BACKGROUND & AIMS: :The incidence of thromboembolism is higher in mitral regurgitation. Mean platelet volume (MPV), which is calculated automatically in the complete blood count tests, indicates platelet production, function and activation. Elevated MPV levels in cardiovascular diseases and some heart valve diseases have been shown before. We aimed to investigate the relationship between MPV and mitral regurgitation, and to evaluate the MPV levels according to the presence of atrial fibrillation or left atrial appendage thrombus in patients with mitral regurgitation for the first time. The study included 57 patients who had undergone transthoracic and transesophageal echocardiography for the classic symptoms and diagnosed with primary (organic) mitral regurgitation. The control group was composed of 46 age, sex and BMI-matched healthy individuals who had undergone transthoracic echocardiography and obtained normal findings. Echocardiographic evaluation was performed according to the recommendations of the American Echocardiography Society. Mean MPV values in patients with mitral regurgitation were significantly higher than the control group (P < 0.001). MPV levels and the thrombus risk were correlated with the severity of the disease. When the patients with mitral regurgitation were classified according to the presence of atrial fibrillation and left atrial appendage thrombus, patients with atrial fibrillation had higher MPV levels compared to patients with normal sinus rhythm (P < 0.001). In addition, highest MPV levels were found in patients with both atrial fibrillation and thrombosis (P < 0.001). In conclusion, measurement of MPV may be considered as a quick and reliable guide in the assessment of mitral regurgitation and thrombus, without any cost or any advanced expensive technology.

背景与目标： : 二尖瓣反流中血栓栓塞的发生率较高。在整个血液计数测试中自动计算的平均血小板体积 (MPV) 表示血小板的产生，功能和激活。以前已显示心血管疾病和某些心脏瓣膜疾病中的MPV水平升高。本研究旨在探讨MPV与二尖瓣反流的关系，并根据首次发生二尖瓣反流的患者是否存在心房颤动或左心耳血栓来评估MPV水平。该研究包括57例经胸和经食管超声心动图检查经典症状并被诊断为原发性 (器质性) 二尖瓣反流的患者。对照组由46名年龄，性别和BMI相匹配的健康人组成，他们接受了经胸超声心动图检查并获得了正常的发现。根据美国超声心动图学会的建议进行超声心动图评估。二尖瓣反流患者的平均MPV值明显高于对照组 (p  <  0.001)。MPV水平和血栓风险与疾病的严重程度相关。根据是否存在心房颤动和左心耳血栓对二尖瓣关闭不全患者进行分类时，心房颤动患者的MPV水平高于窦性心律正常患者 (p  <  0.001)。此外，房颤和血栓形成患者的MPV水平最高 (p  <  0.001)。总之，MPV的测量可以被认为是评估二尖瓣反流和血栓的快速可靠的指南，而无需任何成本或任何先进的昂贵技术。

BACKGROUND & AIMS: INTRODUCTION:The antiplatelet effects of low-dose aspirin (LDA) vary between individuals. Here, we investigated the relationship between the incidence of LDA-induced mucosal injury, antiplatelet effects of LDA, and intragastric pH. METHODS:We evaluated gastric injury severity and platelet function using the VerifyNow® System before and after administration of 100 mg aspirin for 7 days to 18 young healthy subjects (study 1). We investigated whether injury was correlated with platelet function and gastric juice pH in 45 patients with cardiovascular disease administered LDA daily (study 2). RESULTS:In study 1, platelet aggregation was attenuated by LDA to different degrees. Although 55.6% of subjects (10/18) developed gastric injury of modified Lanza score (MLS) ≥ 3, no significant difference in platelet function was detected between the mild (n = 8, MLS: 0-2) and severe injury groups (n = 10, MLS: 3-5). In study 2, the severity of LDA-induced injury was associated with gastric juice pH, but not with antiplatelet effects of LDA. DISCUSSION:In contrast to gastric juice pH, the antiplatelet effect had no correlation with the severity of gastric mucosal injury. Monitoring gastric acidity, rather than platelet function, may be useful for predicting the risk of gastric injury during LDA treatment.

背景与目标：

BACKGROUND & AIMS: :Abstract Glucose has been found to impair the inhibition of platelets with aspirin and alter the basal activity of nitric oxide synthase (NOS) in platelets. The aim of this work was to study the effects of glucose on the inhibitory pathways in activated platelets. A short-term incubation of glucose impaired the inhibition of platelet aggregation induced by agents activating an NOS-dependent pathway, such as l-arginine, adenosine and α-tocopherol. However, glucose had no effect on the inhibition induced by iloprost and BW245C, agents that activate the cyclic adenosine monophosphate (cAMP) signaling pathway. Potassium lactate attenuated the effects of the same inhibitors as glucose did. The inhibitors of glucose transport prevented the effect of glucose. Dichloroacetate, known to prevent the conversion of pyruvate to lactate and to decrease lactate in platelets, significantly attenuated the effect of glucose in platelets. The data support the suggestion that the effect of glucose on the inhibition of platelets by agents activating an NOS-dependent pathway is mediated by glucose metabolite lactate.

背景与目标： 摘要: 已发现葡萄糖会损害阿司匹林对血小板的抑制作用，并改变血小板中一氧化氮合酶 (NOS) 的基础活性。这项工作的目的是研究葡萄糖对活化血小板抑制途径的影响。葡萄糖的短期孵育会损害激活NOS依赖性途径的药物 (例如l-精氨酸，腺苷和 α-生育酚) 诱导的血小板聚集的抑制作用。然而，葡萄糖对伊洛前列素和BW245C (激活环磷酸腺苷 (cAMP) 信号通路的药物) 诱导的抑制作用没有影响。乳酸钾减弱了与葡萄糖相同的抑制剂的作用。葡萄糖转运抑制剂阻止了葡萄糖的作用。已知的二氯乙酸酯可防止丙酮酸转化为乳酸并减少血小板中的乳酸，可显着减弱血小板中葡萄糖的作用。数据支持以下建议: 葡萄糖对激活NOS依赖性途径的药物抑制血小板的作用是由葡萄糖代谢产物乳酸介导的。

BACKGROUND & AIMS: :The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the "platelet rich plasma" or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC-PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC-RPC retain much more their in vitro functions than PRP-RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between "modern" RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.

背景与目标： : 随机 (RPC) 和单采 (APC) 血小板浓缩物在各国之间的使用高度异质性，在应该为患者提供类似输血服务的国家中，RPC的使用范围为10至98%。此外，在考虑过去十年中的每个国家时，可以观察到一些国家已经改变了政策，从大多数APC转向RPC，反之亦然。本演示文稿旨在分析哪些因素可能影响此类决策。多年来，唯一可用的血小板成分是通过两个离心步骤 (“富血小板血浆” 或PRP方法) 从全血捐赠中获得的RPC。自20世纪70年代开始以来，apc就可以使用，实际上有许多不同的技术导致许多apc可能不相等。自20世纪80年代结束以来，开发了一种使用血沉棕黄涂层 (bc-pc) 制备RPC的新方法，与通过PRP技术制备的RPC相比，提供了具有高度保留的血小板功能的血液成分。最后，使用这些成分中的每一种，无论是天然的，还是隐色减少的，或者悬浮在存储溶液中，或者用病原体灭活技术处理，都增加了新的复杂性来比较它们。在描述血小板浓缩物体外功能参数的文献中可以找到无数参考文献。尽管很明显bc-rpc比prp-rpc保留了更多的体外功能，这表明没有人应该再使用后者，但区分其他pc之间的差异要困难得多。相反，仅发表了很少的研究与RPC与APC的临床疗效比较有关，终点主要是CCI。与体外研究类似，尽管用PRP方法制备的RPC显示出最低的CCIs，但 “现代” RPC和APC之间没有明显的区别。可能影响政策决策的另一个因素是接受者中不良反应的发生。当仅考虑可比较的数据时，例如leuco降低的RPC与leuco降低的APC，现在有证据表明后者与接受者的不良反应更相关: 法国血液警戒的数据表明，尽管没有发现发热的非溶血性输血反应，也没有发现细菌污染，APC的过敏不良反应发生率是RPC的四倍。其他方面可能会影响该决定: 在某些国家，使用APC代替RPC减少患者的总供体暴露这一事实被认为对于降低血液传播疾病的风险至关重要。最后，可以考虑组件的成本，对于APC来说要高得多。

BACKGROUND & AIMS: OBJECTIVE:Sinus augmentation is a common approach for patients with severe alveolar ridge atrophy. However, autogenous bone sometimes results in donor site complications. Bone substitutes with platelet-rich plasma (PRP) promote early bone formation with autogenous bone. Use of PRP on autogenous bone and a bovine bone substitute were investigated in this split-mouth animal study. STUDY DESIGN:Premolars were extracted from minipigs. Each animal received sinus augmentation using a lateral approach with simultaneous insertion of 3 implants in each site. Groups were randomized using autogenous bone alone and combined with PRP or a bovine hydroxyapatite alone in combination with PRP. RESULTS:Microradiographic findings in the autogenous group did not show significantly different rates by using autogenous bone alone or combined with PRP. Using the bovine hydroxyapatite as augmentation material only at 8 weeks, a nonsignificant effect in the PRP group could be seen. At all other observation periods, no significant influence was observed. CONCLUSION:No significant influence of PRP was found.

背景与目标：

BACKGROUND & AIMS: :Previous studies in healthy subjects have demonstrated a lack of response of platelets to epinephrine at a rate of 16-40% on an aggregometer. An association between the increased procoagulant factors during pregnancy and venous thromboembolism is known, and it has also been shown that prolactin levels increase platelet aggregation. We evaluated whether platelet functions in pregnant women and also assessed the lack of response to epinephrine during this period. We compared 27 healthy and volunteering pregnant women with 26 similar control subjects. Platelet functions were assessed with an aggregometer and a Platelet Function Analyzer (PFA-100). Less than 40% response to epinephrine on the aggregometer was defined as an impaired epinephrine response. The aggregation response of epinephrine was normal in 25 of the 27 pregnant women, while two of them showed a late-rising response. Eight of the 26 subject control group (30.8%) showed an impaired response to epinephrine. When we compared the 25 pregnant and 18 control subjects with normal aggregation responses, the maximum aggregation responses to ADP and epinephrine, and the Col/Epi and Col/ADP cartridge closure time values were significantly lower in pregnant women. There were no difference between second and third trimesters as regards platelet function parameters. The fact that no impaired response to epinephrine was detected in pregnant women while a 30% rate was observed in non-pregnant women indicates that the platelet malfunction caused by a disorder in the Gi protein and intracellular mechanisms is bypassed during pregnancy thanks to some physiological changes.

背景与目标： : 先前对健康受试者的研究表明，在聚集计上血小板对肾上腺素的反应缺乏16-40%。已知怀孕期间增加的促凝因子与静脉血栓栓塞之间的关联，并且还表明催乳素水平会增加血小板聚集。我们评估了孕妇的血小板功能，并评估了在此期间对肾上腺素的缺乏反应。我们比较了27名健康和志愿孕妇与26名相似的对照受试者。用聚集计和血小板功能分析仪 (PFA-100) 评估血小板功能。在凝聚仪上对肾上腺素的反应小于40% 被定义为肾上腺素反应受损。在27名孕妇中，有25名肾上腺素的聚集反应正常，而其中两名则显示出较晚的反应。26个受试者对照组中的8个 (30.8%) 显示出对肾上腺素的反应受损。当我们比较25名孕妇和18名正常聚集反应的对照受试者时，孕妇对ADP和肾上腺素的最大聚集反应以及Col/Epi和Col/ADP盒关闭时间值明显较低。在血小板功能参数方面，妊娠中期和妊娠中期之间没有差异。在孕妇中未检测到对肾上腺素的反应受损，而在非孕妇中观察到30% 率的事实表明，由于某些生理变化，在怀孕期间绕过了由Gi蛋白和细胞内机制障碍引起的血小板功能障碍。

BACKGROUND & AIMS: :Platelet concentrates are routinely manufactured from whole blood by differential centrifugation (random donor platelets-RDP) or by plateletpheresis (single donor platelets-SDP). These platelet concentrates have a storage period of 5 days and many different approaches exist to measure the condition of platelets during their storage. In this study, platelet aggregation testing using adenosine diphosphate (ADP) and collagen and flow cytometric platelet activation analysis using CD41 FITC and CD62 PE before and after ADP was performed on days 1, 3 and 5 of storage of platelet preparations. Thirty three RDPs, stored in Baxter and Kansuk blood bags and 18 SDPs stored in Fresenius blood bags were evaluated. In RDPs and in SDPs; ADP and collagen induced PA responses were decreased significantly on the 3rd and 5th days compared to 1st day. CD62 positive platelet percentage after ADP were decreased significantly on the 3rd and 5th days compared to the 1st day in Kansuk bags. Flow cytometric analysis revealed minor changes in CD41 expression after ADP on the 3rd day compared to 1st day and on the 5th day compared to 3rd day. Differences in CD62 positive platelet percentage were not significant between the RDPs and SDPs. Our results suggest that: (1) ADP and collagen induced PA responses decrease both in RDPs and SDPs during storage. (2) Flow cytometric analysis does not show major significant changes in platelet activation after ADP during storage. (3) Continous shaking on the agitator does not cause a significant change in CD62 positive platelet percentage during storage. (4) Platelet aggregation responses in RDPs stored in Baxter and Kansuk blood bags do not differ during storage.

背景与目标： : 血小板浓缩物通常通过差速离心 (随机供体血小板-RDP) 或血小板电泳 (单供体血小板-SDP) 从全血中制造。这些血小板浓缩物的储存时间为5天，并且存在许多不同的方法来测量血小板在储存过程中的状况。在这项研究中，在储存血小板制剂的第1、3和5天，使用二磷酸腺苷 (ADP) 和胶原蛋白进行血小板聚集测试，并在ADP之前和之后使用CD41 FITC和CD62 PE进行流式细胞术血小板活化分析。评估了存储在Baxter和Kansuk血袋中的33个rdp和存储在费森尤斯血袋中的18个sdp。在RDPs和sdp中; 与第1天相比，第3天和第5天ADP和胶原蛋白诱导的PA反应显着降低。在Kansuk袋中，与第1天相比，ADP后第3天和第5天的CD62阳性血小板百分比显着降低。流式细胞仪分析显示，与第1天相比，ADP后第3天以及与第3天相比，第5天的CD41表达发生了微小变化。RDPs和SDPs之间CD62阳性血小板百分比的差异不显着。我们的结果表明 :( 1) 在储存过程中，ADP和胶原蛋白诱导的PA反应均降低了rdp和sdp。(2) 流式细胞仪分析未显示储存过程中ADP后血小板活化的主要变化。(3) 在搅拌器上持续摇动不会引起储存过程中CD62阳性血小板百分比的显着变化。(4) 储存在Baxter和Kansuk血袋中的RDPs中的血小板聚集反应在储存过程中没有差异。

BACKGROUND & AIMS: :We aimed to investigate whether atorvastatin influenced the CD40-CD40L pathway in atherosclerosis formation in rats fed a high cholesterol diet. Thirty-six male Wistar rats were divided among 4 groups as follows: control (C), statin (S), 5% cholesterol fed (HC), and statin-administered hypercholesterolemic (HCS). Serum levels of lipids, soluble CD40L, platelet factor 4, and interleukin-6 were assayed with commercial kits. The number of platelets expressing surface P-selectin, CD40, and CD40L were determined by flow cytometry. Aortas were examined for fatty streaks. In the HC group, we observed a significant increase in serum lipid levels and platelet activation markers compared with the control group. Rats in the HCS group had a significant decrease in lipid levels and downregulation in the number of platelets expressing surface P-selectin, CD40, and CD40L compared with the HC group. We observed decreased fatty streak formations in aortas in HCS rats. A positive correlation was found for platelet activation markers and atherosclerotic fatty streak formations. Regression analysis revealed that the predictor of atherosclerosis was CD40L. Our study suggests that in a rat hypercholesterolemic model, statin treatment may influence the CD40-CD40L dyad, and that this effect is parallelled by a suppression of progression of atherosclerotic plaque formation.

背景与目标： : 我们的目的是调查阿托伐他汀是否影响高胆固醇饮食的大鼠动脉粥样硬化形成的CD40-CD40L途径。将36只雄性Wistar大鼠分为以下4组: 对照组 (C)，他汀类药物 (S)，5% 胆固醇喂养 (HC) 和他汀类药物给药的高胆固醇血症 (HCS)。用市售试剂盒测定血脂、可溶性CD40L、血小板因子4和interleukin-6的血清水平。通过流式细胞术确定表达表面P-选择素，CD40和CD40L的血小板数量。检查主动脉是否有脂肪条纹。在HC组中，我们观察到与对照组相比，血脂水平和血小板活化标志物显着增加。与HC组相比，HCS组大鼠的脂质水平显着降低，表达表面P-选择素，CD40和CD40L的血小板数量下调。我们观察到HCS大鼠主动脉脂肪条纹形成减少。发现血小板活化标志物与动脉粥样硬化性脂肪条纹形成呈正相关。回归分析显示，动脉粥样硬化的预测因子是CD40L。我们的研究表明，在大鼠高胆固醇血症模型中，他汀类药物治疗可能会影响CD40-CD40L二位，并且这种作用与抑制动脉粥样硬化斑块形成的进展相似。

BACKGROUND & AIMS: :Abstract An accumulating number of studies are revealing that platelet reactivity above specific cut-off scores leads to exponentially increased rates of post-percutaneous coronary intervention (PCI) ischemic events. To evaluate the optimal predictive values for three different platelet function measurement assays of platelet reactivity on early clinical outcomes in Korean patients undergoing PCI, we enrolled 228 patients receiving clopidogrel prior to PCI. Platelet reactivity was measured by light transmittance aggregometry (LTA), VerifyNow P2Y12 assay, and multiple electrode platelet aggregometry (MEA). The primary endpoint was the 30-day occurrence of ischemic events after PCI. MACE occurred in 36 patients (15.8%), including 35 patients (15.4%) with periprocedural MI and the death of one patient (0.4%). ADP-induced LTA and VerifyNow values (pre- and post-PCI) were significantly higher in patients with the subsequent occurrence of periprocedural MI, but the MEA assay data (PCI and post-PCI) displayed no significant differences (pre-PCI p=0.25 and post-PCI p=0.33). ROC curve analysis demonstrated HPR values for LTA (pre-PCI, >66% and post-PCI, >53 %, all p<0.001), VerifyNow (pre-PCI, >347 PRU and post-PCI >272 PRU, all p<0.001) and MEA (pre-PCI, >50 U and post-PCI >39 U, all p>0.05). The platelet reactivity measurements by LTA and the VerifyNow assay can discriminate the risk of 30-day ischemic events after PCI. The predictive cut-off values for adverse events are dependent on sampling time.

背景与目标： : 摘要越来越多的研究表明，超过特定临界值的血小板反应性导致经皮冠状动脉介入治疗 (PCI) 后缺血性事件的发生率呈指数增加。为了评估三种不同的血小板功能测量测定对接受PCI的韩国患者早期临床结局的最佳预测值，我们招募了228例在PCI之前接受氯吡格雷的患者。通过透光率聚集法 (LTA)，VerifyNow P2Y12测定和多电极血小板聚集法 (MEA) 测量血小板反应性。主要终点是PCI术后30天发生缺血事件。MACE发生在36例患者 (15.8% 例) 中，其中35例 (15.4% 例) 患有围手术期MI，1例死亡 (0.4% 例)。在随后发生围手术期MI的患者中，ADP诱导的LTA和VerifyNow值 (PCI前和PCI后) 显着较高，但MEA测定数据 (PCI和PCI后) 显示无显着差异 (PCI前p = 0.25和PCI后p = 0.33)。ROC曲线分析显示了LTA (PCI前，> 66% 和PCI后，> 53%，所有p<0.001) 、VerifyNow (PCI前，> 347 PRU和PCI后> 272 PRU，所有p<0.001) 和MEA (PCI前，> 50 U和PCI后> 39 U，所有p>0.05)。通过LTA和VerifyNow分析进行的血小板反应性测量可以区分PCI后30天缺血事件的风险。不良事件的预测临界值取决于采样时间。

BACKGROUND & AIMS: BACKGROUND:Paronychia has been reported in as many as 10% of patients treated with gefitinib. Although conservative management and treatment with topical or systemic antibiotics are beneficial, no effective method exists for intractable cases. Platelet-rich plasma (PRP)consists of a high concentration of platelets that promote wound healing through chemotaxis, cell proliferation,angiogenesis, and tissue remodeling. OBSERVATIONS:We herein report a refractory case of gefitinib-induced paronychia successfully treated with autologous PRP. A 68-year-old woman who had been diagnosed as having lung adenocarcinoma with multiple bone and brain metastases initiated gefitinib therapy at an oral dose of 250 mg/d. After 1 month, multiple paronychia with periungual granulation appeared on the nailfold of the first, second, and third toenails of both feet.Because the paronychia recurred repeatedly despite use of a topical antibiotic, topical corticosteroid, and short term systemic antibiotic, she started PRP treatment. After 3 months, the lesion showed marked improvement with minimal pain or discharge. CONCLUSION:This case highlights the therapeutic challenges of using PRP to promote tissue repair in intractable gefitinib-induced paronychia and merits further investigation.

背景与目标：

BACKGROUND & AIMS: The prevalence of plasma platelet-activating factor (PAF) acetylhydrolase deficiency was investigated in 477 healthy Japanese individuals and 985 patients with various cardiovascular diseases. The genotype for this enzyme with regard to a G994-->T mutation (MM, normal; Mm, heterozygote; mm, mutant homozygote) was determined by an allele-specific polymerase chain reaction in 80 subjects shown to have no or low plasma activity (<10 nmol/min/ml). In 72 subjects, the genotype was consistent with plasma enzyme activity; 44 individuals with no activity were mm, and 28 with low activity were Mm. However, eight subjects with the MM genotype showed plasma enzyme activities of <10 nmol/min/ml. Determination of the DNA sequence of exon 9 of the plasma PAF acetylhydrolase gene in these eight subjects revealed a previously unidentified A1001-->G missense mutation, resulting in a Gln281-->Arg substitution, in a 72-year-old woman with coronary artery disease, essential hypertension, and no plasma enzyme activity. Site-directed mutagenesis in vitro showed that the corresponding recombinant mutant protein lacked PAF acetylhydrolase activity. Thus, the Gln281-->Arg substitution appears responsible for the loss of plasma PAF acetylhydrolase activity.

背景与目标： 在477名健康的日本人和985名患有各种心血管疾病的患者中，研究了血浆血小板活化因子 (PAF) 乙酰水解酶缺乏症的患病率。关于G994->T突变 (MM，正常; Mm，杂合子; mm，突变纯合子) 的该酶的基因型是通过等位基因特异性聚合酶链反应确定的，在80名受试者中显示无或低血浆活性 (<10 nmol/min/ml)。在72名受试者中，基因型与血浆酶活性一致; 44个无活性的个体为mm，28个低活性的个体为Mm。然而，具有MM基因型的八名受试者的血浆酶活性 <10 nmol/min/ml。在这八名受试者中测定血浆PAF乙酰水解酶基因第9外显子的DNA序列，发现先前未鉴定的A1001->G错义突变，导致Gln281->Arg取代，患有冠状动脉疾病，原发性高血压，没有血浆酶活性。体外定点诱变表明，相应的重组突变蛋白缺乏PAF乙酰水解酶活性。因此，Gln281->Arg取代似乎是造成血浆PAF乙酰水解酶活性丧失的原因。

BACKGROUND & AIMS: :Reduction of ribonucleotide reductase (EC 1.17.4.1) R2 proteins in a frozen glycerol-buffer solution at 77 K by mobile electrons generated by gamma-irradiation produces EPR-detectable iron sites in mixed-valent Fe(II)/Fe(III) states. The primary EPR signals give information about the ligand arrangement of the diferric form of the iron site, whereas secondary signals observed after annealing of the sample show the effects of structural relaxation. In recombinant metR2 proteins (without free radical) from mouse and herpes virus type 1, the mixed-valent sites trapped at 77 K give rise to axial S = 1/2 EPR spectra with g values in the range 1.79-1.94, observable at temperatures up to 110 K. The spectra are assigned to mu-oxo-bridged dinuclear iron sites. In mouse metR2, the primary EPR spectrum is a mixture of two components. Annealing the R2 samples to 160-170 K transforms the primary EPR signals into rhombic spectra, characterized by gav < 1.8, and observable only below 25 K. These spectra are assigned to partially relaxed forms with a mu-hydroxo bridge, formed by protonation of the oxo bridge. Further annealing at 220 K produces new rhombic EPR spectra, which are closely similar with those observed and found to be stable after chemical reduction at room temperature. The EPR signal of the primary mixed-valent iron site in active mouse R2 protein with a tyrosyl radical also has two components. Both are different from those observed in metR2. In herpes simplex virus type 1 protein R2, one primary mixed-valent component was observed for the met protein. The dose-yield curve for the mixed-valent state in active mouse R2 is sigmoidal in shape, indicating that the tyrosyl radical is reduced by mobile electrons before the iron site. Kinetic experiments on the reduction by dithionite on mouse R2 without and with radical show a significantly enhanced rate for reduction of the iron site in the protein without radical. The results suggest that in active mouse R2 only complete diferric sites with neighboring radicals give rise to the mixed-valent spectra, and that these sites may exist in two structurally distinct forms. The results on the mouse R2 proteins confirm and extend previous results obtained on the Escherichia coli protein R2 showing that the presence of the tyrosyl radical significantly affects not only the structure but also the reactivity of the iron site.

背景与目标： : 通过伽马辐照产生的移动电子在77 K的冷冻甘油缓冲溶液中还原核糖核苷酸还原酶 (EC 1.17.4.1) R2蛋白，在混合价的Fe(II)/Fe(III) 状态下产生可检测到EPR的铁位点。初级EPR信号提供有关铁位点二铁形式的配体排列的信息，而样品退火后观察到的次级信号显示了结构弛豫的影响。在来自小鼠和1型疱疹病毒的重组metR2蛋白 (无自由基) 中，捕获在77 k的混合价位点产生轴向S = 1/2 EPR光谱，g值在1.79-1.94范围内，可在高达110 K的温度下观察到。光谱分配给mu-氧桥双核铁位点。在小鼠metR2中，主要EPR光谱是两种成分的混合物。将R2样品退火至160-170 K将初级EPR信号转换为菱形光谱，其特征在于gav <1.8，并且仅在25 k以下可观察到。这些光谱被分配为具有 μ-羟基桥的部分松弛形式，该形式是由氧桥的质子化形成的。在220 K下进一步退火产生新的菱形EPR光谱，该光谱与观察到的光谱非常相似，并且在室温下化学还原后被发现是稳定的。具有酪氨酰自由基的活性小鼠R2蛋白中初级混合价铁位点的EPR信号也有两个成分。两者都不同于在metr2中观察到的。在1型单纯疱疹病毒蛋白R2中，观察到met蛋白的一种主要混合价成分。活性小鼠R2中混合价态的剂量-产量曲线呈s形，表明酪氨酰自由基在铁位点之前被移动电子还原。在没有自由基的情况下，连二亚硫酸盐在小鼠R2上还原的动力学实验表明，没有自由基的蛋白质中铁位的还原速率显着提高。结果表明，在活性小鼠R2中，只有具有相邻自由基的完整二价位点会产生混合价光谱，并且这些位点可能以两种结构上不同的形式存在。小鼠R2蛋白的结果证实并扩展了先前在大肠杆菌蛋白R2上获得的结果，表明酪氨酰自由基的存在不仅显着影响铁位点的结构，而且还影响铁位点的反应性。

BACKGROUND & AIMS: :There is no consensus on the optimal rehabilitation protocol after platelet-rich plasma (PRP) treatment for tendinopathy despite basic science studies showing the critical role of mechanical loading in the restoration of tendon structure and function posttreatment. In this article, we will review tendon mechanobiology, platelet biology, and review levels I and II Achilles tendon clinical studies paying particular attention to the role of mechanical loading in rehabilitation of injured tendons. Animal studies emphasize the synergistic effect of mechanical tendon loading and PRP to treat tendon injury while clinical studies described minimal details on loading protocols.

背景与目标： : 尽管基础科学研究表明机械负荷在治疗后肌腱结构和功能恢复中的关键作用，但富含血小板血浆 (PRP) 治疗肌腱病后的最佳康复方案尚无共识。在本文中，我们将回顾肌腱力学生物学，血小板生物学，并回顾I和II级跟腱临床研究，特别注意机械负荷在受伤肌腱康复中的作用。动物研究强调机械肌腱加载和PRP在治疗肌腱损伤方面的协同作用，而临床研究则描述了加载方案的最低细节。

BACKGROUND & AIMS: BACKGROUND:Wound healing is a dynamic process, involving the recruitment of growth factors, cytokines, chemokines and cellular populations. Recently, the Cord Blood Platelet Gel (CBPG) has been applied successfully in wound closure and tissue regeneration. Moreover, its proper combination with stem cell populations such as Mesenchymal Stromal Cells (MSCs) may positively improve the wound healing process. Based on the above data, this study aimed to the evaluation of wound healing capacity of MSCs combined with CBPG under in vitro conditions. METHODS:Initially, CBPG was developed from Cord Blood Units (CBUs). The determination of wound healing ability of MSCs was performed using the scratch wound assay. In addition, the morphological features, immunophenotypical characteristics and differentiation capacity of MSCs were evaluated. RESULTS:Scratch wound assay results showed, that CBPG could positively stimulate the MSCs migration. Moreover, MSCs cultured in presence of CBPG were characterized by elongated shape and improved stemness properties as it was indicated by flow cytometric analysis and differentiation process. CONCLUSION:These results clearly showed the beneficial effect of CBPG in combination with MSCs in wound healing. The proper combination of CBPG with stem cells strategy may enhance the healing process in patients with skin erosions.

背景与目标：

BACKGROUND & AIMS: :The use of aspirin is considered the "gold standard" for the decrease of major adverse cardiovascular events in patients with atherosclerosis, including peripheral arterial disease (PAD), whereas a dual-antiplatelet regimen with aspirin and clopidogrel is usually indicated for such patients after angioplasty and stent deployment. However, a substantial number of subsequent adverse events still occur, even in patients who receive double-antiplatelet therapy. The "high on-treatment platelet reactivity" (HTPR) phenomenon has been lately recognized and plays a major role in the management of patients with PAD. Greater and more rapid inhibition of platelet aggregation has become the goal for new antiplatelet agents with the expectation of further improving outcomes for percutaneous intervention for PAD. The purpose of this review article is to highlight current evidence regarding the prevalence, aetiology, and clinical implications of HTPR in PAD as well as to discuss the possibilities of novel alternative antiplatelet regiments.

背景与目标： : 阿司匹林的使用被认为是减少动脉粥样硬化患者 (包括外周动脉疾病 (PAD)) 主要不良心血管事件的 “金标准”，而阿司匹林和氯吡格雷的双重抗血小板方案通常适用于此类患者血管成形术和支架部署后。然而，即使在接受双重抗血小板治疗的患者中，仍然会发生大量后续不良事件。最近，人们认识到 “高治疗血小板反应性” (HTPR) 现象，并在PAD患者的管理中起着重要作用。更大，更快速地抑制血小板聚集已成为新型抗血小板药物的目标，并期望进一步改善经皮介入治疗PAD的结果。这篇综述文章的目的是强调有关PAD中HTPR的患病率，病因和临床意义的最新证据，并讨论新型替代抗血小板疗法的可能性。