Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer's disease

Phospholipase A₂ (PLA₂) is a key enzyme in the metabolism of membrane phospholipids. PLA₂ influences the processing and secretion of the amyloid precursor protein, which give rise to the -amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). We investigated the PLA₂ activity in two samples: in post-mortem brains from 23 patients with AD and 20 non-demented elderly controls, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In AD brains PLA₂ activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA₂ activity correlated significantly with an earlier onset of the disease, an earlier age at death and higher counts of neurofibrillary tangles and senile plaques. In platelets PLA₂ activity was also significantly reduced in the AD group as compared with healthy and depressed controls. The reduction of the enzyme activity in platelets correlated with an early disease onset and with the severity of cognitive impairment, indicating a relationship between abnormally low PLA₂ activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA₂ activity may contribute to the production of amyloidogenic peptides in the disease. Further studies are needed to examine whether PLA₂ activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.     

Characterization of soluble platelet guanylyl cyclase with peptide antibodies

Summary Soluble guanylyl cyclase partially purified from bovine and human platelets was characterized with antibodies raised against synthetic peptides corresponding to different sequences of the ₁- and ₁-subunits of the bovine lung enzyme. On immunoblots, the platelet guanylyl cyclase was recognized by the four antisera used, with the exception of an antiserum against the C-terminus of the ₁-subunit which did not react with the human platelet but with the bovine platelet ₁-subunit. Furthermore the human platelet ₁-subunit exhibited a slightly lower molecular mass than the bovine protein. The C-terminal antibodies precipitated native platelet and lung guanylyl cyclase activity. In contrast an antibody against a peptide out of the putative catalytic domain, which is highly conserved between all guanylyl cyclases sequenced so far, did not precipitate native guanylyl cyclase, although it recognized both subunits on immunoblots, suggesting that the respective amino acid sequence is located in an inner site of the protein.Abbreviations GC_pep2 YGPEVWEDIKKEA (one letter code) - GC_pep3 SRKNTGTEETEQDEN - GC_pep5 VYKVETVGDKYMTVSGLP - GC_pep8 KKDVEEANANFLGKASGID - TBS-T Tris-buffered saline, containing 0.0501o Tween 20 Correspondence to E. Böhme at the above address     

Effects of delta-aminolaevulinic acid administration on social behaviour in the laboratory mouse

Platelets were examined to enable a simultaneous investigation to be made of indolylamine and electrolyte metabolism in affective disorder.No significant differences were detected in either platelet membrane ATPase or adenyl cyclase specific activity in any of the groups of patients studied, when compared with appropriate controls. A reduced V _max and for the 5-hydroxy-tryptamine uptake process into platelets was observed in both unipolar and bipolar depressed groups. The K _m for this process was not significantly different in any of the patients from that found in control subjects.Lithium therapy was shown not to influence significantly any of the platelet parameters examined.It is suggested that membrane enzyme changes found in some peripheral cells in patients suffering from affective disorder, i.e. reduced Na⁺+K⁺-ATPase activity in erythrocytes in depression, is not common to all peripheral cells and may or may not reflect central nervous system changes.     

血小板增高与哮喘的关系探讨

目的：观察血小板计数（PLT）、大血小板比例（LPCR）、平均血小板体积（MPV）变化与哮喘发作的的关系。方法：采用日立产1313—2000型血液分析仪检测血小板计数（PLT）、大血小板比例（LPCR）、平均血小板体积（MPV）三项指标,进行统计分析。结果：观察组大血小板比例和血小板体积明显降低（P〈0．05）,血小板计数明显升高（P〈0．05）。结论：血小板计数（PLT）、大血小板比例（LPCR）、平均血小板体积（MPV）的变化与哮喘有重要关系,可作为血小板活化的标志。     

Snake venom C-type lectins interacting with platelet receptors. Structure–function relationships and effects on haemostasis

Snake venoms contain components that affect the prey either by neurotoxic or haemorrhagic effects. The latter category affect haemostasis either by inhibiting or activating platelets or coagulation factors. They fall into several types based upon structure and mode of action. A major class is the snake C-type lectins or C-type lectin-like family which shows a typical folding like that in classic C-type lectins such as the selectins and mannose-binding proteins. Those in snake venoms are mostly based on a heterodimeric structure with two subunits and β, which are often oligomerized to form larger molecules. Simple heterodimeric members of this family have been shown to inhibit platelet functions by binding to GPIb but others activate platelets via the same receptor. Some that act via GPIb do so by inducing von Willebrand factor to bind to it. Another series of snake C-type lectins activate platelets by binding to GPVI while yet another series uses the integrin ₂β₁ to affect platelet function. The structure of more and more of these C-type lectins have now been, and are being, determined, often together with their ligands, casting light on binding sites and mechanisms. In addition, it is relatively easy to model the structure of the C-type lectins if the primary structure is known. These studies have shown that these proteins are quite a complex group, often with more than one platelet receptor as ligand and although superficially some appear to act as inhibitors, in fact most function by inducing thrombocytopenia by various routes. The relationship between structure and function in this group of venom proteins will be discussed.     

血小板膜糖蛋白Ⅰbα基因多态性与复发性脑梗死的分析研究

目 的探讨血小板膜糖蛋白Ⅰbα可变数目串联重复序列（VNTR）基因多态性,了解其等位基因和基因型与复发性脑梗死的相关性.方法 选择2010年2月至2011年1月淄博市中心医院神经内科收治的110例复发性脑梗死患者作为复发组,105例初发脑梗死患者为初发组,采用聚合酶链反应扩增目的片段,根据产物的长度判断V NTR基因多态性.观察比较两组等位基因及基因型出现频率的差异.结果 B等位基因于复发组出现频率显著高于初发组（χ2=10.059,P =0.002）,基因型以CC、CD多见,BC在复发组显著高于初发组（χ2=12.208,P=0.001）.Logistic回归分析结果显示,B等位基因、BC基因型、原发性高血压、糖尿病是脑梗死复发的独立危险因素（P＜0.05）.结论 血小板膜糖蛋白Ⅰbα基因多态性与复发性脑梗死密切相关,B等位基因和BC基因型是其致病危险因素.     

实验性糖尿病大鼠血小板扫描电镜观察

我们应用扫描电镜观察了链菌脲霉素(streptozotocin)引起的糖尿病大鼠血小板的形态改变。并检测了血小板和血清五—羟色胺(5—Hydroxytryptamine,5—HT)、五—羟吲哚乙酸(5—Hydroxy—indole-acetic acid,5—HIAA)含量。实验结果从形态学角度证明了糖尿病血小板聚集和释放活性增强。糖尿病大鼠血小板数明显减少。血清5—HT含量明显减少、5—HIAA含量增加,其原因可能与5—HT移除代谢增多、血小板摄取5—HT增多和5—HT生成减少有关的。     

γ射线辐照和保存期对血小板的影响

目的了解γ射线辐照和保存期对单采血小板的影响。方法单采血小板分为两组:一组25Gy剂量辐照,一组不辐照处理,作为对照组;在贮存的第0、5天分别检测单采血小板计数、pH和表达CD62P的特异性荧光结合阳性血小板百分率(%)。结果保存过程中,辐照组血小板计数及pH值与对照组无显著差异(P>0.05);5天的贮存可显著增加了血小板表达CD62P百分率(P<0.05),但辐照组与对照组的血小板在贮存第5天时表达CD62P百分率无显著差异(P>0.05)。结论25Gy的辐照对血小板制品的质量无明显影响,与普通血小板制品相同,辐照单采血小板可保存5天。     

Value of vanin-1 assessment in adult patients with primary immune thrombocytopenia

Abstract

The diagnosis of primary immune thrombocytopenia (ITP) is clinical and cannot be established by any specific laboratory assay. Perhaps the best diagnostic study is assessment of the patient’s response to ITP therapy. Oxidative stress-related pathways were among the most significant chronic ITP-associated pathways. Overexpression of VNN1 gene, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic ITP. To address this issue, we tested the hypothesis that blood vanin-1 protein level could distinguish between chronic responders and non-responders ITP patients as well as between ITP patients and healthy controls. Vanin-1 protein levels were determined in peripheral blood leukocytes of 80 adult subjects (16 newly diagnosed ITP patients, 24 chronic responders ITP patients, 24 chronic non-responders ITP patients and 16 healthy controls) by enzyme-linked immunesorbent assay (ELISA). Blood vanin-1 protein levels were lower in controls (median?=?18.39?ng) than in ITP patients (median?=?58.78?ng) with a highly significant p value (p?<?0.001). Vanin-1 levels were highly significantly elevated in newly diagnosed ITP patients (median?=?188.62?ng) in comparison to chronic responders (median?=?26.90?ng) and chronic non-responders (median?=?73.87?ng). Vanin-1 level at a cut-off value of >20.73?ng was found to be 100% sensitive and 93.7% specific in discriminating between newly diagnosed ITP patients and healthy controls. Vanin-1 level was found to be 100% sensitive and 100% specific in differentiating between responders and non-responders with a cut-off value of ≤34.5?ng. Our results suggest that vanin-1 can distinguish between chronic responders and non-responders ITP patients as well as between newly diagnosed ITP patients and healthy controls. These findings demonstrate that vanin-1 may contribute to the pathogenesis of ITP, indicating that vanin-1 is an important target for further investigation.