Combination of thrombolytic therapy and angioplastic stent insertion in a patient with Budd-Chiari syndrome

A 31-year-old female who had well-established polycythemia vera one year before, presented with the sudden onset. She had severe ascites and hepatic encephalopathy 12 d prior to admission. Real-time ultrasonography revealed a supra hepatic thrombosis extending toward the inferior vena cava （IVC）. Thrombolytic therapy with systemic streptokinase （250000 IU loading ＋ 100000 IU/h infusion） was started. At the end of 72 h infusion, the patient＇s general condition improved. A color Doppler ultrasonography then showed complete and partial resolution of the thrombosis in the supra hepatic vein and IVC, respectively. Despite this good response, 12 d later, the symptoms recurred. Venography detected complete obstruction of the IVC. Percutanous balloon angioplasty with stent insertion was performed successfully and the patient was discharged without any evidence of liver disease. A combination of systemic streptokinase and radiological intervention was effective in our patient.

A comparative study of the antioxidant,antimicrobial,cytotoxic and thrombolytic potential of the fruits and leaves of Spondias dulcis

Objective:To investigate the antioxidant,antimicrobial,cytotoxic and thrombolytic property of the fruits and leaves of Spondias dulcis（S.dulcis）.Methods:Methanolic extracts of fruits and leaves of S.dulcis were partitioned with chloroform and dichloromethane.The antioxidant potential of the crude extract and partitioned fractions were evaluated in terms of total phenolic content,total flavonoid content,DPPH radical scavenging potential,reducing potential and total antioxidant capacity by specific standard procedures.The antimicrobial activity was evaluated using disc diffusion method.The cytotoxicity was evaluated by using brine shrimp lethality bioassay and compared with vincristine sulfate.The thrombolytic activity was compared with streptokinase.Results:The methanolic fruit extract exhibited the highest phenolic content,flavonoid content and antioxidant capacity,among the other extracts,with the highest DPPH radical scavenging activity at a concentration of 10μg/mL(IC50:1.91μg/mL)and maximum reducing power at a concentration of 100μg/ml.(EC50:3.58μg/mL).Though all extract showed moderate antimicrobial activity against the bacterial strains,weak or no activity against fungus.The range of LC50value of all extracts was 1.335-14.057μg/mL which was far lower than the cut off index for cytotoxicity.All extracts exhibited statistically significant（P【0.001）thrombolytic activity.Conclusions:Our study suggested that 5.dulcis exhibits antimicrobial activities against a wide variety of strains while it possesses significant antioxidant,cytotoxic and thrombolytic aclivily.

Targeted Thrombolytic Therapy

Venous and arterial thrombosis are closely related to many severe diseases, especially to cardiovascular and cerebrovasular disorders. Thrombolytic therapy has been proven to be an effective method to treat such disease, which decreased the mortality and morbidity greatly.

Solid-phase Synthesis of Acyl-plasminogen-Streptokinase Activator Composite(APSAC) and Its Thrombolytic Properties

The dialysis method has been traditionally used for the conversion of native human plasminogen(Glu-Hpg) to lys-plasminogen(Lys-Hpg). Here is described a solid-phase synthesis method for the preparation of an acyl-plasminogen-streptokinase activator complex(APSAC) from Lys-Hpg, streptokinase(SK) and chemical modification (agent(4-amidinophenyl-4′-aminobenzoate hydrochloride)) with the L-lysine-Sepharose 4B Column as the carrier. The new method significantly increases the product yield and purity over the liquid-phase methods. The APSAC prepared with the new method exhibits a significant thrombolytic effect with a long half-life of about 8.8 h in rabbits.

Prognostic Biomarkers in Patients with Ischemic Stroke Who Received Thrombolytic Therapy

Background： The aim of the research was to evaluate the association between CRP （C-reactive protein）, troponin I, d-dimer, creatinine, glucose, GFR （glomerular filtration rate） and LDL-C （low-density lipoprotein cholesterol） levels at the admission and the results of thrombolytic therapy. Materials and methods： 113 patients who underwent thrombolytic therapy for acute ischemic stroke in Pauls Stradins Clinical University Hospital from 01.01.2015 to 01.01.2016 were studied retrospectively. Blood samples were collected in the emergency department. The neurological status was estimated using the NIHSS （National Institute of Health Stroke Scale）. The efficacy of thrombolytic therapy was assessed by comparing NIHSS score at the admission and after treatment. Afterward all patients were divided into three groups-the major improvement （NIHSS 〉 4）, minor improvement （NIHSS ≤ 4） and without any clinical effect. Results： Only the median levels of GFR were significantly （p = 0.015） lower in patients who did not have any clinical improvements after thrombolytic therapy as compared to patients with the major or minor improvements （60.0, IQR （interquartile range） 42.4-72.3 mL/min/1.73m2; 83.2, IQR 65.3-98.3 mL/min/1.73m2 and 75.9, IQR 59.2-94.6 mL/min/1.73m2）. Based on the ROC （receiver operating characteristic） curve, the optimal cut-off value of GFR level as an indicator for prediction of worsen clinical outcome after thrombolytic therapy was projected to be 61.65 mL/min/1.73m2, which yielded a sensitivity of 71.4% and a specificity of 24.5%, the area under the curve was 0.788 （95% CI （confidence interval）, 0.648-0.928）. According Spearman rank correlation test was founded statistically significant indirect correlation between GFR level and NIHSS score after treatment （r = -0.410, p = 0.020） in patients with severe stroke （NIHSS 〉 14）. Conclusions： GFR level lower than 61.65 mL/min/1.73m2 at the admission could predict as a worse outcome, especially in patients with severe stroke.

Thrombolytic activity of cheonggukjang kinase in recovery from brain damage in a rat cerebral embolic stroke model

Cheonggukjang is a soybean paste made by fermenting whole cooked soybeans with Bacillus subtilis. Cheonggukjang contains a fibrinolytic enzyme that could provide clinical applications for removing blood clots. In the present study, the term ＂cheonggukjang kinase＂ （CGK） was used to refer to this fibrinolytic enzyme. The thrombolytic effects of CGK were analyzed in a rat model of cerebral embolic stroke produced by middle cerebral artery occlusion （MCAO）. Results from fibrin and platelet-rich clot lysis assays demonstrated that thrombolytic activity was greatest in CGKs, which were cultured for 40 hours. In addition, T50, the time needed to decompose 50% of the clot, did not change with plasminogen treatment, indicating that CGK was not a plasminogen activator, but was rather presumed to act as a plasmin-like protein. An intravenous infusion of CGK （1 U plasmin-like activity/100 μg CGK/kg） at 1 hour after MCAO resulted in removal of clots in a rat model of cerebral embolic stroke. CGK-treated groups exhibited a significant dose-dependent reduction in infarct volume. CGK treatment also improved functional recovery, as assessed by neurological deficit scores. Decreased infarct volume and improved functional recovery following CGK treatment was greater compared with recombinant tissue plasminogen activator （10 mg/kg）. These results suggested that CGK effectively reduced infarct volume and improved functional recovery following ischemic brain injury. CGK exhibits a number of potential clinical applications ir the treatment of cerebral embolic stroke.

Thrombolytic Activity, Drug Likeness Property and ADME/T Analysis of Isolated Phytochemicals from Ginger (<i>Zingiber officinale</i>) Using <i>In Silico</i>Approaches

This experiment has been carried out to observe the potential thrombolytic activity of naturally occuring phytochemicals in Ginger (Zingiber officinale) and to analyze their drug likeness property and ADME/T profile. Thrombolytic activity of Ginger has already been confirmed in laboratory experiment and this study focuses on the molecular interactions among four phytocompounds (Isovanillin, Gingerol, Beta-sitosterol and 2,6-Dimethyl-2-octene-1,8-diol) found in Ginger and Tissue Plasminogen Activator (tPA). Present experiment is largely based on computer-aided drug design protocol where the strength of interaction is described as binding energy function. Isovanillin exhibited better docking score, and so this compound might have greater thrombolytic activity than others. Moreover, Isovanillin also suggested sound drug likeness property and ADME/T profile which predicts its safeness for consumption in human body. But Beta-sitosterol violated Lipinski’s rule of five and 2, 6-Dimethyl-2-octene-1,8-diol showed the lowest affinity of binding with tPA. However, further in vivo or in vitro study may be required to confirm the thrombolytic activity of Isovanillin.

Antioxidant, Cytotoxic, Thrombolytic and Antimicrobial Activity of <i>Zanthoxylum rhetsa</i>Root Bark with Two Isolated Quinolone Alkaloids

The background of this study was to investigate the antioxidant, cytotoxic, thrombolytic and antimicrobial activity of the petroleum ether (PE), carbon tetrachloride (CTC), chloroform (CF) and aqueous (AQ) soluble fractions of crude methanolic Zanthoxylum rhetsa root bark with two isolated quinolone alkaloids, 8-methoxy-n-methylflindersine (1) and zanthodioline (2). Structures were characterized by 1D NMR analyses. Antioxidant activity was assessed by using DPPH assay and antimicrobial activity was screened by disc diffusion method. An in vitro thrombolytic model was used to evaluate the clot lysis effect of different extracts of root bark of Z. rhetsa along with streptokinase as a positive control and distilled water as a negative control and the cytotoxic activity of different extracts of Z. rhetsa root bark was evaluated by Brine Shrimp Lethality Bioassay. AQ fraction exhibited strongest antioxidant, cytotoxic and thrombolytic activity among four fractions. The CTC and CF soluble fractions exhibited significant antioxidant, cytotoxic and thrombolytic activity. CTC and AQ fractions gave highest anti-bacterial activity against Vibrio cholera and Klebsiella pneumonia respectively. Compound 1 showed significant activity at a concentration of 100 μgm/disc against Sarcina lutea, Staphylococcus aureus and Salmonella paratyphi-A, Shigella dysenteriae, Shigella boydii and Shigella sonnei with high antioxidant activity. The antioxidant, thrombolytic and antimicrobial activity of 8-methoxy-n-methylflindersine and zanthodioline are the first record from root bark of this plant.

The Changes of Vasoactive Substances Originated Endotheiium in Patients with Unstable Angina Pectoris Treated by Improved Thrombolytic Therapy

Objectives To analyze the changes of vasoactive substances originated from endo- theiium in patients with unstable angina pectoris treated by modified thrombolytic therapy and explore the mech- anisms of the drug to treat unstable angina pectoris. Methods 120 patients with unstable angina pectoris who were not well responsed to common medication were studied. Their ECG stress tests were abnormal and there were ischemic changes in Holter. Urokinase 300,000 U was added in 100 ml normal saline and in- jected within 30 min once a day for 3 days. 300 mg as- pirin was administrated a day before and during uroki- nase applications. Before and after urokinase treat- ments , endothelin-1 , plasma tissue plasminogen activa- tor and its inhibitor-lwere determined. Results Compared with pretreatments, after treatments, the ac- tivities of tissue plasminogen activator increased, endo- thelin-1 and the inhibitor-1 decreased. The changes were significant. Conclusions Modified thrombolytic therapy can regulate the vasoactive substances origina- ted endotheiium in patients with unstable angina pecto- ris . The major substances include endothelin-1, plasma tissue plasminogen activator and inhibitor-1. This mechanism may suggest that urokinase can treat coro- nary heart disease effectively.

Stroke nurse-led intravenous thrombolytic therapy strategy for ischemic stroke based on timeline process:A quality improvement program from China

Objective:Early thrombolytic therapy for ischemic stroke within the therapeutic window is associated with improved clinical outcomes.This study investigated whether optimizing intravenous thrombolytic(IVT)therapy strategies for stroke could reduce treatment delays.Methods:To reduce delays in IVT therapy for ischemic stroke,a series of quality improvement measures were implemented at a tertiary hospital in Hangzhou,Zhejiang Province,from June 2021 to August 2023,which included developing a timeline process management system,forming a nurse-led stroke process management team,providing homogeneous training,standardizing the IVT therapy process for ischemic stroke,and introducing an incentive policy.During the pre-(from June 2021 to February 2022,group A)and post-(from March to November 2022,group B1;from December 2022 to August 2023,group B2[implementation of an additional incentive policy])of the implementation the strategy,the door-tocomputed tomographic angiography(CTA)time(DCT),CTA time,neurology consultation to consent for IVT,CTA-to-needle time(CNT),and door-to-needle time(DNT),the percentage of people who underwent CTA within 20 min,15 min,and 10 min and DNT within 60 min,45 min,and 30 min were collected and compared.Results:Following the implementation of the standardized IVT process management strategy for stroke,the DNT for group B1 and group B2 were 30(24,44)min and 31(24,41)min,respectively,both significantly lower than the 46(38,58)min in group A(P<0.001);the median DCT were both 13 min in group B1 and B2 lower than 17min in group A(P<0.001);the median CTA were 12 min in Group B1 and 9 min in Group B2 lower than 14 min in group A(P<0.001);similar results were observed during the neurology consultation to obtain consent for IVT and CNT.Compared with group A,the proportion of DCT
20 min,15 min,and 10 min was higher in groups B1 and B2(P<0.05),and the same result was observed at DNT
60 min,45 min,and 30 min(P<0.05).However,the additional incentive policy did not significantly differ between Group B2 and Group B1.Conclusions:Optimizing IVT therapy for ischemic stroke is a feasible approach to limit the DNT to 30 min in ischemic stroke,significantly reducing delays within the therapeutic window and increasing the number of patients meeting target time segments.Additionally,generating a timeline for the IVT therapy process by scanning positioning quick response codes was a significant breakthrough in achieving the informatization of IVT quality management for stroke.

Atrioventricular block complicating inferior acute myocardial infarction treated with thrombolytic therapy

Objective To investigate the influence and mechanism of incidence of atrioventricular block (AVB) treated with thrombolytic therapy in acute inferior myocardial infarction (AIMI).Methods A total of 46 patients with AIMI were divided into the thrombolytic group (n = 23) and the nonthrornboytic group (n = 23). Intravenous or intracoronary urokinase was given to the former group. We observed the advancing courses of AVB, and further assessed the relationship between occurrence of AVB and stenosis of infarct-related artery (IRA) with coronary angiography.Results Two cases died of Ⅲ o AVB in the non-thrombolytic group, but none was found in the thrombolytic group. The occurrence rate of AVB was similar in both groups; but that of Ⅲ ° AVB was much lower in the thrombolytic group (4 cases) than that in the non-thrombolytic group (11 cases, P ＜ 0.05), and the duration of AVB decreased from 201 ± 113 hours to 102±60 hours after thrombolytic therapy ( P＜0.01 ),which was mainly due to the decrease of AVB in the vanishing interval, but not in the developing interval.The coronary angiography demonstrated that there were an increasing reperfusion flow and a decreasing coronary stenosis of the infarct-related artery after thrombolytic therapy.Conclusion Thrombolytic therapy can reduce the incidence of severe AVB, shorten its duration and decrease the mortality by increasing the coronary reperfusion flow in the patients with AIMI.

A Self-Healing Optoacoustic Patch with High Damage Threshold and Conversion Efficiency for Biomedical Applications

Compared with traditional piezoelectric ultrasonic devices,optoacoustic devices have unique advantages such as a simple preparation process,anti-electromagnetic interference,and wireless long-distance power supply.However,current optoacoustic devices remain limited due to a low damage threshold and energy conversion efficiency,which seriously hinder their widespread applications.In this study,using a self-healing polydimethylsiloxane(PDMS,Fe-Hpdca-PDMS)and carbon nanotube composite,a flexible optoacoustic patch is developed,which possesses the self-healing capability at room temperature,and can even recover from damage induced by cutting or laser irradiation.Moreover,this patch can generate high-intensity ultrasound(>25 MPa)without the focusing structure.The laser damage threshold is greater than 183.44 mJ cm^(-2),and the optoacoustic energy conversion efficiency reaches a major achievement at 10.66×10^(-3),compared with other carbon-based nanomaterials and PDMS composites.This patch is also been successfully examined in the application of acoustic flow,thrombolysis,and wireless energy harvesting.All findings in this study provides new insight into designing and fabricating of novel ultrasound devices for biomedical applications.

Stroke:Evolution of newer treatment modalities for acute ischemic stroke

Acute ischemic stroke is one of the leading causes of morbidity and mortality worldwide.Restoration of cerebral blood flow to affected ischemic areas has been the cornerstone of therapy for patients for eligible patients as early diagnosis and treatment have shown improved outcomes.However,there has been a paradigm shift in the management approach over the last decade,and with the emphasis currently directed toward including newer modalities such as neuroprotection,stem cell treatment,magnetic stimulation,anti-apoptotic drugs,delayed recanali-zation,and utilization of artificial intelligence for early diagnosis and suggesting algorithm-based management protocols.

Evolving of treatment options for cerebral infarction

In this editorial,we comment on a recent article which addressed the therapeutic effect of aspirin plus edaravone in patients with cerebral infarction(CI).Herein,we outline the progress in therapy of CI.Apart from thrombolysis,aspirin is the most effective treatment for CI.Edaravone,a free radical scavenger,reduces endothelial cell damage and delays neuronal cell death.Aspirin plus edaravone mitigates damage to brain tissue by different mechanisms,thereby expediting the reinstation of neurological function.However,the nephrotoxic effect of edaravone,along with gastrointestinal bleeding associated with aspirin,may restrict this combination therapy.Although clinical studies have demonstrated the efficacy of thrombolytic therapy and mechanical thrombectomy,patients receiving these treatments experience modest efficacy and many adverse events.Moreover,interest in exploring natural medicines for CI is increasing,and they appear to have a high potential to protect against CI.The evolution of therapeutic strategies is expected to improve clinical outcomes of patients with CI.

Design, preparation and activity evaluation of novel recombinant thrombolytic proteins

Recombinant tissue plasminogen activator （rPA） has been used as a thrombolytic agent. However, considerable improvements have been done to prolong its plasma half-life （tl/2） and reduce its side effects, such as intracranial hemorrhage. Based on these improvements, a mutant ofrPA, mrPA, was designed by mutating its PAI-1 binding site to extend its tl/2. Furthermore, a fusion protein conjugating mrPA with NR3 was designed, which was a rAcAp5 mutant with a platelet GPIIb/IIIa-binding RGD motif, to enhance the ability of targeted-thrombus and thrombolysis. The synthesized DNA sequences coding the two proteins were amplified by PCR, cloned into pET30a to construct recombinant plasmids pET30a-mrPA and pET30a-mrPA-NR3, and transformed into E. coli BL21 （DE3）. The two proteins were expressed in inclusion bodies induced by isopropy113-D-1-thiogalactopyranoside. After purified to qualified purity using one-step Ni affinity chromatography, the denatured proteins were refolded by dialysis. Their thrombolytic effects in vitro and in vivo were evaluated. In vitro 3.5 and 7 pmol/L of mrPA significantly reduced thrombus weight; 1.75, 3.5 and 7 ~tmol/L of mrPA-NR3 also significantly reduced the thrombus weight, and mrPA-NR3 displayed stronger thrombolytic effects than mrPA at 7 lamol/L. In vivo both mrPA and mrPA-NR3 showed significantly thrombolytic effect at 60-240 ktmol/kg in thrombolytic model of inferior vena cava. Importantly, mrPA-NR3 exhibited more potent thrombolytic effect than both mrPA and rhM-tPA （positive control） at 240 p.mol/kg. In addition, these two novel proteins did not increase bleeding time while they exerted thrombolytic effect. In conclusion, we engineered two novel proteins and proved that fusion protein had better thrombolytic effect than non-fusion protein, and the results suggest that dual thrombolytic mechanism or thrombus-target potentiated the thrombolytic effect ofrPA and alleviated hemorrhage side reaction. This study may shed light on the development of novel thrombolytic agents with targeted thrombolysis and reduced side effects.

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

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. Selective ET-1R antagonists may be beneficial to the treatment of APTE, particularly when used in combination with a thrombolytic agent.

Predictors of long-term clinical outcome of patients with acute massive pulmonary embolism after thrombolytic therapy

To assess the in-hospital clinical course and the long-term evolution of acute massive pulmonary embolism after thrombolytic therapy and to identify predictors of adverse clinical outcome Methods A total of 260 patients hospitalized from January 1989 to October 1998 were retrospectively reviewed and followed up for 3 9 to 8 4 years Baseline characteristics and variables pre- and post-thrombolysis were identified Particular attention was paid to the clinical events, including death, recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, and major bleeding attributable to the use of anticoagulants Kaplan-Meier event-free survival curves were generated Univariate analysis by means of the log-rank test was used to test each candidate variable for association with clinical outcome Multivariate analysis with the Cox proportional hazard model was used to determine independent predictors of the long-term outcome Results The in-hospital mortality rate was 8 5%, with 68 2% due to pulmonary embolism itself, and the follow-up mortality rate was 31 7%, with 29 2% due to recurrent embolism Factors associated with an adverse outcome in univariate analysis were: (1) prior thromboembolic diseases; (2) duration of anticoagulant therapy <6 months; (3) inferior vena caval filter placement; (4) acute right ventricular dysfunction/dilation detected echocardiographically after thrombolysis; (5) Doppler recording of pulmonary artery systolic pressure >50 mmHg after thrombolysis; and (6) greater than 30% obstruction of pulmonary vasculature identified by pulmonary ventilation/perfusion scintigraphy before hospital discharge Multivariate analysis identified three independent predictors of poor long-term outcome for patients with acute massive pulmonary embolism after thrombolysis; which were: (1) Doppler recording of pulmonary artery systolic pressure >50 mm Hg, with relative risk of 3 78 and a 95% confidence interval of 2 70 to 4 86; (2) echocardiographic evidence of right ventricular dysfunction/dilatation (relative risk: 2 18; 95% confidence interval: 1 48 to 2 88); and (3) greater than 30% obstruction of pulmonary vasculature documented by lung scan (relative risk: 1 99; 95% confidence interval: 1 25 to 2 70) Conclusion The study showed that Doppler echocardiographic assessments after thrombolytic therapy and ventilation/perfusion scintigraphy prior to hospital discharge are valuable to establishment of new baseline characteristics, which is informative for risk stratification and prognostication of the long-term outcome for patients with acute massive pulmonary embolism

Thrombolytic therapy for femoral artery thrombosis after left cardiac catheterization in children

Background Femoral artery thrombosis is one of the most common complications of catheterizations in infants and young children. This study was conducted to investigate the feasibility and effectiveness of thrombolytic therapy for femoral artery thrombosis after left cardiac catheterization in children. Methods Thrombolytic therapy with urokinase was carried out in children with femoral artery thrombosis after left cardiac catheterization. Each patient was given a bolus injection of heparin （100 U/kg）. A bolus of urokinase （30 000 - 100 000 U） was injected intravenously, and then a continuous infusion of 10 000-50 000 U/h was administered. Transcatheter thrombolysis was performed once previous procedures failed. Results Eight patients （aged （3.1±2.3） years （8 months to 7 years）, body weight （13.1±4.2） kg （7 to 20 kg）） presented lower limbs ischemia after left cardiac catheterizations was performed. Seven patients accepted thrombolytic therapy with urokinase. In 5 patients, peripheral intravenous thrombolysis was successful with restoration of a normal pulse. In the other 3 cases, peripheral intravenous thrombolysis failed, followed by successful transcatheter thrombolysis. The average duration of therapy was （7.25±5.31） hours （1-17 hours）. The average doses of heparin and urokinase were （1600±723） U （800-3000 U） and （268 571±177 240） U （50 000-500 000 U）, respectively. There were no statistically significant differences in partial thromboplastin time before and during urokinase therapy （（40.6±22.3） to （49.9±39.2） seconds）. However, the prothrombin time was significantly longer （（12.7±2.58） to （48.1±18.6） seconds, P〈0.05）. Patency of the target vessel was evaluated in all the patients for 2 weeks and no occlusion recurred. Conclusion Thrombolytic therapy with urokinase is a safe and useful modality in children with femoral artery thrombosis after left cardiac catheterization.

Translational initiatives in thrombolytic therapy

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.

Starting thrombolytic therapy for patients with acute myocardial infarction in Accident and Emergency Department:from implementation to evaluation

Objective To evaluate the effectiveness of initiating thrombolysis for patients with acute myocardial infarction (AMI) in the Accident and Emergency Department. Methods From January 1993 to December 1995, all AMI patients who were admitted to the United Christian Hospital and given thrombolytic therapy were studied. The patients' demographic data, time and mode of presentation, site of myocardial infarction, treatment modality and timing, and complications related to AMI or treatment were recorded prospectively in our AMI database. The frequency of thrombolysis administered in Accident and Emergency Department and Coronary Care Unit, as well as the median door-to-needle time (time interval between hospital arrival to initiation of thrombolytic therapy) were compared. Cases of inappropriate thrombolysis and complication were also analyzed.Results Over these 3 years, 257 patients received thrombolysis in the United Christian Hospital. The percentage of patients receiving thrombolysis in Accident and Emergency Department increased from 3.2% in 1993 to 12.3% in 1994, and to 39.4% in 1995. The median time interval between arrival to hospital and thrombolysis (door-to-needle time) was 25 minutes, compared with 81 minutes in the Coronary Care Unit. The door-to-needle time also improved over these 3 years: from 95 minutes in 1993 to 75 minutes in 1995 in Coronary Care Unit group, and from 35 minutes in 1993 to 20 minutes in 1995 in the Accident and Emergency Department group. Over these 3 years, 2 cases of inappropriate thrombolysis were reported but these did not result in any mortality. Four complications from thrombolytic therapy were reported, and these were managed appropriately by the staff in Accident and Emergency Department and did not result in mortality. Conclusions Starting thrombolytic therapy in Accident and Emergency Department is safe and effectively decreases the door-to-needle time.