Reverse tracing anti-thrombotic active ingredients from dried Rehmannia Radix based on multidimensional spectrum-effect relationship analysis of steaming and drying for nine cycles.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and modern pharmacodynamics, dried Rehmannia Radix (DRR) possesses prominent anti-thrombotic activity that decreases after processing by nine steaming and drying cycles to develop processed Rehmannia Radix (PRR). Due to the complexity of the DRR components, the chemical mechanism leading to efficacy changes of DRR caused by processing is still unclear. AIM OF STUDY: This study aimed to trace the anti-thrombotic active compounds of DRR and different degrees of processed RR (PRR) and to evaluate the synergistic effects among different active components. MATERIALS AND METHODS: The anti-thrombotic active chemical fraction of DRR extracts was evaluated. Targeted fractions of the processed products of RR were prepared at different processing stages. The changes in monosaccharides, oligosaccharides and secondary metabolites during processing were characterized by multidimensional high-performance liquid chromatography (HPLC). The anti-thrombotic effects of targeted fractions of different RR samples were evaluated by analyzing the length of tail thrombus (LT) and serum biochemical indicators in carrageenan-induced tail-thrombus mice. The spectrum-effect relationships were investigated by partial least squares regression (PLSR) analysis and gray correlation analysis (GRA). Finally, the active compounds were screened by spectrum-effect relationship analysis and validated in vivo, and their synergistic effects were determined by Webb's fraction multiplication method. RESULTS: Six ingredients highly associated with anti-thrombotic activities were screened out by the spectrum-effect relationship analysis, of which oligosaccharides (stachyose, sucrose and raffinose) and iridoid glycosides (catalpol, leonuride and melitoside) possessed a synergistic effect on tumor necrosis factors (TNF-α), interleukin 1ß (IL-1ß) and plasminogen activator inhibitor 1 (PAI-1)/tissue-type plasminogen activator (t-PA) ratio in vivo with synergistic coefficient (SC) > 1. CONCLUSION: The main material basis of the anti-thrombotic activities of DRR is oligosaccharide components of stachyose, raffinose and sucrose, iridoid glycosides components of catalpol, leonuride and melittoside. The two kinds of components exert synergistic anti-thrombotic effects by inhibiting the expression of inflammatory factors and regulating the balance of the fibrinolysis system.

Antiplatelets and profibrinolytic activity of Citrullus colocynthis in control and high-fat diet-induced obese rats: mechanisms of action.

The current study aimed to investigate the effect of Citrullus colocynthis (C. colocynthis) hydro-alcoholic extract on blood haemostasis in control and high-fat diet (HFD) induced obese rats. In control rats, the extract significantly enhanced bleeding time and plasma levels of tPA and significantly decreased plasma levels PAI-1 and serum levels of thromboxane B2 leading to inhibition of platelets aggregation. In HFD induced obese rats, similar effects were seen and the extract was also able to reverse HFD induced increases in fibrinogen and VWF. Searching for the mechanism, C. colocynthis acts by (1) inhibiting of food intake, (2) inhibiting the activity of pancreatic lipase, (3) decreasing levels of TNF-α and IL-6 and (4) decreasing circulatory levels of the prothrombotic adipokine, leptin and enhanced circulatory levels of the antithrombic adipokines and adiopnectin. In conclusion, C. colocynthis has antiplatelets and profibrinolytic activity in both control and HFD induced obese rats.

Multicenter Study of Adverse Events After Intravenous Tissue-Type Plasminogen Activator Treatment of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The approved treatment by the Food and Drug Administration for acute ischemic stroke is intravenous tissue-type plasminogen activator (IV tPA). After IV tPA administration, patients are monitored for adverse events using an American Heart Association/American Stroke Association guideline instituted in 1996. There is limited evidence describing the safest and most efficient method to monitor patients during the first 24 hours after tPA administration. Although the overall rates of adverse events have been reported, the time when patients may be at most risk for an event has not been studied. The purpose of this study was to identify the time of adverse event occurrences in the first 24 hours after IV tPA administration. METHOD: This was a descriptive, retrospective chart review study of patients admitted to an integrated health system and treated with IV tPA for acute stroke between July 2010 and July 2012. Charts were reviewed for adverse events using the Institute for Healthcare Improvement's Global Trigger Tool for Measuring Adverse Events. Possible chart indicators of adverse events or "triggers" included neurological decline, vital signs elevated above specified parameters, and emergent imaging. Adverse events included episodes of neurological decline, angioedema, allergic reactions, bleeding, and intracerebral hemorrhage (ICH). The timing of each detected event was determined, and descriptive statistics were used for data analysis. RESULTS: Fourteen adverse events (2.8%) were detected in a population of 498 patients. Reactions consisted of allergic reaction (n = 1), angioedema (n = 1), neurological decline without ICH (n = 1), gastrointestinal bleeding (n = 1), bleeding gums (n = 1), and high-risk ICH (n = 9). Thirteen of the 14 adverse events (92.9%) occurred within the first 12 hours after IV tPA administration. CONCLUSION: Close monitoring during the first 12 hours after IV tPA treatment may be essential. However, close monitoring after 12 hours may not contribute significantly to improved patient outcomes. Larger studies may provide evidence for the safest and most efficient monitoring protocol for patients treated with IV tPA for ischemic stroke.

Tongqiaohuoxue decoction ameliorates obesity-induced inflammation and the prothrombotic state by regulating adiponectin and plasminogen activator inhibitor-1.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongqiaohuoxue decoction (THD), a water extract of a mixture of eight species of medicinal herbs, has been used for the treatment of blood stasis and hypercoagulation in traditional East Asian medicine since 18th century. AIM OF THE STUDY: To investigate the in vivo efficacy of THD using high-fat diet (HFD)-induced obese mice with chronic inflammation and a prothrombotic state as an early vascular model. MATERIALS AND METHODS: THD was prepared by hot water extraction and freeze-drying. Male C57BL/6 mice were divided into three groups. Group 1 (NC) mice were fed normal chow. Mice in group 2 (HFD) and 3 (HFD+THD) were fed with HFD for 12 weeks. In addition, Group 3 mice were administered with 100mg/kg body weight THD for 4 weeks after onset of obesity by HFD for 8 weeks. Glucose tolerance tests and histological tissue examinations were performed. The levels of adipokines, inflammatory markers, and prothrombotic markers were assessed. RESULTS: The oral administration of THD for 4 weeks had no effect on the liver, adipose tissue, or total body weight when the HFD and HFD+THD groups were compared. Nevertheless, mice treated in THD interestingly showed a significant increase in adiponectin in blood and adipose tissue. To verify the effect of THD on adiponectin, 3T3-L1 adipocytes were treated with THD; it stimulated adiponectin production in a dose-dependent manner. In the HFD+THD group, pro-inflammatory cytokines were significantly down-regulated in the blood, adipose tissue, and liver. Insulin resistance was also notably improved by THD. Simultaneously, THD significantly reduced plasminogen activator inhibitor-1 (PAI-1) levels in serum, adipose tissue, and liver. Fibrin deposition and tPA activity, downstream targets of PAI-1, were also notably reduced in the HFD+THD group compared to the HFD group. CONCLUSIONS: THD improved obesity-induced inflammation and insulin resistance by increasing adiponectin production. Additionally, THD administration exerted an anti-thrombotic effect through the regulation of PAI-1 and fibrinolysis. This study demonstrates the efficacy of a traditional East Asian medicine by providing scientific evidence and suggesting a possible mechanism of action.

Fibrinolytic effects of peroneal nerve stimulation in patients with lower limb vascular disease.

Patients with lower limb vascular disease are at an increased risk of thrombotic events. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) are important components of the fibrinolytic system, responsible for clot lysis. This study aimed to establish whether peroneal nerve stimulation (PNS) could promote fibrinolysis within a cohort of vascular patients. Ethical approval was obtained for this prospective case-controlled study. Patients were randomly assigned to active stimulation or control groups. Arterial flow measurements and venous blood samples were taken bilaterally at baseline and following 45 min of PNS. ELISA analysis for plasma t-PA and PAI-1 was performed utilizing commercially available kits. Statistical analysis evaluated the changes in t-PA and PAI-1 levels from baseline for the active (device active), passive (contralateral limb) and control limbs (inactive device applied).Seventy-seven participants were recruited: 30 claudicants (25 active and five controls), 25 patients postoperative infra-inguinal bypass grafts (19 active and six controls) and 22 patients with varicose veins (17 active and five controls). t-PA levels reduced significantly in all groups; however, intergroup analysis demonstrated no statistically significant difference when comparing the active, passive and control limbs (P = 0.079). PAI-1 levels decreased by 16.2% (34.0 ng/ml, SD 52.2) in the active limbs but only 3.6% (11.4 ng/ml, SD 47.4) and 2.6% (2.7 ng/ml, SD 21.3) in the passive and control limbs, respectively (intergroup analysis P < 0.001). No relationship between changes in flow and plasma of t-PA and PAI-1 were demonstrated. Peroneal nerve stimulation may augment fibrinolysis by decreasing plasma levels of PAI-1 levels in patients with lower limb arterial and venous disease.

[Effects of Huoxue Dingxuan Capsule Glare on Vertebral Artery Blood Flow,Plasma PAI and t-PA in CSA Rat Models.]

OBJECTIVES: To determine the effects of Huoxue Dingxuan Capsule on vertebral artery blood flow,plasma plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in rats with cervical spondylosis of vertebral artery type (CSA). METHODS: Ninety healthy male Wistar rats were equally and randomly divided into control,model and treatment groups.The rats in the model and treatment groups were subject to composite modeling manufacturing CSA.The treatment group was given six-week interventions with Huoxue Dingxuan capsule 4 weeks after the modeling.Vertebral artery blood flow,plasma PAI,and t-PA contents were detected before modeling,prior to the interventions,and post interventions. RESULTS: Before the interventions,the rats in the model and treatment groups had significantly lower blood flow of vertebral artery than the controls (P<0.05).The model rats also had increased serum PAI and t-PA contents (P<0.01).After the interventions,significantly higher vertebral blood flow was found in the treatment group compared with the controls (P<0.05).After the interventions,increased serum PAI and t-PA contents were observed in the rats in the model group (P<0.01);whereas,decreased serum PAI and t-PA contents were observed in the rats in the treatment group (P<0.01).The treatment group had lower levels of serum PAI and t-PA contents than the model group (P<0.01). CONCLUSIONS: Huoxue Dingxuan Capsule glare can improve the blood flow of vertebral artery and reduce serum PAI and t-PA contents.

Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial.

OBJECTIVE: Low vitamin D levels and risk factors for vascular disease are both common in South Asian women. This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels. METHODS: Parallel-group, double-blind, randomised placebo-controlled trial. Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of <75 nmol/L were randomised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo. Outcomes were measured at baseline, 4 and 8 weeks. The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation. Secondary outcomes included blood pressure, arterial stiffness, microvascular function measured using laser Doppler iontophoresis, insulin resistance, serum lipids, circulating markers of inflammation, thrombosis and adipokines. RESULTS: 50 women were randomised, 25 to each group. Mean age was 41 years; mean baseline 25-hydroxyvitamin D level was 27 nmol/L. 25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks (16 nmol/L, 95% CI 11 to 21, p < 0.001). There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks (0.1%, 95% CI -0.9 to 1.1, p = 0.84) or 8 weeks (0.0%, 95% CI -1.4 to 1.4, p = 0.98). There was no improvement in cholesterol, insulin resistance or markers of inflammation. Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks. CONCLUSION: A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels. TRIAL REGISTRATION: ISRCTN75081811.

Icariin attenuates the enhanced prothrombotic state in atherosclerotic rabbits independently of its lipid-lowering effects.

Icariin is a major active component isolated from the traditional Chinese herb Epimedium brevicornum, with a wide range of pharmacological and biological activities. In this paper, we investigated the effects of icariin on hyperlipidemia, and further evaluated whether icariin could improve unfavorable hemorheological parameters, attenuate platelet activation and facilitate the balance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities in rabbits fed a high-cholesterol diet. Icariin reduced the levels of serum total cholesterol and low-density lipoprotein cholesterol, as well as the atherosclerotic burden. In addition, this compound has been found to improve the imbalance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities, reduce platelet adhesiveness and aggregation and modulate unfavorable hemorheological variables in hypercholesterolemia. In conclusion, icariin has lipid-lowering effects and may be used in the treatment and prevention of thrombosis in the atherosclerotic process.

Protective effect of magnesium lithospermate B against dextran sodiumsulfate induced ulcerative colitis in mice.

Anti-platelet drugs have been used to treat inflammatory bowel disease. In this study, we observed the therapeutic effects of magnesium lithospermate B, a main component of salvianolate, on colitis induced by dextran sodiumsulfate (DSS). Colitis was induced by 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (60-240mg/kg) was given by subcutaneous injection for 2 weeks. Then, mice were sacrificed; serum and colon tissues were collected for biomarker assay, histological examination, immunohistochemical study and real-time quantitative polymerase chain reaction. DSS induced gross bleeding, inflammation, crypt damage and mucosal damage in colon. Treatment with magnesium lithospermate B could reduce colon inflammation induced by DSS. Magnesium lithospermate B could reverse the high CD40/CD40L expression and hypercoagulable state induced by DSS in colon. This study showed that magnesium lithospermate B could be used to treat colitis. The protective effects of magnesium lithospermate B may be due to its effects on CD40/CD40L expression and blood clotting status.

Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial.

OBJECTIVE: To investigate the possible effects of low-frequency electroacupuncture (EA) and physical exercise on markers of coagulation and fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women with polycystic ovary syndrome (PCOS). DESIGN: Secondary analyses of a prospective, randomized controlled clinical trial. SETTING: Department of Physiology and Department of Obstetrics and Gynecology, University of Gothenburg. PATIENT(S): Eighty-four women with PCOS were randomized. INTERVENTION(S): Women with PCOS were randomized to 16 weeks of low-frequency EA (14 treatments), physical exercise (at least 3 times/wk), or no intervention. MAIN OUTCOME MEASURE(S): Anthropometrics, circulating coagulation and fibrinolytic markers, insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and adipose tissue morphology/function recorded at baseline, after 16 weeks of intervention, and after a 16-week follow-up. RESULT(S): In the low-frequency EA group, circulating plasminogen activator inhibitor 1 activity decreased by 21.8% after 16 weeks of intervention and by 31.1% at the 16-week follow-up and differed from the physical exercise and the no intervention groups. The EA group had decreases in circulating fibrinogen and tissue plasminogen activator (t-PA), sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen remained lower at the 16-week follow-up. In the physical exercise group, lipoprotein lipase activity increased and diastolic blood pressure decreased after treatment, and both diastolic and systolic blood pressure were lower at follow-up. No other variables were affected. CONCLUSION(S): Low-frequency EA counteracted a possible prothrombotic state in women with PCOS, as reflected by a decrease in plasminogen activator inhibitor 1 activity. Despite within-group improvements, there were no between-group differences in anthropometric, metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at the dose/intensity studied.

Profibrinolytic effect of Enzamin, an extract of metabolic products from Bacillus subtilis AK and Lactobacillus.

Fibrinolytic system impairment contributes to the development of thrombotic disease such as cardiovascular disease and stroke. Therefore, an agent that increases fibrinolytic activity may be useful for the prevention of these diseases. In this study, to explore novel profibrinolytic agents, we examined the profibrinolytic effect of Enzamin, an extract of metabolic products from Bacillus subtilis AK and Lactobacillus in vitro and in vivo. Enzamin directly enhanced plasmin activity generated by tissue-type plasminogen activator (t-PA) by twofold but not by urokinase-type plasminogen activator (u-PA) in vitro, which was measured employing both the chromogenic substrate H-D: -Val-Leu-Lys-pNA (S-2251) and fibrin plate. Enzamin also increased plasmin activity generated by t-PA in the cell lysate and culture medium of endothelial cells, measured by fibrin zymography. Furthermore, the oral administration of a 1% concentration of Enzamin increased plasmin activity generated by t-PA by 1.7-fold but not by u-PA in the euglobulin fraction of mouse plasma. In conclusion, Enzamin has a unique ability to enhance the fibrinolytic activity through an increase in endogenous plasmin activity generated by t-PA released from endothelial cells, and may be a beneficial supplement for the prevention of thrombotic episodes.

[The effects of tea polyphenols on the injury of fibrinolytic functions induced by high-methionine dietary in rats].

OBJECTIVE: To study the protective impact of tea polyphenols (TP) on the injury of fibrinolytic functions induced by high-methionine dietary in rats. METHODS: 50 male Wistar rats were divided by stratified based on body weight into 5 groups with 10 in each group: namely control group, model group, low-dose TP group, medium-dose TP group and high-dose TP group. The rats in model group and TP groups were fed with 3% methionine dietary, control group rats with routine diet. In addition, rats in low-dose, medium-dose and high-dose TP groups were treated with TP at 50, 100 and 200 mg/kg dosage respectively by gavages every day, control group and model group rats were given with same amount distilled water. The animals were sacrificed after 8 weeks. The levels of tissue-type plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1) in plasma were determined by ELISA assays, mRNA levels of t-PA and PAI-1 in aortic arch were detected by RT-PCR, t-PA and PAI-1 expression in aortic arch were detected by immunohistochemistry strept-avidin-biotin complex (SABC). RESULTS: After experiment, the t-PA expression of aortic arch in control group, model group, low-dose TP group, medium-dose TP group and high-dose TP group were 133.03 ± 10.14, 95.46 ± 11.08, 111.97 ± 11.91, 130.23 ± 10.80, 139.39 ± 9.41 (F = 14.15, P < 0.01), respectively, and the PAI-1 expression were 90.91 ± 8.67, 166.76 ± 12.18, 139.63 ± 12.71, 134.66 ± 13.19, 109.49 ± 10.82 (F = 31.44, P < 0.01). The t-PA concentration of plasma were (10.69 ± 1.26), (6.13 ± 0.92), (8.56 ± 1.19), (9.69 ± 0.92), (11.97 ± 1.08) ng/ml, respectively (F = 41.98, P < 0.01), and the PAI-1 concentration of plasma were (6.31 ± 0.81), (16.98 ± 1.27), (11.39 ± 0.82), (8.46 ± 0.67), (8.08 ± 0.91) ng/ml, respectively (F = 207.74, P < 0.01). The mRNA levels of t-PA in aortic arch were 1.12 ± 0.02, 0.75 ± 0.14, 1.01 ± 0.09, 0.95 ± 0.08, 1.05 ± 0.13 (F = 5.77, P < 0.05), and the mRNA levels of PAI-1 in aortic arch were 1.25 ± 0.11, 1.74 ± 0.06, 1.23 ± 0.05, 1.09 ± 0.14, 1.23 ± 0.04 (F = 23.56, P < 0.01). CONCLUSION: The results indicate that TP seems to have regulatory function on transcription and protein levels of t-PA and PAI-1, in addition to maintaining the balance between PAI-1 and t-PA and healing the injury of fibrinolytic functions in rats induced by high-methionine dietary.

[Experimental study on effect of pre-acupuncture and moxibustion on molecular markers in pre-thrombosis state of rats].

OBJECTIVE: To explore the best method for prevention and treatment of thrombosis and its mechanism. METHODS: Forty SD rats were randomly divided into a blank group, a model group, an electroacupuncture group and a crude herb moxibustion group. In the electroacupuncture group and the crude herb moxibustion group. "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Pishu" (BL 20) and "Geshu" (BL 17) were punctured or moxibusted for 2 weeks, then pre-thrombosis model was induced by Adrenalin Hydrochloride and ice water method in the model group, the electroacupuncture group and the crude herb moxibustion group, respectively. Molecular markers in venous blood after the model made in 18 hours were detected. RESULTS: Act: vaty of tissue-type plasminogen activator (t-PA) and content of alpha-granule membrane protein (GMP-140) decreased and content of nitrogen monoxidum (NO) increased after electroacupuncture or crude herb moxibustion. The levels of t-PA and GMP-140 in the model group were higher than those in the electroacupuncture group, the crude herb moxibustion group and the blank group (all P < 0.05), and the content of NO in the model group was lower than those in the electroacupuncture group, the crude herb moxibustion group and the blank group (all P < 0.05), while there was no significant difference in t- PA, GMP-140 and NO among the crude herb moxibustion group, electroacupuncture group and blank group (all P > 0.05). CONCLUSION: Electroacupuncture and crude herb moxibustion can significantly change the contents of t-PA, GMP-140 and NO and there was no significant difference between the two therapies.

Effect of Chinese herbal medicine for activating blood circulation and detoxifying on expression of inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.

OBJECTIVE: To observe the pharmaceutical effect of Chinese drugs for activating blood circulation (Xiongshao Capsule, XSC, ) and for activating blood circulation and detoxification (Xiongshao Capsule and Huanglian Capsule, XSHLC, ) in terms of the indices of thrombosis, inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats. METHODS: Fifty Wistar rats were randomly divided into the sham operation group, the model group, the Simvastatin group (SG), the activating blood circulation (ABC) group, and the activating blood circulation and detoxifying (ABCD) group, with 10 rats in each group. Simvastatin (1.8 mg/kg), XSC (0.135 g/kg) and XSHLC (0.135 g/kg) were administered to Simvastatin, ABC and ABCD group by gastrogavage, and an equal volume of normal saline was given to the sham operation group and the model group. After 2 weeks of successive medication, the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model. The serum levels of matrix metalloproteinases (MMP-9), tissue inhibitors to metalloproteinase (TIMP-1), granule membrane protein-140 (GMP-140), tissue-type plasminogen activator (t-PA), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were detected with enzyme-linked immunoassay 24 h later. RESULTS: Compared with the model group, the levels of serum GMP-140, hs-CRP, IL-6 and MMP-9 were significantly decreased, and the level of t-PA was significantly increased in the ABC and ABCD group ( P<0.05), while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group (P<0.05). CONCLUSIONS: Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis, inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats. The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.

Acute ingestion of long-chain (n-3) polyunsaturated fatty acids decreases fibrinolysis in men with metabolic syndrome.

Individuals with metabolic syndrome (MetS) often have elevated plasma plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA), contributing to an increased risk of cardiovascular disease. PAI-1 and t-PA may be affected by chronic (n-3) long-chain PUFA [(n-3)LCPUFA] supplementation; however, the acute impact of fat ingestion on these risk factors has not been established. Our objective was to investigate the acute effect of (n-3)LCPUFA on plasma PAI-1, t-PA, and platelet aggregation. We conducted a randomized crossover study in which men (n = 8, > or =45 y) with MetS consumed water or a high-saturated fat beverage (1 g fat/kg body weight) with either a high or low content of (n-3)LCPUFA. Blood samples were collected over 8 h to measure triacylglycerol (TAG), PAI-1, t-PA, and platelet aggregation. Both fat loads resulted in a significant increase in whole blood TAG concentration, plasma PAI-1 and t-PA concentrations, and PAI-1 activity, as well as a significant decrease in t-PA activity during the postprandial period. Interestingly, PAI-1 concentration and activity increased more following the high (n-3)LCPUFA compared with the low (n-3)LCPUFA beverage (P < 0.05). Furthermore, the high (n-3)LCPUFA beverage resulted in a lower t-PA activity (P < 0.05), whereas the effects of the 2 fat loads on the plasma t-PA concentration and platelet aggregation did not differ. Overall, acute intake of a high (n-3)LCPUFA beverage shifted the balance between plasma PAI-1 and t-PA, which might indicate a lower capacity for fibrinolysis.

[Effects of Erigeron breviscapus injection on TNF-alpha, PAI-1 and tPA in rats with acute myocardial infarction].

OBJECTIVE: To research the effects of Erigeron breviscapus injection (EBI) on TNF-alpha, PAI-1 and tPA in rats with acute myocardial infarction. METHODS: Models of acute myocardial infarction (AMI)were produced by ligation of left anterior descending coronary artery, then rats were randomly divided into control and experimental groups, then respectively gavaged NS, and the low, middle and high dosage of EBI for one week. The cardiac function index and the expression of TNF-alpha, tPA and PAI-1 were measured. RESULTS: Compared with the NS group, the cardiac function LVEDP, MAP, LVPmax, +/- dp/dt of AMI rat was improved by EBI in all dosage range, and the expression of TNF-alpha and PAI-1, LVEDP were decreased (P < 0.05), the expression of tPA, MAP, LVPmax and +/- dp/dt were increased obviously (P < 0.05) and had a dose-effect relationship. CONCLUSION: EBI can inhibit the expression of TNF-alpha and PAI-1, increase the expression of tPA,which can prevent the ongoing thrombopoiesis after AMI and improve the cardiac function. This maybe attributes to the inhibition of the overexpression of TNF-alpha.

Early initiation of low-dose atorvastatin treatment after an acute ST-elevated myocardial infarction, decreases inflammatory process and prevents endothelial injury and activation.

BACKGROUND: High-dose statin treatment improves clinical outcome of ST-elevated myocardial infarction (STEMI). However, the effect of low-dose atorvastatin treatment on inflammatory and pro-thrombotic molecules during the post-STEMI period is unclear. We investigated the effect of low-dose atorvastatin treatment on the kinetics of cytokine IL-6, vascular cell adhesion molecule (sVCAM-1) and endothelium-derived markers of thrombosis/fibrinolysis such as von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA), post STEMI. METHODS: Twenty-four normocholesterolemic patients with STEMI were randomised to receive atorvastatin 10mg/day or no statin treatment for 6 weeks after the event. Blood samples were obtained by their admission to the hospital as well as at weeks 1 and 6. Circulating levels of IL-6, sVCAM-1, vWF, PAI-1 and tPA were determined by ELISA. RESULTS: Atorvastatin induced a decrease of IL-6 at 1 week, an effect which reached significance compared to baseline at 6 weeks post STEMI (p<0.05 vs baseline). Serum sVCAM-1 was increased in controls both at 1 and 6 weeks post-STEMI (p<0.05 vs baseline), an effect prevented by atorvastatin. Plasma vWF was increased 1 week post-STEMI in controls (p<0.05 vs baseline) and returned to baseline at 6 weeks, an effect prevented by atorvastatin. Plasma PAI-1, tPA and the PAI-1/tPA ratio remained unchanged in both groups. CONCLUSION: Early initiation of low-dose atorvastatin treatment decreases the expression of IL-6 and sVCAM-1 and the release of vWF in patients with STEMI. Therefore, low-dose atorvastatin, modulates inflammatory response and decreases endothelial injury and activation in patients with recent STEMI.

Effects of propyl gallate on carotid artery thrombosis and coagulation/fibrinolysis system in rats.

OBJECTIVE: To investigate the effects of propyl gallate (PrG) on the thrombus formation time and the coagulation/fibrinolysis system in an experimental carotid artery thrombosis model in rats. METHODS: Fifty SD rats were randomly divided into 5 groups (10 animals/group): the normal group (normal saline 2 mL/kg), the model group (normal saline, 2 mL/kg), the heparin control group (1,250 IU/kg), the low dose PrG group (30 mg/kg), and the high dose PrG group (60 mg/kg). Thirty minutes after intravenous injection of saline or the corresponding drugs, a carotid artery thrombus was induced by continuous electric stimulation in all rats except for those in the normal group. The duration from the initiation of the electric stimulation to the sudden drop in carotid temperature was recorded as the thrombus formation time. Levels of plasma tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA. RESULTS: PrG (30 and 60 mg/kg) can prolong the thrombus formation time, but the effect was obviously weaker than that of heparin (P<0.05, P<0.01). Compared with the model group, PrG (30 and 60 mg/kg) elevated the plasma activity of t-PA (both P<0.05) and showed an increasing tendency in elevating the ratio of t-PA/PAI-1 (P>0.05), while it had no significant effect on the level of PAI-1. CONCLUSION: PrG has a certain antithrombotic effect and can slightly regulate the imbalance of the t-PA /PAI-1 ratio.

Chronic dietary fat intake modifies the postprandial response of hemostatic markers to a single fatty test meal.

BACKGROUND: Hemostasis is the result of a complex equilibrium between coagulation and fibrinolysis, and the influence of different dietary models on this equilibrium is not entirely known. OBJECTIVE: The objective was to compare the effects of the chronic intake of different dietary models on postprandial hemostasis. DESIGN: In a randomized crossover design, 20 healthy men consumed for 28 d each diets rich in monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and carbohydrates plus n-3 fatty acids (CHO/N3). Fasting and postprandial hemostatic factors (factor VII coagulant activity, plasminogen activator inhibitor-1, tissue-type plasminogen activator, d-dimer, and thromboxane B(2)) were measured; meal tests for the postprandial measures were based on butter, virgin olive oil, and walnuts for the SFA, MUFA, and CHO/N3 diets, respectively. RESULTS: There were no differences in the fasting variables after the dietary periods. After the 3 fatty meals were consumed, we observed an increase in thromboxane B(2) and d-dimer and a reduction in tissue plasminogen activator, irrespective of the dietary model. The MUFA or CHO/N3 meals lowered postprandial concentrations of factor VII coagulant activity, although the reduction was greater after the MUFA-enriched meal. The concentration of plasminogen activator inhibitor-1 was greater after the SFA meal than after the other 2 meals. CONCLUSIONS: The administration of a fatty meal induces a postprandial procoagulant tendency, irrespective of the type of fat consumed. However, the use of a dietary model rich in SFA creates a more procoagulant environment than does a model that includes MUFA or CHO/N3 as the source of fatty acids.

Effects of long-term erythropoietin therapy on fibrinolytic system in haemodialyzed patients.

INTRODUCTION: Recombinant human erythropoietin (rHuEPO) is the cornerstone of anaemia therapy in uraemic patients however the effects of this hormone on fibrinolytic system are difficult to interpret. MATERIALS AND METHODS: Assessment of fibrinolytic parameters: tissue-type plasminogen activator (tPA) antigen, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1) and plasmin/antiplasmin (PAP) complexes were performed in haemodialyzed (HD) patients without rHuEPO therapy: Group I (n=8, Hg<10 g/dl); Group II (n=12, Hg>10 g/dl); and in HD patients treated with rHuEPO for more than 6 months (Group III, n=10) or for more than 12 months (Group IV, n=9) in relation to the healthy controls. RESULTS: Patients of Group I had the significantly lower haematological parameters than those of Groups II, III and IV. All the fibrinolytic parameters studied, except PAI-1, were significantly higher in HD patients without rHuEPO therapy when compared to the controls. There were no significant differences in fibrinolytic system between the Groups I and II. Erythropoietin therapy resulted in progressive decrease in antigenic tPA levels, which reach normal range values after 6 months rHuEPO administration. uPA and PAP concentrations were also decreased and reached normal values after 12 months of rHuEPO therapy. In these patients a significant decrease in uPAR levels was also observed. Therapy with rHuEPO did not alter PAI-1 concentrations in HD patients. CONCLUSIONS: These results suggest that long-term rHuEPO therapy can correct fibrinolytic parameters in patients undergoing regular HD irrespective from haemoglobin levels and in the absence of concomitant iron supplementation.