Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy

To assess the etiology of influenza-associated encephalopathy (IAE), a surveillance effort was conducted during 2000-2003 in South-West Japan. All fatal and handicapped patients except one (4/34 patients) exhibited a disorder of mitochondrial beta-oxidation evoked by the inactivated carnitine palmitoyltransferase II (CPT II) with transiently elevated serum acylcarnitine ratios (C(16:0) + C(18:1))/C(2) > 0.09 during high-grade fever. Analyses of genotypes and allele compositions of CPT II revealed a thermolabile phenotype of compound heterozygotes for [1055T > G/F352C] and [1102G > A/V368I], which shows a higher frequency in IAE patients than healthy volunteers (P < 0.025). The thermolabile phenotype of CPT II variations may be a principal genetic background of IAE in Japanese.     

可溶性细胞间粘附分子-1在新生儿缺氧缺血性脑病血清中的表达及临床意义

目的：探讨可溶性细胞间粘附分子-1（ICAM-1）在新生儿缺氧缺血性脑病（HIE）血清中的表达及其与病情严重程度的关系。方法：采用酶联免疫吸附双抗体夹心法（ELISA）检测45例HIE新生儿和50例健康新生儿血清中可溶性ICAM-1水平。结果：HIE组血清可溶性ICAM-1浓度为（159．25±25．62）ng／ml,对照组血清可溶性ICAM-1浓度为（53．35±12．42）ng／ml,两组相比较有显著性并差异（P〈0．05）;轻、中、重度HIE患儿血清可溶性ICAM-1浓度与对照组比较显著升高（P〈0．05）,在HIE各组中可溶性ICAM-1浓度为重度〉中度〉轻度,各组相比较有显著性差异（P〈0．05）;HIE患儿血清可溶性ICAM-1水平与临床分度呈正相关相关（r=0．652,P〈0．01）。结论：可溶性ICAM-1在HIE新生儿血清中呈高表达,可溶性ICAM-1的水平与病情严重程度密切相关。可溶性ICAM-1在新生儿缺氧缺血性脑损伤中起着重要作用：     

可溶性细胞间粘附分子-1在新生儿缺氧缺血性脑病血清中的表达及临床意义

目的:探讨可溶性细胞间粘附分子-1(ICAM-1)在新生儿缺氧缺血性脑病(HIE)血清中的表达及其与病情严重程度的关系。方法:采用酶联免疫吸附双抗体夹心法(ELISA)检测45例HIE新生儿和50例健康新生儿血清中可溶性ICAM-1水平。结果:HIE组血清可溶性ICAM-1浓度为(159.25±25.62)ng/ml,对照组血清可溶性ICAM-1浓度为(53.35±12.42)ng/ml,两组相比较有显著性并差异(P<0.05);轻、中、重度HIE患儿血清可溶性ICAM-1浓度与对照组比较显著升高(P<0.05),在HIE各组中可溶性ICAM-1浓度为重度>中度>轻度,各组相比较有显著性差异(P<0.05);HIE患儿血清可溶性ICAM-1水平与临床分度呈正相关相关(r=0.652,P<0.01)。结论:可溶性ICAM-1在HIE新生儿血清中呈高表达,可溶性ICAM-1的水平与病情严重程度密切相关。可溶性ICAM-l在新生儿缺氧缺血性脑损伤中起着重要作用。     

Quantitative metabolome profiling reveals the involvement of the kynurenine pathway in influenza-associated encephalopathy

Introduction

Influenza-associated encephalopathy is a serious complication of influenza and is the most common form of acute encephalitis/encephalopathy in Japan. The number of reports from other countries is increasing, reflecting international recognition and concern.

Objectives

Identification of a specific biomarker could provide important clues about the pathophysiology of influenza-associated encephalopathy.

Methods

During the 2009–2011 flu seasons, 34 pediatric patients hospitalized with influenza complications, including influenza-associated encephalopathy, were enrolled in the study. Serum samples were collected during the acute and convalescent phases of disease. Patients were classified into encephalopathy (n = 12) and non-encephalopathy (n = 22) groups. Serum metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. Quantified data were evaluated for comparative analysis. Subsequently, a total of 55 patients with or without encephalopathy were enrolled for absolute quantification of serum kynurenine and quinolinic acid.

Results

Based on m/z values and migration times, 136 metabolites were identified in serum samples. During the acute phase of disease, three metabolites (succinic acid, undecanoic acid, and kynurenine) were significantly higher, and two other metabolites (decanoic acid and cystine) were significantly lower, in the encephalopathy group compared to the non-encephalopathy group (p = 0.012, 0.022, 0.044, 0.038, 0.046, respectively). In a larger patient group, serum kynurenine and its downstream product in tryptophan metabolism, quinolinic acid, a known neurotoxin, were significantly higher in the encephalopathy than the non-encephalopathy without febrile seizure group.

Conclusion

Comprehensive metabolite profiles revealed five metabolites as potential biomarkers for influenza-associated encephalopathy; the tryptophan–kynurenine metabolic process could be associated with its pathophysiology.

     

仙湖苏铁种群年龄判断及年龄结构特征

根据苏铁类植株体残存的营养叶叶基数、开花痕数以及生长单元发生率等茎干特征, 建立了仙湖苏铁种群年龄判断方法,计算出该种群年龄. 进一步采用年龄结构图、年龄分布 曲线和曲线估计等方法,从基株和无性系水平探讨了仙湖苏铁种群的年龄结构特征.年龄结构 图显示,仙湖苏铁无性系种群为稳定种群,基株种群为衰退种群;年龄分布曲线和曲线估计结 果则表明仙湖苏铁无性系和基株种群均为衰退种群. 综合3种方法的分析结果,仙湖苏铁 种群为衰退种群,必须采取一定措施予以保护.     

The relationship of Helicobacter pylori positivity with age, sex, and ABO/Rhesus blood groups in patients with gastrointestinal complaints in Turkey

BACKGROUND: To determine the magnitude of Helicobacter pylori infection in patients with gastrointestinal complaints in Turkey. METHODS: We studied 1680 patients with variable gastrointestinal complaints. The H. pylori infection status was determined using C-14 urea breath test (UBT). Overall, 1567 patients (548 male, 1019 female; age range 4-80 years, mean 29.37 +/- 17.30 years) were included in this study. The relationship between H. pylori positivity and age, sex, sociodemographic characteristic, blood groups, and gastrointestinal diagnosis was determined. RESULTS: H. pylori positivity was found to be 68%. The difference in positivity rates between age groups 4-9 years and other groups was statistically significant (p = .001). H. pylori positivity was 67.7% in males and 68.2% in females (p = .865). H. pylori positivity was 72.1, 65.1, 70, and 68.4% in blood groups A, B, AB, and O (p = .703), and 68.9% and 76.3% in Rh (+) and Rh (-) blood subgroups, respectively (p = .292). There was no statistically significant difference between H. pylori positivity and gastrointestinal diagnosis (p = .980). There was significant association between increased number of household members and low socioeconomic status, and H. pylori positivity (p < .001). Living in rural and suburban area was significantly associated with H. pylori positivity compared with living in urban. CONCLUSIONS: H. pylori infection positivity rate was 68% in symptomatic subjects in Turkey and the positivity rate was significantly lower at age 4-9 years than the other age groups. It was not related to gender, ABO, and Rh blood groups and gastrointestinal diagnosis. Low socioeconomic conditions and living in rural and suburban area were significantly associated with H. pylori positivity.     

Neuroprotection of aucubin in primary diabetic encephalopathy

Hippocampal neuronal apoptosis accompanied by impairment of cognitive function occurs in primary diabetic encephalopathy. In this study, we investigated the neuroprotective mechanism of the iridoid glycoside, aucubin, using rats (n=8). Diabetes mellitus was induced in the rats by intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg body weight). After 65 d, half of the DM rats were administered aucubin (5 mg/kg; i.p.) for 15 d, yielding treatment DM A. A third group of rats received no strepto- zotocin or aucibin, and served as controls (CON). Encephalopathy was assessed using Y-maze be- havioral testing. Rats were euthanized on Day 87, and hippocampi were excised for visual (light and transmission electron microscopic) and immunochemical (Western blot; immunohistochemical) as- sessments of the CA1 subfield for apoptosis and expression of regulatory proteins Bcl-2 and Bax. Treatment responses to all the parameters examined (body weight, plasma glucose, Y-maze error rates, pyramidal cell ultrastructure, proportions of apoptotic cells, levels of expression of Bcl-2 and Bax, and survivability of neuronal cells) were identical: there were highly significant differences between DM and CON groups (P<0.001), but the effects were significantly moderated (P<0.01) in DM A compared with DM. These findings confirm the association of apoptosis with the encephalopathic effects of diabetes mellitus, and suggest a major role of the expression levels of Bcl-2 and Bax in the regulation of apop- totic cell death. All of the results suggest that aucubin could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.     

Extraordinary Changes in Excitatory Amino Acid Levels in Cerebrospinal Fluid of Influenza-Associated Encephalopathy of Children

The correlation between the glutamate-glutamine cycle and nitric oxide (NO) production in the central nervous system (CNS) of a new type of influenza-associated encephalopathy in children is discussed. When measurements of several amino acids and NOx (nitrite/nitrate) levels in the cerebrospinal fluid (CSF) using HPLC-fluorescence and -UV methods, respectively, were made. the CSF glutamate levels of patients with the new type of encephalitis were significantly lower, and both glutamine and NOx levels were significantly higher than those of the control group and the patients of the meningitis group. Results indicate that the turnover rate of glutamate in CNS, particularly in the brain, increases in the influenza-associated encephalopathy. The high mortality in the disease may correlate with the hyperactivity of supra-spinal glutamate neurons and the subsequent high activity levels of NOx in CNS.     

基于树木起源、立地分级和龄组的单木生物量模型

以马尾松(Pinus massoniana)和落叶松(Larix)的大样本实测资料为建模样本,以独立抽取的样本为验证样本,把样本按起源、立地和龄组进行分级,采用与材积相容的两种相对生长方程,分普通最小二乘和两种加权最小二乘,对地上部分总生物量、地上各部分生物量和地下生物量进行模型拟合和验证,使用决定系数、均方根误差、总相对误差和估计精度等8项统计量对结果进行分析。结果表明:两个树种地上部分总生物量,立地分类方法,模型的拟合结果和适用性都最优;马尾松VAR模型较优,而落叶松CAR模型较好;两种加权最小二乘方法,在建模样本和验证样本中表现得不一致。在建模样本中,加权回归2(权重函数1/f^0.5)略优于加权回归1(权重函数1/y^0.5),但在验证样本中,加权回归1却明显优于加权回归2。而同时满足建模样本拟合结果最优和验证样本检验结果最优的组合中,只有加权回归1。两个树种地上部分各分量生物量,模型拟合结果和适用性,均为干材最优,树叶最差、树枝和树皮居中,样本分类、模型类型和加权最小二乘方法对干材生物量的影响,规律和地上部分总生物量相同;样本分类、模型类型和加权最小二乘方法的最优组合,用验证样本检验的结果,总相对误差树枝不超过±10.0%,树皮不超过±5.0%,树叶马尾松不超过±30.0%,落叶松不超过±20.0%。两个树种地下部分(根)生物量,样本按龄组分类方法,模型拟合结果最优,与材积相容的模型总体上优于与地上部分总生物量相容模型。     

传染性海绵状脑病的诊断进展和存在的问题

传染性海绵状脑病是由朊病毒引起的人和多种哺乳动物以神经退行性变化为主要特征的一种慢性致死性传染病。引起这类疾病的病原因子是一种编码宿主蛋白的PrPC转变为异常的PrPSC沉积在大脑,导致传染性海绵状脑病的发生。本文从临床症状识别、组织病理学诊断、致病性朊蛋白检测、生物学测定以及毒株鉴定等几个方面作一回顾和总结,为揭示朊病毒疾病致病机理和诊断研究提供借鉴。     

分子吸附再循环系统治疗肝功能衰竭合并肝性脑病的临床效果观察

目的探讨分子吸附再循环系统在肝功能衰竭合并肝性脑病治疗中的临床应用效果。方法将我院2015年1月~2016年1月收治的肝功能衰竭合并肝性脑病患者100例,根据治疗方式的不同分为观察组和对照组,每组50例。对照组50例患者接受保肝、维持水电解质平衡以及营养支持等综合治疗,观察组50例患者在综合治疗基础之上接受分子吸附再循环系统治疗,并对两组患者的治疗效果,治疗前后肝功能改善情况、不良反应进行统计分析。结果两组患者治疗前的总胆红素、凝血酶原活动度、血氨以及Glasgow昏迷评分比较差异无统计学意义(P0.05)。观察组患者治疗3天后的总胆红素以及血氨明显低于对照组,两组比较差异有统计学意义(P0.05);而且治疗有效率明显高于对照组(P0.05),治疗后肝性脑病清醒率高于对照组(P0.05)。两组患者治疗期间均无严重不良反应。结论肝功能衰竭合并肝性脑病患者在综合治疗上采取分子吸附再循环系统治疗的效果显著,可明显改善患者肝功能,提高肝性脑病清醒率,且不良反应少,值得临床推广使用。     

Supersensitivity of GABA-A receptors in hepatic encephalopathy

During the past decade a new approach to pathogenetic, studies of hepatic encephalopathy has been undertaken to identify the neurochemical alterations which characterize the syndrome. Using animal models of hepatic encephalopathy electrophysiological, behavioral, pharmacological and biochem evidence were provided of an increased functional activity of the GABA-A receptors, including the Benzodiazepine site. These demonstrations seem to explain the increased sensitivity of patients with acute or chronic liver disease to sedative administration. The described increased tone of the GABAergic receptor complex seems to play a key role in the generalized depression of the central nervous system which characterizes hepatic encephalopathy, but other factors seem to contribute to the neuronal derangement present in this syndrome leading to an imbalance between inhibitory and excitatory receptor systems in the brain. Based on these findings a new symptomatic treatment with antibenzodazepine compounds which seem temporarely to counteract the symptoms of hepatic encephalopathy, was introduced.     

Olfactory deficits in patients affected by minimal hepatic encephalopathy: a pilot study

Minimal hepatic encephalopathy (MHE) is the earliest stage of hepatic encephalopathy and is associated with changes in cognitive functions, in electrophysiological parameters, and in cerebral neurochemical/neurotransmitter homeostasis. MHE can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy (HE). At present, no data are available on a possible olfactory dysfunction in such a syndrome, although the pathophysiology of HE may alter olfactory functions since some of the neurotransmitters impaired in the syndrome are involved in the transmission of olfactory information. In the present paper, we performed a preliminary study aimed at detecting whether identification and recognition odor memory is altered in patients with MHE. Twelve patients diagnosed as MHE on the basis of their scores at the portosystemic encephalopathy (PSE)-syndrome test battery, and 12 age-matched controls were studied. Consistent with the hypothesis, patients performed significantly worse than controls for both odor identification and recognition tasks. In addition, a significant correlation between the two olfactory tests and the PSE-syndrome test score was found. This pattern supports the notion that olfactory alterations related to cognitive dysfunction in patients with MHE may be linked to the pathophysiology of HE.     

Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats

The aim of our study was to investigate the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats. Male Wistar rats were divided among (i) control, saline-treated, and (ii) thioacetamide-treated groups (TAA(300) (300?mg/kg body mass); TAA(600) (600?mg/kg); and TAA(900) (900?mg/kg)). The daily dose of thioacetamide (300?mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)), or 3 times (TAA(900)), on subsequent days. Behavioral manifestations were determined at 0, 2, 4, 6, and 24?h, while electroencephalographic changes were recorded 22-24?h after the last dose. General motor activity and exploratory behavior, as well as head shake, auditory startle reflex, placement, and equlibrium tests were diminished in the TAA(600) and TAA(900) groups compared with the control, and were absent in the TAA(900) group 24?h after treatment. Corneal, withdrawal, grasping, and righting reflexes were significantly diminished in the TAA(900) group compared with the control. Mean electroencephalographic power spectra density was significantly higher in TAA(300) and TAA(600) and lower in the TAA(900) group by comparison with the control. Only a score of 3 (mean dominant frequency?≤ 7.3?Hz and δ relative power?≥ 45%) was observed in the TAA(900) group. Thioacetamide induces encephalopathy in rats in a dose-dependent manner. A dose of 900?mg/kg TAA may be used as a suitable model of all stages of hepatic encephalopathy.     

胰性脑病的诊断治疗

胰性脑病是急性胰腺炎的罕见并发症,诊断治疗困难,死亡率极高。本文详细讨论该病的发病机制、临床表现、诊断、鉴别诊断、预防及治疗方面的进展。     

内蒙古汉族、蒙古族与日本学生身高和体质量的最大发育年龄段差异

分析2014年7-18岁内蒙古汉族、蒙古族和日本学生身高及体质量最大发育年龄差异。汉族和蒙古族数据来自《2014年内蒙古自治区学生体质与健康调查研究》;日本数据来源于"平成26年(2014年)度体育与运动调查统计情报"。结果显示:7-18岁各年龄段汉族男女生身高分别比蒙古族高出1.98 cm和1.54 cm;高出日本2.59 cm和2.91 cm(P<0.05)。汉族男生体质量平均高出蒙古族1.97 kg、高出日本4.01 kg;汉族和蒙古族女生体质量分别比日本高出2.59 kg(P<0.05)和2.67 kg(P<0.05)。2014年内蒙古汉族和蒙古族学生身高和体质量发育水平优于日本学生。汉族男生身高最大发育年龄分别提前蒙古族和日本1.73岁和0.9岁;汉族和蒙古族男生体质量最大发育年龄分别比日本滞后1.17和1.07岁;日本女生身高最大发育年龄比汉族和蒙古族提前0.68岁和0.37岁。     

Glutathione system in erythrocytes and blood plasma in strokes and dyscirculatory encephalopathy

Dyscirculatory encephalopathy and mild ischemic stroke are characterized by solitary changes in components of glutathione metabolism. In moderate and severe ischemic strokes essential changes have been found. Changes in glutathione metabolism are also expressed in hemorrhagic stroke. The clearest increase was found in activities of glutathione peroxidase and glutathione transferase and in rare cases in activities of glutathione reductase and GSH concentration. The increase of enzymes activity was not found in patients with delayed onset of treatment (more than 3 days) and also in severe cases terminated by subsequent death of patients. Glutathione system is obviously important for tolerance to cerebral ischemia.     

Endogenous GABAergic modulators in the pathogenesis of hepatic encephalopathy

Theories on the neurochemical etiology for hepatic encephalopathy have recently focussed on activation of inhibitory neurotransmitter GABA systems. Modulators of the GABA_A receptor complex, including diazepam binding inhibitor, are significantly and selectively altered in hepatic encephalopathy. In animals and humans, benzodiazepine receptor antagonists rapidly ameliorate this syndrome suggesting the possible existence of an endogenous benzodiazepine-like substance. Endogenous GABAergic modulators may contribute to the neurochemical pathogenesis of hepatic encephalopathy.Special issue dedicated to Dr. Erminio Costa     

In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification

The in vitro amplification of prions by serial protein misfolding cyclic amplification has been shown to detect PrP^Sc to levels at least as sensitive as rodent bioassay but in a fraction of the time. Bovine spongiform encephalopathy is a zoonotic prion disease in cattle and has been shown to occur in 3 distinct forms, classical BSE (C-BSE) and 2 atypical BSE forms (L-BSE and H-BSE). Atypical forms are usually detected in asymptomatic, older cattle and are suggested to be spontaneous forms of the disease. Here, we show the development of a serial protein misfolding cyclic amplification method for the detection of H-BSE. The assay could detect PrP^Sc from 3 distinct experimental isolates of H-BSE, could detect PrP^Sc in as little as 1×10^?12 g of brain material and was highly specific. Additionally, the product of serial protein misfolding cyclic amplification at all dilutions of seed analyzed could be readily distinguished from L-BSE, which did not amplify, and C-BSE, which had PrP^Sc with distinct protease K-resistance and protease K-resistant PrP^Sc molecular weights.