替罗非班治疗缺血性脑卒中的应用进展

正替罗非班是一种非肽选择性糖蛋白(GP) Ⅱb/Ⅲa受体抑制剂,它可逆地抑制纤维蛋白原与血小板表面的GP Ⅱb-Ⅲa受体特异性结合,阻断血小板聚集而抑制血栓的形成。血栓的形成是缺血性脑卒中发生的关键一步。目前替罗非班已被应用在短暂性脑缺血发作(TIA)、进展性脑卒中、静脉溶栓(IVT)和血管内治疗(EVT)等临床研究中。它在预防脑卒中进展、支架血栓形成、改善功能独立性和病死率等方面具有重要价值,且已经积累了大量关于与替罗非班相关的风险和益     

血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂治疗急性缺血性卒中的研究进展

血小板活化在血栓形成中起着重要作用,虽然阿替普酶（alteplase,rtPA）静脉溶栓是治疗 急性缺血性卒中（acute ischemic stroke,AIS）的标准治疗,但国内外一直在探索联合或单独使用各类 抗血小板药物在治疗AIS中的作用。抑制血小板聚集过程最后共同通路的新型抗血小板药物血小板 糖蛋白（GP）Ⅱb/Ⅲa受体拮抗剂,在急性冠脉综合征（acute coronary syndrome,ACS）等心血管疾病 中的安全性和有效性已得到验证,但在AIS中的作用尚存争议,本文拟就相关临床研究作一综述。     

《替罗非班在动脉粥样硬化性脑血管疾病中的临床应用专家共识》解读

血小板表面糖蛋白Ⅱb/Ⅲa受体是血小板聚集、血栓形成的最终共同通路,可特异性快速抑制血小板聚集。近年越来越多的证据支持糖蛋白Ⅱb/Ⅲa受体拮抗剂替罗非班可以作为血栓栓塞性疾病的治疗选择,但其在临床实践中的应用经验仍相对不足。为了临床更合理、规范地应用替罗非班,中国卒中学会组织国内神经介入领域知名专家成立撰写委员会,制定了《替罗非班在动脉粥样硬化性脑血管疾病中的临床应用专家共识》,为替罗非班在脑血管病领域中的应用提供了临床经验和指导,并对医疗行为中安全、有效的用药提供了保障。     

血小板糖蛋白Ⅱb／Ⅲa受体拮抗剂在缺血性脑卒中应用的现状

血小板糖蛋白（GP）Ⅱh／Ⅲa受体拮抗剂是一类新型抗血小板聚集药物,它通过抑制纤维蛋白原（Fg）与GPⅡb／Ⅲa特异性结合,有效地阻止各种途径诱导的血小板聚集,从而达到最大程度的抗血小板作用。在心血管领域已有大量的临床循证医学证据表明,GPⅡb／Ⅲa受体拈抗剂在急性冠脉综合征（ACS）和经皮冠状动脉介入治疗（PCI）抗栓中的疗效和安全性。近年来,国外开始陆续有GPⅡb／Ⅲa受体拮抗剂应用于缺血性脑卒中的报道,而国内的研究几乎是空白。藉此,本文就这一方面的相关研究综述如下。     

血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂替罗非班在急性缺血性脑卒中血管内治疗中的研究进展

正急性缺血性脑卒中(acute ischemic stroke,AIS)经血管内治疗 (endovascular treatment,EVT)可有效改善血运及临床症状,但EVT可能会损伤血管内皮细胞,导致血小板聚集及血栓形成。颅内血管再闭塞是EVT的常见并发症[1],脑血管成功再通后22%～34%发生再闭塞[2]。GP Ⅱ b/Ⅲa受体拮抗剂已被证实可降低经皮冠状动脉介入治疗(percutaneous transluminal coronary intervention,PCI)并发症的风险及血     

替罗非班治疗进展性缺血性脑卒中的疗效观察

目的探讨替罗非班治疗进展性脑卒中(progressive ischemic stroke,PIS)的有效性和安全性。方法收集解放军第371中心医院神经内科2016-01—2017-12确诊的PIS并应用盐酸替罗非班氯化钠注射液治疗的5例患者,记录其人口学特征,发病时间,替罗非班应用的持续时间,不同时间点的美国国立卫生研究院卒中量表(NIHSS)评分以及并发症。结果 5例患者应用替罗非班后NIHSS评分下降4～13分,平均7.2分。在应用替罗非班注射液后血凝系列出现变化的3例,血栓弹力图均未见明显变化;5例患者在应用替罗非班前、后和应用替罗非班过程中均未出现出血并发症。结论替罗非班作为一种新型、高效、可逆的抗血小板聚集药物,通过阻断糖蛋白ⅡbⅢa受体与纤维蛋白原结合这一血小板聚集的最后、唯一途径,发挥高效的抗血小板聚集作用,其治疗PIS的价值值得进一步研究。     

巴曲酶对血小板膜蛋白GPⅡb/Ⅲa受体的影响及应用研究

目的:1.明确巴曲酶有无血小板膜蛋白GPⅡb/Ⅲa受体拮抗作用。2.探讨巴曲酶与阿司匹林联合治疗急性缺血性脑梗死的协同作用。方法:采用随机、开放及疗程平行组进行临床研究。将102例急性缺血性脑梗死患者随机分成单用阿司匹林组(n=23)、单用DF-521组(n=35)及两者联合治疗组(n=44),观察治疗前后血小板聚集率、GPⅡb/Ⅲa受体表达、纤维蛋白原水平、TXB2、影像学变化、生活自理能力(HBI)及3个月时功能随访。结果:3种治疗方案均有抗血小板聚集作用,联合治疗组作用最明显(P<0.05)。单用阿司匹林及联合治疗组TXB2水平明显降低,单用巴曲酶及联合治疗组治疗后GPⅡb/Ⅲa、纤维蛋白原水平降低差异有统计学意义。3个月生活自理能力随访显示联合治疗组(70.45%)优于单用巴曲酶组(45.71%)优于单用阿司匹林组(17.399%)。结论:DF-521有GPⅡb/Ⅲa受体拮抗作用,与ASA合用后从不同的作用机制发挥抗栓作用。     

替罗非班对血管内介入治疗急性缺血性脑卒中患者预后的影响

目的 探讨替罗非班对血管内介入治疗急性缺血性脑卒中(AIS)患者预后的影响。方法选取2020年3月至2022年3月重庆市开州区人民医院和恩施土家族苗族自治州中心医院共同收治的102例AIS患者,随机分为观察组(51例)和对照组(51例)。对照组接受血管内介入术治疗,观察组在对照组基础上给予替罗非班治疗。比较两组治疗有效率、药物安全性、治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、改良RANKIN量表(mRS)评分、脑源性神经营养因子(BDNF)、神经生长因子(NGF)、S100 β及血小板功能指标。结果 观察组和对照组治疗总有效率分别为74.51%、60.78%,差异无统计学意义(P>0.05)。治疗后,观察组NIHSS评分、mRS评分、血清S100 β水平及血小板聚集率、血小板黏附率、最大聚集时间均低于对照组,而血清BDNF、NGF水平明显高于对照组(P<0.05)。两组患者任何出血、症状性颅内出血(sICH)、复发率及病死率差异无统计学意义(P>0.05)。结论 替罗非班辅助血管内介入术治疗AIS可有效改善患者血小板功能,促进神经功能恢复,且安全性良好。     

血小板膜GPⅡb/Ⅲa及其在脑梗死防治中应用的研究进展

动脉粥样硬化性、血栓性脑梗死是脑梗死中最常见的类型,而血小板活化是导致血栓形成的重要原因.活化的血小板膜糖蛋白可以作为血小板活化的标志,因此检测血小板膜糖蛋白可了解血小板活化程度,从而为预防和治疗脑梗死提供准确而可靠的依据.糖蛋白Ⅱb/Ⅲa(GPⅡ b/Ⅲa)是血小板膜糖蛋白中含量最高的,本文对GP Ⅱ b/Ⅲ a及其在脑梗死防治中的应用作一综述.     

替格瑞洛的神经科应用：未来路在何方？——急性非致残性脑血管事件高危人群血小板反应性研究的启示

正抗血小板聚集药物在神经科具有广泛的临床应用。阿司匹林作为抗血小板聚集治疗的元老级药物,多项临床研究已经明确其在预防缺血性脑血管病领域的有效性及安全性。氯吡格雷则是继阿司匹林后又一重磅药物,对于神经内科缺血性卒中患者安全有效。除阿司匹林及氯吡格雷外,近年来还有替格瑞洛、西洛他唑、普拉格雷、双嘧达莫、阿西单抗和替罗非班等     

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。     

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     

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.     

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.     

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.     

Developmental effects of in vivo and in vitro inhibition of nitric oxide synthase in neurons

The diffusible chemical messenger nitric oxide (NO) is involved in neuronal plasticity and it is, therefore, supposed to play a role in brain development. A shortage of NO during the critical period of brain maturation may theoretically have long-lasting consequences on the organization of the adult brain. We have performed in neonatal rats a chronic inhibition of the enzyme responsible for NO production, nitric oxide synthase (NOS), from postnatal day 3 to postnatal day 23, through administration of the competitive antagonist N-nitro-L-arginine methylester (L-NAME). The calcium-dependent catalytic activity resulted almost completely inhibited throughout the period of treatment and it took more than 4 days after its suspension to get a full recovery. The expression of the neuronal isoform of the enzyme (nNOS), revealed by immunoblotting, was unchanged during the treatment and after it. The histochemical reaction for NADPH diaphorase was reduced at the end of the treatment and recovered in concomitance with the recovery of the catalytic NOS activity. No gross structural alterations were detected in brain morphology. The levels of three neurotransmitter-related and one astrocytic marker were unchanged in the cerebellum, hippocampus and cortex of 60-day-old rats which had been neonatally treated. A similar lack of significant effects on neurochemical brain maturation was also noticed in a parallel series of experiments, in which a short pulse of NOS inhibition was performed at a critical prenatal time of brain development, from gestational day 14 to gestational day 19. In vitro, chronic exposure of cerebellar granule cells to L-NAME (500 microM) resulted in slight decrease of surviving neurons after 8 days in culture and in better resistance to the challenge of stressful culture conditions. The present results suggest that the basic plan of brain organization can be achieved despite an almost complete NOS inhibition during the maturation period. In vitro, NOS inhibition may bring to more pronounced consequences on neuronal viability and function.     

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。     

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.