Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin

The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.     

综合性心理干预对产后抑郁症患者抑郁情绪和自我概念的影响

目的探讨综合性心理干预对产后抑郁症患者抑郁情绪和自我概念的影响。方法采用自身对照研究的方法,对30例住院产后抑郁症患者实施综合性心理干预,时间为4周,干预前后,采用爱丁堡产后抑郁量表(EPDS)和田纳西自我概念量表(TSCS)进行效果评价。结果 1)干预前,EPDS评分为(15.62±2.32)分,干预后,EPDS评分为(8.21±1.56)分,差异具有统计学意义(t=11.06,P<0.01);2)干预前,TSCS评分为(246.28±18.67)分,干预后,TSCS评分为(264.52±19.46)分,差异具有统计学意义(t=3.71,P<0.01)。结论综合性心理干预能够改善产后抑郁症患者抑郁情绪,矫正负性自我概念,有助于促进患者的心理康复。     

A Prolonged Nitric Oxide-Dependent,Opioid-Mediated Antinociceptive Effect of Hyperbaric Oxygen in Mice

Hyperbaric oxygen (HBO₂) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO₂ treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO₂-induced antinociception was significantly attenuated by pretreatment before HBO₂ exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N^G-nitro-l-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl-l-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N⁵-(1-iminoethyl)-l-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin_1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO₂-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO₂ treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO₂ exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO₂ treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO₂ may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect.PerspectiveThis article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems.     

Initial symptoms of vertebrobasilar artery occlusions and the outcomes after endovascular treatment

Journal of Neurology - Acute vertebrobasilar artery occlusion (VBAO) is a devastating disease in stroke patients. This study was aimed to identify the initial symptoms of patients with acute VBAO...     

Preliminary clinical report of alternate episodes of Posner–Schlossman syndrome and viral keratitis

Posner–Schlossman syndrome (PSS) and viral keratitis have a shared pathogen and are common diseases in China, but there are few case reports on whether these two diseases occur concurrently or alternately. After long-term clinical observations, six patients with alternating episodes of PSS and viral keratitis were confirmed at our hospital in the past 10 years. Of the six patients, three were female and three were male. Four patients had monocular PSS with ipsilateral monocular viral keratitis, one had monocular PSS with bilateral viral keratitis, and one had bilateral PSS with bilateral viral keratitis. Of the six cases, three had epithelial viral keratitis and three had endothelial viral keratitis. In four cases, the interval between the onset of the two diseases ranged from 8 days to 3 years, and two cases showed overlapping manifestations of the two diseases in 3 to 6 days, both with incomplete absorption of keratic precipitates. The six cases had intermittent episodes of both diseases and significant loss of corneal sensation during the onset of viral keratitis, and were effectively treated with antiviral therapy. PSS and viral keratitis may alternate episodically, and clinical attention should be paid to these conditions. The mechanism of the alternate episodes might be associated with viral infection and the use of glucocorticoids.