缺血性脑血管病患者用天新利博前后血小板聚集的变化

目的探讨天新利博对缺血性脑血管病(ICVD)患者血小板聚集影响的程度.方法比浊法测定12例ICVD患者治疗前后,用二种诱聚剂诱导的血小板聚集率.结果(-x±S)ICVD组用药后第5天、第10天ADP诱导血小板聚集率(32.87%±14.2%,44.99%±12.3%)显著低于用药前(71.9%±11.1%)P<0.01;Adr诱导的血小板聚集率与用药前比较则无显著性差异(P>0.05).结论天新利博对ICVD患者ADP诱导的血小板聚集有明显抑制作用,对Adr诱导的血小板聚集无影响.监测其血小板聚集率时,应选用ADP作为诱聚剂.     

当药水提物对大鼠中性白细胞活性氧生成和兔血小板聚集的影响

目的 研究当药水提物对大鼠中性白细胞性细胞内内Ca^2 浓度增加、活性氧生成及兔血小板聚集的影响。方法 用酵母多糖、FMLP和A23 187活化大鼠中性白细胞,用化学发光法测定活性氧,用荧光光度法测细胞内Ca^2 浓度,用比浊法测血小板聚集。结果 当药水提物浓度依赖性地抑制酵母多精、FMLP和A23 187诱导的大鼠中性白细胞内Ca^2 浓度增加及活性氧生成;也抑制花生四稀酸、胶原及ADP诱导的兔血小板聚集。和吲哚美辛比较,当药水提物抑制活性氧生成的作用较强而抑制血小板聚集的作用较弱,其作用远强于swertiamarin。结论 当药水提物是极强的中性白细胞活性氧生成抑制剂,其作用强于swertiamarin。     

基于多尺度特征融合与反向注意力的COVID-19病灶分割

针对新型冠状病毒肺炎（COVID-19）分割问题中感染区域具有高变异性以及病灶与背景对比度低等问题,提出一种基于多尺度特征融合与反向注意力的COVID-19感染分割网络。首先,利用残差网络作为主干网络进行特征提取,并使用全局上下文聚合策略对不同层次特征进行融合得到粗略的分割结果;其次,在网络瓶颈处添加多尺度特征融合模块,利用空洞卷积与多核池化增强网络分割不同尺度病变的能力;最后,设计一种级联结构的反向注意力模块,利用互补区域的细节特征增强背景与目标的对比度。本文方法在COVID-19 CT分割测试集上的准确率、特异性、灵敏度分别达到0.714、0.700和0.958,误检和漏检区域明显减少,细小病灶的分割能力显著提升。     

The Relationship Between Protein Aggregation and Molecular Mobility Below the Glass Transition Temperature of Lyophilized Formulations Containing a Monoclonal Antibody

Purpose. To find out if the physical instability of a lyophilized dosage form is related to molecular mobility below the glass transition temperature. Further, to explore if the stability data generated at temperatures below the glass transition temperature can be used to predict the stability of a lyophilized solid under recommended storage conditions. Methods. The temperature dependence of relaxation time constant, , was obtained for sucrose and trehalose formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy relaxation studies using differential scanning calorimetry. The non-exponentiality parameter, , in the relaxation behavior was also obtained using dielectric relaxation spectroscopy. Results. For both sucrose and trehalose formulations, the variation in with temperature could be fitted Vogel-Tammann-Fulcher (VTF) equation. The two formulations exhibited difference sensitivities to temperature. Sucrose formulation was more fragile and exhibited a stronger non-Arrhenius behavior compared to trehalose formulation below glass transition. Both formulations exhibited <2% aggregation at t values <10, where t is the time of storage. Conclusions. Since the relaxation times for sucrose and trehalose formulations at 5°C are on the order of 10⁸ and 10⁶ hrs, it is likely that both formulations would undergo very little (<2%) aggregation in a practical time scale under refrigerated conditions.     

Nitroglycerin-inhibited whole blood aggregation is partially mediated by calcitonin gene-related peptide–a neurogenic mechanism

1. The role of the vasculature and calcitonin gene-related peptide (CGRP) in nitroglycerin (NTG)-mediated platelet inhibition was studied.
2. In vitro incubations of CGRP in whole blood induced a dose-dependent inhibition of platelet aggregation with an IC₅₀ of 62.1 nM.
3. The platelet inhibition induced by CGRP was blocked by co-incubation of 0.53 μM CGRP_8-37, as well as 30 μM N^G-nitro-monomethyl-L-arginine (L-NMMA).
4. In a separate group of experiments, 100 nM NTG in rat whole blood (WB) induced platelet inhibition of 6.0±1.3% (mean±s.d.), which was enhanced to 77.6±3.5% by the addition of rat aortic tissue (AT) (P<0.001). The inclusion of CGRP_8-37 with NTG and AT in WB reduced platelet inhibition to 31.6±6.8% (P<0.01). Incubation of WB and AT with 30 μM L-NMMA reduced NTG-induced inhibition of platelet aggregation to 26.4±4.2% (P<0.001).
5. It is concluded that vascular tissue contributes to the antiplatelet mechanism of action of NTG. Furthermore, NTG apparently evokes the release of CGRP from vascular tissue and this neuropeptide contributes to the antiplatelet actions of NTG.
6. The antiplatelet activity of CGRP in whole blood is mediated primarily through the activation of nitric oxide synthase.

     

碱离子水饮用后血小板聚集率的的变化(附30例报告)

目的:报告30例饮用豪斯牌碱离子水前、后血小板聚集率的变化。方法:饮用碱离子水前、后(2～3月,>3～6月)作比浊法血小板聚集试验,以1分钟、5分钟及5分钟内最大聚集率(Max％)为指标,同时检测部分血粘度指标及凝血因子,并用自动生化仪检测血糖、血脂、主要电解质及部分肝、肾功能。结果:饮碱离子水后,血小板聚集率明显下降,而以疾病组(Max>80％)下降尤为明显,P均<0.001。饮碱离子水后血小板聚集率的下降,部分可能与损伤的血管内皮得到修复有关。主要电解质及部分肝、肾功能无明显异常改变。结论:由于心、脑血管血栓性疾病患者血小板聚集率多明显升高,饮碱离子水后血小板聚集率明显下降,且长期饮用对主要电解质及部分肝、肾功能无明显异常改变,作者认为碱离子水使用方例、安全、有效、价廉,因而对心、脑血管血栓性疾病防治方面可能是一种积极的辅助方法,值得临床进一步探索。     

API0134对血小板α颗粒膜蛋白和血小板聚集的影响

２０例急性心肌梗死患者在溶栓后随机分为穿心莲有效成分（ＡＰＩ０１３４,ＡＰＩ）组与对照组,治疗１５ｄ,均同时给予阿司匹林等药物。检测溶栓前后血浆α颗粒膜蛋白（ＧＭＰ－１４０）浓度和ＡＤＰ诱导的血小板聚集反应。结果表明,ＡＰＩ组溶栓后７２ｈ血浆ＧＭＰ－１４０浓度轻度增加,对照组显著性增加（Ｐ＜０．０１）。ＡＰＩ组ＧＭＰ－１４０在溶栓后７２ｈ和１５ｄ均低于对照组,差异有显著意义（均为Ｐ＜０．０５）。ＡＰＩ组１ｍｉｎ和５ｍｉｎ血小板聚集率均低于对照组,差异均有显著意义（７２ｈ,Ｐ＜０．０５;１５ｄ,Ｐ＜０．０１）。研究表明,ＡＰＩ与阿司匹林联合应用可抑制溶栓后血小板的活化,优于阿司匹林单独应用,因此ＡＰＩ有可能用于临床预防溶栓后的再闭塞。     

The amyloid precursor protein of Alzheimer's disease and the Abeta peptide

Alzheimer's disease is characterized by the accumulation of beta amyloid peptides in plaques and vessel walls and by the intraneuronal accumulation of paired helical filaments composed of hyperphosphorylated tau. In this review, we concentrate on the biology of amyloid precursor protein, and on the central role of amyloid in the pathogenesis of Alzheimer's disease. Amyloid precursor protein (APP) is part of a super-family of transmembrane and secreted proteins. It appears to have a number of roles, including regulation of haemostasis and mediation of neuroprotection. APP also has potentially important metal and heparin-binding properties, and the current challenge is to synthesize all these varied activities into a coherent view of its function. Cleavage of amyloid precursor protein by beta-and gamma-secretases results in the generation of the Abeta (betaA4) peptide, whereas alpha-secretase cleaves within the Abeta sequence and prevents formation from APP. Recent findings indicate that the site of gamma-secretase cleavage is critical to the development of amyloid deposits; Abeta1-42 is much more amyloidogenic than Abeta1-40. Abeta1-42 formation is favoured by mutations in the two presenilin genes (PS1 and PS2), and by the commonest amyloid precursor protein mutations. Transgenic mouse models of Alzheimer's disease incorporating various mutations in the presenilin gene now exist, and have shown amyloid accumulation and cognitive impairment. Neurofibrillary tangles have not been reproduced in these models, however. While aggregated Abeta is neurotoxic, perhaps via an oxidative mechanism, the relationship between such toxicity and neurofibrillary tangle formation remains a subject of ongoing research.     

山蒟醇提取物的抗血小板聚集作用?

以山蒟醇提取物在兔的体内和体外-体内进行抗血小板聚集实验。结果表明山蒟醇提取物可抑制由血小板活化因子和花生四烯酸所致的血小板聚集,对2者所致的血小板聚集（体外试验）的IC_（50）。分别为40． 34、345． 46 mg／L。静脉注射山蒟醇提取物30 mg／kg,15 min后产生的抗血小板聚集作用最明显,其对血小板活化因子和花生四烯酸所致的血小板聚集（体内-体外试验）的抑制率分别为82．75％和33．34％;血小板聚集的持续时间分别为60、30 min。这表明山蒟醇提取物对血小板活化因子作用有一定的选择性。     

Stability of Interleukin 1β (IL-1β) in Aqueous Solution: Analytical Methods,Kinetics, Products,and Solution Formulation Implications

The thermal stability of IL-1 in aqueous solution as a function of temperature (5–60°C), pH (2–9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 at or above 39°C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30°C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5°C suggests that a solution formulation may be feasible for IL-1.