Improvement of platelet storage conditions by using new polyolefin containers

BACKGROUND : Storage of pooled platelet concentrates (PCs) with yields above 3.0 × 10¹¹ platelets per unit in a 1-L PL-732 polyolefin container for 5 days often results in a drop in pH to below 6.0. Recently, new oxygen-permeable platelet containers (1-L PL-2410, 1-L and 1.5-L Compoflex) have been developed. The maximal platelet storage capacities of the new containers and the PL-732 were compared. STUDY DESIGN AND METHODS : Large platelet pools (n = 27) with platelet concentrations between 1.2 and 1.4 × 10¹¹ per L were made from 3 to 5 PCs prepared from buffy coats. The pools were divided in equal volumes among the PL-732 and the three new platelet containers. Platelet counts in the PCs ranged from 1.0 to 5.0 × 10¹¹ per unit. All PCs were stored on a flatbed shaker at 22 ± 2°C and evaluated on Days 1, 3, 5, and 7 by measuring platelet count, pH, pO₂, pCO₂, HCO₃-, glucose, lactate, platelet swirling, and soluble p-selectin. RESULTS : Day 7 storage of PCs (n = 6) with yields between 3.0 and 4.0 × 10¹¹ platelets in PL-732 showed mean ± SD pH values of 5.93 ± 0.05 and lactate values of 32.3 ± 7.9 mmol per L; in 4 of these 6 PCs, pH was below 6.0. In contrast, storage of these PCs in 1-L PL-2410 and 1.5-L Compoflex containers and of 2 of these 6 PCs in 1-L Compoflex containers showed pH values above 6.8. Lactate values were 15.5 ± 1.3, 15.3 ± 1.8, and 19.5 ± 4.7 mmol per L, respectively (p < 0.001 vs. PL-732). The platelet storage capacity of the new containers with platelet yields between 4.0 and 5.0 × 10¹¹ per unit (n = 6) was evaluated. Day 7 storage of these PCs in the 1.5-L Compoflex showed an average pH value of 6.74 ± 0.20; in 2 of 6 PCs, pH was below 6.8. The average pH value in the PL-2410 was 6.38 ± 0.31, and in all PCs, pH was below 6.8. Average lactate values were 17.8 ± 5.7 and 25.8 ± 5.6 mmol per L (p < 0.05), respectively. Soluble p-selectin values on Day 7 of storage increased approximately twofold in all PCs. CONCLUSION : The new oxygen-permeable containers showed platelet quality comparable to that with the PL-732 and for longer storage periods and at higher platelet counts.     

The influence of vitamin E quinone on platelet structure, function, and biochemistry

Although the effects of vitamin E on platelet function have been investigated in vivo and in vitro, vitamin E quinone, a natural metabolite of vitamin E, has been virtually overlooked. This oxidized form of vitamin E inhibits platelet aggregation and secretion induced by various aggregating agents more effectively than vitamin E by a magnitude of 5-10-fold. Vitamin E and vitamin E quinone do not alter platelet ultrastructure or cellular concentrations of serotonin and adenine nucleotides, including cAMP. Inhibition of aggregation by vitamin E quinone occurs in the absence of detectable reduction of vitamin E quinone or oxidation of vitamin E and is readily reversed by washing the platelet. Only vitamin E quinone prevents arachidonic acid release and slightly inhibits cyclooxygenase, whereas both agents partially prevent calcium release from a platelet subcellular organelle. Vitamin E quinone also inhibited synthesis of prostacyclin by endothelial cells with basal synthesis in the presence of external arachidonic acid being less affected than thrombin-stimulated PGI2 production. The greater potency of vitamin E quinone in suppressing platelet function compared to vitamin E suggests that this quinone metabolite may be the better antithrombotic agent and possibly responsible for in vivo effects previously attributed to vitamin E.     

Incidence of neonatal diabetes in Austria–calculation based on the Austrian Diabetes Register

Wiedemann B, Schober E, Waldhoer T, Koehle J, Flanagan SE, Mackay DJG, Steichen E, Meraner D, Zimmerhackl LB, Hattersley AT, Ellard S and Hofer S. Incidence of neonatal diabetes in Austria–calculation based on the Austrian Diabetes Register.
Background: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes which is diagnosed in the first 6 months of life. Several studies in the last few years provide information on genetic causes for NDM.
Objective: The aim of this study was to identify all patients with diabetes in the first 6 months of life through the Austrian Diabetes Register, which is available since 1989. A retrospective data analyses was performed to calculate the current incidence of NDM.
Subjects and Methods: Ten patients were registered with diabetes onset within the first 6 months of life in the Austrian Diabetes Register. Evaluation of detailed clinical data was performed by sending a questionnaire to all diabetes centers.
Results: Ten patients from nine different families with NDM were diagnosed in Austria from 1989 until September 2007. Seven patients (one male, six females) had transient NDM (TNDM), three (two males, one female) showed a permanent course [permanent neonatal diabetes mellitus (PNDM)]. One had immunodeficiency, polyendocrinopathy and enteropathy X-linked (IPEX) syndrome and another showed aplasia of the pancreas; no genetic etiology was found in the third case. In three out of seven patients with a transient course of NDM a genetic diagnosis was possible. Two female siblings had activating point mutations in the ABCC8 gene, although one patient had paternal uniparental isodisomy of chromosome 6q24. One patient's family did not consent to genetic testing.
Conclusions: The incidence of NDM in Austria is 1/160 949, with an incidence of 1/ 536 499 for PNDM and 1/229 928 for TNDM.     

小分子干扰RNA和反义寡核苷酸技术的比较及其应用意义

目的:分析比较小分子干扰RNA和反义寡核苷酸技术的作用机制、作用靶点、设计方法和临床应用的异同。资料来源:应用计算机检索PubMed数据库1990-01/2007-02相关小分子干扰RNA和反义寡核苷酸方面的文献,检索词"siRNA;accessible site;antisense oligonucleotides;RNA Interference;mechanism;chemically modified siRNA;chemically modified oligonucleotides",限定文献语言种类为English。资料选择:对资料进行初审,选取有关小分子干扰RNA和反义寡核苷酸的文献,开始查找全文。纳入标准:关于RNA干扰和反义寡核苷酸作用机制的研究;探讨如何在mRNA上寻找小分子干扰RNA和反义寡核苷酸作用靶点的论文;解释反义寡核苷酸化学修饰和小分子干扰RNA分类的文章;应用小分子干扰RNA治疗肿瘤的探索性研究。排除标准:非原创性的文章。资料提炼:共检索到200多篇关于小分子干扰RNA和反义寡核苷酸的文献,最终纳入40篇符合标准的文献。资料综合:尽管小分子干扰RNA和反义寡核苷酸作用机制不尽相同,但两者在很多方面如选择mRNA的作用靶点、化学修饰和应用等方面,是相通的。研究反义寡核苷酸的经验可以使小分子干扰RNA的研究事半功倍。本文对小分子干扰RNA和反义寡核苷酸技术进行了比较,这将有助于小分子干扰RNA的研究与应用。结论:研究反义寡核苷酸技术的经验对小分子干扰RNA的研究有指导意义,小分子干扰RNA是非常有希望被用于肿瘤治疗的新型药物。     

Regulation of expression of a human intercellular adhesion molecule (ICAM-1) during lymphohematopoietic differentiation

The intercellular adhesion molecule (ICAM-1) is a cell-surface molecule which binds to leukocyte function antigen-1 (LFA-1) and regulates both leukocyte adhesion to endothelial cells and immune functions requiring cell-cell contact. Membrane expression of ICAM-1 is highly regulated on all hematopoietic lineages. Cell membrane antigen is significantly expressed on a small subset of bone marrow (BM) progenitors but is weak or absent on all cell lineages once they enter the circulation. However, strong expression on tissue macrophages and germinal center B cells suggested that activated cells may show upregulated expression. When B cells, T cells, macrophages, or granulocytes were activated in vitro by suitable mitogens, ICAM-1 expression was induced in all cases. Parallel studies of hematopoietic tumors demonstrated a heterogeneity of expression which correlated with expression on their normal cellular counterparts. In particular, a striking correlation between expression on B-cell tumors and corresponding stages of B-cell differentiation was noted. The widely varying expression of ICAM-1 contrasts with LFA-1 which, while variable, is nevertheless significantly positive at all stages of differentiation. This suggests that the major regulation of homotypic adhesion mediated by the LFA-1/ICAM-1 linkage occurs through control of ICAM-1 expression. In keeping with this notion, ICAM-1 expression was also correlated with the "adhesiveness" of B-lymphoid tumors. Large solitary lymphoma masses showed intense expression of ICAM-1. Conversely, chronic lymphocytic leukemia (CLL) cells and lymphoma cells from tumors exhibiting diffuse, widespread lymph node disease showed weak expression. These observations are discussed in relation to the role of ICAM-1 in regulation of lymphoid recirculation and the biology of lymphoid tumors.