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1.
Ana Portelinha Ana Sofia Cerdeira Jorge Braga Ana Pinto Maria José Areias Irene Rebelo 《Thrombosis research》2009,124(1):52-56
Objective
Evaluation of haemostatic parameters - Plasma tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1) and fibrin fragment D-dimer several years after the end of pregnancy to investigate if they are modified in women with history of preeclampsia (PE). Study design: 65 healthy women with history of PE and 54 control women with previous normal pregnancy were enrolled in this study. Groups were matched for age, time period since delivery, smoking status and alcohol consumption. t-PA, PAI-1 and fibrin fragment D-dimer antigen levels were quantified using standards commercial ELISA methods. Plasma fibrinogen was measured using automated capillary zone electrophoresis.Results
Systolic and diastolic blood pressures were higher in women with history of PE. Levels of t-PA, PAI-1 and fibrinogen were similar between groups as well as the t-PA/PAI-1 ratio. A significant increase in D-dimer levels was observed in women with history of PE.Conclusion
The increase in D-dimer level suggests an abnormal haemostatic potential namely increased intravascular coagulation. This, together with the increased blood pressure, can reflect a tendency for an increased risk of cardiovascular/thrombotic events later in life. 相似文献2.
George Mitsiakos Evaggelia Giougi Paraskevi Karagianni Christos Tsakalidis Pavlos Malindretos 《Thrombosis research》2010,126(2):103-106
Background
The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood.Objective
To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration.Study design
We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) < 37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters.Results
Premature SGA infants presented significantly lower levels of fibrinogen (p < 0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p < 0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters.Conclusions
Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms. 相似文献3.
Introduction
In COMET (Carvedilol or Metoprolol European Trial), carvedilol reduced mortality compared with metoprolol in patients with chronic heart failure. We hypothesized that carvedilol might have greater effects on endothelial derived haemostatic factors than metoprolol. We aimed to study the effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure.Material and Methods
We recruited 260 patients (134 on carvedilol, 126 on metoprolol), mean age 66 years and 84% of them men. Plasma mass concentrations of tPA and PAI-1and percent of VWF were measured at baseline and after one and two years of treatment.Results
Plasma tPA, PAI-1 and VWF were similar between treatment groups at baseline and no significant differences between groups emerged after one or two years of treatment. In paired analyses in patients assigned to carvedilol, median PAI-1 level decreased from 37.2 to 32.1 µg/l at two years (p = 0.034) and of VWF decreased from baseline to one year (240 vs. 218%, p = 0.023) in patients assigned to carvedilol but were not reduced at any time in patients assigned to metoprolol. Plasma tPA increased over time in both treatment groups (p = 0.013 and 0.027 respectively).Conclusion
We found no significant difference in the effects of carvedilol or metoprolol on tPA, PAI-1 and VWF. Comparison over time within treatment groups suggested that PAI-1 and VWF might have declined on carvedilol but not on metoprolol. Our hypothesis is not proved but this may reflect an inadequate sample size rather than lack of an effect. 相似文献4.
Mitsiakos G Papaioannou G Papadakis E Chatziioannidis E Giougi E Karagianni P Evdoridou J Malindretos P Athanasiou M Athanassiadou F Nikolaidis N 《Thrombosis research》2009,124(3):288-291
Background
Small for Gestational Age (SGA) neonates often appear with haemostatic alterations, principally due to hepatic dysfunction that results from chronic intrauterine hypoxia. Polycythaemia and thrombocytopenia are common findings in this neonatal population.Study design
We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born full term [gestational age (G.A.) > 37 weeks]. Study population consisted of 188 healthy newborns, 90 of whom were SGA (62 females and 28 males), while the rest were the control group (44 females and 54 males). Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test was used to compare the differences between the values of haemostatic parameters.Results
Statistical analysis revealed a significant prolongation in PT, INR, elevated levels of tPA (p < 0.015, 0.01 and 0.002 respectively) and a decrease in the values of XII and free protein S (p < 0.045 and 0.007 respectively) in SGA full term neonates. The two groups had similar demographic characteristics (except birth weight), without significant differences in the values of other haemostatic parameters.Conclusions
Despite of statistically significant differences in PT, INR, values of tPA, XII and free protein S, levels of haemostatic factors range within laboratory references for healthy full term newborns. These findings were not accompanied with clinical manifestations of altered haemostasis. 相似文献5.
Markers of fibrinolysis as predictors for maintenance of sinus rhythm after electrical cardioversion
Andersson J Almroth H Höglund N Jensen S Tornvall P Englund A Rosenqvist M Boman K 《Thrombosis research》2011,127(3):189-192
Introduction
Inflammation, endothelial dysfunction and metabolic pathways provide possible links between the inflammatory and hypofibrinolytic states in atrial fibrillation. Our aim was to explore the role of mass concentrations of PAI-1 and tPA, activities of PAI-1 and tPA as predictors of recurrence of atrial fibrillation adjusted for CRP.Materials and methods
The study included 129 patients with persistent atrial fibrillation. Laboratory analyses were performed including PAI-1 activity, PAI-1 mass, tPA activity, tPA mass and CRP in baseline. Patients were then randomized to atorvastatin (40 mg, two tablets once daily) or placebo, initiated at least 14 days before the elective cardioversion. Further samples and follow-up were made at day 2 and 30 days after cardioversion.Results
In univariate logistic regression no fibrinolytic variable was significantly correlated with rhythm in day 30. In multivariate analysis lower PAI-1 mass was significantly associated with sinus rhythm in all models including fibrinolytic variables, CRP, metabolic components, age, hypertension and smoking. After adding treatment allocation to the fully adjusted model, PAI-1 mass remained significantly associated with sinus rhythm both at day 2 and 30 (OR 0.98; 95% CI 0.95-1.00).Conclusions
No fibrinolytic component alone was found to be a predictor of recurrence of atrial fibrillation. In multivariate models lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP, markers of the metabolic syndrome and treatment with atorvastatin. Our findings suggest a patophysiological link between AF and PAI-1 mass but the relation to inflammation remains unclear. 相似文献6.
Lutz Koch Stefan Hofer Markus A. Weigand David Frommhold Johannes Poeschl 《Thrombosis research》2009,124(4):463-467
Introduction
Although precisely balanced hemostasis in newborns is rapidly changing during early development. During gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and hemostasis. In the present study we compared LPS-induced activation of coagulation in cord blood (CB) samples of healthy newborns to whole blood (WB) samples from healthy adult volunteers.Materials and Methods
Samples were incubated with LPS for various incubation periods (0-2-3-4 hrs), and coagulation was measured by rotation thrombelastography (TEG).Results
All parameters (clotting time (CT), clot formation time (CFT), maximal clot formation (MCF), and angle α) were affected with increasing incubation period with LPS (100 ng/ml) in adult and cord WB. In the absence of LPS, CTs and CFTs were significantly shorter and MCFs and angels α were significantly longer in cord than in adult WB samples. Reduction of CT due to LPS incubation was significantly stronger in CB than in adult WB samples. Pyrrolidine dithiocarbamate, a specific inhibitor of the NFκB pathway, inhibited the effects of LPS on CT in adult and cord WB.Conclusion
In summary, TEG proved to be a sensitive and reliable tool for the determination of LPS-induced tissue factor mediated activation of hemostasis in whole blood samples from adults and neonates. 相似文献7.
Raffaele Palmirotta Patrizia Ferroni Annalisa Savonarola Francesca Martini Filippo Ciatti Anastasia Laudisi Valentina Sini Girolamo Del Monte Fiorella Guadagni Mario Roselli 《Thrombosis research》2009,124(4):403-408
Introduction
Plasminogen activator inhibitor (PAI-1) may have an independent prognostic value in breast cancer (BC). PAI-1 4G/5G polymorphism may have significance for antigen expression. Thus, we analyzed the possible associations between PAI-1 4G/5G polymorphism, plasma PAI-1 levels, and clinicopathological features of breast cancer (BC) patients.Patients and Methods
PAI-1 4G/5G polymorphism (both on germinal and tumor DNA) and plasma PAI-1 levels were investigated in 99 BC patients and 50 unrelated healthy women similar for age and menopausal status.Results
No association was found between allele frequencies and clinicopathological features of BC or plasma antigen levels. Plasma PAI-1 levels were higher in BC compared to controls (p = 0.002), particularly in patients with large tumors (p < 0.001). 5-year follow-up was achieved in 79 patients: 30% had relapsing disease, 63% with positive compared to 37% with negative PAI-1 levels (p < 0.05). 5-year relapse-free survival rate of positive PAI-1 was 46% vs., 77% of negative patients (p = 0.02).Conclusions
We may conclude that plasma PAI-1 levels in BC patients could represent a useful prognostic variable for relapse, although PAI-1 polymorphism might not represent a genetic susceptibility factor. 相似文献8.
Introduction
Mechanisms to explain the different course of coronary thrombosis between ST elevation myocardial infarction (STEMI) and non-STEMI patients remain poorly defined. We hypothesize, however, that STEMI patients may present lower tissue factor plasma inhibition to partly account for their more persistent coronary thrombotic occlusion.Materials and Methods
Total (t-TFPI ) and free tissue factor plasma inhibitor (f-TFPI), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), and fibrinogen were measured on admission and at 3 and 6 months in patients with a first STEMI (n:69) or non-STEMI (n:60). C reactive protein (CRP) was also measured on admission and at 3 months.Results
STEMI patients showed lower admission levels of t-TFPI (p = 0.001), f-TFPI (p = 0.030) and fibrinogen (p = 0.022), and higher vWF levels (p = 0.005) than non-STEMI whereas TAT, PAI and CRP levels were comparable. At 3 and 6 months VWF, t-TFPI, f-TFPI, and TAT levels declined significantly in the 2 groups (p = 0.002) reaching similar values. CRP levels also declined at 3 months (p = 0.002). Moreover, the rate of cardiac mortality, non fatal MI or stroke during a 6 year follow-up were unrelated to admission coagulation parameters.Conclusions
The lower inhibition of tissue factor and greater endothelial dysfunction in STEMI than in non-STEMI patients may enhance thrombosis at the culprit lesion and adjacent coronary plaques, and hence, account at least in part for their different pathophysiology. This condition, however, is limited to the acute phase. 相似文献9.
Van De Craen B Scroyen I Abdelnabi R Brouwers E Lijnen HR Declerck PJ Gils A 《Thrombosis research》2011,128(1):68-76
Introduction
PAI-1 is the main physiological inhibitor of t-PA and u-PA. Elevated PAI-1 levels have been implicated in the pathogenesis of several thrombotic and non-thrombotic diseases. The effect of PAI-1 inhibition can be studied in mouse models, when appropriate immunological tools are available. The majority of the available monoclonal antibodies against PAI-1 have been raised against human PAI-1. Even though some of these antibodies cross-react with non-glycosylated PAI-1 from different species, these antibodies often do not cross-react sufficiently with glycosylated mouse PAI-1. Moreover, the antibodies that cross-react with glycosylated mouse PAI-1 often have decreased inhibitory properties in the presence of vitronectin. Our objective was the generation of a panel of monoclonal antibodies reacting with vitronectin-bound glycosylated mouse PAI-1.Results
Five monoclonal antibodies revealed binding to glycosylated mouse PAI-1 and exerted a strong (i.e. 58-80% inhibition of PAI-1 activity) inhibitory effect toward mouse PAI-1. Similar inhibitory effects were seen in the presence of a 33-fold molar excess of vitronectin. The PAI-1 inhibitory potential of the antibodies in vivo was demonstrated in a thromboembolism model, in which the evaluated antibodies significantly increased the percentage of mice with normal physical activity in comparison to mice treated with negative control antibody.Conclusions
To the best of our knowledge this is the first panel of monoclonal antibodies that can inhibit mouse PAI-1 in the presence of vitronectin and that show a profibrinolytic effect in vivo. Therefore these antibodies provide excellent immunological tools to further investigate the role of PAI-1 in mouse models. 相似文献10.
Katsaros KM Kastl SP Huber K Zorn G Maurer G Glogar D Wojta J Christ G Speidl WS 《Thrombosis research》2008,123(1):79-84
Background
Plasminogen activator inhibitor-1 (PAI-1) has been shown to increase after percutaneous coronary intervention (PCI). Whether activated platelets, local trauma with activation of resident vascular cells or the acute phase response is the source of this PAI-1 increase is not well defined. Therefore we examined whether intensive platelet inhibition may modulate PAI-1 levels or whether the PAI-1 increase is associated with the acute phase protein C-reactive protein (CRP).Methods
We included 51 patients with stable angina who underwent elective PCI with stent implantation. At the time of study, routine pretreatment with clopidogrel before PCI was not standard of care, but left to the discretion of the referring cardiologist. We matched 17 patients with stable angina that were not pretreated with clopidogrel but received a loading dose of 300 mg immediately after stent implantation according age, sex and smoking with 34 patients that received clopidogrel at least 12 to 24 hours before PCI. Blood samples for measurement of PAI-1, t-PA and CRP were taken directly before and 24 hours after the procedure.Results
PAI-1 and t-PA active antigen plasma levels before PCI were not different in patients with and without clopidogrel pretreatment. Whereas PCI induced a significant increase of PAI-1 levels in patients without pretreatment (p < 0.05), the procedure had no effect on PAI-1 active antigen in patients pretreated with clopidogrel. This resulted in significant lower PAI-1 plasma levels 24 hours after PCI in patients with pretreatment (p < 0.05). CRP was not associated with pre- or postprocedural PAI-1 levels.Conclusion
Clopidogrel pretreatment completely abolishes the increase of PAI-1 active antigen after coronary stent implantation. This suggests that peri-procedural platelet activation might play a major role for the increase of PAI-1 after PCI thus increasing the risk of acute and subacute thrombus formation based on a reduced endogenous fibrinolytic system. 相似文献11.
K Maruyama E Morishita T Yuno A Sekiya H Asakura S Ohtake A Yachie 《Thrombosis research》2012,130(3):e188-e193
Introduction
Heme oxygenase-1 (HO-1) is the rate limiting enzyme that catalyzes the conversion of heme into biliverdin, free iron, and carbon monoxide (CO). The first human case of HO-1 deficiency showed abnormalities in blood coagulation and the fibrinolytic system. Thus, HO-1 or HO-1 products, such as CO, might regulate coagulation and the fibrinolytic system. This study examined whether tricarbonyldichlororuthenium (II) dimer (CORM-2), which liberates CO, modulates the expression of tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1) in human umbilical vein endothelial cells (HUVECs), and TF expression in peripheral blood mononuclear cells (PBMCs). Additionally, we examined the mechanism by which CO exerts its effects.Materials and Methods
HUVECs were pretreated with 50 μM CORM-2 for 3 hours, and stimulated with tumor necrosis factor-α (TNF-α, 10 ng/ml) for an additional 0-5 hours. PBMCs were pretreated with 50-100 μM CORM-2 for 1hour followed by stimulating with lipopolysaccharid (LPS, 10 ng/ml) for additional 0-9 hours. The mRNA and protein levels were determined by RT-PCR and western blotting, respectively.Results
Pretreatment with CORM-2 significantly inhibited TNF-α-induced TF and PAI-1 up-regulation in HUVECs, and LPS-induced TF expression in PBMCs. CORM-2 inhibited TNF-α-induced activation of p38 MAPK, ERK1/2, JNK, and NF-κB signaling pathways in HUVECs.Conclusions
CORM-2 suppresses TNF-α-induced TF and PAI-1 up-regulation, and MAPKs and NF-κB signaling pathways activation by TNF-α in HUVECs. CORM-2 suppresses LPS-induced TF up-regulation in PBMCs. Therefore, we envision that the antithrombotic activity of CORM-2 might be used as a pharmaceutical agent for the treatment of various inflammatory conditions. 相似文献12.
Raeven P Feichtinger GA Weixelbaumer KM Atzenhofer S Redl H Van Griensven M Bahrami S Osuchowski MF 《Thrombosis research》2012,129(5):e238-e245
Introduction
Plasminogen activator inhibitor type 1 (PAI-1) co-induces septic coagulopathy. We aimed to characterize spatiotemporal PAI-1 gene/protein changes occurring in acute sepsis and tested whether PAI-1 fluctuations correlate with sepsis severity and early outcome.Materials and Methods
Female mice underwent cecal ligation and puncture (CLP) in three experiments. I: mild (23G needle) CLP to compare circulating PAI-1 to its organ gene expression within 0-24 h. II: mild or severe (17G) CLP to asses differences in PAI-1 organ-specific expression and in coagulation/fibrinolysis. III: moderate (18G) CLP to characterize circulating PAI-1 in survivors (SUR), and to retrospectively compare it to dying (DIE) mice.Results
In mild sepsis, the trajectory of circulating PAI-1 (1089 ng/ml peak at 24 h) was identical to PAI-1 gene expression in the left cranial vena cava (LCVC; 39-fold peak at 24 h). PAI-1 expression rise was immediate (60-fold at 6 h) and sustained in the liver, but marginal in the kidney, lungs and heart. Body temperature decrease correlated with the PAI-1 expression increase in the liver (rho = − 0.79), and blood (protein, rho = − 0.53). Regardless of severity, PAI-1 gene expression remained unaltered except the LCVC where it was > 3-fold higher in 17G (vs. 23G). Severe sepsis extended activated partial thromboplastin/pro-thrombin time and increased circulating PAI-1, while antithrombin and fibrinogen decreased at 6 and/or 24 h (vs. 23G). Within 24 h of death, circulating PAI-1 in DIE was > 3-fold higher versus SUR.Conclusions
Polymicrobial sepsis caused a gradual circulating PAI-1 release and highly variable gene expression response pattern in organs. Only circulating PAI-1 and PAI-1 expression in the LCVC correlated with response severity and/or outcome. 相似文献13.
Anna C. Phillips G. David Batty Alexander Weiss Catharine R. Gale Douglas Carroll 《Journal of psychosomatic research》2010,69(2):193-201
Objectives
The purpose of this study is to explore the association of neuroticism with the metabolic syndrome, separate components of the metabolic syndrome, and the number of components of metabolic syndrome an individual possesses. The purpose of this study is to examine also the extent to which any associations are accounted for by sociodemographic factors, health behaviors, and cognitive ability.Method
Participants were 4208 men drawn from the Vietnam Experience Study. From military archives, and a later telephone interview and psychological and medical examination, sociodemographic, health behavior, cognitive ability, neuroticism, and health data were collected. Neuroticism and cognitive ability were assessed with standardized tests during the medical examination. Presence of the metabolic syndrome was based on body mass index, fasting blood glucose or a diagnosis of diabetes, high blood pressure or taking antihypertensive medication, high-density lipoprotein cholesterol, and triglyceride levels.Results
Neuroticism was positively associated with the occurrence of the metabolic syndrome and several of its components in both age-, and sociodemographic- and health behavior-adjusted analyses. Many associations were accounted for by individual difference in cognitive ability. Neuroticism was robustly associated with the number of components of the metabolic syndrome after adjustment.Conclusions
Individuals with higher neuroticism scores had a higher prevalence of the metabolic syndrome and a larger number of its components. On the whole, differences in cognitive ability appeared to partially mediate the relationship between neuroticism and the metabolic syndrome. 相似文献14.
Introduction
Abdominal aortic aneurysm is a common condition with high mortality when rupturing. However, the condition is also associated with nonaneurysmal cardiovascular mortality. A possible contributing mechanism for the thrombosis related cardiovascular mortality is an imbalance between the activation of the coagulation system and the fibrinolytic system. The aim of the present study was to investigate haemostatic markers in patients with nonruptured abdominal aortic aneurysm with special regard to the influence of aneurysm size and smoking habits.Methods
Seventy-eight patients with infrarenal aortic aneurysm and forty-one controls without aneurysm matched by age, gender and smoking habits were studied. Thrombin-antithrombin (TAT), prothrombin fragment 1 + 2 (F 1 + 2) - markers of thrombin generation, and von Willebrand factor antigen (vWFag) - considered as a reliable marker of endothelial dysfunction - were measured. Plasma levels of tissue plasminogen activator antigen (tPAag), and plasminogen activator inhibitor type 1 (PAI-1) were measured as markers of fibrinolytic activity. D-dimer, a marker of fibrin turnover, was also measured.Results
There were significantly higher levels of TAT and D-dimer in patients with abdominal aortic aneurysm. The highest level of TAT and D-dimer were detected in patients with large compared to small AAA.Conclusions
The present data indicate a state of activated coagulation in patients with abdominal aortic aneurysm which is dependent by aneurysm size. The activated coagulation in AAA patients could contribute to an increased cardiovascular risk in patients also with small AAA. The possible impact of secondary prevention apart from smoking cessation has to be further evaluated and is maybe as important as finding patients at risk of rupture. 相似文献15.
Trifiletti A Gaudio A Lasco A Atteritano M Scamardi R Pizzoleo MA Morabito N Frisina N 《Thrombosis research》2008,123(2):231-235
Introduction
Genistein is an isoflavone phytoestrogen derived from the soybean which acts as natural selective estrogen receptor modulator. Various studies have pointed out its cardioprotective role. The aim of the study was to evaluate the haemostatic effects of genistein in postmenopausal women.Material and methods
In this double-blind placebo-controlled trial we enrolled 104 healthy postmenopausal women with osteopenia. 53 patients (mean age 54.9 ± 4.2 yr; BMI 23.4 ± 3.2 Kg/m2) received genistein (54 mg/day) and 51 patients (mean age 55.4 ± 4.3 yr; BMI 23.6 ± 3.6 Kg/m2) received an identical placebo-tablet. Both groups received a calcium and vitamin D supplement. Plasma levels of D-dimer (DD), plasminogen activator inhibitor-1 (PAI-1) and prothrombin fragment 1 + 2 (F1 + 2) were measured at baseline and after 6 and 12 months of treatment.Results
Baseline characteristics of the two groups were similar. Compared with placebo, genistein decreased significantly DD (p < 0.001), but did not affect PAI-1 and F 1 + 2 plasma levels.Conclusion
The results of our study do not confirm effects of genistein on activation of the haemostatic system, but on the contrary the significant decrease of DD could indicate a possible cardioprotective role of genistein in postmenopausal women. 相似文献16.
Ramón LA Gilabert-Estellés J Cosín R Gilabert J España F Castelló R Chirivella M Romeu A Estellés A 《Thrombosis research》2008,122(6):854-860
Introduction
Endometriosis is a benign gynecologic disease with a high prevalence. It is a multifactorial and polygenic entity in which the fibrinolytic system may be implicated. The objective of this study was to evaluate the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism in a group of women with and without endometriosis and to analyze the influence of this polymorphism in PAI-1 expression in endometrial tissue and peritoneal fluid.Material and methods
In 389 women (170 patients with endometriosis and 219 controls) PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Quantitative real-time RT-PCR assay was used to quantify PAI-1 mRNA and PAI-1 antigen (ag) levels were quantified by ELISA.Results
The genotype and allele frequencies of PAI-1 4G/5G polymorphism did not differ significantly between patients and controls. Control women with the 4G/4G genotype had higher endometrial PAI-1ag (P = 0.026) and mRNA (P = 0.014) levels than those with the 5G/5G genotype. Control carrying the 4G/4G genotype tended to have higher peritoneal fluid PAI-1ag levels than those carrying the 5G/5G genotype. Moreover, PAI-1ag levels in peritoneal fluid were higher in patients than in controls (P = 0.003).Conclusions
The PAI-1 genotype distribution was similar in patients and controls. PAI-1 levels in endometrial tissue and peritoneal fluid seem to be associated with PAI-1 4G/5G polymorphism in controls. The increased PAI-1ag levels observed in peritoneal fluid from patients could contribute to increase the peritoneal adhesions observed in endometriosis. 相似文献17.
Introduction
In vitro studies indicate an anticoagulant effect of 1,25-dihydroxyvitamin D, and sun exposure may lower the risk of thrombotic events. Accordingly, an effect on haemostatic parameters could be expected after supplementation with vitamin D.Materials and Methods
158 obese or overweight subjects were included in a one year intervention study with supplementation with 40.000 IU vitamin D3 per week or placebo. All subjects were given 500 mg calcium daily. Plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (tPA Ag), and tissue factor-induced thrombin generation over time in plasma assessed by the calibrated automated thrombogram (CAT) method as a parameter of over all thrombotic activity, were measured before and at the end of the study.Results
Mean baseline serum 25(OH)D level was 61.8 nmol/L and increased in the vitamin D group to 145.6 nmol/L at the end of the study. At baseline there was a significant decrease in the CAT variables lag time and time to peak of the thrombogram across increasing serum 25(OH)D quartiles, whereas no significant associations between serum 25(OH)D and PAI-1 or tPA Ag were found. After one year, no significant differences were found between the vitamin D and placebo groups regarding change in any of the haemostatic parameters.Conclusions
The association between lag time and time to peak in the CAT assay and serum 25(OH)D levels could indicate a pro-thrombotic state in subjects with high serum 25(OH)D levels, whereas the lack of effect of high dose vitamin D supplementation questions the causality of this relation. 相似文献18.
Introduction
Heparin, a potent blood anticoagulant, has been shown to exert a variety of pharmacological activities. The purpose of this study was to investigate whether heparin has a beneficial effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and to further explore the possible underlying mechanisms.Materials and methods
Adult Sprague-Dawley rats were randomly assigned into the control, heparin, LPS, and LPS plus heparin groups. ALI was induced by intratracheal instillation of LPS at a dose of 1 mg/kg. Rats in the LPS plus heparin group were intravenously received 50 U/ kg heparin every 1 h after the induction of ALI.Results
We found that heparin significantly improved LPS-induced lung pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced malondialdehyde (MDA) level and lung wet/dry weight ratio. Heparin also inhibited the release of tumor necrosis factor (TNF)-α and interleukin (IL)-6, and markedly decreased the expression of inducible nitric oxide synthase (iNOS) in lung tissues and thus prevented nitric oxide (NO) release in response to LPS challenge. Additionally, heparin decreased the expression of transforming growth factor-β1 (TGF-β1), p-Smad 2, and p-Smad 3, which are all important molecules of the TGF-β1/Smad signaling pathway.Conclusions
Heparin significantly ameliorated the lung injury induced by LPS in rats via the inhibition of nitric oxide synthase expression and the TGF-β/Smad pathway. Heparin may be a potential therapeutic reagent for treating ALI in the future. 相似文献19.
Mitsiakos G Giougi E Papaioannou G Karagianni P Papadakis E Nikolaidis N 《Thrombosis research》2009,123(3):476-481
Background
Clinical and experimental researches have linked smoking to disturbances of coagulation and fibrinolysis. Several potential mechanisms are incriminated involving inflammation, fibrinogen synthesis and clotting factors. Based on the fact that the majority of tobacco components cross the placental barrier, the objective of our current study is to investigate the influence of smoking during pregnancy on neonatal haemostasis.Study design
The study was based on a comparative evaluation of coagulation and fibronolysis between healthy full term infants of women who smoked during pregnancy and a control group. Subjects consisted of 39 newborns of smoking and 43 newborns of nonsmoking mothers. Blood samples were obtained shortly after birth and before the administration of vitamin K. Investigation included: PT, INR, aPTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand (vWF), protein C and S, APCr, anti-thrombin (AT), t-PA and PAI-1. The independent t- test was used to compare the differences between the values of coagulation and fibrinolytic parameters at the p < 0.05 level.Results
We discovered a statistically significant decrease in factor II and protein S levels and an elevation in t-PA and factor VIII concentrations in newborns of smoking mothers, without clinical manifestations of altered haemostasis. There were no significant differentiations in other coagulation or fibrinolytic parameters.Conclusion
The alteration in factor II, protein S, t-PA and factor VIII in neonates exposed in utero to tobacco smoke is not accompanied by loss in the balance between coagulation and fibrinolytic pathways. 相似文献20.