Thromboembolism is a crucial part of the global disease burden. It has high incidence, high mortality and disability rates, and the mechanism of occurrence and development is extremely complex. It is difficult to detect the disease in the early stage so that we have trouble with clinical prevention and treatment in general. At present, four items of blood coagulation and D-dimer have been widely used in the evaluation and auxiliary diagnosis of thromboembolism, the monitoring of effect for antithrombotic drugs and other fields. The thrombus biomarkers including thrombin-antithrombin complex (TAT), thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC) and α2-plasmin inhibitor-plasmin complex (PIC) fill the gap of laboratory diagnosis before clinical symptoms appear in some degree. This article aims to explain the current application status of TAT, TM, t-PAIC and PIC in thromboembolism and explore their potential application value, so as to provide a reference for selecting appropriate early monitoring indicators for high-risk population of thromboembolism.
Humans ; Tissue Plasminogen Activator ; Plasminogen Inactivators ; Thrombomodulin ; Thromboembolism ; Biomarkers

Thromboembolism is a crucial part of the global disease burden. It has high incidence, high mortality and disability rates, and the mechanism of occurrence and development is extremely complex. It is difficult to detect the disease in the early stage so that we have trouble with clinical prevention and treatment in general. At present, four items of blood coagulation and D-dimer have been widely used in the evaluation and auxiliary diagnosis of thromboembolism, the monitoring of effect for antithrombotic drugs and other fields. The thrombus biomarkers including thrombin-antithrombin complex (TAT), thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC) and α2-plasmin inhibitor-plasmin complex (PIC) fill the gap of laboratory diagnosis before clinical symptoms appear in some degree. This article aims to explain the current application status of TAT, TM, t-PAIC and PIC in thromboembolism and explore their potential application value, so as to provide a reference for selecting appropriate early monitoring indicators for high-risk population of thromboembolism.
Humans ; Tissue Plasminogen Activator ; Plasminogen Inactivators ; Thrombomodulin ; Thromboembolism ; Biomarkers

BACKGROUND: Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are Involved. One of these enzymes is the urokinase - type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) a]so have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the love]s of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement Here, we measured the concentration of plasma u-PA and PAI- 1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. METHODS: We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. RESULTS: The concentration of u-PA was 1.0α0.3ng/mL in controls, 1.0α0.3ng/mL in benign lung disease patients and 0.9α0.3ng/mL in lung cancer patients. The concentration of PAI-1 was 14.2α6.7ng/mL in controls, 14.9α6.3ng/mL in benign lung disease patients, and 22.1 α9.8ng/mL in lung cancer patients. The concentration of PAI- 1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was 0.7α0.4ng/mL in squamous cell carcinoma, 0.8α 0.3ng/mL in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and 1.1α0.7ng/mL in small cell carcinoma. The concert traction of PAI-1 was 22.3α7.2ng/mL in squamous cell carcinoma, 22.6α9.9ng/mL in adenocarcinoma, 42ng/mL in large cell carcinoma, and 16.0α14.2ng/mL in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, 1.2α0.6ng/mL in stage II, 0.7 α 0.4ng/mL in stage IIIA, 0.7α0.4ng/mL in stage IIIB, and 0.7α0.3ng/mL in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, 22.7α8.7ng/mL in stage II, 18.4 α4.9ng/mL in stage IIIA, 25.3α9.0ng/mL in stage IIIB, and 21.5α10.8ng /mL in stage IV. When we divided T stage unto T1-3 and 74, the concentration of u-PA was 0.8α 0.4ng/mL in T1-3 and 0.7α0.4ng/mL in T4, and the concentration of PAI-1 was 17.9α 5.6ng/mL in T1-3 and 26.1α9.1ng/mL in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was 0.8α 0.4ng/mL in M0 and 0.7α0.3ng/mL in Ml, and the concentration of PAI-1 was 23.6α8.3ng/mL in M0 and 21.5α10.8ng/mL in M1 CONCLUSIONS: The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and control, and the plasma levels of PAI-1 in 74 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.
Adenocarcinoma ; Carcinoma, Large Cell ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix ; Humans ; Lung Diseases ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Neoplasm Metastasis ; Peptide Hydrolases ; Plasma* ; Plasminogen ; Plasminogen Activator Inhibitor 1* ; Plasminogen Activators ; Plasminogen Inactivators ; Proteolysis ; Traction ; Urokinase-Type Plasminogen Activator*

Plasminogen activator(PA) and plasminogen activator inhibitor(PAI) are involved in many physiological or pathological events. The Sertoli cells, the important elements within the seminiferous epithelium, are thought to play a key role in spermatogenesis. The Sertoli cells secrete PA and PAI. The levels of them are modulated by hormonal and cell-mediated influences. They play a fundamental role in the maintenance of spermatogenesis, sperm motility and fertilization.
Humans ; Male ; Plasminogen Activators ; metabolism ; physiology ; Plasminogen Inactivators ; metabolism ; physiology ; Sertoli Cells ; metabolism ; physiology ; Testis ; cytology

OBJECTIVETo investigate the effects of chronic mercury poisoning on blood coagulation and fibrinolysis systems, and the possible mechanism.

METHODSTwenty-seven patients with chronic mercury poisoning were studied with 30 healthy people as control. Thrombomodulin (TM), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), interleukin-13 (IL-13), interleukin-18 (IL-18), soluble intercellular adhesion molecule-1 (SICAM-1) were examined with ELISA methods, and superoxide dismutase (SOD) and lipid peroxidation (LPO) was examined with chemical catalysis methods. Two to three weeks after treatment with reduced glutathione, tiopronin and daidzein, blood was used for determin the above items again.

RESULTS(1) The concentration of TM in patients [(2.36 +/- 0.16) ng/ml] was significantly lower than in the control [(4.36 +/- 0.24) ng/ml] (P < 0.01), while TM tended to be higher after treatment [(4.82 +/- 0.34) ng/ml] (P < 0.05). (2) The concentration of t-PA in patients [(3.44 +/- 0.34) ng/ml] was significantly lower than in the control [(4.52 +/- 0.16) ng/ml] (P < 0.05), and was higher significantly [(5.63 +/- 0.58) ng/ml] after treatment (P < 0.05); The concentration of PAI in patients [(48.23 +/- 3.59) ng/ml] was significantly higher than in the control [(31.59 +/- 2.13) ng/ml] (P < 0.05), but after treatment no significant change [(50.71 +/- 4.29) ng/ml] was found (P > 0.05). (3) The activity of SOD in patients [(953.85 +/- 9.56) U/g Hb] was significantly lower than in the control [(1,308.75 +/- 10.21) U/g Hb] (P < 0.01), and was higher significantly [(1,217.95 +/- 6.29) U/g Hb] after treatment (P < 0.05); and the concentration of LPO in patients [(9.53 +/- 0.26) nmol/ml] was significantly higher than in the control (P < 0.05), and significantly lower [(7.29 +/- 0.35) nmol/ml] after treatment (P < 0.05). (4) The concentrations of IL-13 [(35.93 +/- 5.28) pg/ml], IL-18 [(28.79 +/- 2.53) pg/ml], SICAM-1 [(603.16 +/- 29.12) ng/ml] were significantly higher than those in the controls (P < 0.05, P < 0.01), but no significant difference was found after treatment.

CONCLUSIONDysfunction of the TM/protein C system and t-PA/PAI system (i.e. the decrease of anti-coagulation activity and the inhibition of the function for the fibrolysis system) may play a key role in the secondary hypercoagulable state induced by chronic mercury poisoning.

Adult ; Blood Coagulation ; physiology ; Case-Control Studies ; Chronic Disease ; Female ; Fibrinolysis ; physiology ; Humans ; Male ; Mercury Poisoning ; blood ; physiopathology ; Plasminogen Inactivators ; blood ; Thrombomodulin ; blood ; Tissue Plasminogen Activator ; blood

BACKGROUND: After multiple trauma, blood coagulation activity is enhanced and fibrinolytic activity is suppressed. Due to high tissue thromboplastin concentration in cerebral tissue, more serious coagulation and fibrinolytic abnormalities may occur when concomitant head trauma is present. The aim of this study was to determine the changes in coagulation and fibrinolysis after trauma and the effects of head trauma on coagulation and fibrinolysis. METHODS: This study includes 35 trauma patients: 16 patients with head trauma (group A) and 19 patients without head trauma (group B). We measured the plasma levels of functional protein C, antithrombin III (AT III), thrombin antithrombin III complex (TAT), plasmin alpha 2 plasmin inhibitor complex (PIC), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 antigen (PAI-1) on admission and on days 1, 2, 4, and 6 after the trauma. RESULTS: The TAT and the TAT/PIC were significantly higher in group A than in group B on all days. PIC was significantly lower in group A than in group B on all days except the day of admission. Over the course of time, the TAT and the TAT/PIC decreased in both groups and PIC increased. On admission, the PAI-1 of both groups was increased, but it decreased over the course of time. The t-PA was increased on admission, was suppressed on the 1st day, and then increased again. The PAI-1 and the t-PA showed no significant difference between the two groups. CONCLUSIONS: After multiple trauma, coagulation was enhanced and fibrinolysis was suppressed. Enhanced coagulation and suppressed fibrinolysis were significantly greater in group A than in group B.
alpha-2-Antiplasmin ; Antithrombin III ; Blood Coagulation ; Craniocerebral Trauma ; Fibrinolysin ; Fibrinolysis* ; Humans ; Multiple Trauma* ; Plasma ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Protein C ; Thrombin ; Thromboplastin ; Tissue Plasminogen Activator

Animals ; Calcitonin Gene-Related Peptide ; blood ; Cerebral Infarction ; blood ; Endothelins ; blood ; Humans ; Nitric Oxide ; blood ; Plasminogen Inactivators ; blood ; Thromboxane B2 ; blood

OBJECTIVETo explore curative machanism of Shenle capsule on the 5/6 nephrectomy rats.

METHODFibrin plate method was applied to examine activity of urinary plasminogen activator(PA). Semi-quantitative analysis was used to observe stained intensity and area of tissue-type plasminogen activator, urokinas-type plasminogen activator/ plasminogen activator inhibitor(tPA, uPA/PAI-1)in remnant renal tissue. Northern blot was employed to analyze the expression of transforming growth factor (TGF-beta) mRNA.

RESULTIn model control group, the urinary PA activity and protein expression of tPA, uPA were down-regulated, but protein expression of PAI-1, TGF-beta mRNA was up-regulated in remnant renal tissue. In each treated group, the urinary PA activity and protein expression of tPA/uPA were enhanced,but the protein expression of PAI-1, TGF-beta mRNA decreased simultaneously.

CONCLUSIONShenle capsule can delay glomerulosclersis and tubulointerstitial fibrotic lesions of remnant kidney by improving the activity of urinary PA and modulating the expression of tPA, uPA/PAI-1 and TGF-beta mRNA.

Animals ; Capsules ; Codonopsis ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Kidney ; metabolism ; Kidney Failure, Chronic ; drug therapy ; metabolism ; Leeches ; chemistry ; Male ; Materia Medica ; isolation & purification ; pharmacology ; Nephrectomy ; Plasminogen Inactivators ; metabolism ; Polyporales ; chemistry ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Tissue Plasminogen Activator ; metabolism ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Urokinase-Type Plasminogen Activator ; metabolism

OBJECTIVETo observe the effects of Danhong Injection (丹红注射液) and its main components, including daiclzein and hydroxysafflor yellow A (HSYA), on the anticoagulation, fibrinolysis, anti-apoptosis in hypoxia model of vein endothelial cells (VECs).

METHODSVECs were prepared and were put in a hypoxia environment, which consisted of mixed gas of 95% N and 5% CO mixed gas, when reached confluent culture. Five groups used different treatments, including normal control group, hypoxia group, daiclzein group, HSYA group and Danhong Injection group. The VECs were identified by fluorescence double labeling methods. The morphology was observed by a phase contrast microscopy. The effects of Danhong Injection, daiclzein and HSYA on 6 keto prostaglandin F1α (6-keto-PGF1α) level was measured by the method of radioimmunoassay (RIA). Superoxide dismutase (SOD) activity was tested by water soluble tetrazolium salt. The content of malondialdehyde (MDA) was measured by thiobarbituric acid. The activities of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured by the method of chromogenic substrate. The contents of endothelin (ET) and nitric oxide (NO) were detected by non-equilibrium RIA and enzymelinked immunosorbent assay. Cells apoptosis rate was determined by flow cytometry.

RESULTSCompared with the normal control group, the floating cells number, PAI activity, ET and MDA contents, and cells apoptosis rate in the culture solution of hypoxia group were all significantly increased, whereas the 6-keto-PGF1α and NO contents, and t-PA and SOD activities were decreased significantly (P<0.01). Compared with the hypoxia group, Danhong Injection markedly increased the 6-keto-PGF1α content and SOD activity, regulated PAI and t-PA activities, ET and NO contents, and decreased MDA content and cells apoptosis rate (P<0.05 or P<0.01).

CONCLUSIONSDanhong Injection and its main components played an important role in protecting primary VECs from hypoxic damage by regulating the secretion and vasomotor function of VECs. The function of Danhong Injection was most remarkable.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Coagulation ; drug effects ; Cell Count ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Endothelins ; metabolism ; Factor VIII ; metabolism ; Fibrinolysis ; drug effects ; Fluorescent Antibody Technique ; Humans ; Infant, Newborn ; Injections ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Plasminogen Inactivators ; metabolism ; Rabbits ; Superoxide Dismutase ; metabolism ; Tissue Plasminogen Activator ; metabolism ; Umbilical Veins ; cytology

OBJECTIVETo evaluate the effect of decoction for invigorating the kidney and improving blood circulation to thrombosis on rabbits blood stasis model.

METHODThirty rabbits were randomly divided into normal group, model group, heavy dose group, slight dose group and xue shuan ning group. Tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), fibrinogen (Fbg) and D-dimer (DD) were investigated after those rabbits had been treated. One was selected randomly from each group to observe pathological changes.

RESULTThere was significant difference in t-PA, PAI, Fbg and DD between normal group and other groups (P < 0.01). Among groups of heavy dose, slight dose, xue shuan ning and model, the statistical differences were significant, as well as among groups of heavy dose, slight dose and xue shuan ning (P < 0.05). However, there was no statistical difference between heavy dose group and slight dose group (P > 0.05). The pathological changes in model group were most serious, and those in xue shuan ning were less serious. There were slight pathological change in heavy dose group and light dose group.

CONCLUSIONModels were made successfully. Heavy dose group and slight dose group have stronger effect on thrombosis than xue shuan ning group.

Animals ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Kidney ; pathology ; Liver ; pathology ; Lung ; pathology ; Male ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry ; Plasminogen Inactivators ; blood ; Rabbits ; Random Allocation ; Thrombosis ; blood ; pathology ; Tissue Plasminogen Activator ; blood