NADPH oxidase inhibition rescues keratinocytes from elevated oxidative stress in a 2D atopic dermatitis and psoriasis model

Emerging evidence suggests oxidative stress plays a role in the pathophysiology of both atopic dermatitis (AD) and psoriasis (PSO). We established in vitro models of AD and PSO skin, and characterized these models in regard to their oxidative stress state. Both AD and PSO model keratinocytes exhibited elevated reactive oxygen species (ROS) levels and accumulated more DNA damage than control cells after oxidative stress induced by 250 µmol/L H₂O₂. Elevated ROS levels and DNA damage accumulation could be inhibited by the NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI). Further, immunofluorescence analysis revealed the presence of both NOX1 and NOX4 in keratinocytes. By inhibiting NOX1, stress-related signalling cascades and elevated ROS levels could be abrogated, and survival of AD and PSO cells improved. Taken together, this study reveals that inhibition of NOX inhibition could abrogate elevated oxidative stress in a 2D model of AD and PSO.     

试析老年痴呆患者的被窃妄想

目的了解老年痴呆患者被窃妄想的临床特征。方法将83例老年痴呆患者按有无嫉妒妄想分为两组，并就痴呆严重度、类型、伴随症状等进行对照分析。结果被窃妄想在老年痴呆患者中的发生率较高（56．％）；痴呆严重程度轻于无被窃妄想者；被窃妄想在阿尔茨海默病（AD）中的发生率高于血管性痴呆（VD）；有被窃妄想者伴有较多嫉妒妄想（P均〈0．05）。结论被窃妄想可能是老年痴呆较敏感的临床症状之一，尤其对轻度AD的诊断有一定意义。     

“维生素AD、铁营养强化奶的研制”研究报告

目的:研制维生素AD、铁营养强化奶,用于群体有效防治维生素AD、铁缺乏.方法:应用微胶囊技术科学配方成维生素AD、铁营养粉,添加到鲜牛奶中.结果:工业化生产维生素AD、铁营养强化奶.结论:该产品取得了很好的社会效益和经济效益.     

药物浓度和病因对三磷酸腺苷治疗阵发性室上性心动过速的影响

本文报告23例次ATP治疗PSVT的效果,总有效率56.5％,9例次高浓度快速注射者8例转复。器质性心脏病者副作用较多,1例冠心速注高浓度ATP后,发生心室颤动和阿-斯氏综合征。这一结果提示:药物浓度和注射速度是影响疗效的主要因素,PSVT伴AVB者疗效也很低;病因和药物浓度是决定副作用的因素。因此,对于器质性心脏病者,尤其冠心病人,应避免高浓度快速静脉注射ATP。     

肝素雾化治疗小儿哮喘性疾病的疗效观察

应用肝素雾化治疗小儿哮喘性疾病（包括以喘为主的支气管肺炎）１６例，其咳喘症状消失和肺部体征消失时间校对照组快，总显效率高。文中还就７例肝素雾化治疗前后血气结果对照，进一步阐述肝素雾化有利于改善通气功能，促进二氧化碳排出和炎症吸收，从而解除支气管痉挛的机理。具有疗效显著，安全可靠，无任何副作用的特点，值得临床推广应用。     

椎管内转移癌病人氨甲喋呤配伍高渗盐水硬膜外灌注治疗顽固性疼痛的临床探讨

１０例椎管内转移癌病人曾长期使用大剂量镇痛药难以奏效，而少数病例便采用硬膜外腔注射吗啡２～４ｍｇ疼痛缓解仅１ｈ。采用硬膜外腔灌注氨甲喋呤配伍高渗盐水，使抗癌药直接与肿瘤接触，几分钟内杀死癌细胞，加之高渗盐水能促使肿瘤和神经干脱水，肿瘤体积缩小和破坏，改善局部动脉缺血和组织水肿，从而减轻或消除肿瘤对神经根的压迫，缓解和消除神经痛。     

The <Emphasis Type="Italic">Arg</Emphasis>194<Emphasis Type="Italic">Trp</Emphasis> polymorphism in DNA repair gene XRCC1 and the risk for sporadic late-onset Alzheimer's disease

Abstract Alzheimer's disease (AD) is defined pathologically by the presence of β-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically significant (OR=1.95, 95% CI 0.88–4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96–4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the development of AD.     

脑健冲剂对AD模型大鼠行为学及线粒体结构影响的实验研究

目的：研究脑健冲剂对AD模型大鼠行为学及线粒体超微结构的影响。方法：采用D-半乳糖致衰老与β-淀粉样蛋白注射联合所致的AD大鼠模型，服用脑健冲剂，测试大鼠在迷宫中的学习及记忆能力和海马CAl区线粒体体密度、面数密度等形态学指标。结果：脑健冲剂能有效的改善AD模型大鼠的学习、记忆障碍，并能很好地改善线粒体结构的受损程度。结论：脑健冲剂对AD有较明显的治疗作用，为临床应用脑健冲剂治疗AD提供实验依据。     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

Role of ubiquitin-mediated proteolysis in the pathogenesis of neurodegenerative disorders

Intraneuronal inclusions containing ubiquitylated filamentous protein aggregates are a common feature of many of the major human neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Loss of function mutations in enzymes of the ubiquitin conjugation/deconjugation pathway are sufficient to cause familial forms of neurodegenerative diseases, suggesting that failure of ubiquitin-mediated proteolysis could also be central to inclusion formation in the more common sporadic cases. Examination of ubiquitin-positive inclusions at the protein level provides evidence of attempted proteasomal proteolysis, however close inspection of the temporal aspects of inclusion formation indicates that ubiquitylation is probably a late event. In this regard, the presence of ubiquitin within inclusions of idiopathic neurodegenerative disorders may indicate not a primary dysfunction of ubiquitin-mediated proteolysis, but rather a secondary, presumably protective cellular response. Within this model, other factors are likely to be initiating in inclusion biogenesis. Consistent with these proposals, non-ubiquitylated forms of the principal ubiquitylated components of Alzheimer's disease neurofibrillary tangles and Parkinson's disease Lewy bodies, tau and alpha-synuclein proteins, respectively, can be degraded by proteasomes in a pathway which does not have an absolute requirement for ubiquitylation. Inhibition of proteasome function in the pathological state, as has been reported in both Alzheimer's and Parkinson's disease, could therefore contribute both to accumulation of non-ubiquitylated forms of aggregation-prone neuronal proteins, as well as impaired clearance of ubiquitylated aggregates.