Calibrated automated thrombin generation in normal uncomplicated pregnancy

2008 ◽  
Vol 99 (02) ◽  
pp. 331-337 ◽  
Author(s):  
Andrea Rosenkranz ◽  
Michael Hiden ◽  
Bettina Leschnik ◽  
Weiss Eva-Christine ◽  
Dietmar Schlembach ◽  
...  
Keyword(s):  
Protein C ◽  
Thrombin Generation ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Plasminogen Activator Inhibitor 1 ◽  
S Protein ◽  
Endogenous Thrombin Potential ◽  
Time To Peak ◽  
Uncomplicated Pregnancy ◽  
Pai 1

SummaryPregnancy is associated with substantial changes in the haemostatic system and a six-fold higher incidence of venous thromboembolism. Conventional global tests, such as prothrombin time and activated partial thromboplastin time, do not definitely detect this hypercoagulable condition. We investigated whether the changes in haemostatic system during pregnancy are reflected in the calibrated automated thrombography (CAT). Thrombin generation was measured in platelet-poor plasma (PPP) of 150 healthy pregnant women without any pregnancy associated diseases by means of CAT. In addition, prothrombin (FII), antithrombin (AT), protein S, protein C, tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and prothrombin fragments 1+2 (F1+2) were measured. Endogenous thrombin potential (ETP) and peak of thrombin generation increased significantly with gestational weeks, while lag time and time to peak remained unchanged. A significant increase of PAI-1,TFPI,F1+2 and TAT as well as a significant decrease of free protein S, protein S antigen, and protein S activity was observed. Levels of AT and protein C remained stable during pregnancy. Division of population in trimester of pregnancy and analysis of differences between the trimesters showed rather similar results. Our study shows that endogenous thrombin potential does increase with duration of normal uncomplicated pregnancy. Whether parameters of continuous thrombin generation will correlate with thrombembolic disease remains to be shown.

Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 328-333 ◽  
Author(s):  
N J de Fouw ◽  
Y F de Jong ◽  
F Haverkate ◽  
R M Bertina
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Blood Platelets ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Activator Inhibitor ◽  
Pai 1

summaryThe effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.

scholarly journals Liraglutide in polycystic ovary syndrome: a randomized trial, investigating effects on thrombogenic potential

2017 ◽  
Vol 6 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Malin Nylander ◽  
Signe Frøssing ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Sven O Skouby
Keyword(s):  
Thrombin Generation ◽  
Polycystic Ovary ◽  
Plasminogen Activator Inhibitor ◽  
Lag Time ◽  
Plasminogen Activator Inhibitor 1 ◽  
Cvd Risk ◽  
Ovary Syndrome ◽  
Time To Peak ◽  
Thrombogenic Potential ◽  
Activator Inhibitor

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulin-resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0–7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32–31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01–0.25, P < 0.05) and 0.38 min (95% CI 0.09–0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.

Biological Rational for the Use of Heparin in Septic Shock: Translational Data from the Halo Pilot RCT

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2336-2336
Author(s):  
Brett L. Houston ◽  
Dhruva J. Dwivedi ◽  
Peter Grin ◽  
Michelle Kwong ◽  
Enrico Rullo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Lysis Time ◽  
Activator Inhibitor ◽  
Clot Lysis Time

Abstract BACKGROUND: Sepsis is a leading cause of mortality among critically ill patients and is associated with both systemic inflammation and up-regulation of coagulation. In the translational sub-study of the HALO (Heparin AnticoaguLation to improve Outcomes in septic shock) pilot trial, we evaluated the mechanisms by which unfractionated heparin (UFH) may reduce inflammation and coagulation in patients with septic shock. METHODS: In this multicenter pilot randomized trial of 69 patients diagnosed with septic shock, we evaluated the feasibility of administering therapeutic dose intravenous UFH (18 IU/kg/hr) compared to thromboprophylactic subcutaneous dalteparin (5000 IU daily). Blood samples were collected on days 1 (baseline prior to study infusion), 2, 3, 5, and 7. We evaluated coagulation using assays for protein C, activated protein C, thrombin-antithrombin (TAT), thrombin generation, clot lysis, plasminogen activator inhibitor-1 (PAI-1) and cell-free DNA (cf-DNA). Systematic inflammation was evaluated by measuring inflammatory cytokines (interleukin (IL)-6, IL-8, IL-10, and IL-17). RESULTS: The mean age of the study population was 61 years, of whom 43% were male. Thirty two patients (46%) were randomized to receive unfractionated heparin while 37 (54%) received dalteparin. The baseline mean aggregate Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 25 ± 7.8, and Multiple Organ Dysfunction Score (MODS) 5.6 ± 2.38. Baseline laboratory testing (coagulation assays and inflammatory cytokines) was not statistically different between UFH vs. LMWH treated patients. On day 2, the median clot lysis time in UFH-treated patients compared to those receiving dalteparin was significantly decreased [6630 (IQR 0 - 14156) seconds vs. 9615 (IQR 8209 - 11018) seconds; p = 0.008] (Figure 1). UFH administration was associated with increased protein C levels [66.4% of normal (IQR 9.9 - 122.9) vs. 41.1% of normal (IQR 4.8 - 77.4); p = 0.02], and reduced thrombin generation of 0 (IQR 0 - 1725) units/min vs. 3393 (IQR 0 - 8519) units/min; p<0.001]. On day 2, we observed no differences between thrombin-antithrombin complex (TAT), activated protein C, plasminogen activator inhibitor-1 (PAI-1) or cell-free DNA (cf-DNA). Similarly, there were no differences between treatment groups in inflammatory markers, including IL-6, IL-8, IL-10 or IL-17. Analysis thus far is limited to samples collected on days 1 and 2; day 3-7 analyses are ongoing. CONCLUSION: In patients diagnosed with septic shock, IV UFH reduces thrombin generation, shortens clot lysis time and improves endogenous protein C levels compared to dalteparin administered for thromboprophylaxis. Analyses for samples obtained on days 3, 5 and 7 are ongoing. These preliminary data provide a biologic rational for the use of heparin in sepsis. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Disclosures No relevant conflicts of interest to declare.

scholarly journals Coagulopathy is Initiated with Endothelial Dysfunction and Disrupted Fibrinolysis in Patients with COVID-19

2021 ◽  
Author(s):  
FATMA BURCU BELEN APAK ◽  
Gulbahar Yuce ◽  
Deniz Ilhan Topcu ◽  
Ayse Gultekingil ◽  
Yunus Emre Felek ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Endothelial Protein C Receptor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background: A substantial group of patients suffer coagulopathy of Covid-19 (CAC) and are presented with thrombosis. The pathogenesis involved in CAC is not fully understood.Objectives: We evaluated the hemostatic and inflammatory parameters of 51 hospitalized Covid-19 adult patients and 21 controls. The parameters analyzed were danger signal molecule (High molecular weight group box protein-1/HMGBP-1), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, endothelial protein C receptor (EPCR), soluble E-selectin, soluble P-selectin, thrombomodulin, tissue plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1), soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), β-thromboglobulin, antithrombin and protein C. The main objective of our study was to investigate which part of the hemostatic system was mostly affected at the admission of Covid-19 patients and whether these parameters could differentiate intensive care unit (ICU) and non-ICU patients. Patients and Methods:In this prospective case-control study, 51 patients ≥18 years who are hospitalized with the diagnosis of Covid-19 and 21 healthy control subjects were included. We divided the patients into two groups according to their medical progress, either into ICU and non-ICU group. Regarding the outcome, patients were again categorized as survivor and non-survivor groups. Blood samples were collected from patients at admission at the time of hospitalization before administration of any treatment for Covid-19. The analyzes of the study were made with the IBM SPSS V22 program. p < 0.05 was considered statistically significant.Results:A total of 51 adult patients (F/M: 24/27) (13 ICU and 38 non-ICU) were included in the study cohort. The mean age of the patients was 68.1 ± 14.4 years. The control group consisted of 21 age and sex-matched healthy individuals. All of the patients were hospitalized, in a group of 13 patients, Covid-19 progressed to severe form and were hospitalized at ICU. We found out that the levels of fibrinogen, prothrombin time (PT), endothelial protein-C receptor (EPCR), D-dimer, soluble E-selectin, soluble P-selectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) were increased; whereas, the levels of soluble fibrin monomer complex (SFMC), platelet-derived microparticles (PDMP), antithrombin and protein-C were decreased in Covid-19 patients compared to the control group at hospital admission. Tissue plasminogen activator was the only marker that had a significantly different median level between ICU and non-ICU groups (p<0.001).Conclusions:In accordance with the previous literature, we showed that Covid-19 associated coagulopathy is distinct from sepsis-induced DIC with prominent early endothelial involvement and fibrinolytic shut-down. Reconstruction of endothelial function at early stages of infection may protect patients to progress to ICU hospitalization. We believe that after considering the patient’s bleeding risk, early administration of LMWH therapy at Covid-19 even in at outpatient setting may be useful both for restoring endothelial function and anticoagulation. The intensity of anticoagulation in non-ICU and ICU Covid-19 patients should be clarified with further studies.

Procoagulant State in Current and Former Anabolic Androgenic Steroid Abusers

2018 ◽  
Vol 47 (04) ◽  
pp. 647-653
Author(s):  
Jon Rasmussen ◽  
Mikkel Frandsen ◽  
Morten Schou ◽  
Marie Johansen ◽  
Jens Faber ◽  
...  
Keyword(s):  
Linear Regression ◽  
Protein C ◽  
Thrombin Generation ◽  
Protein S ◽  
Lag Time ◽  
Anabolic Androgenic Steroid ◽  
Thrombotic Risk ◽  
Time To Peak ◽  
Androgenic Steroid ◽  
Cardiovascular Morbidity And Mortality

Background Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. Methods Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers or controls. Morning blood samples were collected after overnight fasting. Thrombin generation (lag time, time to peak, peak height, and endogenous thrombin potential [ETP]) and coagulation factor II (prothrombin), VII and X, antithrombin, protein C, free protein S and tissue factor pathway inhibitor (TFPI) were assessed. Groups were compared by ANOVA or Kruskal–Wallis test and probabilities were corrected for multiple comparisons. Associations were evaluated using linear regression models. Results ETP was increased around 15% in current (n = 37) and former (n = 33) AAS abusers compared with controls (n = 30; p < 0.001). Prothrombin and factor X were increased ≥10% in AAS abusers and prothrombin was a predictor of ETP (p < 0.0005). Lag time and time to peak were increased 10 to 30% in current AAS abusers (p < 0.001) and associated with higher concentrations of TFPI, antithrombin, protein C and protein S (p < 0.0005; = 0.005). Multivariate linear regression, with all coagulation inhibitors as covariates, identified TFPI to be independently associated with lag time and time to peak (p < 0.0005). Conclusion Thrombin generation is augmented in current and former AAS abusers, reflecting a procoagulant state, with altered concentrations of coagulation proteins. Prospective studies are needed to clarify whether these findings translate into an increased thrombotic risk in AAS abusers potentially even after cessation.

Distribution of Hypercoagulation Laboratory Diagnoses among Patients with History of Thromboembolic Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3952-3952
Author(s):  
Murray M. Bern ◽  
Nancy McCarthy ◽  
Jamie Bonner
Keyword(s):  
Protein C ◽  
Elective Surgery ◽  
Factor V Leiden ◽  
Protein S ◽  
Thromboembolic Disease ◽  
Factor V ◽  
Plasminogen Activator Inhibitor 1 ◽  
Total N ◽  
Increased Risk ◽  
Pai 1

Abstract This abstract demonstrates the distribution of hypercoagulation diagnosis among patients with histories of thromboembolic disease (TED) among a group of patients detected at surgery prescreening clinic or through other referral sources. The consulting hematologists determined which laboratory tests were ordered; thus not all patients had all tests. This abstract describes the results of those clinical consultations. For this study the hospital’s computer logs were probed for patients having had measurements of protein C and factor V Leiden from 11/7/01until 8/1/07. The laboratory records of identified patients were searched for additional hypercoagulation laboratory parameters. A total of 383 patients have been identified, among whom abnormal diagnostic results were found for 231. Genomic assays were performed often for the commonly found defects (i.e., factor V Leiden and prothrombin 20210) and selectively for other situations, such 4G/5G for patients with elevated plasminogen activator inhibitor 1 (PAI-1) and unresolved venous thrombus, or methylene tetrahydrofolate (MTH) reductace for unexplained elevation of homocysteine. The table demonstrate the distribution of these laboratory diagnoses. The risk of having TED associated with these results will be stratified to emphasize the increased risk associated with the more severe abnormalities of protein C, protein S, ATIII, PAI-1, and homocysteine. These results demonstrate that laboratory explanations for TED may be found in a large proportion of patients with TED, which thereafter can be used to design prophylactic programs for at risk patients upon entry to hospital, especially elective surgery. Hypercoagulation Parameters Patients Protein C* (&lt;60%) Protein S* (&lt;60%) AT III (&lt;80%) Homocysteine (&gt;12 um/L) Lupus anticoagulant Anti-phospholipid syndrome** * excludes patients taking warfarin; includes functional and antigen assays. ** combines anticardiolipin; anti-beta2, glycoprotein1; and anti-phosphotidyl -serine, -ethanolamine and -choline antibodies. total n 350 358 244 252 166 234 abnormal n (%) 7(2) 64(18) 29 (12) 89(35) 18 (11) 41 (18) PAI-1 (&gt;42) ng/ml) APC Resistance (&lt;2.1) VIII:c & VIII:vW (&gt;180%) Factor V Leiden Prothrombin 20210 MTH Folate Reductace 4G/5G 36 75 61 225 219 10 9 22 (61) 10 (13) 11 (18) 37 (16) 16 (7) 8 (80) 8 (90)

A Comparison Of Hemostatic and Inflammatory Markers In Overt and Non-Overt DIC

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3577-3577
Author(s):  
Debra Hoppensteadt ◽  
Kazuhisa Tsuruta ◽  
Joe Hirman ◽  
Inder Kaul ◽  
Yutaka Osawa ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Research Funding ◽  
Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Interleukin 10 ◽  
Plasminogen Activator Inhibitor 1 ◽  
Double Blind ◽  
Hemostatic System ◽  
Recombinant Thrombomodulin ◽  
Pai 1

Abstract Disseminated intravascular coagulation (DIC) is a complex pathophysiologic syndrome with marked alterations in the hemostatic system, which may lead to microvascular thrombosis and multi-organ failure. The International Society of Thrombosis and Hemostasis (ISTH) classifies DIC into two distinct categories; overt and non-overt DIC (NO). Overt DIC is characterized by a decompensated hemostatic system whereas non-overt is characterized as a stressed, compensated system. DIC is a frequently observed in sepsis patients. An association between the hemostatic aberrations and inflammation has been previously reported. Therefore we studied the level of hemostatic activation and inflammation in patients with sepsis and suspected DIC enrolled in the ART-123, Phase 2b study. The level of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), and protein C (Pr C) were evaluated in 617 subjects enrolled in a randomized, double-blind, placebo-controlled, Phase-2b study evaluating the safety and efficacy of recombinant thrombomodulin (ART-123) in subjects with sepsis and suspected DIC. When the subjects with overt DIC and with NO DIC were compared, the PrC level was lower and PCT, PAI-1, IL-6 and IL-10 levels were higher, in the overt DIC subjects (Table). The upregulation of the inflammatory cytokines observed in this study may contribute to the decreased levels of Pr C. Inflammatory cytokines may dysregulate the endothelial thrombomodulin resulting impaired hemostatic regulation. Pr C levels are also low due to consumption and impaired synthesis, especially in the overt DIC patients. These results suggest that profiling these mediators may be useful in the diagnostic and prognostic management of sepsis and differentiation between overt and non-overt DIC.BiomarkerGroupNMeanSEMMedianP ValuePr C (%)Normal4094.52.491.80.0043Overt9824.71.828.30.0043NO15746.52.637.00.0043PCTNormal240.260.020.270.0001(ng/ml)Overt9836.87.011.220.0001NO51918.031.45.330.0001PAI-1Normal3120.62.118.7<0.0001(ng/ml)Overt98232.925.0137.5<0.0001NO519147.18.676.0<0.0001Il-6Normal306.80.536.10.0003(pg/ml)Overt981017.6121.7374.40.0003NO519576.739.6174.70.0003IL-10Normal3210.42.43.50.0049(pg/ml)Overt98187.339.146.00.0049NO518108.114.831.00.0049 Disclosures: Hoppensteadt: Asahi Kasei Pharma: Research Funding. Tsuruta:Asahi Kasei Pharma: Employment. Hirman:Asahi Kasei Pharma: Consultancy. Kaul:Asahi Kasei Pharma: Employment. Osawa:Asahi Kasei Pharma: Employment. Fareed:Asahi Kasei Pharma: Research Funding.

Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4061-4068 ◽  
Author(s):  
Marina Marchetti ◽  
Elisabetta Castoldi ◽  
Henri M. H. Spronk ◽  
René van Oerle ◽  
Donatella Balducci ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Protein S ◽  
Factor V ◽  
Endogenous Thrombin Potential ◽  
Apc Resistance ◽  
Mutational Status

Abstract We used the thrombin generation assay to evaluate the hypercoagulable state according to JAK2V617F mutational status in essential thrombocythemia (ET) and polycythemia vera (PV) patients. Thrombin generation was determined in the presence and absence of activated protein C (APC), and APC resistance was expressed as normalized APC sensitivity ratio (nAPCsr). Tissue factor pathway inhibitor (TFPI), total and free protein S (PS), prothrombin (FII), factor V (FV), and neutrophil elastase were measured in plasma; CD11b was measured on neutrophils. Compared with normal controls, patients had a lower endogenous thrombin potential in the absence of APC but had a higher endogenous thrombin potential in the presence of APC, showing the occurrence of APC resistance. The nAPCsr increased in JAK2V617F carriers compared with noncarriers and was highest in JAK2V617F homozygous patients. FII, FV, free PS, and TFPI levels were reduced in patients, mainly in JAK2V617F carriers. Multiple regression analysis indicated the low free PS level as major determinant of the increased nAPCsr. Elastase was increased in patients and inversely correlated with free PS. In conclusion, these data indicate the occurrence of acquired APC resistance in ET and PV patients, probably because of a reduction in free PS levels. The APC-resistant phenotype is influenced by the JAK2V617F mutational load.

scholarly journals Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice

2007 ◽  
Vol 56 (6) ◽  
pp. 803-808 ◽  
Author(s):  
Shih-Ming Tsao ◽  
Wen-Hu Liu ◽  
Mei-Chin Yin
Keyword(s):  
Staphylococcus Aureus ◽  
Plasma Levels ◽  
Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Inhibitory Effect ◽  
Diabetic Mice ◽  
Plasminogen Activator Inhibitor 1 ◽  
At Iii ◽  
Mrsa Infection ◽  
Pai 1

The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS) against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic mice was studied. The influence of these agents on the plasma levels of fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-α (TNF-α), and on the activity of plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected diabetic mice was examined. To induce diabetes, mice were treated intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA isolates obtained from infected patients were used in this study. Diabetic mice were infected by injecting 200 μl MRSA/PBS suspension containing 107 c.f.u. via the tail vein. At day 4 post-infection, 200 μl DAS or DADS was administrated twice orally with an interval of 12 h. Eight hours after each administration, the blood and organs of mice were collected. Results showed that DAS and DADS significantly decreased MRSA viability in the kidney (P <0.05), with administration of each agent twice showing a greater inhibitory effect than when given once (P <0.05). MRSA infection in diabetic mice significantly elevated the plasma levels of IL-6 and TNF-α (P <0.05). DAS or DADS given once did not affect the plasma levels of IL-6 and TNF-α (P >0.05); however, DAS or DADS given twice significantly decreased the plasma levels of both IL-6 and TNF-α (P <0.05). DAS and DADS treatments also significantly reduced the plasma levels of CRP, fibronectin and fibrinogen (P <0.05). DAS or DADS treatment did not affect PAI-1 activity (P >0.05), but DAS or DADS given twice significantly increased AT-III activity (P <0.05). DADS given twice elevated protein C activity (P <0.05). MRSA infection significantly increased malondialdehyde levels in the kidney and spleen (P <0.05), and these levels were significantly decreased by treatment with DAS or DADS (P <0.05). These data suggest that DAS and DADS could provide multiple protective functions against MRSA infection in diabetic mice.

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