Effects of inorganic nitrate and nitrite consumption on cognitive function and cerebral blood flow: A systematic review and meta-analysis of randomized clinical trials

ABSTRACT

We conducted a systematic review and meta-analysis of randomized clinical trials examining the effect of inorganic nitrate or nitrite supplementation on cognitive function (CF) and cerebral blood flow (CBF). Two databases (PubMed, Embase) were searched for articles from inception until May 2017. Inclusion criteria were: randomized clinical trials; participants >18 years old; trials comparing a nitrate/nitrite intervention with a control. Thirteen and nine trials were included in the meta-analysis to assess CF and CBF, respectively. Random-effects models were used and the effect size described as standardized mean differences (SMDs). A total of 297 participants (median of 23 per trial) were included for CF; 163 participants (median of 16 per trial) were included for CBF. Nitrate/nitrite supplementation did not influence CF (SMD +0.06, 95% CI: -0.06, 0.18, P = 0.32) or CBF under resting (SMD +0.14, 95% CI: -0.13, 0.41, P = 0.31), or stimulated conditions (SMD + 0.23, 95% CI: -0.11, 0.56, P = 0.19). The meta-regression showed an inverse association between duration of the intervention and CBF (P = 0.02) but no influence of age, BMI or dose (P < 0.05). Nitrate and nitrite supplementation did not modify CBF or CF. Further trials employing larger samples sizes and interventions with longer duration are warranted.     

成人自发性基底节区脑出血患者日常生活活动能力的影响因素

目的探讨未行手术治疗的成人首发基底节区脑出血患者日常生活活动能力的影响因素,以期早期制定干预措施,提高患者日常生活活动能力。方法采用前瞻性队列研究连续收集成人首发基底节区脑出血未行手术治疗且存活的患者97例。人院当天记录人口基线资料,进行卒中危险因素调查,行美国国立卫生研究所脑卒中评分（nationalinstitute of health stroke scale,NIHSS）和格拉斯哥昏迷评分（GCS）;人院次日清晨行白细胞计数、空腹血糖等多项实验室指标的测定;发病3周行NIHSS评分及Barthel指数（Barthel index,BI）评分;出院时记录住院期间肺部感染、尿路感染的发生情况;发病3个月时通过门诊或电话随访BI评分。结果脑出血患者发病3周及3个月时BI评分的影响因素为出血量、入院首次空腹血糖、自细胞计数及首次NIHss评分,发病3个月时影响因素还包括既往缺血性卒中病史、住院期间并发尿路感染。结论早期采取措施控制影响因素,有利于提高脑出血患者日常生活活动能力及工作能力。     

垂体后叶素治疗剖宫产术中胎盘源性难治性产后出血的疗效

目的探讨垂体后叶素治疗剖宫产术中胎盘源性难治性产后出血的临床疗效。方法将43例胎盘源性难治性产后出血患者按随机数字表法分为2组：研究组20例和对照组23例。对照组患者均采用嚼服米索前列醇片、按摩子宫、宫内肌内注射卡前列素、传统的子宫动脉结扎及宫腔内填塞纱条治疗。研究组在对照组治疗的基础上加用胎盘剥离面局部多点注射垂体后叶素治疗。观察2组患者平均手术时间、术中和术后2 h出血量、总出血量及临床疗效等情况。结果研究组、对照组平均手术时间分别为（62.80±10.38）min和（91.57±21.11）min,2组比较差异有统计学意义（P〈0.01）。研究组术中、术后2 h出血量、总出血量均少于对照组,差异均有统计学意义（均P〈0.01）。研究组有效20例（100.0%）,对照组有效21例（91.3%）,2组有效率比较差异有统计学意义（P〈0.05）。结论垂体后叶素治疗胎盘源性难治性产后出血能明显减少产后出血量,缩短手术时间,降低了子宫切除率。     

尿钚快速测定的优化设计

钚-239属极高放射毒性核素,对人体危害极大,而尿钚的快速测定有利于对易转移性钚造成的急性内污染进行快速诊断,为医学处理争取时间.本文采用正交设计方法,对放化测量尿钚的分析条件进行了优化,能在6小时内完成样品采集、处理和制源工作.方法的加标回收率为97.1%,探测下限为4.2×10-4 Bq,可以在24小时内提供是否存在钚-239急性内污染的判据.     

中国海外留学人员和"海归派"的状况调研报告

八十一万留学生中归国创业者近二十万人,“留学热”和“回国潮”是当代人才流动的一道风景线。上海十一位首席科学家青一色是“海归派”人士。在全球人才争夺战中,我国海外留学生成了发达国家猎取的目标。留在海外的近千名“尖子人才”、五万多名“优秀人才”和数量可观的“特殊人才”有待于我们吸引、招聘和充分利用。     

黑果小檗果实中锦葵素-3-O-葡萄糖苷的分离纯化及安全性研究

目的 建立并验证黑果小檗果实中锦葵素-3-O-葡萄糖苷(malvidin 3-O-glucoside, Ma-3G)的分离纯化方法,并评估其安全性。方法 利用超声辅助浸提法提取黑果小檗果实中的花色苷(Berberis atrocarpa Schneid anthocyanin,BHSA)粗提物,将BHSA粗提物用乙酸乙酯萃取,AB-8大孔吸附树脂、聚酰胺树脂纯化,采用Sephadex LH-20凝胶柱对纯化后BHSA进行分离,分别考察洗脱液浓度、上样量对花色苷不同组分分离效果的影响,并筛选出最佳分离条件,将最佳条件下分离得到的Ma-3G进行紫外可见光谱扫描及高效液相色谱法检测。采用固定剂量法对小鼠以2000 mg/kg Ma-3G的单次口服剂量进行安全性实验。结果 经乙酸乙酯萃取、AB-8大孔吸附树脂、聚酰胺树脂纯化后得到BHSA粗品纯度为50.76%, Sephadex LH-20凝胶柱层析的最佳分离条件为上样量20 mg,洗脱液为含有0.5%HCl的20%甲醇溶液,在此条件下成功获得了Ma-3G单体。使用面积归一化法进行纯度测定,结果显示其纯度为99.48%。黑果小檗果实中Ma-3...     

TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies

Subarachnoid hemorrhage is associated with severe neurological deficits for survivors. Among survivors of the initial bleeding, secondary brain injury leads to additional brain damage. Apart from cerebral vasospasm, secondary brain injury mainly results from cerebral inflammation taking place in the brain parenchyma after bleeding. The brain’s innate immune system is activated, which leads to disturbances in brain homeostasis, cleavage of inflammatory cytokines and, subsequently, neuronal cell death. The toll-like receptor (TLR)4 signaling pathway has been found to play an essential role in the pathophysiology of acute brain injuries such as subarachnoid hemorrhage (SAH). TLR4 is expressed on the cell surface of microglia, which are key players in the cellular immune responses of the brain. The participants in the signaling pathway, such as TLR4-pathway-like ligands, the receptor itself, and inflammatory cytokines, can act as biomarkers, serving as clues regarding the inflammatory status after SAH. Moreover, protein complexes such as the NLRP3 inflammasome or receptors such as TREM1 frame the TLR4 pathway and are indicative of inflammation. In this review, we focus on the activity of the TLR4 pathway and its contributors, which can act as biomarkers of neuroinflammation or even offer potential new treatment targets for secondary neuronal cell death after SAH.     

Blood-Brain Barrier Disintegration in Growth-Restricted Fetuses with Brain Sparing Effect

The endothelial cells of the blood-brain barrier adhere closely, which is provided by tight junctions (TJs). The aim of the study was to assess the damage to the endothelial TJs in pregnancy, complicated by fetal growth restriction (FGR) and circulatory centralization (brain-sparing effect, BS). The serum concentrations of NR1 subunit of the N-methyl-D-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), and zonula occludens protein – 1 (zo-1), and the placental expressions of OCLN, claudin-4 (CLN4), CLN5, and zo-1 were assessed with ELISA. The significantly higher serum NME1 concentrations and the serum CLN5/zo-1 index were observed in FGR pregnancy with BS, as compared to the FGR group without BS. The FGR newborns with BS were about 20 times more likely to develop an intraventricular hemorrhage (IVH) than the FGR infants without BS. The cerebroplacental ratio (CPR) allowed to predict the IVH in growth-restricted fetuses. The significantly lower placental CLN4 expression was observed in the FGR group with BS and who postnatally developed an IVH, as compared to the growth-restricted infants with BS without IVH signs. Pregnancy complicated by FGR and BS is associated with the destabilization of the fetal blood-brain barrier. The IVH in newborns is reflected in the inhibition of the placental CLN4 expression, which may be a useful marker in the prediction of an IVH among growth-restricted fetuses.     

Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts

Phosphorylcholine (PC) is one of the main oxLDL epitopes playing a central role in atherosclerosis, due to its atherogenic and proinflammatory effects. PC can be cleared by natural IgM antibodies and low levels of these antibodies have been associated with human vein graft (VG) failure. Although PC antibodies are recognized for their anti-inflammatory properties, their effect on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH)—interdependent processes contributing to plaque rupture—are unknown. We hypothesized that new IgG phosphorylcholine antibodies (PC-mAb) could decrease vulnerable lesions in murine VGs.Therefore, hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery and weekly IP injections of (5 mg/kg) PCmAb (n = 11) or vehicle (n = 12) until sacrifice at day 28. We found that PCmAb significantly decreased vein graft media (13%), intima lesion (25%), and increased lumen with 32% compared to controls. PCmAb increased collagen content (18%) and decreased macrophages presence (31%). PCmAb resulted in 23% decreased CD163+ macrophages content in vein grafts whereas CD163 expression was decreased in Hb:Hp macrophages. PCmAb significantly lowered neovessel density (34%), EC proliferation and migration with/out oxLDL stimulation. Moreover, PCmAb enhanced intraplaque angiogenic vessels maturation by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a 62% decrease in IPH. PCmAb effectively inhibits murine atherosclerotic lesion formation in vein grafts by reducing IPA and IPH via decreased neovessel density and macrophages influx and increased neovessel maturation. PC-mAb therefore holds promise as a new therapeutic approach to prevent vein graft disease.