expression of COX5a and an elevated ΔΨm following PD, suggesting that retrograde signaling plays a role in the effects of 670 nm light on Müller cell gene expression. Our data indicates that 670 nm light reduces Müller cell-mediated retinal inflammation, and offers a potential cellular mechanism for 670 nm light therapy in regulating inflammation associated with retinal degenerations.This work was supported by the Australian Government National Health and Medical Research Council Grant (APP1049990), Taiwan-ANU scholarship, the Australian Government Research Training Program and the Gretel and Gordon Bootes Foundation

Calcolare la magnitudo è semplice!

Si tratta di un laboratorio attraverso il quale il pubblico può calcolare la magnitudo di un ipotetico terremoto

Compound formation and melting behavior in theAB compound and rare earth oxide systems

Compound formation in the systems of the covalent compounds BeO, AlN, and SiC withR2O3(rare earth oxides) is described. Tentative phase diagrams of the AlNNd2O3 and AlNEu2O3 systems are presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28688/1/0000507.pd

Enhanced Responsivity of Photodetectors Realized via Impact Ionization

To increase the responsivity is one of the vital issues for a photodetector. By employing ZnO as a representative material of ultraviolet photodetectors and Si as a representative material of visible photodetectors, an impact ionization process, in which additional carriers can be generated in an insulating layer at a relatively large electric field, has been employed to increase the responsivity of a semiconductor photodetector. It is found that the responsivity of the photodetectors can be enhanced by tens of times via this impact ionization process. The results reported in this paper provide a general route to enhance the responsivity of a photodetector, thus may represent a step towards high-performance photodetectors