PECAM—1、P—选择素在血小板上表达改变与急性脑梗死关系

目的:探讨血小板表面血小板源内皮细胞粘附分子(PECAM-1)、P-选择素的不同作用及表达变化在急性脑梗死时的意义。方法:应用流式细胞术测定85例脑缺血急性期患者和32例健康人周围血血小板表面PECAM-1和P-选择素,部分患者2周后复查。结果:脑梗死患者病初PECAM-1增高,与脑梗死体积呈正相关,P-选择素增高程度大于前者,PECAM-1/P-选择素比例明显下降。结论:PECAM-1通过抑制血小板聚集防止脑缺血发生,PECAM-1/P-选择素比例下降可能导致脑缺血发生。     

急性脑梗死患者血小板表达血小板内皮细胞黏附分子-1、P选择素的改变及其意义

目的观察急性脑梗死(AC I)患者血小板表达血小板内皮细胞黏附分子-1(CD31)、P选择素(CD62p)的改变及其意义。方法采用全血流式细胞术测定53例AC I患者发病48 h内血小板CD31、CD62p的表达水平,并与有脑梗死易患因素组及健康对照组比较。结果AC I组血小板表达CD31、CD62p[(90.91±15.39)%,(7.00±2.96)%]明显高于易患因素组和健康对照组(均P<0.001);AC I组中合并高血压或糖尿病患者血小板CD62p表达高于无高血压和糖尿病的患者(均P<0.01);血小板CD31、CD62p的表达与脑梗死体积正相关(r=0.39,P<0.05;r=0.63,P<0.01)。结论AC I发病后血小板表达CD31、CD62p显著增高,其表达程度与脑梗死体积以及是否合并高血压或糖尿病有关。     

miR-26b与血小板P选择素(CD62p)在脑梗死患者血清中的表达及临床意义

目的 探究微小RNA(miR)-26b与血小板P选择素(CD62p)在急性脑梗死患者血清中表达及其临床意义。方法 以本院128例急性脑梗死患者(病例组)和128例体检结果健康者(健康组)为研究对象。分析病例组血清miR-26b、CD62p表达水平与患者临床病理参数关系,以及对发病后3个月预后不良的预测效能。结果 病例组miR-26b表达水平显著低于健康组,CD62p表达水平高于健康组(P<0.05)。不同神经功能缺损程度、脑梗死体积及预后患者血清miR-26b、CD62p表达水平差异有统计学意义(P<0.05)。病例组血清miR-26b与mRS评分、脑梗死体积及NIHSS评分均存在负相关,而CD62p与mRS评分、脑梗死体积及NIHSS评分存在正相关(P<0.05)。NIHSS评分及脑梗死体积增加、miR-26b低表达、CD62p高表达是急性脑梗死患者预后不良的危险因素(P<0.05)。ROC曲线显示,血清miR-26b联合CD62p预测急性脑梗死预后不良的曲线下面积为0.950。结论 血清miR-26b、CD62p与急性脑梗死患者梗死体积、神经功能缺损程度及发...     

急性脑梗死患者内源性红细胞生成素的变化及临床意义

目的探讨急性脑梗死患者血清内源性红细胞生成素(erythropoietin,EPO)的变化与临床意义。方法研究对象为56例发病2周内并经头部CT或MRI确诊的急性脑梗死患者,按责任病灶的梗死面积大小分为3个亚组:A组20例患者,为大面积脑梗死,梗死灶直径>5cm;B组20例,中等面积脑梗死,梗死灶直径为3～5cm;C组16例为小面积梗死,梗死灶直径<3cm(包括腔隙性脑梗死)。入院后第2天根据美国国立卫生研究院卒中量表(NationalInstitutesofHealthStrokeScale,NIHSS)进行神经功能缺损程度评分,血清红细胞生成素检测采用化学发光免疫法。观察在脑梗死急性期内源性红细胞生成素的变化与梗死灶面积大小、神经功能缺损程度之间的关系。结果正常对照组受试者红细胞生成素水平为(13.30±4.29)U/L;脑梗死A、B及C组患者的红细胞生成素水平分别为(5.55±2.14)U/L,(9.07±2.53)U/L和(15.59±7.49)U/L;NIHSS评分A、B及C组分别为(19.00±6.48)分,(8.75±7.01)分以及(4.81±5.33)分。A,B两组血清红细胞生成素水平低于对照组,差异具有显著性意义(P<0.01);血清红细胞生成素水平与NIHSS评分呈负相关(r=0.569,P<0.05)。结论急性脑梗死患者内源性红细胞生成素变化与梗死面积大小有关,与神经功能缺损程度呈负相关,红细胞生成素变化轻微者预后好,提示红     

急性脑梗死患者循环miR-124表达水平与脑梗死体积、神经功能缺损程度的关系及其诊断价值

目的 观察急性脑梗死(ACI)患者循环miR-124表达水平的变化及其与脑梗死体积和神经功能缺损程度的关系和其诊断价值。方法 选择ACI患者90例为观察组,另选取同期体检健康者40例作为对照组; 按梗死体积将ACI患者分为3个亚组:小梗死组(<5 cm³,n=38),中梗死组(5～10 cm³,n=31),大梗死组(>10 cm³,n=21); 根据美国国立卫生研究院卒中量表(NIHSS)评分,将ACI患者分为3个亚组:轻度组(≤6分,n=30)、中度组(7～14分,n=34)、重度组(≥15分,n=26)。通过定量逆转录聚合酶链反应(qRT-PCR)检测循环miR-124相对表达水平; 分析miR-124表达水平与脑梗死体积、神经功能缺损严重程度的关系。结果 观察组miR-124相对表达水平(2.93±1.21)明显高于对照组(1.09±0.55)(t=10.198,P<0.01); 不同脑梗死体积3个亚组间miR-124相对表达水平比较有明显差异(F=20.963,P<0.01),即脑梗死体积越大,miR-124相对表达水平越低; 相关性分析显示,miR-124相对表达水平与梗死体积呈负相关(r=-0.564,P<0.01); 不同NIHSS评分3个亚组间miR-124相对表达水平比较无明显差异(F=1.170,P>0.05)。结论 ACI患者循环miR-124水平明显升高,且其水平与脑梗死体积密切相关。     

血小板激活在氧化应激诱发小鼠短暂性脑缺血发作中的作用和替罗非班的干预作用

目的:探讨氧化应激在小鼠短暂性脑缺血发作中的作用及其病理生理学机制。方法:采用尾静脉注射过氧化物加缺氧诱发的小鼠TIA模型,通过测定血清可溶性P-选择素水平的变化和小鼠症状的出现时间、模型评分,观察血小板激活和替罗非班的干预作用。结果:模型组血清可溶性P-选择素显著高于对照组,分别为(4.19±0.17)ng/ml和(0.82±0.07)ng/ml,替罗非班组与模型组比较无显著差异(P>0.05);替罗非班组小鼠症状的出现时间明显晚于模型组,分别为(4.95±1.19)d和(3.75±1.12)d;症状评分也低于模型组(P<0.05)。结论:氧化应激通过激活血小板,进而诱发微血栓的形成导致小鼠TIA发作;血小板活化后伴随的炎症反应可能也起了一定的作用。     

急性脑梗死患者血小板-白细胞聚集体的动态变化及意义

目的探讨急性脑梗死患者血小板-白细胞聚集体(platelet-leukocyte aggregation,PLA)的动态变化及其临床意义。方法收集作者医院就诊的158例急性脑梗死患者以及30名健康体检者(对照组)为研究对象,根据瘫痪肢体肌力或神经功能评分量表(NIHSS)评分变化将脑梗死患者分为进展性脑梗死组和无进展脑梗死组,采用流式细胞技术检测健康对照组以及脑梗死患者不同时期的PLA水平。结果进展性脑梗死组血小板-单核细胞聚集体(platelet-monocyte aggregations,PMA)水平在进展期明显升高,而后逐渐下降(P<0.05),无进展脑梗死组PMA水平逐渐下降,差异有统计学意义(P<0.05);进展性和无进展脑梗死组PLA、血小板-淋巴细胞聚集体(platelet-lymphocyte aggregations,PLyA)、血小板-中性粒细胞聚集体(platelet-neutrophilic aggrega-tions,PNA)水平无明显动态变化(P>0.05);PMA水平与NIHSS评分呈正相关(r=0.12,P<0.05)。结论 PLA不仅在脑梗死的发病中发挥作用,而且可反映急性脑梗死患者病情的严重程度。     

活化白细胞黏附分子与血小板内皮细胞黏附分子-1在2型糖尿病并发急性脑梗死患者中的变化及意义

目的探讨活化白细胞黏附分子(ALCAM)、血小板内皮细胞黏附分子-1(PECAM-1)的变化与2型糖尿病(T2DM)并发急性脑梗死患者神经功能、颈动脉斑块形成的关系。方法选取南阳医专第一附属医院收治的120例T2DM并发急性脑梗死患者为病例组A,120例不伴T2DM的急性脑梗死患者为病例组B,120例未发生脑血管疾病的志愿者为对照组。检测3组研究对象的血清ALCAM、PECAM-1水平,并根据颈动脉粥样硬化斑块特征、斑块内部新生血管分级进行分层对比;采用线性相关分析法分析血清ALCAM、PECAM-1与美国国立卫生研究院卒中量表(NIHSS)的相关性。结果病例组A的血清ALCAM、PECAM-1水平均高于病例组B、对照组,差异有统计学意义(P<0.05);病例组B的血清ALCAM、PECAM-1水平均高于对照组(P<0.05)。病例组A检出不稳定斑块患者67例,稳定斑块患者36例,未发现斑块患者17例;不稳定斑块患者的血清ALCAM、PECAM-1水平高于稳定斑块和无斑块患者,差异有统计学意义(P<0.05);稳定斑块患者的血清ALCAM、PECAM-1水平均高于无斑块患者(P<0.05)。病例组A中颈动脉粥样硬化斑块中新生血管2~3级患者的血清ALCAM、PECAM-1水平均高于新生血管0~1级患者,差异有统计学意义(P<0.05)。病例组A患者的NIHSS评分为(13.9±3.6)分,NIHSS评分与血清ALCAM、PECAM-1水平呈显著的正相关关系(r=0.573,r=0.530,P<0.05)。结论T2DM并发急性脑梗死患者血清ALCAM、PECAM-1水平较单纯的脑梗死患者显著增高,且与患者颈动脉粥样硬化斑块特征及内部血管形成、神经功能受损严重程度具有相关性。     

急性脑梗死患者血清P-选择素和CRP含量动态变化研究

目的 探讨缺血性脑卒中患者血清P-选择素和C反应蛋白（CRP）含量的动态变化和临床意义.方法 分别运用酶联免疫吸附测定（ELISA）的方法和免疫透射比浊法检测30例脑梗死患者和30名健康对照者例健康对照者P-选择素、CRP的血清水平.结果 缺血性脑卒中患者急性期血清P-选择素和CRP水平显著高于其恢复期及健康对照组（均P＜0.01）,恢复期P-选择素和CRP水平仍高于健康对照组（P＜0.05）.不同体积脑梗死患者的P-选择素和CRP水平不同,大梗死灶组和中梗死灶组比小梗死灶组P-选择素和CRP水平明显升高,差异具有统计学意义（P＜0.01）.结论 P-选择素和CRP参与了缺血性脑卒中炎症反应和血小板活化的病理过程,血清P-选择素和CRP水平可作为缺血性脑血管病发生发展及病情监测的参考指标.     

急性脑梗死患者的血小板活化、聚集状态及其临床意义

目的 探讨急性脑梗死患者的血小板活化、聚集状态及其临床意义.方法 97例急性脑梗死患者按梗死体积和卒中类型分别分为小体积和中-大体积脑梗死亚组,大动脉粥样硬化性卒中(LAA)和小动脉闭塞性卒中(SAO)亚组.在脑梗死患者发病48 h内(治疗前)和病程第12 d,采用全血流式细胞术检测血小板CD62P表达,用比浊法检测花生四烯酸、二磷酸腺苷诱导的血小板最大聚集率(MARAA,MARADP);并与正常对照者(n=99)比较.结果 脑梗死组发病48 h内血小板CD62P表达水平和MARAA、MARADP显著高于正常对照组(P＜0.05 ～0.01),且发病第12 d比发病48 h内明显降低(均P＜0.01).中-大体积脑梗死亚组、LAA亚组的血小板CD62P表达和MARAA、MARADp分别显著高于小体积脑梗死亚组和SAO亚组(均P＜0.01).结论 急性脑梗死患者发病后血小板活化、聚集程度增高,脑梗死体积大、大血管病变的患者增高更明显.观察急性脑梗死患者的血小板活化、聚集状态,有助于对其病情的判断.     

视频脑电图在小儿癫痫诊断中的应用

目的评价视频脑电图(video-EEG)在小儿癫诊断中的应用价值。方法对126例具有发作性症状的患儿进行连续8h的包括清醒、睡眠、诱发试验及必要的认知测验的视频脑电图监测。结果经发作期视频脑电图证实,39例初诊为癫性发作的患儿中14例(35%)为非癫性发作;15例其他症状发作中13例(86%)为非癫性发作。64例样放电患儿中51例(80%)确定发作类型,22例(34%)确定癫类型。视频脑电图可发现短暂轻微的癫发作及样放电引起的一过性认知损伤。结论视频脑电图在排除非癫性发作、确定癫性发作的类型、评价脑电-临床关系方面可提供准确可靠的证据,进一步提高癫的临床诊断水平。     

Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity

The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the N-methyl-D-aspartate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the anti-excitotoxic properties of memantine, a well-tolerated low affinity uncompetitive NMDA-R antagonist presently used as an anti-dementia agent. We explored in a series of models of increasing complexity, whether this voltage-dependent channel blocker had neuroprotective properties at clinically relevant concentrations. As expected, memantine protected neurons in organotypic hippocampal slices or dissociated cultures from direct NMDA-induced excitotoxicity. However, low concentrations of memantine were also effective in neuronal (cortical neurons and cerebellar granule cells) stress models dependent on endogenous glutamate stimulation and mitochondrial stress, i.e. exposure to hypoxia, the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) or a nitric oxide (NO) donor. Furthermore, memantine reduced lethality and brain damage in vivo in a model of neonatal hypoxia-ischemia (HI). Finally, we investigated functional rescue (neuronal capacity to migrate along radial glia) by memantine in cerebellar microexplant cultures exposed to the indirect excitotoxin 3-nitropropionic acid (3-NP). Potent NMDA-R antagonists, such as (+)MK-801, are known to block neuronal migration in microexplant cultures. Interestingly, memantine significantly restored the number of neurons able to migrate out of the stressed microexplants. These findings suggest that inhibition of the NMDA-R by memantine is sufficient to block excitotoxicity, while still allowing some degree of signalling.     

Storage of lipofuscin in neurons in mucopolysaccharidosis

Summary A histochemical and ultrastructural study was made on the brain of a 23-year-old man with Sanfilippo's syndrome. In accordance with previous reports the cortical nerve cells contained a PAS-positive lipid storage substance. This showed intense autofluorescence in UV-light and was positive with various stains for lipofuscin. The storage material appeared ultrastructurally as inclusion bodies composed of short lamellated membranes, granular material, and vacuoles. In addition, concentrically and transversely lamellated membranous cytoplasmic bodies were observed in the nerve cells. It is concluded that the PAS-positive lipid storage material in the neurons was composed partly of lipofuscin in addition to other lipids presumably glycosphingolipids.Supported by a grant from the Expressen Prenatal Research Foundation     

脑电图预测痫性发作研究进展

癫痫(epilepsy)是由脑部神经元高度同步化异常放电所致的临床综合征,系神经系统的常见病,困扰着全世界约1%的人群.每次神经元的阵发性放电或短暂的脑功能异常称为痫性发作(seizures).     

Midazolam in treatment of various types of seizures in children

Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. There are limited studies that midazolam can be used successfully to treat seizures in adults and children. In this study, 0.2 mg/kg intramuscular (IM) midazolam was administered to 11 children (eight boys and three girls), aged 3 days to 4 years (mean age 1.8±1.4 years), with seizures of various types. In all but one child, seizures stopped in 15 s–5 min after injection. No side effects were observed. These results suggest that IM administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (IV) line problem.     

Role of vincristine in the inhibition of angiogenesis in glioblastoma

Objective: Vincristine, a microtubule-destabilizing drug, was found to exhibit anti-angiogenic effects and anti-tumoral activity. However, the precise mechanism by which vincristine inhibits angiogenesis in glioblastomas is not well understood. Our aim was to investigate whether vincristine affects vascular endothelial growth factor (VEGF) expression in glioblastoma cells and determine whether it is mediated by the downregulation of hypoxia-inducible factor-1α (HIF-1α).

Methods: We investigated the expression of HIF-1α in glioblastoma tissues resected from patients and in human glioblastoma cell lines using immunohistochemistry, Western blot analysis, and immunocytochemistry. In addition to an MTT assay assessing the effect of vincristine on cell proliferation and viability, the effects of vincristine on VEGF mRNA expression and HIF-1α protein were examined using real-time RT-PCR and Western blot analysis under 1% O₂ (hypoxia).

Results: HIF-1α was expressed in the majority of glioblastoma tissues and was detected mainly in the nucleus. Strong immunoreactivity for HIF- 1 α was found often in the hypercellular zones. Under hypoxic conditions, HIF-1α protein levels in the glioblastoma cell lines increased, primarily localizing into the nucleus similar to glioblastoma tissues. Exposure of glioblastoma cells to vincristine resulted in enrichment of the G₂-M fraction of the cell cycle, which suggests that vincristine-mediated growth inhibition of glioblastoma is correlated with mitotic inhibition. Using doses lower than those found to reduce the viability and proliferation of cells by 50% (IC₅₀), vincristine decreased both the expression of VEGF mRNA and the level of HIF-1α protein in hypoxic glioblastoma cells. In addition, following exposure to vincristine, the expression of VEGF mRNA was correlated with HIF-1α protein levels.

Conclusions: Our results suggest that the mechanism by which vincristine elicits an anti-angiogenic effect in glioblastomas under hypoxic conditions might be mediated, in part, by HIF-1α inhibition.     

The Burden of Agoraphobia in Worsening Quality of Life in a Community Survey in Italy

ObjectiveCurrent nosology redefined agoraphobia as an autonomous diagnosis distinct from panic disorder. We investigated the lifetime prevalence of agoraphobia, its association with other mental disorders, and its impact on the health-related quality of life (HR-QoL). MethodsCommunity survey in 2,338 randomly selected adult subjects. Participants were interviewed with the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by clinicians. The diagnoses were based on the ICD-10 criteria. The Short-Form Health Survey (SF-12) was used to quantify HR-QoL. ResultsIn the sample, 35 subjects met the criteria for agoraphobia (1.5%), with greater prevalence among women (2.0%) than men (0.9%): odds ratio (OR) 2.23; 95% CI: 1.0-5–2. Agoraphobia was more often seen among those with (n=26; 1.1%) than without (n=9; 0.4%) panic disorder: OR=8.3; 2.9–24.4. Co-morbidity with other mental disorders was substantial. The mean score of SF-12 in people with agoraphobia was 35.2±7.8, with similar levels of HR-QoL in people with (35.3±7.9) or without (34.8±7.3) panic disorder: ANOVA: F(1;33)=0.0; p=1.00. ConclusionOne out of seventy people may suffer from agoraphobia in their lifetime. The attributable burden in terms of HR-QoL is substantial and comparable to the one observed for chronic mental disorders such as major depression, post-traumatic stress disorder, or obsessive-compulsive disorder.     

自噬参与帕金森病发病的研究进展

近年来,蛋白质的降解障碍被认为是帕金森病（Parkinson’Sdisease,PD）发病过程中的重要因素,人们已经公认泛素一蛋白酶体系统（ubiquitin--pro—teasomesystem,UPS）功能异常或衰竭能够导致细胞内异常蛋白蓄积、细胞功能障碍,甚至细胞凋亡。与此同时,蛋白降解的另一条途径——自噬-溶酶体途径（autophagy—lysosomepathway,ALP）也已成为了生命科学领域的研究热点,自噬与神经变性疾病,尤其是PD的关系日益受到人们的重视。     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.