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Objective:To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method:A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (40 cases) and therapy group (40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group, the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine(TCM) syndrome, chronic obstructive pulmonary disease and asthma physiology Score (CAPS), and chronic obstructive pulmonary disease patients self-assessment test questionnaire (CAT) were compared. The secondary indicators were pulmonary function, arterial blood gas analysis, and blood rheology indexes. In addition, the levels of serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), transforming growth factor-beta1 (TGF-β1) and plasma tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-willebrand factor (v-WF), clinical efficacy and safety were evaluated. Result:The total clinical effective rate was 94.74% in therapy group,which was higher than 78.38% in control group (χ2=4.341,P2, serum NF-κB, IL-6, IL-8, MMP-2, TIMP-2, TGF-β1 and plasma PAI-1, v-WF in therapy group were lower than those in control group(P2, PaO2, FEV1, FEV1%, FEV1/FVC in therapy group were higher than those in control group(PPConclusion:Modified Qingqi Huatan Wan can control the symptoms safely, alleviate CAPS and lung function, effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis, and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.
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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 preliminarily discuss the mechanism of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of lipid metabolism through regulating the imbalance of fibrinolytic system in rats with non-alcoholic fatty liver. Methods:The model of non-alcoholic fatty liver in rats was duplicated by high-fat diet feeding. Totally 60 adult Wistar rats were randomly divided into 6 groups (n=10 per group), namely the control group, the model group, Salvia miltiorrhiza group, Rrhizoma alismatis group, Salvia miltiorrhiza and Rrhizoma alismatis group,and Dongbaogantai group. The control group and the model group were given distilled water,and the other group was given Salvia miltiorrhiza,Rrhizoma alismatis,Salvia miltiorrhiza combined with Rrhizoma alismatis and Dongbaogantai,respectively. Rhizoma Alismatis decoction at high dose and low dose as well as Dongbaogantai was respectively adminis-trated in the designed groups,and the corresponding indices were detected 4 weeks later. Results:In the model control group,the con-tents of TC、TG、FFA in serum and the expression of PAI-1 were significantly elevated(P<0.05 or P<0.01),while the expression of t-PA was significantly reduced(P<0.01).After treatment,the contents of TC、TG、FFA in serum and the expression of PAI-1 in every treatment groups were reduced(P<0.01),while the expression of t-PA was elevated(P<0.01).Conclusion: Increasing the expres-sion of t-PA and reducing the expression of PAI-1 might be viewed as the mechanisms of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of non-alcoholic fatty liver disease.
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<p>A 41-year-old man had undergone mitral valve replacement (On-X 27/29 mm) and tricuspid valve replacement (TVR) (On-X 31/33 mm) for infectious endocarditis of the mitral valve and severe tricuspid regurgitation 6 years ago. Postoperative echocardiography showed aortic regurgitation and perivalvular leakage of the prosthetic mitral valve and left ventricular (LV) septal perforation. He therefore underwent aortic valve replacement (On-X 25 mm), patch closure of a leak around the prosthetic mitral valve, direct closure of the LV septal perforation, and re-TVR (On-X 31/33 mm). After discharge, he was placed on anticoagulant therapy with warfarin (international normalized ratio of prothrombin time target : 2.0-2.5). Transthoracic echocardiography three and -a half years after the operation revealed an increased mean tricuspid valvular pressure gradient (14 mmHg) compared with that seen on an echocardiograph of previous year. Cine-fluoroscopy showed almost no movement of the leaflets of the mechanical tricuspid valve. Tricuspid valve thrombosis or pannus formation was suspected. He was placed on thrombolytic therapy using tissue plasminogen activator (monteplase 1.6 million units). Five days later, cine-fluoroscopy showed movement of the mechanical tricuspid valve leaflets, and echocardiography revealed recovery of the mean tricuspid valve pressure gradient (4 mmHg). Valvular thrombosis was diagnosed as the cause of the non-moving valve. Hemorrhagic and embolic complications were not observed. Thrombolytic therapy was extremely useful.</p>
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Natural fibrinolytic enzymes have been focused recently when compared to chemically synthesize thrombolytic drugs as they are more economical and believe to have less adverse reaction. Belacan (shrimp paste), Budu (fish sauce) and Cencaluk (shrimp sauce) were traditional fermented Malay seafood products used as sources for this study. The isolation and screening resulted in the discovery of 43 potential isolates with the ability as an extracellular fibrin degrader. Each isolate were unique due to differences in morphology characteristics and the amounts of fibrinolytic enzyme secretes under standard growth condition. Furthermore, it has been demonstrated that some strains posses the ability to act as tissue plasminogen activator (t-PA) which in deed has beneficial to many medicinal and therapeutic purposes. Of these 43 strains investigated for the fibrinolytic enzyme production, three species, mainly the best producer from each food sample were chosen for further molecular identification. This lead to the discovery of B. cereus 13BN, B. subtilis 2CN and B. subtilis 9BD strains, which posses both high fibrinolytic and t-PA activities, making it extremely valuable and promising producer.
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Background and Aims: A substantial number of diabetic patients, diagnosed at relatively younger age, who don’t fit to typical type 2 and type 1 class of diabetes. These patients usually present with very high level of glycemia. The uniqueness of this group of patient provide the opportunity to explore the pathophysiology of nerve functional status at an early stage of diabetes. The present study was aimed to determine markers of endothelial dysfunction and evaluate nerve functional status of a group of newly diagnosed clinically uncomplicated young diabetic patients. Material and Methods: A total number of 32 (male-13 and female-19) newly diagnosed young (diabetes diagnosed under 30 yrs) were consecutively recruited from BIRDEM Out-patient department and 30 age-, BMI-matched healthy subjects with no family history of diabetes up to second generation served as controls. Serum fructosamine was measured by reduction test with NBT method. Serum C-peptide, endothelin-1 and tissue plasminogen activator (t-PA) by ELISA and von Willibrand factor (vWF) by Radial Immunodiffusion (RID) methods. Urinary albumin measured by immunoturbidimetry method. Nerve functional status was evaluated by nerve conduction velocities (NCV), distal latencies (DL), compound muscle action potential (CAMP), F wave latencies (FWL), nerve action potential (SNAP) for motor and sensory nerve as appropriate following the standard protocol. Results: Severe hyperglycemia in the diabetic group was reflected in their mean (SD) fasting C-peptide and fructosamine level. Altered endothelial dysfunction, as evidenced by significantly high tissue plasminogen activator (t-PA) (p<0.001) in the diabetic group. Albumin creatinine ratio (ACR) was almost similar in the two groups. Ulnar distal latency was similar in both the groups. But its CAMP and NCV were significantly lower in the diabetic group (p<0.02-0.001). Ulnar F wave latency were significantly higher (p=0.016) in the diabetic group. Ulnar sensory conduction parameters did not show any difference between two groups. Peroneal motor and sural sensory functional status of the diabetic subjects showed similar trend like that of ulnar motor and sensory status. Peroneal nerve motor NCV was significantly negtively correlated with fasting glucose [r=- 0.456, p=0.001]. Peroneal motor distal latency was significantly correlated with fasting fractosamine [r=0.439, p=0.012]. Fasting fructosamine showed significant negative correlation with motor peroneal NCV [r=-0.572, p=0.001], motor ulnar NCV [r=-0.468, p=0.007], both ulnar and sural sensory NAP (p=0.02 for both]. On the basis of F wave latency 53% of diabetic subjects had diabetic neuropathy and markedly higher t-PA compared to nonneuropathy groups (p=0.001). Conclusions: The data suggest that (i) Young type 2 diabetic subjects had endothelial dysfunction at the time of diagnosis even in the presence of normoalbuminuria state; (ii) Motor nerve conduction parameters are affected more than the sensory component; (iii) F wave latencies are more frequently and early to be involved in these subjects and linked to high serum t-PA.
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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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We describe the case of a 67-year-old female patient with a history of femoral-distal bypass graft with sudden onset of unremitting leg pain, who had recently received tissue plasminogen activator (t-PA). The patient reported non-compliance with her warfarin regimen. Angiography revealed occlusion of the bypass graft. Infusion of t-PA was performed via a right femoral artery approach. On hospital day two, the patient developed nausea and abdominal pain with associated hypotension. A CT scan showed a massive intra-abdominal and pelvic free fluid consistent with blood. The spleen was enlarged and fluid noted around the liver. At laparotomy, a grade III splenic laceration at the hilum was identified and a splenectomy performed. The patient recovered completely. Although rare, spontaneous splenic rupture should be considered in the differential diagnosis of patients undergoing thrombolytic therapy who develop signs of hemodynamic instability.
Descrevemos o caso de uma paciente de 67 anos com histórico de enxerto fêmoro-distal com início súbito de dor repetitiva em membro inferior e que havia recebido ativador de plasminogênio tecidual (AP-t) recentemente. A paciente relatou não adesão ao seu tratamento com warfarina. A angiografia revelou oclusão do enxerto. O AP-t foi administrado via artéria femoral direita. No segundo dia de hospitalização, a paciente apresentou náuseas e dor abdominal com hipotensão associada. Uma tomografia computadorizada revelou a existência de um fluido pélvico e intra-abdominal livre em grande quantidade, com suspeita de que fosse sangue. O baço estava crescido, e o fluido foi observado em torno do fígado. A laparotomia identificou uma laceração grau III no hilo esplênico, e uma esplenectomia foi realizada. A paciente teve recuperação completa. Embora rara, a ruptura esplênica espontânea deve ser considerada no diagnóstico diferencial de pacientes submetidos a terapia trombolítica que apresentem sinais de instabilidade hemodinâmica.
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Humans , Female , Aged , Tissue Plasminogen Activator/administration & dosage , Splenic Rupture/complications , Splenic Rupture/diagnosis , Thrombolytic Therapy/adverse effectsABSTRACT
Objective To investigate the effect of polymorphism of plasminogen activator inhibitor-1(PAI-1) promotor region gene,plasma tissue plasminogen activator(t-PA)and PAI-1 on patients with acute pulmonary thromboembolism(APTE).Method Fifty-two patients with APTE were divided into two groups according to the presence or absence of traditional enviromnent risk facters,and there were26 patients in each gnup,and auother 57 healthy indiriduals as controls were analyzed.The genotypos of subjects were determined for the 4G/5G polymorphism of PAI-1 gene using polymerase chain reaction based restriction fragment length polymorphism analysis.Plasma PAI-1 and tPA were measured by ELISA.Results(1)The ratio of 4G/4G genotype in group without traditional environment risk factors was much higher than that of the other two groups.(2)Plasma t-PA decreased and plasma PAI-1 elevated significantly in group without traditional environment risk factors compared with that of the other two groups.(3)Except the 5G homozygous,plasma PAI-1 level in group without traditional environgment risk factors was significantly higher than the other two groups.There existed correlation between 4G allele and plasma PAI-1.Conclusions 4G/5G polymorphism of PAI-1 gene is associated with AFFE.4G/4G genotype increases the risk of APTE for individuals without traditional risk factors.There are hypercoagulation and hypofibrinolysis in APTE patients without traditional risk factors.
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Objective:To discuss the relation among t-PA,PAI,unstable angina risk strati cation and its TCM syndrome.Methods:Syndrome di erentiation,coronary angiography and risk strati cation for 86 cases of unstable angina pectoris were carried out,and Gensini scoring system was used to assess the results of coronary angiography,blood stasis score was used to assess the degree of blood stasis.Serum blood serum t-PA and PAI levels were detected for statistical analysis.Results:In 86 cases of patients with low-risk,middle-risk and high-risk groups,with the incremental risk strati cation,blood stasis and Gensini score were increased,by comparison among the three groups,the di erences was existed(P
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Objective To explore the mechanism of QHR (main ingredients:Gypsum, Anemarrhema Asphodeloides Bge, Paeonia Lactiflora Pall) on secretive function of vaso-endothelial cells in rabbits with of endotoxemia. Methods Endotoxemia model was induced by colibacillary endotoxin via auricular intravenous injection in rabbits. The changes on pathomorphology and secretive function of vaso-endothelial cells in the model and QHR group were observed. Results It showed the existence of microthrombus in the lung via microscope in the model. The balance destruction of t-PA/PAI, NO/ET, TXB2/6-K-PGF1? in the model (P
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Objective :To study the effect of MMP-1,TIMP-1,VEGF and t-PA,PAI-1 in the inflammatory process of endometrium cell and the active components of SQ.Methods: ICC,ISH and WB was used to test the level of protein of MMP-1,TIMP-1,VEGF and t-PA,PAI-1 and mRNA of MMP-1,TIMP-1 and VEGF of endometrium cell in regular group,pattern group,GongXueNing group and SQ group.Result: In contrast with model group,the level of MMP-1protein and mRNA expression obviously decreased,but the level of TIMP-1 and VEGF increased in SQ group,there were signifi cant differences(P
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Objective:To explore the pathologic mechanism of blood-stasis syndrome in cardiopathy(BSSC) and its different syndrome types from the activity of fi brinolytic system.Methods:72 cases with BSSC,20 cases with non-blood-stasis syndrome in cardiopathy(NBSSC) were observed at random,20 healthy cases as control.The levels of tissue-plasminogen activator(t-PA) and plasminogen activator inhibitor-1(PAI-1) in blood plasma were detected by ELISA.Results:①The level of t-PA in the group of BSSC was signifi cantly lower than that in the groups of healthy control and NBSSC(P
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@#ObjectiveTo observe the effects of XinShu parenteral solution (XSPS) on the activation of platelet, the activity of fibrinolysis system after intima denudation of rabbits.Methods20 male Japanese white rabbits (2.5±0.5)kg were randomly divided into the control group and XSPS group .The celiac arterial endothelium of all rabbits were denuded with balloon. Before the operation and 3d, 7d, after balloon denudation, vein blood samples were obtained from each group rabbits for measurement of α granule membrane protein of platelets(GMP-140), tissue-type plasminogen activator(t-PA) and plasminogen activator inhibitor-type Ⅰ(PAI-1).ResultsPlasma GMP-140 and PAI-1 activity obviously elevated after balloon injury, and there was a little elevation in plasma t-PA activity in control group. Activity of plasma GMP-140 in XSPS group remained bottom level after balloon injury, and there was a significant increase in plasma t-PA activity and a marked reduce in PAI-1 activity in XSPS group. There was a notable difference between group B and group C (P<0.05). ConclusionXSPS obviously inhibits platelet activation, and improves fibrinolysis activity after balloon injury.
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AIM This study is to observe the effects of acutobin on the activity of tissue type plasminogen activitor(t PA) and tissue plasminogen activitor inhibitor(PAI) in the cultured human umbilical vein endothelial cells, aiming at disclosing some of the mechanisms of thrombolysis of acutobin. METHODS Endothelial cells were isolated from fresh human umbilical cords by trypsin digestion of the interior surface of the umbilical vein. Cultured cells were examined by light, phase contrast and electron microscopy. The factorⅧ related antigen and CD34 of the cells were detected by AEC and DAB staining. Chromogenic assay was used to identify the activity of t PA and PAI in the medium of culture cells. Fibrin degradation products(FDPs) were measured using ELISA kit. RESULTS The cultured human umbilical endothelial cells were shown as monolayers of closely opposed, polygonal cobblestone shape by light and phase contrast microscopy. By transmission electron microscopy, cultured endothelial cells contained Weibel Palade body and showed tight junction with each other. The cells contained abundant quantities of CD34 and factorⅧ related antigen. The intercellular space among individual cell enlarged and lost polygonal cobblestone shape in the present of acutobin. Activity of t PA increased, the activity of PAI did not change significantly and FDPs increased significantly in the culture medium. CONCLUSIONS The study demonstrates the culture cells was endothelial cells according to morphologic and immunohistologic criteria. Acutobin increases the fibrinolytic activity of cultured endothelial cells and may exhibit antithrombotic effect in vivo.
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0.05). Conclusion The human body blood coagulation or fibrinolytic system was not activated or inhibited by ETUS under the condition of this study.
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Objectives:To study the effects of gene therapy with tissue type plasminogen activator(t PA)cDNA on the formation of thrombo embolism in vascular anastomotic sites. Methods:①The cDNA encoding t PA was amplified by RT PCR using the isolated total RNA as the template from the Bowes melanoma cells.②Recombinant plasmid pAdCMV t PA was cotransfected into 293 cells with pJMa 17 ,and the infectious but replication deficient AdCMV t PA was generated.③The rats were randomly divided into the control and treatment groups.11 0 nylone medical suture was applied to perform rat carotid artery end to end anastomoses.In the treatment group,AdCMV t PA solution was injected into the vascular anastomotic site while AdCMV (no containing t PA DNA) solution was injected into the control group. By means of RT PCR and chromogenic plasmin substrates,the following results were obtained. Results:①The t PA cDNA was successfully cloned and its eukaryotic expressing vector was constructed.②When the isolated RNA was performed with RT PCR,1.69 kb band appeared in the treatment group while the band could not be found in the control group.The t PA activity could be detected postoperatively on the 1st,2 nd,3 rd,4 th,5 th,6 th,7 th,10 th and 13 th day of the treatment,but could not be detected in the control group. Conclusions:The t PA gene can produce t PA having biological activity at anastomotic sites, possibly prevent the formation of thrombus embolism effectively and develop the anastomotic patency.
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Animals , Humans , Rabbits , Administration, Intravenous , Ear , Femoral Vein , Jaw , Needles , Phenobarbital , Sodium Chloride , Thrombosis , Tissue Plasminogen Activator , VeinsABSTRACT
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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OBJECTIVES: Plasma fibrinolytic activity is determined by the balance between plasmonogen activators and their inhibitors. The aim of this study was to compare the fibrinolytic activity before and after exercise of the type 2 diabetic patients with control group. METHODS: We measured plasma tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen before and after standardized treadmill exercise in 21 type 2 diabetic patients (14 men, 11 women, ages 46.2+/-5.6 years) and 21 sex and age- matched control group (10 men, 11 women, ages 48.6+/-5.4 years). RESULTS: 1) Post exercise t-PA antigen increased in both diabetic group (from 7.36+/-3.89 to 10.62+/-4.81 ng/ml, p0.05) and control group (from 30.04+/-10.40 ng/ml to 31.06+/-10.88 ng/ml, p>0.05). 3) In diabetic group, significant correlations between base line PAI-1 antigen levels and serum triglyceride levels were observed. And post exercise PAI-1 antigen levels were correlated with systolic blood pressure. CONCLUSION: The results show that plasma t-PA antigen level is increased after vigorous exercise in patients with type 2 diabetes mellitus and plasma PAI-1 antigen level is not changed. The increment of plasma t-PA level is not different with healthy subjects.