Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease

Diagnosing Alzheimer's disease (AD) in the early stage is challenging. Informative biomarkers can be of great value for population-based screening. Metabolomics studies have been used to find potential biomarkers, but commonly used tissue sources can be difficult to obtain. The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD. Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue, erythrocytes are plentiful and easily accessed. Moreover, erythrocytes are metabolically active, a feature that distinguishes this sample source from other bodily fluids like plasma and urine. In this preliminary pilot study, the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD (control (CTRL)) were compared. Whole blood was collected post-mortem and erythrocytes were analyzed using ultra-performance liquid chromatography tandem mass spectrometry. Over 750 metabolites were identified in AD and CTRL erythrocytes. Seven were increased in AD while 24 were decreased (P<0.05). The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism. Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients. Sphingolipids have been previously implicated in AD and other neurological conditions. Furthermore, previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal, healthy adults. Together, these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.     

Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.     

不同术后镇痛模式对红细胞免疫功能的影响

目的探讨不同术后镇痛模式对红细胞免疫功能的影响。方法50例妇科手术患者,按术后不同镇痛模式分为硬膜外自控镇痛(PCEA)组和静脉自控镇痛(PCIA)组。并分别于术前、术后1、3、7 d采静脉血样检测红细胞C3b受体花环率(RCR)、红细胞免疫复合物花环率(RICR)、红细胞免疫粘附促进因子(RFER)和红细胞免疫粘附抑制因子(RFIR)。结果与术前比,PCEA组术后1 d RCR、RFER显著上升(P<0.05),RFIR显著下降(P<0.05),术后3 d RCR、RFER仍显著上升(P<0.05),而RICR显著下降(P<0.05);PCIA组术后1 d RCR、RFER显著下降(P<0.05),RFIR、RICR显著上升(P<0.05);PCIA组术后1、3 d RCR、RFER比PCEA组显著降低(P<0.05),而RICR显著上升(P<0.05);两组各参数在术后7 d基本恢复至术前水平。结论PCEA对红细胞免疫功能的稳定和恢复作用明显强于PCIA。     

体外循环对瓣膜置换术病人血细胞胰岛素受体和红细胞ATP含量的影响

目的：观察体外循环（ＣＰＢ）对１０例瓣膜置换术病人全血细胞胰岛素受体和红细胞ＡＴＰ含量的影响。方法：利用放射配体结合试验，测定全血细胞胰岛素受体密度和亲和力；用高效液相色谱法测定红细胞ＡＴＰ含量，同时监测血糖和胰岛素浓度。结果：转流３０分钟，血细胞高亲和胰岛素受体（Ｒ１）密度明显增加（Ｐ＜０．０１），亲和力（Ｋ１）明显降低（Ｐ＜０．０１），低亲和胰岛素受体（Ｒ２）密度也明显增加（Ｐ＜０．０１），但亲和力（Ｋ２）变化不大（Ｐ＞０．０５）；停机３０分钟，上述变化有所恢复，但未到转流前的水平。转流３０分钟红细胞ＡＴＰ含量明显降低（Ｐ＜０．０１），并持续到停机后３０分钟，同时伴随血糖明显升高（Ｐ＜０．０１），胰岛素／血糖比值明显降低（Ｐ＜０．０１）。结论：ＣＰＢ可致血细胞胰岛素受体密度增加而亲和力下降，以及红细胞ＡＴＰ含量下降。     

维生素E的抗脂质过氧化作用

本研究观察到:维生素 E 能抑制 H_2O_2引起的大鼠红细胞脂质过氧化和红细胞溶血,也能抑制分别由维生素 C-NADPH 和 Fe~(2+)-半胱氨酸诱发的大鼠肝、脑微粒体的脂质过氧化,可能还有清除过氧化氢、超氧自由基和羟自由基的作用。     

烧伤后红细胞损伤的机制——过氧化脂质、维生素E与溶血的关系

本实验发现大鼠体表面积20％Ⅲ°烧伤后,皮肤内产生了大量丙二醛(MDA),第二天达最高,第七天有第二高峰,血浆和红细胞(RBC)MDA第三天达最高,血浆和RBC维生素E(VE)于伤后第二天后迅速下降,RBC溶血第三天最甚。对皮肤MDA、血浆MDA、RBCMDA、血浆VE、BBC VE、1％H_2O_2溶血进行相关分析后发现在不同时相,有不同的相关关系,但基本遵循烧伤皮肤MDA增加、血浆MDA增加、RBC MDA增加、血浆和RBC VE降低,溶血增加的规律。文中讨论了RBC损伤的机制。     

红细胞衰老过程中渗透脆性的变化

作者在用抗体诱发红细胞溶血清建立的红细胞在体衰老模型的基础上，研究了红细胞衰老过程中渗透脆性的变化。结果显示，随着红细胞年龄的增加，其渗透脆性增加，推论其渗透脆性的变化可能与红细胞膜结构及红细胞几何形状（即红细胞表面积与体积之比）的变化有关。     

Red blood cell glutathione peroxidase activity in multiple sclerosis

Summary Glutathione peroxidase (GSH-Px) activity of red blood cells of 23 multiple sclerosis (MS) patients (10 men and 13 women, aged 22–64 years) was examined and compared to the enzyme activity of 26 healthy persons (15 men and 11 women, aged 19–50 years). It was found that the mean GSH-Px activity was significantly higher (P<0.001) in red blood cells of MS patients (39.1±8.1 IU/g Hb) as compared to the group of healthy persons (25.9±5.2 IU/g Hb). There was no difference according to sexes in both the MS patients and the control group. The results are discussed based on the hypothesis that organic peroxides play a role in the etiology of multiple sclerosis.     

The instability of membrane markers expressed by human monocytes and macrophages in culture

Surface markers were tested on freshly isolated human monocytes and following their in vitro maturation to macrophages. The markers tested were HLA-DR antigens, receptors for the Fc of IgG and complement as well as membrane markers defined by monoclonal antibodies. The results revealed a dynamic expression of some of the markers on monocytes which was influenced by several variables. The expression of the markers was modulated by the presence of different sera, by treatment with lymphokines and interferon and following the in vitro maturation of monocytes to macrophages. The most unstable marker was found to be the HLA-DR, which was modulated by all these variables. The 63D3 was affected by different sera and culture supernatant, as well as following the maturation of monocytes to macrophages, but not by lymphokines and interferon. One of the markers, the Mac 120, was found to be relatively stable and did not change significantly following the maturation of monocytes to macrophages. The Fc and complement receptors were also stable in their expression under these conditions, but were probably partially blocked in the presence of human serum. These results indicated that at least some of the heterogeneity related to the monocyte population was probably not due to the occurrence of stable subsets of cells, but rather to reversible changes in marker expression.     

肾阳虚证患者红细胞LPO、SOD和ATP酶活性的变化

目的 :探讨肾阳虚证患者红细胞LPO、SOD和ATP酶活性的特点及其意义。方法 :观察 19例肾阳虚证患者和 2 1例正常人红细胞LPO、SOD和红细胞膜Na+ K+ ATP酶、Mg2 + ATP酶、Ca2 + ATP酶、Ca2 + Mg2 + ATP酶活性的变化。结果 :与对照组比较 ,肾阳虚证患者红细胞LPO含量升高 (P <0 .0 1) ,红细胞SOD活性降低 (P <0 .0 1) ;红细胞膜Na+ K+ ATP酶活性显著升高 (P <0 .0 1) ,而Mg2 + ATP酶活性变化无显著性差异 ,Ca2 + ATP酶活性升高 (P <0 .0 1) ,Ca2 + Mg2 + ATP酶活性也显著升高 (P <0 .0 1)。结论 :肾阳虚证患者红细胞内脂质过氧化反应增强 ,而抗氧化能力降低 ,红细胞膜Na+ K+ ATP酶、Ca2 + ATP酶和Ca2 + Mg2 + ATP酶活性升高 ;本研究为理解肾阳虚证的病理生理基础提供了初步实验依据