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Objective:To observe the protective effect and mechanism of combination of puerarin combined with tanshinone ⅡA on diabetes mellitus (DM) rats with vascular lesions. Method:The SD rats (fed with high-fat diet) were administrated with streptozotocin(STZ) through intravenous injection to make the model of diabetic vascular lesions. The successfully modeled rats were randomly divided into the model control group, the high-dose group (0.5 g·kg-1+1.0 g·kg-1), the middle-dose group (0.25 g·kg-1+0.5 g·kg-1), the low-dose group (0.05 g·kg-1+0.1 g·kg-1), the puerarin group (0.25 g·kg-1), the tanshinone ⅡA group (0.5 g·kg-1) and the positive control group (Metformin, 0.09 g·kg-1). Each group was administrated with drugs respectively by gavage for 70 days. After intervention in each group, the general conditions and body weight of the rats were observed. The contents of blood grucose and blood lipids were determined by automatic biochemical analyzer. The contents of insulin, advanced glycation end products (AGEs), superoxide dismutase(SOD), glutathione peroxidase (GSH-Px) in serum, the contents of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and thromboxane B2 (TXB2) in plasma, as well as the contents of AGEs and oxidized low-density lipoprotein(ox-LDL) in aorta homogenate were detected by enzyme-linked immunosorbent assay(ELISA). The content of malondialdehyde(MDA) in serum was determined by chemical colorimetry. Pathological changes of coronary tissue were observed by htoxylin eosin(HE) staining. The expression of PAI-1 protein of aorta was observed by immunohistochemistry. Result:Compared with the normal control group, in the model group, the levels of blood grucose and blood lipids (PPPP2 in plasma (PPPPPPPPP2 in plasma (PPPPPPPConclusion:Puerarin combined with Tanshinone ⅡA could relieve vascular lesions of DM rats. The mechanisms may be related to the reduction of oxidative stress and the regulation of coagulation-fibrinolysis system.
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Objective To investigate the change of dynamic expression of t-PA and PAI-1 during early venous crisis after free perforator flap transplantation.Methods Thirty healthy New Zealand white rabbits weighed 2.5-3.0 kg were chosen and randomly divided into experimental group (n =15) and control group (n =15).Free transplantation of superficial epigastric artery perforator flap (SEAPF) was implemented in all rabbits firstly.Then the model of venous crisis was established by ligating the anastomosis vein in order to interrupt venous blood outflow in experimental group.The blood supply of all flaps was monitored by observing their color,swelling degree and the filling reaction of the capillaries after operation.Peripheral blood was drawn from femoral artery at different time point for measuring the concentration of t-PA and PAI-1 by Elisa.Partial flap tissue was harvested for pathological examination at corresponding time point.Data analysis was performed by using SPSS 17.0 statistical software.P ＜ 0.05 was considered statistically significant.Results One rabbit died of anesthesia,and the venous congestion was observed in 1 rabbit in control group.The models of free transplantation of SEAPF and venous crisis were established successfully in the remaining rabbits.No significant appearance change was observed within 1 h after the outflow vein being ligated,while typical appearance of venous crisis could be observed 2 hours after the outflow vein being ligated.Compared with the control group,the concentration of t-PA was lower,but the concentration of PAI-1 was higher in experimental group at 2 hours,4 hours,6 hours,8 hours after the outflow vein being ligated(P ＜ 0.05).However,there was no obvious differences between two groups at other time points (P ＞ 0.05).The pathological examination showed the red cells gradually got together and adhered to the venous wall,eventually the microcirculation had been blocked completely and theflap became necrosis after venous crisis being occurred.Conclusion t-PA and PAI-1 can't be used to diagnose early venous crisis of perforator flap transplantation.
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@#Objective To investigate the relationship between carotid artery intima-media thickness and plasminogen activator inhibitor-1(PAI-1)in patients with metabolic syndrome(MS).Methods According to the definition of MS by NCEP-ATP Ⅲ,323 patients were divided into the MS group(160 cases)and without MS group(163 cases).The PAI-1 level was assayed by ELISA.The carotid artery intima-media thickness(IMT)and atherosclerotic plaque were measured by high-frequency Doppler ultrasound.Results The PAI-1 level,carotid IMT and incidence rate of plaque of the MS group were 30.52±11.02 ng/ml,0.92±0.21 mm and 63.1% respectively.Those of the without MS group were 26.57±11.09 ng/ml,0.86±0.20 mm and 49.1% respectively.There was a significant difference between two groups(P<0.05～0.01).Moreover,with the increasing of the number of MS components,the carotid artery intima-media thickness(IMT)and incidence rate of plaque were gradually increased(P<0.05).The stepwise regression analysis showed that PAI-1 was independently associated with the carotid IMT(standardized coefficients=0.105,P<0.05).Conclusion MS tends to cause carotid atherosclerosis,the increase of PAI-1 is possibly correlated with carotid artery atherosclerosis.
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BACKGROUND: An elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration has been identified as a factor for the development of macroangiopathy including myocardial infarction, and an association between polymorphism of the PAI-1 promoter and plasma PAI-1 levels has been described. PAI-1 gene is thought to be one of candidate genes in development of diabetic nephropathy. We studied association between polymorphism of PAI-1 promoter and the development of diabetic renal failure in type 2 DM. METHODS: We reviewed the past clinical records of 4, 500 diabetic patients who were registered in KyungHee university hospital. We selected 85 diabetic patients without nephropathy for more than 10 years and 92 diabetic patients in which Kidney failure was developed within 20 years. We investigated promoter -675 and -844 region polymorphisms in type 2 DM patients with ESRD compared with patients without nephropathy by using PCR-RLFP. RESULTS: The genotypes of group of type 2 DM with ESRD and control group were consistent with Hardy-Weingerg equation. There was no significant difference between two groups in the polymorphisms of PAI-I promoter -675 region. Similarly, there was no significant difference between two groups in the polymorphisms of PAI-I promoter -844 region. CONCLUSION: The results suggest that the polymorphisms of PAI-1 gene are not associated with development of diabetic renal failure in Korean patients with type 2 DM.
Subject(s)
Humans , Diabetic Nephropathies , Genotype , Kidney Failure, Chronic , Myocardial Infarction , Plasma , Plasminogen Activator Inhibitor 1 , Plasminogen Activators , Plasminogen , Renal InsufficiencyABSTRACT
Objective To investigate the effect of Astragalus Membranaceus( Ast) and Angelica Sinensis( Ang) on antithrombosis and explore the molecular mechanism. Methods Plasminogen activator inhibitor-1 ( PAI-1) expression and activity were selected to observe the antithrombosis effect of Ast and Ang ( 3 and 6 mg/ml) on 0. 5 ng/ml TGF-?1 treated endothelial cells. PAI-1mRNA expression was detected by RT-PCR,PAI-1 antigen assay was detected by specific enzyme-linked immunosorbent assays( ELISA) ,and PAI-1 activity was measured by amidolytical assay. Results Ast and Ang significantly inhibited PAI-1 mRNA expreesion,antigen and activity in endothelial cells. The more powerful effects could be observed when treated by Ast and Ang together. Conclusion The PAI-1 mRNA expression,antigen and activity is inhibited effectively by Ast and Ang,which may be the mechanism of their treatment for antithrombosis.
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Effects of 38°C 30-minute bathing on hemostatic function and autonomic nervous function were studied in 15 48-to-72-year-old patients with cerebral infarction. Blood samples were collected three times: immediately before the bathing, at the end of 30 minutes of bathing, and 30 minutes after the bathing. Hematocrit values and fibrinogen concentrations decreased during bathing and returned to the pre-bathing levels 30 minutes after bathing. This indicates that bathing caused hemodilution due to the fluid shift. During bathing, noradrenaline decreased at a rate significantly higher than that of hemodilution while the sympathetic nervous function, which was evaluated by spectral analysis of sequential variation in arterial blood pressure, was not suppressed. The autonomic nervous system seemed to be inactive in these patients. Coagulation time (PT and APTT) and platelet factor (β-TG and PF4) showed few changes. In the fibrinolytic system, however, tissue plasminogen activator (t-PA) antigen levels increased and plasminogen activator inhibitor type-1 (PAI-1) levels decreased after 30 minutes of bathing. This suggests that fibrinolytic activity was enhanced by 38°C bathing for 30 minutes. Thus, subthermal bathing with comfort may be useful in preventing cerebral infarction.
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The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.
Subject(s)
Humans , Biology , Follow-Up Studies , Hope , Lymph Nodes , Neoplasm Metastasis , Neoplasm, Residual , Ovarian Neoplasms , Phenotype , Plasminogen Activator Inhibitor 1 , Plasminogen Activators , Plasminogen , Prognosis , Proteolysis , Recurrence , Retrospective Studies , Survival Rate , Urokinase-Type Plasminogen ActivatorABSTRACT
The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.
Subject(s)
Humans , Biology , Follow-Up Studies , Hope , Lymph Nodes , Neoplasm Metastasis , Neoplasm, Residual , Ovarian Neoplasms , Phenotype , Plasminogen Activator Inhibitor 1 , Plasminogen Activators , Plasminogen , Prognosis , Proteolysis , Recurrence , Retrospective Studies , Survival Rate , Urokinase-Type Plasminogen ActivatorABSTRACT
Studies on the effects of heating as well as the mineral components of hot spring water have been conducted to investigate the effects of balneotherapy. However, few studies have been conducted on the effects of hydrostatic pressure and buoyancy during water immersion. Therefore, we investigated the effect of water immersion up to the neck at thermoneutral temperature on hemostatic activity.<br>Nine healthy men aged 22 to 34 were immersed up to the neck in the standing position in thermoneutral water (34.0±0.5°C) for two hours. The heart rate decreased immediately after starting water immersion and remained low during the immersion. Hematocrit values (Ht) of the blood samples taken from the ante-cubital vein decreased by 3.4% in average. The decrease in Ht was more prominent in the blood samples taken from the earlobe (4.0%), suggesting that hemodilution due to fluid shift was stronger in the upper part of the body. The time until euglobulin clot lysis shortened immediately after starting the immersion. Although fibrinolytic activity was enhanced, the concentration of tissue plasminogen activator (t-PA) antigen in the blood decreased gradually during the immersion and tended to return to the original level 30 minutes after immersion. A larger decrease in the concentration of plasminogen activator inhibitor-1 (PAI-1) antigen in the blood was observed immediately after starting the immersion, and it remained low for 30 minutes after immersion. An increase in fibrinolytic activity due to the decrease in PAI-1, not in t-PA, was observed during water immersion at thermoneutral temperature and the activation of fibrinolytic system without activation of the coaguration system was also observed.
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BACKGROUND: It is well known that coronary arterial thrombosis plays an important role in the pathogenesis of acute coronary syndrome and this has focused interest on the role of the fibrinolytic system, especially tissue plasminogen activator(t-PA) and plasminogen activator inhibitor-1(PAI-1), which are major determinants of fibrinolytic system. But there are considerable variations in the reported association between these two components and acute coronary syndrome. METHODS: To evaluate association between t-PA, PAI-1 and myocardial infarction, plasma level of t-PA and PAI-1 in resting state and after venous occlusion were measured and analysed in patients with previous myocardial infarction at least 6 months after the acute phase, who showed less than 70% luminal narrowing angiographically and control group. The relationship between t-PA, PAI-1 antigen and activity and relation to age, serum triglyceride, cholesterol, and peak creatine kinase(CK) enzyme were also analyzed. RESULTS: 1) In resting state, there was a significant difference of plasma level of both t-PA and PAI-1 antigen, activity between patient and control group(10.72+/-3.28 vs 8.16+/-4.03ng/ml, 0.53+/-0.34 vs 0.02+/-0.07U/ml, 26.24+/-8.30 vs 20.82+/-8.82ng/ml, 14.62+/-5.97 vs 6.99+/-6.44U/ml)(p<0.05), and resting plasma level of PAI-1 activity showed a good correlation with peak creatine kinase(CK) enzyme(r=0.76, p<0.01). 2) After venous occlusion, plasma level of t-PA antigen was significantly increased(8.16+/-4.03 vs 9.87+/-3.86ng/ml)(p<0.05) whereas t-PA activity and PAI-1 antigen were not significantly changed in control group. In patient group, t-PA antigen, t-PA activity and PAI-1 antigen were significantly inceased after venous occlusion(10.72+/-3.28 vs 14.66+/-5.41ng/ml, 0.53+/-0.34 vs 1.41+/-1.69U/ml, 26.24+/-8.30 vs 29.87+/-8.78ng/ml)(p<0.05). PAI-1 activity was significantly decreased after venous occlusion in both groups(6.99+/-6.44 vs 6.06+/-5.99U/ml, 14.62+/-5.97 vs 12.67+/-6.46U/ml)(p<0.05). CONCLUSION: Both fibrinolytic and anti-fibrinolytic systems are augmented in resting and after fibrinolysis stimulation test in patient group. These findings suggested a impairment of fibrinolytic system in patient group and a possibility that both elevated plasma levels of t-PA and PAI-1 may be markers of coronary artery disease.
Subject(s)
Humans , Acute Coronary Syndrome , Cholesterol , Coronary Artery Disease , Creatine , Fibrinolysis , Myocardial Infarction , Phenobarbital , Plasma , Plasminogen Activator Inhibitor 1 , Plasminogen Activators , Plasminogen , Thrombosis , Tissue Plasminogen Activator , TriglyceridesABSTRACT
Obejective To study the effects of polysaccharide L01 from Laminaria on the expression and secretion of plasminogen activator inhibitor- 1 (PAI- 1) stimulated by adrenaline in cultured human umbilical vein endothelial cells (HUVEC). Methods With adrenaline added, human umbilical vein endothelial cell line ECV- 304 was exposed to different concentrations of polysaccharide L01 of Laminaria and cultured for 24, 48, and 72 hours respectively in vitro. The levels of PAI- 1 in cultured supernants were measured with enzyme- linked immunosorbent assay( ELISA) .Reverse transcriptase chain reaction( RT- PCR) was used to detect the expression of PAI- 1 messenger RNA( mRNA) in HUVEC, and the related products were examined by density scan and half- quantitative analysis after electrophoresis. Results Stimulated by 10 ? g/mL adrenaline for 48h and 72 h, the levels of PAI- 1 in cultured supernants increased significantly (P