Preoperative co-application of bevacizumab and tissue plasminogen activator in vitrectomy for proliferative diabetic retinopathy

ABSTRACT Purpose: To investigate the clinical benefits of the co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy. Methods: Patients who underwent vitrectomy for proliferative dia-betic retinopathy complications were preoperatively given in-travitreal injection with either bevacizumab and tissue plasminogen activator (Group 1) or bevacizumab alone (Group 2). Primary outcomes were surgery time and number of intraoperative iatrogenic retinal breaks. Secondary outcomes included changes in the best-corrected visual acuity and postoperative complications at 3 months postoperatively. Results: The mean surgery time in Group 1 (52.95 ± 5.90 min) was significantly shorter than that in Group 2 (79.61 ± 12.63 min) (p<0.001). The mean number of iatrogenic retinal breaks was 0.50 ± 0.59 (0-2) in Group 1 and 2.00 ± 0.83 (0-3) in Group 2 (p<0.001). The best-corrected visual acuity significantly improved in both groups (p<0.001). One eye in each group developed retinal detachment. Conclusion: Preoperative co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy shortens the surgery time and reduces the number of intraoperative iatrogenic retinal breaks.

The clinical efficacy and safety evaluation of butyphthalide-combined thrombolytic therapy on acute cerebral infarction in the elderly / 中华老年医学杂志

Objective:To evaluate the clinical effect and safety of the thrombolysis-combined butyphthalide therapy on acute cerebral infarction.Methods:A total of 58 patients with acute cerebral infarction receiving thrombolytic therapy in Henan Provincial People's Hospital from June 2016 to August 2018 were randomly divided into the thrombolytic group(recombinant tissue type plasminogen activator i. e.rt-PA, n=29)and the group of butyphthalide plus rt-PA(n=29). Neurological function(National Institutes of Health Stroke Scale, NIHSS), daily living ability(Barthel index score)and the ultrasound-detected cerebral blood flow were compared between the two groups to evaluate the clinical efficacy and safety.Results:After the treatment, NIHSS score was significantly lower in the group of butyphthalide plus rt-PA than in the thrombolysis group(5.24±2.61 vs.8.15±2.55 points, P=0.015). The Barthel index was significantly higher in the group of butyphthalide plus rt-PA than in the thrombolysis group(75.32±4.42 vs.57.37±3.54 points, P=0.024). The cerebral blood supply was improved in both groups after treatment as compared with pre-treatment.After treatment, the peak flow velocity of middle cerebral artery was 78.34±4.82 cm/s and 67.16±3.37 cm/s( P=0.017)and the average flow velocity of the middle cerebral artery was(44.19±2.18)cm/s and(37.49±2.16)cm/s( P=0.029)in the group of butylphthalide plus rt-PA than in the thrombolysis group, respectively, which showed the blood supply of the middle cerebral artery was better in butyphthalide plus rt-PA therapy than in thrombolytic therapy.Clinical effective rate was 89.7%(26/29)in butyphthalide plus rt-PA group, which was better than that in the thrombolysis group(65.5%, 19/29)( χ2=4.851, P=0.029). During the treatment, 2 patients had mild gastrointestinal reactions in both groups, which were relieved after treatment of symptoms, and no serious adverse reaction occurred in other patients. Conclusions:The combined therapy of butyphthalide and thrombolysis can improve clinical efficacy rate on acute cerebral infarction, improve the cerebral hemodynamics, promote the recovery of neurological function, and improve the quality of life of patients.

Efficacy analysis of intravenous thrombolysis in patients with mild ischemic stroke / 中国脑血管病杂志

Objective: To investigate the effectiveness and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with minor ischemic stroke. Methods: From April 2016 to January 2018, 117 consecutive patients with acute mild cerebral infarction admitted to the Department of Neurology, Guangzhou First People's Hospital were enrolled retrospectively. Their onset was 0. 05). In the intravenous thrombolysis group, the time from onset to thrombolysis was 75-260 min,and the median time was 161.5 (129.5,185.0) min. (2) There were no significant differences in the NIHSS scores at 24 h and 7 d after treatment between the two groups (P>0.05). Among the patients with good prognosis at 90 d of intravenous thrombolysis,9/10 had good prognosis in patients with disabled stroke symptom and 81.5% (44/54) had good prognosis in those with non-disabled stroke symptom. There was no significant difference in the proportion of good prognosis between the two groups (P =0.512). Among the non-intravenous thrombolysis group with good prognosis at 90 d,8/12 had good prognosis in patients with disabled stroke, and the good prognosis rate in those with non-disabling stroke was 65. 9% (27/41). There was no significant difference in the proportion of good prognosis (P =0.413). The good prognosis rate of the intravenous thrombolytic group at 90 d was higher than that of the non-intravenous thrombolysis group. The difference between the groups was statistically significant (82.8% [53/64] vs. 66. 0% [35/53],χ2 =4. 376,P = 0. 036). (3) In the intravenous thrombolysis group, two patients developed intracerebral hemorrhage transformation during the treatment period;one patient stopped anti-platelet aggregation treatment because of hemorrhage in other parts; one died of intracranial hemorrhage after thrombolytic bridging of cerebrovascular thrombectomy. There were no bleeding and death events during the treatment in the non-intravenous thrombolysis group. There were no significant differences in the incidence of intracerebral hemorrhage transformation and mortality between the two groups (P>0.05). (4) The symptoms in three patients in the intravenous thrombolysis group aggravated, they were treated with the bridge mechanical thrombectomy. Two of them were assessed as non-disabled stroke before thrombolysis, and one patient with carotid artery stenosis underwent carotid artery stent implantation during hospitalization. In the non-intravenous thrombolysis group, 1 patient underwent carotid artery stent implantation and 1 underwent right middle cerebral artery Ml stent implantation. There was no significant difference in the incidence of intracranial macrovascular stenosis, extracranial macrovascular stenosis and total stenosis rate between the two groups (P>0.05). Conclusion: Intravenous thrombolysis is safe and effective for mild ischemic stroke patients with or without disability.

Evaluation of Salivary Levels of Plasminogen Activator Inhibitor-2 in Patients with Moderate Generalized Chronic Periodontitis: A Case- Control Study

Objective: To compare salivary levels of PAI-2 in patients with moderate generalized chronic periodontitis before and after treatment and healthy subjects. Material and Methods: The present case-control study evaluated patients with generalized moderate chronic periodontitis (the case group) and subjects with healthy gingiva (the control group). The healthy subjects were evaluated once and the cases were evaluated twice (before and after treatment) by collecting their salivary samples. ELISA technique was used to determine PAI-2 salivary levels. Data were analyzed with the use of SPSS 17. The level of significance was set at 5%. Results: The mean salivary levels of PAI-2 in the case and control groups were 45.63 ± 8.63 and 22.01 ± 9.77 ng, respectively (p<0.0001). In addition, PAI-2 salivary levels in the case group subjects after treatment was 27.43 ± 5.79 ng, which was lower than that before treatment (45.63 ± 8.63 ng) (p<0.0001). The mean salivary level of PAI-2 in subjects with periodontitis after treatment (27.43 ± 5.79) was not significantly different from that in healthy subjects (22.01 ± 9.77) (p>0.05). Conclusion: The salivary levels of PAI-2 in patient with moderate generalized chronic periodontitis were higher than these in healthy subjects. However, the salivary levels of PAI-2 decreased in the case group subjects after treatment, with no significant difference from the healthy subjects.

Comparison and contrast of different treatments for severe spontaneous cerebellar hemorrhage with intraventricular hemorrhage in elderly patients / 中华老年医学杂志

Objective To compare four therapies for elderly patients with cerebellar hemorrhage breaking into the ventricles.Methods Clinical data of 158 elderly patients with severe spontaneous cerebellar hemorrhage breaking into the ventricles were retrospectively analyzed.There were 28 cases in the conservative management (CM) group and 130 cases in the surgical therapy (ST) group with an external ventricular drainage (EVD) subgroup (n=40),an external ventricular drainage combined with intraventricular fibrinolysis (EVD + IVF) subgroup (n =43),and a clot evacuation (CE) subgroup (n=47).The mortality at 1 month and modified Rankin Scale (mRS) at 6 months were employed to evaluate clinical effectiveness.In addition,statistical analysis of correlative factors for prognosis was conducted.Results The 1-month mortality (x2 =7.529,P =0.006) and 6-month mRS in the CM group (x2 =4.819,P =0.028) were significantly higher than those in the ST group.There was no significant difference in mortality after one month among the three ST subgroups (x2 =0.143,P=0.931),whereas significant differences were observed in 6-month mRS among them (x2 =7.209,P=0.027),and the scale in the EVD+IVF subgroup was significantly lower than in the CE and EVD subgroups.The incidence of complications such as pulmonary infections and stress ulcers in the CM group was significantly higher than in the ST group.Statistical differences were found in the incidence of pulmonary infections among the three ST subgroups (x2 =6.694,P=0.035),and the incidences in the EVD subgroup and the EVD+IVF subgroup were lower than the incidence in the CE subgroup.Nevertheless,there was no significant difference in the incidence of stress ulcers among the three ST subgroups (x2 =0.547,P=0.776).Conclusions EVD+ IVF is an effective treatment for cerebellar hemorrhage breaking into the ventricles in elderly patients,especially for those who cannot withstand a craniotomy or those who have primary diseases.It may speed up the absorption of hematoma,and decrease the operative risk and the incidence of postoperative complications.

t-PA negatively regulating p75NRT for involving in atherosclerosis by changing reconstruction of vascular outer membrane autonomic nerve / 重庆医学

Objective To study the effect of tissue plasminogen activator (t-PA) on p57NTR ,inflammatory reaction ,immune regulation and oxidative stress and its effect on intimal hyperplasia .Methods The vascular injury treatment was performed in the diabetic rabbit model with carotid arterial adventitia stripping ,meanwhile t-PA controlled release microspheres were given ,the nerve distribution in the local blood vessels was observed by immunohistochemical staining .The change of nerve remodeling in the control group and treatment group was observed ,meanwhile the effect of giving t-PA controlled release microspheres on the release of ace-tylcholine and norepinephrine was detected .RT-PCR was used to detect local vascular tissue inflammation ,immune effects and oxi-dative stress .The sympathetic neurons and smooth muscle cell co-culture was adopted ,then giving glyoxal treatment as the athero-sclerosis cell model .With the t-PA treatment group as the intervention group ,the effect of t-PA on the number of cholinergic neu-ron ,and synaptic connections between the smooth muscle cells and acetylcholine secretion was observed .The change of t-PA-MMP-p75NTR and NF-kappa B signaling pathway were detected by RT-PCR .Results The vascular injury treatment was performed in the diabetic rabbit model with carotid arterial adventitia stripping ,meanwhile t-PA controlled release microspheres were given ,the nerve distribution in the local blood vessels was observed by immunohistochemical staining .The change of nerve remodeling in the control group and treatment group was observed ,meanwhile the effect of giving t-PA controlled release microspheres on the release of acetylcholine and norepinephrine was detected .RT-PCR was used to detect local vascular tissue inflammation ,immune effects and oxidative stress .The sympathetic neurons and smooth muscle cell co-culture was adopted ,then giving glyoxal treatment as the ath-erosclerosis cell model .With the t-PA treatment group as the intervention group ,the effect of t-PA on the number of cholinergic neuron ,and synaptic connections between the smooth muscle cells and acetylcholine secretion was observed .The change of t-PA-MMP-p75NTR and NF-kappa B signaling pathway were detected by RT-PCR .Conclusion t-PA activates MMPs and feedback in-hibits p75NTR-NF-kappa B signaling pathway to increase vascular adventitia autonomic nerve reconstruction and delay the occur-rence and development of atherosclerosis disease .

Experiencia de trombolisis sistematizada en infarto cerebral agudo en un hospital público de Chile / Thrombolysis for acute ischemic stroke with recombinant tissue plasminogen activator in a Chilean public hospital

Background: The only accepted treatment for acute ischemic stroke is thrombolysis with recombinant tissue plasminogen activator (t-PA). It was implemented in Chile in 1996, although its use was mainly restricted in Chile to private clinics. Recently, at year 2009, we have implemented this treatment in a public hospital. Aim: To describe the results of treatment of acute ischemic stroke with t-PA in a public hospital in Chile. Material and Methods: Prospective analysis of all eligible patients with acute ischemic stroke that were admitted within 4 hours of its onset and had no contraindications for thrombolysis. Results: In an eight months period, a total of 19 intravenous thrombolyses were performed in 12 males and seven females aged 28 to 79 years old. The mean lapse between onset of symptoms and onset of thrombolysis was 190 ± 57 min. Results were favorable, according to Rankin and National Institute of Health Stroke scales. Ninety days after treatment, 63 percent of patients had minimal or absent disability, 26 percent had moderate disability and only one (5 percent) had severe disability. One patient had a clinically not significant intracranial hemorrhage and one patient died six days after thrombolysis. Conclusions: These results indicate that thrombolysis can be successfully implemented in Chilean public hospitals. The limitations for its use in this setting are mostly administrative.

Variation and clinical significance of circulation annexin Ⅱ in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To compare the level of Annexin Ⅱ in patients with systemic lupus erythematosus(SLE),diabetic nephropathy(DN),chronic glomerulonephritis and normal controls,and explorle the significance of the annexin Ⅱ in SLE.Methods Thirty-five cases of patients with SLE,ten cases of patients with DN,ten cases of patients with chronic glomerulonephritis were enrolled in this study,twenty cases of healthy controls were also enrolled.Circulating annexin Ⅱ in white blood cells was detected bv flow cytometry.Student's t test,variance analysis and Lineat correlation analysis were used for statistial analysis.Resuits Compared with healthy controls,the level of annexin Ⅱ in white blood cells in SLE patients (7.1±2.9)%and DN patients(8.0±3.7)%were significantly lower than that of the healthy controls(P<0.01,p<0.05).In the SLE group,the level of annexin Ⅱ of patients who had more active disease(SLEDAI≥9)decreased more thall those with less active disease(SLEDAI<9),(P<0.05).A positive correlation was found between annexin Ⅱ and serum albumin level(r:0.439,P<0.01),but negative correlation was found between annexin and urine protein/urine creatinine(r=-0.382,P<0.05),SLEDAI(r=-0.417,P<0.05),D-dimer(r=-0.336.p＜0.05) levels.Conclusion The level of annexin Ⅱ is decreased in patients with SLE,so it can renectthe abnormality of coagulation and fibrinolytic systems,and it may be used as a good indicator for prothrombotic status in SLE patients.It can be helpful to evaluatethe activity of the disease and the therapeutic efficacy.

Isolation and purification of plasminogen activator of Yersinia pestis / 中国地方病学杂志

Objective To find methods to isolate and purify plasminogen activator (Pla) from artificial culture of Yersinia pestis. Methods Ultrasonication and urea extracting combined by ammonium sulfate salting-out were tried to extract Pla. High performance liquid chromatography(HPLC) was used to purify Pla. The first step was ion exchange and the second was gel filtration, Preparative electrophoresis was used to purify Pla, too. The enzyme activity of the isolated or purificated Pla was detected. Results Both 50% - 60% saturated ammonium sulfate deposition of supernatant of plague bacilli ultrasonication and 0 - 10% saturated ammonium sulfate deposition of supernatant of plague bacilli powder soaked by urea had three bands(Mr about 31×103, 35×103 and 37×103) and lysis rings were 6.5 and 7.2 mm in diameter respectively when the enzyme activity was detected. Pla purified by HPLC was mainly composed of three bands(Mr about 31×103, 35×103 and 37×103), occupying more than 80% of total protein weight and lysis ring was 5.0 mm in diameter. Pla purified by preparative electrophoresis mainly consisted of three bands(Mr about 31×103, 35×103 and 37×103) with other proteins of low concentration nearby, no lysis ring was detected. Conclusions Pla is collected by the methods of ultrasonication and urea extracting. Priliminary purification of Pla can be achieved by HPLC and preparative electrophoresis.

Vitrectomy combined with tissue plasminogen activator and fraxiparine for fibrin exudation caused by bacterial endophthalmitis in rabbits / 中华眼底病杂志

Objective To observe the therapeutic effects of vitrectomy combined with tissue plasminogen activator(r-tPA) and fraxiparine on bacterial endophthalmitis. Methods Forty pigmented rabbits were randomly divided into experimental and control group with 20 rabbits in each. The left eyes underwent intra-vitreous injection with 105/ml bacteria of staphylococcus epidermidis 0.1 ml. After 8-14 hours, vitrectomy was performed on all of the animals. Fraxiparine with the final concentration of 6 IU/ml was only added to balanced salt solution in the experimental group during the operation, and the extend of intraocular fibrin exudation was observed by slit lamp and indirect ophthalmoscope after the operation. If the exudation occurred on the 1st, 3rd, 7th, 14th and 21st day postoperatively, 125 mg/ml r-tPA 0.1 ml should be injected into vitreous from the 1st day after operation on. Results Fibrin exudation in the pupil area and vitreous body was much less in experimental group than that in the control group after the surgery. Conclusion vitrectomy combined with r-tPA and fraxiparine may alleviate the extent of fibrosis in bacterial endophthalmitis and improve the prognosis.

SPECIAL ATTENTION SHOULD BE GIVEN TO THE RESEARCH ON EXTRACELLULAR MATRIX DEGRADATIVE SYSTEMS IN KIDNEY DISEASES / 解放军医学杂志

Alterations in the balance between synthesis and degradation of extracellular matrix (ECM) and its remodeling may result in an accumulation of ECM molecules and lead to glomerulosclerosis. Recent studies have focused on the role of degradative systems, especially the roles of plasminogen activators/plasminogen activator inhibitors (PA/PAI), matrix metalloproteinases, and their inhibitors[GK2*4/5!2*4/5] (MMP/TIMP) in the initiation and pathogenesis of renal diseases. Previously, attention has been paid to the study of inhibitors of ECM degrading enzymes, such as PAI and TIMP. Recent researchs showed that there existed complex dynamic expressions of enzymes and their inhibitors. Although many studies have tried to elucidate the pathogenesis of renal diseases, the exact underlying mechanisms are still not completely understood. For better understanding of the mechanism of chronic progressive renal diseases, the underlying genetic and molecular regulation of each component of PA/PAI and MMP/TIMP systems should be elucidated in different renal physiological and pathophysiological processes. Future studies are needed to manipulate activity or expression of these proteinases in order to treat and/or prevent glomerular diseases.

Effects of mutant tPA gene transfer on tPA activity and adherence of endothelial cells seeded onto graft vessel / 中国普通外科杂志

Objective To evaluate the activity of tissue plasminogen activator (tPA) gene transduced endothelial cells (EC) and the cell retention on graft vessel. MethodsKG1 EC were transduced with pseudotyped vectors carrying genes coding for either the wild type tPA or mutant tPA. The supernatants were collecteJPd and assayed for tPA activity in the presence and absence of fibrin. Polytetrafluoroethylene (PTFE) vessel grafts were seeded with EC, and then exposed to an in vitro flow system for 1 h. The number of EC on grafts were counted and the retention of EC were evaluated. ResultsWT5”BZ The tPA activity of the nontransduced EC was (1 5?1 0) IU/ml, while that of wild type tPA gene transduced EC increased to (30.0?8 0) IU/ml, mutant type tPA gene transduced EC increased to (14.1?1 0) IU/ml( P

Changes of fibrinolytic activity and D-Dimer level in the primary hypertention of the elderly and their significance / 中国综合临床

Objective To investigate the changes of plasma fibrinolytic activity and D dimer level in the primary hypertension of the elderly.Methods ELISA was applied to measure blood and urine D dimer.Chromophore substrate method was used to detect PL,Plg,t PA and PAI 1.Results The levels of PAI 1,D dimer and Plg were obviously higher in the elderly primary hypertension and hypertentive kidney disease than those in the control group,while t PA and PL activity were lower than in the control group.Conclusion The changes of PLA and D dimer play an important role in hypertension and hypertentive renal disease of the elderly,on which the early diagnosis can be based.

The study on hematological changes of nontraumatic osteonecrosis of the femoral head / 中华骨科杂志

Objective To study the hematological changes o f nontraumatic osteonecrosis of the femoral head,select the sensitive molecular symbols for early diagnosis and distinguish the high risk peopl e.Methods The studied subjects were divided in to three groups:1)NONFH early stage group(n=30);2)NONFH late stage group(n=30);3)the normal controlled group(n=30).Blood samples from cubital veins were collected.GMP -140,PC,D -Dime r were examined using ELISA.PAI was e xamined with chromogenic assay.Results1)The platelet GMP -140levels of early or late stage groups NONFH were signi ficantly higher than that of the normal contro lled group;the plasma PC levels of both groups were lower than that of the normal controlled group significan tly(P

Experimental study on the effects of tumor necosis factor on the cultured human umbilical vein endothelial cells / 第三军医大学学报

The effects of tumor necrosis factor (TNF) on the activity of plasmogen acitva-tor inhibitor (PAD and the morphology of the cells were observed in the original passage of cultured human umbilical vein endothelial cells (HUVEC). It was found that the TNF effect on the PAI was determined by the dosage of TNF, that is, 500U/ml of TNF could significantly activate PAT activity while 2500U/ml markedly inhibit it. Morphdogical observation canfirmed that 2500U/ml of TNF could injure HUVEC to form a kind of cells whose morphology was quite similar to that of circulating endothelial cells originating from peripheral blood.These findings suggest that TNF can stimulate HUVEC to increase the PAI acivity but too large a dosage of TNF could injure the metabolic function and structure of HUVEC.

Pulmonary effect on anticoagulants and the activity of total plasminogen activator in blood during superior mesenteric artery occlusion (SMAO) shock / 中国病理生理杂志

Abstract The variation of functional protein C (PC), the activities of total plas. minogen activator and antithrombin Ⅲ (ATⅢ) were observed in canine SMAO shock. The results indicated that under normal conditions, compared with into-pulmonary blood (IPB), in out-pulmonary blood (OPB) the functional PC increased and ATⅢ activity decreased significantly (P

Experimental study of fibrinolytic activation-effect of catecholamines on fibrinolytic activity / 中国病理生理杂志

The present study, using the different catecholamines, observed the effects on plasminogen activator (PA) activity release in the vascular wall of rat hindlegs. The results showed that adrenaline perfusion induced the highest PA activity in three different catecholamines. Propranolol completely blocked PA activity induced by isoprenaline. PA activity induced by adrenaline or noradrenaline was completely inhibited by propranolol combined with phentolamine. During physiological stress the increase of plasma noradrenaline level was accompanied with higher PA activity. These data indicated that exogenous catecholamines produced a increase of PA activity via ?-adrenoreceptors stimulation mainly, as well as ?-receptors partially. The endogenous increase of catecholamines showed the same effect on fibrinolytie system.

The effect of Radix Sal viae Miltiorrhizaon the inhibitory activity of vascular smooth muscle cells to the plasminogen activators secreted by endothelial cells / 中国病理生理杂志

Cultured porcine endothelial cells (EC) produce and secrete plasminogen activators (PA). If the serum free medium conditioned by vascular smooth muscle cells (SMC-CM) mixed with the medium conditioned by endothelial cells (EC-CM), the PA activities of the latter decreased significantly. Coeultivation of EC with SMC inhibited 70.7% PA activity of EC. Gel eletrophoretic analysis (SDS-PAGE) of SMC-CM followed by reverse fibrin autography demonstrated PA inhibitory activity in the molecular weight range of 49, 000-52, 000 similar to those identified by Laug (1985).In this study it was also investigated the effect of a Chinese herbal medicine-Radix Salviae Miltiorrhizae (RSM) on the inhibitory activity. SMC were incubated with RSM (0.1% in M-199, the final concentration was 1.5mg/ml) for 24hr. The SMC-CM collected before and after RSM treatment were mixed with EC-CM and urokinase respectively. The results show that the residual PA activities in EC-CM or urokinase samples mixed with SMC-CM treated with RSM were significantly higher than that mixed with SMC-CM without treatment with RSM. SMC-CM neutralized the PA activities in EC-CM or urokinase samples in a concentration dependent manner (P

Effects of insulin and glucose on secretion of tissue-type plasminogen activator and its inhibitor-1 in hypoxic vascular endothelial cells / 中国病理生理杂志

AIM: To study the effects of insulin and glucose on tissue-type plamingen activator (tPA) and its inhibitor-1 (PAI-1) secretion in cultured human endothelial cells. METHODS: Human endothelial cell line ECV-304 was cultured with glucose and/or insulin at different concentrations with or without hypoxic exposure. RESULTS: The tPA, PAI-1 secretion and ratio of tPA/PAI-1 increased in endothelial cells during hypoxia. Insulin and glucose increased the tPA and PAI-1 secretion in endothelial cells exposed to hypoxia, and increase in tPA/PAI-1 ratio was also observed at 4 h and 8 h. CONCLUSION: Hypoxia stimulates the release of tPA and PAI-1. Insulin and glucose also stimulate the tPA and PAI-1 secretion during hypoxia.