Differential influence of increased polyol pathway on protein kinase C expressions between endoneurial and epineurial tissues in diabetic mice

To explore the relationship between polyol pathway and protein kinase C (PKC), we examined PKC activities and expressions of PKC isoforms separately in endoneurial and vessel-rich epineurial tissues in diabetic mice transgenic for human aldose reductase (Tg). Tg and littermate control mice (Lm) were made diabetic by streptozotocin at 8 weeks of age and treated orally with aldose reductase inhibitor (ARI) (fidarestat 3-5 mg/kg/day) or placebo for 12 weeks. At the end, compared with non-diabetic state, sorbitol contents were increased 6.4-fold in endoneurium and 5.1-fold in epineurium in diabetic Tg, whereas the increase was detected only in endoneurium in diabetic Lm. Endoneurial PKC activity was significantly reduced in diabetic Tg. By contrast, epineurial PKC activity was increased in both diabetic Lm and diabetic Tg and there was no significant difference between the two groups. These changes were all corrected by ARI treatment. Consistent with the changes of PKC activities, diabetic Tg showed decreased expression of PKC alpha in endoneurium, whereas there was an increased expression of PKC beta II in epineurium in both diabetic Tg and diabetic Lm. These findings suggest the presence of dichotomous metabolic pathway between neural and vascular tissues in the polyol-PKC-related pathogenesis of diabetic neuropathy.     

Diabetes is not a potent inducer of neuronal cell death in mouse sensory ganglia,but it enhances neurite regeneration in vitro

We examined the effects of diabetes on the morphological features and regenerative capabilities of adult mouse nodose ganglia (NG) and dorsal root ganglia (DRG). By light and electron microscopy, no apoptotic cell death was detected in the ganglia obtained from either streptozotocin (STZ)-induced diabetic or normal C57BL/6J mice in vivo. Neurite regeneration from transected nerve terminals of NG and DRG explants in culture at normal (10 mM) and high (30 mM) glucose concentrations was significantly enhanced in the diabetic mice. Chromatolytic changes (i.e. swelling and migration of the nucleus to an eccentric position in the neurons, and a loss of Nissl substance in the neuronal perikarya) and apoptotic cell death (less than one-fifth of the neurons) in the cultured ganglia were present, but neither hyperglycemia in vivo nor high glucose conditions in vitro altered the morphological features of the ganglia or the ratios of apoptotic cells at 3 days in culture. By semiquantitative RT-PCR analysis, the mRNA expressions of ciliary neurotrophic factor (CNTF) in DRG from both mice were down-regulated at 1 day in culture. The expression in diabetic DRG, but not in control DRG, was significantly up-regulated at later stages (3 and 7 days) in culture. In summary, hyperglycemia is unlikely to induce cell death in the sensory ganglia, but enhances the regenerative capability of vagal and spinal sensory nerves in vitro. The up-regulation of CNTF mRNA expression during the culture of diabetic DRG may play a role in the enhanced neurite regeneration.     

Statistical and Frequency-Amplitude Characteristics of Ultraweak Emissions of the Loach Eggs and Embryos under the Normal Conditions and upon Their Optic Interactions. 2. Changes in Characteristics of Ultraweak Emissions upon Optic Interaction of Groups of Embryos of Different Ages

We compared the characteristics of ultraweak emissions from groups of loach embryos of different ages in the presence or absence of optic interaction. The percentage of zero values of emission gradually increased during the first hour of optic interaction. The number and height of rare big pulses estimated by the value of kurtosis increased in parallel. In addition, the correlation between the Fourier spectra of optically interacting samples decreased at a higher rate than in the absence of optical contact. Just after the 1-hour optic interaction was terminated, the number of high pulses decreased in a younger interacting group and increased in the older one and the farther away the partner groups were in developmental stages, the more pronounced these differences were. Measurements of the Fourier spectra after long-term (12–22-hour) optic interactions have shown that an exchange of autocorrelation characteristics of the spectra took place among the samples: the sums of autocorrelation coefficients were inverted in the vast majority of cases, often with an overshoot or, at least, were smoothed over with reference to the control samples. We conclude that the previously described effects of optic interactions between groups of loach embryos of different ages could be due to changes in the frequency spectra of their ultraweak emissions.     

Long-term culture of purified postnatal oligodendrocyte precursor cells. Evidence for an intrinsic maturation program that plays out over months

Oligodendrocytes myelinate axons in the vertebrate central nervous system (CNS). They develop from precursor cells (OPCs), some of which persist in the adult CNS. Adult OPCs differ in many of their properties from OPCs in the developing CNS. In this study we have purified OPCs from postnatal rat optic nerve and cultured them in serum-free medium containing platelet-derived growth factor (PDGF), the main mitogen for OPCs, but in the absence of thyroid hormone in order to inhibit their differentiation into oligodendrocytes. We find that many of the cells continue to proliferate for more than a year and progressively acquire a number of the characteristics of OPCs isolated from adult optic nerve. These findings suggest that OPCs have an intrinsic maturation program that progressively changes the cell's phenotype over many months. When we culture the postnatal OPCs in the same conditions but with the addition of basic fibroblast growth factor (bFGF), the cells acquire these mature characteristics much more slowly, suggesting that the combination of bFGF and PDGF, previously shown to inhibit OPC differentiation, also inhibits OPC maturation. The challenge now is to determine the molecular basis of such a protracted maturation program and how the program is restrained by bFGF.     

Induction of 72-kDa Inducible Heat Shock Protein (HSP72) in Cultured Rat Astrocytes After Energy Depletion

Abstract: Protein synthesis is important in the readaptive processes for cultured astrocytes after hypoxia and subsequent reoxygenation. We have identified 72-kDa inducible heat shock protein (HSP72) as a major stress protein in reoxygenated astrocytes. To assess the mechanism for reoxygenation-mediated induction of HSP72, a reporter gene that consists of a human HSP promoter fused to the luciferase gene was transfected into cultured astrocytes. Analysis of cellular energy nucleotides showed an increase of the ADP/ATP ratio after reoxygenation, which synchronized with activation of the HSP promoter. Activation of the HSP promoter was also observed after an addition of iodoacetic acid to hypoxic astrocytes, which reached the maximum when the ADP/ATP ratio reached 50%, but further decline in the energy profile caused inactivation of this promoter. Inhibition of protein synthesis after reoxygenation resulted in temporary restoration of the energy profile and suppression of the DNA binding activity of the heat shock factor. Addition of quercetin greatly decreased the [³H]leucine incorporation in the polysome fraction without any effect on the mature mRNA formation. These data suggest that the energy depletion in reoxygenation triggers induction of HSP72 after reoxygenation, which may act as a pivotal mediator in the stress response of reoxygenated astrocytes by facilitating protein synthesis.     

糖尿病植物神经病变病人心率变异的非线性定量分析

目的：研究糖尿病人植物神经病变与心率变异的关系。对象：正常对照组和根据临床有无糖尿病神经病变（ＤＡＮ）分组的糖尿病病人,方法：应用２４小时动态心电图对正常和糖尿病人进行心率变异的线性,非线性散点图和非线性定量参数分析,结果：单纯糖尿病组ＳＤＮＮ,ＳＤＡＮＮ和ＰＮＮ５０低于正常组（Ｐ〈０．０５）;糖尿病＋ＤＡＮ组各项线性时域分析指标均低于正常和单纯糖尿病组（Ｐ〈０．０１－０．００１）,散点图分析结果     

TLR9信号通路介导缺血性脑损伤的研究进展

炎症反应是缺血性脑损伤的重要机制之一,过度的炎症免疫反应会加剧脑损伤的程度。作为先天免疫系统的重要组成部分,Toll样受体9(Toll like receptor 9,TLR9)通过识别其特异性的配体Cp G-DNA,从而激活先天免疫系统,释放大量前炎症细胞因子,参与缺血性脑损伤的炎症反应过程。近年来,有学者提出将TLR9作为一个新的缺血预处理靶点,即通过启动TLR9信号转导通路增加体内炎症细胞因子的水平来对抗缺血损伤。本文通过对近年TLR9信号通路介导的炎症反应与缺血性脑损伤相关研究进展作一综述,为寻求临床安全高效的缺血性脑损伤防治措施提供理论依据。     

多模式磁共振指导超时间窗急性缺血性卒中的静脉溶栓治疗研究

目的:评价多模式磁共振指导下超时间窗静脉应用重组组织型纤溶酶原激活剂rt PA治疗急性缺血性卒中的疗效及安全性。方法:将68例急性脑梗塞患者分为rt PA静脉溶栓组A组、强化抗栓治疗组B组,各组按药物干预时间再分为4.5小时亚组及4.5-6小时亚组。A组给予rt PA静脉溶栓治疗和常规治疗,B组给予首剂氯吡格雷300毫克+阿司匹林100毫克和常规治疗。治疗前行急诊头多模式磁共振检查,治疗24小时后复查头CT,分别于治疗前后不同时间点进行NIHSS评分和3个月MRS评分,记录不良事件的发生情况。结果:A组两个亚组治疗后各时间点NIHSS评分均明显低于B组,且A组4.5小时亚组治疗后NIHSS评分低于其4.5-6小时亚组,A组3个月预后良好患者比例显著高于B组,差异均有统计学意义(P0.05)。A组症状性颅内出血的发生率高于B组。结论:多模式头磁共振指导下超时间窗rt PA静脉溶栓治疗安全有效,远期疗效优于强化抗栓治疗,但颅内症状性出血风险略高于强化抗栓治疗。     

血栓通配合康复训练对缺血性脑卒中恢复期患者肢体康复的疗效

目的:探究血栓通配合康复训练对缺血性脑卒中(cerebral arterial thrombosis,CAT)恢复期患者肢体康复的疗效情况。方法:选取2011年3月-2013年3月我院收治的84例CAT患者按数字表法随机分为观察组和对照组,各42例。对照组单纯采用康复训练治疗,观察组在对照组康复训练的基础上服用血栓通配合治疗,分别观察治疗前、治疗后1个月、3个月、6个月的各项基本指标并对比研究。结果:两组患者治疗前和治疗1月后Barthel评分无明显差异(P0.05);观察组治疗后3、6个月Barthel评分显著高于对照组,差异有统计学意义(P0.05),两组患者治疗前和治疗1月后肢体Fugl-Meyer评分无明显差异(P0.05);观察组治疗后3、6个月肢体Fugl-Meyer评分显著高于对照组,差异有统计学意义(P0.05),且对照组出院时上肢依然未完全恢复。通过对对照组和观察组患者的生活质量评分比较,观察组生活质量的各项评分均明显高于对照组,两组比较差异有统计学意义(P0.05)。结论:对缺血性脑卒中恢复期患者采用血栓通药物配合适当的康复训练疗效较好,术后肢体恢复理想,值得作为治疗CAT的首选方法在临床上推广应用。