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Recent advances in nanomedicines for the treatment of ischemic stroke

Acta Pharmaceutica Sinica B 2021年第7期11卷 1767-1788页

作者： Chao Li Tao Sun Chen Jiang Key Laboratory of Smart Drug Delivery Ministry of EducationState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceDepartment of PharmaceuticsSchool of PharmacyResearch Center on Aging and MedicineFudan UniversityShanghai 201203China

Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the *** would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain,where the ischemic cascade eventually leads to cell death and brain *** researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic ***,traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment *** provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo,achieve effective drug accumulation at the target site,enhance the therapeutic effect and meanwhile reduce the side *** this review,we comprehensively describe the pathophysiology of stroke,traditional treatment strategies and emerging nanomedicines,summarize the barriers and methods for transporting nanomedicine to the lesions,and illustrate the latest progress of nanomedicine in treating ischemic stroke,with a view to providing a new feasible path for the treatment of cerebral ischemia.

关键词： Stroke Ischemic cascade Reperfusion Neuroprotectant thrombolytics Nanomedicine Blood-brain barrier

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Translational initiatives in thrombolytic therapy

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Frontiers of Medicine 2017年第1期11卷 1-19页

作者： Melvin E. Klegerman Department of lnWrnal Medicine Division of Cardiovascular Medicine University of Texas Health Science Center at Houston (UTHealth) Houston TX 77054 USA

Once thrombi have formed as part of the pathology defining myocardial infarction, ischemic stroke, peripheral arterial disease, deep venous thrombosis or other embolic disorders, the only clinically meaningful thrombolytic agents available for reversing the thrombogenic process are various plasminogen activators. These agents are enzymes that reverse fibrin polymerization underlying the coagulation process by converting endogenous plasminogen to plasmin, which cleaves the fibrin network to form increasingly smaller protein fragments, a process known as fibrinolysis. For the most part, the major clinically used thrombolytics, tissue plasminogen activator, urokinase and streptokinase, as well as the experimentally investigated agent staphylokinase, are the products of recombinant DNA technology, which permits molecular optimization of clinical efficacy. In all cases of molecular optimization and targeting, however, the primary challenge of thrombolytic therapy remains hemorrhagic side effects, which are especially devastating when they occur intracerebrally. Currently, the best strategy to ameliorate this adverse effect is nanoparticulate encapsulation or complexation, and many strategies of this sort are being actively pursued. This review summarizes the variety of targeted and untargeted thrombolytic formulations that have been investigated in preclinical studies.

关键词： thrombolytics nanomedicine plasminogen activators

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Intra-arterial thrombolysis for early hepatic artery thrombosis after liver transplantation

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World Journal of Clinical Cases 2021年第7期9卷 1592-1599页

作者： Ting Li Xiao-Dong Sun Ying Yu Guo-Yue Lv Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient *** such as re-transplantation and re-anastomosis are conventional therapeutic methods which are restricted by the shortage of donors and the patient’s postoperative intolerance to *** to the advances in interventional techniques and thrombolytics,endovascular treatments are increasingly being selected by more and more *** study reviews and reports our single-center experience with intra-arterial thrombolysis as the first choice therapy for E-HAT after deceased donor *** To evaluate the feasibility and reasonability of intra-arterial thrombolysis for EHAT after deceased donor *** A total of 147 patients who underwent deceased donor LT were retrospectively reviewed in our hospital between September 2011 and December *** patients were diagnosed with *** of these patients underwent intraarterial thrombolysis with alteplase as the first choice therapy after *** method of arterial anastomosis and details of the diagnosis and treatment of EHAT were *** long-term prognosis of E-HAT patients was also *** median follow-up period was 26 mo(range:23 to 30 mo).RESULTS The incidence of E-HAT was 2.7%(4/147).E-HAT was considered when Doppler ultrasonography showed no blood flow signals and a definite diagnosis was confirmed by immediate hepatic arterial angiography when complete occlusion of the hepatic artery was *** patients were given temporary thrombolytics(mainly alteplase)via a 5-Fr catheter which was placed in the proximal part of the thrombosed hepatic artery followed by continuous alteplase using an infusion *** dose was adjusted according to activated clotting *** recanalization rate of intra-arterial thrombolysis in our study was 100%(4/4)and no thrombolysis-related mortality was *** the f

关键词： Early hepatic artery thrombosis Liver transplantation Intra-arterial thrombolysis thrombolytics Hepatic arterial angiography Prognosis

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Evolving paradigm of thrombolysis in pulmonary embolism:Comprehensive review of clinical manifestations,indications,recent advances and guideline

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World Journal of Clinical Cases 2023年第8期11卷 1702-1711页

作者： Rohan Kumar Ochani Rafi Aibani Hafsa Nazir Jatoi Masroor Anwar Syed Anjum Khan Iqbal Ratnani Salim Surani Department of Internal Medicine Dow University of Health ScienceKarachi 74200SindhPakistan Department of Internal Medicine Khyber Teaching HospitalPeshawar 00000Pakistan Department of Critical Care Medicine Mayo Clinic Health SystemMankatoMN 56001United States Department of Anesthesiology&Critical Care Houston Methodist HospitalHoustonTX 77030United States Department of Medicine Texas A&M UniversityCollege StationTX 77843United States Department of Medicine Aga Khan UniversityNairobiKenya

Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE,in addition to hemodynamic instability *** prevents the progression of right heart failure and impending hemodynamic *** PE can be challenging due to the variety of presentations;therefore,guidelines and scoring systems have been established to guide physicians to correctly identify and manage the ***,systemic thrombolysis has been utilized to lyse the emboli in ***,newer techniques for thrombolysis have been developed,such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediatehigh submassive risk *** newer techniques explored are the use of extracorporeal membrane oxygenation,direct aspiration,or fragmentation with *** of the constantly changing therapeutic options and the scarcity of randomized controlled trials,choosing the best course of treatment for a given patient may be *** help,the Pulmonary Embolism Reaction Team is a multidisciplinary,rapid response team that has been developed and is used at many *** to bridge the knowledge gap,our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.

关键词： Pulmonary embolism thrombolytics Systemic Catheter-directed Pulmonary embolism reaction team Guidelines

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Effects of thrombolytic drugs and a selective endothelin-1 receptor antagonist on acute pulmonary thromboembolism in dogs

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Chinese Medical Journal 2010年第4期123卷 395-400页

作者： HAN Li LI Qing-yun ZHOU Ling WANG Xi BAO Zhi-yao LI Min WAN Huan-ying SHI Guo-chao Department of Respiratory Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Background It has been shown that neurohumoral factors other than mechanical obstruction are involved in the pathophysiology of acute pulmonary thromboembolism （APTE）. The aim of this study was to investigate the effects of thrombolytic drugs, a selective endothelin-1 receptor （ET-1 R） antagonist alone or their combination on APTE in a canine model. Methods Twenty dogs were randomly assigned to five groups： sham, model, urokinase （UK）, BQ123, and combination （UK plus BQ123）. The dogs in the sham group underwent sham surgery. APTE was induced in the other four groups by intravenous injection of autologous blood clots. Dogs in the UK, BQ123 and combination groups received UK, BQ123 （a selective ET-1R antagonist）, or UK plus BQ123, respectively. The dogs in the model group were given saline. Mean pulmonary artery pressure （mPAP）, serum concentrations of ET-1, thromboxane （TXB2）, and tumor necrosis factor （TNF）-α were determined at different time points following the induction of APTE. Results UK and BQ123 alone markedly decreased mPAP in APTE. By comparison, the reduction was more significant in the combination group. Compared with the sham group （（-0.90±0.61） mmHg）, mPAP increased by （7.44±1.04）, （3.42±1.12） and （1.14±0.55） mmHg in the model group, UK alone and BQ123 alone groups, respectively, and decreased by （2.24±0.67） mmHg in the combination group （P 〈0.01）. Serum ET-1 concentrations in the BQ123 and combination groups were （52.95±8.53） and （74.42±10.27） pg/ml, respectively, and were significantly lower than those in the model and UK groups （（84.56±7.44） and （97.66±8.31） pg/ml respectively; P 〈0.01）. Serum TNF-α concentrations were significantly lower in the BQ123 group than in the model, UK and combination groups （P 〈0.05）. Conclusions Our results indicate that the selective ET-1R antagonist BQ123 not only reduces the increase of mPAP and serum ET-1 level, but also inhibits the production of TNF-α, and attenuates the local inflammatory response induced by APTE.

关键词： acute pulmonary thromboembolism thrombolytics endothelin-1 receptor antagonist pulmonary artery pressure

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