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.

scholarly journals Meticillin-resistant Staphylococcus aureus infection in diabetic mice enhanced inflammation and coagulation

2006 ◽  
Vol 55 (4) ◽  
pp. 379-385 ◽  
Author(s):  
Shyh-Ming Tsao ◽  
Cheng-Chin Hsu ◽  
Mei-Chin Yin
Keyword(s):  
Staphylococcus Aureus ◽  
Protein C ◽  
Interleukin 2 ◽  
Endothelial Injury ◽  
Diabetic Mice ◽  
Plasminogen Activator Inhibitor 1 ◽  
At Iii ◽  
Mrsa Infection ◽  
Pai 1 ◽  
Mssa Infection

BALB/cA mice were used to study the interaction of diabetes and meticillin-resistant Staphylococcus aureus (MRSA) infection on pathogen distribution, cytokine profile and inflammatory and endothelial-injury markers, as well as coagulation and anticoagulation factors. Meticillin-susceptible S. aureus (MSSA) infection did not cause death within the experimental period. MRSA-infected nondiabetic and diabetic mice died on 19·1±1·4 and 10·6±0·7 days post-infection (p.i.), respectively. MRSA and MSSA infection in diabetic mice did not result in symptomatic bacteraemia; however, MRSA infection in diabetic mice significantly reduced glucose levels (P<0·05). Diabetic mice showed significantly higher levels of C-reactive protein, fibrinogen, fibronectin and von Willebrand factor than nondiabetic mice (P<0·05), and MRSA infection further elevated the plasma levels of these inflammatory and endothelial markers (P<0·05). Before infection, diabetic mice had significantly higher plasminogen activator inhibitor-1 (PAI-1) activity, lower antithrombin III (AT-III) and protein C activities (P<0·05), and MRSA infection significantly increased PAI-1 activity further and reduced the activity of AT-III and protein C (P<0·05). MRSA infection increased the production of three Th1 cytokines, interleukin 2 (IL-2), tumour necrosis factor alpha and gamma interferon, in diabetic mice (P<0·05); however, three Th2 cytokines, IL-4, IL-6, IL-10, were elevated at 2 and 4 days p.i., and then dropped gradually. MRSA infection in diabetic mice accelerated the inflammation process, endothelial injury and blood coagulation in diabetic mice. Therefore, the development of proper infection diagnosis and timely use of effective treatments for MRSA-infected diabetic individuals is important and necessary.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke

2011 ◽  
Vol 38 (8) ◽  
pp. 5355-5360 ◽  
Author(s):  
Adriano de Paula Sabino ◽  
Daniel Dias Ribeiro ◽  
Caroline Pereira Domingueti ◽  
Mariana Silva dos Santos ◽  
Telma Gadelha ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Young Patients ◽  
Plasminogen Activator Inhibitor ◽  
Promoter Polymorphism ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

W1490: Association Between Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Colorectal Adenomas

2010 ◽  
Vol 71 (5) ◽  
pp. AB341
Author(s):  
Eun Ran Kim ◽  
Moon Hee Yang ◽  
Yeun Jung Lim ◽  
Jin Hee Lee ◽  
Byung-Hoon Min ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Plasminogen Activator Inhibitor ◽  
Colorectal Adenomas ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1

2016 ◽  
Vol 116 (07) ◽  
pp. 162-171 ◽  
Author(s):  
Amirhossein Sahebkar ◽  
Cristiana Catena ◽  
Kausik Ray ◽  
Antonio Vallejo-Vaz ◽  
Željko Reiner ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Plasminogen Activator ◽  
Publication Bias ◽  
Plasma Levels ◽  
Meta Analysis ◽  
Plasminogen Activator Inhibitor ◽  
Lipid Lowering ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryElevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I2 test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and “trim and fill” tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: –15.72 ng/ml, 95 % confidence interval [CI]: –25.01, –6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: –21.32 ng/ml, 95 % CI: –32.73, –9.91, I2=99 %) and particularly atorvastatin (WMD: –20.88 ng/mL, 95 % CI: –28.79, –12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.

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.

Involvement of RAGE, NADPH Oxidase, and Ras/Raf-1 Pathway in Glycated LDL-Induced Expression of Heat Shock Factor-1 and Plasminogen Activator Inhibitor-1 in Vascular Endothelial Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4455-4466 ◽  
Author(s):  
Ganesh V. Sangle ◽  
Ruozhi Zhao ◽  
Tooru M. Mizuno ◽  
Garry X. Shen
Keyword(s):  
Vascular Endothelial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Heat Shock Factor 1 ◽  
Vascular Endothelial ◽  
Diabetic Mice ◽  
Plasminogen Activator Inhibitor 1 ◽  
Small Interference Rna ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Interference Rna

Atherothrombotic cardiovascular diseases are the predominant causes of mortality of diabetic patients. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor for fibrinolysis, and it is also implicated in inflammation and tissue remodeling. Increased levels of PAI-1 and glycated low-density lipoprotein (glyLDL) were detected in patients with diabetes. Previous studies in our laboratory demonstrated that heat shock factor-1 (HSF1) is involved in glyLDL-induced PAI-1 overproduction in vascular endothelial cells (EC). The present study investigated transmembrane signaling mechanisms involved in glyLDL-induced HSF1 and PAI-1 up-regulation in cultured human vascular EC and streptozotocin-induced diabetic mice. Receptor for advanced glycation end products (RAGE) antibody prevented glyLDL-induced increase in the abundance of PAI-1 in EC. GlyLDL significantly increased the translocation of V-Ha-Ras Harvey rat sarcoma viral oncogene homologue (H-Ras) from cytoplasm to membrane compared with LDL. Farnesyltransferase inhibitor-277 or small interference RNA against H-Ras inhibited glyLDL-induced increases in HSF1 and PAI-1 in EC. Treatment with diphenyleneiodonium, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor, blocked glyLDL-induced translocation of H-Ras, elevated abundances of HSF1 and PAI-1 in EC, and increased release of hydrogen peroxide from EC. Small interference RNA for p22phox prevented glyLDL-induced expression of NOX2, HSF1, and PAI-1 in EC. GlyLDL significantly increased V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) phosphorylation. Treatment with Raf-1 inhibitor blocked glyLDL-induced increase of PAI-1 mRNA in EC. The levels of RAGE, H-Ras, NOX4, HSF1, and PAI-1 were increased in hearts of streptozotocin-diabetic mice and positively correlated with plasma glucose. The results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress.

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