Trauma-induced coagulopathy is classified into primary and secondary coagulopathy, with the former elicited by trauma and traumatic shock itself and the latter being acquired coagulopathy induced by anemia, hypothermia, acidosis, and dilution. Primary coagulopathy consists of disseminated intravascular coagulation and acute coagulopathy of trauma shock (ACOTS). The pathophysiology of ACOTS is the suppression of thrombin generation and neutralization of plasminogen activator inhibitor-1 mediated by activated protein C that leads to hypocoagulation and hyperfibrinolysis in the circulation. This review tried to clarify the validity of activated protein C hypothesis that constitutes the main pathophysiology of the ACOTS in experimental trauma models.
Acute Disease ; Animals ; Blood Coagulation Disorders ; etiology ; Disease Models, Animal ; Disseminated Intravascular Coagulation ; etiology ; Humans ; Mice ; Plasminogen Activator Inhibitor 1 ; Protein C ; physiology ; Thrombin ; Wounds and Injuries ; complications

OBJECTIVETo explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats.

METHODSDiabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB (NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four.

RESULTSIn diabetic model rats, PNS could not only reduce blood glucose and lipid (P<0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P<0.01) and in turn suppress the transcription of TGF-β1 (P<0.05) and MCP-1 (P<0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P<0.05) and SOD was up-regulated (P<0.01), which were both induced by SIRT1 up-regulation.

CONCLUSIONSPNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins.

Acetylation ; drug effects ; Animals ; Antioxidants ; metabolism ; Blood Glucose ; metabolism ; Bone Morphogenetic Protein 7 ; metabolism ; Chemokine CCL2 ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; genetics ; physiopathology ; Gene Knockdown Techniques ; Immunohistochemistry ; Kidney ; drug effects ; pathology ; Kidney Function Tests ; Lipids ; blood ; Male ; Malondialdehyde ; metabolism ; Mesangial Cells ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Panax notoginseng ; chemistry ; Plasminogen Activator Inhibitor 1 ; genetics ; metabolism ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; therapeutic use ; Sirtuin 1 ; genetics ; Superoxide Dismutase ; metabolism ; Transcription Factor RelA ; metabolism ; Transcription, Genetic ; drug effects ; Transforming Growth Factor beta1 ; metabolism ; Up-Regulation ; drug effects

BACKGROUNDPrevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.

METHODSSeventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated.

RESULTSThe PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group.

CONCLUSIONSResveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.

Animals ; Disease Models, Animal ; Femur Head Necrosis ; chemically induced ; prevention & control ; Lipopolysaccharides ; toxicity ; Magnetic Resonance Imaging ; Methylprednisolone ; toxicity ; Plasminogen Activator Inhibitor 1 ; blood ; Rabbits ; Stilbenes ; pharmacology ; therapeutic use ; Thrombomodulin ; blood ; Tissue Plasminogen Activator ; blood ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo study the expression of transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1) and its significance in premature infants with bronchopulmonary dysplasia (BPD).

METHODSA retrospective analysis was performed on the clinical data of 96 very low birth weight infants (gestational age of ≤ 32 weeks) who survived for more than 28 days and were admitted to the Neonatal Intensive Care Unit between January 2010 and December 2012. These subjects were divided into BPD group (n=21) and non-BPD group (n=75). The expression of TGF-β1 and PAI-1 in blood was measured by ELISA.

RESULTSThe levels of TGF-β1 and PAI-1 in the BPD group increased gradually from the 7th day to the 14th day and then to the 21st day after birth, and were significantly higher than in the non-BPD group at all time points (P<0.01). The TGF-β1 and PAI-1 levels in the non-BPD group on the 7th, 14th, and 21st days after birth were not significantly different from each other (P>0.05).

CONCLUSIONSThe expression of TGF-β1 and PAI-1 in blood is elevated in premature infants with BPD, which may be associated with the development of BPD.

Bronchopulmonary Dysplasia ; etiology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Plasminogen Activator Inhibitor 1 ; blood ; Retrospective Studies ; Transforming Growth Factor beta1 ; blood

BACKGROUND: Gestational diabetes mellitus (GDM) is a hyperglycemic condition caused by increased insulin resistance and impaired insulin secretion during pregnancy. It is known to be temporary, but it can cause perinatal complications in the mother and baby. Additionally, it may progress to type 2 diabetes mellitus (T2DM). In the present study, we evaluated the risk factors for complications and progression to T2DM in patients with GDM. METHODS: The study included 130 pregnant women who were diagnosed with GDM at gestational weeks 24-28 in 2011. Body mass index and the levels of glucose, total cholesterol, lipoproteins, and coagulation factors (von Willebrand factor and plasminogen activator inhibitor-1) were assessed in all patients. RESULTS: The level of high-density lipoprotein (HDL) was significantly lower and the triglyceride/HDL ratio and coagulation factor levels were significantly higher in the group of patients with perinatal complications compared to those in the group of patients without complications. After delivery, the level of HDL was lower and the value of homeostasis model assessment of insulin resistance (HOMA-IR) was higher in women with impaired glucose metabolism compared to those in women with normal glucose metabolism. In logistic regression analysis, perinatal complications were independently associated with HDL and PAI-1 levels (OR = 0.929 and 1.101, respectively). CONCLUSION: The findings of our study show that the levels of HDL and coagulation factors are notable risk factors of perinatal complications. Additionally, we showed that lower HDL level may influence the progression to T2DM. Large-scale population studies are needed to verify our findings.
Blood Coagulation Factors ; Body Mass Index ; Cholesterol ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Diabetes, Gestational* ; Female ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Lipoproteins ; Lipoproteins, HDL ; Logistic Models ; Metabolism ; Mothers ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Postpartum Period* ; Pregnancy ; Pregnant Women ; Risk Factors* ; von Willebrand Factor

OBJECTIVE: To observe the changes of plasminogen activator inhibitor-1 and D-dimer during continuous blood purification (CBP) and related factors. METHODS: Sixteen patients who were diagnosed with multiple organ dysfunction syndrome (MODS) were randomly divided into 2 groups: 8 patients received standard continuous blood purification with heparin anticoagulation, and the other 8 received CBP without anticoagulation. Ten normal blood samples were collected from healthy volunteers as controls. All patients underwent CBP for 8 h. Blood was taken from those patients at 0, 15, 60, 120 and 480 min during the CBP. Plasma plasminogen activator inhibitor-1, D-dimer and serum TNF-α and IL-1β were measured by ELISA. RESULTS: Plasma levels of PAI-1 and D-dimer were increased significantly compared with those in the control group (P<0.05). Plasma level of PAI-1 was reduced (P<0.05) and D-dimer was increased (P<0.05) after the CBP. The level of plasma PAI-1 in the heparin group was significant reduced compared with the group of CBP without anticoagulation (P<0.05). There was negative correlation between the level of PAI-1 and the dosage of heparin used during a CBP session in the heparin group (r=-0.746, P<0.001). CONCLUSION The level of PAI-1 and D-dimer is higher in patients with MODS than that in the normal controls. After the CBP treatment, there is significant decrease in PAI-1 and increase in D-dimer in both groups. Heparin used during CBP can reduce PAI-1 which intensifies its function of anticoagulation.
Anticoagulants ; therapeutic use ; Fibrin Fibrinogen Degradation Products ; analysis ; Heparin ; therapeutic use ; Humans ; Interleukin-1beta ; blood ; Plasminogen Activator Inhibitor 1 ; blood ; Renal Dialysis ; Tumor Necrosis Factor-alpha ; blood

In order to discover the mechanism of Xuebijing oral effervescent tablet (XBJOET) to treat infectious diseases, the effect of XBJOET on endotoxin induced rabbit fever and disseminated intravascular coagulation (DIC) was investigated. Auricle microcirculation in rabbit was detected by laser speckle blood perfusion imager system; coagulation function was measured by coagulation analyzer, fibrinolytic system was quantified by Elisa assay and micro thrombosis in tissues was observed with HE staining under light microscope. The results demonstrated that the body temperature of rabbit decreased significantly at 1-3 h after administration with 4.8, 2.4 and 1.2 g x kg(-1) XBJOET to endotoxin induced DIC rabbit model, the auricle microcirculation blood flow in model group (54.45 +/- 14.53) PU was lower than that in control group (77.18 +/- 12.32) PU. The auricle microcirculation blood flow increased markedly and there was significant difference between model group and 1.2 g x kg(-1) XBJOET group. There was significant difference between model group and control group in the content of PAI1 and FIB. The PAI1 levels in model and control groups were (30.48 +/- 2.46) ng x mL(-1) and (20.93 +/- 3.25) ng x mL(-1), respectively. The FIB levels in model and control group were (3.34 +/- 1.09) g x L(-1) and (4.84 +/- 1.10) g x L(-1), respectively. The content of PAI1 in rabbit plasma decreased notably, there were significant differences between model group and 4.8, 2.4 g x kg(-1) XBJOET groups. On the contrary the content of FIB increased. XBJOET possessed pharmacological activities of curing infectious fever and DIC, the mechanism of which is related to amelioration of microcirculation disturbance, inhibition of fibrinolytic system activation and coagulation and micro thrombosis elimination.
Administration, Oral ; Animals ; Blood Coagulation ; drug effects ; Body Temperature ; drug effects ; Disseminated Intravascular Coagulation ; blood ; chemically induced ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ear Auricle ; blood supply ; Endotoxins ; Female ; Fever ; chemically induced ; drug therapy ; physiopathology ; Fibrinogen ; metabolism ; Male ; Microcirculation ; Partial Thromboplastin Time ; Plasminogen Activator Inhibitor 1 ; blood ; Prothrombin Time ; Rabbits ; Tablets ; Thrombosis ; pathology

OBJECTIVE: To investigate the effect of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (t-PA), and endothelin-1 (ET-1) on the atherosclerosis progress in the maintenance hemodialysis patients. METHODS: We enrolled 19 patients with maintenance hemodialysis (MHD) and 11 healthy people as control. Patients were divided into 2 groups according to their age above or below 40 years old (11 and 8 in each, respectively), whereas the subjects in control group were below 40 years old. All the clinical information of the research subjects was collected: including age, gender, time of hemodialysis, blood pressure, blood urea nitrogen (BUN), and serum creatinine (SCr). Immunohistochemistry and pathological image analysis were used to investigate the pathological changes, calcification and the expression of PAI-1, t-PA, and ET-1 on the blood vessel. RESULTS: Compared with the age-matched healthy control group, there were higher blood vascular media thickness, blood vascular media thickness/diagmeter ratio, blood vascular media thickness area/vascular inter-wall area ratio (P<0.05) and more calcification (P<0.05) in the the internal iliac artery in the chronic renal failure MHD patients. All the results were similar when compared the above 40 years old group with the below 40 years old one in the chronic renal failure MHD patients. There were positive correlation of blood vascular media thickness with age and blood pressure (P<0.05). Expression of PAI-1, ET-1, t-PA on the internal iliac artery vessel was elevated in the chronic renal failure MHD patients compared with the health control (P<0.05). The level of PAI-1 or ET-1 was much higher in the above 40 years old group than the below 40 years old one in the chronic renal failure MHD patients, whereas there was no significant difference in the t-PA expression between the 2 groups (P<0.05). There were positive correlation of PAI-1 or ET-1 expression with age and blood pressure (P<0.05). There were positive correlation of PAI-1 or ET-1 expression with blood vascular media thickness and calcification (P<0.05 or P<0.01). There was no correlation of hemodialysis time with blood vascular media thickness, calcification, PAI-1, t-PA, or ET-1 expressions. CONCLUSION MHD patients accompany with atherosclerosis which is severer in the patients above 40 years old than the patients below 40 years old. The higher of the blood pressure, the severer of the atherosclerosis. Abnormal expression of PAI-1 plays an important role in the progress of the atherosclerosis in the chronic renal failure MHD patients, whereas t-PA has no function in this process. The level of PAI-1 and ET-1 would be helpful to evaluating the degree of atherosclerosis in the chronic renal failure MHD patients. Hemodialysis time may not be a potential accelerator for atherosclerosis progression.
Adult ; Atherosclerosis ; blood ; etiology ; Endothelin-1 ; blood ; Female ; Humans ; Kidney Failure, Chronic ; therapy ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1 ; blood ; Renal Dialysis

To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication.
Acute Disease ; Adult ; Aged ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Herbicides/blood/*poisoning ; Humans ; Male ; Middle Aged ; Paraquat/blood/*poisoning ; Plasminogen Activator Inhibitor 1/*blood ; Reactive Oxygen Species/metabolism ; Risk Factors ; Tissue Plasminogen Activator/*blood ; Tomography, X-Ray Computed

OBJECTIVETo study the correlation between prethrombotic biomarkers and traditional Uyghur medicinal syndromes of malignant tumor.

METHODSOne hundred and fifty-nine malignant tumor inpatients were randomly selected and typed according to traditional Uyghur medicine theories. The expressions of peripheral platelet membrane glucoprotein (CD41 and CD62p), levels of serum endothelin (ET-1), plasma tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), plasma fibrinogen (FIB), prothrombin time (PT), and thrombin time (TT), and activated partial thromboplastin time (APTT) were detected by flow cytometry, radioimmunoassay, and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTSThe patients were typed as 68 of abnormal Savda syndrome, 34 of abnormal Khan syndrome, 31 of the abnormal Sepra syndrome, and 26 of the abnormal Belghem syndrome. Compared with the control group, the levels of CD62p, PAI, and ET-1 increased, levels of FIB and t-PA decreased, PT prolongated and APTT shortened in the abnormal Savda group and the non-abnormal Savda group (including abnormal Khan, abnormal Sepra, and abnormal Belghem types) (all P < 0.05). No significant difference of CD41 or TT was shown in inter-group comparison (P > 0.05). Compared with abnormal Khan and Belghem groups, the ET-1 level increased in the abnormal Savda group (P < 0.05). Compared with the abnormal Sepra group, the CD62p positive percentage increased in abnormal Savda group (P < 0.05). No significant difference in CD41 positive percentage, t-PA or PAI-1 contents, PT, TT, or APTT was shown in patients of different traditional Uyghur medicine syndrome groups (P > 0.05).

CONCLUSIONSPrethrombotic changes existed in malignant tumor patients of different Uyghur abnormal syndrome types, manifested as injuries of vessel epithelial cells, platelet activation, increased blood viscosity, lowered fibrinolytic function. The prethrombotic changes were more obviously seen in the abnormal Savda group.

Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Minority Groups ; Neoplasms ; blood ; diagnosis ; Partial Thromboplastin Time ; Plasminogen Activator Inhibitor 1 ; metabolism ; Platelet Membrane Glycoproteins ; metabolism ; Tissue Plasminogen Activator ; metabolism