ObjectiveTo investigate the therapeutic effect of kinetin on bleomycin A5 (BLM-A5)-induced pulmonary fibrosis in rats.
MethodsSixty female Wistar rats were randomly divided into three groups. Group A (n=20) was intratracheally injected with saline as control. Group B (n=20) were intratracheally injected with BLM-A5 to establish pulmonary fibrosis model. Group C (n=20) was intratracheally injected with BLM-A5 and received intraperitoneal injection of kinetin at 0.5 mL/100 g once daily. The rats were sacrificed on the 3rd,7th,14th and 28th day respectively. HE and Masson staining were performed to observe lung pathological changes. The contents of hydroxyproline (HYP),urokinase-type plasminogen activator (u-PA),tissue-type plasminogen activator (t-PA),and PAI-1 in lung and plasma were measured by ELISA.
ResultsAlveolitis was most obvious on the 7th day and pulmonary fibrosis was most severe on the 28th day in group B compared with other two groups (P<0.05). Alveolitis and pulmonary fibrosis in group C were significantly alleviated compared with group B (P<0.05),but still more severe than group A (P<0.05). The HYP contents in group B,coincided with fibrosis,began to increase on the 7th day and reached the peak on the 28th day,significantly higher than those in other two groups (P<0.05). The u-PA contents of lung tissue in group B began to decline on the 3rd day,reached the minimum on the 7th day,and was still significantly lower than those in other two groups (P<0.05).On the 14th day, the u-PA contents had no significant difference among three groups. The u-PA plasma contents in group B began to decline on the 3rd day,reached the minimum and had significant difference compared with other two groups on the 7th day (P<0.05),and there was no significantly difference among three groups after the 14th day. The t-PA contents change of lung tissue and plasma in three groups were generally consistent with u-PA,but the t-PA plasma contents in group B were still significantly lower than those in group A on the 14th day (P<0.05). The PAI-1 contents of lung tissue in group B began to increase on the 3rd day,reached the maximum on the 7th day,was still significantly higher than those in other two groups (P<0.05),and there was no significant difference among three groups on the 14th day. The PAI-1 contents in group C decreased compared with those in group B (P<0.05),but still higher than those in group A (P<0.05),and there was no difference among them on the 14th day. The PAI-1 plasma contents in group B began to increase on the 3rd day,reached the maximum and was significantly higher than other two groups on the 7th day (P<0.05),and there was no significant difference among three groups on the 14th day.
ConclusionThe contents of u-PA and t-PA are increased by inhibiting PAI-1 generation in lung tissue through kinetin treatment,so that,kinetin can suppress pulmonary fibrosis induced by BLM-A5.
Objective To assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke. Methods A systematic review of all the relevant randomized controlled trials (RCTs) was performed. RCTs were identified from the Cochrane Stroke Group trials register, Embase (1980 to 1997), handsearching Japanese and Chinese journals, and personal contact with pharmaceutical companies. We included randomised and quasi-randomised trials in patients with confirmed acute ischaemic stroke comparing different doses of a thrombolytic agent, or different thrombolytic agent, or the same agent given by different routes. Results Eight trials involving 1 334 patients were included. Concealment of allocation was generally adequate. All the trials were conducted in Japan. Different doses (of tissue plasminogen activator or urokinase) were compared in six trials. Different agents (tissue plasminogen activator versus urokinase,or tissue-cultured urokinase versus conventional urokinase) were compared in three trials. Few data were available for functional outcomes. A higher dose of thrombolytic therapy was associated with a five-fold increase in fatal intracranial haernorrhages (odds ratio 5.02, 95% confidence interval 1.56 to 16.18). There was a non-significant trend towards more early deaths or clinically significant intracranial haemorrhages in higher dose group. No difference in late deaths or extra-cranial haemorrhages was shown between low and higher doses. However, very few of these events occurred. No difference was shown between the different thrombolytic agents tested. Conclusions There is not enough evidence to conclude whether lower doses of thrombolytic agents might be safer or more effective than higher doses in acute ischaemic stroke. It is not possible to conclude whether one agent might be better than another, or which route of administration might be best.
Objective To explore the effect of renal microcirculation following severity acute pancreatitis （SAP） on renal injury and to explore the protection effect of urokinase on them. Methods A total of 192 Wistar rats were randomized divided into normal control group， SAP group， and urokinase group， then rats of 3 groups were sub-divided into 2， 6， 12， and 24 hours group， each group enrolled 16 rats. Of the 16 rats in each subgroup， 8 rats underwent blood flow of renal test， other 8 rats were sacrificed to get blood samples and to perform histopathological examination. The rat models of SAP were established by retrograde injecting with 5% sodium taurocholate into the cholangiopancreatic duct. Radioactive biomicrosphere technique was used to measure the blood flow of renal， levels of plasma thromboxane B2（TXB2） and 6-keto-prostaglandin F1α （6-Keto-PGF1α） were tested by the TXB2 kit and 6-Keto-PGF1α kit， and histopa-thological changes of renal tissues were observed by using HE staining. Results Compared with normal control group at the same time point， the blood flow of renal were lower （P＜0.05）， activity ratio of TXB2 to 6-Keto-PGF1α were higher（P＜0.01）， and the histopathological injury were worse （P＜0.01） in rats of SAP group and urokinase group. Compared with SAP group， the blood flow of renal at 2， 6， and 12 hours in urokinase group were higher （P＜0.01）， the activity ratios of TXB2 to 6-Keto-PGF1α were lower （P＜0.01）， and the histopathological injury were lighter （P＜0.05） in all the 4 time points of urokinase group. Conclusions The renal microcirculation dysfunction and increase of activity ratio of TXB2 to 6-Keto-PGF1α may play an important role in renal injury following SAP in early stage. Urokinase can protect the renal from such injuries.
ObjectiveTo evaluate the therapeutic effects of super-selective arterial catheterization with thrombolysis for central retinal artery occlusion (CRAO).MethodsThe clinical data of 16 patients with CRAO were collected. Aortic arch angiography with the catheterization through femoral artery firstly, and then the selective internal carotid artery angiography had been performed on all of the patients, including 12 ones who had undergone the urokinase thrombolysis therapy.ResultsIn the 16 patients, 3 with the severe straitness of the internal carotid artery and 1 with occlusion of incision of the ocular artery had not been treated by thrombolysis; and the others with occlusion of arterial trunk and CRAO had undergone thrombolysis therapy successfully. After the treatment, the visual acuity of the patients had improved in different degree and no systemic side effect had been found during the treatment.ConclusionsSuper-selective arterial catheterization with thrombolysis for CRAO may improve the visual acuity of the patients. The effects and risks of this treatment should be evaluated in further study.(Chin J Ocul Fundus Dis, 2005,21:20-21)
Objective
To inspect the effects of recombinant staphylokinase (r-Sak) and the changes of fibrinolytic activity in the systemic circulation in the treatment of experimental central retinal artery occlusion (CRAO)．
Methods
The animal model of CRAO in 15 cats (30 eyes) was set up by laser irradiating a branch of central retinal artery after intravenous injection of 3% rose bengal，and then the arterial thrombi were dissolved by intravenous injection of r-Sak and urokinase (UK)．The pat ency of the arteries was evaluated by FFA．Moreover，the changes of fibrinolitic activity in the blood were examined by phlebotomizing．
Results
The model of CRAO was successfully set up.Four hours after injection of thrombolysis drugs,the completely reopened proportion in r-Sak group was 100%，while in UK group the proportion was 60%．At the same time， no significant systemic fibinnolytic activation was observed in r-Sak group．
Conclusions
An experimental CRAO model,which has the similar pathological processes of occlusion of central retinal artery and intra arterial thrombosis as those in clinic，can be set up by using photochemical method，and r-rak is capable of lysing thrombus without significant activation of circulating plasminogen．
(Chin J Ocul Fundus Dis，2000，16：71-138)
Objective To evaluate the efficacy of intrapleural urokinase treatment for unloculated tuberculous pleural effusion. Methods Chinese Conference Data, Chinese Biomedical Database, VIP Database,Wanfang Database, Cochrane Library, PubMed, and Evidence-based Medical Evaluation Database were searched up to February 2012, and the studies as references of eligible articles were also searched. Randomized controlled trials were included for evaluating the efficacy of intrapleural urokinase treatment for unloculated tuberculous pleural effusion. Mean difference MD and 95% confidence interval ( 95% CI) were calculated for the efficacy of urokinase in the treatment. After the test for heterogeneity, forest map was used to analyze the efficacy of intrapleural urokinase treatment. The funnel plot was used to discuss the publication bias. Results Nine randomized controlled trials met all eligible criteria. This meta-analysis indicated that compared with the conventional treatment, the urokinase treatment increased total drainage( pumping liquid) ( P lt; 0. 000 01) , decreasd residual pleural thickening ( P lt; 0. 000 01) , improved lung function with significant increase in FEV1% pred ( P lt; 0. 000 01) . Conclusions Compared with the conventional treatment( anti-tubercular treatment in combination with pumping pleural effusion) , the treatment which injects urokinase to chest cavity can increase total pleural effusion, decrease residual pleural thickening, and improve the lung function.
Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i.e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
Bloodstream infections are featured by acute onset, rapid progression and high mortality. Early identification and accurate prognostic assessment are crucial for improving patient outcomes. This article reviews five novel biomarkers in assessing the severity and prognosis of patients with acute bloodstream infection, namely soluble triggering receptor expressed on myeloid cell-1, soluble form of the urokinase plasminogen activator receptor, presepsin, heparin-binding protein and microRNAs, all of which are positively correlated with the severity of patients’ condition, and some perform better than traditional biomarkers. However, they still have limitations such as inadequate specificity or sensitivity and lack of large-scale verification. In the future, it is necessary to integrate molecular detection and artificial intelligence to optimize application strategies and provide personalized diagnosis and treatment.
