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.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

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。     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

人参总皂甙溶血作用的研究

本实验研究了人参总皂甙在体外对人红细胞及在体内对狗红细胞的溶血作用。结果表明：人参总皂甙在体外对人的红细胞有溶血作用，表现为游离血红蛋白升高，人参总皂甙在体内对狗的红细胞有溶血作用，表现为游离血红蛋白升高，结合珠蛋白下降，网织红细胞升高等。同时，人参总皂甙对肾脏有一定毒性，表现为血尿及蛋白尿，但这种损伤可能为可逆性的。