Urokinase Group Research Articles

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study

ObjectiveTo analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome.MethodsA total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children’s Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded.ResultsA total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group.ConclusionThe rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Ultrasound combined with urokinase under key-shaped bone window enhances blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage.

Minimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage. The blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group. A total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342). Our study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results.

Intrapleural Instillation of Sodium Bicarbonate versus Urokinase in Management of Complicated Pleural Effusion: A Comparative Cohort Study.

The main target is evacuation; however, with evidence about the value of intrapleural instillation of different fibrinolytic agents still under evaluation, our aim was comparing the effectiveness and safety of intrapleural instillation of sodium bicarbonate (NaHCO3) in comparison with urokinase in patients with infected pleural effusion. Our prospective cohort study included 40 patients with complicated empyema; the diagnosis was based on analysis of aspirated fluid in association with radiological and bacteriological culture. The patients were subjected to instillation of two different fibrinolytic agents; the first one was NaHCO3, the second was urokinase. The commonest underlying chest infection that was visualized by CT was pneumonia 70%. Nearly half of cases had community-acquired infection (45%), and more than half of them (55%) had anaerobic infection, and only five cases had TB pleural effusion based on ADA-positive, tuberculin skin test in addition to Abram's needles closed biopsy. The rate of repeated therapeutic thoracentesis success in each group was 85%; 80% in NaHCO3 group, and 90% in urokinase group, both of them was significantly equal, P=0.37. Moreover, the frequency of complications in all patients was less than 13%, hence hemothorax and iatrogenic pneumothorax was 12.5%, and only 10% of cases were admitted in ICU after the maneuver, with insignificant difference in between the groups. However, looking at the smaller rate of RTT failure of NaHCO3 or urokinase, the logistic regression model showed that RTT-NaHCO3 was insignificantly related to failure in both unadjusted and adjusted models, P=0.37 and 0.32, respectively, and only smoking habits increase the likelihood of failure 9-fold (OR=8.9, P=0.04) with respect to age, sex, and treatment methods. The efficacy of repeated therapeutic thoracentesis (RTT) with intrapleural instillation of NaHCO3 was effective and safe, the same as urokinase, with consideration that NaHCO3 was much more available and affordable than urokinase.

Urokinase Regulates Heat Shock Protein 27 to Treat Chronic Glaucoma Rats

This study explored urokinase’s effect on the production of heat shock protein 27 in chronic glaucoma rats. 45 SD rats were equally assigned into healthy group, glaucoma group, and urokinase group followed by analysis of intraocular pressure by TONO-PENAVVI tonometer, apoptosis of retinal ganglion cells by TUNEL staining, pathological morphology by H&amp;E staining, levels of SOD, MDA, and NO as well as the expression of HSP27 and p-p38MAPK. After treatment, the intraocular pressure was increased in glaucoma group and decreased in urokinase group (P &lt; 0.05). In addition, glaucoma group showed significantly increased apoptosis rate (P &lt; 0.05) which was decreased in urokinase group (P &lt; 0.05). In glaucoma group, the nerve fibers were disorderly arranged and ganglion cells were greatly reduced which were improved in urokinase group. Compared to healthy group, glaucoma group had lower MDA level and higher SOD levels (P &lt; 0.05) which were reversed in urokinase group (P &lt; 0.05). HSP27 and P-P38MAPK levels in glaucoma group were higher than healthy group (P &lt; 0.05) and urokinase group (P &lt; 0.05). In conclusion, urokinase can reduce the apoptosis of retinal ganglion cells in glaucoma rats and protect the function of the optic nerve by reducing the level of HSP27.

Comparison of Streptokinase and Urokinase for Thrombolysis in Blocked Tunnel Cuffed Catheter Among the Patients of Chronic Renal Failure Undergoing Hemodialysis

Objective: To compare the efficacy of Streptokinase and Urokinase for thrombolysis in blocked tunnel cuffed catheter among the patients with chronic renal failure undergoing hemodialysis.&#x0D; Study Design: Comparative prospective study.&#x0D; Place and Duration of Study: Department of nephrology Pak Emirates Military Hospital Rawalpindi Pakistan, from Aug 2019 to Mar 2020.&#x0D; Methodology: A total of 100 cases were included in the study which was undergoing hemodialysis in the nephrology department and had a poorly functioning or blocked tunnel cuffed catheter. These patients were either given Urokinase or Streptokinase in standard doses for thrombolysis. The lottery method was used to designate the patient either in the Streptokinase or Urokinase groups. The primary endpoint was the resolution of blocking and regain of proper functioning of the catheter.&#x0D; Results: In our study, 54 (54%) patients were males, and 46 (46%) were females. The mean age of the study participants was 44.63 ± 3.782 years, and the mean duration of chronic kidney disease was 2.19 ± 6.814 years. 43 (43%) patients were given Urokinase, while 57 (57%) were given Streptokinase. After applying the logistic regression, we found that the use of Streptokinase had a significant association with the resolution of blocking and regain of proper functioning of the catheter compared to the use of Urokinase.&#x0D; Conclusion: This study concluded that most catheters regain the proper functioning after thrombolysis with either Urokinase or Streptokinase. However, Streptokinase emerged as a better agent for this purpose in our study.

Local Intra-arterial Thrombolysis during Mechanical Thrombectomy for Refractory Large-Vessel Occlusion: Adjunctive Chemical Enhancer of Thrombectomy.

Data on adjunctive intra-arterial thrombolysis during mechanical thrombectomy for refractory thrombus are sparse. The aim of this study was to evaluate the efficacy and safety of local intra-arterial urokinase as an adjunct to mechanical thrombectomy for refractory large-vessel occlusion. We retrospectively evaluated patients with acute ischemic stroke who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion between January 2016 and December 2019. Patients were divided into 2 groups based on the use of intra-arterial urokinase as an adjunctive therapy during mechanical thrombectomy for refractory thrombus: the urokinase and nonurokinase groups. Herein, refractory thrombus was defined as the target occlusion with minimal reperfusion (TICI 0 or 1) despite >3 attempts with conventional mechanical thrombectomy. The baseline characteristics, procedural outcomes, and clinical outcome were compared between the 2 groups. One hundred fourteen cases of refractory thrombus were identified. A total of 45 and 69 patients were in the urokinase and the nonurokinase groups, respectively. The urokinase group compared with the nonurokinase group showed a higher rate of successful reperfusion (82.2% versus 63.8%, P = .034), with lower procedural times (54 versus 69 minutes, P = .137). The rates of good clinical outcome, distal embolism, and symptomatic intracranial hemorrhage were similar between the 2 groups. The use of intra-arterial urokinase (OR = 3.682; 95% CI, 1.156-11.730; P = .027) was an independent predictor of successful reperfusion. The use of local intra-arterial urokinase as an adjunct to mechanical thrombectomy may be an effective and safe method that provides better recanalization than the conventional mechanical thrombectomy for refractory thrombus in patients with embolic large-vessel occlusion.

Fibrinolysis with Lower Dose Urokinase in Patients with Complicated Parapneumonic Effusion.

BackgroundIntrapleural urokinase is one of the most widely used fibrinolytic agents in the treatment of complicated parapneumonic effusion (CPPE). However, little research has been performed on the optimal urokinase dosage. The aim of this study was to evaluate the treatment efficacy of half dose urokinase compared with conventional dose urokinase.MethodsWe retrospectively enrolled 92 patients with CPPE or empyema who underwent intrapleural urokinase treatment at two tertiary hospitals. Patients received antibiotics, chest tube drainage, and other treatments as part of routine care. The primary outcome was the treatment success rate in the half dose urokinase group (50,000 IU daily for maximal 6 days) and the conventional dose urokinase group (100,000 IU daily). Treatment success was defined as clinical and radiological improvements without surgical treatment or re-admission within one month.ResultsForty-four patients received half dose urokinase, whereas 48 patients were treated with conventional dose urokinase. Both groups were relatively well matched at baseline, excluding higher serum white blood cell count and higher empyema prevalence in the half dose urokinase group. The treatment success rate was not different between the two groups (p=0.048). There were no differences in the rate of in-hospital death and surgical treatment, hospitalization duration, and indwelling catheter duration. In the multivariate analysis, urokinase dose was not a predictor of treatment success.ConclusionHalf dose intrapleural urokinase is equally effective conventional dose urokinase in treating patients with CPPE or empyema.

Heron-mouth neuroendoscopic sheath-assisted neuroendoscopy plays critical roles in treating hypertensive intraventricular hemorrhage.

IntroductionNeuroendoscopy is widely applied for treating hypertensive intracerebral hemorrhage.AimTo explore the effects of heron-mouth neuroendoscopic sheath-assisted neuroendoscopy on treatment of hypertensive intraventricular hemorrhage.Material and methodsA type of heron-mouth neuroendoscopic sheath combining the advantages of minimally invasive columnar endoscopic sheath and open operation methods was designed. The end of sheath catheter could be dilated if necessary, without increasing risk of cortex injury. Heron-mouth neuroendoscopic sheath-assisted neuroendoscopy was applied in treatment of hypertensive intraventricular hemorrhage. A total of 19 patients with hypertensive intraventricular hemorrhage were selected and divided into an external ventricular drainage + urokinase group and a neuroendoscopy group. Hematoma clearance rate, surgical time, ventricular drainage time, intracranial infection, hydrocephalus and Glasgow Outcome Score (GOS) at 3 months after the operation were compared between two groups.ResultsHematoma clearance rate, ventricular drainage time, mortality rate and GOS at 3 months after surgery in the neuroendoscopy group were significantly better compared to those in the external ventricular drainage + urokinase group (p < 0.05). Postoperative complications, including intracranial infection hydrocephalus and pulmonary infection in the neuroendoscopy group, were less numerous compared to those in the external ventricular drainage + urokinase group, but without statistical significance (p > 0.05). However, surgical time was significantly longer in the neuroendoscopy group compared to that in the external ventricular drainage + urokinase group (p < 0.05). There was no significant difference in incidence rate of hydrocephalus between the two groups (p > 0.05).ConclusionsClinical effects of heron-mouth neuroendoscopic sheath-assisted neuroendoscopy were better than those of external ventricular drainage combining urokinase dissolution in treating hypertensive intraventricular hemorrhage.

A thrombolytic therapy using diagnostic ultrasound combined with RGDS-targeted microbubbles and urokinase in a rabbit model

This study aimed to explore thrombolysis therapy based on ultrasound combined with urokinase and Arg–Gly–Asp sequence (RGDS)-targeted microbubbles by evaluating the histological changes in a thrombotic rabbit model. Forty-two New Zealand rabbits featuring platelet-rich thrombi in the femoral artery were randomized to (n = 6/group): ultrasound alone (US); urokinase alone (UK); ultrasound plus non-targeted microbubbles (US + M); ultrasound plus RGDS-targeted microbubbles (US + R); RGDS-targeted microbubbles plus urokinase (R + UK); ultrasound, non-targeted microbubbles and urokinase (US + M + UK); and ultrasound, RGDS-targeted microbubbles and urokinase (US + R + UK) groups. Diagnostic ultrasound was used transcutaneously over the thrombus for 30 min. We evaluated the thrombolytic effect based on ultrasound thrombi detection, blood flow, and histological observations. Among all study groups, complete recanalization was achieved in the US + R + UK group. Hematoxylin and eosin staining showed that the thrombi were completely dissolved. Scanning electron microscopy examination demonstrated that the fiber network structure of the thrombi was damaged. Transmission electron microscopy showed that the thrombus was decomposed into high electron-dense particles. Histology for von Willebrand factor and tissue factor were both negative in the US + R + UK group. This study revealed that a thrombolytic therapy consisting of diagnostic ultrasound together with RGDS-targeted and urokinase coupled microbubbles.

Long-term outcome of patients with ST-segment elevation myocardial infarction treated with low-dose intracoronary thrombolysis during primary percutaneous coronary intervention: the 5-year results of the DISSOLUTION Trial.

We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47). After PCI, a greater proportion of patients receiving urokinase had an improvement in myocardial perfusion, as indicated by a significantly higher final Thrombolysis in myocardial infarction (TIMI) grade 3, myocardial blush grade, and 60-min ST-segment resolution > 70%, as well as lower corrected TIMI frame count. At 1-year echocardiography, urokinase-treated patients exhibited significantly lower LV dimension, as well as higher LV ejection fraction and wall motion score index as compared with placebo-treated patients. At 5years, major acute cardiovascular events (MACEs) were significantly less common in the urokinase group (P = 0.023), mainly due to a lower occurrence of hospitalisation for heart failure (P = 0.038). Multivariate analysis showed that factors independently associated with 5-year occurrence of MACEs were LV remodelling at 1-year echocardiography (P = 0.0001), 1-year LV ejection fraction (P = 0.0001), TIMI grade flow 0-2 (P = 0.0019), and age at time of PCI (P = 0.0173). In conclusion, low-dose intracoronary urokinase during primary PCI is associated with a more favourable 5-year outcome of patients with STEMI.

Comparison of urokinase and reteplase thrombolytic treatment in patients with high-risk pulmonary embolism.

Thrombolytic treatment is recommended for patients with high-risk pulmonary embolism. The present study compared thrombolytic therapy with urokinase and reteplase. A total of 37 patients presenting with acute high-risk pulmonary embolism at the Intensive Care Unit of Weinan Central Hospital of Shaanxi Province (Weinan, China) between June 2013 and January 2017 were retrospectively analyzed. According to their treatment, these subjects were assigned to the reteplase group (n=16) or the urokinase group (n=21). Systolic blood pressure (SBP), heart rate (HR) and respiratory rate (RR) were recorded prior to, and at 2, 4, 24 and 48 h after thrombolytic therapy. Complications, including bleeding, were closely monitored. Changes in blood gas analysis, troponin-T (TNT), pro-B-type natriuretic peptide (pro-BNP) and D-dimer (D-D) were observed. In the reteplase and urokinase group, 11 and 13 cases exhibited marked improvement, treatment was rated as effective in 4 and 6 cases, and 1 and 2 mortalities occurred, resulting in an overall effective rate of 93.8 and 90.5%, respectively (P>0.05). In the reteplase group, one patient was unsuccessfully resuscitated and died. In the urokinase group, one patient died of gastric hemorrhage after 22 h of thrombolysis, while another patient died of brain failure resuscitation. The treatment improved the SBP in each of the two groups (P<0.05), and this outcome was similar between these two groups (P>0.05). HR and RR were similar prior to and after thrombolytic therapy (P>0.05). In contrast to the urokinase group, TNT was significantly decreased after thrombolyis compared with the baseline in the reteplase group. Complications in the reteplase group were higher, but in contrast to the urokinase group, no life-threatening bleeding occurred. Although reteplase is as effective as urokinase in treating high-risk pulmonary embolism, reteplase may reduce myocardial damage.

Curative effect of minimally invasive puncture and drainage assisted with alteplase on treatment of acute intracerebral hemorrhage

Objective: To investigate the different effects on evacuation of hematoma, the severity of nerve injury, inflammatory reaction and oxidative stress response in the treatment of acute intracerebral hemorrhage by using minimally invasive puncture and drainage assisted with alteplase or urokinase. Methods: A total of 114 patients with acute intracerebral hemorrhage treated with minimally invasive puncture and drainage in our hospital from May 2012 to October 2015 were retrospectively analyzed and divided into alteplase group and urokinase group, which received adjuvant therapy with alteplase and urokinase, respectively. Before and after treatment, CT was used for scanning, and the volume of hematoma and edema and the distance of midline shift were examined. After treatment, serum was collected for detecting the contents of molecular markers of nerve injury, inflammatory reaction and oxidative stress response. Results: On the 3rd day after treatment, the volume of hematoma and edema and the distance of midline shift in minimally invasive group were significantly lower than those of craniotomy group, and incidence of intracranial infection was lower than that of craniotomy group. There was no significant difference of rebleeding incidence compared to craniotomy group. The serum contents of osteopontin, S100β, glial fibrillary acidic protein, neuron-specific enolase, myelin basic protein, neuropeptide Y, ischemia modified albumin, tumor necrosis factor alpha, interleukin-1β, interleukin-6, interleukin-8, soluble intercellular adhesion molecule-1, high- mobility group protein 1, malonaldehyde, advanced oxidation protein products and 8-hydroxy- 2'-deoxyguanosine urine of patients from alteplase group were significantly lower than those of urokinase group. The content of total antioxidant capacity was obviously higher than that of urokinase group. Conclusions: As for the effect on evacuation of hematoma and also the ameliorative effect on nerve injury, inflammatory reaction and oxidative stress response in treatment of acute intracerebral hemorrhage, minimally invasive puncture and drainage assisted with alteplase was superior to adjuvant therapy with urokinase.

The expression of von willebrand factor(vWF) and tissue factor(TF) in ultrasound combined with urokinase and RGDS-targeted microbubbles for recanalization of occluded rabbit femoral artery

Objective To explore the express of von willebrand factor(vWF) and tissue factor(TF) in ultrasound combined with urokinase and RGDS-targeted microbubbles for recanalization of occluded rabbit femoral artery. Methods A total of 42 rabbits with platelet-rich thrombi in the femoral artery were randomized into 7 treatment groups (n=6 in each group): ①ultrasound alone (US) group; ②ultrasound, non-targeted microbubbles (US+ M) group; ③urokinase alone (UK) group; ④ultrasound, non-targeted microbubble and urokinase (US+ M+ UK) group; ⑤ultrasound, platelet-targeted microbubble (US+ R) group; ⑥platelet-targeted microbubble, urokinase (R+ UK) group; ⑦ultrasound, platelet-targeted microbubble and urokinase (US+ R+ UK) group. A total of 6 ml of infusion liquor of urokinase, RGDS and microbubbles (SonoVue) were mixed by the direct conjugation method, infusion via vein within 20 min. Ultrasound was conducted to lyse the clot for 30 min. The recanalization and the velocity tracing change of blood flow in thrombolytic process and the express of vWF and TF were evaluated at 120 min post treatment. Results For US, UK, US+ M, US+ R and US+ M+ UK groups, recanalization were failed. The R+ UK and US+ R+ UK groups were partly recanalizated or completed recanalized (P<0.001). vWF and TF were positive in US, US+ M, US+ R and R+ UK group. vWF and TF were negative in US+ M+ UK, UK and US+ R+ UK groups. Conclusions The combined effects of low frequency ultrasound and targeted microbubble combined with urokinase can inhibit the expression of vWF and TF, and then promote the thrombolysis, however it can affect the expression of vWF and TF after reperfusion. Key words: Ultrasonography; Targeted microbubbles; Thrombolytic therapy

Tirofiban combined with urokinase selective intra-arterial thrombolysis for the treatment of middle cerebral artery occlusion.

The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group). The recanalization rate, relative-apparent diffusion coefficient (rADC) and neurological function deficit score (NFDS) values were compared among the four groups. The recanalization rate, rADC and NFDS values were improved in the T + UK group compared with the other groups. In summary, the intra-arterial administration of tirofiban combined with urokinase thrombolysis was a more effective intervention in an MCAO model compared with intra-arterial urokinase alone, and may promote reperfusion and reduce infarct volume.

Treatment of free-flowing tuberculous pleurisy with intrapleural urokinase.

Patients with loculated tuberculous pleurisy (TBP) treated with urokinase suffer less from residual pleural thickening (RPT) than those treated with simple drainage. However, the role of intrapleural urokinase in free-flowing TBP patients remains unclear. A total of 318 patients with presumed TBP were screened. The final 171 patients who participated in the study were randomly allocated to the urokinase group (n = 86) and the control group (n = 85). Personalised doses of urokinase were infused via a catheter. This procedure was repeated every 24 h until the volume of pleural fluid obtained was less than 50 ml after three injections. Changes in lung function and pleural thickening were recorded and compared between both groups periodically for 24 weeks. Seven patients (9.1%) had restrictive functional sequelae in the control group, while no patient in the urokinase group suffered from sequelae (P < 0.05). The incidence of RPT (⩾10 mm) was 0 for the urokinase group and 9.1% for the control group (P < 0.05). A lower percentage of patients treated with intrapleural urokinase had blunted costophrenic angle than controls (5.1% vs.19.5%, P < 0.05). Patients with free-flowing TBP treated with urokinase suffered less from RPT than those treated with drainage.

Clinical significance of vascular endothelial growth factor levels in bronchoalveolar lavage fluid of patients with acute lung injury

Objective To test the levels of vascular endothelial growth factor (VEGF) in bronchoalveolar lavage fluid (BALF) during acute lung injury (ALI)/ acute respiratory distress syndome (ARDS) after the interference with anticoagulation and fibrinolytic in an attempt to find a possible treatment plan for ALI/ARDS. Methods Oleic acid-induced ALI models were used in this study. A total of 96 rats were randomly assigned oleic acid group, salvianolate group, urokinase group, and saline group according to the random number table, with 24 animals per group. In oleic acid group, oleic acid (0.2 ml/kg, caudally) was administered alone. In addition to the oleic acid, the rats in salvianolate and urokinase groups received caudal injection with 10 ml/kg of 0.06% salvianolate and 5, 000 U/kg of urokinase respectively. In saline group, saline solution with an equal volume of oleic acid was caudally administered alone. Effect of the early use of salvianolate and urokinase on levels of VEGF in BALF was measured. Clinically, patients with ALI/ARDS composing survivor and death groups were enrolled and assessed by acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and multiple organ dysfunction syndrome (MODS) score. Besides, healthy population was included as the controls to comparatively analyze the levels of VEGF in BALF in ALI/ARDS group. Results Of the rat models of ALI, early use of salvianolate or urokinase was associated with elevated level of VEGF in BALF(P<0.05), which subsequently attenuated the lung injury. In the clinical research, it was found that the level of VEGF in BALF in ALI/ARDS group was much lower than that in control group [(45.9±5.7)pg/ml vs (60.6±4.5)pg/ml] (P<0.01). The level of VEGF in BALF was negatively correlated with APACHEⅡor MODS scores(r=-0.542, -0.659, P<0.01). Moreover, patients in death group appeared lower VEGF level in BALF than those in survivor group(t=2.68, P<0.05). Conclusion VEGF level in BALF can be taken as an indicator of patient condition and outcome. Early use of anticoagulation or thrombolytic drugs may play a positive role on patients with ALI/ARDS. Key words: Acute lung injury; Vascular endothelial growth factors; Salvia miltiorrhiza; Urokinase

Initial treatment of septated parapneumonic empyema with drainage plus fibrinolytic agents is equally effective as video-assisted thoracoscopic surgery, and is suitable as first-line therapy.

It is thought that 0.6-2% of cases of pneumonia in children are complicated by parapneumonic empyema. The mainstay treatment options for empyema are pleural chest drainage plus fibrinolysis or video-assisted thoracoscopic surgery (VATS). Marhuenda et al. reported the results of a prospective, multicenter, clinical trial in which patients with parapneumonic empyema were randomized to either drainage plus urokinase or to VATS. That showed that the median postoperative stay, median hospital stay, and number of febrile days after treatment were not significantly different between the VATS group and the urokinase group. Only three other prospective randomized trials have been conducted with the same objective. The results in these studies had partially different among four trials. But all studies described that it is apparent that VATS is not more effective than fibrinolytic treatment. Intrapleural fibrinolytic treatment, which is much less invasive and lower inexpensive than VATS, is an effective and safe alternative to surgical treatment of complicated empyema. VATS would be reserved for patients who fail to respond to chemical/enzymatic debridement. We need additional randomized controlled trials with relevant inclusion/exclusion criteria and adequate sample sizes to determine the optimal therapy for parapneumonic-complicated empyema in children.

VATS or urokinase for treatment of empyema?

This randomized, multicenter clinical trial enrolled 103 children hospitalized with septated parapneumonic empyema (PPE) who were randomized to receive thoracoscopy (n=53) or urokinase (n=50). The main outcome variable was the length of hospital stay after treatment. The secondary outcomes were total length of hospital stay, number of days with the chest drain, number of days with fever, and treatment failures. No statistically significant differences were found between thoracoscopy and urokinase in the median postoperative stay (10 vs 9 days), median hospital stay (14 vs 13 days), or days febrile after treatment (4 vs 6 days). A second intervention was required in 15% of children in the thoracoscopy group versus 10% in the urokinase group (P = 0.47). The authors concluded that drainage plus urokinase instillation is as effective as video-assisted thoracoscopic surgery as first-line treatment of septated PPE in children.

Pro-urokinase promotes angiogenesis but does not reduce neuronal apoptosis in infarcted cerebral tissue.

Ischemic stroke is most commonly caused by vascular occlusion due to thrombosis or arterial embolism. Recently, thrombolysis has been used with increasing frequency for the treatment of acute ischemic stroke. Among the drugs used for thrombolysis, only recombinant tissue plasminogen activator is widely accepted internationally (Albers et al., 2008). In China, urokinase has been widely used for thrombolysis after acute ischemic stroke. Pro-urokinase is the precursor of urokinase. Compared with urokinase, pro-urokinase has greater ability to dissolve thrombus and is safer to use. A previous study found that the recanalization rate was significantly higher after arterial thrombolysis with pro-urokinase than with recombinant tissue plasminogen activator (Fischer et al., 2005). This study compared the thrombolytic effects of pro-urokinase, recombinant tissue plasminogen activator, and urokinase in a dog model of acute cerebral embolism. For each dog used, 10 mL of arterial blood was taken and placed at room temperature for 3 hours to allow natural consolidation. Blood clots were then pressed into a 2-mm diameter cylinder and cut into 2–3 mm lengths. After general anesthesia, dogs were fixed on an operating table and the trachea was intubated. A 5F sheathing canal was placed in the right femoral artery using a modified Seldinger method (Marx et al., 1996). The sheathing canal was advanced into the internal carotid artery guided by digital subtraction angiography. Vascular traveling to the anterior and middle cerebral arteries was observed in the anteroposterior view (Figure ​(Figure1A1A–C). A mixture of autologous blood clots and physiological saline was injected into the internal carotid artery using a 5 mL syringe. If no embolization was observed on digital subtraction angiography after the first injection of blood clots, the process was repeated (Takano et al., 1998; Oureshi et al., 2004; Harris et al., 2007). When anterior or middle cerebral artery embolization was confirmed, the sheathing canal was withdrawn. Digital subtraction angiography was repeated every 30 minutes for 3 hours to confirm embolization (Figure ​(Figure1D1D–F). Figure 1 Digital subtraction angiography images before and after treatment of acute cerebral embolism in dogs using pro-urokinase, recombinant tissue plasminogen activator, or urokinase. Stroke was successfully induced in 24 dogs. These 24 dogs were randomly divided into four groups: (1) Pro-urokinase group: 1.2 × 105 U/kg pro-urokinase was administered via the femoral vein. One-third of the pro-urokinase was dissolved in physiological saline and administered over 3 minutes, and the remainder was dissolved in 100 mL of physiological saline and administered over 30 minutes. (2) Recombinant tissue plasminogen activator group: 1.37 mg/kg of recombinant tissue plasminogen activator was administered via the femoral vein. One-tenth of the recombinant tissue plasminogen activator was administered over 1 minute, and the remainder was administered over 60 minutes. (3) Urokinase group: 2.15 × 106 U/kg urokinase was dissolved in 100 mL of physiological saline and administered by intravenous infusion over 30 minutes. (4) Model group: 100 mL of physiological saline was administered by intravenous infusion over 30 minutes. Digital subtraction angiography was performed every 30 minutes for 3 hours after thrombolysis. Based on assessment of the Thrombolysis In Myocardial Infarction flow grade, the recanalization rate was higher in the urokinase group than in the model group (Table 1, Figure ​Figure1G1G–U). Hematoxylin and eosin staining showed no hematoma in the infarcted area at 3 hours after thrombolysis in any of the groups, but nerve cells in the infarcted tissues showed degeneration, coagulative necrosis, vacuole-like structures, indistinct cell borders, and pyknotic or absent nuclei. In addition, the nerve cells and glial cells were obviously reduced in number or even absent. Infiltration of neutrophilic leukocytes and microglial proliferation or phagocytosis were observed in some regions. There were no obvious differences in cell apoptosis among the groups (Figure ​(Figure2A2A–E). Hemorrhage was observed in the infarcted area in one dog from each of the pro-urokinase and urokinase groups (Figure ​(Figure2F2F–H). Table 1 Effectiveness of pro-urokinase, recombinant tissue plasminogen activator, and urokinase for the treatment of acute cerebral embolism Figure 2 Histological findings in the area of cerebral infarction at 3 hours after thrombolysis (hematoxylin and eosin staining). Previous studies reported that patients who underwent thrombolysis over 3 hours had a high incidence of hemorrhage (Camerlingo et al., 2005). Obvious hematoma was not observed in this dog model of stroke because dogs have abundant collateral cerebrovascular circulation, resulting in a limited area of infarction, and thrombolysis was performed early. The results of this study show that recanalization after thromboembolism was similar after thrombolysis with pro-urokinase and recombinant tissue plasminogen activator, and that both these drugs were more effective than urokinase (both P < 0.05). However, pro-urokinase and recombinant tissue plasminogen activator did not have any definite protective effects against neuronal injury.

Effectiveness of papaverine cisternal irrigation for cerebral vasospasm after aneurysmal subarachnoid hemorrhage and measurement of biomarkers

Cisternal irrigation with thrombolytic agents was used to prevent post-SAH vasospasm, but its role remained inconclusive. To verify effectiveness of papaverine (PPV) in preventing vasospasm, we studied relationship between inflammatory biologic markers and vasospasm. This prospective study included 121 patients with clipped anterior circulation aneurysms that had ruptured, and 372 control patients. Patients were divided into three groups according to cisternal irrigation method: simple drain, papaverine group, and urokinase (UK) group. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in CSF and serum on days 3 and 7 after SAH. The PPV group showed similar incidence of vasospasm with UK group, but lower incidence than the simple drain group. The levels of ICAM-1 and VCAM-1 were significantly higher in the SAH group than in the control group. CSF and serum levels were more elevated on day 7 than day 3, and the degree of elevation were more marked when measured in the CSF than in the serum. However, there was no statistical difference between measured levels of ICAM-1 and VCAM-1, and vasospasm development. PPV cisternal irrigation was similarly effective as UK at preventing vasospasm. Although neither PPV nor UK irrigation could reduce the concentration of adhesion molecules compared with simple drain, we found levels of ICAM-1 and VCAM-1 were specifically elevated in the CSF. Therefore, further research should focus on anti-inflammation as a therapeutic target against cerebral vasospasm and on the CSF as the optimum place where such inflammatory action practically brought about.