Rabs and axonal regeneration

Membrane trafficking processes are presumably vital for axonal regeneration after injury, but mechanistic understanding in this regard has been sparse. A recent loss-of-function screen had been carried out for factors important for axonal regeneration by cultured cortical neurons and the results suggested that the activity of a number of Rab GTPases might act to restrict axonal regeneration. A loss of Rab27b, in particular, is shown to enhance axonal regeneration in vitro, as well as in C. elegans and mouse central nervous system injury models in vivo. Possible mechanisms underlying this new finding, which has important academic and translational implication, are discussed.     

Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

经皮椎弓根技术治疗胸腰椎骨折的临床探讨

目的:探讨微创经皮椎弓根螺钉内固定手术治疗胸腰椎骨折的可行性及其疗效。方法:20例胸腰椎骨折病例,男13例,女7例;年龄28~65岁,平均48·2岁。其中16例损伤平面以下无神经功能损害、无双下肢和大小便障碍;4例有不同程度的脊髓损伤,按Frankel分级:C级1例,D级3例。在C形臂X线的定位下确定需要固定的椎弓根根部,做4个1·5cm长的切口,固定与复位均在4个小切口内完成。结果:所有病例均获随访,时间9~18个月,平均15个月。术后患者椎体高度均有不同程度恢复,椎体后凸畸形获得不同程度矫正。手术时间约1·5h,出血量约80ml。结论:微创经皮椎弓根螺钉内固定手术操作简便、安全可靠,具有创伤小、出血少、疼痛轻、恢复快、住院时间短等优点。     

足部骨筋膜室综合征早期诊断与治疗

目的:探讨足部骨筋膜室综合征早期诊断与治疗结果。方法:1998年1月-2003年12月收治15例足骨筋膜室综合征患者(均为男性:年龄15～55岁,平均32岁),行足背双切口减压4例,足底内侧减压9例,足内外两侧减压2例。1周后行减张缝合或植皮术。结果:15例随访9～24个月,12例恢复佳,足运动感觉正常;2例有足底感觉减退、足趾麻木;1例遗留前足挛缩、无力,足趾麻木。无爪形趾及功能障碍者。结论:足损伤后,Whiteside法测定组织间隙压力是诊断足骨筋膜室综合征的可靠方法。治疗时足部如有骨折、血肿者,骨筋膜室减张切口,宜选择足底内侧切开效果较好。     

Pulmonary Lophomonas blattarum infection in patients with kidney allograft transplantation

The aim of the study was to analyse the clinical manifestation and management of pulmonary Lophomonas blattarum infection in four allograft transplantation recipients retrospectively. Four patients with pulmonary L. blattarum infection were diagnosed by using Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) examination. Their clinical manifestation and management are summarized. Four cases of pulmonary L. blattarum were found during the period from the second month to the third month after transplantation. Concurring infection by other pathogens was found in three of them. Common initial symptoms included fever (>38 degrees C) without cough and breathlessness. Lower lobe shadowing could be found on chest X-ray. Body temperature decreased to the normal range in three patients and to 37.5 degrees C in the other one, after intravenous injection of metronidazole and tapering immunosuppressant. Radiological examination confirmed improved health condition of the patients afterwards. Two patients received repeated FOB and only dead L. blattarum was found. Pulmonary L. blattarum infection in allograft transplant recipients carry relatively obscure initial symptoms. Possible L. blattarum infection needs to be screened in post-transplantation pulmonary infection patients with similar symptoms, especially in those who respond poorly to anti-infection treatment. Microscopic examination of BAL fluid can help to identify pulmonary L. blattarum infection and metronidazole is an ideal treatment choice.     

慢性阻塞性肺病患者营养与餐后低氧的关系

目的研究慢性阻塞性肺病(COPD)患者的营养状况与餐后低氧的关系.方法51例COPD急性加重期后的患者连续监测就餐前后SpO2,同时记录饮食情况并换算为各营养素的量.结果营养不良组COPD患者餐后SpO2低于餐前,降低幅度超过3%(P＜0.05),进餐时间相对延长,营养物质摄入减少.SpO2变化与单位体质量总热量的摄入呈负相关(P＜0.05).结论重度COPD患者的营养状况可能与患者进餐后发生的缺氧、低氧血症有关,在营养支持中应考虑采取适当措施干预就餐引起的相关低氧血症的发生.