[Effect of gum chewing on bowel function recovery in patients after radical cystectomy with urinary diversion].

OBJECTIVE: To determine whether chewing gum during the postoperative period facilitates the recovery of bowel function in patients after radical cystectomy with ileum urinary diversion. METHODS: In the study, 60 patients who underwent radical cystectomy followed by ileum urinary diversions during Nov. 2014 and Nov. 2015 in Department of Urology of Peking University First Hospital were randomized into three groups: gum chewing group, placebo group treated with the abdomen physical therapy machine and control group treated with ordinary method. Time to flatus, time to bowel movement, incidence of postoperative distension of the abdomen and abdominal pain, and gut related complications (such as ileus, intestinal fistula, and volrulus) of all the patients were recorded and analysed. RESULTS: In gum chewing group, the median time to flatus was 57 hours (49-72 hours), and the median time to bowel movement was 95 hours (88-109 hours), which were significantly shortened compared with the other two groups of patients (82 hours, 109 hours in placebo group and 81 hours, 108 hours in control group, respectively). No significant difference of the median time to flatus and to bowel movement was observed between placebo group and control group. There were no significant differences in the incidence of postoperative distension of the abdomen and abdominal pain, and gut related complications among the three groups. CONCLUSION: Chewing gum had stimulatory effect on bowel function recovery after cystectomy followed by ileum urinary diversion. Chewing gum was safe and simple, and could be routinely used for postoperative treatment after cystectomy and ileum urinary diversion.

L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer's disease via activating dopamine D1 receptor/PKA signaling pathway.

It is accepted that amyloid ß-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer's disease (AD). However, there is still no effective treatment for preventing or reversing the progression of the disease. Targeting α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway.

GluR6-FasL-Trx2 mediates denitrosylation and activation of procaspase-3 in cerebral ischemia/reperfusion in rats.

Global cerebral ischemia/reperfusion (I/R) facilitates the activation of procaspase-3 and promotes apoptosis in hippocampus. But the mechanisms have remained uncharacterized. Protein S-nitrosylation and denitrosylation is an important reversible posttranslational modification, which is a common mechanism in signal transduction and affects numerous physiological and pathophysiological events. However, it is not known whether S-nitrosylation/denitrosylation modification of procaspase-3 serves as a component of apoptosis and cell death induced by cerebral I/R. Here we show that procaspase-3 is significantly denitrosylated and activated after I/R in rat hippocampus. NS102, a glutamate receptor 6 (GluR6) antagonist, can inhibit the denitrosylation of procaspase-3 and diminish the increased Fas ligand (FasL) and thioredoxin (Trx)-2 expression induced by cerebral I/R. Moreover, downregulation of FasL expression by antisense oligodeoxynucleotides inhibits the denitrosylation and activation of procaspase-3. Auranofin, a TrxR inhibitor or TrxR2 antisense oligodeoxynucleotide, has similar effects. In primary hippocampal cultures, Lentiviral-mediated knockdown of FasL and TrxR2 before the oxygen and glucose deprivation/reoxygenation further verifies that FasL and TrxR2 are involved in the denitrosylation of procaspase-3. In situ TUNEL staining and cresyl violet staining validate that inhibiting denitrosylation of procaspase-3 may exert neuroprotective effect on apoptosis and cell death induced by cerebral I/R in hippocampal CA1 pyramidal neurons. This is the first evidence that cerebral I/R mediates procaspase-3 denitrosylation and activation through GluR6-FasL-Trx2 pathway, which leads to neuronal apoptosis and cell death.