The electronic structures of LiYF4：Ce^3＋ and LiYF4 crystal simulated by an embedded （in a microcrystal containing 1938 ions） cluster CeY4Li8F24, and Y5LisF24 respectively, were computed by the ab initio self-consi...The electronic structures of LiYF4：Ce^3＋ and LiYF4 crystal simulated by an embedded （in a microcrystal containing 1938 ions） cluster CeY4Li8F24, and Y5LisF24 respectively, were computed by the ab initio self-consistent relativistic DV-Xa （discrete variational Xa） method. The ground-state calculation showed that only the lowest 5d level Ed of Ce^3＋ ion lies around the BCB （bottom of the conduction band） while the lowest 4f levels is 2.5 eV lower than BCB. The CB states consist of 4d of Y mixed with 5d of Ce, even for the wavefunctions （WFS） with energy Ed under BCB there are still 24% of Y-4d and 9% of F-2p as components. So, they are not pure crystal-field states at all. Furthermore, transition state （TS） calculation was performed to obtain the 4f→5d transition energies Efd, to improve the previous calculation performed by Andriessen et al, in which a small CeF8 cluster embedded in an array of point charge was used and the results of ground-state calculation were roughly used to compare with the observed 4f→5 d transition energies. The ionic radius of Ce^3＋ is larger than that of y^3＋ , so we had also modeled approximately the lattice relaxation. As results, the CeY4Li8F24 cluster with 4.56 % outward relaxation （of the nearest-neighbor and next nearest-neighbor eight fluorines） has the lowest total energy and gave satisfactory 4f→5d energies Efd, but the ground-state calculated Ed is 0.68 eV higher than BCB. For another cluster with 7.36% outward relaxation the Ed is 0.43 eV lower than BCB, which makes the observation of fine structure （including zero-phonon line） of the lowest 5 d band understandable easier, but the splits between the transition energies Efd were not as good as the former. Therefore, we consider the relaxation is some how around 4. 56% -7.36% outward, not as large as 10% proposed by Andriessen et al.展开更多
The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a...The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a = 5.7900（12）, b = 13.086（3）, c = 12.889（3） A, β= 100.86（3）°, V = 959.1（3） ）k3, Z = 2, Dc= 1.489 g/cm3, F（000） = 444,μ= 0.342 mm-l, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections （I 〉 20（I）. The absolute configuration of the stereogenic center in the title compound was confirmed to be S by single-crystal X-ray diffraction. Four existing intermolecular hydrogen bonds help to stabilize the lattice and the molecule in the lattice to adopt an L-shape conformation. Zifaxaban was slightly more active than rivaroxaban 1 in in vitro assay against human FXa and therefore is promising as a drug candidate.展开更多
Two components of anticoagulant protein were isolated from the leech Haemendipsa yanyuanensis by heparin agarose affinity chromatography and ultracentrifugation. The determination of anticoagulant activity and cha...Two components of anticoagulant protein were isolated from the leech Haemendipsa yanyuanensis by heparin agarose affinity chromatography and ultracentrifugation. The determination of anticoagulant activity and characterization analysis of the protein using the method of chromogenic substrate indicates that the anticoagulant protein is thrombin specific but not factor Xa specific. The results lay a foundation for the research of the anticoagulant mechanism and application of anticoagulant protein from H. yanyuanensis.展开更多
Venous thromboembolism(VTE) encompasses deep vein thrombosis and pulmonary embolism and is a major health burden, both medically and economically. Anticoagulation is the primary treatment and can be divided into three...Venous thromboembolism(VTE) encompasses deep vein thrombosis and pulmonary embolism and is a major health burden, both medically and economically. Anticoagulation is the primary treatment and can be divided into three stages: initial, long term and extended treatment. Initial anticoagulation is given to reduce the risk of complications including fatal pulmonary embolism, while long term and extended treatment are aimed at prevention of recurrent VTE. Until recently, initial anticoagulation has only been achievable with administration of parental agents such as unfractionated or low molecular weight heparin, while vitamin K antagonists such as warfarin, have been the mainstay of long term and extended treatment. Factor-Xa inhibitors and direct thrombin inhibitors are oral anticoagulants that are being increasingly utilized as an alternative form of anticoagulation. This article aims to review the current guidelines in the management of VTE, the recent literature regarding novel anticoagulants in VTE, suggested treatment regimes and limitations.展开更多
A rapid, simple, and reproducible method for the preparation of porcine thrombin was investigated. Porcine prothrombin was isolated by carrying out isoelectric precipitation. Porcine thrombin was prepared from prothro...A rapid, simple, and reproducible method for the preparation of porcine thrombin was investigated. Porcine prothrombin was isolated by carrying out isoelectric precipitation. Porcine thrombin was prepared from prothrombin which was activated by the prothrombinase complex containing Factor Xa, Factor V, Ca2+ and phospholipids. Factor Xa and Factor V were isolated by DEAE-cellulose chromatography respectively. They were both identified by SDS-PAGE. Yields and specific activity of porcine thrombin were 107 μg per milliliter plasma and 4 U per milligram protein.展开更多
Objective: In the present study, we report on the results of our investigation of optimum dose monitoring using coagulation and fibrinolytic system indicators during obstetric prophylactic anticoagulant therapy with e...Objective: In the present study, we report on the results of our investigation of optimum dose monitoring using coagulation and fibrinolytic system indicators during obstetric prophylactic anticoagulant therapy with enoxaparin. Study Design: Of 103 cases of cesarean section performed at our hospital, 37 cases were selected for this study after obtain ing their consent for blood collection. Variables of the coagulation and fibrinolytic systems [anti-factor Xa activity, endogenous thrombin potential (ETP), prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (APTT) and D-dimer levels] were determined. Results: In the 5-day administration group, the anti-factor Xa activitywas 0.0 U/ml on the postoperative day 1, increased to 0.05 U/ml ± 0.04 U/ml on the postoperative day 3, and mildly increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 5. On the other hand, the anti-factor Xa activity in the 3-day administration group was 0.0 U/ml on the postoperative day 1 (before enoxaparin administration), increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 3, and significantly decreased to 0.02 U/ml ± 0.03 U/ml on the postoperative day 5 (p = 0.003);thus, the pattern of change was significantly different from that in the 5-day administration group (p = 0.004). Enoxaparin administration did not result in any significant fluctuation of the ETP, and no significant difference was observed between the 5-day and 3-day administration groups. Conclusion: Enoxaparin administration was associated with increase of the anti-factor Xa activity, and prolonged administration led to more sustained increase of the activity.展开更多
Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K an...Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.展开更多
目的:评价Xa因子(FXa)抑制剂对急性冠脉综合征(ACS)的疗效及安全性。方法:计算机检索Cochrane Central Register of Controlled Trials、MEDLINE、EMbase、万方数据、中国知网数据库、中国生物医学文献数据库及维普数据库从建库至今有关...目的:评价Xa因子(FXa)抑制剂对急性冠脉综合征(ACS)的疗效及安全性。方法:计算机检索Cochrane Central Register of Controlled Trials、MEDLINE、EMbase、万方数据、中国知网数据库、中国生物医学文献数据库及维普数据库从建库至今有关FXa抑制剂对ACS患者疗效及安全性的临床随机对照试验(RCT)。由3名研究者进行文献提取和质量评价,对符合纳入标准的研究采用Review 5.1软件进行偏倚定性和Meta分析。结果:共纳入6篇RCT,均采用随机、双盲、安慰剂对照组,且数据完整,非选择性结果报道为低偏倚风险。Meta分析结果显示,低、中、高剂量FXa抑制剂均不能降低ACS患者全因死亡风险[RR=0.92,95%CI(0.80,1.07);RR=0.95,95%CI(0.48,1.87);RR=0.97,95%CI(0.38,2.52)];仅低剂量FXa抑制剂可以降低ACS患者再发心肌梗死风险[RR=0.87,95%CI(0.77,0.98)];FXa抑制剂不能明显降低ACS患者缺血性卒中风险[RR=0.98,95%CI(0.74,1.31)];低、中、高剂量FXa抑制剂均可增加ACS患者主要出血事件风险[RR=2.31,95%CI(1.66,3.21);RR=6.69,95%CI(2.73,16.43);RR=6.23,95%CI(2.75,14.14)]。结论:低剂量FXa抑制剂治疗ACS患者可以降低再发心肌梗死风险;FXa联合抗血小板药物治疗ACS对降低患者全因死亡、缺血性卒中和主要出血事件风险与既往抗血小板治疗比较并无明显优势。展开更多
文摘The electronic structures of LiYF4：Ce^3＋ and LiYF4 crystal simulated by an embedded （in a microcrystal containing 1938 ions） cluster CeY4Li8F24, and Y5LisF24 respectively, were computed by the ab initio self-consistent relativistic DV-Xa （discrete variational Xa） method. The ground-state calculation showed that only the lowest 5d level Ed of Ce^3＋ ion lies around the BCB （bottom of the conduction band） while the lowest 4f levels is 2.5 eV lower than BCB. The CB states consist of 4d of Y mixed with 5d of Ce, even for the wavefunctions （WFS） with energy Ed under BCB there are still 24% of Y-4d and 9% of F-2p as components. So, they are not pure crystal-field states at all. Furthermore, transition state （TS） calculation was performed to obtain the 4f→5d transition energies Efd, to improve the previous calculation performed by Andriessen et al, in which a small CeF8 cluster embedded in an array of point charge was used and the results of ground-state calculation were roughly used to compare with the observed 4f→5 d transition energies. The ionic radius of Ce^3＋ is larger than that of y^3＋ , so we had also modeled approximately the lattice relaxation. As results, the CeY4Li8F24 cluster with 4.56 % outward relaxation （of the nearest-neighbor and next nearest-neighbor eight fluorines） has the lowest total energy and gave satisfactory 4f→5d energies Efd, but the ground-state calculated Ed is 0.68 eV higher than BCB. For another cluster with 7.36% outward relaxation the Ed is 0.43 eV lower than BCB, which makes the observation of fine structure （including zero-phonon line） of the lowest 5 d band understandable easier, but the splits between the transition energies Efd were not as good as the former. Therefore, we consider the relaxation is some how around 4. 56% -7.36% outward, not as large as 10% proposed by Andriessen et al.
基金Supported by Key Projects of Tianjin Science and Technology Support Plan(12ZCZDSY01100)
文摘The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a = 5.7900（12）, b = 13.086（3）, c = 12.889（3） A, β= 100.86（3）°, V = 959.1（3） ）k3, Z = 2, Dc= 1.489 g/cm3, F（000） = 444,μ= 0.342 mm-l, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections （I 〉 20（I）. The absolute configuration of the stereogenic center in the title compound was confirmed to be S by single-crystal X-ray diffraction. Four existing intermolecular hydrogen bonds help to stabilize the lattice and the molecule in the lattice to adopt an L-shape conformation. Zifaxaban was slightly more active than rivaroxaban 1 in in vitro assay against human FXa and therefore is promising as a drug candidate.
文摘Two components of anticoagulant protein were isolated from the leech Haemendipsa yanyuanensis by heparin agarose affinity chromatography and ultracentrifugation. The determination of anticoagulant activity and characterization analysis of the protein using the method of chromogenic substrate indicates that the anticoagulant protein is thrombin specific but not factor Xa specific. The results lay a foundation for the research of the anticoagulant mechanism and application of anticoagulant protein from H. yanyuanensis.
文摘Venous thromboembolism(VTE) encompasses deep vein thrombosis and pulmonary embolism and is a major health burden, both medically and economically. Anticoagulation is the primary treatment and can be divided into three stages: initial, long term and extended treatment. Initial anticoagulation is given to reduce the risk of complications including fatal pulmonary embolism, while long term and extended treatment are aimed at prevention of recurrent VTE. Until recently, initial anticoagulation has only been achievable with administration of parental agents such as unfractionated or low molecular weight heparin, while vitamin K antagonists such as warfarin, have been the mainstay of long term and extended treatment. Factor-Xa inhibitors and direct thrombin inhibitors are oral anticoagulants that are being increasingly utilized as an alternative form of anticoagulation. This article aims to review the current guidelines in the management of VTE, the recent literature regarding novel anticoagulants in VTE, suggested treatment regimes and limitations.
文摘A rapid, simple, and reproducible method for the preparation of porcine thrombin was investigated. Porcine prothrombin was isolated by carrying out isoelectric precipitation. Porcine thrombin was prepared from prothrombin which was activated by the prothrombinase complex containing Factor Xa, Factor V, Ca2+ and phospholipids. Factor Xa and Factor V were isolated by DEAE-cellulose chromatography respectively. They were both identified by SDS-PAGE. Yields and specific activity of porcine thrombin were 107 μg per milliliter plasma and 4 U per milligram protein.
文摘Objective: In the present study, we report on the results of our investigation of optimum dose monitoring using coagulation and fibrinolytic system indicators during obstetric prophylactic anticoagulant therapy with enoxaparin. Study Design: Of 103 cases of cesarean section performed at our hospital, 37 cases were selected for this study after obtain ing their consent for blood collection. Variables of the coagulation and fibrinolytic systems [anti-factor Xa activity, endogenous thrombin potential (ETP), prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (APTT) and D-dimer levels] were determined. Results: In the 5-day administration group, the anti-factor Xa activitywas 0.0 U/ml on the postoperative day 1, increased to 0.05 U/ml ± 0.04 U/ml on the postoperative day 3, and mildly increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 5. On the other hand, the anti-factor Xa activity in the 3-day administration group was 0.0 U/ml on the postoperative day 1 (before enoxaparin administration), increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 3, and significantly decreased to 0.02 U/ml ± 0.03 U/ml on the postoperative day 5 (p = 0.003);thus, the pattern of change was significantly different from that in the 5-day administration group (p = 0.004). Enoxaparin administration did not result in any significant fluctuation of the ETP, and no significant difference was observed between the 5-day and 3-day administration groups. Conclusion: Enoxaparin administration was associated with increase of the anti-factor Xa activity, and prolonged administration led to more sustained increase of the activity.
文摘Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.
文摘目的:评价Xa因子(FXa)抑制剂对急性冠脉综合征(ACS)的疗效及安全性。方法:计算机检索Cochrane Central Register of Controlled Trials、MEDLINE、EMbase、万方数据、中国知网数据库、中国生物医学文献数据库及维普数据库从建库至今有关FXa抑制剂对ACS患者疗效及安全性的临床随机对照试验(RCT)。由3名研究者进行文献提取和质量评价,对符合纳入标准的研究采用Review 5.1软件进行偏倚定性和Meta分析。结果:共纳入6篇RCT,均采用随机、双盲、安慰剂对照组,且数据完整,非选择性结果报道为低偏倚风险。Meta分析结果显示,低、中、高剂量FXa抑制剂均不能降低ACS患者全因死亡风险[RR=0.92,95%CI(0.80,1.07);RR=0.95,95%CI(0.48,1.87);RR=0.97,95%CI(0.38,2.52)];仅低剂量FXa抑制剂可以降低ACS患者再发心肌梗死风险[RR=0.87,95%CI(0.77,0.98)];FXa抑制剂不能明显降低ACS患者缺血性卒中风险[RR=0.98,95%CI(0.74,1.31)];低、中、高剂量FXa抑制剂均可增加ACS患者主要出血事件风险[RR=2.31,95%CI(1.66,3.21);RR=6.69,95%CI(2.73,16.43);RR=6.23,95%CI(2.75,14.14)]。结论:低剂量FXa抑制剂治疗ACS患者可以降低再发心肌梗死风险;FXa联合抗血小板药物治疗ACS对降低患者全因死亡、缺血性卒中和主要出血事件风险与既往抗血小板治疗比较并无明显优势。
