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  1. Article ; Online: Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

    Hua, Rui / Li, Mingxi / Lin, Qingxia / Dong, Mengying / Gong, Xiaoxuan / Lin, Zhenyu / Li, Yule / Li, Chen / Wu, Tian / Tan, Chunyue / Zhang, Wenhao / Wang, Qin / Wu, Tianyu / Zhou, Xiaoyu / Yang, Fang / Li, Chunjian

    ACS applied materials & interfaces

    2024  Volume 16, Issue 17, Page(s) 21438–21449

    Abstract: Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic ... ...

    Abstract Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.
    MeSH term(s) Animals ; Rabbits ; Humans ; Thrombosis/drug therapy ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Fibrinolytic Agents/chemistry ; Fibrinolytic Agents/therapeutic use ; Fibrinolytic Agents/pharmacology ; Metalloendopeptidases/metabolism ; Thrombolytic Therapy ; Recombinant Proteins/therapeutic use ; Male ; Cell Membrane/metabolism ; Cell Membrane/drug effects
    Chemical Substances Fibrinolytic Agents ; Metalloendopeptidases (EC 3.4.24.-) ; auR protein, Staphylococcus aureus (EC 3.4.24.29) ; Recombinant Proteins
    Language English
    Publishing date 2024-04-16
    Publishing country United States
    Document type Journal Article
    ISSN 1944-8252
    ISSN (online) 1944-8252
    DOI 10.1021/acsami.3c18402
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Discordance Between Self-Reported and Performance-Based Physical Function in Patients Who Have Knee Osteoarthritis: Associations With Pain Intensity and Negative Affect.

    Pua, Yong-Hao / Tan, Bryan Yijia / Low, Juanita / Woon, Ee-Lin / Yeo, Seng-Jin / Clark, Ross A / Bettger, Janet P / Pereira, Michelle J / Tan, Chun-Yue / Thumboo, Julian

    The Journal of arthroplasty

    2023  Volume 38, Issue 9, Page(s) 1705–1713.e1

    Abstract: Background: Although self-reported measures of physical disability are strong indication criterion for total knee arthroplasty (TKA) in painful knee osteoarthritis (OA), some patients may report greater-than-observed disability. Contributing factors to ... ...

    Abstract Background: Although self-reported measures of physical disability are strong indication criterion for total knee arthroplasty (TKA) in painful knee osteoarthritis (OA), some patients may report greater-than-observed disability. Contributing factors to this discordance are relatively unexplored. We aimed to examine whether pain and negative affect, including anxiety and depression, were associated with the discordance of self-reported measures with performance-based measures (PPM) of physical function.
    Methods: We used cross-sectional data (n = 212) from two randomized rehabilitation trials in knee OA. All patients were assessed for knee pain intensity and symptoms of anxiety and depression. Self-reported function was assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical-function subscale. Objective performance-based measures (PPMs) of physical function were assessed by timed gait and stair tests. Continuous discordance scores were quantified by the difference in percentiles between WOMAC and PPMs (WOMAC-PPM), where a positive discordance, WOMAC-PPM >0, implied greater perceived than observed disability.
    Results: Around 1 in 4 patients had >20 percentile units in WOMAC-PPM discordance. In Bayesian regression analyses, knee pain intensity had >99% posterior probability of positive associations with WOMAC-PPM discordance. Among patients awaiting TKA, anxiety intensity had approximately 99% probability of positive associations with discordance, and these associations had >65% probability of exceeding 10 percentile units. In contrast, depression had low (79% to 88%) probability of any association with discordance.
    Conclusion: In patients who have knee OA, a sizable proportion reported substantially greater physical disability than actually observed. Pain and anxiety intensity, but not depression, were meaningful predictors of this discordance. If validated, our findings may help in refining patient selection criteria for TKA.
    MeSH term(s) Humans ; Osteoarthritis, Knee/complications ; Osteoarthritis, Knee/surgery ; Self Report ; Pain Measurement ; Cross-Sectional Studies ; Bayes Theorem ; Pain/complications ; Affect
    Language English
    Publishing date 2023-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632770-9
    ISSN 1532-8406 ; 0883-5403
    ISSN (online) 1532-8406
    ISSN 0883-5403
    DOI 10.1016/j.arth.2023.03.044
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  3. Article ; Online: Efficacy and safety of a bolus of half-dose r-SAK prior to primary PCI in ST-elevation myocardial infarction: Rationale and design of the OPTIMA-6 trial.

    Li, Chen / Eikelboom, John W / Zhong, Zihang / Zhang, Xiwen / Liu, Kun / Zhu, Li / Yang, Naiquan / Chen, Xin / Wang, Xiaoyan / Zhao, Xin / Jiang, Jun / Pu, Jun / Zhao, Bo / Zhang, Fumin / Zhu, Jun / Huang, Jun / Kong, Xiangqing / Yu, Hao / Tan, Chunyue /
    Zhang, Wenhao / Wang, Qin / Gong, Xiaoxuan / Bai, Jianling / Li, Chunjian

    American heart journal

    2023  Volume 265, Page(s) 31–39

    Abstract: Background: Time to reperfusion is the key to the treatment of patients with ST-elevation myocardial infarction (STEMI). It is uncertain whether adjunctive thrombolytic therapy combined with contemporary antiplatelet agent ticagrelor improves outcomes ... ...

    Abstract Background: Time to reperfusion is the key to the treatment of patients with ST-elevation myocardial infarction (STEMI). It is uncertain whether adjunctive thrombolytic therapy combined with contemporary antiplatelet agent ticagrelor improves outcomes as administered prior to primary percutaneous coronary intervention (PCI) expected to be performed within 120 minutes.
    Methods: OPTIMA-6 is a multicenter, randomized, double-blind, placebo-controlled, and superiority trial to evaluate the efficacy of a bolus of half-dose recombinant staphylokinase (r-SAK) vs placebo prior to timely primary PCI in patients with STEMI. Enrollment began in April 2023 and is expected to enroll 2,260 patients at approximately 50 centers. Patients with acute STEMI presenting ≤12 hours of symptom onset and expected to undergo primary PCI within 120 minutes but more than 30 minutes are to be randomized to a bolus of half-dose r-SAK or placebo. All recruited patients will be mandatory to take aspirin and ticagrelor and receive a bolus of loading dose heparin before the thrombolytic therapy. The primary efficacy endpoint is major adverse cardiovascular events (MACE) within 90 days, and the MACE is defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, and major ventricular arrhythmia. The primary safety endpoints are major bleeding events (BARC 3, 5) within 90 days.
    Conclusions: OPTIMA-6 will reveal the efficacy and safety of a contemporary facilitated PCI with a bolus of half-dose r-SAK in combination with ticagrelor in patients with STEMI.
    Language English
    Publishing date 2023-06-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80026-0
    ISSN 1097-6744 ; 0002-8703
    ISSN (online) 1097-6744
    ISSN 0002-8703
    DOI 10.1016/j.ahj.2023.06.012
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  4. Article ; Online: Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction.

    Chen, Pengsheng / Eikelboom, John W / Tan, Chunyue / Zhang, Wenhao / Xu, Yi / Bai, Jianling / Wang, Jun / Wang, Tong / Gong, Xiaoxuan / Liu, Kun / Chen, Xin / Wang, Xiaoyan / Zhu, Li / Zhao, Xin / Yang, Naiquan / Jiang, Jun / Pu, Jun / Zhao, Bo / Chen, Zengguang /
    Li, Baihong / Wang, Guoyu / Lu, Chuan / Ying, Lianghong / Jiang, Meng / Zhu, Xiaomei / Ma, Jiazheng / Dong, Zhou / Li, Chen / Zong, Jiaxin / Zhang, Fumin / Zhu, Jun / Huang, Jun / Kong, Xiangqing / Yu, Hao / Li, Chunjian

    Circulation. Cardiovascular interventions

    2024  Volume 17, Issue 2, Page(s) e013455

    Abstract: Background: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine ... ...

    Abstract Background: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment-elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size.
    Methods: This is an open-label, prospective, multicenter, randomized study. We enrolled patients aged 18 to 75 years who were within 12 hours of symptom onset of ST-segment-elevation myocardial infarction and expected to undergo PCI within 120 minutes. Patients were administered loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive 5 mg bolus of r-SAK or normal saline intravenously before PCI. The primary end point was Thrombolysis in Myocardial Infarction flow grade 2 to 3 or grade 3 in the infarct-related artery 60 minutes after thrombolysis. The infarct size was detected by cardiac magnetic resonance 5 days after randomization. The safety end point was major bleeding (Bleeding Academic Research Consortium ≥3) during 30-day follow-up.
    Results: A total of 283 patients were screened from 8 centers and 200 were randomized (median age, 58.5 years; 14% female). The median symptom to thrombolysis time was 252.5 (interquartile range, 142.8-423.8) minutes and thrombolysis to coronary arteriography was 50.0 (interquartile range, 37.0-66.0) minutes. Patients randomized to r-SAK compared with normal saline more often had Thrombolysis in Myocardial Infarction flow grade 2 to 3 (69.0% versus 29.0%;
    Conclusions: A single bolus r-SAK before primary PCI for ST-segment-elevation myocardial infarction improves infarct-related artery patency and reduces infarct size without increasing major bleeding.
    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05023681.
    MeSH term(s) Female ; Humans ; Male ; Middle Aged ; Hemorrhage/chemically induced ; Metalloendopeptidases ; Myocardial Infarction/etiology ; Percutaneous Coronary Intervention/adverse effects ; Prospective Studies ; Saline Solution/therapeutic use ; ST Elevation Myocardial Infarction/diagnostic imaging ; ST Elevation Myocardial Infarction/therapy ; ST Elevation Myocardial Infarction/etiology ; Treatment Outcome ; Adolescent ; Young Adult ; Adult ; Aged
    Chemical Substances auR protein, Staphylococcus aureus (EC 3.4.24.29) ; Metalloendopeptidases (EC 3.4.24.-) ; Saline Solution
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2450797-0
    ISSN 1941-7632 ; 1941-7640
    ISSN (online) 1941-7632
    ISSN 1941-7640
    DOI 10.1161/CIRCINTERVENTIONS.123.013455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6746: Show issues Location:
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