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排序方式: 共有379条查询结果,搜索用时 15 毫秒
1.
Natalia Cadaxo Rochael Luize Gon?alves Lima Sandra Maria Pereira de Oliveira Marcello André Barcinski Elvira Maria Saraiva Robson Queiroz Monteiro Lucia Helena Pinto-da-Silva 《Memórias do Instituto Oswaldo Cruz》2013,108(6):679-685
Leishmania parasites expose phosphatidylserine (PS) on their
surface, a process that has been associated with regulation of host''s immune
responses. In this study we demonstrate that PS exposure by metacyclic
promastigotes of Leishmania amazonensis favours blood
coagulation. L. amazonensis accelerates in vitro coagulation of
human plasma. In addition, L. amazonensis supports the assembly
of the prothrombinase complex, thus promoting thrombin formation. This process
was reversed by annexin V which blocks PS binding sites. During blood meal,
Lutzomyia longipalpis sandfly inject saliva in the bite
site, which has a series of pharmacologically active compounds that inhibit
blood coagulation. Since saliva and parasites are co-injected in the host during
natural transmission, we evaluated the anticoagulant properties of sandfly
saliva in counteracting the procoagulant activity of L.
amazonensis . Lu. longipalpis saliva reverses
plasma clotting promoted by promastigotes. It also inhibits thrombin formation
by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS
vesicles or in L. amazonensis . Sandfly saliva inhibits factor
X activation by the intrinsic tenase complex assembled on PC/PS vesicles and
blocks factor Xa catalytic activity. Altogether our results show that metacyclic
promastigotes of L. amazonensis are procoagulant due to PS
exposure. Notably, this effect is efficiently counteracted by sandfly
saliva. 相似文献
2.
《Expert review of proteomics》2013,10(6):653-655
The structure of prothrombin has eluded investigators for decades but recent efforts have succeeded in revealing the architecture of this important clotting factor. Unanticipated features have emerged outlining the significant flexibility of the zymogen due to linker regions connecting the γ carboxyglutamic domain, kringles and protease domain. A new, structure-based framework helps in defining a molecular mechanism of prothrombin activation, rationalizes the severe bleeding phenotypes of several naturally occurring mutations and identifies targets for drug design. 相似文献
3.
《Critical reviews in biochemistry and molecular biology》2013,48(4):326-336
AbstractThe plasma coagulation system in mammalian blood consists of a cascade of enzyme activation events in which serine proteases activate the proteins (proenzymes and procofactors) in the next step of the cascade via limited proteolysis. The ultimate outcome is the polymerization of fibrin and the activation of platelets, leading to a blood clot. This process is protective, as it prevents excessive blood loss following injury (normal hemostasis). Unfortunately, the blood clotting system can also lead to unwanted blood clots inside blood vessels (pathologic thrombosis), which is a leading cause of disability and death in the developed world. There are two main mechanisms for triggering the blood clotting, termed the tissue factor pathway and the contact pathway. Only one of these pathways (the tissue factor pathway) functions in normal hemostasis. Both pathways, however, are thought to contribute to thrombosis. An emerging concept is that the contact pathway functions in host pathogen defenses. This review focuses on how the initiation phase of the blood clotting cascade is regulated in both pathways, with a discussion of the contributions of these pathways to hemostasis versus thrombosis. 相似文献
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Active hemostatic agents can play a crucial role in saving patients’ lives during surgery. Active hemostats have several advantages including utilization of natural blood coagulation and biocompatibility. Among them, although human neutrophil peptide‐1 (HNP‐1) has been previously reported with the hemostatic mechanism, which part of HNP‐1 facilitates the hemostatic activity is not known. Here, a partial peptide (HNP‐F) promoting hemostasis, originating from HNP‐1, has been newly identified by the blood coagulation ability test. HNP‐F shows the best hemostatic effect between the anterior half and posterior half of peptides. Moreover, microscopic images show platelet aggregation and an increase in the concentration of platelet factor 4, and the scanning electron microscope image of platelets support platelet activation by HNP‐F. Thromboelastography indicates decreased clotting time and increased physical properties of blood clotting. Mouse liver experiments demonstrate improved hemostatic effect by treatment of peptide solution. Cell viability and hemolysis assays confirm the HNP‐F's biosafety. It is hypothesized that the surface charge and structure of HNP‐F could be favorable to interact with fibrinogen or thrombospondin‐1. Collectively, because HNP‐F as an active peptide hemostat has many advantages, it could be expected to become a potent hemostatic biomaterial, additive or pharmaceutical candidate for various hemostatic applications. 相似文献
7.
天然地球化学过程导致全球范围内广泛存在地下水氟污染,饮用水氟超标人口达5亿.控制以高氟地下水为饮用水源的氟污染及其健康风险,成为饮用水质安全保障的核心问题之一.全世界在饮用水除氟方面做了大量努力,但成效十分有限.在此背景下,深刻认识氟污染形成机制与地球化学特征,结合地理信息、遥感等手段预测区域风险水平,优先考虑“更换水源”,仍是饮用水氟污染控制的重要策略.此外,在研究层面上,应以净水药剂、环境功能材料创新为基础,以混凝沉淀、吸附、膜分离为重要技术方向,开发适用于发展中国家或欠发达地区的高效、经济、方便、稳定的除氟关键技术和成套设备;在工程应用层面上,应加强饮用水除氟设施设计、建设、运行与监管,确保设施长期稳定运行,实现工程效益. 相似文献
8.
Cristina Lemini Ruth Jaimez Alejandra Figueroa Lucía Martinez-Mota María Estela Avila Martha Medina 《Experimental Animals》2015,64(1):81-89
Rodent ovariectomy is an experimental method to eliminate the main source of sexual
steroids. This work explored for the first time the ovariectomy temporal changes induced
in the hemostatic coagulation markers: prothrombin time (PT), activated partial
thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration (FIB) along
with uterine weight on adult female CD1 mice and Wistar rats. Uterine weight (Uw) was
assessed before ovariectomy (control), and 1, 3, 5, 7, 9, 16, and 21 days after surgery.
PT, aPTT, TT and FIB were estimated the same days, using reported standard techniques.
Ovariectomy decreased Uw, since day 1; and from day 10 to 21 reached the lowest values for
both species. After day 1, mice hemostatic parameters changed (PT +10%,
P<0.05; aPTT +53%, P<0.05; TT −24%,
P<0.05; FIB +67%, P<0.05). Rats showed
significant changes only in TT and FIB (TT −13%, P<0.001; FIB +65%,
P<0.001). Neither mice PT, aPTT and TT, recovered control values
after 21 days. In the rats from day 5 to 16 aPTT diminished (18–23%,
P<0.05) recovering to control values on day 21, TT after 9 days and PT
on day 16. In both species, FIB returned to its control values after 9 days. Ovariectomy
differentially altered the PT hemostatic parameter of mice and rats indicating a
non-equivalence among both species behaviour for experimental studies of blood
coagulation. 相似文献
9.
Ryan Roth Richard Swanson Gonzalo Izaguirre Susan C. Bock Peter G. W. Gettins Steven T. Olson 《The Journal of biological chemistry》2015,290(47):28020-28036
Past studies have suggested that a key feature of the mechanism of heparin allosteric activation of the anticoagulant serpin, antithrombin, is the release of the reactive center loop P14 residue from a native state stabilizing interaction with the hydrophobic core. However, more recent studies have indicated that this structural change plays a secondary role in the activation mechanism. To clarify this role, we expressed and characterized 15 antithrombin P14 variants. The variants exhibited basal reactivities with factors Xa and IXa, heparin affinities and thermal stabilities that were dramatically altered from wild type, consistent with the P14 mutations perturbing native state stability and shifting an allosteric equilibrium between native and activated states. Rapid kinetic studies confirmed that limiting rate constants for heparin allosteric activation of the mutants were altered in conjunction with the observed shifts of the allosteric equilibrium. However, correlations of the P14 mutations'' effects on parameters reflecting the allosteric activation state of the serpin were inconsistent with a two-state model of allosteric activation and suggested multiple activated states. Together, these findings support a minimal three-state model of allosteric activation in which the P14 mutations perturb equilibria involving distinct native, intermediate, and fully activated states wherein the P14 residue retains an interaction with the hydrophobic core in the intermediate state but is released from the core in the fully activated state, and the bulk of allosteric activation has occurred in the intermediate. 相似文献
10.